Melbourne, Australia
Melbourne, Australia

Monash University is a university based in Melbourne, Australia. It was founded in 1958 and is the second oldest university in the State of Victoria. Monash is a member of Australia's Group of Eight and the ASAIHL, and is the only Australian member of the influential M8 Alliance of Academic Health Centers, Universities and National Academies.Monash enrolls approximately 45,000 undergraduate and 17,000 graduate students, making it the university with the largest student body in Australia. It also has more applicants than any university in the state of Victoria.Monash is home to major research facilities, including the Australian Synchrotron, the Monash Science Technology Research and Innovation Precinct , the Australian Stem Cell Centre, 100 research centres and 17 co-operative research centres. In 2011, its total revenue was over $1.5 billion, with external research income around $282 million.The university has seven campuses, five of which are in Victoria , one in Malaysia, and one in South Africa. Monash also has a research and teaching centre in Prato, Italy, a graduate research school in Mumbai, India and a graduate school in Jiangsu Province, China. Since December 2011, Monash has had a global alliance with the University of Warwick in the United Kingdom.The Clayton campus contains the Robert Blackwood Hall, named after the university's founding Chancellor Sir Robert Blackwood and designed by Sir Roy Grounds, which boasts superb acoustics and is considered Melbourne's best music venue outside the CBD.In 2014, the University ceded its Gippsland campus to Federation University. Wikipedia.


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Patent
Monash University | Date: 2015-03-23

A visual image processing method is based on received spatial field information (302) from a spatial field sensor (116). A data store (804) is accessed, which contains a sensor map data structure (206) comprising a set of predefined regions (208) within a spatial field corresponding with the information received via the sensor input. Each predefined region is associated in the data structure with one or more of a set of stimuli (204) applicable to a biological visual system, and each stimulus corresponds with a visual percept (210). The spatial field information associated with each region is processed to generate stimulus control information which is applied to select, from within the sensor map data structure, stimuli from the set of stimuli for application to the biological visual system. Output stimulus signals (310) are generated, which are suitable for application to the biological visual system based upon the selected stimuli. Flexible mappings are thus provided between visual percepts, stimuli which may be applied (e.g. via a prosthetic implant) in order to generate the percepts, and associations between those stimuli and regions of the spatial field corresponding with the visual percepts.


Patent
Monash University | Date: 2015-03-17

A method for the preparation of a cohesive non-porous perovskite layer on a substrate (104) comprising: forming a thin film of a solution containing a perovskite material dissolved in a solvent onto the substrate to form a liquid film (104) of the solution on the substrate, applying a crystallisation agent (112) to a surface of the film to precipitate perovskite crystals from the 5 solution to form the cohesive non-porous perovskite layer (116) on the substrate.


Patent
Monash University | Date: 2017-01-18

A gas permeable or breathable electrode and method of manufacture thereof. In one example there is an electrolytic cell having an electrode comprising a porous material, wherein gas produced at the electrode diffuses out of the cell via the porous material. In operation the gas is produced at the at least one electrode without substantial bubble formation. In another example there is an electrode having a porous conducting material with a hydrophobic layer or coating applied to a side of the porous conducting material. A catalyst may be applied to another side. The gas permeable or breathable electrode can be used in an electrolytic cell, electrochemical cell, battery and/or fuel cell. Gas produced at the electrode diffuses out of a cell via at least part of the electrode, separating the gas from the reaction at the electrode.


Psaltis P.J.,University of Adelaide | Psaltis P.J.,Monash University | Simari R.D.,University of Kansas
Circulation Research | Year: 2015

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease. © 2015 American Heart Association, Inc.


Prowle J.R.,Royal London Hospital | Kirwan C.J.,Royal London Hospital | Bellomo R.,Monash University
Nature Reviews Nephrology | Year: 2014

In patients with acute kidney injury (AKI), optimization of systemic haemodynamics is central to the clinical management. However, considerable debate exists regarding the efficacy, nature, extent and duration of fluid resuscitation, particularly when the patient has undergone major surgery or is in septic shock. Crucially, volume resuscitation might be required to maintain or restore cardiac output. However, resultant fluid accumulation and tissue oedema can substantially contribute to ongoing organ dysfunction and, particularly in patients developing AKI, serious clinical consequences. In this Review, we discuss the conflict between the desire to achieve adequate resuscitation of shock and the need to mitigate the harmful effects of fluid overload. In patients with AKI, limiting and resolving fluid overload might prompt earlier use of renal replacement therapy. However, rapid or early excessive fluid removal with diuretics or extracorporeal therapy might lead to hypovolaemia and recurrent renal injury. Optimal management might involve a period of guided fluid resuscitation, followed by management of an even fluid balance and, finally, an appropriate rate of fluid removal. To obtain best clinical outcomes, serial fluid status assessment and careful definition of cardiovascular and renal targets will be required during fluid resuscitation and removal. © 2014 Macmillan Publishers Limited.


Von Lueder T.G.,University of Oslo | Krum H.,Monash University
Nature Reviews Cardiology | Year: 2015

Heart failure (HF) can rightfully be called the epidemic of the 21 st century. Historically, the only available medical treatment options for HF have been diuretics and digoxin, but the capacity of these agents to alter outcomes has been brought into question by the scrutiny of modern clinical trials. In the past 4 decades, neurohormonal blockers have been introduced into clinical practice, leading to marked reductions in morbidity and mortality in chronic HF with reduced left ventricular ejection fraction (LVEF). Despite these major advances in pharmacotherapy, our understanding of the underlying disease mechanisms of HF from epidemiological, clinical, pathophysiological, molecular, and genetic standpoints remains incomplete. This knowledge gap is particularly evident with respect to acute decompensated HF and HF with normal (preserved) LVEF. For these clinical phenotypes, no drug has been shown to reduce long-term clinical event rates substantially. Ongoing developments in the pharmacotherapy of HF are likely to challenge our current best-practice algorithms. Novel agents for HF therapy include dual-acting neurohormonal modulators, contractility-enhancing agents, vasoactive and anti-inflammatory peptides, and myocardial protectants. These novel compounds have the potential to enhance our armamentarium of HF therapeutics. © 2015 Macmillan Publishers Limited.


Sgro C.M.,Monash University | Lowe A.J.,University of Adelaide | Hoffmann A.A.,University of Melbourne
Evolutionary Applications | Year: 2011

Evolution occurs rapidly and is an ongoing process in our environments. Evolutionary principles need to be built into conservation efforts, particularly given the stressful conditions organisms are increasingly likely to experience because of climate change and ongoing habitat fragmentation. The concept of evolutionary resilience is a way of emphasizing evolutionary processes in conservation and landscape planning. From an evolutionary perspective, landscapes need to allow in situ selection and capture high levels of genetic variation essential for responding to the direct and indirect effects of climate change. We summarize ideas that need to be considered in planning for evolutionary resilience and suggest how they might be incorporated into policy and management to ensure that resilience is maintained in the face of environmental degradation. © 2010 Blackwell Publishing Ltd.


Selmi C.,University of Milan | Bowlus C.L.,University of California at Davis | Gershwin M.E.,University of California at Davis | Coppel R.L.,Monash University
The Lancet | Year: 2011

Primary biliary cirrhosis is a chronic liver disease characterised by intrahepatic bile-duct destruction, cholestasis, and, in some cases, cirrhosis. Evidence supporting the autoimmune nature of this disorder includes the appearance of highly specific antimitochondrial antibodies (AMAs) and autoreactive T cells. Concordance rates in monozygotic twins, familial prevalence, and genetic associations underscore the importance of genetic factors, whereas findings of epidemiological studies and murine models suggest a possible role for exogenous chemicals and infectious agents through molecular mimicry. The incidence of primary biliary cirrhosis has increased over recent decades, possibly attributable to augmented testing of liver biochemistry rather than a rise in disease incidence. AMAs remain the hallmark of diagnosis in most cases and allow detection of asymptomatic patients. Symptomatic individuals usually present with either pruritus or fatigue and, more rarely, with either jaundice or complications of cirrhosis. The prognosis of primary biliary cirrhosis has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. Although not a cure, treatment can slow disease progression and delay the need for liver transplantation. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches. © 2011 Elsevier Ltd.


Leech M.T.,Monash University | Bartold P.M.,University of Adelaide
Best Practice and Research: Clinical Rheumatology | Year: 2015

The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis. © 2015 Elsevier Ltd. All rights reserved.


Yu D.,Garvan Institute of Medical Research | Yu D.,Monash University
Trends in Immunology | Year: 2010

Follicular helper T (Tfh) cells provide help to B cells and allow formation of long-lived antibody responses. Despite an improved understanding of the molecular program that drives Tfh cell formation, their definition remains elusive: neither follicular homing ability, Bcl-6 expression nor IL-21 secretion are exclusive properties of T cells that help B cells, and not all follicular T cells are B cell helpers. Indeed some follicular T cells appear to be suppressive. Furthermore, Tfh cells evolve during an immune response and B cells that have recently bound antigen, germinal center (GC) B cells and plasmablasts interact with phenotypically distinct Tfh cells. Here we propose that distinction between non-GC Tfh and GC Tfh cells might reconcile emerging controversies on Tfh cytokine secretion and the requirement of T-B cell interactions and SAP expression for Tfh formation. © 2010 Elsevier Ltd.


Hashemi S.,Monash University | Al-Mahaidi R.,Swinburne University of Technology
Construction and Building Materials | Year: 2012

The strengthening and rehabilitation of structures are major issues worldwide. In most situations, strengthening is required when there is an increase in the applied load, human error in the initial construction, a legal requirement to comply with updated versions of existing codes, or as a result of the loss of strength due to deterioration over time. Fiber-Reinforced Polymer (FRP) strengthening systems are enjoying a great deal of popularity as a result of the unique properties of FRPs, namely, their light weight, fatigue resistance non-corrosive characteristics and ease of application. The repair and strengthening technique with epoxy-bonded advanced composites has been applied to a large number of bridges around the world. At elevated temperatures, normally beyond the glass transition temperatures of epoxy adhesive, the mechanical properties of the polymer matrix deteriorate rapidly. It will be very beneficial if they can be replaced by cementitious (mineral)-based bonding agents such as modified concrete, in order to produce fire-resistant strengthening systems. Tests conducted for this paper include the investigation of the flexural behavior of FRP-strengthened reinforced concrete beams using cement-based adhesives. It is concluded that the use of cement-based bonding materials is a promising technique in FRP applications for structures located in hot regions or in danger of fire. © 2011 Elsevier Ltd. All rights reserved.


Liaw H.C.,National University of Singapore | Shirinzadeh B.,Monash University
IEEE Transactions on Industrial Electronics | Year: 2011

This paper presents a robust adaptive constrained motion tracking control methodology for piezo-actuated flexure-based micro/nano manipulation mechanisms. This unique control approach is established for the tracking of desired motion trajectories in a constrained environment exhibiting some degree of uncertain stiffness. The control methodology is also formulated to accommodate not only the parametric uncertainties and unknown force conversion function, but also nonlinearities including the hysteresis effect and external disturbances in the motion systems. In this paper, the equations for the dynamic modeling of a flexure-hinged four-bar micro/nano manipulation mechanism operating in a constrained environment are established. A lumped parameter dynamic model that combines the piezoelectric actuator and the micro/nano manipulation mechanism is developed for the formulation of the control methodology. Stability analysis of the proposed closed-loop system is conducted and the convergence of the motion tracking errors is proven theoretically. Furthermore, precise motion tracking ability in following a desired motion trajectory is demonstrated in the experimental study. An important advantage of this control approach is that it does not require the exact values for the system parameters and the force conversion function in the physical realization. This proposed constrained motion tracking control methodology is very useful for applications demanding high-precision motion tracking with force sensing and feedback. © 2011 IEEE.


Von Lueder T.G.,Monash University | Von Lueder T.G.,University of Oslo | Atar D.,University of Oslo | Krum H.,Monash University
Pharmacology and Therapeutics | Year: 2014

Cardiovascular diseases (CVD) continue to represent the major cause of death, morbidity and healthcare expenditure worldwide. Current medical therapy fails to effectively halt disease progression and to reduce adverse clinical outcomes, reflecting incomplete understanding of pathomechanisms as well as the need to expand current pharmacotherapeutic strategies. Hypertension and heart failure, the most important CVD entities, are associated with imbalance in neurohormonal systems activity such as the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system and the endothelin system. Blockade of the RAAS constitutes the most successful pharmacotherapeutic concept in hypertension and heart failure to date. The RAAS-opposing natriuretic peptide system constitutes the body's own BP-lowering system, and mediates a multitude of beneficial actions within cardiovascular tissues. The metallopeptidase neprilysin (NEP) hydrolyzes natriuretic peptides. Conceptually, NEP inhibition would increase salutary natriuretic peptide actions in CVD. However, stand-alone NEP inhibitors (NEPi) lacked efficacy beyond standard pharmacotherapy. Combined blockers of NEP and the endothelin system demonstrated efficacy in preclinical studies but have not been evaluated in clinical trials. A decade ago, omapatrilat and other dual-acting NEPi-ACEi (vasopeptidase-inhibitors) were promising agents for hypertension and heart failure. Despite greater efficacy, development of vasopeptidase-inhibitors was halted due to significant off-target effects in some cohorts, most notably increased frequency of angioedema in hypertensive subjects. Novel angiotensin-receptor-neprilysin-inhibitors (ARNi) seek to fully exploit clinical efficacy of combined RAAS-blockade and NEPi-mediated natriuretic peptide augmentation, and hopefully do so with improved clinical safety. We herein review current knowledge of NEPi as stand-alone and combined pharmacotherapeutic agents in hypertension and heart failure. © 2014 Elsevier Inc.


Williams G.,University of Swansea | Birbilis N.,Monash University | Mcmurray H.N.,University of Swansea
Electrochemistry Communications | Year: 2013

The behaviour of anodically-polarised magnesium (Mg) appears counter-intuitive to conventional electrochemical theory, where the application of increasingly positive potentials or higher currents produce progressively greater rates of hydrogen evolution. Presently this observation is explained by a theory involving Mg dissolution through a Mg+ intermediate, which undergoes chemical reaction with water to produce hydrogen. Here we report the use of an in-situ scanning vibrating electrode technique (SVET) to characterise local current density distributions over anodically-polarised Mg surfaces immersed in sodium chloride containing electrolyte. Anodic dissolution is shown to be highly localised in nature and accompanied by significant cathodic activity. The area occupied by local cathodes increases with time and both total anodic and cathodic currents emerging from the exposed Mg surface are shown to rise accordingly. It is also demonstrated that increasing the anodic current supplied to the Mg causes local cathode areas to grow more rapidly, hence accounting for progressively greater hydrogen evolution rates. These observations demonstrate that hydrogen evolution remains a cathodic process, thus invalidating the Mg+ theory of dissolution. © 2013 Elsevier B.V.


Kong D.L.Y.,Monash University | Sanjayan J.G.,Swinburne University of Technology
Cement and Concrete Research | Year: 2010

Geopolymers are generally believed to provide good fire resistance due to their ceramic-like properties. Previous experimental studies on geopolymer under elevated temperatures have mainly focused on metakaolin-based geopolymers. This paper presents the results of a study on the effect of elevated temperature on geopolymer paste, mortar and concrete made using fly ash as a precursor. The geopolymer was synthesized with sodium silicate and potassium hydroxide solutions. Various experimental parameters have been examined such as specimen sizing, aggregate sizing, aggregate type and superplasticizer type. The study identifies specimen size and aggregate size as the two main factors that govern geopolymer behavior at elevated temperatures (800 °C). Aggregate sizes larger than 10 mm resulted in good strength performances in both ambient and elevated temperatures. Strength loss in geopolymer concrete at elevated temperatures is attributed to the thermal mismatch between the geopolymer matrix and the aggregates. © 2009 Elsevier Ltd. All rights reserved.


Pimbblet K.A.,Monash University | Jensen P.C.,Swinburne University of Technology
Monthly Notices of the Royal Astronomical Society | Year: 2012

We present an analysis of the galaxy population of the intermediate X-ray luminosity galaxy cluster, Abell 1691, from Sloan Digital Sky Survey (SDSS) and Galaxy Zoo data to elucidate the relationships between environment and galaxy stellar mass for a variety of observationally important cluster populations that include the Butcher-Oemler blue fraction, the active galactic nucleus (AGN) fraction and other spectroscopic classifications of galaxies. From 342 cluster members, we determine a cluster recession velocity of 21257 ± 54 kms -1 and velocity dispersion of 1009-36+40 kms -1 and show that although the cluster is fed by multiple filaments of galaxies it does not possess significant sub-structure in its core. We identify the AGN population of the cluster from a Baldwin, Phillips & Terlevich diagram and show that there is a mild increase in the AGN fraction with radius from the cluster centre that appears mainly driven by high-mass galaxies [log(stellar mass) > 10.8]. Although the cluster blue fraction follows the same radial trend, it is caused primarily by lower mass galaxies [log(stellar mass) < 10.8]. Significantly, the galaxies that have undergone recent starbursts or are presently starbursting but dust-shrouded [spectroscopic e(a) class galaxies] are also nearly exclusively driven by low-mass galaxies. We therefore suggest that the Butcher-Oemler effect may be a mass-dependent effect. We also examine red and passive spiral galaxies and show that the majority are massive galaxies, much like the rest of the red and spectroscopically passive cluster population. We further demonstrate that the velocity dispersion profiles of low- and high-mass cluster galaxies are different. Taken together, we infer that the duty cycle of high- and low-mass cluster galaxies is markedly different, with a significant departure in star formation and specific star formation rates observed beyond r 200 and we discuss these findings. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.


Burgess S.C.,University of California at Davis | Marshall D.J.,Monash University
Oikos | Year: 2014

Anticipatory parental effects (APE's) occur when parents adjust the phenotype of their offspring to match the local environment, so as to increase the fitness of both parents and offspring. APE's, as in the evolution of adaptive phenotypic plasticity more generally, are predicated on the idea that the parental environment is a reliable predictor of the offspring environment. Most studies on APE's fail to explicitly consider environmental predictability so risk searching for APE's under circumstances where they are unlikely to occur. This failure is perhaps one of the major reasons for mixed evidence for APE's in a recent meta-analysis. Here, we highlight some often-overlooked assumptions in studies of APE's and provide a framework for identifying and testing APE's. Our review highlights the importance of measuring environmental predictability, outlines the minimal requirements for experimental designs, explains the important differences between relative and absolute measures of offspring fitness, and highlights some potential issues in assigning components of offspring fitness to parental fitness. Our recommendations should result in more targeted and effective tests of APE's. Synthesis A decent set of theory is available to understand when certain kinds of parental effects might act to increase parental fitness (i.e. be 'adaptive'). This theory could be better incorporated into empirical studies on anticipatory parental effects (APE's). Here, we provide practical advice for how empirical studies can more closely align with the theoretical underpinnings of adaptive parental effects. In short, robust inferences on APE's require quantitative estimates of environmental predictability in the field over the space and time scales relevant to the life history of the study organism as well as an understanding of when to use absolute or relative offspring fitness. © 2014 The Authors.


Pan Z.,Monash University | Sanjayan J.G.,Swinburne University of Technology
Cement and Concrete Composites | Year: 2012

This paper presents the effects of cation type, silicate concentration, compositions of low-calcium fly ash and test load on softening temperature and hot-strength (loaded while at high temperature) of fly ash-based geopolymers. It was found that softening temperature (T s) of sodium (Na) based-geopolymer remained the same (610 °C ± 20 °C) regardless of the silicate concentration, fly ash composition, and test load. However, when the cation was changed from sodium to potassium (K), the T s increased to 800 °C. Further, when Na/K is mixed, the T s dropped to 570 °C. Significant increases in hot-strengths (at 530 °C and 730 °C) were found in all geopolymers. This increase in strength was observed to be in conjunction with heat release, indicating an exothermic reaction. Since the reaction between fly ash and activators is exothermic, this reaction is believed to be the reason for the strength gain at high temperatures. © 2011 Elsevier Ltd. All rights reserved.


Bowman J.L.,Monash University | Bowman J.L.,University of California at Davis
Plant and Cell Physiology | Year: 2016

While written accounts of plants date back thousands of years, due to the degradation of scientific literature during the dark ages descriptions descended from Greek writings are sometimes equivocal as to species identity. Such is the case with Marchantia in the pre-Renaissance literature; however, indisputable illustrations of Marchantia polymorpha were made as early as the mid-15th century, beginning a rich historical literature on its taxonomy, development and physiology. In this review, I present three vignettes, each of which are themselves abbreviated due to space constraints. The first presents the role of Marchantia and related liverwort species in the discovery of sex in cryptogams, from the elucidation of liverwort life cycles the 18th century to the sequence of the Y chromosome in the 21st. A second vignette describes the use of M. polymorpha as a model organism in the early 19th century debate concerning the cellular nature of organisms and the origin of new cells - an endeavor that provided us with Charles-François Brisseau de Mirbel's mémoire containing beautiful, if slightly fanciful, illustrations of the Marchantia life cycle. The final vignette chronicles the use of M. polymorpha gemmae over the past two centuries to elucidate the mechanism by which a dorsiventral body plan is established from an initially apolar gemma. While only covering a fraction of the literature available, these vignettes provide a glimpse of historical and recent discoveries available upon which to build a molecular genetic and genomic understanding of Marchantia. © The Author 2015.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: FoF.NMP.2012-4 | Award Amount: 18.22M | Year: 2013

The overarching goal of AMAZE is to rapidly produce large defect-free additively-manufactured (AM) metallic components up to 2 metres in size, ideally with close to zero waste, for use in the following high-tech sectors namely: aeronautics, space, automotive, nuclear fusion and tooling. Four pilot-scale industrial AM factories will be established and enhanced, thereby giving EU manufacturers and end-users a world-dominant position with respect to AM production of high-value metallic parts, by 2016. A further aim is to achieve 50% cost reduction for finished parts, compared to traditional processing. The project will design, demonstrate and deliver a modular streamlined work-flow at factory level, offering maximum processing flexibility during AM, a major reduction in non-added-value delays, as well as a 50% reduction in shop-floor space compared with conventional factories. AMAZE will dramatically increase the commercial use of adaptronics, in-situ sensing, process feedback, novel post-processing and clean-rooms in AM, so that (i) overall quality levels are improved, (ii) dimensional accuracy is increased by 25% (iii) build rates are increased by a factor of 10, and (iv) industrial scrap rates are slashed to <5%. Scientifically, the critical links between alloy composition, powder/wire production, additive processing, microstructural evolution, defect formation and the final properties of metallic AM parts will be examined and understood. This knowledge will be used to validate multi-level process models that can predict AM processes, part quality and performance. In order to turn additive manufacturing into a mainstream industrial process, a sharp focus will also be drawn on pre-normative work, standardisation and certification, in collaboration with ISO, ASTM and ECSS. The team comprises 31 partners: 21 from industry, 8 from academia and 2 from intergovernmental agencies. This represent the largest and most ambitious team ever assembled on this topic.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SST-2007-4.1-01;SST-2007-4.1-02 | Award Amount: 5.28M | Year: 2009

Powered Two Wheeler (PTW) users are greatly over-involved in serious and fatal crashes. They have between 5 and 25 times the risk of having a fatal crash compared to car drivers, depending on the country. The number of PTWs on European roads has more than doubled over the last two decades. The recent MAIDS (Motorcycle Accident In-Depth Study) study of PTW crashes in Europe found that behavioural and ergonomic issues were major contributing factors to PTW crashes: the primary accident cause for PTW crashes was the failure of drivers to perceive two-wheelers; and human error was a major contributing factor to most crashes, for both PTW and car drivers. The majority of PTW crashes involved a collision with a car. Many large-scale research programs have been undertaken to understand the behavioural and ergonomic factors that contribute to crashes involving 4-wheeled vehicles. These have been effective in informing countermeasure development, which has led to significant reductions in crashes. To our knowledge, no comparable human factors and behavioural research programs have been initiated in the PTW domain, in Europe or elsewhere. The high rate of motorcycle-related deaths and injuries calls for new and refined countermeasures, deriving from solid behavioural and ergonomics research. In this proposal we outline an innovative program of research, involving partners from Europe, Israel and Australia, that directly targets those behavioural and ergonomic factors cited in the MAIDS study as contributing to PTW crashes. This includes research on crash causes and human error, the worlds first naturalistic riding study involving instrumented PTWs, research on motorcycle rider risk awareness and perception, the development of new research tools to support the research program, in-depth research on the factors that underlie driver failures to see PTWs and their riders, and the development of recommendations for practical countermeasures for enhancing PTW rider safety.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2009.3.1.1.1 | Award Amount: 10.66M | Year: 2010

IPCC climate change scenarios have a global perspective and need to be scaled down to the local level, where decision makers have to balance risks and investment costs. Very high investments might be a waste of money and too little investment could result in unacceptable risk for the local community. PREPARED is industry driven, 12 city utilities are involved in the project and the RDT carried out is based on the impacts of climate change the water supply and sanitation industry has identifed as a challenge for the years to come. The result of PREPARED will be an infrastructure for waste water, drinking water and storm water management that will not only be able better cope with new scenarios on climate change but that is also managed in a optimal way. We will have complexes monitoring and sensor systems, better integration and handling of complex data, better exploitation of existing infrastructures through improved real time control, new design concepts and guidelines for more flexible and more robust infrastructures. PREPARED will involve the local community in problem identification and in jointly finding acceptable system solutions, that are supported by all, through active learning processes. Activities and solutions in PREPARED will be based on a risk assessment and risk management approach for the whole urban water cycle, through the development of innovative Water Cycle Safety Plans. Other innovations are sensors and models that will enable faster and better actions on changes and new design rules for more resilient design. We will combine European knowledge with valuable knowledge from Australia and the USA, to make the European Water sector more competitive. This to enable our industrial partners to export the products developed in PREPARED to other regions of the world, thus contributing to the Lisbon Goals but also to the MDGs. To ensure this exploitation the PREPARED consortium consist of more than 50% industrial partners and is demand driven.


Patent
Polychip Pharmaceuticals Pty Ltd and Monash University | Date: 2011-05-25

A dicarba analogue of insulin comprising an A-chain and a B-chain or fragments, salts, solvates, derivatives, isomers or tautomers of the A-chain, the B-chain or both, provided that the dicarba analogue is not [A7,B7-(2,7-diaminosuberoyl]-des-(B26-B30)-insulin B25-amide.


Patent
Polychip Pharmaceuticals Pty Ltd. and Monash University | Date: 2012-02-16

According to the present invention, there is provided a range of new conotoxin derivatives and methods for synthesizing these analogues and other intramolecular dicarba bridge-containing peptides, including dicarba-disulfide bridge-containing peptides.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-1 | Award Amount: 39.56M | Year: 2013

Traumatic Brain Injury (TBI) is a major cause of death and disability, leading to great personal suffering to victim and relatives, as well as huge direct and indirect costs to society. Strong ethical, medical, social and health economic reasons therefore exist for improving treatment. The CENTER-TBI project will collect a prospective, contemporary, highly granular, observational dataset of 5400 patients, which will be used for better characterization of TBI and for Comparative Effectiveness Research (CER). The generalisability of our results will be reinforced by a contemporaneous registry level data collection in 15-25,000 patients. Our conceptual approach is to exploit the heterogeneity in biology, care, and outcome of TBI, to discover novel pathophysiology, refine disease characterization, and identify effective clinical interventions. Key elements are the use of emerging technologies (biomarkers, genomics and advanced MR imaging) in large numbers of patients, across the entire course of TBI (from injury to late outcome) and across all severities of injury (mild to severe). Improved characterization with these tools will aid Precision Medicine, a concept recently advocated by the US National Academy of Science, facilitating targeted management for individual patients. Our consortium includes leading experts and will bring outstanding biostatistical and neuroinformatics expertise to the project. Collaborations with external partners, other FP7 consortia, and international links within InTBIR, will greatly augment scientific resources and broaden the global scope of our research. We anticipate that the project could revolutionize our view of TBI, leading to more effective and efficient therapy, thus improving outcome and reducing costs. These outcomes reflect the goals of CER to assist consumers, clinicians, health care purchasers, and policy makers to make informed decisions, and will improve healthcare at both individual and population levels.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: AAT.2010.1.1-1.;AAT.2010.1.1-3. | Award Amount: 4.02M | Year: 2010

The objective of AFDAR is to develop, assess and demonstrate new image-based experimental technologies for the analysis of aerodynamic systems and aerospace propulsion components. The main development focus is on new three-dimensional methods based on Particle Image Velocimetry (PIV) to measure the flow field around aircraft components, and on the high-speed version of the planar technique for the analysis in time-resolved regime of transient/unsteady aerodynamic problems. The progress beyond the state of the art with respect to current technologies is summarized by three aimed breakthroughs: 1) three-dimensional volumetric measurements over wings and airfoils; 2) time-resolved measurements and aerodynamic analysis several orders of magnitude faster than today; 3) turbulence characterization in aerodynamics wind-tunnels at resolution orders of magnitude higher than today by Long-Range Micro-PIV. The project ultimately aims to support the design of better aircraft and propulsion systems by enabling the designer to use experimental data during the development cycle of unprecedented completeness and quality. The work also covers the simultaneous application of PIV-based techniques and other methods to determine aeroacoustic noise emissions from airframe and to improve combustion processes to lower NOx, CO2 and soot emissions from engines. The consortium is led by a Dutch Technical University and lists 10 partners including a Russian research Institute and an Australian University. Three industries are involved in this work either as participant or contributing under subcontract and providing testing facilities. As final results of the project, a detailed analysis of the new measurement systems will be delivered and a number of demonstrations will be performed to validate the concepts in industrial environments. Special emphasis is given to the dissemination of results by meetings, publications and workshops.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP-2010-4.0-3 | Award Amount: 22.10M | Year: 2011

The core concept of Accelerated Metallurgy is to deliver an integrated pilot-scale facility for the combinatorial synthesis and testing of many thousands of unexplored alloy formulations. This facility would be the first of its kind in the world and would represent a significant advance for metallurgy. The novel technology that enables this HTT facility is based on automated, direct laser deposition (DLD). The key feature of this technology is the way in which a mixture of elemental powders is accurately and directly fed into the lasers focal point, heated by the laser beam, and deposited on a substrate in the form of a melt pool, which finally solidifies to create a unique fully-dense alloy button with precise stoichiometry. This robotic alloy synthesis is 1000 times faster than conventional manual methods. Once produced, these discrete mm-sized samples are submitted to a range of automated, standardised tests that will measure chemical, physical and mechanical properties. The vast amount of information will be recorded in a Virtual Alloy Library and coupled with computer codes such as neural network models, in order to extract and map out the key trends linking process, composition, structure and properties. The most promising alloy formulations will be further tested, patented and exploited by the 20 end-users. Industrial interests include: (i) new lightweight fuel-saving alloys (<4.5 g/cm3) for aerospace and automotive applications; (ii) new higher-temperature alloys (stable>1000C) for rockets, gas turbines, jet-engines, nuclear fusion; (iii) new high-Tc superconductor alloys (>30K) that can be wire-drawn for electrical applications; (iv) new high-ZT thermoelectric alloys for converting waste heat directly into electricity; (v) new magnetic and magnetocaloric alloys for motors and refrigeration; and (vi) new phase-change alloys for high-density memory storage. The accelerated discovery of these alloy formulations will have a very high impact on society.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2008.1.2.1.1. | Award Amount: 6.08M | Year: 2009

The rapid worldwide increase in mobile phone use in adolescents and, more recently, children has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. The current project aims to assess the potential carcinogenic effects of childhood and adolescent exposure to RF and ELF from mobile telephones on tumours of the central nervous system. The study will include approximately 1,000 cases of malignant and benign brain tumours aged 10 to 24 years and their respective controls from 15 countries (7 of which have funding under this contract). The project will build upon the methodological experience (both in terms of exposure assessment and epidemiological design) collected within the INTERPHONE study. Particular attention will be paid to issues of: potential selection bias related to the very low response rates of population-based controls by selecting hospitalized controls with specific diagnoses, representative of the general population and unrelated to mobile phone use ; and potential recall errors by validating questionnaire responses with the help of network operators and repeat questionnaires. Improved exposure indices for RF will be derived taking into account spatial distribution of energy in the brain at different ages; ELF from the phones will also be considered, as well as other important sources of EMF in the general environment of young people. The proposed age range is the most cost efficient to answer the question (because of latency) of brain cancer risk from exposure in childhood and adolescence. The timing of the project is optimal (2010-2014) because of the increasing prevalence of heavy use among adolescents and, in the last 5-10 years, children, without hands-free kits, particularly in Southern European countries and Israel.


Optical fiber chemical sensors based on optical absorption feature high specificity, fast response, and a much longer lifetime compared to other chemical sensors, qualities that offer significant potential for application in pollution monitoring, environmental protection, and hazardous-material detection. Now by integrating metal organic framework (MOF) materials—a new class of highly porous crystalline material—with optical fibers, researchers from Victoria University and Monash University, Australia, have co-developed a novel, highly sensitive chemical sensor based on an optical fiber coated with a thin film of a specific MOF (namely, UiO-66), which could be potentially used for real-time detection of heavy organic contaminants such as herbicides or pesticides in water. In a paper published this week in the journal Optics Letters, from The Optical Society (OSA), the researchers described their work. "Metal organic frameworks (MOFs) are networks of metal atoms linked and separated by carbon-based (organic) compounds. The UiO-66 MOF we used in the experiment is made from Zirconium and is well known for the stability in water," said Stephen Collins, professor of engineering, Victoria University, Australia. "We have demonstrated for the first time that the advanced porous material MOFs can be coated onto the end-face of optical fibers to create a novel, faster and more sensitive chemical sensor potentially used for measuring heavy organic contaminants on site and in real-time." Collins said various porous adsorbents such as pyrene-labeled monomer, silica sol-gel and zeolites have been studied recently by scientists for detecting hazardous compounds. However, the low porosity and small pores of the above adsorbents limit their use in the sensing area to small molecules. That is, they cannot detect larger or heavy organic molecules (e.g. herbicides or pesticides) in water. Metal organic frameworks are about 10 times more porous than any material previously known, so they can absorb larger molecules. MOFs form as crystals and careful selection of MOF constituents can yield crystals of ultrahigh porosity and high thermal and chemical stability. To fabricate the MOF-fiber sensor, the researchers removed the polymer coating of a conventional single mode fiber several centimeters from the end and activated the fiber surface using plasma. Then, the fiber was placed in MOF liquid solution and heated at 120 degrees Celsius for 24 hours, which allowed the activated fiber surface to attract the MOF to grow on the end-face of the fiber, resulting in a MOF thin film of 17- to 22-micrometer thickness. Collins explained that the MOF-fiber sensor can be used as an in-fiber Fabry-Perot interferometer, which is a well-established method for detecting the "optical thickness" of a thin film by studying the interference signals generated by the film interfaces. As the MOF-fiber sensor absorbs more and more contaminants, the optical thickness of the MOF thin film increases accordingly, leading to a change in the interference spectra. By using the established optical model and mathematical procedure, the researchers can calculate the optical thickness of the MOF thin film from the experimentally measured interference spectra, and hence infer the concentration of contaminants in water. In the experiment, Collin's team used the MOF-fiber sensor to detect a specific contaminant in water called Rhodamine-B (RhB) dye, a bright pink dye known as Opera Rose, which is used in the textile industry and is known to be potentially carcinogenic if ingested. "Our experimental results showed a positive detection response of the MOF-fiber sensor to RhB in water down to 48 parts per million or 0.1 millimolar, which is a very promising result, demonstrating the sensor's ability to detect pollutants at a low concentration before the pollution goes worse," said Collins. He explained the high sensitivity and fast response of the MOF-fiber sensor are attributed to the MOF's ability to pre-concentrate molecules, which can be imaged as a sponge "soaking" up molecules into its pores. Additionally, the MOF sponge selectively absorbs molecules to fit into its pores and rejects unfit ones, which enhance the sensor's sensitivity and reliability. The researchers also found the sensor's absorption process of RhB dye is non-reversible, which is ideal for long-term monitoring where RhB concentrations are minimal and a marked increase in the dye's concentration would be recognized easily, said Collins. "While the non-reversible mode suits many applications, we have also developed methods of releasing absorbed molecules by shining light down the fiber, which would make the sensor re-usable," Collin said. The researchers' next step is to further explore the MOF-fiber sensor's responses to other heavy organic contaminants such as pesticides and herbicides in water. More information: M. Nazari, M. Forouzandeh, C. Divarathne, F. Sidiroglou, M. Martinez, K. Konstas, B. Muir, A. Hill, M. Duke, M. Hill and S. Collins. "UiO-66 MOF End-Face-Coated Optical Fiber in Aqueous Contaminant Detection" Optics Letters 41, 1696 – 1699. DOI: 10.1364/OL.41.001696


News Article | October 6, 2016
Site: phys.org

The formation of quasiparticles, such as polarons, in a condensed-matter system usually proceeds in an extremely fast way and is very difficult to observe. In Innsbruck, Rudolf Grimm's physics research group, in collaboration with an international team of theoretical physicists, has simulated the formation of polarons in an ultracold quantum gas in real time. The researchers have published their findings in the journal Science. The concept of quasiparticles is a powerful tool to describe processes in many-body quantum systems, such as solid-state materials. For example, when an electron moves through a solid, it generates polarization in its environment because of its electrical charge. This "polarization cloud" moves together with the electron and the resulting "dressed electron" can be theoretically described as quasiparticle or a polaron. "You could picture it as a skier on a powder day," says Grimm. "The skier is surrounded by a cloud of snow crystals. Together they form a system that has different properties than the skier without the cloud." The challenge in an experiment is to measure the quasiparticles. "These processes last only attoseconds, which makes a time-resolved observation of their formation extremely difficult," explains Grimm. His research group uses ultracold quantum gases for simulations to study the many-body physics of complex quantum systems. Ultracold quantum gases are an ideal experimental platform to study physical phenomena in solid-state materials and also exotic states of matter, for example neutron stars. Because of the well-controlled environment, the scientists are able to create many-body states and manipulate interactions between particles in these gases. Rudolf Grimm's research group, working at the Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, and the Institute for Experimental Physics, University of Innsbruck, is a leader in this research field. In collaboration with theoretical physicists from Harvard University, the TU Munich and Monash University in Australia, the researchers have now studied quasiparticle dynamics in real time. In a vacuum chamber, using laser trapping techniques, the researchers created an ultracold quantum gas made up of lithium atoms and a small sample of potassium atoms in the center. For both types of atoms they used isotopes of fermionic nature, which belong to the same fundamental class as electrons. Magnetic fields were used to tune interactions, which produced Fermi polarons, i.e. potassium atoms embedded in a lithium cloud. "In condensed matter, the natural time scale of these quasiparticles is on the order of 100 attoseconds," explains Grimm. "We simulated the same physical processes at much lower densities. Here, the formation time for polarons is a few microseconds." "We developed a new method for observing the 'birth' of a polaron virtually in real time," says quantum physicists Grimm. Looking into the future, he says: "This may turn out to be a very interesting approach to better understand the quantum physical properties of ultrafast electronic devices." More information: Ultrafast many-body interferometry of impurities coupled to a Fermi sea. Marko Cetina, Michael Jag, Rianne S. Lous, Isabella Fritsche, Jook T. M. Walraven, Rudolf Grimm, Jesper Levinsen, Meera M. Parish, Richard Schmidt, Michael Knap, Eugene Demler. Science. science.sciencemag.org/cgi/doi/10.1126/science.aaf5134


News Article | March 1, 2017
Site: www.businesswire.com

WALTHAM, Mass.--(BUSINESS WIRE)--Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, today announced it has elected Dion Weisler to its board of directors, effective today. Mr. Weisler’s appointment brings the total number of Thermo Fisher board members to 12. Mr. Weisler has been president and chief executive officer of HP Inc. since November 2015, following the separation of Hewlett-Packard into two independent companies. He also serves on the HP board of directors. Prior to that, Mr. Weisler was executive vice president of Hewlett-Packard’s Printing and Personal Systems Business for four years. During his more than 25 years of experience in the information technology industry, Mr. Weisler has led businesses in at least eight international markets. Before joining HP, he was with Lenovo as vice president and chief operating officer of its Product and Mobile Internet Digital Home groups, and led the company’s Global Transaction Model worldwide. Previously, Mr. Weisler served as general manager of Lenovo’s operations in Korea, Southeast Asia, Australia and New Zealand. Earlier in his career, he was general manager at Telstra Corporation, Australia’s leading telecommunications company, and also had an 11-year career at Acer Inc., where he became managing director of the company’s operations in the United Kingdom after establishing and leading the company’s businesses in Central and Eastern Europe. He holds a Bachelor’s Degree in Applied Science - Computing from Monash University in Australia. “We are delighted to welcome Dion to our board,” said Jim Manzi, chairman of the board of Thermo Fisher Scientific. “He brings many years of experience in international business and digital technology strategies. Given his background and global perspective, Dion will add valuable insights as we focus more and more on leveraging new digital capabilities to create a differentiated experience for our customers.” Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, with revenues of $18 billion and more than 55,000 employees globally. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics and increase laboratory productivity. Through our premier brands – Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific and Unity Lab Services – we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive support. For more information, please visit www.thermofisher.com.


News Article | November 30, 2016
Site: www.eurekalert.org

Monash University scientists have played a key role in discovering the origin of filter feeding in baleen whales -- the largest animal known to have ever existed. The discovery is detailed in a paper co-written with international researchers and palaeontologists from Museum Victoria. 'Alfred' the 25- million-year-old fossilised whale skull was unveiled at the Museum today. "Alfred shows how ancient baleen whales made the evolutionary switch from biting prey with teeth to filtering using baleen," said Monash Science Senior Research Fellow, Dr Alistair Evans, one of the authors of the paper. "They first became suction feeders. Feeding in this way resulted in reduced need for teeth, so over time their teeth were lost before baleen appeared." There has been a lot of mystery around how and when baleen first formed. "But we now have long-sought evidence of how whales evolved from having teeth to hair-like baleen - triggering the rise of the biggest beasts on the planet," said Dr Evans. Nick-named 'Alfred', the fossil skull is from an extinct group of whales called aetiocetids, which despite having teeth were an early branch of the baleen whale family tree. Alfred's teeth show exceptionally rare evidence of feeding behaviour suggesting an entirely new evolutionary scenario - before losing teeth and evolving baleen, these whales used suction to catch prey. Today's baleen whales -- such as the Blue and Humpback -- don't have teeth. Instead, they have evolved the hair-like structure called baleen that allows them to filter huge amounts of tiny plankton, like krill, from seawater. "Filter-feeding is the key to the baleen whales' evolutionary success," said Dr Erich Fitzgerald, Senior Curator of Vertebrate Palaeontology, Museums Victoria. "But what has really eluded scientists since Charles Darwin is exactly how whales made the complex evolutionary change from biting prey with teeth to filtering plankton using baleen." This unusual type of tooth wear is only seen in a few living marine mammals (such as walrus) that use a back-and-forth movement of their tongue to suck in prey, and incidentally rough material like sand. Alfred shows how ancient baleen whales made the evolutionary switch from biting prey with teeth to filtering using baleen: they first became suction feeders. Feeding in this way resulted in reduced need for teeth, so over time their teeth were lost before baleen appeared. The research team is now uncovering the rest of Alfred's skeleton, as well as other fossils from Australia that provide exciting insights on how baleen whales began. The research was supported by a Marie Sklodowska-Curie Global Postdoctoral fellowship to Felix Marx, an Australian Research Council Future Fellowship to Alistair Evans, an Australian Research Council Linkage Project to Alistair Evans and Erich Fitzgerald and an Australian Postgraduate Award to Travis Park. 'Alfred' was collected and generously donated to Museums Victoria by J. and G. Goedert, S. Benham and D. Reed. The research is published in Museums Victoria's peer-reviewed scientific journal Memoirs of Museums Victoria and available via the link https:/


News Article | December 15, 2016
Site: www.materialstoday.com

The porous crystals known as metal-organic frameworks (MOFs) consist of metallic intersections connected by organic molecules. Thanks to their high porosity, MOFs have an extremely large surface area: a teaspoonful of MOF has the same surface area as a football pitch. The large number of pores situated in an extremely small space offer room for ‘guests’, allowing MOFS to be used for gas storage or as a ‘molecular gate’ for separating chemicals. But MOFs have a much greater potential, and this is what Paolo Falcaro from the Institute of Physical and Theoretical Chemistry (PTC) at the Graz University of Technology (TU Graz) in Austria wants to unlock. “MOFs are prepared by self-organization,” Falcaro explains. “We don’t have to do anything other than mix the components, and the crystals will grow by themselves. However, crystals grow with random orientation and position, and thus their pores. Now, we can control this growth, and new properties of MOFs will be explored for multifunctional use in microelectronics, optics, sensors and biotechnology.” In a paper in Nature Materials, Falcaro and his team report a method for growing MOFs on a comparatively large surface area of 1cm2 that offers an unprecedented level of control over the orientation and alignment of the crystals. Other members of the team include Masahide Takahashi from Osaka Prefecture University in Japan and researchers from the University of Adelaide, Monash University and the Commonwealth Scientific and Industrial Research Organisation (CSIRO), all in Australia. Incorporating functional materials into these precisely-oriented crystals allows the creation of anisotropic materials, which are materials with directionally-dependent properties. In the paper, the research team describes incorporating fluorescent molecules into a precisely-oriented MOF. Just by rotating the film, the fluorescent signal can be turned ‘on’ or ‘off’, producing an optically-active switch. “This has many conceivable applications and we’re going to try many of them with a variety of different functionalities,” says Falcaro. “One and the same material can show different properties through different orientations and alignments. Intentional growth of MOFs on this scale opens up a whole range of promising applications which we’re going to explore step by step.” A major aim of Falcaro and his team at TU Graz is developing MOFs for biotechnological applications. “We are trying to encapsulate enzymes, proteins and even DNA in MOFs and to immunize their activity against fluctuations in temperature,” he says. “The crystalline structure surrounding the ‘guest’ in the pore has a protective effect, like a tough jacket. We want to check out the possibilities more accurately.” This story is adapted from material from TU Graz, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.


News Article | March 17, 2016
Site: www.sciencenews.org

Brazil, now a poster child for mosquito-borne virus spread, was once a model for mosquito eradication. “It was amazing,” says Dan Strickman, medical entomologist with the Bill and Melinda Gates Foundation. The Aedes aegypti mosquito, today identified by epidemiologists as one of the carriers of the Zika virus, was attacked in the 1930s with the simple tools then available. By 1965, the mosquito was certified as eradicated from Brazil and 17 other countries in the Americas (but not the United States). The feat took ferocious effort, but as the threat dwindled, so did money and the political will to stay vigilant. Whether eradication would even be possible now is unclear. But the question of how to cope with Ae. aegypti has taken on new urgency as that mosquito species sweeps Zika virus through South and Central America and into parts of North America. Known as the yellow fever mosquito, Ae. aegypti can also spread dengue, chikungunya and West Nile viruses (SN: 6/13/15, p. 16). Here's what we know about Zika How Zika became the prime suspect in microcephaly mystery It’s “the most difficult mosquito in the Americas to control,” says Michael Doyle, director of mosquito control for the Florida Keys. The mosquito’s resistance to major pesticides and its unusual biology foil many standard control measures. Some scientists have developed high-tech control approaches. Other specialists are going back to the basics to search for biological vulnerabilities that have been overlooked. Casual slappers of mosquitoes tend to lump all of them into one annoying category, but there are 3,500 or so species, with a wide range of idiosyncrasies. Some species, for instance, don’t drink blood. As a group, though, mosquitoes are among the most dangerous animals on Earth, claiming more than 400,000 lives a year just from spreading malaria. Researchers propose that several species might spread Zika, depending on location: Ae. hensilli was suspected in a previous outbreak on Yap in Micronesia and Ae. polynesiensis in French Polynesia. In the Americas, epidemiologists are watching two widespread invasives: the Asian tiger mosquito Ae. albopictus (SN: 6/29/13, p. 26) as well as the notorious Ae. aegypti. A forest-dwelling form of Ae. aegypti, native to Africa, frequents tree holes and sucks blood from animals. The worldwide invaders, however, have become domesticated. “They bite almost exclusively humans; they live almost exclusively within feet of humans,” Doyle says. For many mosquitoes, blood is for motherhood, usually one drink per batch of eggs. The insects meet everyday energy needs with plant sugars such as flower nectar. Ae. aegypti females, however, sip blood often, raising the chances of passing on disease. That’s because they’re unusually adept at extracting energy from blood instead of nectar, Laura Harrington, who studies mosquito biology at Cornell University, and her colleagues found. A common way to fight bloodsuckers is spraying pesticides from trucks or aircraft. But spraying often does little to Ae. aegypti holing up in houses, resting on clothing in closets or hiding under beds. And don’t count on nighttime protection from bed nets. Ae. aegypti readily bite during the day. In a test near Juazeiro, Brazil, the density of adult Aedes aegypti mosquitoes dwindled (black line) with releases of genetically sterilized Oxitec male mosquitoes. In untreated areas, egg-laying (blue line) continued. To fight such a foe, crews start by trying to kill larvae before they reach vampire age. Mosquitoes generally go through their first life stage in water, and Ae. aegypti needs only a little containerful. So Doyle sends inspectors on house-by-house quests for stray minipools: in a bucket, a Fritos bag, old tires, a kayak and plant saucers by the dozens. And that could be in just one yard. His difficulties make a fine case study in how hard — and expensive — fighting a human-specialist mosquito can be. The human-versus-mosquito battle isn’t all door-to-door. The company Oxitec, based in the United Kingdom, engineered male Ae. aegypti mosquitoes to carry genes that cause their offspring to die (SN: 7/14/12, p. 22). Using an old insect-control strategy, mass releases of dysfunctional males seduce wild females and, in time, shrink the problem population. Experimental releases of Oxitec’s genetically modified Ae. aegypti males have reduced the size of mosquito populations by more than 80 percent in a test site of about 5.5 hectares in a suburb of Juazeiro, Brazil. The Brazilian government has approved these engineered mosquitoes for widespread use. Oxitec has applied for U.S. Food and Drug Administration approval to do a similar test in the Florida Keys. On March 11, the FDA released a draft statement predicting “no significant impact” to the environment from the test (SN Online: 3/11/16). Efforts to genetically sterilize mosquitoes may improve with advances in CRISPR/Cas9 techniques to cut and paste genes (SN: 12/12/15, p. 16). And an advance in the genetics of sex determination last year opens new possibilities for refining sterile-male releases. What’s called an M factor determines maleness in certain insects, and for the first time in any mosquito, researchers determined the sequence of the genetic components of Ae. aegypti’s M factor. Manipulating it to produce entire generations of only males could have many uses, says Virginia Tech’s Zach Adelman. In a different approach to reengineering mosquitoes (SN: 7/14/12, p. 22), researchers with the international consortium called Eliminate Dengue are testing a nongenetically modified mosquito in Brazil among other places. Instead of wiping out a population, the goal is to reduce its disease-spreading power. Infection with a strain of Wolbachia, bacteria common in insects, can render these mosquitoes less likely to transmit dengue virus. A paper due out soon will show that the Wolbachia-carrying mosquitoes are also less likely than uninfected ones to transmit chikungunya, as well as  Zika, says Wolbachia project leader Scott O’Neill at Monash University in Melbourne, Australia. What interests Cornell’s Harrington are the undiscovered mosquito-fighting targets. Her lab studies courtship and reproduction in mosquitoes. “I really believe that’s where their Achilles’ heel is,” she says. Courtship among Ae. aegypti is unusual and more complex than anyone had imagined, Harrington, her student Lauren Cator and colleagues reported in 2009. The scent of a human host attracts amorous male mosquitoes, which fly nearby until a female arrives looking for a blood meal. Male mosquitoes’ wide, feathery antennae pick up harmonic overtones of the whine of female wingbeats. The mosquitoes then synchronize one of the wingbeat overtones. “They’re singing to each other,” says Ethan Degner, a Harrington graduate student. Perhaps there’s a way to disrupt this courtship. Another of the Harrington lab’s findings might be more immediately relevant. Conventional wisdom is that Ae. aegypti mosquitoes mate only once in their lives. Degner offered lab females a second chance to mate, but with a collaborating lab’s genetically engineered males that produce fluorescent red sperm. In lab conditions, a low percentage of females showed red in their reproductive tracts, indicating they mated twice, Degner and Harrington reported online February 15 in the American Journal of Tropical Medicine and Hygiene. This result agrees with observations of what looked like occasional second matings in the wild. With millions of dollars going into mass releases of sterile competitors to local fertile males, female willingness takes on new importance. If biologists come up with some new way to eradicate Ae. aegypti, then humankind would have to decide whether to use it. Aside from moral questions, removing any species from an ecosystem can have unexpected risks and consequences. The weighing of arguments will differ species by species, even for mosquitoes. But the human-seeking form is a relative newcomer to the Americas. So in this era of Zika and other rampant mosquito-borne diseases, whether to blast this mosquito out of the hemisphere, should it ever be possible, might not be a difficult decision at all. This article appears in the April 2, 2016 issue with the headline, "Science versus mosquito: Controlling one of the world’s most dangerous animals takes on new urgency."


