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Madden J.A.,Medical College of Wisconsin | Madden J.A.,Research Service
Neurology | Year: 2012

The underlying cause of stroke lies in the damage to the arterial endothelial cell layer. The most profound damage is due to atherosclerosis, which can either occlude an artery or produce a thromboembolism. Diabetes and inflammation contribute to atherosclerosis and the associated endothelial damage by initiating and promoting the deposition of modified lipids in the subendothelium and by inhibiting endothelial nitric oxide (NO) production. At the same time, both production of endothelin-1 and generation of reactive oxygen species increase. In addition, leukocytes adhere to the endothelium and levels of C-reactive protein increase. The stroke that ensues upon cerebral artery occlusion or plaque rupture continues and exacerbates endothelial damage. Statins have been shown to be helpful in preventing stroke and diminishing its consequences. An international clinical trial to determine if an NO donor is effective (Efficacy of Nitric Oxide in Stroke study) is currently under way. Other interventions such as antioxidants, ρ kinase inhibition, and endothelial progenitor cells offer promising avenues of research and perhaps therapeutic avenues for treatment of stroke. This article discusses the role of the vascular endothelium in ischemic stroke and those interventions that may provide plausible avenues for future therapy. © 2012 American Academy of Neurology.

News Article | February 16, 2017

The report of an independent review of UK tidal lagoon energy was published on 12 January 2017 by a former UK energy Minister Charles Hendry. The report praises the proposed ‘pathfinder’ tidal lagoon in Swansea Bay as a ‘no-regrets option’, and sets out a supportive case for developing the sector. The Hendry Review was commissioned in February 2016 by UK Government to assess the strategic case for tidal lagoon energy as a new industry in the UK. This followed a successful planning proposal by Tidal Lagoon Power (TLP) to develop the world’s first tidal lagoon in Swansea Bay, as well as a subsequent programme for a ‘fleet’ of five larger projects, including three in Welsh waters (Cardiff, Newport and Colwyn Bay). Despite the Swansea Bay project appearing in the 2015 UK Conservative Party manifesto and receiving development consent in June 2015, uncertainties around cost and subsidy subsequently prompted the UK Government to commission an independent review. Its aim was to examine the ability of tidal lagoon energy to cost-effectively contribute to the UK’s energy mix, and the level of subsidy required to do so. Tidal lagoons generate electricity by enclosing an area of sea adjacent to coastline with a sea wall, and capturing the energy from the rise and fall of tides using turbines. A number of lagoon projects in Wales have been proposed due to the significant tidal range along the Welsh coastline – particularly in the Severn Estuary, which has the second largest range in the world. The case for tidal lagoon energy in Wales The Hendry report (PDF, 2.72MB) highlighted the predictability of electricity output and extremely low carbon emissions (less than 20 grams of CO equivalent per kWh – on par with onshore wind and nuclear) as major advantages of tidal lagoons. Moreover, a lagoon’s estimated operating lifetime of 120 years or more is unparalleled by any energy technology. In combination, the Review found that they could make a strong contribution to UK energy security and decarbonisation targets. TLP estimate that their fleet of lagoons could supply 8% of future UK electricity demand. According to the report, the potential benefits to Welsh economy are significant, and there have been many expressions of support from Assembly Members on a cross-party basis. The Review found that the Swansea Bay project would bring ‘very real and substantial economic and recreational benefits’ to the area (p.37) – drawing upwards of an estimated 70,000 tourists per year (p.51) – as well as wider economic benefits across the country. Supply chain development and employment opportunities are thought to be considerable; TLP told the Review that over 1000 UK businesses have registered an interest in supplying parts and skills to the Swansea Bay project, and the company is aiming to source 50% of the materials and components from Wales. Many companies – including from within the steel sector – described the potential TLP programme as a ‘lifeline’ for their operations (p.47). With construction costs of £1.3 billion, there were fears that the 320 megawatt (MW) Swansea Bay project would not be cost effective for bill payers. Under the ‘Contracts for Difference’ (CfD) scheme, it was initially estimated that the ‘strike price’ – the guaranteed price needed for the sale of its electricity – would be more expensive than, for example, nuclear power from Hinkley Point C, and this would be met in part through increased consumers’ bills. However, such costs were calculated on the basis of a 30-year model. As highlighted by the report, key economic characteristics of lagoons are low operation costs, and an ability to spread total costs across the very long operating life. When pricing over a longer 60- or 90-year CfD model, tidal lagoon energy becomes much more competitive. Swansea Bay, it concludes, would cost each Welsh household 30 pence per year, for 30 years, and could potentially be subsidy-free after 60 years (p.75). As a pathfinder lagoon, it is projected to bring about large cost reductions for any subsequent projects, making them very competitive with other low carbon technologies over project lifetimes. The Review is clear in its support of developing a small-scale project in Swansea Bay ‘as soon as reasonably practicable’ (p.91), calling it a ‘no-regrets’ policy (p.89), and encourages the UK Government to build upon the progress it has made with TLP to move towards a final stage negotiation. TLP is also awaiting a marine licence from Natural Resources Wales. A key recommendation in the report was that the Swansea Bay lagoon should be operational for a reasonable period before construction commences on any large-scale projects, so that the full range of impacts can be monitored over time. This is in part a response to environmental concerns over potential lagoon impacts on marine habitats and species, which carry considerable uncertainties that stem from the technology’s infancy. To help maintain the supply chain during such a ‘pause’, the report calls for the development of a series of small-scale lagoons between larger projects. The Cabinet Secretary for Economy and Infrastructure said in Plenary on 25 January 2017 that the Welsh Government is working with local government, skills providers and businesses to identify opportunities to maintain a constant pipeline of projects. There have been expressions of interest by the Welsh Government in taking a stake in the Swansea Bay project, and Plaid Cymru have proposed a not-for-profit public energy company as a suitable organisation for doing so. A Welsh Government Debate will take place on 14 February 2017 to discuss these proposals, as well as the Review’s findings, in detail. The UK Government will respond to the Review’s findings after it has assessed the report’s recommendations. Jack Miller began his PhD with SPRU and CIED in September 2014, conducting research into the role of energy efficiency in economic growth.  His work centres upon the concepts of ‘exergy’ and ‘useful work’, or the portions of energy inputs into the economy which can prove useful to economic activity and societal needs.  He completed an MSc in Energy Policy for Sustainability with SPRU in 2014, having undertaken a project looking at the prospects for future shale gas development in the US.  He has a degree in Physics (MPhys hons, University of Sussex, 2013), and has previously taught maths and physics from KS3 to first-year undergraduate level. This blog was originally posted on 02/10/17 on the National Assembly for Wales Research Service’s blog, ‘In Brief‘, where it is also available in Welsh.

