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The University of Oslo , formerly The Royal Frederick University , is the oldest and largest university in Norway, located in the Norwegian capital of Oslo. The university is recognized as one of Northern Europe's most prestigious universities. The Academic Ranking of World Universities has ranked it the 67th best university in the world.The university has approximately 27,700 students and employs around 6,000 people. Its faculties include Theology , Law, Medicine, Humanities, Mathematics, natural science, social science, Dentistry, and Education. The university's original neoclassical campus is located in the centre of Oslo; it is currently occupied by the Faculty of Law. Most of the university's other faculties are located at the newer Blindern campus in the suburban West End. The Faculty of Medicine is split between several university hospitals in the Oslo area.The university was founded in 1811 and was modelled after the University of Copenhagen and the recently established University of Berlin. It was originally named for King Frederick VI of Denmark and Norway, and received its current name in 1939. The university is informally also known as Universitetet , having been the only university in Norway until 1946, and was commonly referred to as "The Royal Frederick's" prior to the name change.The University of Oslo is home to five Nobel Prize winners. The Nobel Peace Prize was awarded in the university's Atrium from 1947 to 1989. Since 2003, the Abel Prize is awarded in the Atrium. Wikipedia.


Jardine A.G.,University of Glasgow | Gaston R.S.,University of Alabama at Birmingham | Fellstrom B.C.,Uppsala University | Holdaas H.,University of Oslo
The Lancet | Year: 2011

Although advances in immunosuppression, tissue typing, surgery, and medical management have made transplantation a routine and preferred treatment for patients with irreversible renal failure, successful transplant recipients have a greatly increased risk of premature mortality because of cardiovascular disease and malignancy compared with the general population. Conventional cardiovascular risk factors such as hyperlipidaemia, hypertension, and diabetes are common in transplant recipients, partly because of the effects of immunosuppressive drugs, and are associated with adverse outcomes. However, the natural history of cardiovascular disease in such recipients differs from that in the general population, and only statin therapy has been studied in a large-scale interventional trial. Thus, the management of this disease and the balance between management of conventional risk factors and modification of immunosuppression is complex. © 2011 Elsevier Ltd.


Arntzen M.O.,University of Oslo
Molecular & cellular proteomics : MCP | Year: 2012

Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt-KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no.


Kululanga L.I.,University of Oslo
African journal of reproductive health | Year: 2012

This study was conducted in Mwanza district in southern Malawi with the aim of investigating the individual's, community's and health workers' perception of male involvement in maternal health care. In-depth interviews and focus group discussions were the methods used for data collection. The participants' responses generated two main themes namely male involvement in health facility care and outside the health facility. The participants' perception of male involvement in facility care concentrated around six sub-themes describing male involvement as; couple HIV counselling and testing; a government law; a strategy for fast services for women; unfair programme for women without partners; a foreign concept; an act of love. We conclude that male involvement in the health facility care was fragmented and associated mainly with first antenatal care; couple HIV counselling and testing; suggesting poor integration of male involvement into the existing maternal and child health programmes and that there is need to engender maternal health care services.


Seljebotn D.S.,University of Oslo
Astrophysical Journal, Supplement Series | Year: 2012

We present Wavemoth, an experimental open source code for computing scalar spherical harmonic transforms (SHTs). Such transforms are ubiquitous in astronomical data analysis. Our code performs substantially better than existing publicly available codes owing to improvements on two fronts. First, the computational core is made more efficient by using small amounts of pre-computed data, as well as paying attention to CPU instruction pipelining and cache usage. Second, Wavemoth makes use of a fast and numerically stable algorithm based on compressing a set of linear operators in a pre-computation step. The resulting SHT scales as O(L 2log 2 L) for the resolution range of practical interest, where L denotes the spherical harmonic truncation degree. For low- and medium-range resolutions, Wavemoth tends to be twice as fast as libpsht, which is the current state-of-the-art implementation for the HEALPix grid. At the resolution of the Planck experiment, L 4000, Wavemoth is between three and six times faster than libpsht, depending on the computer architecture and the required precision. Because of the experimental nature of the project, only spherical harmonic synthesis is currently supported, although adding support for spherical harmonic analysis should be trivial. © 2012. The American Astronomical Society. All rights reserved.


Jenssen T.,University of Tromso | Hartmann A.,University of Oslo
Nature Reviews Nephrology | Year: 2015

Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM), occurs in 10-15% of renal transplant recipients and is associated with cardiovascular disease and reduced lifespan. In the majority of cases, PTDM is characterized by β-cell dysfunction, as well as reduced insulin sensitivity in liver, muscle and adipose tissue. Glucose-lowering therapy must be compatible with immunosuppressant agents, reduced glomerular filtration rate (GFR) and severe arteriosclerosis. Such therapy should not place the patient at risk by inducing hypoglycaemic episodes or exacerbating renal function owing to adverse gastrointestinal effects with hypovolaemia. First-generation and second-generation sulphonylureas are generally avoided, and caution is currently advocated for the use of metformin in patients with GFR <60 ml/min/1.73 m 2. DPP-4 inhibitors do not interact with immunosuppressant drugs and have demonstrated safety in small clinical trials. Other therapeutic options include glinides and glitazones. Evidence-based treatment regimens used in patients with type 2 diabetes mellitus cannot be directly implemented in patients with PTDM. Studies investigating the latest drugs are required to direct the development of improved treatment strategies for patients with PTDM. This Review outlines the modern principles of glucose-lowering treatment in PTDM with specific reference to renal transplant recipients. © 2015 Macmillan Publishers Limited.


Furberg A.,University of Oslo
International Journal of Computer-Supported Collaborative Learning | Year: 2016

This paper reports on a study of teacher support in a setting where students engaged with computer-supported collaborative learning (CSCL) in science. The empirical basis is an intervention study where secondary school students and their teacher performed a lab experiment in genetics supported by a digital learning environment. The analytical focus is on student-teacher interactions taking place in help-seeking settings during group-based activities where students analysed and reported their findings from the lab experiment. A combination of quantitative methods in the form of frequency counts of students’ help requests and detailed micro-analyses of student-teacher interactions are used. The findings are that the majority of challenges faced by students concerned conceptually oriented issues and procedural challenges in the sense of how to practically solve the assignments provided to them in the digital learning environment. Most importantly, the analyses of student-teacher interactions provide insight into the considerable amount of support that is needed from the teacher to bridge the conceptual gap between the lab experiment and the students’ understanding of the underlying scientific principles and procedures. The findings are discussed according to possible implications for the design of digital support tools and instruction. © 2016, The Author(s).


Von Soest T.,University of Oslo | Von Soest T.,Norwegian Social Research | Wichstrom L.,Norwegian University of Science and Technology
Journal of Abnormal Child Psychology | Year: 2014

Several survey studies among adolescents have shown increasing rates of depressive symptoms over the last two to three decades. We know however little about mechanisms that might explain this increase. The present study uses data from three nationwide representative surveys of 16-17 year-old Norwegian adolescents that were conducted according to identical procedures in 1992, 2002, and 2010 (response rates 97.0, 91.0, 84.3 %, respectively). At each time point, approximately 3,000 adolescents participated (48.8 % girls and 51.2 % boys). Questionnaire data on depressive symptoms and a variety of potential risk and protective factors that might explain time trends in such symptoms were assessed at all time points. The results showed that the prevalence of high scores on depressive symptoms increased significantly between 1992 and 2002 among both boys and girls. No significant changes were observed between 2002 and 2010. The increase from 1992 to 2002 among girls and boys could be partially attributed to increases in eating problems and cannabis use, while reduced satisfaction with own appearance among girls contributed as well. Although the study does not provide information about the causal direction between putative risk factors and depressive symptoms, the results provide some indication that eating problems, cannabis use, and appearance related factors may contribute in explaining secular trends in depressive symptoms. © 2013 Springer Science+Business Media New York.


Van Hinsbergen D.J.J.,University Utrecht | Vissers R.L.M.,University Utrecht | Spakman W.,University Utrecht | Spakman W.,University of Oslo
Tectonics | Year: 2014

The western Mediterranean recorded subduction rollback, slab segmentation and separation. Here we address the questions of what caused Oligocene rollback initiation, and how its subsequent evolution split up an originally coherent fore arc into circum-southwest Mediterranean segments. We kinematically reconstruct western Mediterranean geology from subduction initiation to present, using Atlantic plate reconstructions as boundary condition. We test possible reconstructions against remnants of subducted lithosphere imaged by seismic tomography. Transform motion between Africa and Iberia (including the Baleares) between ∼120 and 85 Ma was followed by up to 150 km convergence until 30 Ma. Subduction likely initiated along the transform fault that accommodated pre-85 Ma translation. By the ∼30 Ma inception of rollback, up to 150 km of convergence had formed a small slab below the Baleares. Iberia was disconnected from Sardinia/Calabria through the North Balearic Transform Zone (NBTZ). Subduction below Sardinia/Calabria was slightly faster than below the Baleares, the difference being accommodated in the Pyrenees. A moving triple junction at the trench-NBTZ intersection formed a subduction transform edge propagator fault between the Baleares and Calabria slab segments. Calabria rolled back eastward, whereas the Baleares slab underwent radial (SW-S-SE) rollback. After Kabylides-Africa collision, the western slab segment retreated toward Gibraltar, here reconstructed as the maximum rollback end-member model, and a Kabylides slab detached from Africa. Opening of a slab window below the NBTZ allowed asthenospheric rise to the base of the fore arc creating high-temperature metamorphism. Western Mediterranean rollback commenced only after sufficient slab-pull was created from 100 to 150 km of slow, forced subduction before ∼30 Ma. ©2014. American Geophysical Union. All Rights Reserved.


Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.


Jimenez J.B.,Leuven University | Koivisto T.S.,University of Oslo | Koivisto T.S.,KTH Royal Institute of Technology
Classical and Quantum Gravity | Year: 2014

In this paper we consider an extended Gauss-Bonnet gravity theory in arbitrary dimensions and in a space provided with a Weyl connection, which is torsion-free but non-metric-compatible, the non-metricity tensor being determined by a vector field. The action considered consists of the usual Einstein-Hilbert action plus all the terms quadratic in the curvature that reduce to the usual Gauss-Bonnet term for vanishing Weyl connection, i.e., when only the Levi-Civita part of the connection is present. We expand the action in terms of Riemannian quantities and obtain vector-tensor theories. We find that all the free parameters only appear in the kinetic term of the vector field, so two branches are possible: one with a propagating vector field and another one where the vector field does not propagate. We focus on the propagating case. We find that in four dimensions, the theory is equivalent to Einstein's gravity plus a Proca field. This field is naturally decoupled from matter, so it represents a natural dark matter candidate. Also for d = 4, we discuss a non-trivial cubic term in the curvature that can be constructed without spoiling the second-order nature of the field equations, because it leads to the vector-tensor Horndeski interaction. In arbitrary dimensions, the theory becomes more involved. We show that, even though the vector field presents kinetic interactions which do not have symmetry, there are no additional propagating degrees of freedom with respect to the usual massive case. We show that, interestingly, this relies on the fact that the corresponding Stückelberg field belongs to a specific class within the general Horndeski theories. Finally, since Weyl geometries provide the natural ground on which to build scale invariant theories, we apply the usual Weyl gauging in order to make the Horndeski action locally scale invariant, and discuss new terms that can be added. © 2014 IOP Publishing Ltd.


Kumar M.,KTH Royal Institute of Technology | Persson C.,KTH Royal Institute of Technology | Persson C.,University of Oslo
Applied Physics Letters | Year: 2013

Cu3BiS3 is a potential photovoltaic material. Employing a first-principles approach, we calculate the structural, electronic, and optical properties of Cu3BiS3, and we demonstrate that Cu3BiS3 is an indirect band gap semiconductor in contrast to similar chalcogenide semiconductors. The fundamental band gap energy is estimated to be Eg ≈ 1.5-1.7 eV. The analysis reveals that Cu 3BiS3 has a much stronger absorption coefficient (>105 cm-1) compared to other Cu-S based materials like CuInS2 and Cu2ZnSnS4. This is explained by the presence of localized Bi 6p states in the band gap region, generating a flat lowest conduction band. © 2013 American Institute of Physics.


Djenouri D.,CERIST Research Center | Balasingham I.,University of Oslo
IEEE Transactions on Mobile Computing | Year: 2011

A new localized quality of service (QoS) routing protocol for wireless sensor networks (WSN) is proposed in this paper. The proposed protocol targets WSN's applications having different types of data traffic. It is based on differentiating QoS requirements according to the data type, which enables to provide several and customized QoS metrics for each traffic category. With each packet, the protocol attempts to fulfill the required data-related QoS metric(s) while considering power efficiency. It is modular and uses geographical information, which eliminates the need of propagating routing information. For link quality estimation, the protocol employs distributed, memory and computation efficient mechanisms. It uses a multisink single-path approach to increase reliability. To our knowledge, this protocol is the first that makes use of the diversity in data traffic while considering latency, reliability, residual energy in sensor nodes, and transmission power between nodes to cast QoS metrics as a multiobjective problem. The proposed protocol can operate with any medium access control (MAC) protocol, provided that it employs an acknowledgment (ACK) mechanism. Extensive simulation study with scenarios of 900 nodes shows the proposed protocol outperforms all comparable state-of-the-art QoS and localized routing protocols. Moreover, the protocol has been implemented on sensor motes and tested in a sensor network testbed. © 2011 IEEE.


Skarstad K.,University of Oslo | Katayama T.,Kyushu University
Cold Spring Harbor Perspectives in Biology | Year: 2013

The replication origin and the initiator protein DnaA are the main targets for regulation of chromosome replication in bacteria. The origin bears multiple DnaA binding sites, while DnaA contains ATP/ADP-binding and DNA-binding domains. When enough ATP-DnaA has accumulated in the cell, an active initiation complex can be formed at the origin resulting in strand opening and recruitment of the replicative helicase. In Escherichia coli, oriC activity is directly regulated by DNA methylation and specific oriC-binding proteins. DnaA activity is regulated by proteins that stimulate ATP-DnaA hydrolysis, yielding inactive ADP-DnaA in a replication-coupled negative-feedback manner, and by DnaA-binding DNA elements that control the subcellular localization of DnaA or stimulate the ADP-to-ATP exchange of the DnaA-bound nucleotide. Regulation of dnaA gene expression is also important for initiation. The principle of replication-coupled negative regulation of DnaA found in E. coli is conserved in eukaryotes as well as in bacteria. Regulations by oriC-binding proteins and dnaA gene expression are also conserved in bacteria. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.


Hammersvik E.,University of Oslo
International Journal of Drug Policy | Year: 2015

Background: Cannabis markets are often described as less violent than other drug markets. Domestic cannabis cultivation markets seem to be especially non-violent. However, few studies have investigated why this might be. Methods: Two and half years of ethnographic fieldwork among indoor cannabis growers and interviews and conversations with 52 growers in Norway. Results: This study identified four barriers and a set of values that prevent violence among growers. (1) Violence attracts increased attention from police and enemies, which inhibits 'business as usual' and reduces profits. (2) Careful attention to profits makes growers calculate and prepare for financial losses. (3) The prospect of covering debt by producing more cannabis makes it possible to choose non-violent sanctions. (4) Tight social ties and friendships prevent violence when conflicts erupt. However, the cannabis culture of the actors and the transactions stands out as the main reason why these four barriers are more important in cannabis markets than in other drug markets. Conclusion: This paper discusses how policymakers can benefit from the market changes that follow 'import substitution' to construct policies that prevent violence and facilitate peaceful drug markets and drug cultures. © 2014 Elsevier B.V.


Pedersen W.,University of Oslo
Addiction Research and Theory | Year: 2015

While the use of legal medical cannabis is increasing in the USA, the trend is less pronounced in Europe. However, several studies indicate that illegal cannabis use is increasingly given medical justification even in European countries. In this qualitative study of cannabis users in Norway (N = 100), a considerable proportion reported that they used cannabis for allegedly medical reasons, even if none of them had obtained cannabis legally. Attention deficit hyperactivity disorder (ADHD) was the most prevalent medical motive reported (n = 18), although most users had self-diagnosed this condition. We found that: (i) the ADHD diagnosis was typically a response to various social problems in the participants' lives; (ii) cannabis reduced symptoms believed to be associated with ADHD and thus reinforced the perceived validity of the diagnosis; (iii) symbolic boundaries were drawn to cannabis used for intoxication and pleasure; and (iv) cannabis was compared with traditional ADHD medications, which were described as more harmful. The findings suggest that stigmatising social problems and drug use may be transformed into "illness" by means of an ADHD diagnosis, reflecting widespread processes of medicalisation. However, at the same time, drawing on the "green" values in the cannabis culture, participants substituted traditional ADHD medication with cannabis. © 2014 Informa UK Ltd.


Karterud S.,University of Oslo
Group Analysis | Year: 2015

Mentalization-based group therapy (MBT-G) has its roots in group analytic psychotherapy. Modifications were made in order to suit the needs of more disturbed personality disordered patients, and to avoid the chaotic and destructive processes often encountered in groups dominated by these patients. In this article I outline the kind of leadership, structure and authority that MBT proscribes and discuss these principles in comparison with group analysis. I also comment upon a study of a MBT group that failed to establish a good mentalizing culture, with reference to Bion’s concept of ‘attack on linking’. This study reminds us that strong professional support and competent supervision is necessary in order to achieve sound communicational ideals, when the group is composed of members who easily resort to prementalistic modes of thinking. © The Author(s), 2015.