Porous crystals called metal-organic frameworks (MOFs) consist of metallic intersections with organic molecules as connecting elements. Thanks to their high porosity, MOFs have an extremely large surface area. A teaspoonful of MOFs has the same surface area as a football pitch. These countless pores situated in an extremely small space offer room for "guests" and can, for example, be used for gas storage or as "molecular gate" for separation of chemicals. But MOFs have a much greater potential and it is what Paolo Falcaro from TU Graz's Institute of Physical and Theoretical Chemistry (PTC) wants to unlock. "MOFs are prepared by self-organisation. We don't have to do anything other than mix the components, and the crystals will grow by themselves. However, crystals grow with random orientation and position, and thus their pores. Now, we can control this growth, and new properties of MOFs will be explored for multifunctional use in microelectronics, optics, sensors and biotechnology." In the current issue of Nature Materials, a research activity lead by Paolo Falcaro and Masahide Takahashi (Osaka Prefecture University - Japan) together with Australian colleagues at the University of Adelaide, Monash University and The Commonwealth Scientific and Industrial Research Organisation (CSIRO) describes a method of growing MOFs on a comparatively large surface area of one square centimetre rapidly achieving an unprecedented controlled orientation and alignment of the crystals. The big advantage of precisely oriented crystals in MOFs makes every materials scientist excited. Functional materials can be infiltrated in the pores of the crystals to generate anisotropic materials; in other words, materials with directionally dependent properties. In the journal Nature Materials, the research team shows how the controlled synthesis of a MOF film behaves in the presence of fluorescent dye. Just by rotating the film, the fluorescent signal is turned "on" or "off" and an optically active switch has been created. Paolo Falcaro: "This has many conceivable applications and we're going to try many of them with a variety of different functionalities. One and the same material can show different properties through different orientations and alignments. Intentional growth of MOFs on this scale opens up a whole range of promising applications which we're going to explore step by step." A major aim of Paolo Falcaro and his team at TU Graz is the development of MOFs for biotechnological applications: "We are trying to encapsulate enzymes, proteins and even DNA in MOFs and to immunise their activity against fluctuations in temperature. The crystalline structure surrounding the "guest" in the pore has a protective effect, like a tough jacket. We want to check out the possibilities more accurately," explains Falcaro. Explore further: 'Seeding' the next generation of smart materials More information: Paolo Falcaro et al. Centimetre-scale micropore alignment in oriented polycrystalline metal–organic framework films via heteroepitaxial growth, Nature Materials (2016). DOI: 10.1038/nmat4815


MINNEAPOLIS, Dec. 07, 2016 (GLOBE NEWSWIRE) -- Sun BioPharma, Inc. (OTCQB:SNBP), a biopharmaceutical company developing disruptive therapeutics for the treatment of patients with pancreatic diseases, today announced that the Data Safety Monitoring Board (DSMB), an independent group of medical experts closely monitoring the Company’s clinical study, has completed its safety review of the data from cycle 1 dosing of the fourth cohort of patients. As a result of this review by the DSMB, Sun Biopharma has begun recruiting patients for the fifth patient cohort in the dose escalation phase of the study. The Company currently expects to begin dosing patients in the fifth cohort as early as December 12, 2016, which is approximately 60 days after the fourth patient cohort commenced dosing. “Our safety data from this Phase 1 Study continue to be encouraging,” said Suzanne Gagnon, M.D., Sun BioPharma’s Chief Medical Officer. “Once again there were no dose-limiting toxicities in the fourth group and no drug-related serious adverse events occurred. Patients are tolerating SBP-101 very well! We continued to see no evidence of bone marrow toxicity. Based on the unconditional approval by the DSMB we will immediately commence with the recruitment of the fifth cohort of patients using a higher dose of SBP-101.” “We are encouraged by the enthusiasm for our Phase 1 trial at the study sites as we continued the rapid pace of enrollment with our fourth cohort allowing us to move quickly into the fifth cohort. Through our first four cohorts, we have dosed and captured data from 15 patients, some of whom have completed multiple dosing cycles. This represents a significant base of safety data for SBP-101,” commented David B. Kaysen, President and CEO of Sun BioPharma. “We are extremely grateful for the dedication of the clinical teams at our study sites and for the patients who have volunteered to be part of our study.” Two of the Company’s study sites are in the United States: Mayo Clinic Scottsdale and HonorHealth, both in Scottsdale, AZ and three study sites are in Australia: The Ashford Cancer Centre in Adelaide, the Olivia Newton-John Cancer & Wellness Centre and Box Hill Hospital at Monash University, both in Melbourne. About SBP-101 SBP-101 is a first-in-class, proprietary, polyamine compound designed to exert therapeutic effects in a mechanism specific to the pancreas. Sun BioPharma originally licensed SBP-101 from the University of Florida in 2011. The molecule has been shown to be highly effective in human pancreatic cancer models, demonstrating superior activity to existing FDA approved chemotherapy agents. Combination therapy potential has also been shown for pancreatic cancer. SBP-101 is expected to differ from current pancreatic cancer therapies in that it specifically targets the exocrine pancreas and has shown efficacy against primary and metastatic disease in animal models of human pancreatic cancer. Therefore management believes that SBP-101 may effectively treat both primary and metastatic pancreatic cancer, while leaving the insulin-producing islet cells and non-pancreatic tissue unharmed. About the Phase 1 Safety Study of SBP-101 in Patients with Previously Treated Pancreatic Cancer Sun BioPharma is currently conducting a clinical trial of SBP-101 in patients with previously treated locally advanced or metastatic pancreatic cancer. This is a Phase 1, first-in-human study with a dose-escalation phase and an expansion phase at the anticipated recommended treatment dose. This study is being conducted at clinical sites in both the United States and Australia including Mayo Clinic Scottsdale and HonorHealth in Scottsdale, AZ, the Austin Health Cancer Trials Centre and the Box Hill Hospital in Melbourne, Australia and the Ashford Cancer Centre in Adelaide, Australia. About Sun BioPharma Sun BioPharma Inc. is a clinical-stage biopharmaceutical company developing disruptive therapeutics for urgent unmet medical needs. The Company’s development programs target diseases of the pancreas, including pancreatic cancer and pancreatitis; the Company’s initial product candidate is SBP-101 for the treatment of patients with pancreatic cancer. SBP-101 was invented by Ray Bergeron, Ph.D. Distinguished Professor Emeritus, University of Florida. Sun BioPharma has scientific collaborations with pancreatic disease experts at Cedars Sinai Medical Center in Los Angeles, the University of Miami, the University of Florida, the Mayo Clinic Scottsdale, the Austin Health Cancer Trials Centre and the Box Hill Hospital in Melbourne, Australia and the Ashford Cancer Centre in Adelaide, Australia. Further information can be found at: www.sunbiopharma.com. Sun BioPharma’s common stock is currently quoted on the OTCQB tier of the over-the-counter markets administered by the OTC Markets Group, Inc. under the symbol: SNBP. Forward-Looking Statements Safe Harbor Statements pertaining to future financial and/or operating results, future growth in research, technology, clinical development, and potential opportunities for Sun BioPharma, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute “forward-looking statements” For purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1955. Any statements that are not historical fact (including, but not limited to statements that contain words such as “will,” “believes,” “may,” “anticipates,” “expects,” “estimates” or “plans”) should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, our need to obtain additional capital to support our business plan, which may not be available on acceptable terms or at all, risks inherent in the development and/or commercialization of potential products, uncertainty in the pace of enrollment and results of clinical trials or regulatory approvals and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect Sun BioPharma and its business, particularly those disclosed from time to time in Sun BioPharma’s filings with the Securities and Exchange Commission. Shareholders and other readers are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they are made. Sun BioPharma disclaims any intent or obligation to update these forward-looking statements.


News Article | November 22, 2016
Site: www.eurekalert.org

An Australian-first study conducted by Monash University has found that from 2003-2013 nearly five deaths per 1000 employed Australian health care professionals were caused by drugs, with a significant association between specific professions and drug type. These deaths were more likely to involve females in their mid-40s, with a mental health condition, professional and/or personal stress and the intent to self-harm. With the aim of identifying best approaches to health care professionals' drug use and their mental health care needs, the major study investigated drug-caused deaths of health care professionals including physicians, nurses, dentists, psychologists and psychiatrists, physiotherapists, pharmacists, paramedics and veterinarians. A total of 404 drug-caused HCP deaths were reported to Australian coroners during this investigated timeframe, averaging 37 deaths per year. Head of the Drug Harm Prevention Unit at Monash's Department of Forensic Medicine, Dr Jennifer Pilgrim said the study found a significant association between specific professions and drugs of choice. "The mortality rate was highest in veterinarians, of which most involved death by suicide using potent barbiturates usually used in animal euthanasia. "Our research also observed some different trends to existing literature on occupation-specific drug choice. For example, nurses, dentists and pharmacists reportedly gravitate towards misuse of opioids however in this study, these health care professionals misused opioids along with other substances, namely benzodiazepines," Dr Pilgrim said. A mental health diagnosis and/or previous self-harm was reported in almost half the cohort and 50 per cent of the deaths were intentional self-harm deaths. The use of psychoactive drugs, both licit and illicit, is reportedly higher among medical practitioners than in the general population - a trend that was observed in this study. Numerous factors put health care professionals at a higher risk of substance abuse and premature death including high-stress jobs, access to controlled substances, long hours of practice and constant contact with the critically ill. "By analysing deaths reported to the coroner, the study provides new data of confirmed drug misuse in health care professionals and avoids the limitations of studies that rely on self-reports of drug use. "We hope that our research can help inform best approaches to health care professionals' drug use and mental health care needs," Dr Pilgrim said.


News Article | November 28, 2016
Site: www.eurekalert.org

A research team led by University of Minnesota School of Physics and Astronomy Professor Yong-Zhong Qian uses new models and evidence from meteorites to show that a low-mass supernova triggered the formation of our solar system. The findings are published in the most recent issue of Nature Communications, a leading scientific journal. About 4.6 billion years ago, a cloud of gas and dust that eventually formed our solar system was disturbed. The ensuing gravitational collapse formed the proto-Sun with a surrounding disc where the planets were born. A supernova--a star exploding at the end of its life-cycle--would have enough energy to compress such a gas cloud. Yet there was no conclusive evidence to support this theory. In addition, the nature of the triggering supernova remained elusive. Qian and his collaborators decided to focus on short-lived nuclei present in the early solar system. Due to their short lifetimes, these nuclei could only have come from the triggering supernova. Their abundances in the early solar system have been inferred from their decay products in meteorites. As the debris from the formation of the solar system, meteorites are comparable to the leftover bricks and mortar in a construction site. They tell us what the solar system is made of and in particular, what short-lived nuclei the triggering supernova provided. "This is the forensic evidence we need to help us explain how the solar system was formed," Qian said. "It points to a low-mass supernova as the trigger." Qian is an expert on the formation of nuclei in supernovae. His previous research has focused on the various mechanisms by which this occurs in supernovae of different masses. His team includes the lead author of the paper, Projjwal Banerjee, who is a former Ph.D. student and postdoctoral research associate, and longtime collaborators Alexander Heger of Monash University, Australia, and Wick Haxton of the University of California, Berkeley. Qian and Banerjee realized that previous efforts in studying the formation of the solar system were focused on a high-mass supernova trigger, which would have left behind a set of nuclear fingerprints that are not present in the meteoric record. Qian and his collaborators decided to test whether a low-mass supernova, about 12 times heavier than our sun, could explain the meteoritic record. They began their research by examining Beryllium-10, a short-lived nucleus that has 4 protons (hence the fourth element in the periodic table) and 6 neutrons, weighing 10 mass units. This nucleus is widely distributed in meteorites. In fact the ubiquity of Beryllium-10 was something of a mystery in and of itself. Many researchers had theorized that spallation--a process where high-energy particles strip away protons or neutrons from a nucleus to form new nuclei--by cosmic rays was responsible for the Beryllium-10 found in meteorites. Qian said that this hypothesis involves many uncertain inputs and presumes that Beryllium-10 cannot be made in supernovae. Using new models of supernovae, Qian and his collaborators have shown that Beryllium-10 can be produced by neutrino spallation in supernovae of both low and high masses. However, only a low-mass supernova triggering the formation of the solar system is consistent with the overall meteoritic record. "The findings in this paper have opened up a whole new direction in our research," Qian said. "In addition to explaining the abundance of Beryllium-10, this low-mass supernova model would also explain the short-lived nuclei Calcium-41, Palladium-107, and a few others found in meteorites. What it cannot explain must then be attributed to other sources that require detailed study." Qian said the group would like to examine the remaining mysteries surrounding short-lived nuclei found in meteorites. The first step, however is to further corroborate their theory by looking at Lithium-7 and Boron-11 that are produced along with Beryllium-10 by neutrino spallation in supernovae. Qian said they may examine this in a future paper and urged researchers studying meteorites look at the correlations among these three nuclei with precise measurements. The research is funded by the Department of Energy Office of Nuclear Physics. Qian, Banerjee, and Heger are also scientific participants of the Joint Institute for Nuclear Astrophysics-Center for the Evolution of the Elements, a National Science Foundation Physics Frontier Center. To read the full paper, entitled "Evidence from stable isotopes and Be-10 for solar system formation triggered by a low-mass supernova," visit the Nature Communications website.


With an upcoming publication in the Worldwide Leaders in Healthcare, Nyree L. Parker, RN/Clinical Nurse Specialist, Dip. Health Science, BN, Graduate Certificate of Health Education, Graduate Certificate Health Promotion, Graduate Diploma Critical Care/Emergency, MN, Master Degree in Disaster Health, joins the prestigious ranks of the International Nurses Association. She is a Registered Nurse with twenty-four years of experience in her field and extensive expertise in all facets of nursing, including emergency care and Disaster Health. Nyree is currently serving patients as Clinical Nurse Specialist in the Emergency Department and Emergency Management and BCP Consultant in the Facilities Management Department at Peninsula Health in Victoria, Australia. This involves policy and procedure/plan writings for i.e. mass casualties incidents, CBR decontamination processes, pandemics, heatwaves, bushfires and severe weather impacting on the public hospital organisation. Furthermore, she works as Assistance in Care Emergency Volunteer Coordinator in the Emergency Departments at Peninsula Health Frankston Hospital in Frankston, Victoria, Australia. Nyree acquired her graduate diploma in applied sciences in 1991 at Monash University, where she also received her bachelor degree of nursing in 1992. She also obtained a diploma of critical care nursing majoring in Emergency care (1997), a master degree of nursing (2001), and a Master Degree in emergency Disaster Health (2013) at Monash University. In 1998, Nyree earned a postgraduate certificate in health promotion from Deakin University. She is a Clinical Nurse Specialist and was a Trauma Nursing Core Course Instructor as well as a member of the Australian College of Emergency Nursing, the Victoria Hospital Management Forum, the Royal College of Nursing Australia, the Australian Nurses Federation, and an active member of the Nursing Section of the World Association of Disaster Emergency Medicine. Furthermore, she was honoured with the Dux of Group Award in 2009 and was a volunteers with St. John’s Ambulance. Nyree credits her success to being a third generation nurse in her family. She also has acted as a Clinical Instructor of Emergency Management and Critical Care at Monash University. Nyree is aiming to commence her PhD in Disaster Health looking at topics of climate change implications on emergency nurses and the role of an Emergency Management Consultant in the hospital environment. In her spare time, Nyree enjoys reading the Great Hospital Emergency Disaster Relief Journal and the Emergency Medicine News Journal. She also dedicates to dog walking and antique shopping and driving her 1948 Morris car! Learn more about Nyree here: http://inanurse.org/network/index.php?do=/4125803/info/ and read her upcoming publication in the Worldwide Leaders in Healthcare.


News Article | December 15, 2015
Site: cleantechnica.com

With a successful climate accord reached in Paris, Australia faces a tough road ahead to even begin to contribute effectively to halting global warming. As we have already seen, Australia saw a mild change in energy policy throughout 2015 which allowed its representatives to attend and contribute to the Paris negotiations without looking like the world’s most petulant supporter of coal mining ever. Whether Australia’s representatives in Paris managed to contribute anything helpful is another question, but with a legally-binding climate accord reached for 2020 onwards, Australia’s energy and climate policies will need to be radically improved if it is to meet its contribution to the global agreement. “Although imperfect, the deal struck in Paris is likely to require Australia to significantly strengthen it’s 2030 emissions reduction commitment in the 5 yearly review points, starting in 2020,” said Kobad Bhavnagri, Head of Australia, Bloomberg New Energy Finance, via email this week. “It also naturally implies that global usage of coal will need to be curbed if the stated ambitions are to be met, which will reduce demand for Australia’s exports. However the agreement falls well short of actually requiring global fossil fuel usage to be curbed via any concrete measures.” Australia has been one of the world’s leading coal miners for decades, and under former-Prime Minister Tony Abbott, coal mining was only further entrenched into the country’s economy. There are several small signposts that things may be changing — and a few more that suggests nothing has changed at all, with the country’s Environment Minister approving the construction of a new coal mine earlier this month — but without concrete measures being forced upon Australia to curb its production of coal, things are going to take even longer to change. “Australia’s current pledge of 26-28% below 2005 levels by 2030 is — like most countries — not consistent with the agreed goal of limiting global warming to 2°C above pre-industrial levels,” Kobad Bhavnagri continued. “It will thus likely need to be deepened towards the 45-65% range recommended by the Climate Change Authority as Australia’s fair contribution in reaching this temperature goal. “Deeper cuts in emissions imply that Australia will also need to hasten the deployment of renewable energy, make more concrete steps to reduce usage of fossil-fuels, especially coal, and develop more robust, scalable and non-government funded carbon policy if the emissions reductions are to be achieved domestically. This could involve a 2030 Renewable Energy Target, specific policy aimed at retiring coal-fired generators and increased regulations on, or pricing of, carbon emissions.” The transition to renewable energy was similarly halted by former-Prime Minister Tony Abbott, and has similarly seen a shift in attention, following numerous public declarations of support from Australia’s new Prime Minister, Malcolm Turnbull, and his Environment Minister, Greg Hunt, and Minister for Resources, Energy and Northern Australia, Josh Frydenberg. “We have already seen huge changes recently in the way we produce and use energy, and this is just the beginning. New technologies such as battery storage will completely revolutionise the way we think about energy within a decade,” said Kane Thornton, Chief Executive of Australia’s Clean Energy Council. “The deal announced in Paris will accelerate a change that is already happening – a shift towards a zero-carbon energy sector in the decades ahead. It is no longer a question of whether or not this will happen. The question is now about what we need to do to prepare for the changes that have already begun.” This is not just a view held by incumbents in the renewable energy industry itself — though Kane Thornton goes on to say that “Australia is blessed with some of the best renewable energy resources in the world, and we have a once-in-a-generation opportunity to create the jobs of the 21st Century,” highlighting the huge role Australia could have with the right policy. The Managing Director of one of Australia’s leading energy suppliers, Origin Energy, is of a similar mind to those in the renewable energy industry. “The targets set in Paris will frame action on climate change and support the development of sound and enduring policy for the decades ahead,” said Grant King, Origin’s Managing Director (PDF). “The next step is for Australia to develop the right settings for our own economy and our own conditions.” More important, Mr King went on to highlight the role Australia’s energy sector will be faced with in the next fifteen years. “Australia’s 2030 target will require a significant transformation of the energy sector. Given Origin’s track record in renewables and strategic interests in gas-fired generation, we’re ready and willing to lead the response, and look forward to working with government, industry and the broader community on the right policies and initiatives to achieve or better the target.” Origin was the world’s first energy company to sign on to all seven of the We Mean Business coalition’s commitments on climate change, and further went on to announce that it would exit from all coal-fired generation by 2030. Image Credit: Leard State Forest, via Flickr; Monash University, via Flickr    Get CleanTechnica’s 1st (completely free) electric car report → “Electric Cars: What Early Adopters & First Followers Want.”   Come attend CleanTechnica’s 1st “Cleantech Revolution Tour” event → in Berlin, Germany, April 9–10.   Keep up to date with all the hottest cleantech news by subscribing to our (free) cleantech newsletter, or keep an eye on sector-specific news by getting our (also free) solar energy newsletter, electric vehicle newsletter, or wind energy newsletter.  


In an experiment carried out at MPQ, the fastest ever switching of electric currents in semiconductors has been achieved with few-cycle laser pulses. GARCHING, 21-Nov-2016 — /EuropaWire/ — Modern electronics and digital technologies rely on the control of electric current in semiconductor devices, from computers to smartphones and amplifiers. An international study by scientists from Monash University (Melbourne, Australia) and the Max Planck Institute of Quantum Optics (Garching, Germany) lays foundations for a dramatic performance increase of semiconductor-based signal-processing technologies. (Optica, 14 November 2016, DOI: 10.1364/OPTICA.3.001358). The work, published in Optica, found that electric current can be turned on and off in a semiconductor (gallium nitride in this case) at unprecedented speeds by using engineered light as a means of control. These findings pave the way for the design of optically controlled semiconductor electronic devices that can operate at frequencies much larger than those demonstrated until now. “The time it takes to switch electric current on and off in a semiconductor, determines the rate at which electronic devices can perform. We found that by using few-cycles laser pulses with engineered optical field waveforms – which are the fastest tools available to researchers – electric current can be controlled in a semiconductor at rates thousands of times higher than those achieved in state-of-the-art electronics,” said Monash researcher and ARC Future Fellow, Dr. Agustin Schiffrin, the lead investigator of the study. “We successfully investigated how these devices operate in various regimes by comparing the circuits with two different materials: gallium nitride and fused silica. In both cases, laser field induces interference of electronic excitations and allows controlling them on a femtosecond timescale. Our current setup performs at much lower field intensities than those required for dielectrics, so it can work even with non-amplified laser pulse sources,” said Dr. Stanislav Kruchinin, a researcher from MPQ. This work showcases the fastest control of electric currents ever measured in a semiconductor, opening the door to the design of novel optically controlled electronics.


News Article | December 1, 2016
Site: www.eurekalert.org

Washington, DC--A large international survey of women with a common condition called polycystic ovary syndrome (PCOS), which is characterized by reproductive and metabolic problems, found nearly two in three were dissatisfied with the length of time they waited and the number of healthcare professionals they had to see before they received a diagnosis, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. Nearly half of the 1,385 women surveyed internationally saw three or more healthcare providers before they were diagnosed. The diagnostic process took more than two years for a third of the survey respondents. PCOS is a chronic disorder that impacts numerous aspects of a woman's health. Women who have the condition face an increased risk of developing metabolic problems such as diabetes, reproductive issues such as infertility, and psychological issues including anxiety and depression. Women are diagnosed when they have at least two of the three key features of the condition: Between 9 percent and 18 percent of women of childbearing age have PCOS, according to currently accepted Rotterdam diagnosis, international prevalence studies and guidelines. "Given the prevalence of PCOS, it is important for women and healthcare professionals to be more aware of the condition," said one of the study's authors, Helena Teede, FRACP, PhD, of Monash University in Melbourne, Australia. "Despite the misleading name, PCOS is not primarily an ovarian condition, but instead is a hormonal disturbance with diverse health effects that is largely inherited. The process of diagnosing PCOS needs to be improved, and the diverse set of metabolic, reproductive and psychological features need to be understood and addressed." In the cross-sectional study, women with PCOS who were at least 18 years old and had been diagnosed with the condition by a physician were asked to complete an online questionnaire. Researchers built on initial studies in Australia and worked with two large PCOS patient support groups--U.S.-based PCOS Challenge and U.K.-based Verity--to distribute the questionnaire to their website visitors, mailing lists and social media followers with an international reach. "We were interested in women's diagnosis experience and satisfaction with information and educational materials they received at the time of diagnosis," Teede said. A total of 1,550 women responded to the survey, but 165 were excluded because they didn't meet the eligibility criteria or they completed less than half of the questions. Respondents lived in 32 countries. Reports of months- or years-long waits for a diagnosis and visits to multiple healthcare professionals were common among the survey respondents. Women who waited more than six months for a diagnosis were more likely to report being dissatisfied with the process than those who were diagnosed in a shorter period. Less than a quarter of the survey respondents were satisfied with the information they received about common treatments for PCOS, including lifestyle management and medications, when they were diagnosed with the condition. More than half reported that they didn't receive any information about long-term PCOS complications or emotional counseling or support. "Our findings show women are dissatisfied with the diagnosis experience and that there are clear opportunities to improve awareness, diagnosis and health outcomes for women with PCOS," Teede said. "The survey results, along with a new international guideline and awareness ad education initiative, will be used to inform international efforts to improve PCOS education and care." The study, "Delayed Diagnosis and a Lack of Information Associated with Dissatisfaction in Women with Polycystic Ovary Syndrome," will be published online at http://press. , ahead of print. Other authors of the study include: Melanie Gibson-Helm of Monash University in Melbourne, Australia; Andrea Dunaif of Northwestern University's Feinberg School of Medicine in Chicago, IL; and Anuja Dokras of the University of Pennsylvania in Philadelphia, PA. The research received no direct funding. Gibson-Helm and Teede are research fellows with Australia's National Health and Medical Research Council. For more information on PCOS, check out the Hormone Health Network's digital toolkit. Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions. The Society, which is celebrating its centennial in 2016, has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www. . Follow us on Twitter at @TheEndoSociety and @EndoMedia.


News Article | December 13, 2016
Site: www.prnewswire.co.uk

HOUSTON, Dec. 13, 2016 /PRNewswire/ -- Vinson & Elkins announces the promotion of eight lawyers to its partnership, effective January 1, 2017: Mark Brasher, Jason McIntosh, Becky Petereit, Bailey Pham, Simon Rootsey, Lande Spottswood, Thomas Zentner and Craig Zieminski. "Our new partners are outstanding attorneys who have shown tremendous dedication to the firm and its clients," said V&E Chairman Mark Kelly. "From the courtroom to the boardroom, each of these exceptional lawyers has demonstrated a high level of skill in their respective practice area. We are thrilled to call them partners." The new partners span six of the firm's key practice areas, including complex commercial litigation, energy transactions and projects, finance, mergers and acquisitions and capital markets, restructuring and reorganization and tax. "We are proud to welcome these talented and accomplished lawyers to the firm's partnership," said V&E Managing Partner Scott Wulfe. "We are grateful for the contributions these deserving attorneys have made to V&E and we look forward to their continued success." The following is a list of V&E's new partners by practice: Craig Zieminski, Dallas. Zieminski's practice focuses on representing companies and their directors in lawsuits brought by Delaware stockholders, master limited partnership (MLP) unitholders and deal partners. Zieminski has helped secure key victories for major energy clients. He played a significant role on the V&E team that represented Energy Transfer Equity in its successful defense of litigation concerning a $37.7 billion merger with The Williams Companies. Zieminski also helped win dismissal of a stockholder suit challenging C&J Energy's $2.9 billion merger with a unit of Nabors Industries. He has also helped companies defeat expedited lawsuits seeking to enjoin major transactions, such as a lawsuit that sought to enjoin Targa Resources' $6.7 billion merger with an affiliated entity and a lawsuit that attempted to enjoin Inergy's $2 billion merger with an affiliated partnership. Zieminski received his law degree from Stanford Law School in 2008 and graduated from Southern Methodist University in 2005 with degrees in economics and accounting. Mark Brasher, Houston. Brasher's practice focuses on project development and related business transactions concerning domestic and international energy and infrastructure projects. His clients include a wide range of participants in the oil and gas industry, renewable energy companies, power producers, infrastructure developers, banks and private equity funds. Brasher is the lead attorney advising Noble Energy on the project development aspects of its 20Tcf Leviathan natural gas project, offshore Israel. He counsels a number of Occidental Petroleum's business units in relation to projects in the United States and the Middle East. He is also an integral member of the V&E team representing Texas Central Partners in connection with the Dallas to Houston high-speed rail project. Recently, Brasher played a key role advising Riverstone in its acquisition from Kinder Morgan of a 50 percent interest in the Utopia Pipeline Project, a common carrier pipeline that will connect ethane gas sources from Ohio to Sarnia, Canada. Brasher received his LL.M. from the University of Texas at Austin in 2011 and his LL.B. from Monash University in Australia in 2006. Bailey Pham, Dallas. Pham's practice focuses on representing financial institutions, corporate lenders and businesses in all types of financing arrangements, including acquisition loans, asset-based loans and energy loans. She assists in the representation of both agent banks, including JPMorgan Chase Bank, N.A. and Wells Fargo Bank, N.A., and borrowers in domestic and international syndicated loan transactions, particularly in secured, leveraged credits covering various markets and industries, including retail, manufacturing and oilfield services. Pham has also advised on a number of high-stakes deals, including Holly Corporation's $7 billion merger with Frontier Oil Corporation, which created one of the largest independent refiners in the United States. Pham received her law degree from Southern Methodist University in 2008 and her bachelor's and master's degrees in accountancy from Wake Forest University in 2002. Simon Rootsey, London. Rootsey's practice focuses on cross-border M&A and private equity, advising on all aspects of private cross-border M&A, private equity transactions, joint ventures and public takeovers. His experience includes advising the Vitol Group on its recent sale of a 50% stake in the VTTI Group to Buckeye Partners for US$1.15 billion, and advising the Vitol Group and Helios Investment Partners in their US$1 billion acquisition of an 80 percent stake in the African downstream oil operations of Royal Dutch Shell plc, and acquisition of a 60 percent stake in the Nigerian downstream oil operations of Oando plc. On the private equity side, he advises leading private equity houses based in Europe and the United States investing in the U.K., Europe and Africa. Rootsey is a graduate of the University of Western Australia, where he received both his Bachelor of Laws (Honours) and his Bachelor of Commerce. Lande Spottswood, Houston. Spottswood advises public and private companies, including MLPs, private equity investors and their portfolio companies, in connection with mergers, acquisitions, dispositions, restructurings, spinoffs, joint ventures and other strategic transactions. She also advises on public company change-of-control transactions. Her experience also includes advising issuers in initial public offerings, as well as public and private offerings of equity and debt securities, and on general corporate matters. She has teamed on some of V&E's largest recent deals, including representing Sunoco Logistics in its pending $22 billion acquisition of Energy Transfer; Plains GP Holdings in its simplification transaction with Plains All American Pipeline for $7.2 billion; Nexeo Solution's $1.575 billion merger with WL Ross Holding Corp.; and Western Refining's $2.4 billion merger agreement with Northern Tier Energy LP. Spottswood received her law degree from Harvard Law School in 2008 and her bachelor's degree from Harvard College in 2005. Thomas Zentner, Houston. Zentner's practice focuses on corporate finance and securities law, including securities offerings, mergers and acquisitions and general corporate representation. His capital markets experience includes representation of both issuers and underwriters in initial public offerings, as well as public and private offerings of equity and debt securities. He also works with public and private companies, including private equity funds and their portfolio companies, in connection with mergers, acquisitions, dispositions and strategic investments. Zentner advised Anadarko Petroleum Corporation in its $2.1 billion public offering of common stock and in its $3 billion offering of senior notes. He also advised Targa Resources Corp. in its $360 million initial public offering and in its $6.7 billion acquisition of Targa Resources Partners in an all stock-for-unit transaction. Zentner received his law degree in 2008 and bachelor's degree in 2005, both from the University of Texas at Austin. Becky Petereit, Dallas. Petereit's practice focuses on all aspects of restructuring and reorganization work, including the representation of debtors, lenders, creditors, landlords and trustees. She represents clients in lawsuits, contested matters, adversary proceedings and other actions before federal district courts, state courts and bankruptcy courts with respect to all types of litigation arising from financially distressed situations. She has represented debtors in complex cross-border insolvency proceedings; tried several fraudulent transfer actions (both jury and bench trials); represented the administrative agent for syndicated secured lenders who were owed approximately $7 billion in a Chapter 11 case of one of the largest publishers of yellow pages directories in the United States; and represented the liquidating trustee of a bankrupt financial services firm in litigation against its former officers and directors. Petereit received her J.D. from University of California, Los Angeles School of Law in 2005 and her bachelor's degree from University of Delaware in 2002. Jason McIntosh, Houston. McIntosh focuses on tax planning with respect to complex international and domestic transactions. His experience spans a broad range of industries, including energy, banking and finance, power generation, petrochemicals, shipping and transport, aircraft leasing and sales, manufacturing and distribution of consumer products and real estate. Among his notable representations, McIntosh was part of the V&E team advising Riverstone Holdings in the formation and $525 million (aggregate) initial capitalization of Sierra Oil & Gas, Mexico's first independent exploration and production company. He recently represented Buckeye Partners in structuring its $1.15 billion acquisition of a 50% interest in VTTI BV, which operates one of the world's largest global energy terminal businesses. McIntosh received his law degree from the University of Virginia School of Law and his bachelor's degree from the University of Nebraska-Lincoln. Vinson & Elkins LLP is an international law firm with approximately 700 lawyers across 16 offices worldwide. For more information, please contact Carrie Dugas at +1.713.758.4330. This communication may be considered advertising under law regulating the use of e-mail. This communication is provided by Vinson & Elkins LLP for educational and informational purposes only and is not intended, nor should it be construed, as legal advice.


News Article | October 7, 2016
Site: www.rdmag.com

The formation of quasiparticles, such as polarons, in a condensed-matter system usually proceeds in an extremely fast way and is very difficult to observe. In Innsbruck, Rudolf Grimm's physics research group, in collaboration with an international team of theoretical physicists, has simulated the formation of polarons in an ultracold quantum gas in real time. The researchers have published their findings in the journal Science. The concept of quasiparticles is a powerful tool to describe processes in many-body quantum systems, such as solid-state materials. For example, when an electron moves through a solid, it generates polarization in its environment because of its electrical charge. This "polarization cloud" moves together with the electron and the resulting "dressed electron" can be theoretically described as quasiparticle or a polaron. "You could picture it as a skier on a powder day," said Grimm. "The skier is surrounded by a cloud of snow crystals. Together they form a system that has different properties than the skier without the cloud." The challenge in an experiment is to measure the quasiparticles. "These processes last only attoseconds, which makes a time-resolved observation of their formation extremely difficult," said Grimm. His research group uses ultracold quantum gases for simulations to study the many-body physics of complex quantum systems. Ultracold quantum gases are an ideal experimental platform to study physical phenomena in solid-state materials and also exotic states of matter, for example neutron stars. Because of the well-controlled environment, the scientists are able to create many-body states and manipulate interactions between particles in these gases. Rudolf Grimm's research group, working at the Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, and the Institute for Experimental Physics, University of Innsbruck, is a leader in this research field. In collaboration with theoretical physicists from Harvard University, the TU Munich and Monash University in Australia, the researchers have now studied quasiparticle dynamics in real time. In a vacuum chamber, using laser trapping techniques, the researchers created an ultracold quantum gas made up of lithium atoms and a small sample of potassium atoms in the center. For both types of atoms they used isotopes of fermionic nature, which belong to the same fundamental class as electrons. Magnetic fields were used to tune interactions, which produced Fermi polarons, i.e. potassium atoms embedded in a lithium cloud. "In condensed matter, the natural time scale of these quasiparticles is on the order of 100 attoseconds," added Grimm. "We simulated the same physical processes at much lower densities. Here, the formation time for polarons is a few microseconds." "We developed a new method for observing the 'birth' of a polaron virtually in real time," said quantum physicists Grimm. Looking into the future, he says: "This may turn out to be a very interesting approach to better understand the quantum physical properties of ultrafast electronic devices."


News Article | December 22, 2016
Site: www.eurekalert.org

An international team of scientists has identified variants of the gene EBF3 causing a developmental disorder with features in common with autism. Identification of these gene variants leads to a better understanding of these complex conditions and opens the possibility of diagnosing other previously undiagnosed patients with similar clinical disorders. The study appears in the American Journal of Human Genetics. "We investigate the genetic causes of complex neurological conditions of various types, such as autism spectrum disorders and intellectual disability," said first author Dr. Hsiao-Tuan Chao, postdoctoral research fellow of pediatric-neurology at Baylor College of Medicine. "Such conditions are long-lasting, manifest very early in life and range from mild to severe. They can affect different neurological functions; however, sometimes they have overlapping similarities. For many of these conditions there is no definite diagnosis, treatments are limited and there is no cure." Chao and colleagues have taken a step toward better understanding some of these conditions. They discovered new mutations of the gene EBF3 in three patients presenting with a newly described syndrome. "The patients' main features include developmental delay, coordination problems, limited facial expressions at an early age and abnormal verbal communication and social behaviors. They can also present with repetitive motor movements, high threshold to pain and cognitive impairments," said Chao. "This newly described syndrome has many similarities with what we see in autism spectrum disorders, but also important differences." The researchers used whole exome sequencing, a laboratory technique that allows the identification of all the genes in an individual's genome. In the patients, they identified two new variants of the gene EBF3 that were not present in the patients' parents. Mutations of EBF3 are rare in the general population but more common in a population of individuals with autism spectrum disorders and intellectual disability. "The gene is known to be essential for normal development of the nervous system," said Chao. "It is one of the key factors involved in how neurons develop and connect with each other, but has not been studied in detail. In animal models, mutations that cause the gene to lose its function result in death of the embryo. EBF3 had never before been associated with a disease." That the three patients with developmental disorders have mutations in the same gene is not sufficient proof that the mutations cause the condition. To determine whether the mutations can cause neurodevelopmental problems the scientists tested the effect of the mutations in the laboratory fruit fly, Drosophila melanogaster. "We genetically engineered fruit flies to carry the mutations present in the patients," said Chao. "The defective gene product was not able to carry on the functions of the normal gene; the effect is so severe that the fly embryos do not survive. On the other hand, when we introduced the normal version of the human gene, the files developed normally." The identification of variants of EBF3 that can cause neurodevelopmental disorders has improved the genetic diagnosis of these conditions."We are able to provide a genetic diagnosis for patients who did not know the cause of their condition," said Chao. "This provides some relief to their parents and the possibility of reaching for support from a community of parents whose children are affected by similar disorders. In addition, by gaining a better understanding of how people are affected by EBF3 dysfunction, we as physicians are better equipped to prognosticate the developmental outcomes for these children." "Being able to see our research in fruit flies help us diagnose a patient in our own hospital was very gratifying. Knowing the genetic basis allows for more insights into this disorder of the brain," said Dr. Michael F. Wangler, assistant professor of molecular and human genetics at Baylor, a senior author on the paper. Other contributors to this work include Mariska Davids, Elizabeth Burke, John G. Pappas Jill A. Rosenfeld, Alexandra McCarty, Taylor Davis, Lynne Wolfe, Camilo Toro, Cynthia Tifft, Fan Xia, Nicholas Stong, Travis K. Johnson, Coral G. Warr, Members of the UDN, Shinya Yamamoto, David Adams, Thomas C. Markello, William A. Gahl, Hugo J. Bellen and May Christine V. Malicdan. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children's Hospital, National Institutes of Health, National Human Genome Research Institute, New York University, Baylor Genetics Laboratories, Columbia University, the Howard Hughes Medical Institute and Monash University. This work was supported in part by U54NS093793, R24OD022005, and R01GM067858, by the Intramural Research Program of the National Human Genome Research Institute and by the Common Fund, Office of the Director of the National Institutes of Health. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the clinical exome sequencing offered at Baylor Genetics.


News Article | October 28, 2015
Site: www.nature.com

Bonn climate talks A draft text for a global greenhouse-gas-reduction agreement was drawn up at talks in Bonn, Germany, between 19 and 23 October. During the talks, Sri Lanka and the United Arab Emirates became the 155th and 156th countries to submit pledges for mandatory domestic action, which will be at the core of any United Nations climate agreement made in Paris this December. Meanwhile, in a briefing released on 21 October, the International Energy Agency said that US$13.5 trillion need to be invested globally in energy-efficiency and low-carbon technologies over the next 15 years to compensate for the planned reduction in fossil-fuel use. Marine reserve The Congress of Palau approved plans to create a 500,000-square-kilometre marine reserve around the Pacific island nation on 22 October. The announcement came in the same week as an analysis showed that the amount of the world’s oceans that is ‘strongly protected’, with some fishing allowed, or ‘fully protected’ has increased from 0.1% to 1.6% in the past decade (J. Lubchenco and K. Grorud-Colvert Science 350, 382–383; 2015). The area that is afforded some level of protection is 3.5%, still well short of the internationally agreed target of 10% by 2020. Climate regulation Pakistani Prime Minister Nawaz Sharif endorsed proposals to regulate hydrofluorocarbons (HFCs) under the Montreal Protocol on Substances that Deplete the Ozone Layer. Commonly used as refrigerants, HFCs were created as alternatives to chlorofluorocarbons, which damage the ozone layer — but HFCs are still powerful greenhouse gases. Sharif declared his support in a joint statement with US President Barack Obama on 22 October after a visit to the White House. At a meeting in Dubai on 1–5 November, parties to the Montreal Protocol will consider amendments intended to phase out HFCs. Hurricane Patricia smashes records Hurricane Patricia broke a slew of meteorological records just before it pounded the west coast of Mexico on 23 October (pictured in an infrared satellite image). The category-5 storm intensified rapidly before making landfall, with wind speeds of almost 324 kilometres per hour and a central pressure of 87.9 kilopascals, making it the strongest hurricane ever recorded in the Western Hemisphere. Heavy rains raked the coast between the cities of Puerto Vallarta and Manzanillo, causing landslides, but the devastation was less than feared because the most intense winds and storm surge struck in relatively lightly populated areas. Afghan quake At least 300 people have been killed, with the number expected to rise, after a magnitude-7.5 earthquake hit northeast Afghanistan on 26 October. The strong quake, which according to the US Geological Survey struck 76 kilometres south of the city of Fayzabad at a depth of around 210 kilometres, caused landslides and avalanches in the remote Hindu Kush region and sent tremors that were felt in neighbouring Pakistan and as far away as Delhi in India. Earthquakes in the tectonically active region result from the collision of the Indian subcontinent with central Asia. Science subpoenaed The chairman of a US congressional committee has issued a subpoena requesting to see all documents and communications related to a June study by federal scientists showing that global warming has continued unabated over the past 15 years. Lamar Smith (Republican, Texas), chair of the Committee on Science, Space, and Technology, issued the subpoena on 13 October after the National Oceanic and Atmospheric Administration refused to provide internal communications. The subpoena came to light publicly on 23 October after Democrat Bernice Johnson from Texas objected to the “illegitimate harassment of our Nation’s research scientists”. Meltdown payout Japan’s Ministry of Health, Labour and Welfare has said that it will pay industrial-accident compensation to a member of the clean-up crew who worked on the damaged Fukushima Daiichi nuclear power plant and who has recently developed cancer. According to the Japanese media, the ministry said on 20 October that the causal link between the worker’s exposure and his leukaemia was “unclear”. The government could be exposed to many more claims. Thousands of workers took part in the clean-up operations after three reactors went into meltdown in March 2011, following an earthquake and a tsunami. Mars lander Europe’s first Mars rover, ExoMars, looks set to land on a vast, clay-rich plain called Oxia Planum, the European Space Agency (ESA) announced on 21 October. ExoMars, a joint endeavour between ESA and Russia’s space agency Roscosmos, will land in 2019 and is designed to look for evidence of life. The craft’s instruments will include a drill capable of burrowing 2 metres into the Martian surface. Oxia Planum was picked from a shortlist of four potential landing sites (see Nature 508, 19–20; 2014); the agencies will confirm the choice six months before the mission’s 2018 launch. Lisa Jardine dies Historians of science, politicians and researchers paid tribute on 26 October after it was announced that historian Lisa Jardine (pictured) had died. Jardine’s hugely varied career included work on eighteenth-century scientist Robert Hooke and the scientific revolution. She chaired Britain’s Human Fertilisation and Embryology Authority between 2008 and 2014, during a period when the agency led the way in regulating mitochondrial replacement and other cutting-edge scientific advances. Mitochondrial-replacement therapy was made legal in Britain in February 2015. Science top job Australia’s new prime minister, Malcolm Turnbull, appointed engineer Alan Finkel as chief scientist on 27 October. Finkel, who co-founded the popular-science magazine Cosmos and is currently chancellor of Monash University, is a vocal advocate of nuclear power as a carbon-neutral energy source, and of the need for policies to combat climate change. Media reports suggest that Finkel’s appointment may signal a policy shift in a country in which nuclear energy is banned and whose previous prime minister was a notorious climate-change sceptic. Finkel said in a press conference that he wanted to see the end of the use of coal, oil and gas in the country, with renewables and nuclear power being explored to achieve zero-emissions energy. Telescope closed The United Kingdom Infrared Telescope (UKIRT) atop Mauna Kea in Hawaii will be permanently shuttered, making it the third closed to accommodate the next-generation Thirty Meter Telescope (TMT). The University of Hawaii took over the UKIRT — the most scientifically productive ground-based telescope worldwide — from the UK Science and Technology Facilities Council last year. The decision to close stems from a long-term decommissioning plan, which identifies the UKIRT as a site to be restored to its natural state. Hawaii’s governor has called for closure of one-quarter of Mauna Kea’s 13 telescopes by the time the TMT becomes operational in the 2020s (see Nature 526, 24–28; 2015). 23andMe revamp Genetic-testing company 23andMe, based in Mountain View, California, launched a revamped consumer test on 21 October. The product offers information about a customer’s genetic-carrier status for 36 diseases, marking the first time that 23andMe has been allowed to provide medically relevant results since the US Food and Drug Administration banned the inclusion of detailed predictive information in tests in November 2013. Previously, the product tested for 240 health conditions. With a few exceptions, carrier-status tests do not say anything about the health of the individual and are mostly for rare diseases. See go.nature.com/5vicei and page 609 for more. The number of US biomedical postdocs fell 5.5% between 2010 and 2013, to just over 38,000, with losses getting bigger each year, according to an analysis (H. H. Garrison et al. FASEB J. http://doi.org/8m3; 2015). The main reason for the drop seems to be fewer positions for postdocs, but the time that individuals spend as postdocs is also falling. From 1979 to 2010, the number of US postdocs in the biomedical sciences rose steadily, from just over 10,000 to more than 40,000. See go.nature.com/fbkl5y for more. 1–4 November Researchers hoping to catch up on the latest in cancer genomics can do so at a European Molecular Biology Laboratory conference in Heidelberg, Germany. go.nature.com/p5uqwp 1–4 November The Geological Society of America holds its annual meeting in Baltimore, Maryland. go.nature.com/ks35w9


News Article | October 26, 2016
Site: www.nature.com

The scientific enterprise is stuck in a catch-22. Researchers are charged with advancing promising new questions, but receive support and credit only for revisiting their past work. For example, while studying the epidemiology of HIV and tuberculosis, one of us (T.O.) realized that many people with these infectious diseases in urban areas also have non-infectious conditions, including hypertension and obesity. Hardly anyone was examining how and why, or investigating strategies for integrated prevention and management. Her proposals to research these topics were not well received by peer reviewers, who commented that she had not asked such questions before. We, the authors of this Comment, met earlier this year, having been selected by the World Economic Forum as part of a group of scientists under the age of 40 who “play a transformational role in integrating scientific knowledge into society for the public good”. Through hours of discussion, we realized that we share many challenges, despite the recognition we have achieved and the diverse disciplines and geographical regions we represent. Most striking are the barriers to achieving impact. Our research often led us to questions that had greater potential than our original focus, typically because these new directions encompassed the complexities of society. We realized that changing tack could lead to more important work, but the policies of research funders and institutions consistently discourage such pivots. When reviewers assess grants or academic performance, they focus largely on track records in a particular field. Young scientists, who must focus on developing their careers, are thus discouraged from exploration. Our own experiences provide a glimpse of the well-intentioned forces that can keep researchers from trying other paths (see ‘Four tales of turning’). This challenge is not new. Physicist-turned-structural biologist Venkatraman Ramakrishnan, who is president of the Royal Society, worked for several years in a job with funding that was contingent on a steady stream of publications. This forced him to ask safe but incremental questions. To pursue what became his Nobel-prizewinning work (on the structure of the ribosome), he moved to another institution where he could ask the questions that interested him, irrespective of the chances for publication. As he describes in his Nobel biography, the decision required an international move and a large pay cut. For every story like this, there are too many where investigators have made a rational choice not to pursue areas outside their core expertise. We spend so much effort trying to find our way that we risk losing the drive to apply skills to the broader world, and stick instead to the less-fulfilling security of ‘productivity’. More bold is Eva Alisic, a psychologist and senior research fellow at Monash University Accident Research Centre in Victoria, Australia. Earlier this year, Alisic began studying how refugee children from places such as Syria cope with trauma. Her institute has supported her so far, but this research is not the safest choice for a conventional career trajectory. She told us that she would rather give up an academic career than end this line of study. If we feel that we must leave academia to better contribute to society, the scholarly endeavour is compromised. We are not saying that scientists should dabble. Executing a pivot should still require conviction and risk, but the current strictures are too tight. Enabling early-career researchers to change trajectories is necessary to encourage the highest-impact research. Theories of brain plasticity and team productivity support this. Alongside specialization, diverse and varied experiences foster discoveries and promote the decision-making skills that are needed to lead research ( & Psychol. Aging 23, 692–701; 2008). Grant programmes do exist in some parts of the world to promote highly innovative projects for promising early- and mid-career researchers. Examples include the European Research Council’s Starting and Consolidator grants and the International Research Scholars programme, which is jointly funded by the Howard Hughes Medical Institute, the Bill & Melinda Gates Foundation, the Wellcome Trust and the Calouste Gulbenkian Foundation. These pockets of funding are not enough. In 2015, the US National Institutes of Health (NIH) awarded 78 grants specifically for high-risk research. That same year, it gave out more than 15,000 conventional awards. These are typically granted to applicants with strong preliminary data in fields where they are already recognized as experts. Although it is logical to assess a researcher’s body of work over time, universities, research councils and other funding bodies should create a formal mechanism that explicitly accommodates pivots. If candidates can provide a convincing case for their own credibility and for studying new questions, they should be able to get support. Two simple changes could make a big difference. Create a ‘pivot narrative’. Funding applications should give researchers who are in the midst of a shift an opportunity to describe their rationale. The significance and potential of the proposed work should be assessed alongside the researcher’s proven abilities for research in other fields. Alisic, for example, could explain how her work with young people sensitized her to a growing need for evidence-based interventions to treat trauma in children fleeing conflict. A ‘pivot narrative’ would also explain dry spells and the lack of a track record in the proposed area. The simple step of adding a text box to an application form could expand scientists’ willingness to explore, and help assessors to support such exploration. Revise peer review. There is little to no emphasis on peer-review training. Equipping scientists with skills for more nuanced appraisal will help them to consider varied attributes, particularly how to address complex societal challenges and to evaluate broader interdisciplinary questions. This could eventually change institutional cultures. The greatest risk is that innovation will be stifled by failing to invest in the best emerging scientists, who are approaching the peak of their creativity.