BOULDER, Colo.--(BUSINESS WIRE)--A new white paper from Navigant Research analyzes five global trends for distributed natural gas (DNG) in 2017 and beyond, including the key determinants driving global investment and related opportunities. Thanks to key developments in technology, new business models, and the changing regulatory environment, established DNG technologies are now being used in new applications. Access to cheap natural gas, demand for resilient onsite power, and improved controls offerings are improving the value proposition for customers, and regulators are recognizing the benefits of cleaner, dispatchable distributed generation as grids experience growing supply variability from intermittent renewables. Click to tweet: According to a new white paper from @NavigantRSRCH, despite its relative maturity, DNG-fueled generation is undergoing a transformation. “As natural gas becomes more globally available, opportunities are growing for DNG generation,” says Adam Forni, senior research analyst with Navigant Research. “Mature technologies like generators are developing personality and becoming more interactive thanks to smarter controls, demand for resiliency, and a need to balance increasingly variable grids.” According to the report, as macroeconomic, regulatory, and technological forces push the DNG industry into a new era, the following five trends are expected to be the most impactful in the next few years: The white paper, Distributed Natural Gas: Five Trends for 2017 and Beyond, analyzes five global trends for DNG in 2017 and beyond. The study examines the key determinants driving global investment in DNG and the related opportunities. Each of the topics in this white paper is examined more deeply in research reports and ongoing research from Navigant Research’s Distributed Natural Gas Research Service. An Executive Summary of the report is available for free download on the Navigant Research website. Navigant Research, the dedicated research arm of Navigant, provides market research and benchmarking services for rapidly changing and often highly regulated industries. In the energy sector, Navigant Research focuses on in-depth analysis and reporting about global clean technology markets. The team’s research methodology combines supply-side industry analysis, end-user primary research and demand assessment, and deep examination of technology trends to provide a comprehensive view of the Energy Technologies, Utility Transformations, Transportation Efficiencies, and Buildings Innovations sectors. Additional information about Navigant Research can be found at Navigant Consulting, Inc. is a specialized, global professional services firm that helps clients take control of their future. Navigant’s professionals apply deep industry knowledge, substantive technical expertise, and an enterprising approach to help clients build, manage and/or protect their business interests. With a focus on markets and clients facing transformational change and significant regulatory or legal pressures, the Firm primarily serves clients in the healthcare, energy and financial services industries. Across a range of advisory, consulting, outsourcing, and technology/analytics services, Navigant’s practitioners bring sharp insight that pinpoints opportunities and delivers powerful results. More information about Navigant can be found at * The information contained in this press release concerning the report, Distributed Natural Gas: Five Trends for 2017 and Beyond, is a summary and reflects Navigant Research’s current expectations based on market data and trend analysis. Market predictions and expectations are inherently uncertain and actual results may differ materially from those contained in this press release or the report. Please refer to the full report for a complete understanding of the assumptions underlying the report’s conclusions and the methodologies used to create the report. Neither Navigant Research nor Navigant undertakes any obligation to update any of the information contained in this press release or the report.