α2-Adrenoceptors lower central sympathetic output and peripheral catecholamine release, and thus may prevent sympathetic hyperactivity and hypertension. α2AR also influence vascular tension. These α2AR are malfunctioning in spontaneously hypertensive rats (SHR). Here I tested if an interaction between α2AR subtypes and the angiotensin AT1 receptor (AT1R) precipitated these disorders. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in anesthetized rats. Catecholamine concentrations were determined in plasma collected at the end of a 15-min tyramine-infusion. Tyramine stimulates norepinephrine release through the re-uptake transporter, thus preventing re-uptake. Presynaptic control of vesicular release is therefore reflected as differences in overflow to plasma. Previous experiments showed surgical stress to activate some secretion of epinephrine, also subjected to α2AR-auto-inhibition. Normotensive rats (WKY) and SHR were pre-treated with (1) vehicle or α2AR-antagonist (L-659,066), followed by fadolmidine (α2C>B>A + α1AR-agonist), ST-91 (α2non-A-selective agonist), or m-nitrobiphenyline (α2CAR-agonist + α2A+B-antagonist), or (2) AT1R-antagonist losartan, losartan + L-659,066, or losartan + clonidine. In WKY, L-659,066 alone, L-659,066 + agonist or losartan + L-659,066 increased catecholamine overflow to plasma after tyramine and eliminated the norepinephrine-induced rise in total peripheral vascular resistance (TPR). In SHR, L-659,066 + fadolmidine/ST-91/m-nitrobiphenyline and losartan + L-659,066 greatly increased, and losartan + clonidine reduced, catecholamine concentrations, and L-659,066 + ST-91, losartan + L-659,066 and losartan + clonidine eliminated the tyramine-induced rise in TPR. Separately, these drugs had no effect in SHR. In conclusion, peripheral α2CAR-stimulation or AT1R-inhibition restored failing α2AAR-mediated auto-inhibition of norepinephrine and epinephrine release and control of TPR in SHR. © 2013 Berg.


Ben Ari T.,University of Oslo
PLoS pathogens | Year: 2011

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations.


The aim was to compare the protein release from normal human osteoblasts (NHO) cultured on scaffolds with similar morphology but different coatings. Different ceramic coatings; TiO(2), SiO(2) and calcium phosphate (CaP); Ca(9)HPO(4)(PO(4))(5)OH, were applied to porous TiO(2) scaffolds prepared by polymer sponge replication. NHO were cultured on scaffolds in triplicates. The concentration of cytokines and Ca(2+), and alkaline phosphatase (ALP) activity in the cell media was quantified. The secretion of osteopontin, osteoprotegerin, vascular endothelial growth factor and interleukin-6 was higher from NHO on TiO(2) compared to SiO(2) and CaP. The secretion from cells on the three scaffolds was, however, either similar or lower than the control cells cultured on plastic. The Ca(2+) concentration was higher in cell media on CaP the first week, and no difference in ALP activity was observed. TiO(2) coating induced a higher secretion of factors indicating enhanced osteoblast differentiation as compared to CaP and SiO(2).


Asdal K.,University of Oslo
Science Technology and Human Values | Year: 2012

Since the early 1980s, actor-network theory has contested the status of "context" as an explanatory resource. Expressions and concepts such as "transformations of social worlds," "enactments," and "ontological politics" provide resources for grasping the ways in which agents actively transform the world and add something new. This has been of immense importance and serves as a warning against reducing events and actors to a given context. But a side effect of this forward looking move is that not enough attention is given to that which enables issues and situations to emerge in the first place. Moreover, the focus on that which is constantly being enacted seems to have privileged the contemporary as the object of study and ethnography as the method of inquiry. History and the study of texts-from the past-seem, increasingly, to get lost in Science and Technology Studies. The aim of this article is instead to use actor-network theory resources as a historicizing method. The article explores the tense concern for the animal in political debates at the turn of the twentieth century. The article argues that contexts should not be seen as something external, but rather integral to the relevant text and situation, thus the very issue at stake. © The Author(s).


Brown I.A.,University of Oslo
Astrophysical Journal | Year: 2011

Forthcoming data sets from the Planck experiment and others are in a position to probe the cosmic microwave background (CMB) non-Gaussianity with higher accuracy than has yet been possible, and potentially open a new window into the physics of the very early universe. However, a signal need not necessarily be inflationary in origin, and possible contaminants should be examined in detail. One such is provided by early universe magnetic fields, which can be produced by a variety of models including during an inflationary phase, at phase transitions, or seeded by cosmic defects. Should such fields have been extant in the early universe, they would provide a natural source of CMB non-Gaussianity. Knowledge of the CMB angular bispectrum requires the complete Fourier-space (or "intrinsic") bispectrum. In this paper, I consider in detail the intrinsic bispectra of an early-universe magnetic field for a range of power-law magnetic spectra. © 2011. The American Astronomical Society. All rights reserved.


Sachs-Olsen C.,University of Oslo
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2010

Fractional exhaled nitric oxide (FE(NO) ) has been proposed as a diagnostic test of asthma. We aimed to investigate in a population based birth cohort of children the usefulness of FE(NO) as a diagnostic tool. The 10-yr follow up of the Environment and Childhood Asthma Study in Oslo included 616 children representative of the prospective birth cohort. Both FE(NO) (single breath technique) and skin prick test (SPT) were measured in 331, limited at the time by equipment availability. Structural parental interview, spirometry, methacholine challenge and exercise test were performed. FE(NO) was significantly elevated in children with current asthma (geometric mean 9.6 (95% confidence interval (CI) (6.9, 13.4) p.p.b.) compared with healthy children (5.8 (5.4, 6.3) p.p.b.; p < 0.001). FE(NO) was highest among children with current allergic asthma (asthma and positive SPT) (14.0 (8.9, 22.1) p.p.b.), whereas children with non-allergic asthma (6.1 (4.0, 9.2) p.p.b.) had comparable FE(NO) levels to healthy children (p = 0.99). Allergic sensitization was most closely associated with FE(NO) . A FE(NO) cut-off value of 20.4 p.p.b. had a high specificity (0.97), but a low sensitivity (0.41) and a Positive Likelihood Ratio of 16.1 for current allergic asthma. In the present childhood population-based study, high FE(NO) levels were closely associated with current allergic asthma and not with current asthma without allergic sensitization. Estimating the individual predictive probability of having asthma by use of FE(NO,) improves the diagnostic utility of the test. © 2010 John Wiley & Sons A/S.


To explore direct associations between home and school availability of fruit and fruit intake, and the mediating role of attitude towards fruit, liking, perceived barriers and self-efficacy. Cross-sectional study. Primary schools in nine European countries. Within the Pro Children study, data were collected on perceived home and school availability of fruit, psychosocial factors related to fruit intake and its frequency among 13 305 11-year-old schoolchildren. Significant overall associations were found between child-reported home availability of fruit and fruit intake in all countries and in the total sample. School availability of fruit was associated with fruit intake in the pooled sample and in country-specific analyses in Sweden and the Netherlands. Liking (13·2-49·4 %) and self-efficacy (14·0-25·1 %) were the strongest mediators in the home availability-fruit intake relationship, but there was also a direct association between home availability and fruit intake, except in Spain and the Netherlands. Mediating pathways of the school availability-fruit intake relationship could only be assessed for Norway, Sweden and the total sample. Attitude was a significant mediator in Norway (80·4 %) and in Sweden (25·3 %), while in the total sample also liking (38·7 %) and self-efficacy (23·0 %) were identified as significant mediators. The association between home availability of fruit and fruit intake is at least partly mediated by personal factors such as liking and self-efficacy indicates that fruit intake is not a complete automatic or unconscious behaviour.


Johannessen A.,University of Oslo
Journal of Viral Hepatitis | Year: 2015

Viral hepatitis claims one million lives each year. Scaling up treatment for hepatitis B and C in resource-limited settings is not possible without access to reliable diagnostic tools. This article gives an overview of current technologies and the pipeline for easy-to-use assays for serological and virological analyses, which can be performed at the site of patient care ('point-of-care assays'). Furthermore, the utility of dried blood spots for hepatitis B and C viral load testing is discussed. In addition to simple and reliable diagnostics, there is a need for a sustainable funding scheme and generic production of antiviral drugs to reduce the burden of viral hepatitis worldwide. © 2015 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.


Putora P.M.,Kantonsspital St. Gallen | Oldenburg J.,University of Oslo
Journal of Medical Internet Research | Year: 2013

Occasionally, medical decisions have to be taken in the absence of evidence-based guidelines. Other sources can be drawn upon to fill in the gaps, including experience and intuition. Authorities or experts, with their knowledge and experience, may provide further input-known as "eminence-based medicine". Due to the Internet and digital media, interactions among physicians now take place at a higher rate than ever before. With the rising number of interconnected individuals and their communication capabilities, the medical community is obtaining the properties of a swarm. The way individual physicians act depends on other physicians; medical societies act based on their members. Swarm behavior might facilitate the generation and distribution of knowledge as an unconscious process. As such, "swarm-based medicine" may add a further source of information to the classical approaches of evidence- and eminence-based medicine. How to integrate swarm-based medicine into practice is left to the individual physician, but even this decision will be influenced by the swarm.


Enserink J.M.,University of Oslo
Cell Division | Year: 2015

The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which Sumo can regulate transcription. Although many individual substrates have been described that are sumoylated during the Sumo stress response, an emerging concept is modification of entire complexes or pathways by Sumo. This review focuses on the function and regulation of Sumo during the stress response. 2015 © Enserink.