HOUSTON -- A Phase III clinical trial involving 101 centers in 21 countries revealed the monoclonal antibody blinatumomab to be more effective than standard chemotherapy for treatment of advanced acute lymphoblastic leukemia (ALL). Study findings were published in the March 1 online issue of the New England Journal of Medicine. The study, led by The University of Texas MD Anderson Cancer Center, randomly assigned 405 patients 18 years or older to groups receiving either blinatumomab or chemotherapy. Overall survival was significantly longer in the blinatumomab group with median survival of 7.7 months versus four months for those on chemotherapy. Remission rates within 12 weeks after treatment began were higher in the blinatumomab group with complete remission rates of 34 percent reported in this group versus 16 percent for those on chemotherapy. The study also showed that patients treated with blinatumomab had a lower rate of adverse effects. While the prognosis for newly diagnosed ALL has improved over the last three decades with intensive chemotherapy regimens resulting in complete remission rates of 85 to 90 percent and long-term survival rates of 30 to 50 percent, most adult patients with the B-cell precursor ALL, the most common form, ultimately relapse and die from disease complications. The accepted standard of care is to help the patient maintain remission long enough to receive allogeneic or donor stem-cell transplantation, considered the most effective therapy. "Among adults with relapsed ALL, remission rates are18 to 44 percent with standard chemotherapy but the duration of remission is typically short. A major goal for these patients is to induce remission with sufficient duration to prepare for stem-cell transplantation," said Hagop Kantarjian, M.D., chair of the Department of Leukemia, and lead author for the New England Journal of Medicine paper. "In this study, 24 percent of patients in each treatment group underwent allogeneic stem cell transplantation." Blinatumomab, developed by Amgen, works by binding simultaneously to specific cytotoxic T-cells and B-cells, which allows the patient's healthy T-cells to recognize and eliminate cancer stem cells called blasts. "The activity of an immune-based therapy such as blinatumomab, which depends on functioning T-cells for its activity, provides encouragement that responses may be further enhanced and made durable with additional immune activation strategies," said Kantarjian. The study, designed and funded by Amgen, did not include patients who had other active cancers, relevant central nervous system conditions, autoimmune disease, acute or chronic graft-versus-host disease, chemotherapy or radiotherapy within two weeks before the study, donor stem cell transplantation within 12 weeks before the trial or autologous stem cell transplantation within six week preceding the study. Patients who received immunotherapy in the month before the trial or who were undertaking other investigational treatments were also excluded. Authors from the paper include investigators from City of Hope National Medical Center, Duarte, Calif.; Amgen, Thousand Oaks, Calif. and Washington D.C.; Frankfurt am Main University Hospital Schleswig Holstein, Kiel, Germany; Mediziniche Klinik und Poliklinik II, Universitätsklinikums, Wurzburg, Germany; Princess Margaret Cancer Centre, Toronto; Hôpital Maisonneuve-Rosemont, Montreal; Universitat Autonoma de Barcelona and the University of Valencia, Spain; Alfred Hospital and Monash University, Melbourne, Australia; Hôpital Saint-Louis, Paris; Centre Hospitalier Lyon Sud, Pierre-Benite, France; Universitá Sapienza di Roma, Rome; Aziendo Unitá Locale Socio Sanitaria 12 Veneziana Ospedale Dell Angelo, Venice, Italy; Universitá Statale di Milano, Milan; Ankara Universitesi, Ankara, and Dokuz Eylul Universitesi Tip Facultesi, Izmir, both in Turkey; Instytut Hematologii i Transfuzjologii and Centrum Medcyzne Kszta?cenia Podyplomowego, Warsaw, Poland; and the University of Washington Medical Center, Seattle.


News Article | November 7, 2016
Site: www.eurekalert.org

A new comprehensive study of Australian natural hazards paints a picture of increasing heatwaves and extreme bushfires as this century progresses, but with much more uncertainty about the future of storms and rainfall. Published today (Tuesday 8 November) in a special issue of the international journal Climatic Change, the study documents the historical record and projected change of seven natural hazards in Australia: flood; storms (including wind and hail); coastal extremes; drought; heatwave; bushfire; and frost. "Temperature-related hazards, particularly heatwaves and bushfires, are increasing, and projections show a high level of agreement that we will continue to see these hazards become more extreme into the 21st century," says special issue editor Associate Professor Seth Westra, Head of the Intelligent Water Decisions group at the University of Adelaide. "Other hazards, particularly those related to storms and rainfall, are more ambiguous. Cyclones are projected to occur less frequently but when they do occur they may well be more intense. In terms of rainfall-induced floods we have conflicting lines of evidence with some analyses pointing to an increase into the future and others pointing to a decrease. "One thing that became very clear is how much all these hazards are interconnected. For example drought leads to drying out of the land surface, which in turn can lead to increased risk of heat waves and bushfires, while also potentially leading to a decreased risk of flooding." The importance of interlinkages between climate extremes was also noted in the coastal extremes paper: "On the open coast, rising sea levels are increasing the flooding and erosion of storm-induced high waves and storm surges," says CSIRO's Dr Kathleen McInnes, the lead author of the coastal extremes paper. "However, in estuaries where considerable infrastructure resides, rainfall runoff adds to the complexity of extremes." This special issue represents a major collaboration of 47 scientists and eleven universities through the Australian Water and Energy Exchange Research Initiative, an Australian research community program. The report's many authors were from the Centre of Excellence for Climate System Science, the CSIRO, Bureau of Meteorology, Australian National University, Curtin University, Monash University, University of Melbourne, University of Western Australia, University of Adelaide, University of Newcastle, University of New South Wales, University of Tasmania, University of Western Australia and University of Wollongong. The analyses aim to disentangle the effects of climate variability and change on hazards from other factors such as deforestation, increased urbanisation, people living in more vulnerable areas, and higher values of infrastructure. "The study documents our current understanding of the relationship between historical and possible future climatic change with the frequency and severity of Australian natural hazards," says Associate Professor Westra. "These hazards cause multiple impacts on humans and the environment and collectively account for 93% of Australian insured losses, and that does not even include drought losses. "We need robust decision-making that considers the whole range of future scenarios and how our environment may evolve. The biggest risk from climate change is if we continue to plan as though there will be no change. One thing is certain: our environment will continue to change." Some of the key findings from the studies include: Associate Professor Seth Westra Special Issue Editor School of Civil, Environmental and Mining Engineering University of Adelaide Phone: 61-8-8313-1538. Mobile: 61-0-414-997-406 seth.westra@adelaide.edu.au


News Article | November 23, 2015
Site: phys.org

The researchers from the University of New South Wales, Swinburne University of Technology, Monash University and the University of Parma in Italy used a chemical and biochemical sensing technique called surface-enhanced Raman spectroscopy (SERS), which is used to understand more about the make-up of materials. They were able to greatly amplify the technique's performance by taking advantage of metal nanostructures, which help generate 'hotspots' in close proximity to the metal surfaces. The sensor was created using gold nanoparticles which self-assemble onto a gold- and silica-coated silicon base.  This approach means the nanoparticles find the perfect spacing to achieve lots of uniformly distributed hotspots on the surface. The hotspots also used a heat responsive polymer which acted as a gate to trap molecules, but importantly also allow them to be released down the track. "The sensor shows not only a good SERS reproducibility but also the ability to repetitively catch and release molecules for single-molecular sensing," postdoctoral fellow at Swinburne's Centre for Micro-Photonics, Dr Lorenzo Rosa, said. "This reversible trapping process makes it possible to detect an abundance of analytes in one measurement, but also to reuse the SERS substrate multiple times." The technique used in this work has various applications for other measurement and detection systems sensitive to humidity, pH and light. More information: Yuanhui Zheng et al. Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection, Nature Communications (2015). DOI: 10.1038/ncomms9797


News Article | November 7, 2016
Site: www.sciencedaily.com

A new comprehensive study of Australian natural hazards paints a picture of increasing heatwaves and extreme bushfires as this century progresses, but with much more uncertainty about the future of storms and rainfall. Published in a special issue of the international journal Climatic Change, the study documents the historical record and projected change of seven natural hazards in Australia: flood; storms (including wind and hail); coastal extremes; drought; heatwave; bushfire; and frost. "Temperature-related hazards, particularly heatwaves and bushfires, are increasing, and projections show a high level of agreement that we will continue to see these hazards become more extreme into the 21st century," says special issue editor Associate Professor Seth Westra, Head of the Intelligent Water Decisions group at the University of Adelaide. "Other hazards, particularly those related to storms and rainfall, are more ambiguous. Cyclones are projected to occur less frequently but when they do occur they may well be more intense. In terms of rainfall-induced floods we have conflicting lines of evidence with some analyses pointing to an increase into the future and others pointing to a decrease. "One thing that became very clear is how much all these hazards are interconnected. For example drought leads to drying out of the land surface, which in turn can lead to increased risk of heat waves and bushfires, while also potentially leading to a decreased risk of flooding." The importance of interlinkages between climate extremes was also noted in the coastal extremes paper: "On the open coast, rising sea levels are increasing the flooding and erosion of storm-induced high waves and storm surges," says CSIRO's Dr Kathleen McInnes, the lead author of the coastal extremes paper. "However, in estuaries where considerable infrastructure resides, rainfall runoff adds to the complexity of extremes." This special issue represents a major collaboration of 47 scientists and eleven universities through the Australian Water and Energy Exchange Research Initiative (www.ozewex.org), an Australian research community program. The report's many authors were from the Centre of Excellence for Climate System Science, the CSIRO, Bureau of Meteorology, Australian National University, Curtin University, Monash University, University of Melbourne, University of Western Australia, University of Adelaide, University of Newcastle, University of New South Wales, University of Tasmania, University of Western Australia and University of Wollongong. The analyses aim to disentangle the effects of climate variability and change on hazards from other factors such as deforestation, increased urbanisation, people living in more vulnerable areas, and higher values of infrastructure. "The study documents our current understanding of the relationship between historical and possible future climatic change with the frequency and severity of Australian natural hazards," says Associate Professor Westra. "These hazards cause multiple impacts on humans and the environment and collectively account for 93% of Australian insured losses, and that does not even include drought losses. "We need robust decision-making that considers the whole range of future scenarios and how our environment may evolve. The biggest risk from climate change is if we continue to plan as though there will be no change. One thing is certain: our environment will continue to change." Some of the key findings from the studies include: • Historical information on the most extreme bushfires -- so-called "mega fires" -- suggests an increased occurrence in recent decades with strong potential for them to increase in frequency in the future. Over the past decade major bushfires at the margins of Sydney, Canberra, and Melbourne have burnt more than a million hectares of forests and woodlands and resulted in the loss of more than 200 lives and 4000 homes. • Heatwaves are Australia's most deadly natural hazard, causing 55% of all natural disaster related deaths and increasing trends in heatwave intensity, frequency and duration are projected to continue throughout the 21st century. • The costs of flooding have increased significantly in recent decades, but factors behind this increase include changes in reporting mechanisms, population, land-use, infrastructure as well as extreme rainfall events. The physical size of floods has either not changed at all, or even decreased in many parts of the country.


News Article | October 27, 2015
Site: www.greentechmedia.com

New York Times: Despite Risks, Cuomo Bets on Solar Power to Lift Buffalo On the often cloudy shores of the Buffalo River, where a steel factory once thrived, lies the rising framework of one of New York’s most ambitious economic endeavors ever: a giant solar panel factory that the state says will be the largest of its kind in the Western Hemisphere. Gov. Andrew M. Cuomo has committed up to $750 million to the project, the biggest economic development effort he has undertaken in his five years as governor. In doing so, he has bet big not just on solar energy, a competitive and rapidly growing business, but also on the success of SolarCity, a fast-growing California company that will operate out of the factory that New York state will own. RenewEconomy: Australian Rooftop PV the Cheapest in the World, Finds IEA The cost of installing solar PV systems at Australian households and businesses is among the cheapest in the world, according to the latest global PV report from the International Energy Agency, released on Monday. The IEA’s 20th Trends in Photovoltaic Applications report shows that in Australia, as in many regions of the world, solar PV is now recognized as one of the least-cost options for electricity generation. Australia has some of the world’s cheapest installed system prices for grid-connected residential and commercial solar PV systems, at USD $1.76/W and $1.61/W, respectively. A vocal advocate of nuclear power in Australia, Dr. Alan Finkel, is set to be named as the country’s next chief scientist. The appointment of Finkel, an engineer and former neuroscience research fellow who has served as the chancellor of Monash University since 2008, is due to be announced by Malcolm Turnbull this week. It is not yet clear whether the prime minister’s choice, first reported by the Herald Sun on Monday, signals a new openness by the government to consider nuclear power generation. Vox's David Roberts: The House Science Committee Is Worse Than the Benghazi Committee Last Thursday, the nation watched with a mix of amusement and horror as the House Benghazi committee spent 11 hours grilling Hillary Clinton on a bizarre farrago of issues, many of which bore only tangential connection to the Benghazi attack. Over the past few weeks, the political narrative seems to have shifted from "Clinton in trouble" to "congressional witch hunt seeks to take down Clinton." Between McCarthy's accidental truth-telling, an ex-staffer confirming the worst reports about the committee, and another House Republican conceding the obvious, it has become clear that the Benghazi committee is a thoroughly partisan political endeavor. Opinion has turned, but Republicans are trapped. The thing is: The Benghazi committee is not even the worst committee in the House. I'd argue that the House science committee, under the chairmanship of Lamar Smith (R-TX), deserves that superlative for its open-ended, Orwellian attempts to intimidate some of the nation's leading scientists and scientific institutions. Climate Progress: Why This Republican Senator Just Came Out in Support of Obama’s Climate Rule As soon as the EPA’s Clean Power Plan hit the Federal Register, the rule was met with a flurry of lawsuits from fossil-fuel-producing states, utility groups and the coal industry. Republicans in Congress have pledged to block the rule, and could try to kill the rule through the Congressional Review Act this week. But in a chorus of Republican opposition, the Obama administration won a new ally over the weekend, when Kelly Ayotte (R-NH) became the first Republican senator to openly voice support for the Clean Power Plan.


News Article | November 10, 2016
Site: www.eurekalert.org

PHILADELPHIA - A five-year evaluation involving nearly 20,000 kindergarten through 12th grade under-resourced public school students shows that taking part in Project BioEYES, with one center based in Philadelphia at the Perelman School of Medicine at the University of Pennsylvania, increases students' science knowledge and positive attitudes about science. Younger students had the greatest attitude changes. The study covered five years and tested students before and after the one-week BioEYES program. The research is published in PLOS Biology. BioEYES uses live zebrafish to teach basic scientific principles, animal development, and genetics. The zebrafish embryo is clear, making it ideal for observations. As of spring 2016, 100,000 students and 1,400 teachers in six states and two countries have participated in the week-long program. Each BioEYES Center, including programs at Penn, Carnegie Institution, and the University of Utah or Monash University in Australia, is a partnership between local educators, school districts, and researchers. First author Jamie Shuda, EdD, director of Outreach and Education at Penn's Institute for Regenerative Medicine, and senior author Steve Farber, PhD, from the Carnegie Institution in Baltimore, started BioEYES as a grass-roots collaboration between a scientist and teacher. "We share a vision of providing high quality science experiences for all students and building sustainable teacher partnerships," Shuda said. "We expected the students to increase their understanding of the concepts they learned, but what is most promising is the positive increases in their attitudes towards the practice of science." Over the course of a week, students collect zebrafish embryos and watch them develop from a single cell to a swimming larva, with a beating heart and a distinct pigmentation pattern. Elementary students learn about human and fish anatomy, habitats, cells, and DNA. Middle school students identify the observable traits of their zebrafish offspring, while high school students delve into the ways modern scientists determine the genetic makeup of parents by studying their offspring. At week's end, students analyze these data and discuss their results with their classmates much the way scientists do. From 2010 to 2015, the team assessed students before and after a week-long experiment. They asked students to answer knowledge-based questions as well as questions about their attitudes toward science and scientific careers. Following a BioEYES class, all grade levels showed significant positive gains in learning. Seven of the eight knowledge questions had significant positive gains for elementary students. At the middle school level, eight of the nine knowledge questions had significant positive gains. For example, students are asked about basic science concepts focused on cell biology, genetics, and how to develop a hypothesis. Some middle school questions that showed the greatest gains involved concepts in genetics, with changes from 72 to 87 percent, depending on the question. For example, students were asked to identify a Punnett Square based on the next generation cross of their offspring. The high school questions with the greatest gains were those identifying characteristics of model organisms in research such as having DNA and providing insight into human health, with a 64 percent change, and a basic understanding of stem cells, with a 56 percent change. Interestingly, for all grade levels BioEYES increased students' ability to imagine themselves as scientists. The largest effect on attitudes occurred at the elementary school level - six out of eleven statements showed significant positive changes. Among all grade levels, the strongest attitude shift was in the statement, "I know what it's like to be a scientist." The second-largest attitude change was observed in elementary and high school grades, and the third-largest in middle school, was an increase in agreement with the statement, "Science is becoming more popular than it used to be." The work of BioEYES, locally and nationally, is supported by many foundations, corporations, and individuals (see S10 Table in the original paper for a comprehensive list of corporate and nonprofit support). The Penn BioEYES program that serves the Philadelphia area is supported by the Institute for Regenerative Medicine, Mr. and Mrs. Bernard Spain, The Brook J. Lenfest Foundation, Children Can Shape the Future, The Scholler Foundation, and The Seybert Foundation. Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise. The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year. The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.


News Article | December 1, 2016
Site: www.eurekalert.org

They're flexible, cheap to produce and simple to make - which is why perovskites are the hottest new material in solar cell design. And now, engineers at Australia's University of New South Wales in Sydney have smashed the trendy new compound's world efficiency record. Speaking at the Asia-Pacific Solar Research Conference in Canberra on Friday 2 December, Anita Ho-Baillie, a Senior Research Fellow at the Australian Centre for Advanced Photovoltaics (ACAP), announced that her team at UNSW has achieved the highest efficiency rating with the largest perovskite solar cells to date. The 12.1% efficiency rating was for a 16 cm2 perovskite solar cell, the largest single perovskite photovoltaic cell certified with the highest energy conversion efficiency, and was independently confirmed by the international testing centre Newport Corp, in Bozeman, Montana. The new cell is at least 10 times bigger than the current certified high-efficiency perovskite solar cells on record. Her team has also achieved an 18% efficiency rating on a 1.2 cm2 single perovskite cell, and an 11.5% for a 16 cm2 four-cell perovskite mini-module, both independently certified by Newport. "This is a very hot area of research, with many teams competing to advance photovoltaic design," said Ho-Baillie. "Perovskites came out of nowhere in 2009, with an efficiency rating of 3.8%, and have since grown in leaps and bounds. These results place UNSW amongst the best groups in the world producing state-of-the-art high-performance perovskite solar cells. And I think we can get to 24% within a year or so." Perovskite is a structured compound, where a hybrid organic-inorganic lead or tin halide-based material acts as the light-harvesting active layer. They are the fastest-advancing solar technology to date, and are attractive because the compound is cheap to produce and simple to manufacture, and can even be sprayed onto surfaces. "The versatility of solution deposition of perovskite makes it possible to spray-coat, print or paint on solar cells," said Ho-Baillie. "The diversity of chemical compositions also allows cells be transparent, or made of different colours. Imagine being able to cover every surface of buildings, devices and cars with solar cells." Most of the world's commercial solar cells are made from a refined, highly purified silicon crystal and, like the most efficient commercial silicon cells (known as PERC cells and invented at UNSW), need to be baked above 800?C in multiple high-temperature steps. Perovskites, on the other hand, are made at low temperatures and 200 times thinner than silicon cells. But although perovskites hold much promise for cost-effective solar energy, they are currently prone to fluctuating temperatures and moisture, making them last only a few months without protection. Along with every other team in the world, Ho-Baillie's is trying to extend its durability. Thanks to what engineers learned from more than 40 years of work with layered silicon, they're are confident they can extend this. Nevertheless, there are many existing applications where even disposable low-cost, high-efficiency solar cells could be attractive, such as use in disaster response, device charging and lighting in electricity-poor regions of the world. Perovskite solar cells also have the highest power to weight ratio amongst viable photovoltaic technologies. "We will capitalise on the advantages of perovskites and continue to tackle issues important for commercialisation, like scaling to larger areas and improving cell durability," said Martin Green, Director of the ACAP and Ho-Baillie's mentor. The project's goal is to lift perovskite solar cell efficiency to 26%. The research is part of a collaboration backed by $3.6 million in funding through the Australian Renewable Energy Agency's (ARENA) 'solar excellence' initiative. ARENA's CEO Ivor Frischknecht said the achievement demonstrated the importance of supporting early stage renewable energy technologies: "In the future, this world-leading R&D could deliver efficiency wins for households and businesses through rooftop solar as well as for big solar projects like those being advanced through ARENA's investment in large-scale solar." To make a perovskite solar cells, engineers grow crystals into a structure known as 'perovskite', named after Lev Perovski, the Russian mineralogist who discovered it. They first dissolve a selection of compounds in a liquid to make the 'ink', then deposit this on a specialised glass which can conduct electricity. When the ink dries, it leaves behind a thin film that crystallises on top of the glass when mild heat is applied, resulting in a thin layer of perovskite crystals. The tricky part is growing a thin film of perovskite crystals so the resulting solar cell absorbs a maximum amount of light. Worldwide, engineers are working to create smooth and regular layers of perovskite with large crystal grain sizes in order to increase photovoltaic yields. Ho-Baillie, who obtained her PhD at UNSW in 2004, is a former chief engineer for Solar Sailor, an Australian company which integrates solar cells into purpose-designed commercial marine ferries which currently ply waterways in Sydney, Shanghai and Hong Kong. The Australian Centre for Advanced Photovoltaics is a national research collaboration based at UNSW, whose partners are the University of Queensland, Monash University, the Australian National University, the University of Melbourne and the CSIRO Manufacturing Flagship. The collaboration is funded by an annual grant from ARENA, and partners include Arizona State University, Suntech Power and Trina Solar. UNSW's Faculty of Engineering is the powerhouse of engineering research in Australia, comprising of nine schools, 21 research centres and participating or leading 10 Cooperative Research Centres. It is ranked in the world's top 50 engineering faculties, and home to Australia's largest cohort of engineering undergraduate, postgraduate, domestic and international students. UNSW itself and is ranked #1 in Australian Research Council funding ($150 million in 2016); ranked #1 in Australia for producing millionaires (#33 globally) and ranked #1 in Australia for graduates who create technology start-ups.


Research and Markets has announced the addition of the "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026 " report to their offering. The "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026" report provides an extensive study of the current landscape and the growing pipeline of new generation antibiotics targeting drug-resistant bacteria. As indicated earlier, owing to the over-prescription of antibiotics due to improper diagnosis, lack of adherence to proper dosage regimens, their widespread availability as over-the-counter (OTC) drugs, and overuse in agriculture and poultry farming, most antibiotics have been rendered ineffective. Moreover, there currently exists an expanding lag between the pace at which drug resistant bacteria evolve and the time taken for new drugs to reach the market. As a result, antibiotic drug resistance has escalated into a global threat. There are concerns that the lack of effective drugs in this domain may soon trigger the relapse of the pre-antibiotic era, in which individuals died due to day-to-day bacterial infections. According to certain studies, currently, an estimated 700,000 deaths annually are known to occur due to anti-microbial resistance worldwide. In future, the growing threat of antibiotic resistance is anticipated to prove to be more fatal than cancer. The current scenario depicts an urgent need for new antibiotics with novel mechanisms of action, having the ability to combat antibiotic resistance. The US and EU governments have amended their action plans and conducted many conferences to raise awareness about the situation among both experts in the domain and the general public. Such initiatives are addressed to support R&D strategies of companies engaged in the development of drugs to combat antibiotic resistance. Efforts are underway to assist drug developers in their clinical trial design issues, and even the simplification of regulatory pathways to expedite the time to market for such drugs. In addition, such initiatives endorse public-private partnerships in advancing scientific and clinical efforts in this domain, aid the setting up of surveillance programs to track the widespread use of antibiotics and the development of resistance, and track the growing economic burden due to this phenomenon as well. The new generation antibiotics pipeline comprises of several molecules that target infections caused by deadly pathogens classified under ESKAPE or as urgent threats by the CDC. Several start-ups have entered the market and undertaken various initiatives to develop novel antibiotics with unique mechanisms of action. - An overview of the current state of the market with respect to the key players involved, phase of development of pipeline products (clinical and preclinical/discovery), target classes of pathogens (Gram-negative versus Gram-positive), drug classes and key disease indications. In addition, we have included an insightful representation of the developer landscape, highlighting the geographical presence of key players in the industry. - Detailed profiles of approved drugs, as well as those in phase III of clinical development, highlighting information on clinical trials, their current status of development, recent developments and associated collaborations. - Insights on novel alternative therapies that are being explored/evaluated to target antibiotic resistant pathogenic bacteria; these include teixobactin, anti-microbial peptides, antisense antibacterials, quorum sensing inhibition, nano-metal based therapies and anti-biofilm agents. - Details on the most popular therapeutic areas, namely acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP) Clostridium difficile infections (CDIs), complicated intra-abdominal infections (cIAIs), complicated urinary tract infections (cUTIs) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). For each indication, we have provided a brief description of the disease, information on its epidemiology, available treatment plans and active comparator studies of approved drug candidates that are prescribed for the aforementioned indications. - An illustrative grid representation and a bulls-eye analysis of the pipeline molecules, based on their development stage, spectrum of activity and the key indications. - Future commercial potential of the market based on a detailed opportunity analysis, for the period between 2016 and 2026. The research, analysis and insights presented in this report include potential sales of approved antibiotics and those in late stages of development. 1. Preface 2. Executive Summary 3. Introduction 4. Antibiotic Drug Resistance: Development Pipeline and Market Landscape 5. Clinical Development Analysis and Key Comparator Studies 6. New Generation Antibiotics: Marketed Drugs 7. New Generation Antibiotics: Phase III Drugs 8. Emerging Therapies to Combat Antibiotic Resistance 9. Key Therapeutic Areas 10. Market Forecast and Opportunity Analysis 11. Conclusion 12. Interview Transcripts 13. Appendix 1: Tabulated Data 14. Appendix 2: List of Companies and Organization - AAIPharma Services - ABAC Therapeutics - ANTABIO - Abbott Laboratories - Abgentis - Absynth Biologics - Achaogen - Acino Holdings - Actavis - Actelion Pharmaceuticals - Adenium Biotech - Adimab - Aequor - AiCuris - Alaxia Pharma - Albany Molecular Research (AMRI) - Allecra Therapeutics - Allergan - Angelini - Antibio Tx - Antibiotic Adjuvant - Aphios - Appili Therapeutics - Arietis Pharma - Arpida - Arsanis - Assembly Biosciences - AstraZeneca - Austell Laboratories - Aventis Pharma - BKG Pharma - BUGWORKS - Basilea Pharmaceutica - Bayer Pharma - BioVersys - Biocidium Biopharmaceuticals - Biocon - Biosearch Italia - Biovertis - Blueberry Therapeutics - C3 Jian - Calixa Therapeutics - Cantab Anti-infectives - Cardiome Pharma - Cellceutix Corporation - Cempra - Cerexa - Clinigen Group - ContraFect - Crestone - Crystal Genomics - Cubist Pharmaceuticals - CyDex Pharmaceuticals - DSM Sinochem Pharmaceuticals - Da Volterra - Daiichi Sankyo - Debiopharm International - Deinove - Demuris - Discuva - Dong Wha Pharmaceuticals - Dong-A Pharmaceutical - Durata Therapeutics - Eli Lilly - Eligo Bioscience - EnBiotix - Entasis Therapeutics - Eurofarma Laboratórios - Evolva Holding - Evotec - Eydo Pharma - FOB Synthesis - Fedora Pharmaceuticals - Forest Laboratories - Fujisawa Pharmaceuticals - GSK - Galapagos - GangaGen - GeneWEAVE - Hikma Pharmaceuticals - IASO Pharma - iNtRON Biotechnology - Immuron - Indel Therapeutics - Institute of Metagenomics and Microbial Technologies (IMMT) - InterMune - Ionis Pharmaceuticals - Isis Pharmaceuticals - Janssen-Ortho - Japan Radio Company - Johnson & Johnson - Kyorin Pharmaceutical - LegoChem Biosciences - Ligand Pharmaceuticals - Lyndra - MGB Biopharma - Macrolide Pharmaceuticals - MarBiLeads - Matinas BioPharma - MedImmune - Meiji Seika Pharma - Melinta Therapeutics - MerLion Pharmaceuticals - Merck - MethylGene - Microbecide - MicuRx Pharmaceuticals - Mirati Therapeutics - Monash University - MorphoSys - Morphochem - Motif Bio - Mutabilis - Nabriva Therapeutics - Naicon - NanoSafe Coatings - Nanotherapeutics - Navigen Pharmaceuticals - Nemesis Bioscience - Nexgen Biosciences - Nobelex Biotech - Northeastern University - Northern Antibiotics - Nosopharm - NovaBiotics - NovaDigm Therapeutics - Novexel - NovoBiotic Pharmaceuticals - Nuprim - OJ-Bio - Optimer Biotechnology - Optimer Pharmaceuticals - Osel - PENDOPHARM - Pacific Beach BioSciences - Par Pharmaceutical - Paratek Pharmaceuticals - Patheon - Peninsula Pharmaceuticals - Peptilogics - Pfizer - Pherecydes Pharma - Phico Therapeutics - Polyphor - Procarta Biosystems - Pure Actives - R-Pharm - RQx Pharmaceuticals - RaQualia Pharma - Rebiotix - Redx Pharma - Rempex Pharmaceuticals - RexC Pharmaceuticals - Rib-X Pharmaceuticals - Roche - Rx3 Pharmaceuticals - Sanofi-Aventis - SciClone Pharmaceuticals - Sequella - Seres Therapeutics - SetLance - Shionogi - Shire - SinSa Labs - Specialised Therapeutics Australia - Spero Therapeutics - Sumitomo Dainippon Pharma (DSP) - Summit Therapeutics - Synamp Pharmaceuticals - Synthetic Biologics - TAXIS Pharmaceuticals - TaiGen Biotechnology - Takeda Pharmaceutical - Talon Pharmaceuticals - Targanta Therapeutics - TechnoPhage - Techulon - Tetraphase Pharmaceuticals - The Medicines Company - TheraBor Pharmaceuticals - Theravance Biopharma - Treat Systems - Trius Therapeutics - University of Michigan Life Sciences Institute - University of Pittsburgh - Vaxdyn - VenatoRx Pharmaceuticals - Versicor Pharmaceuticals - VibioSphen - Vicuron Pharmaceuticals - ViroPharma - Vitas Pharma - Vyome Biosciences - Wakunaga Pharmaceutical - Warner Chillcott - Wockhardt - Yamanouchi Pharmaceutical - Zavante Therapeutics For more information about this report visit http://www.researchandmarkets.com/research/gqv9bz/antibacterial


Dublin, Dec. 15, 2016 (GLOBE NEWSWIRE) -- Research and Markets has announced the addition of the "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026 " report to their offering. The "Antibacterial Drug Resistance: Market Landscape, Challenges and Upcoming Opportunities, 2016-2026" report provides an extensive study of the current landscape and the growing pipeline of new generation antibiotics targeting drug-resistant bacteria. As indicated earlier, owing to the over-prescription of antibiotics due to improper diagnosis, lack of adherence to proper dosage regimens, their widespread availability as over-the-counter (OTC) drugs, and overuse in agriculture and poultry farming, most antibiotics have been rendered ineffective. Moreover, there currently exists an expanding lag between the pace at which drug resistant bacteria evolve and the time taken for new drugs to reach the market. As a result, antibiotic drug resistance has escalated into a global threat. There are concerns that the lack of effective drugs in this domain may soon trigger the relapse of the pre-antibiotic era, in which individuals died due to day-to-day bacterial infections. According to certain studies, currently, an estimated 700,000 deaths annually are known to occur due to anti-microbial resistance worldwide. In future, the growing threat of antibiotic resistance is anticipated to prove to be more fatal than cancer. The current scenario depicts an urgent need for new antibiotics with novel mechanisms of action, having the ability to combat antibiotic resistance. The US and EU governments have amended their action plans and conducted many conferences to raise awareness about the situation among both experts in the domain and the general public. Such initiatives are addressed to support R&D strategies of companies engaged in the development of drugs to combat antibiotic resistance. Efforts are underway to assist drug developers in their clinical trial design issues, and even the simplification of regulatory pathways to expedite the time to market for such drugs. In addition, such initiatives endorse public-private partnerships in advancing scientific and clinical efforts in this domain, aid the setting up of surveillance programs to track the widespread use of antibiotics and the development of resistance, and track the growing economic burden due to this phenomenon as well. The new generation antibiotics pipeline comprises of several molecules that target infections caused by deadly pathogens classified under ESKAPE or as urgent threats by the CDC. Several start-ups have entered the market and undertaken various initiatives to develop novel antibiotics with unique mechanisms of action. The report features: - An overview of the current state of the market with respect to the key players involved, phase of development of pipeline products (clinical and preclinical/discovery), target classes of pathogens (Gram-negative versus Gram-positive), drug classes and key disease indications. In addition, we have included an insightful representation of the developer landscape, highlighting the geographical presence of key players in the industry. - Detailed profiles of approved drugs, as well as those in phase III of clinical development, highlighting information on clinical trials, their current status of development, recent developments and associated collaborations. - Insights on novel alternative therapies that are being explored/evaluated to target antibiotic resistant pathogenic bacteria; these include teixobactin, anti-microbial peptides, antisense antibacterials, quorum sensing inhibition, nano-metal based therapies and anti-biofilm agents. - Details on the most popular therapeutic areas, namely acute bacterial skin and skin structure infections (ABSSSIs), community-acquired pneumonia (CAP) Clostridium difficile infections (CDIs), complicated intra-abdominal infections (cIAIs), complicated urinary tract infections (cUTIs) and hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP). For each indication, we have provided a brief description of the disease, information on its epidemiology, available treatment plans and active comparator studies of approved drug candidates that are prescribed for the aforementioned indications. - An illustrative grid representation and a bulls-eye analysis of the pipeline molecules, based on their development stage, spectrum of activity and the key indications. - Future commercial potential of the market based on a detailed opportunity analysis, for the period between 2016 and 2026. The research, analysis and insights presented in this report include potential sales of approved antibiotics and those in late stages of development. Key Topics Covered: 1. Preface 2. Executive Summary 3. Introduction 4. Antibiotic Drug Resistance: Development Pipeline and Market Landscape 5. Clinical Development Analysis and Key Comparator Studies 6. New Generation Antibiotics: Marketed Drugs 7. New Generation Antibiotics: Phase III Drugs 8. Emerging Therapies to Combat Antibiotic Resistance 9. Key Therapeutic Areas 10. Market Forecast and Opportunity Analysis 11. Conclusion 12. Interview Transcripts 13. Appendix 1: Tabulated Data 14. Appendix 2: List of Companies and Organization - AAIPharma Services - ABAC Therapeutics - ANTABIO - Abbott Laboratories - Abgentis - Absynth Biologics - Achaogen - Acino Holdings - Actavis - Actelion Pharmaceuticals - Adenium Biotech - Adimab - Aequor - AiCuris - Alaxia Pharma - Albany Molecular Research (AMRI) - Allecra Therapeutics - Allergan - Angelini - Antibio Tx - Antibiotic Adjuvant - Aphios - Appili Therapeutics - Arietis Pharma - Arpida - Arsanis - Assembly Biosciences - AstraZeneca - Austell Laboratories - Aventis Pharma - BKG Pharma - BUGWORKS - Basilea Pharmaceutica - Bayer Pharma - BioVersys - Biocidium Biopharmaceuticals - Biocon - Biosearch Italia - Biovertis - Blueberry Therapeutics - C3 Jian - Calixa Therapeutics - Cantab Anti-infectives - Cardiome Pharma - Cellceutix Corporation - Cempra - Cerexa - Clinigen Group - ContraFect - Crestone - Crystal Genomics - Cubist Pharmaceuticals - CyDex Pharmaceuticals - DSM Sinochem Pharmaceuticals - Da Volterra - Daiichi Sankyo - Debiopharm International - Deinove - Demuris - Discuva - Dong Wha Pharmaceuticals - Dong-A Pharmaceutical - Durata Therapeutics - Eli Lilly - Eligo Bioscience - EnBiotix - Entasis Therapeutics - Eurofarma Laboratórios - Evolva Holding - Evotec - Eydo Pharma - FOB Synthesis - Fedora Pharmaceuticals - Forest Laboratories - Fujisawa Pharmaceuticals - GSK - Galapagos - GangaGen - GeneWEAVE - Hikma Pharmaceuticals - IASO Pharma - iNtRON Biotechnology - Immuron - Indel Therapeutics - Institute of Metagenomics and Microbial Technologies (IMMT) - InterMune - Ionis Pharmaceuticals - Isis Pharmaceuticals - Janssen-Ortho - Japan Radio Company - Johnson & Johnson - Kyorin Pharmaceutical - LegoChem Biosciences - Ligand Pharmaceuticals - Lyndra - MGB Biopharma - Macrolide Pharmaceuticals - MarBiLeads - Matinas BioPharma - MedImmune - Meiji Seika Pharma - Melinta Therapeutics - MerLion Pharmaceuticals - Merck - MethylGene - Microbecide - MicuRx Pharmaceuticals - Mirati Therapeutics - Monash University - MorphoSys - Morphochem - Motif Bio - Mutabilis - Nabriva Therapeutics - Naicon - NanoSafe Coatings - Nanotherapeutics - Navigen Pharmaceuticals - Nemesis Bioscience - Nexgen Biosciences - Nobelex Biotech - Northeastern University - Northern Antibiotics - Nosopharm - NovaBiotics - NovaDigm Therapeutics - Novexel - NovoBiotic Pharmaceuticals - Nuprim - OJ-Bio - Optimer Biotechnology - Optimer Pharmaceuticals - Osel - PENDOPHARM - Pacific Beach BioSciences - Par Pharmaceutical - Paratek Pharmaceuticals - Patheon - Peninsula Pharmaceuticals - Peptilogics - Pfizer - Pherecydes Pharma - Phico Therapeutics - Polyphor - Procarta Biosystems - Pure Actives - R-Pharm - RQx Pharmaceuticals - RaQualia Pharma - Rebiotix - Redx Pharma - Rempex Pharmaceuticals - RexC Pharmaceuticals - Rib-X Pharmaceuticals - Roche - Rx3 Pharmaceuticals - Sanofi-Aventis - SciClone Pharmaceuticals - Sequella - Seres Therapeutics - SetLance - Shionogi - Shire - SinSa Labs - Specialised Therapeutics Australia - Spero Therapeutics - Sumitomo Dainippon Pharma (DSP) - Summit Therapeutics - Synamp Pharmaceuticals - Synthetic Biologics - TAXIS Pharmaceuticals - TaiGen Biotechnology - Takeda Pharmaceutical - Talon Pharmaceuticals - Targanta Therapeutics - TechnoPhage - Techulon - Tetraphase Pharmaceuticals - The Medicines Company - TheraBor Pharmaceuticals - Theravance Biopharma - Treat Systems - Trius Therapeutics - University of Michigan Life Sciences Institute - University of Pittsburgh - Vaxdyn - VenatoRx Pharmaceuticals - Versicor Pharmaceuticals - VibioSphen - Vicuron Pharmaceuticals - ViroPharma - Vitas Pharma - Vyome Biosciences - Wakunaga Pharmaceutical - Warner Chillcott - Wockhardt - Yamanouchi Pharmaceutical - Zavante Therapeutics For more information about this report visit http://www.researchandmarkets.com/research/gtt9s3/antibacterial


Luo F.,East China Institute of Technology | Batten S.R.,Monash University
Dalton Transactions | Year: 2010

A distinct method, lanthanide(iii)-doped pathway is for the first time utilized to replace lanthanide(iii) MOFs for the access of MOF-based luminescent sensing of metal ions. The research results revealed that this strategy is highly effective and displays several outstanding features. © 2010 The Royal Society of Chemistry.


Jowitt S.M.,Monash University | Ernst R.E.,Carleton University
Lithos | Year: 2013

The lithogeochemistry of eight Proterozoic Large Igneous Provinces (LIPs) within Canada has been studied to determine the Ni-Cu-PGE prospectivity of these major magmatic events. Three of the LIPs, the 1.87. Ga Chukotat, 1.27. Ga Mackenzie and the 2.49-2.45. Ga Matachewan LIPs, are associated with known magmatic Ni-Cu-PGE sulphide mineralisation. Four of the other LIPs, the 1.14. Ga Abitibi, 0.59. Ga Grenville, ~. 1.25. Ga Seal Lake and 1.24. Ga Sudbury (distinct from the Sudbury impact event) LIPs, have no known Ni-Cu-PGE mineralisation. The 0.72. Ga Franklin LIP may be associated with the coeval and mineralised Dovyren intrusion in southern Siberia (in a Rodinia reconstruction); in addition, several Franklin-related Ni-Cu-PGE prospects are known within northern Canada.The mineralised LIPs are characterised by basalts with Ti/V ratios below 50, Gd/Yb ratios close to primitive mantle values and variable La/Sm ratios. The magmas that formed these LIP magmas assimilated significant amounts of crustal material and both chalcophile depleted and undepleted magmas were present during these magmatic events. This indicates that the magmas that formed these LIPs were fertile and S-undersaturated when they left the mantle and subsequently underwent an S-saturation event, forming immiscible magmatic sulphides. The close relationship between chalcophile element depletion and crustal contamination suggests that S-saturation was caused by assimilation of crustal material, most likely by assimilation of crustal sulphides. The magmatic sulphides produced during this event were presumably segregated from magma and deposited in cogenetic mafic-ultramafic sills and intrusives associated with these LIPs.The Grenville and part of the Franklin LIPs have similar magma source characteristics to those with known Ni-Cu-PGE mineralisation. However, although magmas from both LIPs were fertile and assimilated crustal material, the Grenville LIP did not undergo an S-saturation event prior to emplacement. During the Franklin LIP event, chalcophile-element undepleted fertile magmas may have become S-saturated by assimilation of crustal material, most likely crustal sulphides. Identification of the timing and location of this S-saturation event may be a useful guide during exploration for Ni-Cu-PGE mineralisation. The Abitibi, Sudbury and Seal Lake LIPs are dominated by alkali basalts and are characterised by high Gd/Yb ratios, a wide range in La/Sm ratios and Ti/V ratios higher than 50. This suggests that the melting that formed the magmas associated with these LIPs occurred at depths of >. 90. km, and potentially involved melting of enriched mantle sources. All samples from the Abitibi, Seal Lake and Sudbury LIPs are chalcophile element depleted, suggesting that these magmas left residual sulphide within the mantle during melting, and indicating that these LIPs are probably not prospective hosts for Ni-Cu-PGE sulphide mineralisation. © 2012 Elsevier B.V.


Fraser J.,Bristol Royal Hospital for Children | Sidebotham P.,University of Warwick | Frederick J.,Monash University | Covington T.,Review Centre | Mitchell E.A.,University of Auckland
The Lancet | Year: 2014

Despite pronounced reductions in child mortality in industrialised countries, variations exist within and between countries. Many child deaths are preventable, and much could be done to further reduce mortality. For the family, their community, and professionals caring for them, every child's death is a tragedy. Systematic review of all child deaths is grounded in respect for the rights of children and their families, and aimed towards the prevention of future child deaths. In a Series of three papers, we discuss child death in high-income countries in the context of evolving child death review processes. This paper outlines the background to and development of child death review in the USA, England, Australia, and New Zealand. We consider the purpose, process, and outputs of child death review, and discuss how these factors can contribute to a greater understanding of children's deaths and to knowledge for the prevention of future child deaths.


Yeo L.Y.,Monash University | Chang H.-C.,University of Notre Dame | Chan P.P.Y.,Monash University | Friend J.R.,Monash University
Small | Year: 2011

Harnessing the ability to precisely and reproducibly actuate fluids and manipulate bioparticles such as DNA, cells, and molecules at the microscale, microfluidics is a powerful tool that is currently revolutionizing chemical and biological analysis by replicating laboratory bench-top technology on a miniature chip-scale device, thus allowing assays to be carried out at a fraction of the time and cost while affording portability and field-use capability. Emerging from a decade of research and development in microfluidic technology are a wide range of promising laboratory and consumer biotechnological applications from microscale genetic and proteomic analysis kits, cell culture and manipulation platforms, biosensors, and pathogen detection systems to point-of-care diagnostic devices, high-throughput combinatorial drug screening platforms, schemes for targeted drug delivery and advanced therapeutics, and novel biomaterials synthesis for tissue engineering. The developments associated with these technological advances along with their respective applications to date are reviewed from a broad perspective and possible future directions that could arise from the current state of the art are discussed. Microfluidics, which entails the manipulation of fluids and bioparticles at micron and submicron dimensions, is a promising technology that could potentially revolutionize an entire spectrum of chemical and biological processes. This review provides an overview of current technological advances and developments to date across wide and varied themes in medicine and biotechnology from genomic, proteomic, and cellomic analysis to drug delivery, drug screening, and point-of-care diagnostics. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Krum H.,Monash University | Teerlink J.R.,San Francisco Veterans Affairs Medical Center | Teerlink J.R.,University of California at San Francisco
The Lancet | Year: 2011

Understanding of contemporary pharmacological therapy for chronic heart failure continues to evolve. In this Review, we discuss how findings from clinical trials have caused the roles of old therapies to be expanded and past treatment algorithms to be challenged. Several trials investigating preserved ejection fraction as a measure of heart failure had disappointing results, although important studies are in progress. Many novel therapeutic approaches for heart failure have emerged and are discussed in this review. The pharmacological treatments for heart failure continue to change, with many exciting possibilities for the future. © 2011 Elsevier Ltd.


Cobo I.,University of Sydney | Li M.,Tyco Fire Protection Products | Sumerlin B.S.,University of Florida | Perrier S.,University of Warwick | Perrier S.,Monash University
Nature Materials | Year: 2015

The properties and applications of biomacromolecules, for example proteins, can be enhanced by the covalent attachment of synthetic polymers. This Review discusses the modification of these biomacromolecules with stimuli-responsive polymers. © 2015 Macmillan Publishers Limited. All rights reserved.


Shepherd S.J.,La Trobe University | Lomer M.C.E.,King's College London | Gibson P.R.,Monash University
American Journal of Gastroenterology | Year: 2013

Carbohydrates occur across a range of foods regularly consumed including grains such as wheat and rye, vegetables, fruits, and legumes. Short-chain carbohydrates with chains of up to 10 sugars vary in their digestibility and subsequent absorption. Those that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These two effects alone may underlie most of the induction of gastrointestinal symptoms after they are ingested in moderate amounts via luminal distension in patients with visceral hypersensitivity. This has been the basis of the use of lactose-free diets in those with lactose malabsorption and of fructose-reduced diets for fructose malabsorption. However, application of such dietary approaches in patients with functional bowel disorders has been restricted to observational studies with uncertain efficacy. As all dietary poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. In patients with irritable bowel syndrome, there is now an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders, and that a diet low in FODMAPs offers considerable symptom relief in the majority of patients who use it. © 2013 by the american College of Gastroenterology.