VANCOUVER, BC--(Marketwired - March 02, 2017) - Aequus Pharmaceuticals Inc. (TSX VENTURE: AQS) ( : AQSZF) ("Aequus" or the "Company") announced today that through a previously announced Research Service Contract with Transdermal Research Pharma Lab ("TRPL") it has entered into a binding term sheet (the "Term Sheet") to acquire an exclusive world-wide license to a transdermal patch containing cannabinoids, for the use in epilepsy, Multiple Sclerosis (MS), and certain other neurological disorders. Aequus has been focused on expanding treatment options for neurological disorders through its current pipeline of development stage and in-licensed products. Aequus recognizes there has been an increased acceptance around the use of cannabinoids for epilepsy and MS in particular, however, uptake by the medical community has been limited by a need for a product that provides precise, controlled dose delivery. The majority of clinical studies performed to date have used orally ingested or inhaled forms of delivery, and further to the challenges with consistency of dosing, these routes of delivery are commonly associated with gastrointestinal side effects such as diarrhea that would be expected to be significantly reduced with a transdermal form. "Since Aequus' inception our development efforts have largely been focused on differentiated prescription products for the treatment of certain neurological disorders," said Doug Janzen, Chairman and CEO of Aequus. "This announcement broadens our pipeline and is a perfect complement to our growing epilepsy franchise that consists of a long-acting transdermal patch for clobazam currently in development and two recently in-licensed U.S. Food and Drug Association approved slow-release oral anti-epileptics, topiramate extended-release and oxcarbazepine extended-release for the Canadian market." "We are excited about combining the insights from physicians with our existing drug delivery, clinical development and business development skills to pursue cannabinoid products that meet the needs of physicians and patients suffering from neurological disorders," said Anne Stevens, COO and Director of Aequus. TRPL and its affiliates who are expected to develop the formulation for the cannabinoid patch also developed the initial formulations for Aequus' three pipeline programs which are now advancing through human proof of concept studies. In consideration for commercial rights, Aequus will pay royalties on future product revenues. There are no other upfront or milestone payment obligations by Aequus associated with this program. 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. Aequus Pharmaceuticals Inc. (TSX VENTURE: AQS) ( : AQSZF) is a growing specialty pharmaceutical company focused on developing and commercializing high quality, differentiated products. Aequus' development stage pipeline includes several products in neurology and psychiatry with a goal of addressing the need for improved medication adherence through enhanced delivery systems. Aequus intends to commercialize its internal programs in Canada alongside its current portfolio of marketed established medicines and will look to form strategic partnerships that would maximize the reach of its product candidates worldwide. Aequus plans to build on its Canadian commercial platform through the launch of additional products that are either created internally or brought in through an acquisition or license; remaining focused on highly specialized therapeutic areas. For further information, please visit This release may contain forward-looking statements or forward-looking information under applicable Canadian securities legislation that may not be based on historical fact, including, without limitation, statements containing the words "believe", "may", "plan", "will", "estimate", "continue", "anticipate", "intend", "expect", "potential" and similar expressions. Forward-looking statements are necessarily based on estimates and assumptions made by us in light of our experience and perception of historical trends, current conditions and expected future developments, as well as the factors we believe are appropriate. Forward-looking statements in this release include but are not limited to statements relating to: the Company entering into a definitive license agreement with TRPL; the payment of future royalties to TRPL; and the Company's intention to commercialize its internal programs in Canada, form strategic partnerships and build its Canadian commercial platform. Such statements reflect our current views with respect to future events and are subject to risks and uncertainties and are necessarily based upon a number of estimates and assumptions that, while considered reasonable by Aequus, are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies. Many factors could cause our actual results, performance or achievements to be materially different from any future results, performance, or achievements that may be expressed or implied by such forward-looking statements. In making the forward-looking statements included in this release, the Company has made various material assumptions, including, but not limited to: obtaining positive results of clinical trials, obtaining regulatory approvals, general business and economic conditions, the Company's ability to successfully out-license or sell its current products and in-license and develop new products, the assumption that the Company's current good relationships with its manufacturer and other third parties will be maintained, the availability of financing on reasonable terms, the Company's ability to attract and retain skilled staff, market competition, the products and technology offered by the Company's competitors and the Company's ability to protect patents and proprietary rights. In evaluating forward-looking statements, current and prospective shareholders should specifically consider various factors set out under the heading "Risk Factors" in the Company's Annual Information Form dated April 29, 2016, a copy of which is available on Aequus' profile on the SEDAR website at, and as otherwise disclosed from time to time on Aequus' SEDAR profile. Should one or more of these risks or uncertainties, or a risk that is not currently known to us materialize, or should assumptions underlying those forward-looking statements prove incorrect, actual results may vary materially from those described herein. These forward-looking statements are made as of the date of this release and we do not intend, and do not assume any obligation, to update these forward-looking statements, except as required by applicable securities laws. Investors are cautioned that forward-looking statements are not guarantees of future performance and are inherently uncertain. Accordingly, investors are cautioned not to put undue reliance on forward-looking statements.