Holm S.,University of Oslo
Journal of Atmospheric and Solar-Terrestrial Physics | Year: 2014

It has recently been claimed that there is significant coherence between the spectral peaks of the global temperature series over the last 160 years and those of the speed of the solar center of mass at periods of 10-10.5, 20-21, 30 and 60-62 years. Here it is shown that these claims are based on a comparison between spectral peaks in spectral estimates that assume that the global temperature data contains time-invariant spectral lines. However, time-frequency analysis using both windowed periodograms and the maximum entropy method shows that this is not the case. An estimate of the magnitude squared coherence shows instead that under certain conditions only coherence at a period of 15-17 years can be found in the data. As this result builds on a low number of independent averages and also is unwarranted from any physical model it is doubtful whether it is significant. © 2014 Elsevier Ltd.


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.


Sorensen C.S.,Copenhagen University | Syljuasen R.G.,University of Oslo
Nucleic Acids Research | Year: 2012

Mechanisms that preserve genome integrity are highly important during the normal life cycle of human cells. Loss of genome protective mechanisms can lead to the development of diseases such as cancer. Checkpoint kinases function in the cellular surveillance pathways that help cells to cope with DNA damage. Importantly, the checkpoint kinases ATR, CHK1 and WEE1 are not only activated in response to exogenous DNA damaging agents, but are active during normal S phase progression. Here, we review recent evidence that these checkpoint kinases are critical to avoid deleterious DNA breakage during DNA replication in normal, unperturbed cell cycle. Possible mechanisms how loss of these checkpoint kinases may cause DNA damage in S phase are discussed. We propose that the majority of DNA damage is induced as a consequence of deregulated CDK activity that forces unscheduled initiation of DNA replication. This could generate structures that are cleaved by DNA endonucleases leading to the formation of DNA double-strand breaks. Finally, we discuss how these S phase effects may impact on our understanding of cancer development following disruption of these checkpoint kinases, as well as on the potential of these kinases as targets for cancer treatment. © The Author(s) 2011. Published by Oxford University Press.


Buer J.K.,University of Oslo
Inflammopharmacology | Year: 2015

The article outlines a history of the concept of “disease-modifying antirheumatic drugs” or DMARDs—from the emergence in the 1970s of the idea of drugs with decisive long-term effects on bone erosion in rheumatoid arthritis (RA), through the consolidation and popularisation in the term DMARD in 1980s and 1990s. It then examines the usage of the terms “remission-inducing drugs” (RIDs) and “slow-acting anti-rheumatic drugs” (SAARDs), which for some years offered competition to the term DMARDs, thus underscoring the contingency of the establishment of DMARD as a word. Finally, it juxtaposes the apparently spontaneous emergence of the three terms DMARD, SAARD and RID, and the disappearance of the latter two, with a failed attempt in the early 1990s to replace these terms with the new term “disease-controlling antirheumatic treatment” (DC-ART). The analysis highlights the paradoxical qualities of the DMARD concept as robust albeit tension ridden, while playing down the role of identified individuals and overarching explanations of purpose. © 2015, The Author(s).


Heise L.L.,London School of Hygiene and Tropical Medicine | Kotsadam A.,University of Oslo
The Lancet Global Health | Year: 2015

Background: On average, intimate partner violence affects nearly one in three women worldwide within their lifetime. But the distribution of partner violence is highly uneven, with a prevalence of less than 4% in the past 12 months in many high-income countries compared with at least 40% in some low-income settings. Little is known about the factors that drive the geographical distribution of partner violence or how macro-level factors might combine with individual-level factors to affect individual women's risk of intimate partner violence. We aimed to assess the role that women's status and other gender-related factors might have in defining levels of partner violence among settings. Methods: We compiled data for the 12 month prevalence of partner violence from 66 surveys (88 survey years) from 44 countries, representing 481 205 women between Jan 1, 2000, and Apr 17, 2013. Only surveys with comparable questions and state-of-the-art methods to ensure safety and encourage violence disclosure were used. With linear and quantile regression, we examined associations between macro-level measures of socioeconomic development, women's status, gender inequality, and gender-related norms and the prevalence of current partner violence at a population level. Multilevel modelling and tests for interaction were used to explore whether and how macro-level factors affect individual-level risk. The outcome for this analysis was the population prevalence of current partner violence, defined as the percentage of ever-partnered women (excluding widows without a current partner), aged from 15 years to 49 years who were victims of at least one act of physical or sexual violence within the past 12 months. Findings: Gender-related factors at the national and subnational level help to predict the population prevalence of physical and sexual partner violence within the past 12 months. Especially predictive of the geographical distribution of partner violence are norms related to male authority over female behaviour (0·102, p<0·0001), norms justifying wife beating (0·263, p<0·0001), and the extent to which law and practice disadvantage women compared with men in access to land, property, and other productive resources (0·271, p<0·0001). The strong negative association between current partner violence and gross domestic product (GDP) per person (-0·055, p=0·0009) becomes non-significant in the presence of norm-related measures (-0·015, p=0·472), suggesting that GDP per person is a marker for social transformations that accompany economic growth and is unlikely to be causally related to levels of partner violence. We document several cross-level effects, including that a girl's education is more strongly associated with reduced risk of partner violence in countries where wife abuse is normative than where it is not. Likewise, partner violence is less prevalent in countries with a high proportion of women in the formal work force, but working for cash increases a woman's risk in countries where few women work. Interpretation: Our findings suggest that policy makers could reduce violence by eliminating gender bias in ownership rights and addressing norms that justify wife beating and male control of female behaviour. Prevention planners should place greater emphasis on policy reforms at the macro-level and take cross-level effects into account when designing interventions. Funding: What Works to Prevent Violence Against Women and Girls-a research and innovation project funded by UK Aid. © 2015 Heise et al. Open access article published under the terms of CC BY.


Domestic infrastructural information and communication technology (ICT) standards can be items of assertion for newly industrialised countries as they signal a capacity for breaking dependence on foreign technology and potentially drawing revenue from international export. This paper asks, with an in-depth study of a selection of recent South Korean and Chinese infrastructural ICT standards, to what degree it is warranted to correlate the production of standards with dependency-breaking technological capacity. A composite picture is found. On one side, a large portion of promoted domestic standards are creative imitations of foreign technologies with limited, if any, proportions of embedded domestic patents. This indicates a lack of capacity for challenging technological dependence. On the other side, several of the technologies studied signal emerging South Korean and Chinese capacity for embedding cutting-edge patents in infrastructural ICT standards when participating in global standardisation consortiums. © 2011 Elsevier Ltd. All rights reserved.


Redman C.W.,John Radcliffe Hospital | Staff A.C.,University of Oslo
American journal of obstetrics and gynecology | Year: 2015

The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity. Copyright © 2015 Elsevier Inc. All rights reserved.


Hessen D.O.,University of Oslo | Jeyasingh P.D.,Oklahoma State University | Neiman M.,University of Iowa | Weider L.J.,University of Oklahoma
Trends in Ecology and Evolution | Year: 2010

Pervasive relationships between growth rate, genome size and RNA content exist. One interesting potential consequence of these interrelationships is that selection for high growth rate should be associated with small genomes and high RNA content. Here, we use phosphorus (P) and nitrogen (N) demands of growth along with nucleic acid production as the currency to explore the interrelationships between growth rate and genome size in eukaryotes. We argue that reallocation of P (and eventually N) from DNA to RNA under sustained selection for rapid growth in nutritionally limited environments can lead to genome streamlining in eukaryotes, and that this mechanism might contribute to the evolution of reduced genome size. © 2009 Elsevier Ltd.


Brandtzaeg P.,University of Oslo
Beneficial Microbes | Year: 2010

In the process of evolution, the mucosal immune system has generated two layers of anti-inflammatory defence: (1) immune exclusion performed by secretory IgA (and secretory IgM) antibodies to modulate or inhibit surface colonisation of microorganisms and dampen penetration of potentially dangerous antigens; and (2) suppressive mechanisms to avoid local and peripheral hypersensitivity to innocuous antigens, particularly food proteins and components of commensal bacteria. When induced via the gut, the latter phenomenon is called 'oral tolerance', which mainly depends on the development of regulatory T (Treg) cells in mesenteric lymph nodes to which mucosal dendritic cells (DCs) carry exogenous antigens and become conditioned for induction of Treg cells. Mucosally induced tolerance appears to be a rather robust adaptive immune function in view of the fact that large amounts of food proteins pass through the gut, while overt and persistent food allergy is not so common. DCs are 'decision makers' in the immune system when they perform their antigen-presenting function, thus linking innate and adaptive immunity by sensing the exogenous mucosal impact (e.g. conserved microbial molecular patterns). A balanced indigenous microbiota is required to drive the normal development of both mucosa-associated lymphoid tissue, the epithelial barrier with its secretory IgA (and IgM) system, and mucosally induced tolerance mechanisms including the generation of Treg cells. Notably, polymeric Ig receptor (pIgR/SC) knock-out mice that lack secretory IgA and IgM antibodies show reduced epithelial barrier function and increased uptake of antigens from food and commensal bacteria. They therefore have a hyper-reactive immune system and show predisposition for systemic anaphylaxis after sensitisation; but this development is counteracted by enhanced oral tolerance induction as a homeostatic back-up mechanism. © 2010 Wageningen Academic Publishers.