Gooley R.P.,Monash University | Cameron J.D.,Monash Health | Meredith I.T.,Monash Health
JACC: Cardiovascular Interventions | Year: 2015

Objectives This study sought to assess the geometric interaction between the Lotus Valve System transcatheter aortic prosthesis (Boston Scientific, Natick, Massachusetts) and the native aortoventricular interface using multidetector computed tomography (MDCT). Background The interaction between transcatheter aortic valve prostheses and native anatomy is variable, although potentially predictable. The Lotus transcatheter device uses a novel mechanical means of expansion, the effect of which on native anatomic geometry has not previously been described. Methods Forty patients treated with the Lotus prosthesis were enrolled. The patients underwent 320-MDCT imaging before and after implantation. Prosthesis dimensions and relevant interaction parameters, including circularity and expansion, were assessed. The degree of paraprosthetic regurgitation (PAR) and prosthesis gradient were measured by transthoracic echocardiography at the same time points. Results The mean baseline annular eccentricity index (EI) was 0.21 ± 0.06 and left ventricular outflow tract EI was 0.31 ± 0.09. The deployed prostheses had high rates of circularity with a mean EI across all device segments of 0.06 ± 0.04. In noncircular device deployment, an EI >0.1 was identified in 25% of prostheses and was associated with greater native annular eccentricity at baseline compared with circular devices (0.24 ± 0.04 vs. 0.19 ± 0.06; p = 0.01). The median percent of expansion was 97.5 ± 3.8% in the inflow portion of the prosthesis. Twenty-five percent of prostheses were <90% expanded in at least 1 segment with a numerical, but not statistically significant, association between oversizing and underexpansion. No correlation was found between device underexpansion and the mean transprosthesis gradient or between noncircularity and PAR. Conclusions The Lotus prosthesis results in nearly full device expansion and circularization of the native basal plane. Awareness of the anatomic interaction between this unique device and the native architecture may help in the formulation of appropriate device-specific sizing algorithms. © 2015 American College of Cardiology Foundation.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EINFRA-7-2014 | Award Amount: 3.46M | Year: 2015

Five years ago, a global infrastructure to uniquely attribute to researchers their scientific artefacts (articles, data, software) appeared technically and socially infeasible. Since then, DataCite has minted over 3.5m unique identifiers for data. ORCID has deployed an open solution for identification of contributors with over 850,000 registrants in less than 2 years. THOR will leverage these emerging global infrastructures to support the H2020 goal to make every researcher digital and increase creativity and efficiency of research, while bridging the R&D divide between developed and less-developed regions. We will establish interoperability between existing resources, linking digital identifiers across platforms and propagating attribution information. We will integrate PID services across the research lifecycle and data publishing workflows in four advanced research communities, and then roll-out core services and service building blocks for the wider community. These open resources will foster an open and sustainable e-infrastructure across stakeholders to avoid duplications, give economies of scale, richness of services and the ability to respond rapidly to opportunities for innovation. THOR is not just relevant to the EINFRA-7-1024 Call, but will become a pervasive element of the EINFRA family of e-Infrastructure resources over the next 3 years. It will allow data-management and curation services to exploit knowledge of data location and attribution; provide robust and persistent mechanism for linking literature and data; enable search and resolving services and generate incentives for Open Science; deliver provenance and attribution mechanisms to underpin data exchange; and provide minting and resolving services for data citation workflows. Its impact will enable third-party services, no-profit and commercial, to leverage the scholarly record.


Patent
Board Of Regents Of The University Of Texas System, Monash University, University of Washington and Mmv Medicines For Malaria Venture | Date: 2016-09-28

The present invention is related to a use of triazolopyrimidine derivatives in the manufacture of a medicament for preventing or treating malaria. Specifically, the present invention is related to triazolopyrimidine derivatives useful for the preparation of a pharmaceutical formulation for the inhibition of malaria parasite proliferation.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.1.1-1 | Award Amount: 18.17M | Year: 2010

The EUCOMMTOOLS Collaborative Project responds to the topic HEALTH.2010.2.1.1-1: Large-scale efforts in mouse functional genomics to determine the functions of genes and their involvement in disease. EUCOMMTOOLS will provide, in a systematic high-throughput way, genetic tools and resources contributing to the determination of every genes function in any cell type of the entire organism at any given point in time. To contribute to the IKMC goals, EUCOMMTOOLS will establish 250 BAC-CreERT2 transgenic mice allowing inducible conditional gene inactivation in most cell types of the organism at any given point in time. Furthermore, EUCOMMTOOLS will establish 3.500 additional, conditionally targeted mouse ES cells to complete the IKMC resource. In addition, various important technological developments will valorise the EUCOMMTOOLS resources: a genetic toolkit for multipurpose usage of the conditional knockout alleles, and improvements of the Cre-recombinase function. The EUCOMMTOOLS Cre transgenic resource as well as its library of conditionally mutated mouse ES cells enables the establishment of mutant mice world-wide in a standardized, cost-effective and time-saving manner, making mouse mutants more easily available to the wider biomedical research community than possible previously. All EUCOMMTOOLS vectors, mutant ES cells and mice will be displayed via the EUCOMMTOOLS web portal and will be distributed by EuMMCR and EMMA to the scientific community. In general, EUCOMMTOOLS fosters existing European consortia which address mouse functional genomics, mouse mutant phenotyping, and mouse archiving. Taken together, EUCOMMTOOLS will further advance the functional annotation of the entire mouse genome and thereby enhance the understanding of the molecular basis of disease. Furthermore, it will support drug development by SMEs and the pharmaceutical industry.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SST-2007-4.1-02 | Award Amount: 3.33M | Year: 2008

The main objective of INTERACTION project is to identify the patterns of use of in-vehicle technologies by European drivers in everyday life and their long term effects on drivers behaviour and skills in normal and emergency situations. Thus, the project will highlight cultural and individual differences amongst European drivers that influence the nature of drivers interactions in-vehicle technology, and the consequent outcomes of these interactions. To achieve these objectives, a comprehensive research framework to investigate in-vehicle technology use has been developed. This framework is based on an innovative combination of well established research methodologies and technics : focus groups, questionnaire survey, naturalistic observations, and in-depth observations. The purpose of this combined approach is to gather self-reported and observed driver behaviour data and qualitative and quantitative analysis. The target impacts will be the reduction of the risks of systems misuses and of possible human error by drivers. Thus, it will increase the global benefits of in vehicle technology in enhancing road safety. To reach this target, two main operational outcomes will be issued from the knowledge acquired during the project. On the one hand, the knowledge will allow to define actions to strengthen drivers awareness for the use of these technologies and for the consequences that such use has or may have. On the other hand, the knowledge will permit to edit recommendations for the design of future systems and of appropriate instructions for drivers that will use them to favour a safe use of in-vehicle technologies by European drivers.


Proske U.,Monash University | Proske U.,Neuroscience Research AustraliA&M of New South Wales | Gandevia S.C.,Monash University | Gandevia S.C.,Neuroscience Research AustraliA&M of New South Wales
Physiological Reviews | Year: 2012

This is a review of the proprioceptive senses generated as a result of our own actions. They include the senses of position and movement of our limbs and trunk, the sense of effort, the sense of force, and the sense of heaviness. Receptors involved in proprioception are located in skin, muscles, and joints. Information about limb position and movement is not generated by individual receptors, but by populations of afferents. Afferent signals generated during a movement are processed to code for endpoint position of a limb. The afferent input is referred to a central body map to determine the location of the limbs in space. Experimental phantom limbs, produced by blocking peripheral nerves, have shown that motor areas in the brain are able to generate conscious sensations of limb displacement and movement in the absence of any sensory input. In the normal limb tendon organs and possibly also muscle spindles contribute to the senses of force and heaviness. Exercise can disturb proprioception, and this has implications for musculoskeletal injuries. Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly. The more recent information available on proprioception has given a better understanding of the mechanisms underlying these senses as well as providing new insight into a range of clinical conditions. © 2012 the American Physiological Society.


BANDAR SUNWAY, Malaysia, Nov. 14, 2016 /PRNewswire/ -- The Jeffrey Cheah Foundation (JCF) and the United Nations Sustainable Development Solutions Network (SDSN) Association are launching the Jeffrey Sachs Center on Sustainable Development (JSC) at Sunway University in Malaysia, as a catalytic move to mobilise comprehensive collaboration, particularly amongst Southeast Asian nations, to move towards achieving the 17 Sustainable Development Goals (SDGs). The Jeffrey Sachs Center on Sustainable Development is the result of a gift of USD10 million from the Jeffrey Cheah Foundation, Malaysia's largest education-focused social enterprise. To date, the gift is the largest financial commitment focused on SDG education and implementation since 193 members of the UN adopted the 17 goals in September 2015. In conjunction with the launch, there will be an inaugural conference featuring five keynote speakers and pundits in the area of sustainability. The event will be held at Sunway University in Malaysia on 9 December 2016, titled 'Moving Decisively Forward on Sustainable Development Now!' The five experts are: Professor Jeffrey Sachs' talk will be on "What Does Sustainable Development Really Mean?", Professor Tan Sri Zakri Abdul Hamid will be speaking on "Walking the Talk on Implementing the SDGs: A Case for Malaysia and South-East Asia," Professor Daniel Schrag will be covering "Climate Change and Sustainable Development: Opportunities for the Developing World", Professor Angelo Riccaboni will focus on "Food Systems for Sustainable Development: Innovations are Needed" while Professor Xue Lan will be discussing "Policy Challenges in Implementing Sustainable Development Goals." The Jeffrey Cheah Foundation is modelled along the lines of some of the oldest and most eminent universities in the world, such as Harvard University. To date, the Foundation retains ownership and equity of 16 learning institutions, including Sunway University, Monash University Malaysia*, the Jeffrey Cheah School of Medicine and Health Sciences, Sunway College, Sunway TES Centre for Accountancy Excellence and Sunway International School, valued at more than RM720 million (now in excess of RM1 billion). For more information on the Jeffrey Sachs Center on Sustainable Development (JSC) at Sunway University please email: jsc@sunway.edu.my *Monash University Malaysia is jointly-owned by Monash Australia and Jeffrey Cheah Foundation


News Article | November 28, 2016
Site: www.eurekalert.org

The popular Middle Park beach is under the international spotlight following a world-first study by Monash University chemists who have discovered how sand 'holds its breath'. The discovery, published in Nature Geoscience, has astonishing implications and potential uses in the biofuels industry, according to lead authors Associate Professor Perran Cook and PhD student Michael Bourke from the Water Studies Centre, School of Chemistry. Sand is full of algae called diatoms, but this environment is mixed about continuously so these organisms might get light one minute then be buried in the sediment with no oxygen the next. "This is a new mechanism by which this type of algae survive under these conditions," said Associate Professor Cook. "Our work has found that they ferment, like yeast ferments sugar to alcohol. "In this case, the products are hydrogen and 'fats', for example, oleate, which is a component of olive oil." Sand often has high concentrations of algae, which are highly productive and an important food source for food webs in the bay. It is important to understand how these organisms survive in the harsh environment in which they live. In this work, scientists present the first study of the importance of anoxic micro-algal metabolism through fermentation in permeable sediments. They combined flow-through reactor experiments with microbiological approaches to determine the dominant contributors and pathways of dissolved inorganic carbon production in permeable sediments. They show that micro-algal dark fermentation is the dominant metabolic pathway, which is the first time this has been documented in an environmental setting. "The finding that hydrogen is a by-product of this metabolism has important implications for the types of bacteria present in the sediment," said Associate Professor Cook. "It is well known that bacteria in the sediment can 'eat' hydrogen, however, these hydrogen eating bacteria may be more common than we previously thought."


News Article | January 27, 2016
Site: www.scientificcomputing.com

Singapore — An international team of researchers from the Duke-NUS Medical School (Duke-NUS), the University of Bristol, Monash University and RIKEN have developed an algorithm that can predict the factors required to convert one human cell type to another. These game-changing findings, recently published online on January 18, 2016, in the journal Nature Genetics, have significant implications for regenerative medicine and lay the groundwork for further research into cell reprogramming. It is known that cell types are not fixed, and that one cell type can be reprogrammed, or converted, to become another cell type by the addition of a unique set of cellular factors. This approach was brought to the fore by Shinya Yamanaka, whose Nobel prize-winning work involved the reprogramming of fibroblast cells from the skin to induced pluripotent stem cells (iPS). In theory, iPS could then be directly reprogrammed to become, for instance, retinal cells that could help treat macular or eye degeneration. In practice though, it seems there are technical and safety concerns with this approach of cell conversion due to the accumulation of cancerous mutations in the reprogrammed cells, therefore leading to unpredictable behavior. In addition, despite this breakthrough, determining the unique set of cellular factors that is needed to be manipulated for each cell conversion is a long and costly process that involved much trial and error. As a result, this first step of identifying the key set of cellular factors for cell conversion is the major obstacle researchers and doctors face in the field of cell reprogramming. In order to overcome this obstacle, Duke-NUS Senior Research Fellow Dr. Owen Rackham worked for five years to develop a computational algorithm to predict the cellular factors for cell conversions. The algorithm, called Mogrify, is able to predict the optimal set of cellular factors required for any given cell conversion. When tested, Mogrify was able to accurately predict the set of cellular factors required for previously published cell conversions correctly. To further validate Mogrify’s predictive ability, the team conducted two novel cell conversions in the laboratory using human cells, and these were successful in both attempts solely using the predictions of Mogrify. “Mogrify acts like a ‘world atlas’ for the cell and allows us to map out new territories in cell conversions in humans,” explained Rackham, who is from the Systems Genetics of Complex Disease Laboratory at Duke-NUS. “One of the first clinical applications that we hope to achieve with this innovative approach would be to reprogram ‘defective’ cells from patients into ‘functioning’ healthy cells, without the intermediate iPS step. These then can be re-implanted into patients, and should, in practice, effectively enable new regenerative medicine techniques.” Associate Professor Enrico Petretto, co-author of the study and head of the Systems Genetics of Complex Disease Laboratory in the Centre for Computational Biology at Duke-NUS, highlighted that since Mogrify is completely data-driven, its robustness and accuracy can only continue to improve as more comprehensive data are collected and input into the framework. “Mogrify is a game-changing method that leverages big data and systems biology; this will inspire new translational applications as the result of the work and expertise here at Duke-NUS. And as we continue to expand into the clinical applications of this cutting-edge technology, Singapore will be the first to benefit from its success,” said Associate Professor Petretto. Mogrify has been made available online for other researchers and scientists. The team at Duke-NUS now plan to focus on Mogrify’s application in translational medicine. Collaborative efforts between research groups within Duke-NUS are already in place to apply the algorithm to help develop treatments for specific diseases, such as cancer. The study is supported by the Biotechnology and Biological Sciences Research Council, the Japan Society for the Promotion of Science and the Duke-NUS Signature Research Programme, with funding from the Singapore Ministry of Health.


News Article | March 2, 2017
Site: en.prnasia.com

- Final report of initial preclinical study confirms Cymerus™ MSCs have significant beneficial effects on all three key components of asthma: airway hyper-responsiveness, inflammation and airway remodelling- Additional preclinical study expected to pave the way for a potential clinical trialMELBOURNE, Australia, Mar. 2, 2017 /PRNewswire/ -- Australian stem cell and regenerative medicine company, Cynata Therapeutics Ltd (ASX: CYP), has signed an agreement with the Monash Lung Biology Network, a consortia involving researchers from the Monash Biomedicine Discovery Institute and Department of Pharmacology at Monash University, Melbourne, to conduct a further preclinical study to support the use of Cymerus™ mesenchymal stem cells (MSCs) for the treatment of asthma. Asthma is a chronic, long term lung condition recognised by the World Health Organisation as a disease of major public health importance due to its global prevalence. Patients who suffer from chronic asthma manage the disease through the use of steroid type drugs, which can have significant side effects and impact on patients' quality of life. The global market for asthma drugs is expected to reach US$25.6 billion by 2024[1] so this challenging disease represents a highly valuable commercial opportunity for Cynata. In October 2016, Cynata announced compelling initial data from a proof of concept study of Cymerus™ MSCs in an experimental model of asthma, which was conducted under the supervision of Associate Professor Chrishan Samuel and Dr Simon Royce at Monash University. Those initial results clearly demonstrated that Cymerus™ MSCs have a dramatic effect on improving airway hyper-responsiveness. Cynata recently received the final report of that study, which showed that Cymerus™ MSCs also consistently reduced markers of airway inflammation and airway remodelling. The preparation of a manuscript describing these findings is at an advanced stage, and it is expected to be submitted to a leading peer-reviewed journal in the near future. Leading on from these findings, and consequent to the recent capital raising, the Company will now conduct a further study in collaboration with Associate Professor Samuel's group, which will focus on the effects of Cymerus™ MSCs in combination with and in comparison to corticosteroids. This study has direct clinical relevance, as corticosteroids are the most widely used class of drugs currently used to control and/or prevent asthma exacerbations. "Our findings so far are encouraging, in particular because Cymerus™ MSCs exerted effects that had not been seen with equivalent doses of human bone marrow-derived MSCs, or other stem cells, in the same model. We are therefore very pleased to be able to continue our collaboration with Cynata," said Associate Professor Samuel. "The final report of the initial study at Monash has strengthened our confidence that Cymerus™ MSCs could exert substantial disease-modifying effects (rather than just treating the symptoms) in asthma, which is a very exciting prospect, given the large number of people who are unable to gain control of their asthma using existing drugs," said Cynata Vice President of Product Development, Dr Kilian Kelly. "We are optimistic that this accelerated program will pave the way forward for a clinical trial in asthma patients in the near future," added Dr Kelly. Cynata Therapeutics Limited (ASX: CYP) is an Australian stem cell and regenerative medicine company that is developing a therapeutic stem cell platform technology, Cymerus™, originating from the University of Wisconsin-Madison, a world leader in stem cell research. The proprietary Cymerus™ technology addresses a critical shortcoming in existing methods of production of mesenchymal stem cells (MSCs) for therapeutic use, which is the ability to achieve economic manufacture at commercial scale. Cymerus™ utilises induced pluripotent stem cells (iPSCs) to produce a particular type of MSC precursor, called a mesenchymoangioblast (MCA). The Cymerus™ platform provides a source of MSCs that is independent of donor limitations and provides an "off-the-shelf" stem cell platform for therapeutic product use, with a pharmaceutical product business model and economies of scale. This has the potential to create a new standard in the emergent arena of stem cell therapeutics and provides both a unique differentiator and an important competitive position. This message and its attachments may contain legally privileged or confidential information. It is intended solely for the named addressee. If you are not the addressee indicated in this message (or responsible for delivery of the message to the addressee), you may not copy or deliver this message or its attachments to anyone. Rather, you should permanently delete this message and its attachments and kindly notify the sender by reply e-mail. No warranty is made that the e-mail or attachment(s) are free from computer virus or other defect. If you wish to be removed from our contact list please send an email to info@monsoon.com.au immediately. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cynata-advances-development-of-cymerustm-mscs-for-the-treatment-of-asthma-300416530.html


News Article | December 2, 2016
Site: www.eurekalert.org

International research involving a Monash University scientist is using new computer models and evidence from meteorites to show that a low-mass supernova triggered the formation of our solar system. The research is published in the most recent issue of leading scientific journal Nature Communications. About 4.6 billion years ago, a cloud of gas and dust that eventually formed our solar system was disturbed. The ensuing gravitational collapse formed the proto-Sun with a surrounding disc where the planets were born. A supernova--a star exploding at the end of its life-cycle--would have enough energy to induce the collapse of such a gas cloud. "Before this model there was only inconclusive evidence to support this theory," said Professor Alexander Heger from the Monash School of Physics and Astronomy. The research team, led by University of Minnesota School of Physics and Astronomy Professor Yong-Zhong Qian, decided to focus on short-lived radioactive nuclei only present in the early solar system. Due to their short lifetimes, these nuclei could only have come from the triggering supernova. Their abundances in the early solar system have been inferred from their decay products in meteorites. As the debris from the formation of the solar system, meteorites are comparable to the leftover bricks and mortar in a construction site. They tell us what the solar system is made of and in particular, what short-lived nuclei the triggering supernova provided. "Identifying these 'fingerprints' of the final supernova is what we needed to help us understand how the formation of the solar system was initiated," Professor Heger said. "The fingerprints uniquely point to a low-mass supernova as the trigger. "The findings in this paper have opened up a whole new direction of research focusing on low-mass supernovae," he said. In addition to explaining the abundance of Beryllium-10, this low-mass supernova model would also explain the short-lived nuclei Calcium-41, Palladium-107, and a few others found in meteorites. Professor Qian said the group would like to examine the remaining mysteries surrounding short-lived nuclei found in meteorites. The research is funded by the US Department of Energy Office of Nuclear Physics. Professor Heger and a new Monash Future Fellow, Dr Bernhard Mueller, also study such supernovae using computational facilities at the Minnesota Supercomputing Institute. To read the full paper, titled "Evidence from stable isotopes and Be-10 for solar system formation triggered by a low-mass supernova," visit the Nature Communications website


News Article | December 7, 2016
Site: www.eurekalert.org

Every 18 seconds someone dies from tuberculosis (TB). It is the world's most deadly infectious disease. Mycobacterium tuberculosis, the causative agent of TB, has infected over one-third of the entire human population with an annual death toll of approximately 1.5 million people. For the first time, an international team of scientists from Monash and Harvard Universities have seen how, at a molecular level, the human immune system recognises TB infected cells and initiates an immune response. Their findings, published in Nature Communications, are the first step toward developing new diagnostic tools and novel immunotherapies. Lead author, Professor Jamie Rossjohn says one of the main reasons for our current lack of knowledge comes down to the complexity of the bacterium itself. Working with Professor Branch Moody's team at Harvard, they have begun to gain key insight into how the immune system can recognise this bacterium. Crucial to the success of M. tuberculosis as a pathogen is its highly unusual cell wall that not only serves as a barrier against therapeutic attack, but also modulates the host immune system. Conversely, its cell wall may also be the "Achilles' heel" of mycobacteria as it is essential for the growth and survival of these organisms. This unique cell wall is comprised of multiple layers that form a rich waxy barrier, and many of these lipid -- also known as fatty acids -- components represent potential targets for T-cell surveillance. Specifically, using the Australian Synchrotron, the team of scientists have shown how the immune system recognises components of the waxy barrier from the M. tuberculosis cell wall. "With so many people dying from TB every year, any improvements in diagnosis, therapeutic design and vaccination will have major impacts," Professor Moody says. "Our research is focussed on gaining a basic mechanistic understanding of an important biomedical question. And may ultimately provide a platform for designing novel therapeutics for TB and treat this devastating disease," Professor Rossjohn concludes. Professor Jamie Rossjohn is a Chief Investigator on the Australian Research Council Centre of Excellence in Advanced Molecular Imaging. The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact. The Imaging CoE is headquartered at Monash University with four collaborating organisations - La Trobe University, the University of Melbourne, University of New South Wales and the University of Queensland. Professor Rossjohn is also a researcher at the Monash Biomedicine Discovery Institute. Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.


News Article | February 1, 2016
Site: news.yahoo.com

A giant flightless bird known as Genyornis newtoni (R) is surprised on her nest by a 1 ton, predatory lizard named Megalania prisca in Australia roughly 50,000 thousand years ago, in this illustration courtesy of Peter Trusler, Monash University, Melbourne, Australia. Scientists said on 29 January, 2016 that burn patterns detected on Genyornis eggshell fragments indicate that the humans who first arrived to prehistoric Australia roughly 50,000 years ago gathered and cooked the big bird's eggs, playing havoc with its reproductive success and possibly contributing to its extinction. REUTERS/Illustration courtesy of Peter Trusler, Monash University/Handout via Reuters More WASHINGTON (Reuters) - The mystery behind the extinction of a huge flightless bird called Genyornis that flourished in the grasslands and woodlands of prehistoric Australia may have been solved, with burned eggshells as the clue and people as the culprits. Scientists said on Friday burn patterns detected on eggshell fragments indicate that the humans who first arrived in Australia roughly 50,000 years ago gathered and cooked the big bird's eggs, playing havoc with its reproductive success. The study is the first to provide direct evidence that these early human inhabitants preyed on the remarkable large animals that once thrived in Australia but disappeared after people got there, University of Colorado geological sciences professor Gifford Miller said. Genyornis, at almost 7 feet tall (2 meters) and perhaps 500 pounds (225 kg), was much bigger than today's large flightless birds like the ostrich or emu. It possessed powerful legs, small wings, large claws and a big beak for eating fruit, nuts and maybe small prey. It was a member of a family of giant birds called dromornithids, some reaching 10 feet (3 meters) tall and 1,100 pounds (500 kg), that was related to ducks, geese and swans. Genyornis vanished around 47,500 years ago, Miller said. The researchers analyzed burned Genyornis eggshell fragments, some only partially blackened, discovered at more than 200 sites. The eggs were the size of a cantaloupe, weighing about 3-1/2 pounds (1.5 kg). "We conclude that the only explanation is that humans harvested the giant eggs, built a fire and cooked them, which would not blacken them, then discarded the fragments in and around their fire as they ate the contents," Miller said. "Wild or natural fires could not produce such patterns. We have no direct evidence that humans hunted the adults, but loss of eggs certainly reduced reproductive success." There has been a long-running debate over whether people caused the extinction of Australia's unique collection of large animals, also including a 25-feet-long (7.5 meters) monitor lizard called Megalania, a nearly rhinoceros-sized wombat called Diprotodon, large marsupial predators and 1,000-pound (450-kg) kangaroos. More than 85 percent of Australia's large mammals, birds and reptiles disappeared after people arrived. Some experts blame human hunting, while others blame climate shifts, in particular continental drying from about 60,000 to 40,000 years ago. With the new study, published in the journal Nature Communications, the case for a human role becomes stronger, Miller said.


Researchers at Monash University and Peter MacCallum Cancer Centre have identified for the first time how a new class of epigenetic drug engages with the immune system to kill off cancer cells, offering powerful new pathways for enhanced blood cancer therapies. BET-inhibitors are a relatively new class of drug which work to 'switch off' important cancer-causing genes expressed within tumour cells. International clinical trials of BET-inhibitors for the treatment of blood cancers, such as Acute Myeloid Leukaemia, are now underway including at Monash and Peter Mac. However to date, this research has focused on the direct effects of the drugs in inducing cancer cell death and understanding how resistance emerges. In research published today in Cell Reports, the team at Peter Mac and Monash have demonstrated the potential for combining ground-breaking epigenetic and immune-based treatments for more potent results. Experiments conducted as part of the research, showed that immune-competent mice with lymphoma had a far greater response to BET-inhibitors than their immune-deficient counterparts. In addition to their primary function, the research showed the BET inhibitors were able to 'switch off' a protein called PD-L1, which is used by tumour cells to hide from the immune system. Through this mechanism, the BET-inhibitors were making tumour cells more sensitive to attack from the immune system. The power of an activated immune system in eliminating tumour cells has been proven through 'blockbuster' drugs such as 'Keytruda' and 'Opdivo', which also target the PD-L1 pathway. Building on this knowledge, this research confirmed that the combinations of BET-inhibitor with other immune therapies work better in lymphoma than either therapy alone. Based on laboratory research performed at Peter Mac, the Monash team is currently trialling a combination of a different epigenetic drug called Dinaciclib with the anti-PD1 therapy, Keytruda in relapsed lymphoma, myeloma and chronic lymphocytic leukaemia with further clinical trials for the combination therapy likely to emerge as a result of this research. This research was supported by the National Health and Medical Research Council of Australia; Victorian Cancer Agency; Cancer Council Victoria; Snowdome Foundation, The Kids Cancer Project, and Roche. Core technologies enabling the research are supported by the Australian Cancer Research Foundation and Peter MacCallum Cancer Foundation.


News Article | November 9, 2015
Site: cen.acs.org

Some compounds have never shown biological activity, even after being screened repeatedly in many different drug assays. But such “dark chemical matter,” or DCM, might have biological activity that just hasn’t been identified yet. Scientists at pharmaceutical firm Novartis report in a new article that DCM compounds can still be a promising starting point for discovering drug leads (Nat. Chem. Biol. 2015, DOI: 10.1038/nchembio.1936). “This article asks an important question,” says Paul Clemons of the Broad Institute, who was not involved with this study but has collaborated with some of the researchers. “Just because we haven’t seen any effect, does that mean we will continue failing to see any effect if we keep looking?” The Novartis team analyzed the results from more than 650 assays, some from the company’s own drug discovery collection and others from a National Institutes of Health program. They found that 14% of molecules screened in the Novartis assays and 36% of molecules in the NIH assays had never been hits in any test. The DCM compounds tended to be more soluble and less hydrophobic, with lower molecular weights and with fewer aromatic rings than biologically active compounds. But those physical differences alone don’t explain the lack of activity in DCM molecules, the researchers say. “Many of the DCM compounds we have identified have no obvious reason that they would, a priori, be inactive in so many of the screens,” says Anne Mai Wassermann, a former postdoc at Novartis who’s now at Pfizer. “These DCM compounds are not dramatically different in structure from compounds that are commonly identified as hits.” Indeed, almost all of the substructural features in “dark” compounds can be found in active compounds, she says. And just because a compound has not yet been active in a biological assay doesn’t mean that will be the case for all future assays. The Novartis team tested DCM compounds in several of the firm’s assays and identified four DCM compounds with antifungal activity. “This work has increased the visibility of DCM compounds with respect to how they are viewed as potentially unique or privileged when they hit in an assay,” says John W. Davies, head of in silico lead discovery at Novartis. “It is our hope that they may be specific to a particular target class or uniquely selective in their mechanism of action,” says Meir Glick, who led the study at Novartis but is now cheminformatics director at Merck & Co. DCM compounds are on the opposite end of the continuum from a troublesome group of molecules called pan assay interference compounds, or PAINS, which frequently register as hits during assays—and which are often false positives. “Flagging compounds as DCM may prove useful in high-throughput screening to highlight potential opportunity, just as the noting of compounds as PAINS can be used to highlight potential for severe risk,” says Michael A. Walters, a high-throughput screening expert at the University of Minnesota, Twin Cities. In screening DCM compounds, “there is a relatively high risk you may not get a hit,” says Jonathan B. Baell, a screening expert at Monash University. “But if you do, the presumed selectivity is then very valuable.” This article has been translated into Spanish by Divulgame.org and can be found here.


News Article | November 21, 2016
Site: www.eurekalert.org

By charting the slopes and crags on animals' teeth as if they were mountain ranges, scientists at the Smithsonian's National Museum of Natural History have created a powerful new way to learn about the diets of extinct animals from the fossil record. Understanding the diets of animals that lived long ago can tell researchers about the environments they lived in and help them piece together a picture of how the planet has changed over deep time. The new quantitative approach to analyzing dentition, reported Nov. 21 in the journal Methods in Ecology and Evolution, will also give researchers a clearer picture of how animals evolve in response to changes in their environment. "The new method gives researchers a way to measure changes that arose as animals adapted to environments altered by mass extinctions or major climate shifts," said Smithsonian paleontologist Sílvia Pineda-Munoz, who led the technique's development. "By using shape algorithms to examine teeth before and after these perturbations, we can understand the morphological adaptations that happen when there is an [environmental] change. That in turn can help researchers and conservationists predict and plan for such events in the future. It is another tool we can use to understand how present-day communities are going to be affected if something like that happens now." Pineda-Munoz is a postdoctoral fellow in the Natural History Museum's Evolution of Terrestrial Ecosystems Program, which brings together researchers from different disciplines to investigate how terrestrial ecosystems are structured and how they have changed over geologic time. She developed the new method of determining an animal's diet in collaboration with colleagues at Arizona State University, Macquarie University, Monash University and the Museum Victoria in Melbourne. Paleobiologists have long compared the shapes of fossil teeth to those of existing animals to make inferences about what prehistoric species ate millions of years ago. The new method builds on this approach but is more informative and precise, computationally comparing the surfaces of an animal's teeth with those of more than 130 present-day mammals. The technique relies on a three-dimensional scan of a set of teeth, which generates a digital model resembling a topographic map of the Earth's surface. GIS (geographic information system) technology is used to analyze the map, mathematically describing several key features that influence how teeth process food. For example, the program measures how often the slope of tooth surfaces change--an indicator of complexity. Diets made up of foods that require a lot of mechanical processing before they are digested, like tough vegetation, are associated with more complex dentition, Pineda-Munoz explains. While she was a graduate student at Macquarie University, Pineda-Munoz mapped the teeth of 134 contemporary mammals, including representatives from each of eight different dietary categories. "Those categories give detailed information about an animal's primary food source, including plants, meat, fruits, grains, insects, fungus or tree saps, with an additional 'generalist' diet category," Pineda-Munoz said. Pineda-Munoz and her colleagues created a database recording six measurable features of tooth topology for the top and bottom sets of teeth from present-day mammals. Variations in those features reflected differences in the animals' diets. For example, pandas, whose teeth must crush tough leaves, have the most complex teeth, whereas hyenas' scissor-like teeth are efficient for tearing meat. To determine what types of food extinct animals were best equipped to eat, researchers can scan teeth from the fossil record and mathematically compare how their shapes relate to the teeth of animals with known diets--an approach similar to the algorithms websites use to predict what related content a user will enjoy based on past favorites. "Because the method precisely measures the shape of teeth, it will be valuable in assessing how animals' teeth have changed over the course of evolution," Pineda-Munoz said. "It's a method that looks at evolutionary change. It tells you not just what the animal was eating at this point in time, but what the animal was adapted to eating."


News Article | December 14, 2016
Site: www.eurekalert.org

Sydney, Australia: Australian researchers from the National Computational Infrastructure (NCI) and the ARC Centre of Excellence for Climate System Science have produced a remarkable high-resolution animation of the largest El Niño ever recorded. It is so detailed that it took 30,000 computer hours crunching ocean model data on Australia's most powerful supercomputer, Raijin, before it could be extracted by the NCI visualisation team to produce the animation. The animation looks beneath the ocean surface to reveal the oceanic processes that led to the 1997/98 El Niño - an event that caused billions of dollars of damage worldwide and was followed by consecutive strong La Niña events. "The animation shows how shifting pools of warmer or cooler than average water 300m below the surface of the ocean can trigger these powerful events," said Dr Alex Sen Gupta, a member of the visualisation team from the ARC Centre of Excellence for Climate System Science. "When these pools of water burst through to the surface and link up with the atmosphere they can set off a chain reaction that leads to El Niños or La Niñas," The ocean model that produced the animation used a 30km horizontal grid and split the vertical depth into 50 cells, which allowed the researchers to see the development of the El Niño and La Niñas at a high resolution. "Raijin gives us the capacity to model complex global systems like El Niño that require a high resolution for a better accuracy," said a member of the team from the Australian National University, Associate Prof Andy Hogg. "It was these huge volumes of data produced by the model that meant we needed the specialist visualisation expertise from NCI to reveal what happened in detail." The 97/98 El Niño was a particularly damaging event. It was linked to massive forest fires in Indonesia, catastrophic flooding in Peru and the first "global" coral bleaching event that killed 16% of the world's corals in a single year. While it is impossible to prevent such events, researchers believe and the model confirms that better observation systems can help us forecast them earlier. "The animation shows us that a well developed deep ocean observation system can give us advance warning of extreme El Niños and La Niñas," said team member Dr Shayne McGregor from Monash University. "Preserving and expanding the currently sparse observation system is critical to improving our seasonal prediction capability in the future." Research over the past few years led by CSIRO and the University of New South Wales has indicated that "super" El Niños like the 97/98 event are likely to become more frequent as the climate warms. A member of the visualisation team, Dr Agus Santoso found in 2013 that as the climate warms, we are likely to see noticeable changes to El Niños. "As the planet warms it also appears that the swings between the two extremes, from El Niño to La Niña like the 1997 to 1999 sequence, will become more frequent," said Dr Santoso from the University of New South Wales. "For this reason and many others a reliable early warning of El Niño and La Niña will be vital for farmers, industry groups and societies to be better prepared for the extreme conditions they inevitably bring."


News Article | December 13, 2016
Site: www.eurekalert.org

Hoboken, NJ - December 13, 2016 - John Wiley and Sons, Inc. (NYSE: JWa and JWb) and The American Society for Bone and Mineral Research (ASBMR) announced today plans to launch in 2017 a new international, open access peer-reviewed publication, JBMR Plus. JBMR Plus joins ASBMR's flagship subscription journal, Journal of Bone and Mineral Research® (JBMR), the top-ranked journal in the field of bone, mineral and musculoskeletal research, as the favored venue for publishing original research on all aspects of bone and musculoskeletal research through open access publication. JBMR Plus aims to fill a need in the growing interdisciplinary field of research involving endocrinology, orthopedics, and rheumatology. JBMR Plus will publish original research, reviews, detailed protocols and methods, and special articles in basic, translational and clinical science relevant to bone, musculoskeletal metabolism and regenerative medicine research. Jane Cauley, President of ASBMR, said "We are excited to launch a major new addition to ASBMR's publishing program, one that will build on our strong leadership in the promotion of basic and clinical science related to bone, muscle and mineral metabolism. An open access journal in this area will support the evolving and expanding needs of researchers, clinicians, educators and authors and continue to further the mission of the ASBMR. We look forward to working with our publishing partner Wiley, a proven leader in open access and publishing innovation." JBMR Plus will be helmed by Editor-in-Chief Peter Ebeling, A.O., M.D., M.B.B.S., FRACP, Head of the Department of Medicine at Monash University in Melbourne, Australia. In addition to its distinguished Editor-in-Chief, JBMR Plus will be supported by Deputy Editors Bo Abrahamsen, M.D., Ph.D., and Teresita Bellido, Ph.D. Dr. Abrahamsen is a Professor of Clinical Database Studies and Consultant Endocrinologist at the University of Southern Denmark and Dr. Bellido serves as a Professor of Anatomy & Cell Biology at Indiana University in the United States. "JBMR Plus aims to accelerate the research into bone biology that has underpinned the recent innovative and targeted therapeutic advances in bone and mineral and musculoskeletal research. The NIH-mandated needs for reproducibility and excellence in study design, as well as those for open access, will also be well served by JBMR Plus," said Peter Ebeling, Editor-in-Chief. All articles in JBMR Plus will be published under the Creative Commons (CC-BY and CC-BY-NC-ND) licenses on Wiley Online Library. Authors with open access mandates from funders will be fully compliant when publishing with this journal. Waivers and discounts to the article publication fees are available to authors in developing countries and under special circumstances, and authors affiliated with, or funded by, an organization that has a Wiley Open Access Account can publish without directly paying any publication charges. "Wiley is proud to expand on our partnership with ASBMR to launch JBMR Plus," said Colette Bean, Vice President & Society Director at Wiley. "ASBMR has long been the premier society for the research and practice of bone and musculoskeletal biology and we are excited to work with the society and the journal editorial team toward establishing JBMR Plus as the next great destination for the bone community." The journal will begin accepting submissions in January 2017 and plans to publish the first issue online in summer 2017. For more information, visit http://www. . JBMR Plus publishes original research, reviews, detailed protocols and methods, and special articles in basic, translational and clinical science relevant to bone, musculoskeletal metabolism and regenerative medicine research. The journal welcomes research on osteoimmunology as well as research on fat, muscle, cartilage and kidney interactions with bone. Clinical studies, including trials and observational studies, and epidemiology and pharmacoepidemiology studies are encouraged. JBMR Plus also welcomes manuscripts on orthopedics, stem cell therapies, specialized biomechanics protocols, novel imaging techniques and big data. For more information, visit http://www. . About American Society for Bone and Mineral Research The American Society for Bone and Mineral Research (ASBMR) is the leading professional, scientific and medical society established to bring together clinical and experimental scientists involved in the study of bone, mineral and musculoskeletal research. ASBMR encourages and promotes the study of this expanding field through annual scientific meetings, an official journal (Journal of Bone and Mineral Research®), the Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, advocacy and interaction with government agencies and related societies. To learn more about upcoming meetings and publications, please visit http://www. . Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www. .


News Article | October 28, 2016
Site: marketersmedia.com

VANCOUVER, BC / ACCESSWIRE / October 28, 2016 / GB Minerals Ltd. (TSXV: GBL) (the "Company") is pleased to announce the appointment of Mr. Damien Forer interim chief financial officer ("Interim CFO") of the Company for a six month period commencing November 1, 2016. Angel Law, the Company's chief financial officer, will be on maternity leave during the period of Mr. Forer's appointment. Mr. Forer has more than 15 years of accounting, corporate finance and restructuring experience in Canada, the United Kingdom and Australia. He has over 10 years' experience in public practice which included time spent with Deloitte in Australia and BDO Stoy Hayward in the United Kingdom. Damien is a member of both Chartered Professional Accountants British Columbia and Chartered Accountants Australia and New Zealand. He holds a Bachelor of Accounting degree from Monash University, Australia. Luis da Silva, president and chief executive officer of the Company, said, "We are pleased to welcome Damien to our team. The Company is in the midst of an exciting development phase and his skills and experience will be of great benefit to us. We would also like to extend our best wishes to Angel Law and her family during this very special period and thank her for her commitment, support and financial leadership to the Company to date." For further information please contact: On September 14, 2015, the Company announced the results of, and filing on SEDAR, of a new feasibility study on its Farim phosphate project entitled "NI 43-101 Technical Report On the Farim Phosphate Project" (the "2015 Feasibility Study"). The Farim phosphate project is located in the northern part of central Guinea-Bissau, West Africa, approximately 25 kilometres south of the Senegal border, approximately 5 kilometres west of the town of Farim and some 120 kilometres northeast of Bissau, the capital of Guinea-Bissau, on a 30.6 km2 mining lease license granted by the Government of Guinea-Bissau to the Company's wholly owned subsidiary, GB Minerals AG, in May 2009. The Company also holds a production license in relation to the Farim phosphate project. The Farim phosphate project consists of a high grade sedimentary phosphate deposit of one continuous phosphate bed which extends over a known surface area of approximately 40 km2. It is estimated to contain measured and indicated resources of 105.6 million dry tonnes at a grade of 28.4% P2O5 and additional inferred resources of 37.6 million dry tonnes at 27.7% P2O5. The measured and indicated resources include 44.0 million dry tonnes of reserves based on a 25 year mine plan at 1.75 million tonnes per annum ("mtpa") of mine production at the following run of mine grades: 30.0% P2O5, 2.6% Al2O3, 41.0% CaO, 4.7% Fe2O3, and 10.6% SiO2. The phosphate ore will be beneficiated for a final phosphate rock concentrate production of 1.32 mtpa at a 34.0% P2O5 grade at 3% moisture. The 25 year mine plan also assumes a beneficiation process that involves scrubbing (both drum and attrition) followed by particle sizing to remove the fraction under 20 µm. This new beneficiation process will result in a 34.0% P2O5 product grade, mass recovery of 75.5% and 78.4% P2O5 recovery confirmed by a pilot scale test on a one tonne sample that took place in May 2015. After passing through the process plant, the final production of phosphate concentrate, based on 1.75 mtpa of run of mine feed, will be 1.32 mtpa. The life of mine operating costs are approximately US$52.13 per tonne of final concentrate. The initial capital cost for the project is estimated at US$193.8 million and does not include owner's costs which amount to US$11 million and include items such as project insurance, resettlement and owner's team costs. Owner's costs have been included in the financial analysis. For additional information, please visit us at www.gbminerals.com. The Company's Qualified Person is Dan Markovic, P. Eng., who has reviewed and approves this press release. Certain information in this news release relating to the Company is forward-looking and related to anticipated events and strategies. When used in this context, words such as "will", "anticipate", "believe", "plan", "intend", "target" and "expect" or similar words suggest future outcomes. Forward-looking information contained in this press release includes, but may not be limited to the use of proceeds of the Rights Offering, the business plans, statements or information relating to the anticipated development activities of the Company, the Farim Project (including the quantity and quality of mineral resource and mineral reserve estimates), the potential to upgrade inferred mineral resources, the ability of the Company to develop the Farim Project into a commercially viable mine and the proposed new plans relating thereto regarding operations and mine design, estimates relating to tonnage, grades, recovery rates, future phosphate production, future cash flows, life of mine estimates, expectations regarding production and estimates of capital and operating costs. By their nature, such statements are subject to significant risks and uncertainties that may cause actual results or events to differ materially from current expectations. Readers are cautioned not to place undue reliance on forward-looking information as actual results could differ materially from the plans, expectations, estimates or intentions expressed in the forward-looking information. Forward-looking information speaks only as of the date on which it is made and, except as may be required by applicable law, the Company disclaims any obligation to update or modify such forward-looking information, either as a result of new information, future events or for any other reason. Disclosure herein of exploration information and of mineral resources and mineral reserves is derived from the 2015 Feasibility Study. Information relating to "mineral resources" and "mineral reserves" is deemed to be forward-looking information as it involves the implied assessment based on certain estimates and assumptions that the mineral resources and mineral reserves can be profitable in the future. Such estimates are expressions of judgment based on knowledge, mining experience, analysis of drilling results and industry practices. Valid estimates made at a given time may significantly change when new information becomes available. By their nature, mineral resource and mineral reserve estimates are imprecise and depend, to a certain extent, upon statistical inferences which may ultimately prove unreliable. If such estimates are inaccurate or are reduced in the future, this could have a material adverse impact on the Company. Accordingly, readers should not place undue reliance on forward-looking information. Mineral resources that are not mineral reserves do not have demonstrated economic viability. Due to the uncertainty that may be attached to inferred mineral resources, it cannot be assumed that all or any part of an inferred mineral resource will be upgraded to an indicated or measured mineral resource as a result of continued exploration. NEITHER THE TSX VENTURE EXCHANGE NOR ITS REGULATION SERVICES PROVIDER (AS THAT TERM IS DEFINED IN THE POLICIES OF THE TSX VENTURE EXCHANGE) ACCEPTS RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE VANCOUVER, BC / ACCESSWIRE / October 28, 2016 / GB Minerals Ltd. (TSXV: GBL) (the "Company") is pleased to announce the appointment of Mr. Damien Forer interim chief financial officer ("Interim CFO") of the Company for a six month period commencing November 1, 2016. Angel Law, the Company's chief financial officer, will be on maternity leave during the period of Mr. Forer's appointment. Mr. Forer has more than 15 years of accounting, corporate finance and restructuring experience in Canada, the United Kingdom and Australia. He has over 10 years' experience in public practice which included time spent with Deloitte in Australia and BDO Stoy Hayward in the United Kingdom. Damien is a member of both Chartered Professional Accountants British Columbia and Chartered Accountants Australia and New Zealand. He holds a Bachelor of Accounting degree from Monash University, Australia. Luis da Silva, president and chief executive officer of the Company, said, "We are pleased to welcome Damien to our team. The Company is in the midst of an exciting development phase and his skills and experience will be of great benefit to us. We would also like to extend our best wishes to Angel Law and her family during this very special period and thank her for her commitment, support and financial leadership to the Company to date." For further information please contact: On September 14, 2015, the Company announced the results of, and filing on SEDAR, of a new feasibility study on its Farim phosphate project entitled "NI 43-101 Technical Report On the Farim Phosphate Project" (the "2015 Feasibility Study"). The Farim phosphate project is located in the northern part of central Guinea-Bissau, West Africa, approximately 25 kilometres south of the Senegal border, approximately 5 kilometres west of the town of Farim and some 120 kilometres northeast of Bissau, the capital of Guinea-Bissau, on a 30.6 km2 mining lease license granted by the Government of Guinea-Bissau to the Company's wholly owned subsidiary, GB Minerals AG, in May 2009. The Company also holds a production license in relation to the Farim phosphate project. The Farim phosphate project consists of a high grade sedimentary phosphate deposit of one continuous phosphate bed which extends over a known surface area of approximately 40 km2. It is estimated to contain measured and indicated resources of 105.6 million dry tonnes at a grade of 28.4% P2O5 and additional inferred resources of 37.6 million dry tonnes at 27.7% P2O5. The measured and indicated resources include 44.0 million dry tonnes of reserves based on a 25 year mine plan at 1.75 million tonnes per annum ("mtpa") of mine production at the following run of mine grades: 30.0% P2O5, 2.6% Al2O3, 41.0% CaO, 4.7% Fe2O3, and 10.6% SiO2. The phosphate ore will be beneficiated for a final phosphate rock concentrate production of 1.32 mtpa at a 34.0% P2O5 grade at 3% moisture. The 25 year mine plan also assumes a beneficiation process that involves scrubbing (both drum and attrition) followed by particle sizing to remove the fraction under 20 µm. This new beneficiation process will result in a 34.0% P2O5 product grade, mass recovery of 75.5% and 78.4% P2O5 recovery confirmed by a pilot scale test on a one tonne sample that took place in May 2015. After passing through the process plant, the final production of phosphate concentrate, based on 1.75 mtpa of run of mine feed, will be 1.32 mtpa. The life of mine operating costs are approximately US$52.13 per tonne of final concentrate. The initial capital cost for the project is estimated at US$193.8 million and does not include owner's costs which amount to US$11 million and include items such as project insurance, resettlement and owner's team costs. Owner's costs have been included in the financial analysis. For additional information, please visit us at www.gbminerals.com. The Company's Qualified Person is Dan Markovic, P. Eng., who has reviewed and approves this press release. Certain information in this news release relating to the Company is forward-looking and related to anticipated events and strategies. When used in this context, words such as "will", "anticipate", "believe", "plan", "intend", "target" and "expect" or similar words suggest future outcomes. Forward-looking information contained in this press release includes, but may not be limited to the use of proceeds of the Rights Offering, the business plans, statements or information relating to the anticipated development activities of the Company, the Farim Project (including the quantity and quality of mineral resource and mineral reserve estimates), the potential to upgrade inferred mineral resources, the ability of the Company to develop the Farim Project into a commercially viable mine and the proposed new plans relating thereto regarding operations and mine design, estimates relating to tonnage, grades, recovery rates, future phosphate production, future cash flows, life of mine estimates, expectations regarding production and estimates of capital and operating costs. By their nature, such statements are subject to significant risks and uncertainties that may cause actual results or events to differ materially from current expectations. Readers are cautioned not to place undue reliance on forward-looking information as actual results could differ materially from the plans, expectations, estimates or intentions expressed in the forward-looking information. Forward-looking information speaks only as of the date on which it is made and, except as may be required by applicable law, the Company disclaims any obligation to update or modify such forward-looking information, either as a result of new information, future events or for any other reason. Disclosure herein of exploration information and of mineral resources and mineral reserves is derived from the 2015 Feasibility Study. Information relating to "mineral resources" and "mineral reserves" is deemed to be forward-looking information as it involves the implied assessment based on certain estimates and assumptions that the mineral resources and mineral reserves can be profitable in the future. Such estimates are expressions of judgment based on knowledge, mining experience, analysis of drilling results and industry practices. Valid estimates made at a given time may significantly change when new information becomes available. By their nature, mineral resource and mineral reserve estimates are imprecise and depend, to a certain extent, upon statistical inferences which may ultimately prove unreliable. If such estimates are inaccurate or are reduced in the future, this could have a material adverse impact on the Company. Accordingly, readers should not place undue reliance on forward-looking information. Mineral resources that are not mineral reserves do not have demonstrated economic viability. Due to the uncertainty that may be attached to inferred mineral resources, it cannot be assumed that all or any part of an inferred mineral resource will be upgraded to an indicated or measured mineral resource as a result of continued exploration. NEITHER THE TSX VENTURE EXCHANGE NOR ITS REGULATION SERVICES PROVIDER (AS THAT TERM IS DEFINED IN THE POLICIES OF THE TSX VENTURE EXCHANGE) ACCEPTS RESPONSIBILITY FOR THE ADEQUACY OR ACCURACY OF THIS RELEASE


~World-renowned economist Professor Jeffrey Sachs to speak at inaugural conference and launch of the Jeffrey Sachs Center on Sustainable Development at Sunway University~ BANDAR SUNWAY, Malaysia, Nov. 14, 2016 /PRNewswire/ -- The Jeffrey Cheah Foundation (JCF) and the United Nations Sustainable Development Solutions Network (SDSN) Association are launching the Jeffrey Sachs Center on Sustainable Development (JSC) at Sunway University in Malaysia, as a catalytic move to mobilise comprehensive collaboration, particularly amongst Southeast Asian nations, to move towards achieving the 17 Sustainable Development Goals (SDGs). The Jeffrey Sachs Center on Sustainable Development is the result of a gift of USD10 million from the Jeffrey Cheah Foundation, Malaysia's largest education-focused social enterprise. To date, the gift is the largest financial commitment focused on SDG education and implementation since 193 members of the UN adopted the 17 goals in September 2015. In conjunction with the launch, there will be an inaugural conference featuring five keynote speakers and pundits in the area of sustainability. The event will be held at Sunway University in Malaysia on 9 December 2016, titled 'Moving Decisively Forward on Sustainable Development Now!' The five experts are: Professor Jeffrey Sachs' talk will be on "What Does Sustainable Development Really Mean?", Professor Tan Sri Zakri Abdul Hamid will be speaking on "Walking the Talk on Implementing the SDGs: A Case for Malaysia and South-East Asia," Professor Daniel Schrag will be covering "Climate Change and Sustainable Development: Opportunities for the Developing World", Professor Angelo Riccaboni will focus on "Food Systems for Sustainable Development: Innovations are Needed" while Professor Xue Lan will be discussing "Policy Challenges in Implementing Sustainable Development Goals." The Jeffrey Cheah Foundation is modelled along the lines of some of the oldest and most eminent universities in the world, such as Harvard University. To date, the Foundation retains ownership and equity of 16 learning institutions, including Sunway University, Monash University Malaysia*, the Jeffrey Cheah School of Medicine and Health Sciences, Sunway College, Sunway TES Centre for Accountancy Excellence and Sunway International School, valued at more than RM720 million (now in excess of RM1 billion). For more information on the Jeffrey Sachs Center on Sustainable Development (JSC) at Sunway University please email: jsc@sunway.edu.my *Monash University Malaysia is jointly-owned by Monash Australia and Jeffrey Cheah Foundation


News Article | December 7, 2016
Site: www.eurekalert.org

How do seabirds share habitat when food is limited? In the case of frigatebirds, size differences drive them to seek different prey. A study in The Auk: Ornithological Advances uses new technology to explore how closely related Great and Lesser frigatebirds manage to coexist at shared breeding colonies where the need to stick close to their nests prevents them from traveling far in search of food. Past studies have suggested that Great and Lesser frigatebirds have very similar foraging habits, but ecology's "competitive exclusion principle" suggests that they must not be going after exactly the same food, or one would eventually outcompete the other. New advances in GPS tracking and chemical analysis of birds' tissues allowed Rowan Mott of Australia's Monash University and his colleagues to tease out some of the subtle differences that let these species coexist, and they found that the smaller Lesser Frigatebirds were eating prey items from lower on the food chain than their larger relatives, allowing the two species to subsist on the same resource base. "As I began reading about frigatebirds, it seemed as if Great Frigatebirds and Lesser Frigatebirds share a remarkably similar foraging strategy. This didn't sit well with my understanding of the competitive exclusion principle and niche partitioning theory," says Mott. "It turns out that the two species of frigatebirds seem to have slight differences in their diet that are related to body size. The larger-bodied Great Frigatebird eats more prey from higher levels of the food chain than the smaller-bodied Lesser Frigatebird, and this relationship is particularly strong when comparing the diet of females with the male diet, because females are considerably larger than males." Mott and his colleagues carried out their research on an island in the Timor Sea, where they captured birds on their nests during the breeding season, fitting them with GPS devices and collecting feathers and blood for isotope analysis. By analyzing the ratios of nitrogen and carbon isotopes in the birds' tissues, the researchers could glean insights into the types of food they had been eating--for example, predatory fish have higher proportion of a certain nitrogen isotope in their bodies, allowing the researchers to make inferences about prey type. "Ecologists argue that coexistence of similar species can only persist if populations have more resources than they need or if they use different subsets of resources," according to Acadia University's Dave Shutler, a seabird ecologist not involved in the study. "In the latter case, identifying where and how species partition resources can be challenging for mobile species such as birds; using tracking devices and chemical signatures in tissues, Mott and his collaborators have evaluated differences in diets and spatial use of two species of frigatebirds." "Resource partitioning between species and sexes in Great Frigatebirds and Lesser Frigatebirds" will be available December 7, 2016, at http://americanornithologypubs. (issue URL http://americanornithologypubs. ). About the journal: The Auk: Ornithological Advances is a peer-reviewed, international journal of ornithology that began in 1884 as the official publication of the American Ornithologists' Union, which merged with the Cooper Ornithological Society in 2016 to become the American Ornithological Society. In 2009, The Auk was honored as one of the 100 most influential journals of biology and medicine over the past 100 years.