Simcox J.A.,University of Utah | McClain D.A.,University of Utah | McClain D.A.,Research Service
Cell Metabolism | Year: 2013

Iron overload is a risk factor for diabetes. The link between iron and diabetes was first recognized in pathologic conditions - hereditary hemochromatosis and thalassemia - but high levels of dietary iron also impart diabetes risk. Iron plays a direct and causal role in diabetes pathogenesis mediated both by β cell failure and insulin resistance. Iron also regulates metabolism in most tissues involved in fuel homeostasis, with the adipocyte in particular serving an iron-sensing role. The underlying molecular mechanisms mediating these effects are numerous and incompletely understood but include oxidant stress and modulation of adipokines and intracellular signal transduction pathways. © 2013 Elsevier Inc.

Tregellas J.R.,Research Service | Tregellas J.R.,Aurora University
Biological Psychiatry | Year: 2014

Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rationale for the focus of this review, are that the deficits are not dependent upon patients' performance of specific cognitive tasks and they have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia.

Rollenhagen C.,Research Service | Asin S.N.,Research Service
Mucosal Immunology | Year: 2011

Knowledge about early innate immune responses at the mucosal surfaces of the female genital tract is important in understanding the pathogenesis of heterosexual transmission of human immunodeficiency virus type-1 (HIV-1). As estradiol decreases inflammatory responses, we postulated that an estradiol-deficient state such as post-menopause could enhance expression of inflammatory factors that stimulate HIV-1 replication. We compare HIV-1 integration, transcription, and viral p24 release levels among ectocervical tissues obtained from pre- and post-menopausal donors. We detected enhanced HIV-1 p24 release levels in post- compared with pre-menopausal tissues (P<0.0001), but saw no difference in HIV-1 integration. Overall, 100% of post-menopausal tissues exhibited levels of HIV-1 transcription above background compared with only 60% of pre-menopausal tissues. Increased HIV-1 transcription was associated with enhanced interleukin (IL)-1β, IL-6, monocyte chemotactic protein-1, growth-regulated oncogene-α, and interferon-γ-inducible protein-10 expression. Neutralization and nuclear factor-B-targeting small-interfering RNA experiments both decreased HIV-1 transcription, suggesting that the early inflammatory response may facilitate HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women.