In 2004 Norway implemented a food safety reform programme aimed at enhancing inter-organizational coordination processes and outcomes. Has this programme affected inter-organizational coordination processes and outcomes, both vertically and horizontally - and if so how? This article employs the concept of inter-organizational coordination as an analytical tool, examining it in the light of two theoretical perspectives and coupling it with the empirical findings. The argument presented is that the chances of strong coordination outcomes may increase if inter-organizational processes feature a clear division of labour, arenas for coordination, active leadership, a lack of major conflicting goals, and shared obligations. © 2010 The Author. Public Administration © 2010 Blackwell Publishing Ltd.


Holden S.,University of Oslo
Energy Policy | Year: 2013

In many countries, natural resources have been detrimental to the economic development. The literature on "the resource curse" shows a bleak relationship: countries with large natural resources generally experience lower economic growth than other countries. Norway does not fit into this picture. Economic growth has much higher than in most other industrialized countries. This paper describes the key features of the Norwegian management of the petroleum resources. The main focus is on the management of the revenues from the petroleum sector, but the effects of the petroleum sector on the Norwegian economy more generally are also discussed. © 2013 Elsevier Ltd.


Dijkstra M.,University of Oslo | Dijkstra M.,Max Planck Institute for Astrophysics | Ferrara A.,Normal School of Pisa | Mesinger A.,Normal School of Pisa
Monthly Notices of the Royal Astronomical Society | Year: 2014

The nature of the seeds of high-redshift supermassive black holes (SMBHs) is a key question in cosmology. Direct collapse black holes (DCBHs) that form in pristine, atomic-line cooling haloes, illuminated by a Lyman-Werner (LW) UV flux exceeding a critical threshold Jcrit represent an attractive possibility. We investigate when and where these conditions are met during cosmic evolution. For the LW intensity, JLW, we account for departures from the background value in close proximity to star-forming galaxies. For the pristine halo fraction, we account for both (i) supernova-driven outflows and (ii) the inherent pollution from progenitor haloes.We estimate the abundance ofDCBHformation sites, nDCBH(z), and find that it increases with cosmic time from nDCBH(z = 20) ~ 10-12-10-7 cMpc-3 to nDCBH(z = 10) ~ 10-10- 10-5 cMpc-3. Our analysis shows the possible importance of galactic winds, which can suppress the predicted nDCBH by several orders of magnitude, and cause DCBH formation to preferentially occur around the UV-brightest (MUV ~ -21 ± 1) star-forming galaxies. Our analysis further highlights the dependence of these predictions on (i) the escape fraction of LW photons, (ii) Jcrit, and (iii) the galactic outflow prescription.© 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Agewall S.,University of Oslo
Angiology | Year: 2012

Coronary heart disease (CHD) is the leading cause of mortality in the industrialized world and that might also soon be the case in other parts of the world. There are several easily measured and potentially modifiable risk factors that account for a substantial proportion of the risk of CHD. The effect of risk factors interventions appears to be consistent in both genders, across different geographic regions, and by all ethnic groups, suggesting that approaches to prevention can be based on similar principles worldwide. Optimal target levels for serum cholesterol and blood pressure are not yet clear. Future risk CHD reduction will mainly be achieved by improved primary prevention. © SAGE Publications 2012.


Seglen P.O.,University of Oslo | Brinchmann M.F.,Bodo University College
Autophagy | Year: 2010

To facilitate the purification of rat liver autophagosomes, isolated rat hepatocytes are first incubated for 2 h at 37° C with vinblastine, which induces autophagosome accumulation by blocking the fusion of these organelles with endosomes and lysosomes. The hepatocytes are then electrodisrupted and homogenized, and the various cellular organelles sequentially removed by subcellular fractionation. A brief incubation of the homogenate with the cathepsin C substrate, glycyl-phenylalanine-naphthylamide (GPN), causes rapid osmotic disruption of the lysosomes due to intralysosomal accumulation of GPN cleavage products. Nuclei are removed by differential centrifugation, and the postnuclear supernatant subsequently fractionated on a two-step Nycodenz density gradient. Autophagosomes are recovered in an intermediate density fraction, free from cytosol and mitochondria. The autophagosomes are finally separated from the membranes and vesicles of the endoplasmic reticulum, Golgi, endosomes, etc., by sieving through a density gradient of colloidal silica particles (Percoll). The final preparation contains about 95% autophagosomes and 5% amphisomes according to morphological and biochemical criteria. © 2010 Landes Bioscience.


Bordiga S.,University of Turin | Bonino F.,University of Turin | Lillerud K.P.,University of Oslo | Lamberti C.,University of Turin
Chemical Society Reviews | Year: 2010

The large unit cells, the enormous flexibility and variation in structural motifs of MOFs represent a big challenge in the characterization of MOF materials, particularly in cases where single crystal diffraction data are not available. In this critical review it is shown that in cases where only powder diffraction data are available additional structural information, particularly regarding local coordination within the inorganic cluster, are often mandatory in order to solve the structure. There are also cases where the inorganic cluster does not follow the symmetry of the overall structure. In such cases diffraction techniques will just "see" an average structure, missing the local structure: a lack that may be critical for understanding the specific properties of the material. In both cases, EXAFS spectroscopy is the tool that provides complementary structural information on the inorganic cluster and the way it binds to the ligand. Selected examples will show how EXAFS will be relevant in: (i) confirming the structure obtained from diffraction refinements; (ii) highlighting that the inorganic cornerstone has a lower symmetry with respect to that of the organic framework; (iii) obtaining the local structure of the inorganic cluster in the desolvated material when desolvation causes a partial loss of long range order; (iv) obtaining the local structure of the inorganic cluster in the desolvated material after coordination of a probe (or reactant) molecule, including cluster deformation upon molecule coordination and metal-molecule binding distance; (v) evidencing the presence of impurities in the form of amorphous extra-phases (339 references). © 2010 The Royal Society of Chemistry.


Werner S.C.,University of Oslo | Tanaka K.L.,U.S. Geological Survey
Icarus | Year: 2011

For the boundaries of each chronostratigraphic epoch on Mars, we present systematically derived crater-size frequencies based on crater counts of geologic referent surfaces and three proposed " standard" crater size-frequency production distributions as defined by (a) a simple -2 power law, (b) Neukum and Ivanov, (c) Hartmann. In turn, these crater count values are converted to model-absolute ages based on the inferred cratering rate histories. We present a new boundary definition for the Late Hesperian-Early Amazonian transition. Our fitting of crater size-frequency distributions to the chronostratigraphic record of Mars permits the assignment of cumulative counts of craters down to 100. m, 1. km, 2. km, 5. km, and 16. km diameters to martian epochs. Due to differences in the " standard" crater size-frequency production distributions, a generalized crater-density-based definition to the chronostratigraphic system cannot be provided. For the diameter range used for the boundary definitions, the resulting model absolute age fits vary within 1.5% for a given set of production function and chronology model ages. Crater distributions translated to absolute ages utilizing different curve descriptions can result in absolute age differences exceeding 10%. © 2011 Elsevier Inc.


Serebruany V.L.,Johns Hopkins University | Atar D.,University of Oslo
Thrombosis and Haemostasis | Year: 2012

Central adjudication in randomised controlled outcome-driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events. It was the purpose of this investigation to determine the patterns of myocardial infarction (Ml) adjudication in the TRITON, RECORD, and PLATO trials. We were matching centrally-adjudicated Mi's (CAMI's) from the official trial publication with the site-reported Ml (SRMI's) count from the Food and Drug Administration's secondary analyses for the investigational compounds prasugrel (TRITON), rosiglitazone (RECORD), and ticagrelor (PLATO). CAMI numbers showed a remarkable discrepancy to SRMI's by more than a doubling of the difference: from 72 to 145 events in TRITON favoring prasugrel (from a hazard ratio [HR]=0.76, p=0.08; to a HR=0.76, p<0.001), and from 44 to 89 events in favour of ticagrelor in PLATO (from a HR=0.94, p=0.095; to a HR=0.84, p<0.001). In contrast, in the RECORD trial, the CAMI count was less than the SRMI count (from 24 to 8 events, from a HR=1.42, p=0.93; to a HR=1.14, p=0.96), in this case diminishing cardiovascular hazards in favour of rosiglitazone. In conclusion, central adjudication in the TRITON, the RECORD, and the PLATO trial turned out to have a critical impact on study outcomes. Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site reported events influencing the results of a major clinical trial. © Schattauer 2012.


To identify risk factors for knee osteoarthritis (OA) 10-15 years after anterior cruciate ligament (ACL) reconstruction. We hypothesized that quadriceps muscle weakness after ACL reconstruction would be a risk factor for radiographic and symptomatic radiographic knee OA 10-15 years later. Subjects with ACL reconstruction (n=258) were followed for 10-15 years. Subjects with unilateral injury at the 10-15-year followup were included in the present study. Outcomes included the Cincinnati knee score, knee joint laxity, hop performance, and isokinetic muscle strength tests at 6 months, 1 year, and 2 years postoperatively. At the 10-15-year followup, radiographs were taken and graded according to the Kellgren/Lawrence classification (range 0-4). Of the 212 subjects (82%) assessed at the 10-15-year followup, 164 subjects had unilateral injury. The mean±SD age at ACL reconstruction was 27.4±8.5 years. Increased age (odds ratio [OR] 1.06, 95% confidence interval [95% CI] 1.01-1.11) and meniscal injury and/or chondral lesion (OR 2.05, 95% CI 1.00-4.20) showed significantly higher odds for radiographic knee OA. Low self-reported knee function 2 years postoperatively (OR 0.95, 95% CI 0.92-0.98) and loss of quadriceps strength between the 2-year and the 10-15-year followup (OR 1.00, 95% CI 1.00-1.01) showed significantly higher odds for symptomatic radiographic knee OA. Quadriceps muscle weakness after ACL reconstruction was not significantly associated with knee OA. This study detected no association between quadriceps weakness after ACL reconstruction and knee OA as measured 10-15 years later. Copyright © 2010 by the American College of Rheumatology.