Understanding the diets of animals that lived long ago can tell researchers about the environments they lived in and help them piece together a picture of how the planet has changed over deep time. The new quantitative approach to analyzing dentition, reported Nov. 21 in the journal Methods in Ecology and Evolution, will also give researchers a clearer picture of how animals evolve in response to changes in their environment. "The new method gives researchers a way to measure changes that arose as animals adapted to environments altered by mass extinctions or major climate shifts," said Smithsonian paleontologist Sílvia Pineda-Munoz, who led the technique's development. "By using shape algorithms to examine teeth before and after these perturbations, we can understand the morphological adaptations that happen when there is an [environmental] change. That in turn can help researchers and conservationists predict and plan for such events in the future. It is another tool we can use to understand how present-day communities are going to be affected if something like that happens now." Pineda-Munoz is a postdoctoral fellow in the Natural History Museum's Evolution of Terrestrial Ecosystems Program, which brings together researchers from different disciplines to investigate how terrestrial ecosystems are structured and how they have changed over geologic time. She developed the new method of determining an animal's diet in collaboration with colleagues at Arizona State University, Macquarie University, Monash University and the Museum Victoria in Melbourne. Paleobiologists have long compared the shapes of fossil teeth to those of existing animals to make inferences about what prehistoric species ate millions of years ago. The new method builds on this approach but is more informative and precise, computationally comparing the surfaces of an animal's teeth with those of more than 130 present-day mammals. The technique relies on a three-dimensional scan of a set of teeth, which generates a digital model resembling a topographic map of the Earth's surface. GIS (geographic information system) technology is used to analyze the map, mathematically describing several key features that influence how teeth process food. For example, the program measures how often the slope of tooth surfaces change—an indicator of complexity. Diets made up of foods that require a lot of mechanical processing before they are digested, like tough vegetation, are associated with more complex dentition, Pineda-Munoz explains. While she was a graduate student at Macquarie University, Pineda-Munoz mapped the teeth of 134 contemporary mammals, including representatives from each of eight different dietary categories. "Those categories give detailed information about an animal's primary food source, including plants, meat, fruits, grains, insects, fungus or tree saps, with an additional 'generalist' diet category," Pineda-Munoz said. Pineda-Munoz and her colleagues created a database recording six measurable features of tooth topology for the top and bottom sets of teeth from present-day mammals. Variations in those features reflected differences in the animals' diets. For example, pandas, whose teeth must crush tough leaves, have the most complex teeth, whereas hyenas' scissor-like teeth are efficient for tearing meat. To determine what types of food extinct animals were best equipped to eat, researchers can scan teeth from the fossil record and mathematically compare how their shapes relate to the teeth of animals with known diets—an approach similar to the algorithms websites use to predict what related content a user will enjoy based on past favorites. "Because the method precisely measures the shape of teeth, it will be valuable in assessing how animals' teeth have changed over the course of evolution," Pineda-Munoz said. "It's a method that looks at evolutionary change. It tells you not just what the animal was eating at this point in time, but what the animal was adapted to eating." Explore further: Tooth wear patterns suggest Paranthropus early hominins had softer diets than expected More information: Silvia Pineda-Munoz et al, Inferring diet from dental morphology in terrestrial mammals, Methods in Ecology and Evolution (2016). DOI: 10.1111/2041-210X.12691


News Article | January 21, 2017
Site: www.techtimes.com

The extinction of the Australian megafauna - what is the cause - has been the topic of debate for quite some time. According to a new study, the megafauna which became extinct nearly 45,000 years ago, the creatures vanished not because of climatic changes - as previously believed - but because of human hunting. "The debate over megafaunal extinction causes has consistently been between climate and humans. Having eliminated climate as the primary cause of extinction, we turn to consideration of human causation, of which hunting is most favoured as extinction driver," notes the abstract of the research. The cause for the extinction of the Australian megafauna, which comprises quite a few creatures, has been attributed to climate shift. The landscape in southwestern Australia changed to arid from a wooded one nearly 70,000 years ago. Some believe that the animals were unable to adapt and, therefore, died. The other school of thought is that early immigrants hunted the megafauna when they colonized Australia. Researchers also believe that it could be a combination of both the theories. The research which was led by the Monash University in Victoria, Australia, and the University of Colorado Boulder, used data from a sediment core in the Indian Ocean. This information aided the team in recreating the older climatic conditions of the continent. There were chronological layers of brown-colored material which were washed into the ocean. It also contained dust, ash, spores and pollen from a fungus dubbed Sporormiella. Professor Gifford Miller, who was part of the research team, shared that the Sporormiella fungus grows on the waste of plant-eating mammals. Miller further added that the sediment core allowed the researchers to travel back in time. In this case, it took them back 15,000 years. "The abundance of these spores is good evidence for a lot of large mammals on the southwestern Australian landscape up until about 45,000 years ago," said Miller. The giant Kangaroo with a body weight of up to 240 kg walked instead of hopping, alongside with the two ton wombats and a two-meter tail bird have all become extinct. Miller has also scrutinized the burned eggshells of the 400-pound bird Genyornis in 2016, which further asserts that human hunters were the main reason behind the disappearance of the megafuana. It has always been a debatable issue whether human hunting or climate change are to be cited as possible reasons for the extinction of the Australian megafauna. The study led by the two Universities has finally proven that the demise started due to instances of human overkilling and not adverse climatic conditions. The study has been published in the journal Nature Communication on Jan.20. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


Drinkwater N.,Monash University | Mcgowan S.,Monash University
Biochemical Journal | Year: 2014

Despite a century of control and eradication campaigns, malaria remains one of the world's most devastating diseases. Our once-powerful therapeutic weapons are losing the war against the Plasmodium parasite, whose ability to rapidly develop and spread drug resistance hamper past and present malaria-control efforts. Finding new and effective treatments for malaria is now a top global health priority, fuelling an increase in funding and promoting open-source collaborations between researchers and pharmaceutical consortia around the world. The result of this is rapid advances in drug discovery approaches and technologies, with three major methods for antimalarial drug development emerging: (i) chemistry-based, (ii) target-based, and (iii) cell-based. Common to all three of these approaches is the unique ability of structural biology to inform and accelerate drug development. Where possible, SBDD (structure-based drug discovery) is a foundation for antimalarial drug development programmes, and has been invaluable to the development of a number of current pre-clinical and clinical candidates. However, as we expand our understanding of the malarial life cycle and mechanisms of resistance development, SBDD as a field must continue to evolve in order to develop compounds that adhere to the ideal characteristics for novel antimalarial therapeutics and to avoid high attrition rates pre- and post-clinic. In the present review, we aim to examine the contribution that SBDD has made to current antimalarial drug development efforts, covering hit discovery to lead optimization and prevention of parasite resistance. Finally, the potential for structural biology, particularly high-throughput structural genomics programmes, to identify future targets for drug discovery are discussed. © The Authors Journal compilation © 2014 Biochemical Society.


Clarke I.J.,Monash University | Parkington H.C.,Monash University
Molecular and Cellular Endocrinology | Year: 2014

Gonadotropin inhibitory hormone (GnIH) has emerged as a negative regulator of gonadotrope function in a range of species. In rodents, such as rats and mice, GnIH exerts influence upon GnRH cells within the brain. In other species, however, the peptide is secreted into hypophysial portal blood to act on pituitary gonadotropes. In particular, a series of studies in sheep have demonstrated potent actions at the level of the pituitary gland to counteract the function of GnRH in terms of the synthesis and secretion of gonadotropins. This review focuses on the action of GnIH at the level of the gonadotrope. © 2013 Elsevier Ireland Ltd.


Chowdhury M.A.,Monash University
International Journal of Biological Macromolecules | Year: 2014

This article presents the perspectives on the lignin-based controlled release (CR) of bioactive materials which are based on the researches that took place over the last three decades. It encompasses three broad spectra of observations: CR formulations with mixed-matrix of lignin; CR formulations with modified lignin; and the lignin-based CR formulation modelling. The article covers a range of bioactive materials aimed for agricultural utilisations viz. herbicides, pesticides, insecticides and fertilisers for their controlled release studies, which were formulated either with lignin or lignin-based biopolymers. The inherent complexities, structural heterogeneities, and the presence of myriad range of functionalities in the lignin structure make it difficult to understand and explaining the underlying CR behaviour and process. In conjunction to this issue, the fundamental aspects of the synthetic and biocompatible polymer-based drug controlled release process are presented, and correlated with the lignin-based CR research. The articulation of this correlation and the overview presented in this article may be complemented of the future lignin-based CR research gaining better insights, reflections, and understanding. A recommended approach on the lignin depolymerisation is suggested to fragmenting the lignin, which may be tailored further using the re-polymerisation or other synthetic approaches. Thus it may allow more control with flexibilities and improved properties of the modified lignin materials, and help achieve the desired CR outcomes. © 2014 Elsevier B.V.


Medcalf R.L.,Monash University
Blood | Year: 2015

In this issue of Blood, Hijazi et al challenge the view that consumptive coagulopathy that accompanies traumatic brain injury (TBI) results in a sequence of events that lead to intracranial hemorrhage (ICH). © 2015 by The American Society of Hematology.


Vinuesa C.G.,Australian National University | Linterman M.A.,Babraham Institute | Yu D.,Monash University | Maclennan I.C.M.,University of Birmingham
Annual Review of Immunology | Year: 2016

Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination. Copyright © 2016 by Annual Reviews. All rights reserved.


O'Donnell L.,MIMR PHI Institute of Medical Research | O'Donnell L.,Monash University | O'Bryan M.K.,Monash University
Seminars in Cell and Developmental Biology | Year: 2014

Microtubules are dynamic polymers of tubulin subunits that underpin many essential cellular processes, such as cell division and migration. Spermatogenesis is the process by which spermatogenic stem cells undergo mitotic and meiotic division and differentiation to produce streamlined spermatozoa capable of motility and fertilization. This review summarizes the current knowledge of microtubule-based processes in spermatogenesis. We describe the involvement of microtubule dynamics in Sertoli cell shape and function, as well as in the mitotic and meiotic division of germ cells. The roles of microtubules in sperm head shaping, via the development and function of the manchette, and in sperm flagella development are also discussed. The review brings together data from microscopy studies and genetically modified mouse models, and reveals that the regulation of microtubule dynamics is essential for male fertility. © 2014 Elsevier Ltd.


Ilic D.,Monash University
Recent Results in Cancer Research | Year: 2014

Benign prostatic hyperplasia (BPH) and prostate cancer are common diseases of the prostate gland. BPH is commonly treated by pharmaceutical products, which commonly improve symptoms but are often off-set by adverse events including erectile dysfunction, which affect quality of life. Similarly, a variety of treatment options exist for the treatment of prostate cancer. The applicability of these prostate cancer treatments is reliant on stage of disease. Whilst effectiveness of prostate cancer treatments may vary, common adverse effects include erectile dysfunction, incontinence and lower quality of life. Early evidence from systematic reviews has suggested that diet and lifestyle factors may be beneficial in reducing the risk of cancer. Lycopene, a member of the carotenoid family, found commonly in red pigmented fruit and vegetables has been established as having strong antioxidant and pro-oxidant properties. This chapter examines the current evidence on the use of lycopene as a preventive agent for prostate disease. © 2014 Springer-Verlag Berlin Heidelberg.


Davis S.R.,Monash University | Worsley R.,Monash University
Journal of Steroid Biochemistry and Molecular Biology | Year: 2014

Testosterone is physiologically important for women. Serum testosterone levels decline with age, with the most precipitous fall being prior to menopause. There is no level of testosterone which defines a woman as being testosterone deficient. However, there is substantial high quality evidence to support the use of testosterone for the treatment of hypoactive sexual desire disorder in postmenopausal women. Although preliminary data suggests testosterone has favorable effects on bone and muscle mass, cognitive function and the cardiovascular system, further research regarding its therapeutic effects in these domains is warranted. As no testosterone product has been approved for women there is extensive off-label prescribing of testosterone products for women as well as the prescription of compounded therapy. This raises serious safety concerns and together with the evidence for the negative impact of FSD on quality of life, highlights the need for an approved testosterone formulation for women. This article is part of a Special Issue entitled 'Menopause'. © 2013 Elsevier Ltd.


Leong K.T.G.,Changi General Hospital | Walton A.,Alfred Hospital | Krum H.,Monash University
Annual Review of Medicine | Year: 2014

Resistant hypertension poses significant health concerns. There are strong demands for new and safe therapies to control resistant hypertension while addressing its common causes, specifically poor compliance to lifelong polypharmacy, lifestyle modifications, and physician inertia. The sympathetic nervous system plays a significant pathophysiological role in hypertension. Surgical sympathectomy for blood pressure reduction is an old but extremely efficacious therapeutic concept, now abandoned with the dawn of a safer contemporary pharmacology era. Recently, clinical studies have revealed promising results for safe and sustained blood pressure reduction with percutaneous renal sympathetic denervation. This is a novel, minimally invasive, device-based therapy, specifically targeting and ablating the renal artery nerves with radiofrequency waves without permanent implantation. There are also reported additional benefits in related comorbidities, such as impaired glucose metabolism, renal impairment, left ventricular hypertrophy, heart failure, and others. This review focuses on how selective renal sympathetic denervation works, its present and potential therapeutic indications, and its future directions. © 2014 by Annual Reviews. All rights reserved.


Forbes S.J.,University of Edinburgh | Rosenthal N.,Imperial College London | Rosenthal N.,Monash University
Nature Medicine | Year: 2014

Chronic diseases confer tissue and organ damage that reduce quality of life and are largely refractory to therapy. Although stem cells hold promise for treating degenerative diseases by 'seeding' injured tissues, the regenerative capacity of stem cells is influenced by regulatory networks orchestrated by local immune responses to tissue damage, with macrophages being a central component of the injury response and coordinator of tissue repair. Recent research has turned to how cellular and signaling components of the local stromal microenvironment (the 'soil' to the stem cells' seed), such as local inflammatory reactions, contribute to successful tissue regeneration. This Review discusses the basic principles of tissue regeneration and the central role locally acting components may play in the process. Application of seed-and-soil concepts to regenerative medicine strengthens prospects for developing cell-based therapies or for promotion of endogenous repair. © 2014 Nature America, Inc.


Tsai L.M.,Monash University | Yu D.,Monash University
Immunology and Cell Biology | Year: 2014

The generation of immunological memory during an immune response is a hallmark of the adaptive immune system. Follicular helper T (Tfh) cells are a CD4 + T-cell subset specialised to regulate antibody response. Emerging evidence suggests that during antibody response, Tfh memory is generated along with the generation of B-cell memory. There are multiple layers for the differentiation and function of memory Tfh cells. Both early committed precursor Tfh cells and effector Tfh cells exiting germinal centres can contribute to the memory Tfh pool. Functionally, memory Tfh cells not only enhance a secondary response upon antigen rechallenge but also circulate to non-draining lymph tissues to differentiate into effector Tfh cells in the face of systemic antigen/pathogen spreading, thus also promoting a primary response. Circulating memory Tfh cells are a valuable marker to monitor the Tfh programme in human autoimmune diseases, infections and vaccinations. Future studies are required to understand the molecular mechanisms determining the commitment and plasticity of Tfh memory and hence the physiological functions of Tfh memory. © 2014 Australasian Society for Immunology Inc.


Abramson M.J.,Monash University
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and methods of delivery, we updated the systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. SELECTION CRITERIA: Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Three authors independently assessed eligibility of studies for inclusion. Two authors independently performed quality assessment of studies. MAIN RESULTS: Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). AUTHORS' CONCLUSIONS: Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.


Gates W.P.,Monash University | Bouazza A.,Monash University
Geotextiles and Geomembranes | Year: 2010

Strongly alkaline solution pH causes changes to the mineralogy of bentonites which might impact on their performance as environmental barriers. The long term effect of solution pH on the performance of bentonite barriers such as in Geosynthetic Clay Liners needs to be studied from the viewpoint of solubility and stability of the mineral phases present at extreme pH values. Changes to bentonite mineralogy brought about by extended reaction with 1 M sodium hydroxide solutions at 20-25 °C reveal that certain components of bentonites, namely smectite, opaline silica and quartz, are subject to dissolution in alkaline solution. Associated with dissolution is the formation of hydrous hydroxy-aluminosilicate as well as hydrous carbonate mineral phases. It is postulated that these precipitates, formed from reaction of bentonite with alkaline leachates can result in pore filling, which is responsible for recently measured lower hydraulic conductivity of some bentonites to high pH leachates. © 2009 Elsevier Ltd. All rights reserved.


Yao C.K.,Monash University | Gibson P.R.,Monash University | Shepherd S.J.,La Trobe University
American Journal of Gastroenterology | Year: 2013

Clear guiding principles for the design and conduct of dietary intervention trials in functional gastrointestinal disorders (FGID) are lacking. This narrative review examines the specific challenges associated with the design and reporting in dietary intervention trials. Dietary intervention trials need to address the collinearity between food, nutrients, and bioactive components that obscure the relationship between food and their effects in the gut. Randomized, double-blinded, placebo-controlled studies remain the gold standard for dietary trials, but are limited by difficulties in adequate masking of study food or inappropriate choice of placebo food/diets. Provision of study diets as the preferred delivery method can somewhat address these limitations, although allowing good adherence compared with education-based dietary interventions. Issues associated with participant expectancies and dietary behaviors can alter the true effectiveness of a diet. In addition, failure to adjust for or report baseline intake of nutrients of interest can reduce their magnitude of benefit. Bias in subjective reports and choice of measurement tools can preclude accurate assessment of food-intake data. In the design of elimination and rechallenge studies, sufficient time period and adequate exclusion of dietary triggers are essential to ensure symptoms are well-controlled before rechallenging. The route and frequency of challenging, design of test food, and/or placebo should match the aims of the rechallenge phase. Long-term efficacy data of such therapeutic diets has been poorly documented in most studies. Standardized guidelines that address many of the challenges outlined above are suggested to strengthen the quality of evidence for dietary therapies in FGID. © 2013 by the american College of Gastroenterology.


Singh A.,Monash University
Optics Express | Year: 2010

This paper analyze for the first time the impact of the charge carrier transport on the continuously pumped stimulated Raman amplification in silicon waveguides. A novel analytical model is developed using which the coupled differential equations of the pump and the probe optical signals and those of carrier transport are solved concurrently. The simulation and analysis suggest that the neglect of the carrier transport phenomenon, reported in the previously published works, is approximately justified only if the effective carrier lifetime is comparable to the carrier transit time, otherwise it can result in substantial overestimation of the free carrier density at the optical mode center. © 2010 Optical Society of America.


Dommenget D.,Monash University
Geophysical Research Letters | Year: 2010

In a series of Atmospheric model simulations coupled to a simple slab ocean model it is illustrated that El Nio type of SST variability can exist in the absence of any ocean dynamics. Atmospheric feedbacks in cloud cover and changes in the wind field can produce positive and delayed negative feedbacks that together with the heat capacity of the upper ocean can produce a damped interannual oscillation in the equatorial Pacific that is comparable in strength and has characteristics to the observed phenomenon. The evolution of the SST pattern is similar to the SST-mode of El Nio, but is entirely controlled by atmospheric feedbacks. The results challenge and extend our current understanding of the feedback mechanisms of El Nio in climate models and may also highlight possible atmospheric mechanisms that could partly control some observed ENSO events. © 2010 by the American Geophysical Union.


Mijaljica D.,Monash University | Prescott M.,Monash University | Devenish R.J.,Monash University
Autophagy | Year: 2011

The term microautophagy was first used in 1966 by de Duve and Wattiaux 1 and subsequently applied, over the following two decades, to processes described in mammalian cells and involving the presence of lysosome-like organelles having multiple vesicles trapped in their lumen ("multivesicular lysosomes"). Concurrently, many studies suggested a view of microautophagy where the lysosomal membrane was either invaginated or projected arm-like protrusions to sequester cytosolic constituents into intralysosomal vesicles. Although microautophagy in mammalian cells has been traditionally considered as a form of autophagy constitutively active in the turnover of long-lived proteins, little is known about the mechanism and regulation of cargo selection. The lack of specific approaches to directly detect microautophagy in mammalian systems, aside from electron microscopy, is the major current limitation to addressing its physiological role(s) and possible contribution to particular disease states. In this review we consider the current state of knowledge about microautophagic processes. We examine some of the main characteristics of microautophagy in yeast with a view to assessing their relevance for our understanding of microautophagy in mammalian cells. © 2011 Landes Bioscience.


Miragliotta N.,Monash University
Environmental Politics | Year: 2013

During the Australian Greens' first two decades of existence, electoral support for the party grew, and it was rewarded with ever-increasing numbers of its representatives occupying seats in Australian parliaments. The bases of electoral support for the Australian Greens are analysed, and its prospects in a two-party dominant system are considered. While the Australian Greens may never transcend small party status, the nature and source of its electoral support, combined with certain features of the institutional setting, provide it with a basis for a relatively enduring institutional and electoral presence. © 2013 Taylor and Francis Group, LLC.


Better weather and seasonal predictions as well as more reliable climate projections require improved models of the components of the climate systems. It has been shown that the improvement of such models is intricately linked to improving the representation of the physical processes embedded in them. An analysis of the model development process revealed that to accelerate progress in the overall model performance, it is necessary to strengthen the links between model evaluation at the level of the application and the process-oriented refinement of the model formulation, in particular in the area of parameterization. To achieve this requires a closer collaboration of the data, model user, and model development communities on the one hand and the academic and "operational" model development community on the other. It is the responsibility of national and international research programs and the community as a whole to take up the challenge of generating the conditions in which model improvements can be developed on a sound scientific footing at the rate that satisfies society's needs for improved predictions at all time scales. ©2010 American Meteorological Society.


Gniel J.,Golder Associates | Bouazza A.,Monash University
Geotextiles and Geomembranes | Year: 2010

Geogrid encasement has recently been investigated to provide an alternative and perhaps stiffer option to the now established method of geotextile encased columns (GECs). To construct geogrid encasement, the geogrid is typically rolled into a sleeve and welded using a specialized welding frame. However, the process is unlikely to be economical for site construction and therefore an alternative method of encasement construction was investigated in this paper. The technique comprises overlapping the geogrid encasement by a nominal amount and relying on interlock between the stone aggregate and section of overlap to provide a level of fixity similar to welding. A series of small-scale tests were initially used to investigate the technique, followed by medium-scale compression tests using different geogrids and typical stone column aggregates. The results of testing indicate that the "method of overlap" provides a simple and effective method of encasement construction, providing a level of fixity similar to welding. A full circumference of overlap should generally be adopted to achieve adequate fixity. Biaxial geogrids are best suited to the technique, with increased encasement stiffness resulting in increased column capacity and column stiffness. Higher strength geogrids are also more robust, providing a greater resistance to cutting from pieces of angular crushed rock. Site trials are recommended for final confirmation of the technique. © 2009 Elsevier Ltd. All rights reserved.


Leong Y.A.,Monash University
Nature Immunology | Year: 2016

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell–derived malignancies. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


This paper examines how the conduct of a local festival of fashion retailing-the L'Oreal Melbourne Fashion Festival-reinvigorates the commodity fair format of older times. The paper takes a longitudinal view of the festival's evolution and draws on Lefebvre's spatiology, complemented by Terranova's approach to the participatory economy, to explore how it produces monetary value as it produces space. The discussion highlights the contradictory nature of event processes, arguing that they reinforce dominant representations of the city and extend retailers' reach into public space, but at the same time undermine spaces of business activity. The paper suggests that the event's use of participatory economies of cultural mobilisation are similar to the tactics of social movement activism, but that in this context mobilisation works to support the value-capturing strategies of local retailers and to reinscribe urban spaces as spaces of consumption. © 2013 Urban Studies Journal Limited.


Ono M.,Monash University | Harley V.R.,Monash University
Nature Reviews Endocrinology | Year: 2013

Formerly known as 'intersex' conditions, disorders of sex development (DSDs) are congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. A complete revision of the nomenclature and classification of DSDs has been undertaken, which emphasizes the genetic aetiology of these disorders and discards pejorative terms. Uptake of the new terminology is widespread. DSDs affecting gonadal development are perhaps the least well understood. Unravelling the molecular mechanisms underlying gonadal development has revealed new causes of DSDs, although a specific molecular diagnosis is made in only ∼20% of patients. Conversely, identification of the molecular causes of DSDs has provided insight into the mechanisms of gonadal development. Studies of N-ethyl-N-nitrosourea mutagenesis in the mouse, and multigene diagnostic screening and genome-wide approaches, such as array-comparative genomic hybridization and next-generation sequencing, in patients with DSDs are accelerating the discovery of genes involved in gonadal development and DSDs. Furthermore, long-range gene regulatory mutations and multiple gene mutations are emerging as new causes of DSDs. Patients with DSDs, their parents and medical staff are confronted with challenging decisions regarding gender assignment, genital surgery and lifelong care. These advances are refining prognostic prediction and systematically improving the diagnosis and long-term management of children with DSDs. © 2013 Macmillan Publishers Limited. All rights reserved.


Gibson P.R.,Monash University | Shepherd S.J.,Monash University
American Journal of Gastroenterology | Year: 2012

Recognition of food components that induce functional gut symptoms in patient's functional bowel disorders (FBD) has been challenging. Food directly or indirectly provides considerable afferent input into the enteric nervous system. There is an altered relationship between the afferent input and perception/efferent response in FBD. Defining the nature of food-related stimuli may provide a means of minimizing such an input and gut symptoms. Using this premise, reducing the intake of FODMAPs (fermentable oligo-, di-, and mono-saccharides and polyols) - poorly absorbed short-chain carbohydrates that, by virtue of their small molecular size and rapid fermentability, will distend the intestinal lumen with liquid and gas - improves symptoms in the majority of patients. Well-developed methodologies to deliver the diet via dietician-led education are available. Another abundant source of afferent input is natural and added food chemicals (such as salicylates, amines, and glutamates). Studies are needed to assess the efficacy of the low food chemical dietary approach. A recent placebo-controlled trial of FODMAP-poor gluten provided the first valid evidence that non-celiac gluten intolerance might actually exist, but its prevalence and underlying mechanisms require elucidation. Food choice via the low FODMAP and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for functional gut symptoms. © 2012 by the American College of Gastroenterology.


Carter G.P.,Monash University | Rood J.I.,Monash University | Lyras D.,Monash University
Trends in Microbiology | Year: 2012

During the past decade, there has been a striking increase in Clostridium difficile nosocomial infections worldwide predominantly due to the emergence of epidemic or hypervirulent isolates, leading to an increased research focus on this bacterium. Particular interest has surrounded the two large clostridial toxins encoded by most virulent isolates, known as toxin A and toxin B. Toxin A was thought to be the major virulence factor for many years; however, it is becoming increasingly evident that toxin B plays a much more important role than anticipated. It is clear that further experiments are required to accurately determine the relative roles of each toxin in disease. , especially in more clinically relevant current epidemic isolates. © 2011.


Miller J.C.,Monash University
PLoS ONE | Year: 2014

In this paper we extend previous work deriving dynamic equations governing infectious disease spread on networks. The previous work has implicitly assumed that the disease is initialized by an infinitesimally small proportion of the population. Our modifications allow us to account for an arbitrarily large initial proportion infected. This helps resolve an apparent paradox in earlier work whereby the number of susceptible individuals could increase if too many individuals were initially infected. It also helps explain an apparent small deviation that has been observed between simulation and theory. An advantage of this modification is that it allows us to account for changes in the structure or behavior of the population during the epidemic. © 2014 Joel C Miller.


Halmos E.P.,Monash University | Power V.A.,Monash University | Shepherd S.J.,Monash University | Gibson P.R.,Monash University | Muir J.G.,Monash University
Gastroenterology | Year: 2014

Background & Aims A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) often is used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), yet there is limited evidence of its efficacy, compared with a normal Western diet. We investigated the effects of a diet low in FODMAPs compared with an Australian diet, in a randomized, controlled, single-blind, cross-over trial of patients with IBS. Methods In a study of 30 patients with IBS and 8 healthy individuals (controls, matched for demographics and diet), we collected dietary data from subjects for 1 habitual week. Participants then randomly were assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet, followed by a washout period of at least 21 days, before crossing over to the alternate diet. Daily symptoms were rated using a 0- to 100-mm visual analogue scale. Almost all food was provided during the interventional diet periods, with a goal of less than 0.5 g intake of FODMAPs per meal for the low-FODMAP diet. All stools were collected from days 17-21 and assessed for frequency, weight, water content, and King's Stool Chart rating. Results Subjects with IBS had lower overall gastrointestinal symptom scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs, compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P <.001) and the subjects' habitual diet. Bloating, pain, and passage of wind also were reduced while IBS patients were on the low-FODMAP diet. Symptoms were minimal and unaltered by either diet among controls. Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet, but diarrhea-predominant IBS was the only subtype with altered fecal frequency and King's Stool Chart scores. Conclusions In a controlled, cross-over study of patients with IBS, a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms. This high-quality evidence supports its use as a first-line therapy. Clinical Trial number: ACTRN12612001185853. © 2014 by the AGA Institute.


This paper offers a critical discourse analysis of media debate over social sex selection in the Australian media from 2008 to 2014. This period coincides with a review of the National Health and Medical Research Council's Ethical Guidelines on the Use of Assisted Reproductive Technology in Clinical Practice and Research (2007), which underlie the regulation of assisted reproductive clinics and practice in Australia. I examine the discussion of the ethics of pre-implatation genetic diagnosis (PGD) within the media as ‘ethical publicity’ to the lay public. Sex selection through PGD is both exemplary of and interconnected with a range of debates in Australia about the legitimacy of certain reproductive choices and the extent to which procreative liberties should be restricted. Major themes emerging from media reports on PGD sex selection in Australia are described. These include: the spectre of science out of control; ramifications for the contestation over the public funding of abortion in Australia; private choices versus public authorities regulating reproduction; and the ethics of travelling overseas for the technology. It is concluded that within Australia, the issue of PGD sex selection is framed in terms of questions of individual freedom against the principle of sex discrimination – a principle enshrined in legislation – and a commitment to publically-funded medical care. © 2015, © 2015 Taylor & Francis.


Abstract Although the primary visual cortex (V1) is one of the most extensively studied areas of the primate brain, very little is known about how the far periphery of visual space is represented in this area. We characterized the physiological response properties of V1 neurons in anaesthetized marmoset monkeys, using high-contrast drifting gratings. Comparisons were made between cells with receptive fields located in three regions of V1, defined by eccentricity: central (3-5°), near peripheral (5-15°), and far peripheral (>50°). We found that orientation selectivity of individual cells was similar from the center to the far periphery. Nonetheless, the proportion of orientation-selective neurons was higher in central visual field representation than in the peripheral representations. In addition, there were similar proportions of cells representing all orientations, with the exception of the representation of the far periphery, where we detected a bias favoring near-horizontal orientations. The proportions of direction-selective cells were similar throughout V1. When the center/surround organization of the receptive fields was tested with gratings with varying diameters, we found that the population of neurons that was suppressed by large gratings was smaller in the far periphery, although the strength of suppression in these cells tended to be stronger. In addition, the ratio between the diameters of the excitatory centers and suppressive surrounds was similar across the entire visual field. These results suggest that, superimposed on the broad uniformity of V1, there are subtle physiological differences, which indicate that spatial information is processed differently in the central versus far peripheral visual fields. Copyright © Cambridge University Press 2013.


Capitanio F.A.,Monash University
Tectonics | Year: 2014

To elucidate the dynamics of extrusion tectonics, I investigate the relation between subduction processes and intraplate deformation. Three-dimensional numerical models of subducting upper plate systems show that subduction of a heterogeneous buoyancy slab, that is, hosting continental and oceanic lithosphere, causes the retreat of the oceanic trench and the localization of deformation in the back arc. Similar trench evolution is found when the subducting slab partially detaches from the impinging continent; however, deformation in the upper plate interiors widens, with indentation, plastic yielding and rotation of a large block extruding laterally toward the retreating margin. Indentation stresses are consequence of the partial slab breakoff at depth and vanish when the detached slablet reaches the mantle transition zone, resulting in transient extrusion tectonics. The distance to which indentation deformation propagates depends on the ability of subducting lithosphere to propagate stress laterally and is linear with the lithospheric strength. While in the stretching back arc the plate deformation and the underlying mantle flow are coupled, they are uncoupled in the extrusion tectonics, where mostly stresses propagated through the margin drive rotations. The potential role of these diverse subduction processes in the eastern Mediterranean is discussed, suggesting that different mechanisms likely drive the tectonics of this area. ©2014. American Geophysical Union. All Rights Reserved.


Bos J.J.,Monash University | Brown R.R.,Monash University | Farrelly M.A.,Monash University
Global Environmental Change | Year: 2013

Learning nurtured through experimentation is very important for enabling sustainability transitions. Over the last decade, different strands of research have investigated social learning and its associated processes to better understand learning efforts aimed at socio-technical system change. While some necessary process considerations to enable social learning have been established, actual design and organisation of experiments that aim to create a social learning situation remain largely unexplored. Against this background, this paper presents an empirical, mixed-method study that investigated a governance experiment within the Australian urban water sector. This experiment enabled widespread learning, resulting in socio-technical system change. The research reveals that social learning in particular is more complex in reality than in theory and that not all system stakeholders need to learn the same to achieve system change. Further, this paper develops a framework that outlines enabling starting conditions and features for designing and organising social learning situations. The framework comprises focus projects, multi-organisational peer groups, distributed facilitation, adaptability and flexibility, time and science/research. The key findings provide practical strategies for designing and operationalising policy and governance reform agendas that embrace learning situations. © 2012 Elsevier Ltd.


Schellart W.P.,Monash University
Journal of Geophysical Research: Solid Earth | Year: 2010

Three-dimensional laboratory models of upper mantle subduction are presented investigating the effect of the trench velocity (vt) and the slab to upper mantle viscosity ratio (SP/UM) on trench curvature and slab curvature. One set of experiments varies SP/ UM from 66 to 1375. Another set of experiments modifies vt through applying different velocities at the trailing plate. The results show that the radius of trench curvature (RTC) progressively decreases with continuous trench retreat due to quasi-toroidal mantle return flow from the subslab region around the lateral slab edges and toward the mantle wedge region, but starts to increase when trench retreat changes to trench advance due to quasi-toroidal return flow in the opposite direction. Furthermore, R TC increases with increasing SP/UM (i.e., progressively stronger slabs are progressively less curved) following a cubic root function. The force required to curve the slab and trench varies with progressive subduction, but is only 0.1-2.5% of the total negative buoyancy force of the slab, while the viscous dissipation rate due to progressive slab curvature is only 0.01-0.60% of the potential energy release rate. Comparison of trench curvature in the models (scaled slab width w = 750 km) with that of the Scotia subduction zone (w 800 km) indicates that for the Scotia subduction zone the effective SP/UM is of the order 1-2 × 10 2. Finally, the elastic sphere indentation model for arc curvature is revisited, demonstrating that four main predictions are not met by observations, implying that the model should be rejected. Copyright 2010 by the American Geophysical Union.


Tomkins A.G.,Monash University
Geochimica et Cosmochimica Acta | Year: 2010

Understanding the source of metamorphic sulfur is critical to clarifying the complete cycle of ore genesis, from source to sink, for several mineral deposit types. In this study, a mass balance approach and the thermodynamic computer programs Thermocalc and PerpleX were used to constrain the P-T range of pyrite breakdown to pyrrhotite (which liberates sulfur) in common metamorphic lithologies. The results suggest that most of the continental crust's metamorphic sulfur is liberated in a relatively narrow temperature-pressure window corresponding to the terminal breakdown of chlorite at moderate to low pressures. This is because pyrite stability is controlled partly by temperature and pressure, and partly by the amount of H2O present. During prograde metamorphism from the greenschist to the amphibolite facies, metamorphic H2O is produced primarily through chlorite breakdown in mafic to pelitic bulk compositions. As temperature increases, more sulfur is required from pyrite to maintain equilibrium proportions of H2O, H2S and SO2 in the fluid, and in addition, progressively more sulfur is required at lower pressures. At low temperatures, little sulfur is required by metamorphic fluid released during initial chlorite breakdown, whereas at higher temperatures coinciding with the terminal breakdown of chlorite, not only is more fluid present, but the fluid's sulfur requirement has also increased dramatically. In this way, metamorphic dehydration drives pyrite breakdown and generation of sulfur-rich hydrothermal fluids at mesothermal conditions. Beyond the chlorite stability field there is minimal metamorphic fluid production, except at low pressures and high temperatures where muscovite can break down without causing melting; conditions that are a long way from typical crustal geotherms. However, deformation also plays a key role in pyrite breakdown. Without deformation, small amounts of fluid in chemical communication with individual pyrite grains will quickly acquire equilibrium concentrations of the sulfur species and minimal pyrite breakdown is necessary. Whereas during deformation, there may be a continuous fluid flux past pyrite grains, promoting ongoing sulfur liberation. In this way, periods of deformation may be the major sulfur-liberating episodes during a metamorphic cycle. Since hydrothermal fluids are inherently buoyant and consequently tend to migrate upwards and towards cooler temperatures through the crust, these results imply that orogenic gold deposits are most likely to form at lower-amphibolite to prehnite-pumpellyite facies conditions, and unlikely to form at higher temperatures. The pressure constraint on metamorphic sulfur liberation implies that tectonic settings that allow prograde metamorphism to follow low pressure P-T-t paths in an occasionally compressional or transpressional environment are necessary. Settings that promote extensive injection of felsic magma into a mid-crust that contains a significant proportion of pyritic carbonaceous metasediment are shown to be ideal for orogenic gold deposit genesis. Inverted back-arc basins are interpreted to be the most favourable of these. © 2010 Elsevier Ltd.


Nicholls N.,Monash University
Climate Dynamics | Year: 2010

The 1958-2007 decline in March-August rainfall over southern Australia (south of 30°S) is very closely related to an increase in surface atmospheric pressure over Australia. Sea surface temperatures around northern Australia are strongly correlated with southern Australian rainfall but the recent warming of the ocean should have led to increased rainfall rather than the observed rainfall decline. The relationships between the rainfall and indices of several modes of the atmosphere/ocean system are investigated to determine a cause of the rainfall decline. Indices of the modes that only use data remote from the Australian region are used to avoid the possibility that a relationship between the mode and Australian rainfall is simply reflecting the behaviour of "local" portions of the index. Thus a climate mode index that incorporates Australian pressure would, of course, be related to southern Australian rainfall, even if the remote parts of the mode were unrelated to Australian rainfall. Unless the remote contributions to the mode index were also related to Australian rainfall it seems physically unrealistic to consider that the mode, per se, was affecting Australian rainfall (rather than simply reflecting the influence of the local pressure changes). The rainfall decline does not appear to be explainable by a change in the behaviour of the El Niño-Southern Oscillation (remote indices of this phenomenon do not exhibit a trend over this period) or the Indian Ocean Dipole (which is not strongly correlated with Australian rainfall on detrended data). The strong 1958-2007 trend in the southern annular mode (SAM) appears able to explain much of the rainfall decline since its year-to-year variations are correlated with year-to-year variations in southern Australian rainfall, and the sense of the correlation and the SAM trend would lead to a decline in rainfall (and an increase in pressure over Australia). The observed trend in SAM can reproduce over 70% of the observed rainfall trend. All these conclusions also apply to the rainfall declines in the southeast and southwest sub-regions. © Springer-Verlag 2009.


In the Eastern Mediterranean, extension in the Aegean Sea and lateral Anatolian extrusion are contrasting and seemingly unrelated examples of continental tectonics developed during Tethys closure. We use numerical modelling to investigate the relation of the tectonic regimes to the underlying subduction dynamics, during subduction land-locking and slab break-off. We find that the tectonics has a two-phase evolution: 1) an incipient phase, with back arc spreading and transcurrent shear zone formation and lateral escape of a block in the upper plate interiors, and 2) a reorganisation phase, during which the transcurrent shear zone propagates and the extruding block internally stretches, progressively separating from the opening back arc domain, while the collisional margin reactivates into a transform plate boundary. The regimes are explained by two concurring plate margin processes: 1) mantle tractions following the subduction and retreat of a land-locked oceanic slab, and 2) stresses propagated through rigid indentation upon slab break-off. These have different spatial and temporal fingerprints: long-term trench retreat and convergence slow-down follow continental subduction, while stresses localise atop the newly formed slab edge upon slab break-off, fastening up margin reorganisation, driving faulting and extrusion, yet fading rapidly, forcing local tectonics rearrangement. A comparison with the Eastern Mediterranean allows an explanation for the time evolution of the tectonics here, and emphasises the role of the Miocene-to-Pliocene tectonics transition, previously not considered. This offers a novel key to the dynamics of the enigmatic evolution of this area. © 2016 Elsevier B.V.


Candish L.,Monash University | Lupton D.W.,Monash University
Journal of the American Chemical Society | Year: 2013

The N-heterocyclic carbene (NHC)-catalyzed Claisen rearrangement of hybrid Ireland-Coates structures has been achieved, allowing the stereoselective synthesis of highly functionalized β-lactones. The reaction proceeds with high diastereoselectivity (>20:1) and affords a diverse range of β-lactone fused cyclopentanes. Mechanistic studies are detailed. © 2012 American Chemical Society.


Davis M.,Monash University
Culture, Health and Sexuality | Year: 2015

There is great interest in what testing, pharmaceutical, information and social media technology can do for sexual health. Much programmatic and research activity is focused on assessing how these technologies can be used to best effect. Less obvious are analyses that place technology into historical, political and real-world settings. Developing an ‘in-context’ analysis of sexual health technology, this paper draws on interviews with leading community advocates, researchers and clinicians in Australia, Canada and the UK and looks across examples, including social media, rapid HIV testing, pre-Exposure Prophylaxis for HIV and polymerase chain reaction Chlamydia testing. The analysis is framed by studies of techno-society and the dialectics of sex-affirmative advocacy with biomedical authority and attends to: the rationalistic and affective dimensions of the imaginary associated with technology; the role of technology in the re-spatialisation and re-temporalisation of the sexual health clinic; and the re-invention of technology in its real-world contexts. This in-context approach is important for: the effective implementation of new technology; strengthening the social science contribution to the field; and enriching social theory in general on life in techno-societies. © 2014, © 2014 Taylor & Francis.


The stabilization and isolation of highly reactive species has long been the subject of chemical research. This review will focus on a large and important class of reactive species that has only recently received considerable attention: lowvalence element heterocycles of the group 13 and 14 elements. The availability of lithium boryl complexes as sources of boryl anions has also opened up a new synthetic route to other metal boryl complexes, namely, nucleophilic attack on metal halide complexes, leading to lithium halide elimination. Although in its infancy, the chemistry of nucleophilic five-membered boryl lithium complexes holds much potential in organic and inorganic synthesis. Saying this, the thermal instability and steric bulk of such systems will likely hinder the rapid advancement of their use by a broad range of chemists.


McNeill C.R.,Monash University
Journal of Polymer Science, Part B: Polymer Physics | Year: 2011

State-of-the-art solution-processed organic field-effect transistors typically use polycrystalline organic semiconductor thin films as the active layer. Although it is widely regarded that boundaries between polycrystalline domains are a likely source of charge trapping limiting charge carrier mobility, little is known about the detailed domain structure of such films. Furthermore, variations in local order particularly in conjugated polymer films are likely to further impede charge transport. In recent years a number of techniques have been exploited that are able to provide information regarding local domain orientation and molecular order in polycrystalline organic thin films. These techniques have provided new information regarding the nature of domain structure providing an opportunity to directly evaluate the influence of domain structure on device operation. This article aims to provide a timely review of the experimental approaches used to date and provide a perspective for future work. © 2011 Wiley Periodicals, Inc.


Bingham S.,Monash University | Daoud W.A.,Monash University
Journal of Materials Chemistry | Year: 2011

Doping with metals and non-metals is a popular technique that facilitates visible light activity of titanium dioxide. More recently, rare-earth metals have shown tremendous potential as dopants not only in red-shifting the absorption but also in improving the photocatalysis of TiO2. This feature article discusses recent developments in making TiO2 visible-light active through single and co-doping with rare earth metals. An emphasis is placed on wet chemical techniques and their associated effects on the phase, adsorption, surface area, and photocatalytic activity of TiO 2. New techniques, such as electrospinning, magnetron sputtering, co-precipitation, and complexation, as well as the use of nanotubes and physical support are also discussed. © The Royal Society of Chemistry.