Spencer K.M.,Research Service | Spencer K.M.,Harvard University
Frontiers in Human Neuroscience | Year: 2012

Several studies have reported deficits in γ oscillatory activity elicited by sensory stimulation or cognitive processes in schizophrenia patients (SZ) compared to healthy control subjects (HC). However, the evidence for cortical hyperexcitability and reduced function of N -methyl-D-aspartate receptors (NMDARs) on parvalbumin-expressing inhibitory interneurons in schizophrenia leads to the prediction that γ activity should rather be increased in SZ, but data supporting this hypothesis have been lacking. One possibility is that baseline induced γ power is increased, an effect that might have gone unnoticed in studies of stimulus-locked oscillations. Here we addressed this question by re-analyzing the data from a previously published study on the 40 Hz auditory steady-state response (ASSR) in schizophrenia in which dipole source localization was used to examine γ responses in the left and right auditory cortices. Subjects were 16 HC and 18 chronic SZ, who listened to trains of clicks presented at 40 Hz during electroencephalogram recording. Independent component analysis was used to remove ocular artifacts. Power spectra were computed for the pre-stimulus baseline period. We found that baseline power was higher in SZ than HC at 40 Hz in the left auditory cortex. Baseline 40 Hz power in the left auditory cortex was also correlated with ASSR evoked power in SZ. Thus, γ oscillation abnormalities in schizophrenia may include abnormal increases in baseline power as well as deficits in evoked oscillations. These baseline increases could be the sign of NMDAR hypofunction on parvalbumin-expressing inhibitory interneurons, which would be consistent with acute NMDAR antagonism and genetic ablation models of schizophrenia. © 2012 Spencer.

Young J.W.,University of California at San Diego | Geyer M.A.,Research Service
Journal of Psychopharmacology | Year: 2015

Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. While antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult, however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition. © The Author(s) 2014.

Ayers C.R.,Research Service
International journal of geriatric psychiatry | Year: 2013

Hoarding disorder (HD) is a chronic and debilitating psychiatric condition. Midlife HD patients have been found to have neurocognitive impairment, particularly in areas of executive functioning, but the extent to which this is due to comorbid psychiatric disorders has not been clear. The purpose of the present investigation was to examine executive functioning in geriatric HD patients without any comorbid Axis I disorders (n = 42) compared with a healthy older adult comparison group (n = 25). We hypothesized that older adults with HD would perform significantly worse on measures of executive functioning (Wisconsin Card Sort Task [Psychological Assessment Resources, Lutz, Florida, USA] ( Psychological Assessment Resources, 2003) and the Wechsler Adult Intelligence Scale-IV digit span and letter-number sequencing tests [Pearson, San Antonio, TX, USA]). Older adults with HD showed significant differences from healthy older controls in multiple aspects of executive functioning. Compared with healthy controls, older adults with HD committed significantly more total, non-perseverative errors and conceptual level responses on the Wisconsin Card Sort Task and had significantly worse performance on the Wechsler Adult Intelligence Scale-IV digit span and letter-number sequencing tests. Hoarding symptom severity was strongly correlated with executive dysfunction in the HD group. Compared with demographically-matched controls, older adults with HD have dysfunction in several domains of executive functioning including mental control, working memory, inhibition, and set shifting. Executive dysfunction is strongly correlated with hoarding severity and is not because of comorbid psychiatric disorders in HD patients. These results have broad clinical implications suggesting that executive functioning should be assessed and taken into consideration when developing intervention strategies for older adults with HD. Copyright © 2013 John Wiley & Sons, Ltd.

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