Griffiths G.,University of Oslo | Lucocq J.M.,University of St. Andrews
Histochemistry and Cell Biology | Year: 2014

Reliable antibodies represent crucial tools in the arsenal of the cell biologist and using them to localize antigens for immunocytochemistry is one of their most important applications. However, antibody-antigen interactions are much more complex and unpredictable than suggested by the old 'lock and key' analogy, and the goal of trying to prove that an antibody is specific is far more difficult than is generally appreciated. Here, we discuss the problems associated with the very complicated issue of trying to establish that an antibody (and the results obtained with it) is specific for the immunolabeling approaches used in light or electron microscopy. We discuss the increasing awareness that significant numbers of commercial antibodies are often not up to the quality required. We provide guidelines for choosing and testing antibodies in immuno-EM. Finally, we describe how quantitative EM methods can be used to identify reproducible patterns of antibody labeling and also extract specific labeling distributions. © 2014 The Author(s).


Forre M.,University of Bergen | Selsto S.,University of Oslo | Nepstad R.,University of Bergen
Physical Review Letters | Year: 2010

We develop an approximate model for the process of direct (nonsequential) two-photon double ionization of atoms. Employing the model, we calculate (generalized) total cross sections as well as energy-resolved differential cross sections of helium for photon energies ranging from 39 to 54 eV. A comparison with results of ab initio calculations reveals that the agreement is at a quantitative level. We thus demonstrate that this complex ionization process can be described by the simple model, providing insight into the underlying physical mechanism. Finally, we use the model to calculate generalized cross sections for the two-photon double ionization of neon in the nonsequential regime. © 2010 The American Physical Society.


Lenero-Bardallo J.A.,University of Oslo | Serrano-Gotarredona T.,Institute Microelectronica Of Seville | Linares-Barranco B.,Institute Microelectronica Of Seville
IEEE Journal of Solid-State Circuits | Year: 2011

This paper presents a 128 × 128 dynamic vision sensor. Each pixel detects temporal changes in the local illumination. A minimum illumination temporal contrast of 10% can be detected. A compact preamplification stage has been introduced that allows to improve the minimum detectable contrast over previous designs, while at the same time reducing the pixel area by 1/3. The pixel responds to illumination changes in less than 3.6 μs. The ability of the sensor to capture very fast moving objects, rotating at 10 K revolutions per second, has been verified experimentally. A frame-based sensor capable to achieve this, would require at least 100 K frames per second. © 2011 IEEE.


Thorsby E.,University of Oslo
Tissue Antigens | Year: 2011

As the immunobiological function of the HLA (human leucocyte antigen) class I and II molecules was revealed, we have seen an explosive development of the HLA field. Today, the HLA complex occupies a central position in basic and clinical immunology. In this Opinion article, I will briefly discuss some challenges which in my opinion are more important than others in the near future of HLA, with a focus on products of the classical HLA class I and II genes. Matching for HLA antigens will continue to be of importance in organ and hematopoietic stem cell transplantations. In the latter field, induction of graft-versus-leukemia effects will receive greater attention, where HLA will play a central role. It is anticipated that we will see an extensive development in our knowledge of the etiology and pathogenesis of autoimmune diseases, where some HLA class I and II genes by far are the strongest predisposing genes. To predict and prevent autoimmune diseases will be a major challenge for the HLA field in the future. HLA will also be of increasing importance in pharmacogenomics, vaccinations and anthropology. Together, this will leave the HLA field with many new challenges and opportunities, which in the future will require more focus on functional aspects of the immunogenetics of HLA. © 2011 John Wiley & Sons A/S.


Brandtzaeg P.,University of Oslo
Beneficial Microbes | Year: 2013

There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders affecting body surfaces and beyond. The epithelial gate-keeper function is determined by the individual's age (e.g. preterm vs. term infant), diet, genetics, mucus composition, interactions between mast cells, nerves and neuropeptides, concurrent infection, the commensal microbiota and the epithelium-shielding effect of secretory IgA (SIgA) antibodies provided by breast milk or produced in the individual's gut. The integrity of the epithelial barrier furthermore depends on homeostatic regulatory mechanisms, including mucosal induction of regulatory T cells, where commensal microbiota-host interactions apparently play decisive roles. Thus, both extrinsic and intrinsic factors have been identified that may have an impact on the dynamics of the epithelial cell-cell junctions in the gut and thereby increase or reduce paracellular permeability. Experiments have shown that SIgA normally cooperates with innate defence factors to protect the epithelium and reinforce its barrier function. In the absence of SIgA commensal gut bacteria overstimulate innate epithelial immunity at the expense of expression of genes that regulate fat and carbohydrate metabolism, resulting in an epithelial gene signature that correlates with the development of lipid malabsorption. This shows that the intestinal epithelial barrier is a cross-road between defence and nutrition, and that SIgA is essential to keep the balance between these two functions. © 2013 Wageningen Academic Publishers.


Leren T.P.,University of Oslo
Atherosclerosis | Year: 2014

Objective: This article reviews the mechanism by which the low density lipoprotein receptor (LDLR) that has bound proprotein convertase subtilisin/kexin type 9 (PCSK9), is rerouted to intracellular degradation instead of being recycled. Methods: A search of relevant published literature has been conducted. Results: PCSK9 binds to the LDLR at the cell surface. It is the catalytic domain of PCSK9 that binds to the epidermal growth factor repeat A of the LDLR. The LDLR:PCSK9 complex is internalized through clathrin-mediated endocytosis. Due to an additional electrostatic interaction at acidic pH between the C-terminal domain of PCSK9 and the ligand-binding domain of the LDLR, PCSK9 remains bound to the LDLR in the sorting endosome. As a consequence, the LDLR fails to adopt a closed conformation and is degraded instead of being recycled. The mechanism for the failure of the LDLR to recycle appears to involve ectodomain cleavage of the extended LDLR by a cysteine cathepsin in the sorting endosome. The cleaved LDLR ectodomain will be confined to the vesicular part of the sorting endosome for degradation in the endosomal/lysosomal tract. Conclusion: Ectodomain cleavage of an LDLR with bound PCSK9 in the sorting endosome disrupts the normal recycling of the LDLR. © 2014 Elsevier Ireland Ltd.


Wei T.,University of Oslo
Energy Economics | Year: 2010

How do energy efficiency gains affect energy consumption? The effects are generally called "rebound effects" in the literature. Previous studies have extensively focused on only part of the global economy to study rebound effects, e.g. energy consumption by households, one industry, or one country. However, since the global economy is highly connected among countries, these studies may lead to misleading conclusions if the rebound effects in the rest of the economy are significant. Recently Saunders (2008) analyzes the demand side by taking the global economy as a whole. Wei (2007) also provides a general analysis by using Cobb-Douglas production functions for the global economy. The present article expands Wei (2007) general analysis to explore the rebound effects from an economist's viewpoint by taking the global economy as a whole and applying general forms of production functions. The analysis provides new insights related to rebound effects: we highlight the role of energy supply as a determinant of rebound. We show that the substitution between energy resources and other productive resources is more relevant to long term rebound. We predict that long term rebound may be lower than short term rebound. And we also discover that super-conservation can happen in both the short term and the long term. © 2009 Elsevier B.V.


Halvorsen O.,University of Oslo
Polar Biology | Year: 2012

The protostrongylid nematode Elaphostrongylus rangiferi parasitizes reindeer (Rangifer tarandus) and may cause severe disease and death. A relationship between particularly warm summers and the occurrence of the parasite has been suggested. The hypotheses of a positive relationship between the abundance of the parasite and summer warmth were tested by yearly examination of the density of larvae of E. rangiferi in faeces of reindeer in northern Norway. In addition to summer temperature, summer precipitation and reindeer density were included. The abundance of the parasite increased with increasing summer temperature. It is predicted that warming of the Arctic will increase the abundance of E. rangiferi and cause more disease and death in reindeer. © 2012 Springer-Verlag.


Asdal K.,University of Oslo | Moser I.,Diakonhjemmet University College
Science Technology and Human Values | Year: 2012

What is context and how to deal with it? The context issue has been a key concern in Science and Technology Studies (STS). This is linked to the understanding that science is culture. But how? The irreductionist program from the early eighties sought to solve the problem by doing away with context altogether-for the benefit of worlds in the making. This special issue takes its points of departure in this irreductionist program, its source of inspirations, as well as its reworkings. The aim is not to solve the context problem but rather to experiment with context and what we label contexting. © The Author(s).