Drummer O.H.,Monash University
EXS | Year: 2010

Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results.


Chown S.L.,Monash University | Convey P.,Natural Environment Research Council
Annual Review of Entomology | Year: 2016

The Antarctic region comprises the continent, the Maritime Antarctic, the sub-Antarctic islands, and the southern cold temperate islands. Continental Antarctica is devoid of insects, but elsewhere diversity varies from 2 to more than 200 species, of which flies and beetles constitute the majority. Much is known about the drivers of this diversity at local and regional scales; current climate and glacial history play important roles. Investigations of responses to low temperatures, dry conditions, and varying salinity have spanned the ecological to the genomic, revealing new insights into how insects respond to stressful conditions. Biological invasions are common across much of the region and are expected to increase as climates become warmer. The drivers of invasion are reasonably well understood, although less is known about the impacts of invasion. Antarctic entomology has advanced considerably over the past 50 years, but key areas, such as interspecific interactions, remain underexplored. © Copyright 2016 by Annual Reviews. All rights reserved.


Wong B.B.M.,Monash University | Candolin U.,University of Helsinki
Behavioral Ecology | Year: 2015

Humans have brought about unprecedented changes to environments worldwide. For many species, behavioral adjustments represent the first response to altered conditions. In this review, we consider the pivotal role that behavior plays in determining the fate of species under human-induced environmental change and highlight key research priorities. In particular, we discuss the importance of behavioral plasticity and whether adaptive plastic responses are sufficient in keeping pace with changing conditions. We then examine the interplay between individual behavioral responses and population processes and consider the many ways in which changes in behavior can affect ecosystem function and stability. Lastly, we turn to the evolutionary consequences of anthropogenic change and consider the impact of altered behaviors on the evolutionary process and whether behavior can facilitate or hinder adaptation to environmental change. © The Author 2014. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology.


Lawen A.,Monash University | Lane D.J.R.,University of Sydney
Antioxidants and Redox Signaling | Year: 2013

Iron is a crucial factor for life. However, it also has the potential to cause the formation of noxious free radicals. These double-edged sword characteristics demand a tight regulation of cellular iron metabolism. In this review, we discuss the various pathways of cellular iron uptake, cellular iron storage, and transport. Recent advances in understanding the reduction and uptake of non-transferrin-bound iron are discussed. We also discuss the recent progress in the understanding of transcriptional and translational regulation by iron. Furthermore, we discuss recent advances in the understanding of the regulation of cellular and systemic iron homeostasis and several key diseases resulting from iron deficiency and overload. We also discuss the knockout mice available for studying iron metabolism and the related human conditions. © Copyright 2013, Mary Ann Liebert, Inc.


Simula T.,Monash University | Davis M.J.,University of QueenslandQLD | Helmerson K.,Monash University
Physical Review Letters | Year: 2014

We study the relaxation dynamics of an isolated zero temperature quasi-two-dimensional superfluid Bose-Einstein condensate that is imprinted with a spatially random distribution of quantum vortices. Following a period of vortex annihilation the remaining vortices self-organize into two macroscopic coherent "Onsager vortex" clusters that are stable indefinitely - despite the absence of driving or external dissipation in the dynamics. We demonstrate that this occurs due to a novel physical mechanism - the evaporative heating of the vortices - that results in a negative-temperature phase transition in the vortex degrees of freedom. At the end of our simulations the system is trapped in a nonthermal state. Our computational results provide a pathway to observing Onsager vortex states in a superfluid Bose gas. © 2014 American Physical Society.


Insulin resistance is a key pathological feature of type 2 diabetes and is characterized by defects in signaling by the insulin receptor (IR) protein tyrosine kinase. The inhibition of protein tyrosine phosphatases (PTPs) that antagonize IR signaling may provide a means for enhancing the insulin response and alleviating insulin resistance. The prototypic phosphotyrosine-specific phosphatase PTP1B dephosphorylates the IR and attenuates insulin signaling in muscle and liver. Mice that are deficient for PTP1B exhibit improved glucose homeostasis in diet and genetic models of insulin resistance and type 2 diabetes. The phosphatase TCPTP shares 72% catalytic domain sequence identity with PTP1B and has also been implicated in IR regulation. Despite their high degree of similarity, PTP1B and TCPTP act together in vitro and in vivo to regulate insulin signaling and glucose homeostasis. This review highlights their capacity to act specifically and nonredundantly in cellular signaling, describes their roles in IR regulation and glucose homeostasis, and discusses their potential as drug targets for the enhancement of IR phosphorylation and insulin sensitivity in type 2 diabetes. © 2012 The Author Journal compilation © 2012 FEBS.


Forbes J.M.,Baker IDI Heart and Diabetes Institute | Forbes J.M.,Monash University | Forbes J.M.,Materials Medical Research Institute | Cooper M.E.,Baker IDI Heart and Diabetes Institute | And 2 more authors.
Physiological Reviews | Year: 2013

It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant targets of the future, will be highlighted. © 2013 the American Physiological Society.


Alston M.,Monash University
Wiley Interdisciplinary Reviews: Climate Change | Year: 2013

This article addresses the uneven impacts of climate change on women. To date, there has been a significant emphasis on climate science and technological solutions to aid mitigation and adaptation strategies. This has led to a form of global managerialism that presupposes that all people can adapt with the right resources and knowledge. In this article, it is argued that the differential impacts of climate change on women demand that climate actions and strategies require gender sensitivity and that further research on climate change, adaptations, and actions includes a gendered analysis. © 2013 John Wiley & Sons, Ltd.


Lenne M.G.,Monash University
Accident Analysis and Prevention | Year: 2013

For over 40 years transport safety researchers have been using methods of vehicle instrumentation to gain greater insights into the factors that contribute to road user crash risk and the associated crash factors. In the previous decade in particular the widespread availability of lower cost and more advanced methods of vehicle instrumentation and recording technologies are supporting the increasing number of on-road research studies worldwide. The design of these studies ranges from multi-method studies using instrumented test vehicles and defined driving routes, to field operational tests, through to much larger and more naturalistic studies. It is timely to assess the utility of these methods for studying the influences of driver characteristics and states, the design and operation of the road system, and the influences of in-vehicle technologies on behaviour and safety for various road user groups. This special issue considers the extent to which on-road studies using vehicle instrumentation have been used to advance knowledge across these areas of road safety research. The papers included in this issue illustrate how research using instrumented test vehicles continues to generate new knowledge, and how the larger scale United States and European naturalistic and field operational test studies are providing a wealth of data about road user behaviour in real traffic. This is balanced with a number of studies that present methodological developments in data collection and analysis methods that, while promising, need further validation. The use of on-road methods to accurately describe the behaviours occurring in everyday real-world conditions, to quantify risks for safety critical events, and an improved understanding of the factors that contribute to risk, clearly has huge potential to promote further road trauma reductions. © 2013 Elsevier Ltd. All rights reserved.


Powis A.T.,Monash University | Sammut S.J.,Monash University | Simula T.P.,Monash University
Physical Review Letters | Year: 2014

We propose a robust imaging technique that makes it possible to distinguish vortices from antivortices in quasi-two-dimensional Bose-Einstein condensates from a single image of the density of the atoms. Tilting the planar condensate prior to standard absorption imaging excites a generalized gyroscopic mode of the condensate, revealing the sign and location of each vortex. This technique is anticipated to enable experimental measurement of the incompressible kinetic energy spectrum of the condensate and the observation of a negative-temperature phase transition of the vortex gas, driven by two-dimensional superfluid turbulence. © 2014 American Physical Society.


Morris A.P.,Monash University
Current Biology | Year: 2015

Eye movements are essential to human vision. A new study shows that the tiny eye movements we make while holding our gaze on a point of interest are associated with brief, attention-like changes in the sensitivity of visual neurons. © 2015 Elsevier Ltd. All rights reserved.


This paper presents findings drawn from a study of the role of "enabling places" in promoting recovery among a sample of 24 adults living with a mental illness in Melbourne, Australia. Featuring a mix of visual and qualitative methods, the study invited participants to identify local places and place-related activities, which they regarded as supportive of their own health and recovery. The aim was to determine how and under what circumstances local places support recovery, and the ways these places are identified and maintained. Consistent with the logic of "enabling places", the study yielded evidence indicating that the various places identified by participants promoted recovery by facilitating access to an array of social, material and/or affective resources. Participants indicated that they draw on these resources in support of activities and relationships vital to the everyday 'work' of recovery. The paper closes with a discussion of the ways such "enabling" resources may be mobilised in the delivery of novel 'place-based' mental health initiatives. © 2012 Elsevier Ltd. All rights reserved.


Galloway D.K.,Monash University | Lampe N.,Monash University
Astrophysical Journal | Year: 2012

The radius of neutron stars can in principle be measured via the normalization of a blackbody fitted to the X-ray spectrum during thermonuclear (type-I) X-ray bursts, although few previous studies have addressed the reliability of such measurements. Here we examine the apparent radius in a homogeneous sample of long, mixed H/He bursts from the low-mass X-ray binaries GS 1826-24 and KS 1731-26. The measured blackbody normalization (proportional to the emitting area) in these bursts is constant over a period of up to 60s in the burst tail, even though the flux (blackbody temperature) decreased by a factor of 60%-75% (30%-40%). The typical rms variation in the mean normalization from burst to burst was 3%-5%, although a variation of 17% was found between bursts observed from GS 1826-24 in two epochs. A comparison of the time-resolved spectroscopic measurements during bursts from the two epochs shows that the normalization evolves consistently through the burst rise and peak, but subsequently increases further in the earlier epoch bursts. The elevated normalization values may arise from a change in the anisotropy of the burst emission or alternatively variations in the spectral correction factor, f c, of order 10%. Since burst samples observed from systems other than GS 1826-24 are more heterogeneous, we expect that systematic uncertainties of at least 10% are likely to apply generally to measurements of neutron-star radii, unless the effects described here can be corrected for. © 2012. The American Astronomical Society. All rights reserved.


Izgorodina E.I.,Monash University | MacFarlane D.R.,Monash University
Journal of Physical Chemistry B | Year: 2011

The nature of hydrogen bonding was compared in neutral complexes and negatively charged complexes consisting of either the HF molecule or the halide anion (fluoride and chloride) and the C-H bond in the methane molecule with a varying degree of fluorination (such as CH4, CH2F 2, and CHF3). Both linear (C3v symmetry) and nonlinear (C2v symmetry) hydrogen-bonded complexes were studied. Symmetry-adapted perturbation theory was used to decompose interaction energies into fundamental components such as Coulomb, repulsion, induction and dispersion to analyze the interplay among these forces in stabilizing hydrogen bonding. In the linear charged complexes, both Coulomb attraction and induction significantly contributed to the stabilization of hydrogen bonding. In the nonlinear charged complexes, mainly Coulomb attraction contributed to the HB complex stabilization, with the inductive forces playing a less important role. Contrary to the neutral complexes, dispersion forces played only a marginal role in the charged complexes. Interplay between the fundamental forces was also investigated in the ion pairs of the imidazolium-based ionic liquid, [C 2mim]Cl, that were categorized as either (1) typical ion-ion interaction, with the anion interacting from above or below the imidazolium plane; or (2) hydrogen-bonding interaction, with the anion interacting with the C2-H bond of the imidazolium cation. Both types of interactions were found to induce similar charge transfers, and the analysis of the energetic components revealed only a slight difference in the ion pairs studied: (1) both interactions were electrostatically driven, between 86% and 88% of the overall attractive energy, with the electrostatic component being slightly lower in the hydrogen-bonded ion pairs by ∼8 kJ mol-1; and (2) dispersion forces were found to be stronger in the typical ion-ion interactions by ∼15 kJ mol-1 and could be possible only due to the fact that the anion was able to move closer to the cation with no steric hindrance. From the experimental point of view, a vibrational red shift is expected in the hydrogen-bonded complexes of imidazolium-based ionic liquids, whereas the ion-ion interactions are more likely to produce a slight blue shift. © 2011 American Chemical Society.


Campbell D.G.,Monash University
The Medical journal of Australia | Year: 2011

The concept of "social accountability" has underpinned the development of many medical education programs over the past decade. Success of the regionalisation of the general practice training program in Australia will ultimately be measured by the ability of the program to deliver a sufficient rural general practice workforce to meet the health needs of rural communities. Regionalisation of general practice training in Australia arose from the 1998 recommendations of the Ministerial Review of General Practice Training. The resultant competitive structure adopted by government was not the preferred option of the Review Committee, and may be a negative influence on rural workforce, as the competitive corporate structure of regional training providers has created barriers to meaningful vertical integration. Available data suggest that the regionalised training program is not yet providing a sustainable general practice workforce to rural Australia. The current increase in medical student and general practice training places provides an opportunity to address some of these issues. In particular, it is recommended that changes be made to registrar selection processes, the rural pipeline and vertical integration of training, and training for procedural rural practice. To achieve these goals, perhaps it is time for another comprehensive ministerial review of general practice training in Australia.


Hansen S.C.,Monash University | Cally P.S.,Monash University
Astrophysical Journal | Year: 2012

Alfvén waves may be difficult to excite at the photosphere due to low-ionization fraction and suffer near-total reflection at the transition region (TR). Yet they are ubiquitous in the corona and heliosphere. To overcome these difficulties, we show that they may instead be generated high in the chromosphere by conversion from reflecting fast magnetohydrodynamic waves, and that Alfvénic TR reflection is greatly reduced if the fast reflection point is within a few scale heights of the TR. The influence of mode conversion on the phase of the reflected fast wave is also explored. This phase can potentially be misinterpreted as a travel speed perturbation with implications for the practical seismic probing of active regions. © 2012. The American Astronomical Society. All rights reserved..


McKenzie D.P.,Monash University
Social psychiatry and psychiatric epidemiology | Year: 2010

BACKGROUND: Although much has been published on the effects of the 1990/1991 Gulf War on the psychological health of veterans, few studies have addressed the pattern and timing of post-war development of psychological disorders. Our study aims to identify the most common psychological disorders that first appeared post-Gulf War, the period of peak prevalence and the sequence of multiple psychological disorders. METHODS: The temporal progression of psychological disorders in male Australian naval Gulf War veterans with no prior psychological disorders was calculated across each year of the post-Gulf War period. DSM-IV diagnoses were obtained using the Composite International Diagnostic Interview. RESULTS: Psychological disorder rates peaked in the first 2 years (1991-1992) following the Gulf War. Alcohol use disorders were the most likely to appear first. Classification and regression tree analysis found that risk of disorder was exacerbated if veterans had been exposed to a high number of potential psychological stressors during their military service. Lower military rank was associated with increased risk of alcohol disorders, particularly during the first 2 years post-Gulf War. In veterans with two or more disorders, anxiety disorders and alcohol disorders tended to appear before affective disorders. CONCLUSIONS: Our study found that psychological disorders occur in sequence following Gulf War deployment. Our findings may help clinicians to anticipate, and better manage, multiple symptomatology. The findings may also assist veteran and defence organisations in planning effective mental health screening, management and prevention policy.


At the continent-scale, models of Moho depth based on seismic estimates alone can be inadequate due to irregular or sparse data. Gravity-based Moho modelling provides better coverage, however, the methods used are typically hampered by an inability to explicitly honour seismic constraints and are also limited by over simplistic model conditions, e.g. laterally-homogenous layering. I present a new method to generate a continent-scale Moho model, based on the constrained inversion of free-air gravity data. This method explicitly honours seismic Moho estimates and accounts for a laterally heterogeneous crust and mantle. Resolution and sensitivity testing shows that, for wavelengths greater than 200km, crustal density and Moho depth are recovered with reasonable accuracy, ±30kgm±3 and ±3km respectively. MoGGIE uses a six layer model incorporating ocean, sedimentary basin, upper crust, lower/oceanic crust, eclogitised crust and mantle. Inversion variables were the density of the crustal layers, constrained by a standard density model, and the depths to intra-crustal boundaries and the Moho, constrained by 230 seismic depth estimates. The results demonstrate that a balanced approach to seismically-constrained gravity inversion has the capability to generate detailed and well-constrained models of the Moho and crustal density at the continent-scale. For Australia, this is a clear improvement on the sparse and irregular resolution of the Moho provided by seismic estimates of crustal thickness, which fail to resolve short-wavelength features. Newly defined tectonic features include extensive magmatic underplates, crustal-scale shear zones, and the boundaries between tectonic blocks. Isostatic analysis reveals that little of the continent is close to isostatic equilibrium, with isostatic disequilibria preserved at multiple scales, from hundreds of kilometres to the entire continent. These disequilibria are interpreted to indicate long-wavelength flexure of highly competent continental lithosphere. © 2010 Elsevier B.V.


Campbell I.H.,Australian National University | Squire R.J.,Monash University
Geochimica et Cosmochimica Acta | Year: 2010

The consensus view is that the O2 concentration of the Archean atmosphere was very low and that it rose to its present level of 21% in a series of steps, two of which dwarf the others in importance. The first, known as the Great Oxidation Event, occurred at ∼2.4Ga. It involved an increase in the relative abundance of O2, which has been estimated at three orders of magnitude, and it is important because it led to the first surface weathering. The second, although less important in relative terms, involved the addition of 9×1017kg of O2 to the atmosphere, at least ten times as much as that required to produce the Great Oxidation Event. Its importance lies in the fact that it correlates with the rise of animals in the Ediacaran and Early Cambrian periods. Although it is widely accepted that an increase in atmospheric O2 facilitated the appearance of animals at ∼575Ma, followed by the Cambrian Explosion ∼50Myr later, the cause of this increase remains controversial. We show that the surge in the O2 level near the Precambrian-Cambrian boundary correlates with major episodes of continent-continent collision associated with Gondwanas amalgamation, including convergence between East and West Gondwana, which produced the 8000-km-long Transgondwanan Supermountains. The eroded roots of these mountains include the oldest lawsonite-bearing blueschists and eclogites, and ultra high-pressure metamorphic rocks. The sudden appearance of these low-thermal gradient, high-pressure metamorphic rocks implies that the Gondwanan orogenic zones were cooler and stronger than those associated with the assembly of earlier supercontinents and therefore capable of supporting higher mountains.There is a log-linear relationship between relief and erosion rate, and a linear relationship between sedimentation rate and organic C burial. Taken together these two relationships imply a log-linear relationship between relief and C sequestration. We suggest that the Gondwanan supermountains were higher than those produced during the assembly of earlier supercontinents and that rapid erosion of these mountains released a large flux of essential nutrients, including Fe and P, into the rivers and oceans, which triggered an explosion of algae and cyanobacteria. This, in turn, produced a marked increase in the production rate of photosynthetic O2. Rapid sedimentation during this period promoted high rates of burial of biogenic pyrite and organic matter generated during photosynthesis so that they could not back react with O2, leading to a sustained increase in atmospheric O2. © 2010 Elsevier Ltd.


Volcanism in Sicily (Italy) at Mount Etna (0.5 Ma to present) and the Iblean Plateau (ca. 7.0-1.1 Ma) remains enigmatic, because it is located in close proximity to, but is laterally offset from, the Calabrian subduction zone. Previous work suggests that the volcanism results from a plume or from lateral mantle flow from underneath Africa through a slab window across a lithospheric step. Here I propose that Mount Etna and the Iblean volcanics are related to decompression melting of upper mantle material that is flowing around the southern Ionian slab edge to accommodate east-directed rollback of the Ionian slab that resumed in the Late Miocene. New three-dimensional fluid dynamic subduction models demonstrate that rollback-induced mantle return flow occurs in a quasi-toroidal fashion with a component of downwelling directly below and above the slab, and a component of upwelling next to the subduction zone with maximum upwelling observed next to the subslab region. Significant upwelling (≥71% of the maximum) is observed at 90-430 km depth and extends 55-660 km away from the projected distance of inferred arc magmatism above the slab edge. The models can explain the large spatial separation of as much as 430 km between intraplate volcanism in Sicily and arc magmatism during the past ~7 m.y., and their contemporaneous activity. The maximum upwelling velocity in the models composes 32% of the trench rollback velocity. With rollback velocities up to 10-19 cm/yr during the past ~8 m.y., the models predict maximum rollback-induced upper mantle upwelling velocities of 3.2-6.1 cm/yr below Sicily. © 2010 Geological Society of America.


Izgorodina E.I.,Monash University
Physical Chemistry Chemical Physics | Year: 2011

Ionic liquids have attracted a substantial amount of interest as replacement of traditional electrolytes in high efficiency electrochemical devices for generation and storage of energy due to their superior physical and chemical properties, especially low volatility and high electrochemical stability. For enhanced performance of the electrochemical devices ionic liquids are required to be highly conductive and low viscous. Long-range Coulomb and short-range dispersion interactions between ions affect physical and chemical properties of ionic liquids in a very complex way, thus preventing direct correlations to the chemical structure. Considering a vast combination of available cations and anions that can be used to synthesize ionic liquids, development of predictive theoretical approaches that allow for accurate tailoring of their physical properties has become crucial to further enhance the performance of electrochemical devices such as lithium batteries, fuel and solar cells. This perspective article gives a thorough overview of current theoretical approaches applied for studying thermodynamic (melting point and enthalpy of vapourisation) and transport (conductivity and viscosity) properties of ionic liquids, emphasizing their reliability and limitations. Strategies for improving predictive power and versatility of existing theoretical approaches are also outlined. © 2011 the Societies Owner.


Alston M.,Monash University
Journal of Sociology | Year: 2011

Debate continues to rage as to the veracity of evidence around the permanence of climate change. There is no doubt that changes are occurring across the world and that these changes are causing significant social hardship, including food and water insecurity and large-scale movements of people. What is also emerging in research across the world is that these social impacts and adaptations are highly gendered. This article draws on several years of research on the Australian drought and more recent research on declining water availability in the Murray-Darling Basin of Australia. It notes the significant social impacts, particularly in remote and irrigation areas, and draws out the gendered impacts of these changes. The article argues for more sensitive rights-based social policy to address people who are under extraordinary stress during times of unparalleled change. © 2010 The Australian Sociological Association.


Goldberg A.S.,Monash University
Journal of Geodynamics | Year: 2010

The six large fanning dyke swarms mapped here using aeromagnetic data span two periods in the evolution of the Columbia supercontinent: (i) 1.9-1.7. Ga during and immediately following maximum packing of Columbia; and (ii) 1.3-1.2. Ga during the period of final Columbia break-up. The dyke swarms define the locus of hotspot generated magmatism associated with dyke intrusion and their current relationship to continental margins and or intracratonic rifts can be used to identify the tectonic setting associated with each swarm. Three swarms were associated with failed or aborted rifts and indicate multiple hotspots were active during the break-up of Columbia. Three dyke swarms were related to successful rifting and ocean opening. These swarms provide a constraint on palaeo-continental block positions that are not accounted for in the current reconstructions of Columbia. © 2010 Elsevier Ltd.


The wetting behavior of As-rich sulfosalt melts against monosulfide solid solution (MSS) is investigated using experiments to elucidate late-stage fractionation processes in magmatic sulfide systems, which may control the distribution of platinum group elements. A range of As-rich melt compositions is found to wet MSS, including those that contain significant proportions (1%-45%) of precious metals (Pt, Pd, and Au). However, extremely Au rich or Pt rich sulfosalt melts (>~40% Au; >~50% Pt + 5% Au) do not wet MSS. These results imply that if magma contamination and/or fractionation processes were able to produce a late-stage As-rich melt (sulfosalt melts crystallize cooler than MSS) that exceeds ~0.2% of the rock volume, then an interconnected melt drainage network would be able to form along MSS crystal triple junctions. The dense sulfosalt melt could thereby drain downward, progressively sequestering incompatible Bi, Sb, Te, Pt, Pd, and Au to form sulfosalt melt accumulations that continue to fractionate to form the platinum group minerals. This late-stage fractionation model is consistent with the observed mineral distribution in numerous magmatic sulfide deposits. © 2010 Geological Society of America.


Burton P.R.,Monash University | Brown W.A.,Monash University
International Journal of Obesity | Year: 2011

Laparoscopic adjustable gastric banding (LAGB) has rapidly emerged as a popular bariatric procedure because of its safety, efficacy, durability and adjustability. Despite widespread use, there is limited understanding of how it induces weight loss. Previously, it has been classified as a restrictive procedure, physically limiting the patient to a small meal that subsequently slowly empties into the distal stomach. However, the tiny pouch of stomach created above the LAGB appears to be unable to accommodate even the smallest of meals. Therefore, the key mechanism has been hypothesized to be the induction of satiety via, as yet, undefined pathways. The critical question remains: what are the key physiological changes that lead to satiety and weight loss? In successful LAGB patients, a consistent intraluminal pressure at the level of the LAGB of 26.919.8 mm Hg is observed. Studies using semi-solid swallows combined with intraluminal pressure recordings have demonstrated that semi-solid transit across the resistance of the LAGB is mediated by repeated esophageal peristaltic contractions (mean 4.52.9) that produce episodic flow, interspersed by reflux events. Failed transit results in obstruction and regurgitation, whereas dilatation of the supraband stomach induces severe and intolerable reflux. Overall gastric emptying does not appear to be significantly altered following LAGB. Focused investigations have shown that the supraband stomach is empty of an ingested meal 1-2 min after intake ceases. Considerable progress has been made in understanding the mechanical physiological effects of the LAGB on esophageal and proximal gastric function. These have been correlated with patient outcomes and sensations. On the basis of recent data, it appears that the LAGB activates the peripheral satiety mechanism without physically restricting the meal size. Therefore, it should not be classified as a restrictive procedure. The precise mechanism of weight loss with the LAGB remains to be delineated. © 2011 Macmillan Publishers Limited All rights reserved.


BACKGROUND: Poor retention of health workers is a significant problem in rural and remote areas, with negative consequences for both health services and patient care. OBJECTIVE: This review aimed to synthesise the available evidence regarding the effectiveness of retention strategies for health workers in rural and remote areas, with a focus on those studies relevant to Australia. DESIGN: A systematic review method was adopted. Six program evaluation articles, eight review articles and one grey literature report were identified that met study inclusion/exclusion criteria. RESULTS: While a wide range of retention strategies have been introduced in various settings to reduce unnecessary staff turnover and increase length of stay, few have been rigorously evaluated. Little evidence demonstrating the effectiveness of any specific strategy is currently available, with the possible exception of health worker obligation. Multiple factors influence length of employment, indicating that a flexible, multifaceted response to improving workforce retention is required. CONCLUSIONS: This paper proposes a comprehensive rural and remote health workforce retention framework to address factors known to contribute to avoidable turnover. The six components of the framework relate to staffing, infrastructure, remuneration, workplace organisation, professional environment, and social, family and community support. In order to ensure their effectiveness, retention strategies should be rigorously evaluated using appropriate pre- and post-intervention comparisons.


The nature of rainfall events is explored through six years of below average rainfall, associated with negative Southern Oscillation Index (SOI), and three years of above average rainfall, associated with positive SOI (and strong La Niña conditions), at arid Fowlers Gap, Australia. There is a greater probability of rainfall in wet years, but the events themselves also change significantly. Rainfall depth per event was 116% larger on average in wet years than dry, and average event rainfall rate was 85% higher. However, these results are influenced by a small number of very large events in the wet years, and events of <2mm occur at about the same rate in dry and wet years. Rainfall event profiles in dry years showed more Huff first quartile events likely to promote partitioning of rain into infiltration. In contrast, larger events in wet years showed a preponderance of Huff third quartile profiles likely to be associated with greater partitioning of rainfall into overland flow. This co-variation in rainfall event profile with annual rainfall, not previously described, is reasoned to increase the amplitude of ecological impacts of the SOI-related rainfall variability at this site. © 2013 Elsevier Ltd.


Bruce A.I.,Monash University
Proceedings. Biological sciences / The Royal Society | Year: 2012

Leaf-cutting ants (Atta spp.) create physical pathways to support the transport of resources on which colony growth and reproduction depend. We determined the scaling relationship between the rate of resource acquisition and the size of the trail system and foraging workforce for 18 colonies of Atta colombica and Atta cephalotes. We examined conventional power-law scaling patterns, but did so in a multivariate analysis that reveals the simultaneous effects of forager number, trail length and trail width. Foraging rate (number of resource-laden ants returning to the nest per unit time) scaled at the 0.93 power of worker numbers, the -1.02 power of total trail length and the 0.65 power of trail width. These scaling exponents indicate that individual performance declines only slightly as more foragers are recruited to the workforce, but that trail length imposes a severe penalty on the foraging rate. A model of mass traffic flow predicts the allometric patterns for workforce and trail length, although the effect of trail width is unexpected and points to the importance of the little-known mechanisms that regulate a colony's investment in trail clearance. These results provide a point of comparison for the role that resource flows may play in allometric scaling patterns in other transport-dependent entities, such as human cities.


Rachon D.,Medical University of Gdańsk | Teede H.,Monash University
Molecular and Cellular Endocrinology | Year: 2010

Insulin resistance (IR) is a consequence of obesity, and in women it is often inextricably linked with ovarian function leading to clinical reproductive manifestations such as early menarche onset, subfertility and polycystic ovary syndrome (PCOS). Likewise, the dramatic fall in oestrogen production after menopause may contribute to weight gain and changes in adipose tissue distribution. Overall, women who are obese, especially those with reproductive complications including PCOS, have been identified as specific high risk subgroups for further progression through to prediabetes, type 2 diabetes mellitus (T2DM) and potentially cardiovascular disease (CVD). This review focuses on the interrelationship between the ovarian function and obesity as well as its treatment strategies. © 2009 Elsevier Ireland Ltd. All rights reserved.


Gibson P.R.,Monash University
Journal of Gastroenterology and Hepatology (Australia) | Year: 2011

Background and Aim: Food-related symptoms are commonly described by patients with functional bowel disorders, but dietary change as an evidence-based therapy has not been part of routine management strategies. This reviews aims to discuss strategies commonly applied. Method: Published literature was reviewed. Results: Traditional approaches involve elimination diets followed by placebo-controlled reintroduction of specific foods, which is tedious at best and not applied in routine practice. Pathogenically-based approaches include determining what food components are inducing food hypersensitivity responses using specific biomarkers, but this is probably applicable to a small proportion of patients only and has met with only limited success. Food bioactive chemicals, such as salicylates, have been targeted, but there is a paucity of quality evidence for or against this approach. In contrast, targeting poorly absorbed dietary components that might induce luminal distension via osmotic effects and rapid fermentation (FODMAPs) has been successful and the efficacy of the dietitian-delivered low FODMAP diet is now supported by high quality evidence. Improvement of all symptoms of FBD in three out of four patients has been achieved. The diet may potentially improve stool frequency in patients with an ileal pouch or a high output ileostomy, or functional symptoms in patients with inflammatory bowel disease. FODMAPs in enteral formulas may also be responsible for diarrhoea induced by enteral nutrition. Conclusion: Dietary restriction of FODMAPs is an effective therapy in the majority of patients with functional bowel symptoms and, provided dietitians are trained in the technique, should be first line therapy. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.


McLachlan R.I.,Monash Institute of Medical Research | O'Bryan M.K.,Monash University
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Intracytoplasmic sperm injection (ICSI) now provides fertility in many cases of severe idiopathic spermatogenic failure and obstructive azoospermia. Genetic causes must be sought by systematic evaluation of infertile men and affected couples informed about the implications of such diagnoses for assisted reproductive technology outcome and their potential offspring. This review discusses established and emerging genetic disorders related to fertility practice. Chromosomal anomalies are found in about 7% men with idiopathic spermatogenic failure, predominantly numerical/structural in azoospermic men and translocations/inversions in oligospermic men. Routine karyotyping of men with sperm densities less than 10 million/ml, even in the absence of other clinical presentations, is recommended because infertility is associated with higher rates of aneuploidy in ejaculated or testicular sperm and increased chromosomal defects in ICSI offspring. The long arm of the Y chromosome microdeletions are the most common recognized genetic cause of infertility and are found in about 4% men with sperm densities less than 5 million/ml. Routine testing using strict quality assurance procedures is recommended. Azoospermia factor (AZF)-c deletions, the most common form of the long arm of the Y chromosome microdeletions, are usually associated with low levels of sperm in the ejaculate or in testis biopsies, whereas men with AZFa or AZFb+c deletions usually produce no testicular sperm. When AZF-deleted sperm are available and used for ICSI, fertility defects in male offspring seem inevitable. Bilateral congenital absence of the vas is associated with heterozygosity for cystic fibrosis transmembrane receptor mutations making routine gene screening and genetic counseling of the couple essential. Testing for less common genetic associations/defects linked with different reproductive dysfunction may be applicable to specific patients but have not entered routine practice. Copyright © 2010 by The Endocrine Society.


Jackson S.P.,Monash University | Schoenwaelder S.M.,Monash University
Blood | Year: 2010

Apoptosis and necrosis represent distinct cell death processes that regulate mammalian development, physiology and disease. Apoptosis characteristically leads to the silent destruction and removal of cells in the absence of an inflammatory response. In contrast, necrotic cell death can induce physiologic inflammatory responses linked to tissue defense and repair. Although anucleate, platelets undergo programmed cell death, with apoptosis playing an important role in clearing effete platelets from the circulation. While it has long been recognized that procoagulant platelets exhibit characteristic features of dying cells, recent studies have demonstrated that platelet procoagulant function can occur independent of apoptosis. A growing body of evidence suggest that the biochemical, morphologic and functional changes underlying agonist-induced platelet procoagulant function are broadly consistent with cell necrosis, raising the possibility that distinct death pathways regulate platelet function and survival. In this article, we will discuss the mechanisms underlying apoptotic and necrotic cell death pathways and examine the evidence linking these pathways to the platelet procoagulant response. We will also discuss the potential contribution of these pathways to the platelet storage lesion and propose a simplified nomenclature to describe procoagulant platelets. © 2010 by The American Society of Hematology.


Asghari H.R.,Shahrood University of Technology | Cavagnaro T.R.,Monash University
PLoS ONE | Year: 2012

The capacity of mycorrhizal and non-mycorrhizal root systems to reduce nitrate (NO 3 -) and ammonium (NH 4 +) loss from soils via leaching was investigated in a microcosm-based study. A mycorrhiza defective tomato mutant and its mycorrhizal wildtype progenitor were used in this experiment in order to avoid the indirect effects of establishing non-mycorrhizal control treatments on soil nitrogen cycling and the wider soil biota. Mycorrhizal root systems dramatically reduced nitrate loss (almost 40 times less) via leaching, compared to their non-mycorrhizal counterparts, following a pulse application of ammonium nitrate to experimental microcosms. The capacity of AM to reduce nutrient loss via leaching has received relatively little attention, but as demonstrated here, can be significant. Taken together, these data highlight the need to consider the potential benefits of AM beyond improvements in plant nutrition alone. © 2012 Asghari, Cavagnaro.


Hessami M.-A.,Monash University | Bowly D.R.,Monash University
Applied Energy | Year: 2011

This paper presents the details of a theoretical study of the economic advantages of using large-scale energy storage to complement a wind farm in a base-load dominated electricity grid. A computer model is developed which simulates the operation of several energy storage systems when used with the 190-MW Portland Wind Farm (PWF) located in Portland, Victoria, Australia. A variety of operating strategies are compared with the results of a dynamic programming model which finds the maximum possible revenue which a given system can generate for a set of input conditions. Three energy storage systems are modelled and costed: Pumped Seawater Hydro Storage (PSHS), Compressed Air Energy Storage (CAES), and Thermal Energy Storage (TES). It is found that CAES is the most profitable storage medium, requiring a capital expenditure of A$140. M and generating a rate of return (ROR) of 15.4%. The ROR for PSHS was 9.6%, and for TES was 8.0%. Therefore, a significant investment opportunity exists for the installation of an energy storage system in this wind farm. It is therefore highly recommended that CAES is investigated further with the aim of introducing large-scale energy storage to PWF and other similar wind turbine installations. © 2010.


The effects of stratospheric cooling and sea surface warming on tropical cyclone (TC) potential intensity (PI) are explored using an axisymmetric cloud-resolving model run to radiative-convective equilibrium (RCE). Almost all observationally constrained datasets show that the tropical lower stratosphere has cooled over the past few decades. Such cooling may affect PI by modifying the storm's outflow temperature, which together with the sea surface temperature (SST) determines the thermal efficiency in PI theory. Results show that cooling near and above the model tropopause (̃90 hPa), with fixed SST, increases the PI at a rate of 1ms-1 per degree of cooling. Most of this trend comes from a large increase in the thermal efficiency component of PI as the stratosphere cools. Sea surface warming (with fixed stratospheric temperature) increases the PI by roughly twice as much per degree, at a rate of about 2ms-1K-1. Under increasing SST, most of the PI trend comes from large changes in the air-sea thermodynamic disequilibrium. The predicted outflow temperature shows no trend in response to SST increase; However, the outflow height increases substantially. Under stratospheric cooling, the outflow temperature decreases and at the same rate as the imposed cooling. These results have considerable implications for global PI trends in response to climate change. Tropical oceans have warmed by about 0.15Kdecade-1 since the 1970s, but the stratosphere has cooled anywhere from 0.3 to over 1Kdecade-1, depending on the dataset. Therefore, global PI trends in recent decades appear to have been driven more by stratospheric cooling than by surface warming. © 2013 American Meteorological Society.


Climate scientists are practically unanimous in the belief that anthropogenic greenhouse gas contributions have added to the thickness and thus the effectiveness of the greenhouse gas layer, leading to a warming of the planet (IPCC, 2005 [1]). Engineers and scientists around the globe are researching and developing measures to reduce greenhouse gas emissions. These measures have included proposals to sequester carbon dioxide (CO2) in deep geological formations (Perera et al., in press [18]). For CO2 sequestration in deep geological reservoirs to become a feasible strategy to reduce greenhouse gas emissions, a sound understanding of the manner by which mechanical properties and permeability changes with the introduction of CO 2 to the geological reservoir will influence the stability of that reservoir is required. Thus there is a need to develop laboratory equipment capable of simulating the CO2 injection and storage process for deep geological CO2 sequestration under the expected in situ pressure (confinement and fluid) and temperature conditions. Triaxial experiment has been identified as the best method for this purpose (Perera et al., 2011b [19]). Therefore, we present a new high-pressure triaxial apparatus which can provide the high confining and fluid injection pressures and elevated temperatures expected for deep geological CO2 sequestration. The new setup can be used to conduct mechanical and permeability testing on intact or fractured natural rock samples or synthetic rock samples subjected to high-pressure injection of up to three fluid phases (gas and/or liquid) at high pressures and temperatures corresponding to field conditions. The equipment is capable of delivering fluids to the sample at injection pressures of up to 50 MPa, confining pressures of up to 70 MPa and temperature up to 50 °C and will continuously record fluid injection and confining pressures, axial load and displacement, radial displacement and independent outflow rates for liquid and gas fluid phases (under drained conditions). Leakage tests have confirmed the effectiveness of the device at pressures up to its maximum capacities. Additionally the temperature-pressure relationship for the hydraulic oil used to apply confining pressure to the sample has been calibrated to account for the influence of changes in temperature on confining pressure. Several permeability tests (using N2 and CO2 as the injection fluid and 10 MPa confining pressure) and one strength test are reported for black coal samples from the Sydney Basin, New South Wales. According to the results of the permeability tests, coal mass permeability decreases with increasing effective stress for both gases. However, the permeability for N2 gas is much higher than CO2. Moreover, test results are consistent with matrix swelling due to the adsorption of CO2 in coal. The strength testing results are in agreement with the results of testing carried on similar black coal samples from literature, certifying the ability for the new device to accurately measure strength and deformation properties of rock under deep ground conditions. © 2011 Elsevier Ltd. All rights reserved.


Shiddiky M.J.A.,Monash University | Torriero A.A.J.,Monash University
Biosensors and Bioelectronics | Year: 2011

Since 1992, when the room temperature ionic liquids (ILs) based on the 1-alkyl-3-methylimidazolium cation were reported to provide an attractive combination of an electrochemical solvent and electrolyte, ILs have been widely used in electrodeposition, electrosynthesis, electrocatalysis, electrochemical capacitor, and lithium batteries. However, it has only been in the last few years that electrochemical biosensors based on carbon ionic liquid electrodes (CILEs) and IL-modified macrodisk electrodes have been reported. However, there are still a lot of challenges in achieving IL-based sensitive, selective, and reproducible biosensors for high speed analysis of biological and environmental compounds of interest. This review discusses the principles of operation of electrochemical biosensors based on CILEs and IL/composite-modified macrodisk electrodes. Subsequently, recent developments and major strategies for enhancing sensing performance are discussed. Key challenges and opportunities of IL-based biosensors to further development and use are considered. Emphasis is given to direct electron-transfer reaction and electrocatalysis of hemeproteins and enzyme-modified composite electrodes. © 2010 Elsevier B.V.


Merson T.D.,Florey Institute of Neuroscience and Mental Health | Bourne J.A.,Monash University
International Journal of Biochemistry and Cell Biology | Year: 2014

Ischaemic stroke is among the most common yet most intractable types of central nervous system (CNS) injury in the adult human population. In the acute stages of disease, neurons in the ischaemic lesion rapidly die and other neuronal populations in the ischaemic penumbra are vulnerable to secondary injury. Multiple parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. Accumulating evidence indicates that cerebral ischaemia initiates an endogenous regenerative response within the adult brain that potentiates adult neurogenesis from populations of neural stem and progenitor cells. A major research focus has been to understand the cellular and molecular mechanisms that underlie the potentiation of adult neurogenesis and to appreciate how interventions designed to modulate these processes could enhance neural regeneration in the post-ischaemic brain. In this review, we highlight recent advances over the last 5 years that help unravel the cellular and molecular mechanisms that potentiate endogenous neurogenesis following cerebral ischaemia and are dissecting the functional importance of this regenerative mechanism following brain injury. This article is part of a Directed Issue entitled: Regenerative Medicine: the challenge of translation. © 2014 Elsevier Ltd. All rights reserved.


Rafferty A.R.,Monash University
Proceedings. Biological sciences / The Royal Society | Year: 2012

Arrested embryonic development involves the downregulation or cessation of active cell division and metabolic activity, and the capability of an animal to arrest embryonic development results in temporal plasticity of the duration of embryonic period. Arrested embryonic development is an important reproductive strategy for egg-laying animals that provide no parental care after oviposition. In this review, we discuss each type of embryonic developmental arrest used by oviparous reptiles. Environmental pressures that might have directed the evolution of arrest are addressed and we present previously undiscussed environmentally dependent physiological processes that may occur in the egg to bring about arrest. Areas for future research are proposed to clarify how ecology affects the phenotype of developing embryos. We hypothesize that oviparous reptilian mothers are capable of providing their embryos with a level of phenotypic adaptation to local environmental conditions by incorporating maternal factors into the internal environment of the egg that result in different levels of developmental sensitivity to environmental conditions after they are laid.


Weller C.D.,Monash University
The Cochrane database of systematic reviews | Year: 2013

Chronic venous ulcer healing is a complex clinical problem that requires intervention from skilled, costly, multidisciplinary wound-care teams. Compression therapy has been shown to help heal venous ulcers and to reduce the risk of recurrence. It is not known which interventions help people adhere to compression treatments. To assess the benefits and harms of interventions designed to help people adhere to venous leg ulcer compression therapy, and thus improve healing of venous leg ulcers and prevent their recurrence after healing. In May 2013 we searched The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; trial registries, and reference lists of relevant publications for published and ongoing trials. There were no language or publication date restrictions. We included randomised controlled trials (RCTs) of interventions that help people with venous leg ulcers adhere to compression treatments compared with usual care, or no intervention, or another active intervention. Our main outcomes were number of people with ulcers healed, recurrence, time to complete healing, quality of life, pain, adherence to compression therapy and number of people with adverse events. Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial, and assessed overall quality of evidence for the main outcomes in 'Summary of findings' tables. Low quality evidence from one trial (67 participants) indicates that, compared with home-based care, a community-based Leg Club® clinic that provided mechanisms for peer-support, assistance with goal setting and social interaction did not result in superior healing rates at three months (12/28 people healed in Leg Club clinic group versus 7/28 in home-based care group; risk ratio (RR) 1.71, 95% confidence interval (CI) 0.79 to 3.71); or six months (15/33 healed in Leg Club group versus 10/34 in home-based care group; RR 1.55, 95% CI 0.81 to 2.93); or in improved quality of life outcomes at six months (MD 0.85 points, 95% CI -0.13 to 1.83; 0 to 10 point scale). However, the Leg Club resulted in a statistically significant reduction in pain at six months (MD -12.75 points, 95% CI -24.79, -0.71; 0 to 100 point scale), although this was not considered a clinically important difference. Time to complete healing, recurrence of ulcers, adherence and adverse events were not reported.Low quality evidence from another trial (184 participants) indicates that, compared with usual care in a wound clinic, a community-based and nurse-led self-management programme of six months' duration promoting physical activity (walking and leg exercises) and adherence to compression therapy via counselling and behaviour modification (Lively Legs®) may not result in superior healing rates at 18 months (51/92 healed in Lively Legs group versus 41/92 in usual care group; RR 1.24 (95% CI 0.93 to 1.67)); may not result in reduced rates of recurrence of venous leg ulcers at 18 months (32/69 with recurrence in Lively Legs group versus 38/67 in usual care group; RR 0.82 (95% CI 0.59 to 1.14)); and may not result in superior adherence to compression therapy at 18 months (42/92 people fully adherent in Lively Legs group versus 41/92 in usual care group; RR 1.02 (95% CI 0.74 to 1.41)). Time to complete healing, quality of life, pain and adverse events were not reported. We found no studies that investigated other interventions to promote adherence to compression therapy. There is a paucity of trials of interventions that promote adherence to compression therapy for venous ulcers. Low quality evidence from two trials was identified: one promoting adherence via socialisation and support (Leg Club®), and the other promoting adherence to compression, leg exercises and walking via counselling and behaviour modification (Lively Legs®).These trials did not reveal a benefit of community-based clinics over usual care in terms of healing rates, prevention of recurrence of venous leg ulcers, or quality of life. One trial indicated a small, but possibly clinically unimportant, reduction in pain, while adverse events were not reported. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, at present it is not possible either to recommend or discourage nurse clinic care interventions over standard care.


de Veer M.,Monash University
Discovery medicine | Year: 2011

Since the first mass vaccination against smallpox and its eventual eradication, many more vaccines have been developed based on advances in bacteriology and virology and the use of attenuated live or killed whole pathogens. Immunological discoveries have allowed the development of more refined anti-toxin and conjugate vaccines, while biotechnology provided the tools for rationally designed, genetically engineered vaccines. Many challenges remain in developing safer and more effective vaccines against the more complex diseases such as tuberculosis and HIV-AIDS, and for the rapid protection against newly emerging pathogens or pathogen strains. These vaccines are likely to require the isolation of the "protective" antigenic molecules from the whole pathogen, as well as ways to deliver these to induce effective immune responses with minimal side effects. It has long been recognized that most antigens require the addition of an "adjuvant," an ill-defined substance that non-specifically triggers the innate immune system and boosts an immune response, with aluminum-based adjuvants the most commonly used in most present vaccines. Recent immunological breakthroughs have uncovered that the innate immune system has a much higher degree of complexity than previously thought and can be activated along a wide range of different pathways, depending on the engagement of different innate immune receptors. This in turn determines the type of immune response that will be generated against the vaccine antigens or pathogens. Harvesting the complexity and exquisite specificity of this innate immune system has inspired a new direction in vaccine research, towards the generation of novel adjuvant formulations, tailored to induce defined immune responses effective against specific pathogens. This review gives a brief overview of vaccine development and summarizes different aspects of adjuvant formulation that may influence their activity and specificity.


Laibe G.,Monash University | Laibe G.,University of St. Andrews
Monthly Notices of the Royal Astronomical Society | Year: 2014

We aim to study the migration of growing dust grains in protoplanetary discs, where growth and migration are tightly coupled. This includes the crucial issue of the radial-drift barrier for growing dust grains. We therefore extend the study performed in Paper I, considering models for grain growth and grain dynamics where both the migration and growth rate depend on the grain size and the location in the disc. The parameter space of disc profiles and growth models is exhaustively explored. In doing so, interpretations for the grain motion found in numerical simulations are also provided. We find that a large number of cases is required to characterize entirely the grains radial motion, providing a large number of possible outcomes. Some of them lead dust particles to be accreted on to the central star and some of them do not. We find then that q < 1 is required for discs to retain their growing particles, where q is the exponent of the radial temperature profile T (R) ∞ R-q . Additionally, the initial dust-to-gas ratio has to exceed a critical value for grains to pile up efficiently, thus avoiding being accreted on to the central star. Discs are also found to retain efficiently small dust grains regenerated by fragmentation. We show how those results are sensitive to the turbulent model considered. Even though some physical processes have been neglected, this study allows us to sketch a scenario in which grains can survive the radial-drift barrier in protoplanetary discs as they grow. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Exercise is an effective intervention for the prevention of falls; however, some forms of exercises have been shown to be more effective than others. There is a need to identify effective and efficient methods for training health professionals in exercise prescription for falls prevention. The objective of our study was to compare two approaches for training clinicians in prescribing exercise to prevent falls. This study was a head-to-head randomized trial design. Participants were physiotherapists, occupational therapists, nurses, and exercise physiologists working in Victoria, Australia. Participants randomly assigned to one group received face-to-face traditional education using a 1-day seminar format with additional video and written support material. The other participants received Web-based delivery of the equivalent educational material over a 4-week period with remote tutor facilitation. Outcomes were measured across levels 1 to 3 of Kirkpatrick's hierarchy of educational outcomes, including attendance, adherence, satisfaction, knowledge, and self-reported change in practice. Of the 166 participants initially recruited, there was gradual attrition from randomization to participation in the trial (n = 67 Web-based, n = 68 face-to-face), to completion of the educational content (n = 44 Web-based, n = 50 face-to-face), to completion of the posteducation examinations (n = 43 Web-based, n = 49 face-to-face). Participant satisfaction was not significantly different between the intervention groups: mean (SD) satisfaction with content and relevance of course material was 25.73 (5.14) in the Web-based and 26.11 (5.41) in the face-to-face group; linear regression P = .75; and mean (SD) satisfaction with course facilitation and support was 11.61 (2.00) in the Web-based and 12.08 (1.54) in the face-to-face group; linear regression P = .25. Knowledge test results were comparable between the Web-based and face-to-face groups: median (interquartile range [IQR]) for the Web-based group was 90.00 (70.89-90.67) and for the face-to-face group was 80.56 (70.67-90.00); rank sum P = .07. The median (IQR) scores for the exercise assignment were also comparable: Web-based, 78.6 (68.5-85.1), and face-to-face, 78.6 (70.8-86.9); rank sum P = .61. No significant difference was identified in Kirkpatrick's hierarchy domain change in practice: mean (SD) Web-based, 21.75 (4.40), and face-to-face, 21.88 (3.24); linear regression P = .89. Web-based and face-to-face approaches to the delivery of education to clinicians on the subject of exercise prescription for falls prevention produced equivalent results in all of the outcome domains. Practical considerations should arguably drive choice of delivery method, which may favor Web-based provision for its ability to overcome access issues for health professionals in regional and remote settings. Australian New Zealand Clinical Trials Registry number: ACTRN12610000135011; http://www.anzctr.org.au/ACTRN12610000135011.aspx (Archived by WebCite at http://www.webcitation.org/63MicDjPV).


Chamberlain C.,Monash University
The Cochrane database of systematic reviews | Year: 2013

Tobacco smoking in pregnancy remains one of the few preventable factors associated with complications in pregnancy, stillbirth, low birthweight and preterm birth and has serious long-term implications for women and babies. Smoking in pregnancy is decreasing in high-income countries, but counselling strategy is more effective than others (one study; RR 1.15, 95% CI 0.86 to 1.53). In studies comparing counselling and usual care (the largest comparison), it was unclear whether interventions prevented smoking relapse among women who had stopped smoking spontaneously in early pregnancy (eight studies; average RR 1.06, 95% CI 0.93 to 1.21). However, a clear effect was seen in smoking abstinence at zero to five months postpartum (10 studies; average RR 1.76, 95% CI 1.05 to 2.95), a borderline effect at six to 11 months (six studies; average RR 1.33, 95% CI 1.00 to 1.77), and a significant effect at 12 to 17 months (two studies, average RR 2.20, 95% CI 1.23 to 3.96), but not in the longer term. In other comparisons, the effect was not significantly different from the null effect for most secondary outcomes, but sample sizes were small.Incentive-based interventions had the largest effect size compared with a less intensive intervention (one study; RR 3.64, 95% CI 1.84 to 7.23) and an alternative intervention (one study; RR 4.05, 95% CI 1.48 to 11.11).Feedback interventions demonstrated a significant effect only when compared with usual care and provided in conjunction with other strategies, such as counselling (two studies; average RR 4.39, 95% CI 1.89 to 10.21), but the effect was unclear when compared with a less intensive intervention (two studies; average RR 1.19, 95% CI 0.45 to 3.12).The effect of health education was unclear when compared with usual care (three studies; average RR 1.51, 95% CI 0.64 to 3.59) or less intensive interventions (two studies; average RR 1.50, 95% CI 0.97 to 2.31).Social support interventions appeared effective when provided by peers (five studies; average RR 1.49, 95% CI 1.01 to 2.19), but the effect was unclear in a single trial of support provided by partners.The effects were mixed where the smoking interventions were provided as part of broader interventions to improve maternal health, rather than targeted smoking cessation interventions.Subgroup analyses on primary outcome for all studies showed the intensity of interventions and comparisons has increased over time, with higher intensity interventions more likely to have higher intensity comparisons. While there was no significant difference, trials where the comparison group received usual care had the largest pooled effect size (37 studies; average RR 1.34, 95% CI 1.25 to 1.44), with lower effect sizes when the comparison group received less intensive interventions (30 studies; average RR 1.20, 95% CI 1.08 to 1.31), or alternative interventions (two studies; average RR 1.26, 95% CI 0.98 to 1.53). More recent studies included in this update had a lower effect size (20 studies; average RR 1.26, 95% CI 1.00 to 1.59), I(2)= 3%, compared to those in the previous version of the review (50 studies; average RR 1.50, 95% CI 1.30 to 1.73). There were similar effect sizes in trials with biochemically validated smoking abstinence (49 studies; average RR 1.43, 95% CI 1.22 to 1.67) and those with self-reported abstinence (20 studies; average RR 1.48, 95% CI 1.17 to 1.87). There was no significant difference between trials implemented by researchers (efficacy studies), and those implemented by routine pregnancy staff (effectiveness studies), however the effect was unclear in three dissemination trials of counselling interventions where the focus on the intervention was at an organisational level (average RR 0.96, 95% CI 0.37 to 2.50). The pooled effects were similar in interventions provided for women with predominantly low socio-economic status (44 studies; average RR 1.41, 95% CI 1.19 to 1.66), compared to other women (26 studies; average RR 1.47, 95% CI 1.21 to 1.79); though the effect was unclear in interventions among women from ethnic minority groups (five studies; average RR 1.08, 95% CI 0.83 to 1.40) and aboriginal women (two studies; average RR 0.40, 95% CI 0.06 to 2.67). Importantly, pooled results demonstrated that women who received psychosocial interventions had an 18% reduction in preterm births (14 studies; average RR 0.82, 95% CI 0.70 to 0.96), and infants born with low birthweight (14 studies; average RR 0.82, 95% CI 0.71 to 0.94). There did not appear to be any adverse effects from the psychosocial interventions, and three studies measured an improvement in women's psychological wellbeing. Psychosocial interventions to support women to stop smoking in pregnancy can increase the proportion of women who stop smoking in late pregnancy, and reduce low birthweight and preterm births.


O'Brien L.,Monash University
The Cochrane database of systematic reviews | Year: 2013

Keloid and hypertrophic scars are common and are caused by a proliferation of dermal tissue following skin injury. They cause functional and psychological problems for patients, and their management can be difficult. The use of silicone gel sheeting to prevent and treat hypertrophic scarring is still relatively new and started in 1981 with treatment of burn scars. To determine the effectiveness of silicone gel sheeting for:(1) prevention of hypertrophic or keloid scarring in people with newly healed wounds (e.g. post surgery);(2) treatment of established scarring in people with existing keloid or hypertrophic scars. In May 2013 we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL for this second update. Any randomised or quasi-randomised controlled trials, or controlled clinical trials, comparing silicone gel sheeting for prevention or treatment of hypertrophic or keloid scars with any other non surgical treatment, no treatment or placebo. We assessed all relevant trials for methodological quality. Three review authors extracted data independently using a standardised form and cross-checked the results. We assessed all trials meeting the selection criteria for methodological quality. We included 20 trials involving 873 people, ranging in age from 1.5 to 81 years. The trials compared adhesive silicone gel sheeting with no treatment; non silicone dressing; other silicone products; laser therapy; triamcinolone acetonide injection; topical onion extract and pressure therapy. In the prevention studies, when compared with a no treatment option, whilst silicone gel sheeting reduced the incidence of hypertrophic scarring in people prone to scarring (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.21 to 0.98) these studies were highly susceptible to bias. In treatment studies, silicone gel sheeting produced a statistically significant reduction in scar thickness (mean difference (MD) -2.00, 95% CI -2.14 to -1.85) and colour amelioration (RR 3.49, 95% CI 1.97 to 6.15) but again these studies were highly susceptible to bias. There is weak evidence of a benefit of silicone gel sheeting as a prevention for abnormal scarring in high-risk individuals but the poor quality of research means a great deal of uncertainty prevails. Trials evaluating silicone gel sheeting as a treatment for hypertrophic and keloid scarring showed improvements in scar thickness and scar colour but are of poor quality and highly susceptible to bias.


Agyei D.,Monash University | Danquah M.K.,Monash University
Biotechnology Advances | Year: 2011

Recent studies have shown that most peptide sequences encrypted in food proteins confer bioactive properties after release by enzymatic hydrolysis. Such bioactivities, which include antithrombotic, antihypertensive, immunomodulatory and antioxidant properties, are among the traits that are of biological significance in therapeutic products. Bioactive peptides could therefore serve as potential therapeutic agents. Moreover, research has shown that peptide therapeutics are toxicologically safe, and present less side effects when compared to small molecule drugs. However, the major conventional methods i.e. the synthetic and biotechnological methods used in the production of peptide therapeutics are relatively expensive. The lack of commercially-viable processes for large-scale production of peptide therapeutics has therefore been a major hindrance to the application of peptides as therapeutic aids. This paper therefore discusses the plausibility of manufacturing pharmaceutical-grade bioactive peptides from food proteins; the challenges and some implementable strategies for overcoming those challenges. © 2011 Elsevier Inc.


Kerr P.G.,Monash University
American Journal of Kidney Diseases | Year: 2011

There are many variations in the delivery of hemodialysis. These variations include components of conventional dialysis, such as membrane type, dialysis dose, and session duration. In addition, alternative approaches to dialysis, such as hemodiafiltration, nocturnal hemodialysis, and short daily hemodialysis, also may be considered. For some of these practice variations, data exist to support one approach over another (eg, fistulas rather than grafts and catheters), but for many, no such data exist. Very few practice variations have been examined in randomized trials, and we are reliant predominantly on observational data. This review examines some practice variations in hemodialysis delivery, attempting to highlight which of these may be appropriate to consider when optimizing dialysis delivery in the clinic. © 2011 National Kidney Foundation, Inc.


Vesely M.D.,University of Washington | Kershaw M.H.,Peter MacCallum Cancer Center | Kershaw M.H.,University of Melbourne | Kershaw M.H.,Monash University | And 3 more authors.
Annual Review of Immunology | Year: 2011

The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer. © 2011 by Annual Reviews. All rights reserved.


Quenault T.,Monash University | Lithgow T.,Monash University | Traven A.,Monash University
Trends in Cell Biology | Year: 2011

The eukaryotic family of RNA-binding proteins termed PUF (Pumilio and FBF) is known for its roles in cell division, differentiation and development. The best-characterized function of PUFs is as posttranscriptional repressors. Recent studies have indicated that PUFs can also activate gene expression. Moreover, it is becoming clear that PUFs facilitate mRNA localization for spatial control of expression. Here, we review the emerging concept of PUF proteins as versatile posttranscriptional regulators. We discuss how the functions of PUFs as repressors and mRNA targeting factors could be integrated by focusing on Puf3 and Puf6 from yeast and propose a model for how the roles of Puf3 in mRNA targeting to the mitochondria and mRNA repression might promote cotranslational import into mitochondria and mitochondrial biogenesis. © 2010 Elsevier Ltd.


Kitching A.R.,Monash University | Kitching A.R.,Monash Medical Center | Holdsworth S.R.,Monash University
Journal of the American Society of Nephrology | Year: 2011

IL-17-producing Th17 effector cells directly induce renal inflammation by activating neutrophils or by participating in macrophage-mediated tissue injury. Th17 cells and cytokines participate in human and experimental renal disease, especially in proliferative glomerulonephritis where Th17 effector cells are active. Although growing evidence suggests Th17 cells are particularly relevant to effector responses involving neutrophils, there are still important questions to address before the complete functions of Th17 cells in renal disease are understood fully. Copyright © 2011 by the American Society of Nephrology.


Indrawan-Santiago M.,Monash University
Proceedings of the 2012 15th International Conference on Network-Based Information Systems, NBIS 2012 | Year: 2012

The demand to process large sets of data has increased in the last few years from both the scientific and business community. To serve this demand, a number of new databases have been introduced that are not based on relational models. This group of databases is popularly known as NoSQL. The underlying data and transaction models in the NoSQL are different from relational databases. Much interest has been placed by organizations in adopting this new technology and has created a buzz in database research. The fact that the underlying principles are different to relational models has placed a dilemma in the database research community. Would this new technology change the shape of database research and industry? © 2012 IEEE.


Stark R.,Monash University | Kibbey R.G.,Yale University
Biochimica et Biophysica Acta - General Subjects | Year: 2014

Background Plasma glucose levels are tightly regulated within a narrow physiologic range. Insulin-mediated glucose uptake by tissues must be balanced by the appearance of glucose from nutritional sources, glycogen stores, or gluconeogenesis. In this regard, a common pathway regulating both glucose clearance and appearance has not been described. The metabolism of glucose to produce ATP is generally considered to be the primary stimulus for insulin release from beta-cells. Similarly, gluconeogenesis from phosphoenolpyruvate (PEP) is believed to be the primarily pathway via the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). These models cannot adequately explain the regulation of insulin secretion or gluconeogenesis. Scope of review A metabolic sensing pathway involving mitochondrial GTP (mtGTP) and PEP synthesis by the mitochondrial isoform of PEPCK (PEPCK-M) is associated with glucose-stimulated insulin secretion from pancreatic beta-cells. Here we examine whether there is evidence for a similar mtGTP-dependent pathway involved in gluconeogenesis. In both islets and the liver, mtGTP is produced at the substrate level by the enzyme succinyl CoA synthetase (SCS-GTP) with a rate proportional to the TCA cycle. In the beta-cell PEPCK-M then hydrolyzes mtGTP in the production of PEP that, unlike mtGTP, can escape the mitochondria to generate a signal for insulin release. Similarly, PEPCK-M and mtGTP might also provide a significant source of PEP in gluconeogenic tissues for the production of glucose. This review will focus on the possibility that PEPCK-M, as a sensor for TCA cycle flux, is a key mechanism to regulate both insulin secretion and gluconeogenesis suggesting conservation of this biochemical mechanism in regulating multiple aspects of glucose homeostasis. Moreover, we propose that this mechanism may be important for regulating insulin secretion and gluconeogenesis compared to canonical nutrient sensing pathways. Major conclusions PEPCK-M, initially believed to be absent in islets, carries a substantial metabolic flux in beta-cells. This flux is intimately involved with the coupling of glucose-stimulated insulin secretion. PEPCK-M activity may have been similarly underestimated in glucose producing tissues and could potentially be an unappreciated but important source of gluconeogenesis. General significance The generation of PEP via PEPCK-M may occur via a metabolic sensing pathway important for regulating both insulin secretion and gluconeogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. © 2013 Elsevier B.V.


Anko M.-L.,Monash University
Seminars in Cell and Developmental Biology | Year: 2014

Serine-arginine rich splicing factors (SR proteins) are a family of RNA binding proteins that are essential for development in various model organisms. Although SR proteins are necessary for pre-mRNA splicing in metazoans, their binding is not limited to pre-RNA. SR proteins associate with various classes of RNAs, including intronless transcripts and non-coding RNAs, and regulate many processes during the gene expression pathway. Recent studies taking advantage of high-throughput sequencing and other genome-wide approaches have started to shed light into the distinct and overlapping roles of SR proteins in the regulation of gene expression in cells and have led to the identification of endogenous gene targets. These studies together with animal models where individual SR proteins have been depleted in specific tissues suggest that SR proteins may regulate distinct gene expression programmes through their interactions with RNAs and provide crosstalk between splicing and other regulatory processes. © 2014 Elsevier Ltd.


This article is part of a Special Issue "Energy Balance".The interface between metabolic regulators and the reproductive system is reviewed with special reference to the sheep. Even though sheep are ruminants with particular metabolic characteristics, there is a broad consensus across species in the way that the reproductive system is influenced by metabolic state. An update on the neuroendocrinology of reproduction indicates the need to account for the way that kisspeptin provides major drive to gonadotropin releasing hormone (GnRH) neurons and also mediates the feedback effects of gonadal steroids. The way that kisspeptin function is influenced by appetite regulating peptides (ARP) is considered. Another newly recognised factor is gonadotropin inhibitory hormone (GnIH), which has a dual function in that it suppresses reproductive function whilst also acting as an orexigen.Our understanding of the regulation of food intake and energy expenditure has expanded exponentially in the last 3 decades and historical perspective is provided. The function of the regulatory factors and the hypothalamic cellular systems involved is reviewed with special reference to the sheep. Less is known of these systems in the cow, especially the dairy cow, in which a major fertility issue has emerged in parallel with selection for increased milk production.Other endocrine systems - the hypothalamo-pituitary-adrenal axis, the growth hormone (GH) axis and the thyroid hormones - are influenced by metabolic state and are relevant to the interface between metabolic function and reproduction. Special consideration is given to issues such as season and lactation, where the relationship between metabolic hormones and reproductive function is altered. © 2014 Elsevier Inc.


Toh B.-H.,Monash University
Autoimmunity Reviews | Year: 2014

Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus. © 2014 Elsevier B.V.


Joeckel L.T.,Monash University | Bird P.I.,Monash University
Biological Chemistry | Year: 2014

Granzymes are serine proteases mainly found in cytotoxic lymphocytes. The most-studied member of this group is granzyme B, which is a potent cytotoxin that has set the paradigm that all granzymes are cyototoxic. In the last 5 years, this paradigm has become controversial. On one hand, there is a plethora of sometimes contradictory publications showing mainly caspase-independent cytotoxic effects of granzyme A and the so-called orphan granzymes in vitro. On the other hand, there are increasing numbers of reports of granzymes failing to induce cell death in vitro unless very high (potentially supra-physiological) concentrations are used. Furthermore, experiments with granzyme A or granzyme M knock-out mice reveal little or no deficit in their cytotoxic lymphocytes' killing ability ex vivo, but indicate impairment in the inflammatory response. These findings of non-cytotoxic effects of granzymes challenge dogma, and thus require alternative or additional explanations to be developed of the role of granzymes in defeating pathogens. Here we review evidence for granzyme cytotoxicity, give an overview of their non-cytotoxic functions, and suggest technical improvements for future investigations. © 2014 Walter de Gruyter GmbH, Berlin/Boston.


Gardiner E.E.,Monash University | Andrews R.K.,Monash University
Transfusion Medicine Reviews | Year: 2014

Quantity, quality, and lifespan are 3 important factors in the physiology, pathology, and transfusion of human blood platelets. The aim of this review is to discuss the proteolytic regulation of key platelet-specific receptors, glycoprotein(GP)Ib and GPVI, involved in the function of platelets in hemostasis and thrombosis, and nonimmune or immune thrombocytopenia. The scope of the review encompasses the basic science of platelet receptor shedding, practical aspects related to laboratory analysis of platelet receptor expression/shedding, and clinical implications of using the proteolytic fragments as platelet-specific biomarkers in vivo in terms of platelet function and clearance. These topics can be relevant to platelet transfusion regarding both changes in platelet receptor expression occurring ex vivo during platelet storage and/or clinical use of platelets for transfusion. In this regard, quantitative analysis of platelet receptor profiles on blood samples from individuals could ultimately enable stratification of bleeding risk, discrimination between causes of thrombocytopenia due to impaired production vs enhanced clearance, and monitoring of response to treatment prior to change in platelet count. © 2014 Elsevier Inc.


Kramer S.,Monash University
Cochrane database of systematic reviews (Online) | Year: 2013

Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses.Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence. To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children. We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinical study results.org were undertaken. Searches are up to date to 7 November 2012. Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone.Ciclesonide compared to budesonide (dose ratio 1:2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group.Ciclesonide compared to fluticasone (dose ratio 1:1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00).Ciclesonide versus fluticasone (dose ratio 1:2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23).The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1:1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1:1). For ciclesonide versus fluticasone (dose ratio 1:2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1:2). An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects.


Barker A.,Monash University
Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention | Year: 2011

In-hospital fall-related injuries are a source of personal harm, preventable hospitalisation costs, and access block through increased length of stay. Despite increased fall prevention awareness and activity over the last decade, rates of reported fall-related fractures in hospitals appear not to have decreased. This cluster randomised controlled trial (RCT) aims to determine the efficacy of the 6-PACK programme for preventing fall-related injuries, and its generalisability to other acute hospitals. 24 acute medical and surgical wards from six to eight hospitals throughout Australia will be recruited for the study. Wards will be matched by type and fall-related injury rates, then randomly allocated to the 6-PACK intervention (12 wards) or usual care control group (12 wards). The 6-PACK programme includes a nine-item fall risk assessment and six nursing interventions: 'falls alert' sign; supervision of patients in the bathroom; ensuring patient's walking aids are within reach; establishment of a toileting regime; use of a low-low bed; and use of bed/chair alarm. Intervention wards will be supported by a structured implementation strategy. The primary outcomes are fall and fall-related injury rates 12 months following 6-PACK implementation. This study will involve approximately 16,000 patients, and as such is planned to be the largest hospital fall prevention RCT to be undertaken and the first to be powered for the important outcome of fall-related injuries. If effective, there is potential to implement the programme widely as part of daily patient care in acute hospital wards where fall-related injuries are a problem.


Pitt V.,Monash University
The Cochrane database of systematic reviews | Year: 2013

In mental health services, the past several decades has seen a slow but steady trend towards employment of past or present consumers of the service to work alongside mental health professionals in providing services. However the effects of this employment on clients (service recipients) and services has remained unclear.We conducted a systematic review of randomised trials assessing the effects of employing consumers of mental health services as providers of statutory mental health services to clients. In this review this role is called 'consumer-provider' and the term 'statutory mental health services' refers to public services, those required by statute or law, or public services involving statutory duties. The consumer-provider's role can encompass peer support, coaching, advocacy, case management or outreach, health services (case management roles (4 trials), facilitating group quality of life (mean difference (MD) -0.30, 95% confidence interval (CI) -0.80 to 0.20); depression (data not pooled), general mental health symptoms (standardised mean difference (SMD) -0.24, 95% CI -0.52 to 0.05); client satisfaction with treatment (SMD -0.22, 95% CI -0.69 to 0.25), client or professional ratings of client-manager relationship; use of mental health services, hospital admissions and length of stay; or attrition (risk ratio 0.80, 95% CI 0.58 to 1.09) between mental health teams involving consumer-providers or professional staff in similar roles.There was a small reduction in crisis and emergency service use for clients receiving care involving consumer-providers (SMD -0.34 (95%CI -0.60 to -0.07). Past or present consumers who provided mental health services did so differently than professionals; they spent more time face-to-face with clients, and less time in the office, on the telephone, with clients' friends and family, or at provider agencies.Six trials involving 2215 people compared mental health services with or without the addition of consumer-providers. There were no significant to 0.79), attendance rates (SMD 0.52 (95% CI -0.07 to 1.11), hospital admissions and length of stay, or attrition (risk ratio 1.29, 95% CI 0.72 to 2.31) between groups with consumer-providers as an adjunct to professional-led care and those receiving usual care from health professionals alone. One study found a small difference favouring the intervention group for both client and staff ratings of clients' needs adverse outcomes for clients, the potential benefits and harms to the consumer-providers themselves (including need to return to treatment), of the consumer-provider role (eg specific tasks, responsibilities and expected deliverables of the role) and relevant training for the role so that it can be readily implemented. The weight of evidence being strongly based in the United States, future research should be located in diverse settings including in low- and middle-income countries.


Smith G.D.,Monash University
The Cochrane database of systematic reviews | Year: 2013

Patients with the cardiac arrhythmia supraventricular tachycardia (SVT) frequently present to clinicians in the prehospital and emergency medicine settings. Restoring sinus rhythm by terminating the SVT involves increasing the refractoriness of AV nodal tissue within the myocardium by means of vagal manoeuvres, pharmacological agents or electrical cardioversion. A commonly used first-line technique to restore the normal sinus rhythm (reversion) is the Valsalva Manoeuvre (VM). This is a non-invasive means of increasing myocardial refractoriness by increasing intrathoracic pressure for a brief period, thus stimulating baroreceptor activity in the aortic arch and carotid bodies, resulting in increased parasympathetic (vagus nerve) tone. To assess the evidence of effectiveness of the Valsalva Manoeuvre in terminating supraventricular tachycardia. We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1 of 12, 2012); MEDLINE Ovid (1946 to January 2012); EMBASE Ovid (1947 to January 2012); Web of Science (1970 to 27 January 2012); and BIOSIS Previews (1969 to 27 January 2012). Trials registries, the Index to Theses and the bibliographies of all relevant publications identified by these strategies were also checked. We included all randomised controlled trials (RCTs) that examined the effectiveness of the Valsalva Manoeuvre in terminating SVT. Two authors independently extracted the data using a standardised form. Each trial was assessed for internal validity with differences resolved by discussion. Data were then extracted and entered into Review Manager 5.1 (RevMan). We identified three randomised controlled trials including 316 participants. All three studies compared the effectiveness of VM in reverting SVT with that of other vagal manoeuvres in a cross-over design. Two studies induced SVT within a controlled laboratory environment. Participants had ceased all medications prior to engaging in these studies. The third study reported on patients presenting to a hospital emergency department with an episode of SVT. These patients were not controlled for medications or other factors prior to intervention.The two laboratory studies demonstrated reversion rates of 45.9% and 54.3%, whilst the clinical study demonstrated reversion success of 19.4%. This discrepancy may be due to methodological differences between studies, the effect of induced SVT versus spontaneous episodic SVT, and participant factors such as medications and comorbidities. We were unable to assess any of these factors further, nor adverse effects, since they were either not described in enough detail or not reported at all.Statistical pooling was not possible due to heterogeneity between the included studies. We did not find sufficient evidence to support or refute the effectiveness of the Valsalva Manoeuvre for termination of SVT. Further research is needed and this should include a standardised approach to performance technique and methodology.


Gill S.D.,Barwon Health | McBurney H.,Monash University
Archives of Physical Medicine and Rehabilitation | Year: 2013

Objective: To investigate the preoperative effects of exercise-based interventions on pain and physical function for people awaiting joint replacement surgery of the hip or knee. Data Sources: Four computer databases (CINAHL, MEDLINE, Embase, and Cochrane Library) were searched until July 4, 2012. Search terms included knee, hip, joint replacement, arthroplasty, physiotherapy, physical therapy, exercise, hydrotherapy, rehabilitation, and preoperative. Reference lists of retrieved articles were also screened. Study Selection: Randomized or quasi-randomized studies comparing an exercise-based intervention with a no-intervention group for people awaiting hip or knee joint replacement surgery were included. Outcomes were pain and physical function including self-reported function, walking speed, and muscle strength. One of 2 reviewers determined that 18 studies met the inclusion criteria. Data Extraction: The methodologic quality of each study was independently assessed by 2 reviewers using the PEDro scale, and a final PEDro score was determined by discussion and consensus between the reviewers. Participants' characteristics, content and design of the interventions, and data for quantitative synthesis were extracted by 1 reviewer. Data Synthesis: For participants awaiting knee replacement surgery, quantitative data synthesis found no significant differences between the exercise and no-intervention groups for pain, self-reported function, walking speed, or muscle strength. For participants awaiting hip replacement surgery, quantitative data synthesis found a significant difference between the groups, with standardized mean differences (SMDs) indicating a medium-sized effect in favor of intervention for both pain (SMD=.45; 95% confidence interval.15-.75) and self-reported function (SMD=.46; 95% confidence interval.20-.72). Conclusions: Exercise-based interventions can reduce pain and improve physical function for people awaiting hip replacement surgery but not knee replacement surgery. © 2013 by the American Congress of Rehabilitation Medicine.


Wasiak J.,Monash University
The Cochrane database of systematic reviews | Year: 2013

An acute burn wound is a complex and evolving injury. Extensive burns produce systemic consequences, in addition to local tissue damage. Treatment of partial thickness burn wounds is directed towards promoting healing and a wide variety of dressings are currently available. Improvements in technology and advances in understanding of wound healing have driven the development of new dressings. Dressing selection should be based on their effects on healing, but ease of application and removal, dressing change requirements, cost and patient comfort should also be considered. To assess the effects of burn wound dressings on superficial and partial thickness burns. For this first update we searched The Cochrane Wounds Group Specialised Register (searched 8 November 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); Ovid MEDLINE (2008 to October Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, November 07, 2012); Ovid EMBASE (2008 to 2012 Week 44); AND EBSCO CINAHL (1982 to 2 November 2012). All randomised controlled trials (RCTs) that evaluated the effects of burn wound dressings on the healing of superficial and partial thickness burns. Two authors extracted the data independently using standardised forms. We assessed each trial for internal validity and resolved differences by discussion. A total of 30 RCTs are included in this review. Overall both the quality of trial reporting and trial conduct were generally poor and meta analysis was largely precluded due to study heterogeneity or poor data reporting. In the context of this poor quality evidence, silver sulphadiazine (SSD) was consistently associated with poorer healing outcomes than biosynthetic (skin substitute) dressings, silver-containing dressings and silicon-coated dressings. Burns treated with hydrogel dressings appear to heal more quickly than those treated with usual care. There is a paucity of high-quality evidence regarding the effect of different dressings on the healing of superficial and partial thickness burn injuries. The studies summarised in this review evaluated a variety of interventions, comparators and clinical endpoints and all were at risk of bias. It is impossible to draw firm and confident conclusions about the effectiveness of specific dressings, however silver sulphadiazine was consistently associated with poorer healing outcomes than biosynthetic, silicon-coated and silver dressings whilst hydrogel-treated burns had better healing outcomes than those treated with usual care.


Page M.J.,Monash University
The Cochrane database of systematic reviews | Year: 2013

Therapeutic ultrasound may be offered to people experiencing mild to moderate symptoms of carpal tunnel syndrome (CTS). The effectiveness and duration of benefit of this non-surgical intervention remain unclear. To review the effects of therapeutic ultrasound compared with no treatment, placebo or another non-surgical intervention in people with CTS. On 27 November 2012, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2012, Issue 11 in The Cochrane Library), MEDLINE (January 1966 to November 2012), EMBASE (January 1980 to November 2012), CINAHL Plus (January 1937 to November 2012), and AMED (January 1985 to November 2012). Randomised controlled trials (RCTs) comparing any regimen of therapeutic ultrasound with no treatment, a placebo or another non-surgical intervention in people with CTS. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias in the included studies. We calculated risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) for primary and secondary outcomes. We pooled results of clinically homogenous trials in a meta-analysis using a random-effects model, where possible, to provide estimates of the effect. We included 11 studies including 414 participants in the review. Two trials compared therapeutic ultrasound with placebo, two compared one ultrasound regimen with another, two compared ultrasound with another non-surgical intervention, and six compared ultrasound as part of a multi-component intervention with another non-surgical intervention (for example, exercises and splint). The risk of bias was low in some studies and unclear or high in other studies, with only two reporting that the allocation sequence was concealed and six reporting that participants were blinded. Overall, there is insufficient evidence that one therapeutic ultrasound regimen is more efficacious than another. Only two studies reported the primary outcome of interest, short-term overall improvement (any measure in which patients indicate the intensity of their complaints compared with baseline, for example, global rating of improvement, satisfaction with treatment, within three months post-treatment). One low quality trial with 68 participants found that when compared with placebo, therapeutic ultrasound may increase the chance of experiencing short-term overall improvement at the end of seven weeks treatment (RR 2.36; 95% CI 1.40 to 3.98), although losses to follow-up and failure to adjust for the correlation between wrists in participants with bilateral CTS in this study suggest that this data should be interpreted with caution. Another low quality trial with 60 participants found that at three months post-treatment therapeutic ultrasound plus splint increased the chance of short-term overall improvement (patient satisfaction) when compared with splint alone (RR 3.02; 95% CI 1.36 to 6.72), but decreased the chance of short-term overall improvement when compared with low-level laser therapy plus splint (RR 0.87; 95% CI 0.57 to 1.33), though participants were not blinded to treatment, it was unclear if the random allocation sequence was adequately concealed, and there was a potential unit of analysis error. Differences between groups receiving different frequencies and intensities of ultrasound, and between ultrasound as part of a multi-component intervention versus other non-surgical interventions, were generally small and not statistically significant for symptoms, function, and neurophysiologic parameters. No studies reported any adverse effects of therapeutic ultrasound, but this outcome was only measured in three studies. More adverse effects data are required before any firm conclusions on the safety of therapeutic ultrasound can be made. There is only poor quality evidence from very limited data to suggest that therapeutic ultrasound may be more effective than placebo for either short- or long-term symptom improvement in people with CTS. There is insufficient evidence to support the greater benefit of one type of therapeutic ultrasound regimen over another or to support the use of therapeutic ultrasound as a treatment with greater efficacy compared to other non-surgical interventions for CTS, such as splinting, exercises, and oral drugs. More methodologically rigorous studies are needed to determine the effectiveness and safety of therapeutic ultrasound for CTS.


Lancsar E.,Monash University | Swait J.,University of South Australia
PharmacoEconomics | Year: 2014

External validity is a crucial but under-researched topic when considering using discrete choice experiment (DCE) results to inform decision making in clinical, commercial or policy contexts. We present the theory and tests traditionally used to explore external validity that focus on a comparison of final outcomes and review how this traditional definition has been empirically tested in health economics and other sectors (such as transport, environment and marketing) in which DCE methods are applied. While an important component, we argue that the investigation of external validity should be much broader than a comparison of final outcomes. In doing so, we introduce a new and more comprehensive conceptualisation of external validity, closely linked to process validity, that moves us from the simple characterisation of a model as being or not being externally valid on the basis of predictive performance, to the concept that external validity should be an objective pursued from the initial conceptualisation and design of any DCE. We discuss how such a broader definition of external validity can be fruitfully used and suggest innovative ways in which it can be explored in practice. © 2014, Springer International Publishing Switzerland.


Fan S.,Monash University | Hyndman R.J.,Monash University
Energy Policy | Year: 2011

In this paper, the price elasticity of electricity demand, representing the sensitivity of customer demand to the price of electricity, has been estimated for South Australia. We first undertake a review of the scholarly literature regarding electricity price elasticity for different regions and systems. Then we perform an empirical evaluation of the historic South Australian price elasticity, focussing on the relationship between price and demand quantiles at each half-hour of the day.This work attempts to determine whether there is any variation in price sensitivity with the time of day or quantile, and to estimate the form of any relationships that might exist in South Australia. © 2011 Elsevier Ltd.


Dommenget D.,Monash University | Bayr T.,Leibniz Institute of Marine Science | Frauen C.,Monash University
Climate Dynamics | Year: 2013

In this study the observed non-linearity in the spatial pattern and time evolution of El Niño Southern Oscillation (ENSO) events is analyzed. It is shown that ENSO skewness is not only a characteristic of the amplitude of events (El Niños being stronger than La Niñas) but also of the spatial pattern and time evolution. It is demonstrated that these non-linearities can be related to the non-linear response of the zonal winds to sea surface temperature (SST) anomalies. It is shown in observations as well as in coupled model simulations that significant differences in the spatial pattern between positive (El Niño) versus negative (La Niña) and strong versus weak events exist, which is mostly describing the difference between central and east Pacific events. Central Pacific events tend to be weak El Niño or strong La Niña events. In turn east Pacific events tend to be strong El Niño or weak La Niña events. A rotation of the two leading empirical orthogonal function modes illustrates that for both El Niño and La Niña extreme events are more likely than expected from a normal distribution. The Bjerknes feedbacks and time evolution of strong ENSO events in observations as well as in coupled model simulations also show strong asymmetries, with strong El Niños being forced more strongly by zonal wind than by thermocline depth anomalies and are followed by La Niña events. In turn strong La Niña events are preceded by El Niño events and are more strongly forced by thermocline depth anomalies than by wind anomalies. Further, the zonal wind response to sea surface temperature anomalies during strong El Niño events is stronger and shifted to the east relative to strong La Niña events, supporting the eastward shifted El Niño pattern and the asymmetric time evolution. Based on the simplified hybrid coupled RECHOZ model of ENSO it can be shown that the non-linear zonal wind response to SST anomalies causes the asymmetric forcings of ENSO events. This also implies that strong El Niños are mostly wind driven and less predictable and strong La Niñas are mostly thermocline depth driven and better predictable, which is demonstrated by a set of 100 perfect model forecast ensembles. © 2012 Springer-Verlag.


Bayr T.,Leibniz Institute of Marine Science | Dommenget D.,Monash University
Journal of Climate | Year: 2013

This article addresses the causes of the large-scale tropical sea level pressure (SLP) changes during climate change. The analysis presented here is based on model simulations, observed trends, and the seasonal cycle. In all three cases the regional changes of tropospheric temperature (Ttropos) and SLP are strongly related to each other [considerably more strongly than (sea) surface temperature and SLP]. This relationship basically follows the Bjerknes circulation theorem, with relatively low regional SLP where there is relatively high Ttropos and vice versa. A simple physical model suggests a tropical SLP response to horizontally inhomogeneous warming in the tropical Ttropos, with a sensitivity coefficient of about-1.7 hPa K-1. This relationship explains a large fraction of observed and predicted changes in the tropical SLP. It is shown that in climate change model simulations the tropospheric land-sea warming contrast is the most significant structure in the regional Ttropos changes relative to the tropical mean changes. Since the land-sea warming contrast exists in the absence of any atmospheric circulation changes, it can be argued that the largescale response of tropical SLP changes is to first order a response to the tropical land-sea warming contrast. Furthermore, as the land-sea warming contrast is mostly moisture dependent, the models predict a stronger warming and decreasing SLP in the drier regions from South America to Africa and a weaker warming and increasing SLP over the wetter Indo-Pacific warm pool region. This suggests an increase in the potential for deep convection conditions over the Atlantic sector and a decrease over the Indo-Pacific warm pool region in the future. © 2013 American Meteorological Society.


Monaghan J.J.,Monash University
Annual Review of Fluid Mechanics | Year: 2011

This review focuses on the applications of smoothed particle hydrodynamics (SPH) to incompressible or nearly incompressible flow. In the past 17 years, the range of applications has increased as researchers have realized the ability of SPH algorithms to handle complex physical problems. These include the disruption of free surfaces when a wave hits a rocky beach, multifluid problems that may involve the motion of rigid and elastic bodies, non-Newtonian fluids, virtual surgery, and chemical precipitation from fluids moving through fractured media. SPH provides a fascinating tool that has some of the properties of molecular dynamics while retaining the attributes of the macroscopic equations of continuum mechanics.


Kaiserman D.,Monash University | Bird P.I.,Monash University
Cell Death and Differentiation | Year: 2010

Although proteolysis mediated by granzymes has an important role in the immune response to infection or tumours, unrestrained granzyme activity may damage normal cells. In this review, we discuss the role of serpins within the immune system, as specific regulators of granzymes. The well-characterised human granzyme B-SERPINB9 interaction highlights the cytoprotective function that serpins have in safeguarding lymphocytes from granzymes that may leak from granules. We also discuss some of the pitfalls inherent in using rodent models of granzyme-serpin interactions and the ways in which our understanding of serpins can help resolve some of the current, contentious issues in granzyme biology. © 2010 Macmillan Publishers Limited All rights reserved.


Drummond G.R.,Monash University | Sobey C.G.,Monash University
Trends in Endocrinology and Metabolism | Year: 2014

NADPH oxidases (NOXs) are reactive oxygen species (ROS)-generating enzymes implicated in the pathophysiology of vascular diseases such as hypertension and stroke. Endothelial cells express four NOX isoforms including the superoxide-generating enzymes NOX1, NOX2, and NOX5 and the hydrogen peroxide-generating enzyme NOX4. Studies on arteries from patients with coronary artery disease, and in animals with experimentally induced hypertension, diabetes, or atherosclerosis, suggest that NOX1, NOX2, and NOX5 promote endothelial dysfunction, inflammation, and apoptosis in the vessel wall, whereas NOX4 is by contrast vasoprotective in increasing nitric oxide bioavailability and suppressing cell death pathways. Based on these findings and promising preclinical studies with the NOX1/NOX2 antagonist, apocynin, we suggest that the field is poised for clinical evaluation of NOX inhibitors as therapeutics for cardiovascular disease. © 2014 Elsevier Ltd.


Iturbe-Ormaetxe I.,University of Queensland | Walker T.,University of Queensland | O'Neill S.L.,Monash University
EMBO Reports | Year: 2011

Mosquito-borne diseases such as malaria, dengue fever and filariasis cause an enormous health burden to people living in tropical and subtropical regions of the world. Despite years of intense effort to control them, many of these diseases are increasing in prevalence, geographical distribution and severity, and options to control them are limited. The transinfection of mosquitos with the maternally inherited, endosymbiotic bacteria Wolbachia is a promising new biocontrol approach. Fruit fly Wolbachia strains can invade and sustain themselves in mosquito populations, reduce adult lifespan, affect mosquito reproduction and interfere with pathogen replication. Wolbachia-infected Aedes aegypti mosquitoes have been released in areas of Australia in which outbreaks of dengue fever occur, as a prelude to the application of this technology in dengue-endemic areas of south-east Asia. © 2011 European Molecular Biology Organization.


Kemp-Harper B.K.,Monash University
Antioxidants and Redox Signaling | Year: 2011

Nitroxyl (HNO), the one electron reduced and protonated congener of nitric oxide, is emerging as a novel nitrogen oxide with distinct chemistry and biological actions as compared with its redox sibling. The thiophilic nature of HNO underlies many of its unique properties, and attention has been focused on its regulation of cellular function and therapeutic potential, particularly in the treatment of cardiovascular disease. The present Forum issue summarizes the intriguing chemistry and biology of HNO and highlights its impact in the cardiovascular and central nervous systems. Recent advances in the development of new HNO donors and their potential use as tools to study HNO signaling and therapeutic agents are discussed. Evidence is also provided for a role of HNO as a putative, endogenous regulator of vascular function. However, as highlighted in this Forum issue, the development of sensitive methods for HNO detection in a biological system is needed to conclusively prove its in vivo generation. As research expands in this area, it is likely that new targets and pharmacological applications of HNO will be discovered. © 2011 Mary Ann Liebert, Inc.


Davis S.R.,Monash University | Panjari M.,Monash University | Stanczyk F.Z.,University of Southern California
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: It has been proposed that because dehydroepiandrosterone (DHEA) and its sulfate, DHEAS, are important precursors for estrogen and androgen production, treatment with DHEA is a physiologically based strategy for the alleviation of hormone deficiency symptoms in postmenopausal women.Wehave summarized the physiology of DHEA in women and reviewed the findings from randomized controlled trials (RCT) of the effects of DHEA therapy in postmenopausal women with normal adrenal function. Evidence Acquisition: We reviewed the medical literature for key papers investigating DHEA physiology and RCT of the use of DHEA in postmenopausal women through November 2010. The focus was on sexual function, well-being, metabolic parameters, and cognition as study endpoints. Evidence Synthesis: Although cross-sectional studies have indicated a link between low DHEA levels and impaired sexual function, well-being, and cognitive performance in postmenopausal women, placebo-controlled RCT do not show benefits of oral DHEA for any of these outcomes or favorable effects on lipids and carbohydrate metabolism. Conclusions: Taken together, findings from this review of the published literature of studies do not support the use of DHEA in postmenopausal women at this time. Copyright © 2011 by The Endocrine Society.


Dowling D.K.,Monash University
Biochimica et Biophysica Acta - General Subjects | Year: 2014

Background Disorders of the mitochondrial respiratory chain are heterogeneous in their symptoms and underlying genetics. Simple links between candidate mutations and expression of disease phenotype typically do not exist. It thus remains unclear how the genetic variation in the mitochondrial genome contributes to the phenotypic expression of complex traits and disease phenotypes. Scope of review I summarize the basic genetic processes known to underpin mitochondrial disease. I highlight other plausible processes, drawn from the evolutionary biological literature, whose contribution to mitochondrial disease expression remains largely empirically unexplored. I highlight recent advances to the field, and discuss common-ground and -goals shared by researchers across medical and evolutionary domains. Major conclusions Mitochondrial genetic variance is linked to phenotypic variance across a variety of traits (e.g. reproductive function, life expectancy) fundamental to the upkeep of good health. Evolutionary theory predicts that mitochondrial genomes are destined to accumulate male-harming (but female-friendly) mutations, and this prediction has received proof-of-principle support. Furthermore, mitochondrial effects on the phenotype are typically manifested via interactions between mitochondrial and nuclear genes. Thus, whether a mitochondrial mutation is pathogenic in effect can depend on the nuclear genotype in which is it expressed. General significance Many disease phenotypes associated with OXPHOS malfunction might be determined by the outcomes of mitochondrial-nuclear interactions, and by the evolutionary forces that historically shaped mitochondrial DNA (mtDNA) sequences. Concepts and results drawn from the evolutionary sciences can have broad, but currently under-utilized, applicability to the medical sciences and provide new insights into understanding the complex genetics of mitochondrial disease. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. © 2013 Elsevier B.V. All rights reserved.


Brewin L.,Monash University
Classical and Quantum Gravity | Year: 2011

Any practical attempt to solve the Regge equations, these being a large system of non-linear algebraic equations, will almost certainly employ a Newton-Raphson-like scheme. In such cases, it is essential that efficient algorithms be used when computing the defect angles and their derivatives with respect to the leg lengths. The purpose of this paper is to present details of such an algorithm. © 2011 IOP Publishing Ltd.


Andrews Z.B.,Monash University
Peptides | Year: 2011

Ghrelin is a stomach hormone, secreted into the bloodstream, that initiates food intake by activating NPY/AgRP neurons in the hypothalamic acruate nucleus. This review focuses on recent evidence that details the mechanisms through which ghrelin activate receptors on NPY neurons and downstream signaling within NPY neurons. The downstream signaling involves a novel CaMKK-AMPK-CPT1-UCP2 pathway that enhances mitochondrial efficiency and buffers reactive oxygen species in order to maintain an appropriate firing response in NPY. Recent evidence that shows metabolic status affects ghrelin signaling in NPY is also described. In particular, ghrelin does not activate NPY neurons in diet-induced obese mice and ghrelin does not increase food intake. The potential mechanisms and implications of ghrelin resistance are discussed. © 2011 Elsevier Inc. All rights reserved.


Jackson S.P.,Monash University | Jackson S.P.,Scripps Research Institute
Nature Medicine | Year: 2011

The formation of blood clots-thrombosis-at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has led to the development of newer therapeutics, and there is general anticipation that these treatments will have greater efficacy and improved safety. However, major advances in this field require the identification of specific risk factors for arterial thrombosis in affected individuals and a rethink of the 'one size fits all' approach to antithrombotic therapy. © 2011 Nature America, Inc. All rights reserved.


Fulcher A.J.,Monash University | Jans D.A.,Monash University
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2011

Signal-dependent targeting of proteins into and out of the nucleus is mediated by members of the importin (IMP) family of transport receptors, which recognise targeting signals within a cargo protein and mediate passage through the nuclear envelope-embedded nuclear pore complexes. Regulation of this process is paramount to processes such as cell division and differentiation, but is also critically important for viral replication and pathogenesis; phosphorylation appears to play a major role in regulating viral protein nucleocytoplasmic trafficking, along with other posttranslational modifications. This review focuses on viral proteins that utilise the host cell IMP machinery in order to traffic into/out of the nucleus, and in particular those where trafficking is critical to viral replication and/or pathogenesis, such as simian virus SV40 large tumour antigen (T-ag), human papilloma virus E1 protein, human cytomegalovirus processivity factor ppUL44, and various gene products from RNA viruses such as Rabies. Understanding of the mechanisms regulating viral protein nucleocytoplasmic trafficking is paramount to the future development of urgently needed specific and effective anti-viral therapeutics. This article was originally intended for the special issue "Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import". The Publisher apologizes for any inconvenience caused. © 2011 Elsevier B.V.


Mansfield J.H.,Barnard College | McGlinn E.,Monash University
Current Topics in Developmental Biology | Year: 2012

Exquisite regulation of Hox protein activity is fundamental to the regionalization of the early embryo across diverse taxa. Highlighting the critical importance of these transcription factors, an astonishing number of different mechanisms have evolved to tightly coordinate their activity both in time and in space. The recent identification of numerous microRNAs that are not only embedded within Hox clusters but also target numerous Hox genes suggests an important role for these regulatory molecules in shaping Hox protein output. Here, we discuss the positioning of these miRNAs within clusters over evolutionary time, the unexpected complexity in miRNA processing and target interactions, and the current understanding of Hox-embedded miRNA function during development. © 2012 Elsevier Inc.


Gleadow R.M.,Monash University | Moller B.L.,Copenhagen University | Moller B.L.,Carlsberg Laboratory
Annual Review of Plant Biology | Year: 2014

Cyanogenic glycosides (CNglcs) are bioactive plant products derived from amino acids. Structurally, these specialized plant compounds are characterized as α-hydroxynitriles (cyanohydrins) that are stabilized by glucosylation. In recent years, improved tools within analytical chemistry have greatly increased the number of known CNglcs by enabling the discovery of less abundant CNglcs formed by additional hydroxylation, glycosylation, and acylation reactions. Cyanogenesis - the release of toxic hydrogen cyanide from endogenous CNglcs - is an effective defense against generalist herbivores but less effective against fungal pathogens. In the course of evolution, CNglcs have acquired additional roles to improve plant plasticity, i.e., establishment, robustness, and viability in response to environmental challenges. CNglc concentration is usually higher in young plants, when nitrogen is in ready supply, or when growth is constrained by nonoptimal growth conditions. Efforts are under way to engineer CNglcs into some crops as a pest control measure, whereas in other crops efforts are directed toward their removal to improve food safety. Given that many food crops are cyanogenic, it is important to understand the molecular mechanisms regulating cyanogenesis so that the impact of future environmental challenges can be anticipated. Copyright © 2014 by Annual Reviews.


Bach L.A.,Monash University | Bach L.A.,Alfred Hospital
Journal of Molecular Endocrinology | Year: 2015

Endothelial cells line blood vessels and modulate vascular tone, thrombosis, inflammatory responses and new vessel formation. They are implicated in many disease processes including atherosclerosis and cancer. IGFs play a significant role in the physiology of endothelial cells by promoting migration, tube formation and production of the vasodilator nitric oxide. These actions are mediated by the IGF1 and IGF2/mannose 6-phosphate receptors and are modulated by a family of high-affinity IGF binding proteins. IGFs also increase the number and function of endothelial progenitor cells, which may contribute to protection from atherosclerosis. IGFs promote angiogenesis, and dysregulation of the IGF system may contribute to this process in cancer and eye diseases including retinopathy of prematurity and diabetic retinopathy. In some situations, IGF deficiency appears to contribute to endothelial dysfunction, whereas IGF may be deleterious in others. These differences may be due to tissue-specific endothelial cell phenotypes or IGFs having distinct roles in different phases of vascular disease. Further studies are therefore required to delineate the therapeutic potential of IGF system modulation in pathogenic processes. © 2015 Society for Endocrinology.