To compare the efficacy of surgery with disc prosthesis versus non-surgical treatment for patients with chronic low back pain. A prospective randomised multicentre study. Five university hospitals in Norway. 173 patients with a history of low back pain for at least one year, Oswestry disability index of at least 30 points, and degenerative changes in one or two lower lumbar spine levels (86 patients randomised to surgery). Patients were treated from April 2004 to September 2007. Surgery with disc prosthesis or outpatient multidisciplinary rehabilitation for 12-15 days. The primary outcome measure was the score on the Oswestry disability index after two years. Secondary outcome measures were low back pain, satisfaction with life (SF-36 and EuroQol EQ-5D), Hopkins symptom check list (HSCL-25), fear avoidance beliefs (FABQ), self efficacy beliefs for pain, work status, and patients' satisfaction and drug use. A blinded independent observer evaluated scores on the back performance scale and Prolo scale at two year follow-up. The study was powered to detect a difference of 10 points on the Oswestry disability index between the groups at two years. At two years there was a mean difference of -8.4 points (95% confidence interval -13.2 to -3.6) in favour of surgery. In the analysis of prespecified secondary outcomes, there were significant differences in favour of surgery for low back pain (mean difference -12.2, -21.3 to -3.1), patients' satisfaction (63% (n = 46) v 39% (n = 26)), SF-36 physical component score (mean difference 5.8, 2.5 to 9.1), self efficacy for pain (mean difference 1.0, 0.2 to 1.9), and the Prolo scale (mean difference 0.9, 0.1 to 1.6). There were no significant differences in return to work, SF-36 mental component score, EQ-5D, fear avoidance beliefs, Hopkins symptom check list, drug use, and the back performance scale. One serious complication of leg amputation occurred during surgical revision of a polyethylene dislodgement. The drop-out rate was 20% (34) and the crossover rate was 6% (5). Surgical intervention with disc prosthesis for chronic low back pain resulted in a significantly greater improvement in the Oswestry score compared with rehabilitation, but this improvement did not clearly exceed the prespecified minimally important clinical difference between groups of 10 points, and the data are consistent with a wide range of differences between the groups, including values well below 10 points. The potential risks of surgery and the substantial amount of improvement experienced by a sizeable proportion of the rehabilitation group also have to be incorporated into overall decision making. Trial registration NCT 00394732.


Podinovski V.V.,University of Warwick | Forsund F.R.,University of Oslo
Operations Research | Year: 2010

The implicit definition and nondifferentiability of efficient frontiers used in data envelopment analysis are two major obstacles to obtaining their differential characteristics, including various elasticity measures and marginal rates of substitution. In this paper we invoke the theorem of the directional derivative of the optimal value function and show how this can be used to define and calculate the required elasticities without any simplifying assumptions. This approach allows us to extend the known elasticity measures and introduce new ones to the entire efficient frontier, including all its extreme points, in one single development. We also construct linear programs that are required for the calculation of elasticity measures. Our main development is undertaken in the variable returns-to-scale technology but extends to other polyhedral technologies of efficiency analysis. © 2010 INFORMS.


Ronningen K.S.,University of Oslo
Archivum Immunologiae et Therapiae Experimentalis | Year: 2013

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way - the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D. © 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.


Thoresen M.,University of Oslo | Thoresen M.,University of Bristol
Seminars in Fetal and Neonatal Medicine | Year: 2015

Three ongoing challenges have arisen after the introduction of therapeutic hypothermia (TH) as standard of care for term newborns with moderate or severe perinatal asphyxia: (i) to ensure that the correct group of infants are cooled; (ii) to optimize the delivery of TH and intensive care in relation to the severity of the encephalopathy; (iii) to systematically follow up the long-term efficacy of TH using comparable outcome data between centers and countries. This review addresses the entry criteria for TH, and discusses potential issues regarding patient selection, and management of TH: cooling mild, moderate, and very severe perinatal asphyxia, cooling longer or deeper, and/or starting with a greater delay. This includes cooling of patients outside of standard trial entry criteria, such as after postnatal collapse, premature infants, those with infection, and infants with metabolic, chromosomal or surgical diagnoses in addition to perinatal asphyxia. © 2015.


Askevold E.T.,University of Oslo
Journal of the American Heart Association | Year: 2012

Valve calcification and inflammation play key roles in the development of aortic stenosis (AS). The Wnt pathways have been linked to inflammation, bone metabolism, angiogenesis, and heart valve formation. We hypothesized that soluble Wnt modulators may be dysregulated in symptomatic AS. We measured circulating levels (n=136) and aortic valve tissue expression (n=16) of the secreted Wnt modulators secreted frizzled related protein-3, dickkopf-1 (DKK-1), and Wnt inhibitory factor-1 (WIF-1) by enzyme immunoassay, immunostaining, and RT-PCR in patients with symptomatic, severe AS and investigated associations with echocardiographic parameters of AS and cardiac function. Finally, we assessed the prognostic value of these Wnt modulators in relation to all-cause mortality (n=35) during long-term follow-up (median 4.6 years; survivors, 4.8 years; nonsurvivors, 1.9 years) in these patients. Our main findings were: (1) serum levels of all Wnt modulators were markedly elevated in patients with symptomatic AS (mean increase 231% to 278%, P<0.001), (2) all Wnt modulators were present in calcified aortic valves but correlated poorly with systemic levels or degree of AS, (3) some modulators (ie, WIF-1) were associated with the degree of myocardial function and valvular calcification, (4) all Wnt modulators, and DKK-1 in particular, predicted long-term mortality in these patients also after adjusting for conventional predictors including NT-proBNP. Together, these in vivo data support the involvement of Wnt signaling in the development of AS and suggest that circulating Wnt modulators should be further investigated as risk markers in larger AS populations, including patients with asymptomatic disease.


Hurley J.H.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Stenmark H.,University of Oslo
Annual Review of Biophysics | Year: 2011

Over the past 14 years, ubiquitination has emerged as a centrally important mechanism governing the subcellular trafficking of proteins. Ubiquitination, interaction with sorting factors that contain ubiquitin-binding domains, and deubiquitination govern the itineraries of cargo proteins that include yeast carboxypeptidase S, the epithelial sodium channel ENaC, and epidermal growth factor receptor. The molecular structures and mechanisms of the paradigmatic HECT and RING domain ubiquitin ligases, of JAMM- and USP-domain-deubiquitinating enzymes, and of numerous ubiquitin-binding domains involved in these pathways have been worked out in recent years and are described. © 2011 by Annual Reviews. All rights reserved.


Hutchings J.A.,Dalhousie University | Hutchings J.A.,University of Oslo
ICES Journal of Marine Science | Year: 2014

The population dynamics of marine fish at low abundance has long been of interest. One century ago, Johan Hjort drew attention to the importance of understanding "the laws which govern the renewal of the animal population". Integral to the current work on the recovery of collapsed fish stocks is the association between abundance and per capita population growth rate (r), a negative correlation being representative of compensation and a positive correlation indicative of an Allee effect, also termed depensation. Allee effects are predicted to slow the rate, and increase the uncertainty, of recovery. Based on studies having sufficient data at low abundance, the magnitude of depletion experienced by some fish populations appears to have been sufficient to have generated either an Allee effect or a transition from strong to weak (or absent) compensatory dynamics. To a first approximation, empirically based Allee-effect reference points are consistent with suggested thresholds for overfishing and stock collapse. When evaluating Allee effects in marine fish, it is important not to conflate causal mechanism(s) with the pattern between r and abundance; the latter is of greater practical import. An additional caveat is that the longer a population remains at low abundance, the more likely it is that the environment around it will change in ways that are unfavourable to recovery. It might be this "temporal tyranny" of small population size that is most likely to produce an emergent Allee effect and depensatory dynamics in some collapsed marine fish populations. © 2014 International Council for the Exploration of the Sea. All rights reserved.


A new method is here presented for direct measurement of the thermoelectric figure of merit (ZT) at high temperatures by dividing a sampleelectrically into two sections. At temperatures above 423K the heat losses from each section cancel and measurement of ZT is done up to 543K in a nitrogen atmosphere. This is in contrast to the Harman method that is inaccurate at high temperatures due to heat losses. This principle is also applied to a silicon wafer to determine the heat flowing into a ZnSb sample. Errors in the measurements become larger at high temperatures as the temperature is not constant across the sample. Errors are also introduced by the finite sizes of the electrical contacts. This way of measuring ZT allows a simpler setup for rapid measurements. © 2015.


Eggesbo H.B.,University of Oslo
Cancer Imaging | Year: 2012

More than 70 benign and malignant sinonasal tumours and tumour-like conditions have been described. However, sinonasal tumours are rare, and sinonasal cancers comprise only 3% of all head and neck cancers and 1% of all malignancies, with a peak incidence in the 5th to 7th decades and with a male preponderance. The early symptoms and imaging findings of sinonasal tumours are similar to rhinosinusitis with runny and stuffy nose, lacrimation and epistaxis and therefore neglected both by the patients and doctors. When late symptoms such as anosmia, visual disturbances, cranial neuropathy (Cn II, IV, V, VI) or facial swelling appear, the patient is referred to sinonasal endoscopy or imaging. At the time of correct diagnosis more than half of the tumours have reached an advanced stage with a poor prognostic outcome. Even if imaging is performed in the early stages, a radiologist inexperienced with sinonasal anatomy and tumour features may easily interpret early signs of a malignant tumour as rhinosinusitis or a lesion that does not require follow-up. This article presents the imaging findings in some of the most common benign and malignant sinonasal tumours, and the TNM classification and staging of sinonasal carcinomas. © 2012 International Cancer Imaging Society.