Lawen A.,Monash University
Biochimica et Biophysica Acta - General Subjects | Year: 2015

Background Peptidyl-prolyl-cis/trans-isomerases (PPIases) are ubiquitously expressed and have been implicated in a wide range of biological functions. Their inhibition is beneficial in immunosuppression, cancer treatment, treatment of autoimmune diseases, protozoan and viral infections. Scope of review Three classes of PPIases are known, each class having their own specific inhibitors. This review will cover the present knowledge on the biosynthesis of the natural PPIase inhibitors. These include for the cyclophilins: the cyclosporins, the analogues of peptolide SDZ 214-103 and the sanglifehrins; for the FKBPs: ascomycin, rapamycin and FK506 and for the parvulins the naphtoquinone juglone. Major conclusions Over the last thirty years much progress has been made in understanding PPIase function and the biosynthesis of natural PPIase inhibitors. Non-immunosuppressive analogues were discovered and served as lead compounds for the development of novel antiviral drugs. There are, however, still unsolved questions which deserve further research into this exciting field. General significance As all the major natural inhibitors of the cyclophilins and FKBPs are synthesized by complex non-ribosomal peptide synthetases and/or polyketide synthases, total chemical synthesis is not a viable option. Thus, fully understanding the modular enzyme systems involved in their biosynthesis may help engineering enzymes capable of synthesizing novel PPIase inhibitors with improved functions for a wide range of conditions. This article is part of a Special Issue entitled Proline-directed Foldases: Cell signaling catalysts and drug targets. © 2014 Elsevier B.V. All rights reserved.


International collaborative health research is justifiably expected to help reduce global health inequities. Investment in health policy and systems research in developing countries is essential to this process but, currently, funding for international research is mainly channelled towards the development of new medical interventions. This imbalance is largely due to research legislation and policies used in high-income countries. These policies have increasingly led these countries to invest in health research aimed at boosting national economic competitiveness rather than reducing health inequities. In the United States of America and the United Kingdom of Great Britain and Northern Ireland, the regulation of research has encouraged a model that: leads to products that can be commercialized; targets health needs that can be met by profitable, high-technology products; has the licensing of new products as its endpoint; and does not entail significant research capacity strengthening in other countries. Accordingly, investment in international research is directed towards pharmaceutical trials and product development public-private partnerships for neglected diseases. This diverts funding away from research that is needed to implement existing interventions and to strengthen health systems, i.e. health policy and systems research. Governments must restructure their research laws and policies to increase this essential research in developing countries.


Hadlington T.J.,Monash University | Hermann M.,University of Marburg | Frenking G.,University of Marburg | Jones C.,Monash University
Journal of the American Chemical Society | Year: 2014

This study details the first use of well-defined low-valent p-block metal hydrides as catalysts in organic synthesis. That is, the bulky, two-coordinate germanium(II) and tin(II) hydride complexes, L†(H)M: (M = Ge or Sn, L† = -N(Ar†)(SiPri 3), Ar† = C6H2{C(H)Ph 2}2Pri-2,6,4), are shown to act as efficient catalysts for the hydroboration (with HBpin, pin = pinacolato) of a variety of unactivated, and sometimes very bulky, carbonyl compounds. Catalyst loadings as low as 0.05 mol % are required to achieve quantitative conversions, with turnover frequencies in excess of 13 300 h-1 in some cases. This activity rivals that of currently available catalysts used for such reactions. © 2014 American Chemical Society.


Liberman J.,Monash University
Journal of Law, Medicine and Ethics | Year: 2012

This article examines two spheres of global governance in which the World Health Organization (WHO) has sought to exercise international leadership - combating "counterfeit" medicines and illicit trade in tobacco products. Medicines and tobacco products lie at polar opposite ends of the health spectrum, and are regulated for vastly different reasons and through different tools and approaches. Nevertheless, attempts to govern counterfeit trade in each of these products raise a host of somewhat similar challenges, involving normative and operational conflicts that cut across the crowded intersection of health protection and promotion, intellectual property protection, and activity to combat transnational organized crime. As negotiations of an illicit trade protocol to the WHO Framework Convention on Tobacco Control enter their final stages, lessons learned from counterfeit medicines governance need to be applied to ensure that the most appropriate governance arrangements are adopted. © 2012 American Society of Law, Medicine & Ethics, Inc.


Background: Placement programmes are essential to medical education but almost invariably take place in clinical settings, even when community based. Australia's Monash University, however, has included in its core MBBS curriculum a non-clinical placement for second-year students, the Community Based Practice (CBP) programme. This involves partnerships with community organisations that are mostly non-medical. The programme includes a health promotion (HP) component where students respond to a HP or support need nominated by their placement organisation. Though inspired by community-based medical education (CBME) programmes in England and South Australia's Flinders University, its non-clinical focus represents a creative development in Australian medical education. Methods: This article describes the programme, explores its place within CBME and outlines the results of its analysis of student responses using SPSS and NVivo. Results: The evidence showed development of students' communication skills; increased understanding and appreciation of the mainly non-medical health support infrastructure in local communities; increased understanding of HP and community health support at the local level; and contributions to the placement organisations through small-scale research or health support projects. Conclusion: Placement programmes such as this can significantly contribute to medical education, especially in supporting health in local communities and understanding the needs of the marginalised. © 2012 Informa UK Ltd.


Elefanty A.G.,Monash University | Stanley E.G.,Monash University
Nature Cell Biology | Year: 2012

A protocol for efficient differentiation of human pluripotent stem cells into white and brown adipocytes now enables their detailed examination at a cellular and molecular level, facilitating the study of adipocyte dysfunction in a range of metabolic diseases including diabetes, heart disease and obesity. © 2012 Macmillan Publishers Limited. All rights reserved.


Janes P.W.,Monash University | Nievergall E.,Monash University | Lackmann M.,Monash University
Seminars in Cell and Developmental Biology | Year: 2012

Polymeric receptor-ligand complexes between interacting Eph and ephrin-expressing cells are regarded as dynamic intercellular signalling scaffolds that control cell-to-cell contact: the resulting Eph-ephrin signalling clusters function as positional cues that facilitate cell navigation and tissue patterning during normal and oncogenic development. The considerable complexity of this task, coordinating a multitude of cell movements and cellular interactions, is achieved by accurate translation of spatial information from Eph and ephrin expression gradients into fine-tuned changes in cell-cell adhesion and position. Here we review emerging evidence suggesting that the required combinatorial diversity is not only achieved by the large number of possible Eph-ephrin interactions and selective use of Eph forward and ephrin reverse signals, but in particular through the composition and signal capacity of Eph-ephrin clusters, which is adjusted dynamically to reflect overall Eph and ephrin surface densities on interacting cells. Fine-tuning is provided through multi-layered cluster assembly, where homo- and heterotypic Eph and ephrin interactions define the composition - whilst intracellular signalling feedbacks determine the size and lifetime - of signalling clusters. © 2012 Elsevier Ltd.


Lazarou M.,Monash University
Immunology and Cell Biology | Year: 2015

Mitochondria play a central role in many facets of cellular function including energy production, control of cell death and immune signaling. Breakdown of any of these pathways because of mitochondrial deficits or excessive reactive oxygen species production has detrimental consequences for immune system function and cell viability. Maintaining the functional integrity of mitochondria is therefore a critical challenge for the cell. Surveillance systems that monitor mitochondrial status enable the cell to identify and either repair or eliminate dysfunctional mitochondria. Mitophagy is a selective form of autophagy that eliminates dysfunctional mitochondria from the population to maintain overall mitochondrial health. This review covers the major players involved in mitophagy and explores the role mitophagy plays to support the immune system. © 2015 Australasian Society for Immunology Inc.


Yang J.,Monash University | Fuller P.J.,Monash University
Molecular and Cellular Endocrinology | Year: 2012

The mineralocortoid receptor (MR) regulates salt homeostasis in the kidneys and plays a range of other roles in the heart, vasculature, brain and adipose tissue. It interacts with both mineralocorticoids and glucocorticoids to mediate transcription of target genes. The ability of the MR to exert tissue- and ligand-specific effects relies on its interactions with a range of binding partners, including the chaperone proteins, coregulators, other transcription factors, DNA and modifying proteins. Interactions within the domains of the MR also modulate the overall transcriptional complex. This review will discuss the current understanding of interactions involving the MR and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic targets. © 2011 Elsevier Ireland Ltd.


Webster D.E.,Monash University | Thomas M.C.,Baker IDI Heart and Diabetes Institute
Biotechnology Advances | Year: 2012

The complex and diverse nature of the post-translational modification (PTM) of proteins represents an efficient and cost-effective mechanism for the exponential diversification of the genome. PTMs have been shown to affect almost every aspect of protein activity, including function, localisation, stability, and dynamic interactions with other molecules. Although many PTMs are evolutionarily conserved there are also important kingdom-specific modifications which should be considered when expressing recombinant proteins. Plants are gaining increasing acceptance as an expression system for recombinant proteins, particularly where eukaryotic-like PTMs are required. Glycosylation is the most extensively studied PTM of plant-made recombinant proteins. However, other types of protein processing and modification also occur which are important for the production of high quality recombinant protein, such as hydroxylation and lipidation. Plant and/or protein engineering approaches offer many opportunities to exploit PTM pathways allowing the molecular farmer to produce a humanised product with modifications functionally similar or identical to the native protein. Indeed, plants have demonstrated a high degree of tolerance to changes in PTM pathways allowing recombinant proteins to be modified in a specific and controlled manner, frequently resulting in a homogeneity of product which is currently unrivalled by alternative expression platforms. Whether a recombinant protein is intended for use as a scientific reagent, a cosmetic additive or as a pharmaceutical, PTMs through their presence and complexity, offer an extensive range of options for the rational design of humanised (biosimilar), enhanced (biobetter) or novel products. © 2011 Elsevier Inc.


Jamieson S.,Monash University | Fuller P.J.,Monash University
Endocrine Reviews | Year: 2012

Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long delays to tumor recurrence are characteristic of this disease. Unlike the more intensely investigated epithelial ovarian tumors, relatively little is known about the molecular and genetic changes that give rise to GCT. To date, many investigations have centered around pathways known to be involved in normal granulosa cell proliferation, including those activated by FSH receptor stimulation. Most recently, the finding that approximately 97% of adult GCT harbor a somatic missense mutation in the FOXL2 gene (c.402C→G; p.C134W) represents an exciting advancement in the field of GCT research. The high frequency with which the mutation occurs in adult GCT, along with its absence from juvenile GCT and other human malignancies is suggestive of an oncogenic or gain-of-function mutation and, indeed, that the mutation is pathognomonic for adult GCT. In this review, we explore the implications of this finding and the most recent work characterizing molecular pathways of potential pathogenetic significance in GCT. © 2012 by The Endocrine Society.


Majumder M.,Monash University | Corry B.,University of Western Australia
Chemical Communications | Year: 2011

Carbon nanotube membranes have been shown to rapidly transport liquids; but progressive hydrophilic modification - contrary to expectations - induces a drastic reduction of water flow. Enhanced electrostatic interaction and the disruption of the mechanically smooth graphitic walls is the determinant of this behavior. These results have critical implications in the design of nanofluidic devices. © 2011 The Royal Society of Chemistry.


Candish L.,Monash University | Levens A.,Monash University | Lupton D.W.,Monash University
Journal of the American Chemical Society | Year: 2014

The enantioselective vinylogous Michael/aldol cascade is an underdeveloped approach to cyclohexenes. Herein we describe a highly enantioselective (most ≥98:2 er) and diastereoselective (all ≥15:1 dr) N-heterocyclic carbene catalyzed cycloisomerization of acyclic dienyl esters to cyclohexyl β-lactones. Derivatizations avail cyclohexenes bearing four contiguous stereogenic centers, while mechanistic studies support olefin isomerization prior to cyclization. © 2014 American Chemical Society.


Mardling R.A.,Monash University | Mardling R.A.,University of Geneva
Monthly Notices of the Royal Astronomical Society | Year: 2013

Modern applications of celestial mechanics include the study of closely packed systems of exoplanets, circumbinary planetary systems, binary-binary interactions in star clusters and the dynamics of stars near the Galactic centre. While developments have historically been guided by the architecture of the Solar System, the need for more general formulations with as few restrictions on the parameters as possible is obvious. Here, we present clear and concise generalizations of two classic expansions of the three-body disturbing function, simplifying considerably their original form and making them accessible to the non-specialist. Governing the interaction between the inner and outer orbits of a hierarchical triple, the disturbing function in its general form is the conduit for energy and angular momentum exchange and as such, governs the secular and resonant evolution of the system and its stability characteristics. Focusing here on coplanar systems, the first expansion is one in the ratio of inner to outer semimajor axes and is valid for all eccentricities, while the second is an expansion in eccentricity and is valid for all semimajor axis ratios, except for systems in which the orbits cross (this restriction also applies to the first expansion). Our generalizations make both formulations valid for arbitrary mass ratios. The classic versions of these appropriate to the restricted three-body problem are known as Kaula's expansion and the literal expansion, respectively. We demonstrate the equivalence of the new expansions, identifying the role of the spherical harmonic order m in both and its physical significance in the three-body problem, and introducing the concept of principal resonances. Several examples of the accessibility of both expansions are given including resonance widths, and the secular rates of change of the elements. Results in their final form are gathered together at the end of the paper for the reader mainly interested in their application, including a guide for the choice of expansion. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Lewis K.M.,Monash University
Monthly Notices of the Royal Astronomical Society | Year: 2013

The timing errors for individual planetary transits using the photometric transit timing technique (TTVp) are derived for light curves contaminated with either white additive noise, realistic stellar noise or filtered stellar noise. For the case of white noise, the timing errors are derived analytically, while timing errors for realistic and filtered noise are numerically derived using solar data from the Solar and Heliospheric Observatory satellite. These results are then used to explore the conjecture that moons of transiting planets become easier to detect using the TTVp method the farther their planet is from the star. Using transit duration as a proxy for planet-star distance, it is found that in the case of realistic stellar noise, an increase in star-planet distance/transit duration does not necessarily lead to an increase in moon detectability. © 2013 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.


Mason R.R.,Monash University | Watt M.J.,Monash University
Trends in Endocrinology and Metabolism | Year: 2015

The discovery of perilipin (PLIN) 1 provided a major conceptual shift in the understanding of adipose tissue lipolysis and generated intense interest in lipid droplet biology research. The subsequent discovery of other PLIN proteins revealed unique tissue distribution profiles, subcellular locations, and lipid-binding properties and divergent cellular functions. PLIN5 is highly expressed in oxidative tissues such as skeletal muscle, liver, and heart and is central to lipid homeostasis in these tissues. Studies in cell systems have ascribed several metabolic roles to PLIN5 and demonstrated interactions with other proteins that are requisite for these functions. We examine recent in vivo studies and ask whether the evidence from the cell biology approaches is consistent with the physiological roles of PLIN5. © 2015 Elsevier Ltd.


Lyn Chan F.,Monash University | Wong L.H.,Monash University
Nucleic Acids Research | Year: 2012

Recent evidence has shown that transcription is permissible through the purportedly repressive centromere domain, and that this transcriptional activity is of functional consequence. The best-studied example is transcription of the pericentric DNA repeats in the generation of siRNAs required for pericentric heterochromatin assembly in yeast. However, non-siRNA transcripts emanating from both pericentric and centromere core domains have also been detected in a cell cycle and cellular differentiation-dependent manner. Elevated levels of centromeric transcripts have also been detected in some cancers; however, it is still unclear how high levels of centromere transcripts may contribute towards disease progression. More recent studies have demonstrated that careful regulation of the histone modifications and transcription level at the centromere is vital for the recruitment of key centromere proteins and assembly of CENP-A domain. Here, we compare the transcriptional dynamics and function of various transcripts derived from pericentromeric and centromere core regions. We also propose a model in which the chromatin remodelling activity of transcription, and the resultant transcripts, contribute synergistically to perpetuate centromere chromatin identity. © 2012 The Author(s).


Replacement therapy with immunoglobulin G (IgG) given as intravenous or subcutaneous (SC) infusions is the standard treatment for patients with primary immunodeficiency. Due to the life-long need for replacement, increased flexibility in the administration and dosage regimens would improve patients' quality of life. A population pharmacokinetic model that can predict plasma IgG concentrations for various routes, dosage regimens, and patient groups is a valuable tool to improve patient therapy. Such a model was developed based on IgG concentrations from 151 unique adult and pediatric patients who participated in 4 clinical trials of intravenous and SC IgG replacement therapy. Simulations predicted that the same total IgG dose, delivered SC, either in 1 biweekly dose (once every 2 weeks), or in 2 weekly doses, results in IgG peak and trough concentrations that remain within ± 10% of each other throughout the 14-day period. The developed population pharmacokinetic model predicted that biweekly SC Hizentra dosing offers a viable alternative to weekly SC therapy, allowing more flexible and optimized dosage regimens for patients with primary immunodeficiency.


Robert R.,Monash University | Wark K.L.,Victorian Cancer Agency
Archives of Biochemistry and Biophysics | Year: 2012

The accumulation of amyloid-β-peptide (Aβ or A-beta) in the brain is considered to be a key event in the pathogenesis of Alzheimer's disease (AD). Over the last decade, antibody strategies aimed at reducing high levels of Aβ in the brain and or neutralizing its toxic effects have emerged as one of the most promising treatments for AD. Early approaches using conventional antibody formats demonstrated the potential of immunotherapy, but also caused a range of undesirable side effects such meningoencephalitis, vasogenic edema or cerebral microhemorrhages in both murine and humans. This prompted the exploration of alternative approaches using engineered antibodies to avoid adverse immunological responses and provide a safer and more effective therapy. Encouraging results have been obtained using a range of recombinant antibody formats including, single chain antibodies, antibody domains, intrabodies, bispecific antibodies as well as Fc-engineered antibodies in transgenic AD mouse and primate models. This review will address recent progress using these recombinant antibodies against Aβ, highlighting their advantages over conventional monoclonal antibodies and delivery methods. © 2011 Elsevier Inc. All rights reserved.


Federrath C.,Monash University
Monthly Notices of the Royal Astronomical Society | Year: 2013

Compressible turbulence shapes the structure of the interstellar medium of our Galaxy and likely plays an important role also during structure formation in the early Universe. The density probability distribution function (PDF) and the power spectrum of such compressible, supersonic turbulence are the key ingredients for theories of star formation. However, both the PDF and the spectrum are still a matter of debate, because theoretical predictions are limited and simulations of supersonic turbulence require enormous resolutions to capture the inertial-range scaling. To advance our limited knowledge of compressible turbulence, we here present and analyse the world's largest simulations of supersonic turbulence. We compare hydrodynamic models with numerical resolutions of 2563-40963 mesh points and with two distinct driving mechanisms, solenoidal (divergence-free) driving and compressive (curl-free) driving. We find convergence of the density PDF, with compressive driving exhibiting a much wider and more intermittent density distribution than solenoidal driving by fitting to a recent theoretical model for intermittent density PDFs. Analysing the power spectrum of the turbulence, we find a pure velocity scaling close to Burgers turbulence with P(v) α k-2 for both driving modes in our hydrodynamical simulations with Mach number M = 17. The spectrum of the density-weighted velocity p1/3 v, however, does not provide the previously suggested universal scaling for supersonic turbulence. We find that the power spectrum P(p1/3 v) scales with wavenumber as k-1.74 for solenoidal driving, close to incompressible Kolmogorov turbulence (k-5/3), but is significantly steeper with k-210 for compressive driving. We show that this is consistent with a recent theoretical model for compressible turbulence that predicts P(p1/3 v) α k-19/9 in the presence of a strong ∇. v component as is produced by compressive driving and remains remarkably constant throughout the supersonic turbulent cascade. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Kuruppu S.,Monash University | Smith A.I.,Monash University
FEBS Letters | Year: 2012

Endothelin Converting Enzyme-1 (ECE-1) plays a significant role in the regulation of vascular tone and hence blood pressure. It has also been implicated in the pathogenesis of cardiovascular diseases, female malignancies and Alzheimer's disease. Four different isoforms of ECE-1 exist and have varying degrees of distribution throughout the cell. Production of ET-1 by ECE-1 occurs at the cell surface and the expression and localisation of ECE-1 is the rate limiting step in the production of ET-1. This review looks at the current knowledge on ECE-1 phosphorylation and other stimuli which act induce trafficking of ECE-1 to the cell surface. Crown Copyright © 2012 Published by Elsevier B.V. on behalf of Federation of European Biochemical society. All rights reserved.


Watt M.J.,Monash University | Hoy A.J.,Monash University
American Journal of Physiology - Endocrinology and Metabolism | Year: 2012

Fatty acids derived from adipose tissue lipolysis, intramyocellular triacylglycerol lipolysis, or de novo lipogenesis serve a variety of functions in skeletal muscle. The two major fates of fatty acids are mitochondrial oxidation to provide energy for the myocyte and storage within a variety of lipids, where they are stored primarily in discrete lipid droplets or serve as important structural components of membranes. In this review, we provide a brief overview of skeletal muscle fatty acid metabolism and highlight recent notable advances in the field. We then 1) discuss how lipids are stored in and mobilized from various subcellular locations to provide adaptive or maladaptive signals in the myocyte and 2) outline how lipid metabolites or metabolic byproducts derived from the actions of triacylglycerol metabolism or β-oxidation act as positive and negative regulators of insulin action. We have placed an emphasis on recent developments in the lipid biology field with respect to understanding skeletal muscle physiology and discuss unanswered questions and technical limitations for assessing lipid signaling in skeletal muscle. © 2012 the American Physiological Society.


Dunstone M.A.,Monash University | Tweten R.K.,The University of Oklahoma Health Sciences Center
Current Opinion in Structural Biology | Year: 2012

The bacterial cholesterol dependent cytolysins (CDCs) and membrane attack complex/perforin-like proteins (MACPF) represent two major branches of a large, exceptionally diverged superfamily. Most characterized CDC/MACPF proteins form large pores that function in immunity, venoms, and pathogenesis. Extensive structural, biochemical and biophysical studies have started to address some of the questions surrounding how the soluble, monomeric form of these remarkable molecules recognize diverse targets and assemble into oligomeric membrane embedded pores. This review explores mechanistic similarities and differences in how CDCs and MACPF proteins form pores. © 2012 Elsevier Ltd.


St. John J.C.,Monash University
Seminars in Cell and Developmental Biology | Year: 2016

Until recently, it was thought that the role of the mitochondrial genome was confined to encoding key proteins that generate ATP through the process of oxidative phosphorylation in the electron transfer chain. However, with increasing new evidence, it is apparent that the mitochondrial genome has a major role to play in a number of diseases and phenotypes. For example, mitochondrial variants and copy number have been implicated in the processes of fertilisation outcome and development and the onset of tumorigenesis. On the other hand, mitochondrial DNA (mtDNA) haplotypes have been implicated in a variety of diseases and most likely account for the adaptation that our ancestors achieved in order that they were fit for their environments. The mechanisms, which enable the mitochondrial genome to either protect or promote the disease phenotype, require further elucidation. However, there appears to be significant 'crosstalk' between the chromosomal and mitochondrial genomes that enable this to take place. One such mechanism is the regulation of DNA methylation by mitochondrial DNA, which is often perturbed in reprogrammed cells that have undergone dedifferentiation and affects mitochondrial DNA copy number. Furthermore, it appears that the mitochondrial genome interacts with the chromosomal genome to regulate the transcription of key genes at certain stages during development. Additionally, the mitochondrial genome can accumulate a series of mtDNA variants, which can lead to diseases such as cancer. It is likely that a combination of certain mitochondrial variants and aberrant patterns of mtDNA copy number could indeed account for many diseases that have previously been unaccounted for. This review focuses on the role that the mitochondrial genome plays especially during early stages of development and in cancer. © 2016 Elsevier Ltd.


Federrath C.,Monash University
Monthly Notices of the Royal Astronomical Society | Year: 2013

Observations of external galaxies and of local star-forming clouds in the Milky Way have suggested a variety of star formation laws, i.e. simple direct relations between the column density of star formation (σSFR: the amount of gas forming stars per unit area and time) and the column density of available gas (σgas). Extending previous studies, we show that these different, sometimes contradictory relations for MilkyWay clouds, nearby galaxies, and high-redshift discs and starbursts can be combined in one universal star formation law in which σSFRis about 1 per cent of the local gas collapse rate, σgas/tff, but a significant scatter remains in this relation. Using computer simulations and theoretical models, we find that the observed scatter may be primarily controlled by physical variations in the Mach number of the turbulence and by differences in the star formation efficiency. Secondary variations can be induced by changes in the virial parameter, turbulent driving and magnetic field. The predictions of our models are testable with observations that constrain both the Mach number and the star formation efficiency in Milky Way clouds, external disc and starburst galaxies at low and high redshift. We also find that reduced telescope resolution does not strongly affect such measurements when σSFR is plotted against σgas/tff © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Ilic D.,Monash University | Misso M.,Monash University
Maturitas | Year: 2012

Background: Prostate cancer is a leading cancer affecting men worldwide. Benign prostatic hyperplasia (BPH) is a common disease of the prostate affecting men as they age, and a risk factor for developing prostate cancer. Lycopene is a member of the carotenoid family, whose strong anti-oxidant properties have been hypothesised to assist in the prevention and treatment of BPH and prostate cancer. The aim of this systematic review was to examine the effectiveness of lycopene for the prevention and treatment of BPH and prostate cancer. Methods: A search of the MEDLINE, EMBASE, AMED (Allied and Complementary Medicine) and the Cochrane Library databases was performed for published randomised controlled trials (RCTs) comparing lycopene to placebo (or other interventions) for the treatment of BPH and prostate cancer. All included studies were assessed for methodological quality using the Cochrane Collaboration's risk of bias tool. Results: Eight RCTs met the inclusion criteria for this systematic review. All included studies were heterogeneous with respect to their design and implementation of lycopene. Methodological quality of three studies was assessed as posing a 'high' risk of bias, two a 'low' risk of bias and the remaining three an 'unclear' risk of bias. Meta-analysis of four studies identified no significant decrease in the incidence of BPH (RR (relative risk) = 0.95, 95%CI 0.63, 1.44) or prostate cancer diagnosis (RR = 0.92, 95%CI 0.66, 1.29) between men randomised to receive lycopene and the comparison group. Meta-analysis of two studies indicated a decrease in PSA levels in men diagnosed with prostate cancer, who received lycopene (MD (mean difference) = -1.58, 95%CI -2.61, -0.55). Conclusions: Given the limited number of RCTs published, and the varying quality of existing studies, it is not possible to support, or refute, the use of lycopene for the prevention or treatment of BPH or prostate cancer. © 2012 Elsevier Ireland Ltd. All rights reserved.


Halim R.,Monash University | Danquah M.K.,Monash University | Webley P.A.,Monash University
Biotechnology Advances | Year: 2012

The rapid increase of CO 2 concentration in the atmosphere combined with depleted supplies of fossil fuels has led to an increased commercial interest in renewable fuels. Due to their high biomass productivity, rapid lipid accumulation, and ability to survive in saline water, microalgae have been identified as promising feedstocks for industrial-scale production of carbon-neutral biodiesel. This study examines the principles involved in lipid extraction from microalgal cells, a crucial downstream processing step in the production of microalgal biodiesel. We analyze the different technological options currently available for laboratory-scale microalgal lipid extraction, with a primary focus on the prospect of organic solvent and supercritical fluid extraction. The study also provides an assessment of recent breakthroughs in this rapidly developing field and reports on the suitability of microalgal lipid compositions for biodiesel conversion. © 2012 Elsevier Inc.


Smith J.T.,Monash University | Clarke I.J.,Monash University
Trends in Endocrinology and Metabolism | Year: 2010

Reproductive function depends on the stimulatory action of gonadotropin-releasing hormone (GnRH), secreted by the brain. Original work in birds identified and isolated a peptide that inhibits gonadotropin release, named gonadotropin inhibitory hormone (GnIH). There is no evidence for a similar factor operant in mammals. This mammalian orthologue of GnIH has been named RFamide-related peptide (RFRP), and negatively regulates GnRH function and gonadotropin secretion. In particular, mammalian GnIH inhibits the function of GnRH cells and acts at the level of gonadotropes. It appears to play a major role in seasonal regulation of reproduction and also to be involved in regulation of stress and food intake. © 2009 Elsevier Ltd.


Chatel G.,CNRS Poitiers Institute of Chemistry: Materials and Natural Resources | Macfarlane D.R.,Monash University
Chemical Society Reviews | Year: 2014

Ionic liquids, as reaction media, and sonochemistry are two recently developing fields of chemistry that present some similarities. Firstly, they constitute separately unconventional approaches to reaction chemistry that, in many cases, generate improvements in yield, rate and selectivity compared to classical chemistry, or even change the mechanisms or products expected. In addition, both are often associated with green chemistry concepts as a result of their properties and their possible eco-friendly uses. A recent trend has been to combine these two technologies in a range of different applications and the results demonstrate very significant and occasionally surprising synergetic effects. Here we critically review the advantages and limitations of the ionic liquid/ultrasound combination in different applications in chemistry, to understand how, and in which respects, it could become an essential tool of sustainable chemistry in the future. Many practical and theoretical aspects associated with this combination of techniques are not understood or resolved and we discus where fundamental studies might further advance this field. This journal is © the Partner Organisations 2014.


Giles M.L.,Monash University | Giles M.L.,Alfred Hospital
AIDS | Year: 2013

In resource rich settings transmission of HIV from mother to child during pregnancy and post partum has been significantly reduced by access to interventions such as maternal and neonatal antiretroviral therapy, avoidance of breast feeding and consideration to caesarean section. Accumulating observational and randomised controlled studies provide the evidence for development of guidelines for the clinical management of these women. However, despite referencing the same studies, differences exist between recommendations originating from the United States versus the United Kingdom. The particular areas of controversy include use of efavirenz, dose adjustment of antiretrovirals during pregnancy, mode of delivery according to maternal viral load, duration of neonatal zidovudine, use of PJP prophylaxis and number of antiretrovirals to prescribe in a neonate considered high risk of acquiring HIV infection. This article summarises these differences and suggests ways of approaching and adapting these conflicting recommendations to the local setting. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Yao J.,Monash University | Wang H.,Monash University
Chemical Society Reviews | Year: 2014

Zeolitic imidazolate frameworks (ZIFs), a subclass of metal organic frameworks, are built of tetrahedral metal ions bridged by imidazolates. They have permanent porosity and relatively high thermal and chemical stability, which make them attractive candidates for many industrial applications. In recent years, significant progress has been made in developing ZIFs into membranes and thin films for gas separation, liquid separation (pervaporation) and functional devices. Various techniques, such as direct synthesis, secondary synthesis, reactive seeding and functional chemicals as linkers, and contra-diffusion synthesis, have been reported for the fabrication of ZIF membranes and films. As ZIFs have good compatibility with polymers, they have been incorporated into polymers with high loadings to form mixed matrix membranes. The resulting symmetric dense or asymmetric composite membranes exhibit good performance in gas separation and liquid separation via pervaporation. The recent developments of ZIF membranes/films, ZIF-polymer mixed matrix membranes and their applications are reviewed in this article. © 2014 The Royal Society of Chemistry.


Esler M.D.,Baker IDI Heart and Diabetes Institute | Krum H.,Monash University | Schlaich M.,Baker IDI Heart and Diabetes Institute | Schmieder R.E.,University Hospital | And 2 more authors.
Circulation | Year: 2012

BACKGROUND-: Renal sympathetic nerve activation contributes to the pathogenesis of hypertension. Symplicity HTN-2, a multicenter, randomized trial, demonstrated that catheter-based renal denervation produced significant blood pressure lowering in treatment-resistant patients at 6 months after the procedure compared with control, medication-only patients. Longer-term follow-up, including 6-month crossover results, is now presented. METHODS AND RESULTS-: Eligible patients were on ≥3 antihypertensive drugs and had a baseline systolic blood pressure ≥160 mm Hg (≥150 mm Hg for type 2 diabetics). After the 6-month primary end point was met, renal denervation in control patients was permitted. One-year results on patients randomized to immediate renal denervation (n=47) and 6-month postprocedure results for crossover patients are presented. At 12 months after the procedure, the mean fall in office systolic blood pressure in the initial renal denervation group (-28.1 mm Hg; 95% confidence interval,-35.4 to-20.7; P<0.001) was similar to the 6-month fall (-31.7 mm Hg; 95% confidence interval,-38.3 to-25.0; P=0.16 versus 6-month change). The mean systolic blood pressure of the crossover group 6 months after the procedure was significantly lowered (from 190.0±19.6 to 166.3±24.7 mm Hg; change,-23.7±27.5; P<0.001). In the crossover group, there was 1 renal artery dissection during guide catheter insertion, before denervation, corrected by renal artery stenting, and 1 hypotensive episode, which resolved with medication adjustment. CONCLUSIONS-: Control patients who crossed over to renal denervation with the Symplicity system had a significant drop in blood pressure similar to that observed in patients receiving immediate denervation. Renal denervation provides safe and sustained reduction of blood pressure to 1 year. CLINICAL TRIAL REGISTRATION-: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00888433. © 2012 American Heart Association, Inc.


We present numerical subduction models to investigate overriding plate deformation at subduction zones. All models show forearc shortening, resulting predominantly from shear stresses at the subduction zone interface and opposite-sense mantle shear stresses at the base of the forearc lithosphere. Models dominated by backarc extension show that it results from trench-normal positive velocity gradients in the mantle below the overriding plate. Such gradients result from toroidal mantle flow induced by slab rollback, with velocities below the leading part of the backarc faster than the overriding plate velocity. The velocity gradients induce basal shear stresses that increase trenchward and cause trenchward overriding plate motion at a velocity (v OP⊥) whose spatial average is below the trench retreat velocity (vT⊥). The combination of basal shear stresses and average vOP⊥ < vT⊥ causes trench-normal deviatoric tension in the backarc and backarc extension. Models dominated by backarc shortening show that it results from a relatively immobile subduction hinge and trenchward overriding plate motion driven by poloidal mantle flow. The poloidal mantle flow is induced by downdip slab sinking and causes the average v OP⊥ > vT⊥. This results in trench-normal deviatoric compression and shortening in the leading part of the overriding plate as it collides with the subduction hinge. Ultimately, the geodynamic models demonstrate that backarc extension is favored for narrow slabs and near lateral slab edges and is driven by rollback induced toroidal mantle flow, while backarc shortening is favored for the center of wide slabs and is driven by poloidal mantle flow resulting from downdip slab motion. Key Points Slab rollback driven toroidal mantle flow causes trench-normal velocity gradient The velocity gradient induces basal shear stresses that drive backarc extension Backarc shortening results from overriding plate collision with subduction hinge ©2013. American Geophysical Union. All Rights Reserved.


Lithgow T.,Monash University | Schneider A.,University of Bern
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

All eukaryotes require mitochondria for survival and growth. The origin of mitochondria can be traced down to a single endosymbiotic event between two probably prokaryotic organisms. Subsequent evolution has left mitochondria a collection of heterogeneous organelle variants. Most of these variants have retained their own genome and translation system. In hydrogenosomes and mitosomes, however, the entire genome was lost. All types of mitochondria import most of their proteome from the cytosol, irrespective of whether they have a genome or not. Moreover, in most eukaryotes, a variable number of tRNAs that are required for mitochondrial translation are also imported. Thus, import of macromolecules, both proteins and tRNA, is essential for mitochondrial biogenesis. Here, we review what is known about the evolutionary history of the two processes using a recently revised eukaryotic phylogeny as a framework. We discuss how the processes of protein import and tRNA import relate to each other in an evolutionary context. © 2010 The Royal Society.


Munday P.L.,James Cook University | Warner R.R.,University of California at Santa Barbara | Monro K.,Monash University | Pandolfi J.M.,University of Queensland | Marshall D.J.,Monash University
Ecology Letters | Year: 2013

An increasing number of short-term experimental studies show significant effects of projected ocean warming and ocean acidification on the performance on marine organisms. Yet, it remains unclear if we can reliably predict the impact of climate change on marine populations and ecosystems, because we lack sufficient understanding of the capacity for marine organisms to adapt to rapid climate change. In this review, we emphasise why an evolutionary perspective is crucial to understanding climate change impacts in the sea and examine the approaches that may be useful for addressing this challenge. We first consider what the geological record and present-day analogues of future climate conditions can tell us about the potential for adaptation to climate change. We also examine evidence that phenotypic plasticity may assist marine species to persist in a rapidly changing climate. We then outline the various experimental approaches that can be used to estimate evolutionary potential, focusing on molecular tools, quantitative genetics, and experimental evolution, and we describe the benefits of combining different approaches to gain a deeper understanding of evolutionary potential. Our goal is to provide a platform for future research addressing the evolutionary potential for marine organisms to cope with climate change. © 2013 John Wiley & Sons Ltd/CNRS.


Marino E.,Monash University | Grey S.T.,Garvan Institute of Medical Research
Autoimmunity | Year: 2012

A classic understanding of the interplay between B and T cell components of the immune system that drive autoimmunity, where B cells provide an effector function, is represented by systemic lupus erythematosus (SLE), an autoimmune condition characterised by the production of auto-antibodies. In SLE, CD4T cells provide cognate help to self-reactive B cells, which in turn produce pathogenic auto-antibodies (1). Thus, B cells act as effectors by producing auto-antibody aided by T cell help such that B and T cell interactions are unidirectional. However, this paradigm of B and T cell interactions is challenged by new clinical data demonstrating that B cell depletion is effective for T cell mediated autoimmune diseases including type I diabetes mellitus (T1D) (2), rheumatoid arthritis (3), and multiple sclerosis (4). These clinical data indicate a model whereby B cells can influence the developing autoimmune T cell response, and therefore act as effectors, in ways that extend beyond the production of autoantibody (5). In this review by largely focusing on type I diabetes we will develop a hypothesis that bi-directional B and T interactions control the course of autoimmunity. © Informa UK, Ltd.


Jones C.,Monash University
Coordination Chemistry Reviews | Year: 2010

This article summarizes the development of a new class of very bulky guanidinate ligands. These have been used to prepare unprecedented examples of heterocycles containing groups 2, 13, 14 or 15 elements in the +1 oxidation state. The ligands have also been harnessed in the preparation of the only examples of guanidinato, and/or closely related amidinato, complexes of iron(I), cobalt(I) and planar four-coordinate lanthanide(II) metals. Preliminary studies of the further chemistry of these very reactive complexes are also reviewed. Throughout, the tendency of the bulky guanidinate ligands to exhibit ligating and stabilizing properties more akin to those of bulky β-diketiminate ligands than less bulky amidinates or guanidinates, will be discussed. © 2009 Elsevier B.V. All rights reserved.


Tomkins A.G.,Monash University
Economic Geology | Year: 2013

Orogenic gold deposits are unevenly distributed in geologic time. The richest period of orogenic gold depositformation was the Phanerozoic, which followed a >1-b.y. period of relatively meager deposit generation duringthe Proterozoic. This Proterozoic low-gold period developed despite continent-building episodes, whichshould have been appropriate for orogenic gold genesis. Here, a brief review of the changes in global geochemistrybrought on by evolving interactions between plate tectonics and the biosphere is conducted beforethe consequences for gold uptake into sedimentary pyrite are discussed. It is suggested that the extensive oxygenationof the deep oceans during the second Great Oxidation Event, over the period 635 to 510 Ma, producedconditions where gold was soluble in the deep oceans from that point on. Regions where bacterial sulfatereduction drove formation of sedimentary pyrite also destabilized this soluble gold, promoting its uptakeinto pyrite, and allowing formation of metallogenically enhanced sedimentary sequences. These sedimentswould have become ideal source rocks for gold deposits during subsequent collisional tectonics and metamorphism.This biogenic influence on source region enhancement may explain the association during the Phanerozoiceon between some of the world's most gold productive regions and sedimentary sequences that containpyritic carbonaceous rocks. ©2013 by Economic Geology.


Agnew S.R.,University of Virginia | Nie J.F.,Monash University
Scripta Materialia | Year: 2010

Research papers, which will guide future research aimed in magnesium alloys at improving the properties and broadening the structural applications of the metal, are discussed. Three papers in the viewpoint set are devoted to creep mechanisms and development of creep-resistant alloys. The paper by Saddock and co-researchers demonstrate that there is no significant contribution of grain boundary sliding to creep in alloys based on the Mg-Al-Ca system, at least when tested at 175°C. Spigarelli and El Mehtedi make a comparison of the constitutive response in creep and hot torsion of both cast and wrought magnesium alloys, obtained in the temperature range 100-150°C. The potential to develop high-strength low-cost magnesium wrought alloys through precipitation hardening is discussed in the paper by Hono and co-researchers, with emphasis on microalloying additions to Mg-Zn and Mg-Sn alloys. The paper by Kim and researchers predicts that even twinroll cast material is not free from the concerns associated with strong basal texture that have plagued traditional direct-chill cast and hot-rolled materials.


A new volcanic distribution map of the 4.5 Ma-5000 B.P. continental intraplate Newer Volcanics Province in southeastern Australia has been produced in order to document >704 eruption points from >416 volcanic centres. Volcanic centres were classified as either simple or complex, with simple centres featuring few eruption points and simple morphologies, while complex centres have multiple eruption points and complex morphologies. Centres were further characterised according to the nature of their deposits. Simple volcanoes take the form of lava shields, scoria cones, maars, ash cones and domes, and unknown eruption types. Complex centres may feature exclusively magmatic eruption products such as lava and scoria, and are therefore classified as magmatic volcanic complexes; maar volcanic complexes feature exclusively phreatomagmatic eruption products and have erupted under the influence of external water, while maar-cone volcanic complexes feature both magmatic and phreatomagmatic eruption products. Approximately half of the eruption points in the Newer Volcanics Province are associated with complex volcanic centres. The minimum area of the Newer Volcanic Province was calculated to be >19 000 km2, which may be a great underestimation, and it is estimated that the province has an eruption frequency of 1:10 800 yrs. This research has highlighted a need for further research into the Newer Volcanics Province, as many of the apparently 'simple' volcanic centres are likely to be more complex in nature. A spreadsheet database has been made freely available to download for research purposes, along with shapefiles for ArcGIS and kml files for Google Earth. © 2013 Copyright Taylor and Francis Group, LLC.


Tan J.,Monash University | Jakob C.,Monash University
Geophysical Research Letters | Year: 2013

Tropical convection is a key driver in the climate system and is often identified using infrared satellite information or precipitation. Satellite-derived cloud regimes offer an alternative with potentially more informative distinctions between different types of convection. However, current ISCCP cloud regime data sets require visible satellite information and are therefore only available during daytime. We develop a convective regime data set for all three-hour intervals of the day using ISCCP infrared-only retrievals. We show that regimes derived in this way capture the essential properties of the original regimes, in particular, when identifying the state of tropical convection. We give examples for potential applications by illustrating the well-known Madden-Julian Oscillation and the diurnal cycle of convection in the framework of the newly derived regimes. The high temporal resolution, long record and global coverage of the regimes makes them a suitable tool for large-scale studies of tropical convection. Key Points Cloud regimes representing convection are extended to three-hour resolution These new regimes can identify different stages of convection like the original Applications to MJO and diurnal cycle show greater detail over original regimes ©2013. American Geophysical Union. All Rights Reserved.


Singh R.M.,Monash University | Bouazza A.,Monash University
Geotextiles and Geomembranes | Year: 2013

Thermal conductivity is a key property that controls heat migration in a variety of applications including municipal solid waste and/or mining/industrial containment facilities. In particular, heat may be encountered in cases where geosynthetic lining systems are exposed to elevated temperatures due to either waste biodegradation, solar radiation, or mining processes. This paper presents the results of an experimental investigation on thermal conductivity of nonwoven geotextiles, geosynthetic clay liners and an HDPE geomembrane. A steady state method was used to measure the thermal conductivity of a selected number of these materials. The thermal conductivity of the HDPE geomembrane was found to be consistent with the thermal conductivity of HDPE polymer. On the other hand, the thermal conductivity of the nonwoven geotextiles depended on water content and whether they are hydrophobic or hydrophilic. The form of bentonite, its mass per area and water content affected the thermal conductivity of GCLs. The results presented in this paper provide a lower bound of thermal conductivities of geosynthetics routinely used in waste containment facilities. © 2013 Elsevier Ltd.


Keays R.R.,Monash University | Jowitt S.M.,Monash University
Ore Geology Reviews | Year: 2013

The Avebury Ni deposit, which has a resource of 260,000 tons of Ni at a grade of 0.9%, is a unique example of a significant Ni sulfide deposit associated with an ophiolite sequence; the deposit is unique because it was formed by hydrothermal processes and also because ophiolites are generally considered unprospective for magmatic Ni sulfide mineralization. The deposit is hosted by Middle Cambrian cumulate peridotite and dunite rocks that were most probably formed from S-poor boninitic magmas. The mineralization, which consists principally of pentlandite, occurs in both serpentinites and skarns in the ultramafic cumulates. The ultramafic rocks are variably metasomatised as the result of the intrusion of the Late Devonian Heemskirk granite. Sulfide-rich and sulfide-poor portions of the ultramafic rocks are variably enriched in W, Bi, U, Pb, Mo, Sn and Sb relative to the primitive mantle. Modest to strong correlations between Cu, Au, Pd, REE, Sn, Mo, W and Ni provide strong evidence that the mineralization is hydrothermal in origin. In situ metasomatism of a magmatic Ni sulfide deposit is ruled out on the basis of poor or negative correlations between Ir, Ru, Rh and Pt when compared to Ni. Although the sulfide-free ultramafic rocks have high Ni contents, this Ni would have been unavailable to the ore-forming fluids as it was hosted in inaccessible sites, such as oxides and silicates. The strong correlations between Au, Pd and Ni suggest that the source of the Ni was magmatic sulfides somewhere at depth that not only have high Ni but also elevated Pd and Au contents. © 2012 Elsevier B.V.


Duff C.,Monash University
Environment and Planning D: Society and Space | Year: 2010

Michel de Certeau's account of the modern city emphasises the 'doing' and 'making' residents undertake in an attempt to render a city more amenable to an 'art' of resistance. Yet, in attending to this doing and making, de Certeau has largely ignored the felt and affective dimensions of city life. Edward Casey provides a compelling means of interrogating these affective dimensions, distinguishing 'thick' and 'thin' places in everyday life. Thick places are contrived in the imbrications of affect, habit, and practice, presenting opportunities for personal enrichment and a deepening of affective experience. Casey's work restores the affective fecundity of place, even if it fails to provide a clear sense of how thick places might be identified. This paper takes up this challenge in an attempt to clarify the role of affect and practice in the production of place. The paper first reviews the practical and affective dimensions of this place-making before turning to an ethnographic account of young people, place, and urban life recently completed in Vancouver, Canada. This study explored the ways young people negotiate and transform place and the impact these practices have on the characteristic orientations of self and belonging. The experience of place was found to involve a series of affective relays between the cultivation of private places and the negotiation of designated spaces. The affective atmospheres created in these exchanges helped participants transform thin or designated spaces into dynamic thick places. The paper closes with a discussion of the role thick places might play in the design of innovative youth development efforts in urban settings. © 2010 Pion Ltd and its Licensors.


Mortimer D.,Monash University
BMC Health Services Research | Year: 2010

Background. Remarkable progress has been made over the past 40 years in developing rational, evidence-based mechanisms for the allocation of health resources. Much of this progress has centred on mechanisms for commissioning new medical devices and pharmaceuticals. The attention of fund-managers and policy-makers is only now turning towards development of mechanisms for decommissioning, disinvesting or redeploying resources from currently funded interventions. While Programme Budgeting and Marginal Analysis would seem well-suited to this purpose, past applications include both successes and failures in achieving disinvestment and resource release. Discussion. Drawing on recent successes/failures in achieving disinvestment and resource release via PBMA, this paper identifies four barriers/enablers to disinvestment via PBMA: (i) specification of the budget constraint, (ii) scope of the programme budget, (iii) composition and role of the advisory group, and (iv) incentives for/against contributing to a 'shift list' of options for disinvestment and resource release. A number of modifications to the PBMA process are then proposed with the aim of reorienting PBMA towards disinvestment. Summary. The reoriented model is differentiated by four features: (i) hard budget constraint with budgetary pressure; (ii) programme budgets with broad scope but specific investment proposals linked to disinvestment proposals with similar input requirements; (iii) advisory/working groups that include equal representation of sectional interests plus additional members with responsibility for advocating in favour of disinvestment, (iv) 'shift lists' populated and developed prior to 'wish lists' and investment proposals linked to disinvestment proposals within a relatively narrow budget area. While the argument and evidence presented here suggest that the reoriented model will facilitate disinvestment and resource release, this remains an empirical question. Likewise, further research will be required to determine whether or not the re-oriented model sacrifices feasibility and acceptability to obtain its hypothesised greater emphasis on disinvestment. © 2010 Mortimer; licensee BioMed Central Ltd.


Du L.B.,Monash University | Lowery A.J.,Monash University
Optics Express | Year: 2010

Backpropagation has been shown to be the most effective method for compensating intra-channel fiber nonlinearity in long-haul optical communications systems. However, effective compensation is computationally expensive, as it requires numerous steps and possibly increased sampling rates compared with the baud rate. This makes backpropagation difficult to implement in real-time. We propose: (i) lowpass filtering the compensation signal (the intensity waveform used to calculate the nonlinearity compensation) in each backpropagation step and (ii) optimizing the position of the nonlinear section in each step. With numerical simulations, we show that these modifications to backpropagation improve system performance, reducing the number of backpropagation steps and reducing the oversampling for a given system performance. Using our 'filtered backpropagation', with four backpropagation steps operating at the same sampling rate as that required for linear equalizers, the Q at the optimal launch power was improved by 2 dB and 1.6 dB for single wavelength CO-OFDM and CO-QPSK systems, respectively, in a 3200 km (40 × 80km) single-mode fiber link, with no optical dispersion compensation. With previously proposed backpropagation methods, 40 steps were required to achieve an equivalent performance. A doubling in the sampling rate of the OFDM system was also required. We estimate this is a reduction in computational complexity by a factor of around ten. © 2010 Optical Society of America.


Lowery A.J.,Monash University
Optics Express | Year: 2010

All-optical OFDM uses optical techniques to multiplex together several modulated lightsources, to form a band of subcarriers that can be considered as one wavelength channel. The subcarriers have a frequency separation equal to their modulation rate. This means that they can be demultiplexed without any cross-talk between them, usually with a Discrete Fourier Transform (DFT), implemented optically or electronically. Previous work has proposed networks of optical couplers to implement the DFT. This work shows that the topology of an Arrayed Grating Waveguide Router (AWGR) can be used to perform the demultiplexing, and that the AWGR can be considered as a serial-to-parallel converter followed by a DFT. The simulations show that the electrical bandwidths of the transmitter and receiver are critical to orthogonal demultiplexing, and give insight into how crossta