This paper analyses how research on antibiotic resistance has been a driving force in the development of new antibiotics. Drug resistance, while being a problem for physicians and patients, offers attractive perspectives for those who research and develop new medicines. It imposes limits on the usability of older medicines and simultaneously modifies pathologies in a way that opens markets for new treatments. Studying resistance can thus be an important part of developing and marketing antibiotics. The chosen example is that of the German pharmaceutical company Bayer. Before World War Two, Bayer had pioneered the development of anti-infective chemotherapy, sulpha drugs in particular, but had missed the boat when it came to fungal antibiotics. Exacerbated by the effects of war, Bayer's world market presence, which had been considerable prior to the war, had plummeted. In this critical situation, the company opted for a development strategy that tried to capitalise on the problems created by the use of first-generation antibiotics. Part and parcel of this strategy was monitoring what can be called the structural change of infectious disease. In practice, this meant to focus on pathologies resulting from resistance and hospital infections. In addition, Bayer also focused on lifestyle pathologies such as athlete's foot. This paper will follow drug development and marketing at Bayer from 1945 to about 1980. In this period, Bayer managed to regain some of its previous standing in markets but could not escape from the overall crisis of anti-infective drug development from the 1970s on. © The Author 2016. Published by Cambridge University Press.


Mysterud A.,University of Oslo | Bischof R.,Norwegian University of Life Sciences
Journal of Animal Ecology | Year: 2010

There is growing concern about the evolutionary consequences of human harvesting on phenotypic trait quality in wild populations. Undesirable consequences are especially likely with trophy hunting because of its strong bias for specific phenotypic trait values, such as large antlers in cervids and horns in bovids. Selective hunting can cause a decline in a trophy trait over time if it is heritable, thereby reducing the long-term sustainability of the activity itself. How can we build a sustainable trophy hunting tradition without the negative trait-altering effects? We used an individual-based model to explore whether selective compensatory culling of 'low quality' individuals at an early life stage can facilitate sustainability, as suggested by information from managed game populations in eastern and central Europe. Our model was rooted in empirical data on red deer, where heritability of sexual ornaments has been confirmed and phenotypic quality can be assessed by antler size in individuals as young as 1 year. Simulations showed that targeted culling of low-quality yearlings could counter the selective effects of trophy hunting on the distribution of the affected trait (e.g. antler or horn size) in prime-aged individuals. Assumptions of trait heritability and young-to-adult correlation were essential for compensation, but the model proved robust to various other assumptions and changes to input parameters. The simulation approach allowed us to verify responses as evolutionary changes in trait values rather than short-term consequences of altered age structure, density and viability selection. We conclude that evolutionarily enlightened management may accommodate trophy hunting. This has far reaching implications as income from trophy hunting is often channelled into local conservation efforts and rural economies. As an essential follow-up, we recommend an analysis of the effects of trophy hunting in conjunction with compensatory culling on the phenotypic and underlying genetic variance of the trophy trait. © 2009 British Ecological Society.


Opjordsmoen S.,University of Oslo
Schizophrenia Bulletin | Year: 2014

In his textbook from 1838, Esquirol made the first comprehensive psychopathological description of paranoia, which he labeled partial psychosis. This was a condition with encapsulated, well organized, and persistent delusions. These are defended with a great deal of emotions and sharp argument. The individual appears quite convincing, especially because he or she otherwise behaves rationally. The intellectual capacity is used to achieve defined goals according to the delusional content. This condition is difficult to uncover because of dissimulation and adaptation. The frequency in the population is unknown, but the condition is rare in psychiatric treatment facilities, and usually only when the persons become litigious or criminal. In Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the condition is covered by the concept of delusional disorder, but that concept also comprises benign acute/subacute conditions as well as cases that turn out to have the diagnosis changed to schizophrenia. © 2014 The Author. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


Kalager M.,Harvard University | Adami H.-O.,Karolinska Institutet | Bretthauer M.,University of Oslo | Tamimi R.M.,Harvard University
Annals of Internal Medicine | Year: 2012

Background: Precise quantification of overdiagnosis of breast cancer (defined as the percentage of cases of cancer that would not have become clinically apparent in a woman's lifetime without screening) due to mammography screening has been hampered by lack of valid comparison groups that identify incidence trends attributable to screening versus those due to temporal trends in incidence. Objective: To estimate the percentage of overdiagnosis of breast cancer attributable to mammography screening. Design: Comparison of invasive breast cancer incidence with and without screening. Setting: A nationwide mammography screening program in Norway (inviting women aged 50 to 69 years), gradually implemented from 1996 to 2005. Participants: The Norwegian female population. Measurements: Concomitant incidence of invasive breast cancer from 1996 to 2005 in counties where the screening program was implemented compared with that in counties where the program was not yet implemented. To adjust for changes in temporal trends in breast cancer incidence, incidence rates during the preceding decade were also examined. The percentage of overdiagnosis was calculated by accounting for the expected decrease in incidence following cessation of screening after age 69 years (approach 1) and by comparing incidence in the current screening group with incidence among women 2 and 5 years older in the historical screening groups, accounting for average lead time (approach 2). Results: A total of 39 888 patients with invasive breast cancer were included, 7793 of whom were diagnosed after the screening program started. The estimated rate of overdiagnosis attributable to the program was 18% to 25% (P < 0.001) for approach 1 and 15% to 20% (P < 0.001) for approach 2. Thus, 15% to 25% of cases of cancer are overdiagnosed, translating to 6 to 10 women overdiagnosed for every 2500 women invited. Limitation: The study was registry-based. Conclusion: Mammography screening entails a substantial amount of overdiagnosis. © 2012 American College of Physicians.


Ryan S.M.,University of California at San Francisco | Nielsen C.J.,University of Oslo
Anesthesia and Analgesia | Year: 2010

BACKGROUND: Inhaled anesthetics are recognized greenhouse gases. Calculating their relative impact during common clinical usage will allow comparison to each other and to carbon dioxide emissions in general. METHODS: We determined infrared absorption cross-sections for sevoflurane and isoflurane. Twenty-year global warming potential (GWP20) values for desflurane, sevoflurane, and isoflurane were then calculated using the present and previously published infrared results, and best estimate atmospheric lifetimes were determined. The total quantity of each anesthetic used in 1 minimal alveolar concentration (MAC)-hour was then multiplied by the calculated GWP 20 for that anesthetic, and expressed as "carbon dioxide equivalent" (CDE20) in grams. Common fresh gas flows and carrier gases, both air/oxygen and nitrous oxide (N2O)/oxygen, were considered in the calculations to allow these examples to represent common clinical use of inhaled anesthetics. RESULTS: GWP20 values for the inhaled anesthetics were: sevoflurane 349, isoflurane 1401, and desflurane 3714. CDE20 values for 1 MAC-hour at 2 L fresh gas flow were: sevoflurane 6980 g, isoflurane 15,551 g, and desflurane 187,186 g. Comparison among these anesthetics produced a ratio of sevoflurane 1, isoflurane 2.2, and desflurane 26.8. When 60% N2O/40% oxygen replaced air/oxygen as a carrier gas combination, and inhaled anesthetic delivery was adjusted to deliver 1 MAC-hour of anesthetic, sevoflurane CDE20 values were 5.9 times higher with N2O than when carried with air/O2, isoflurane values were 2.9 times higher, and desflurane values were 0.4 times lower. On a 100-year time horizon with 60% N2O, the sevoflurane CDE100 values were 19 times higher than when carried in air/O2, isoflurane values were 9 times higher, and desflurane values were equal with and without N2O. CONCLUSIONS: Under comparable and common clinical conditions, desflurane has a greater potential impact on global warming than either isoflurane or sevoflurane. N2O alone produces a sizable greenhouse gas contribution relative to sevoflurane or isoflurane. Additionally, 60% N2O combined with potent inhaled anesthetics to deliver 1 MAC of anesthetic substantially increases the environmental impact of sevoflurane and isoflurane, and decreases that of desflurane. N2O is destructive to the ozone layer as well as possessing GWP; it continues to have impact over a longer timeframe, and may not be an environmentally sound tradeoff for desflurane. From our calculations, avoiding N2O and unnecessarily high fresh gas flow rates can reduce the environmental impact of inhaled anesthetics. Copyright © 2010 International Anesthesia Research Society.


Moksnes H.,Norwegian School of Sport Sciences | Engebretsen L.,University of Oslo | Risberg M.A.,Norwegian School of Sport Sciences
Journal of Bone and Joint Surgery - Series A | Year: 2012

Background: There is no consensus on the management of anterior cruciate ligament (ACL) injuries in skeletally immature children, and the methodological quality of published studies is questionable. The transphyseal reconstructions, physeal-sparing reconstructions, and nonoperative treatment algorithms that are advocated have little support in the literature. The purpose of this study was to systematically review the methodological quality of the literature on the management of ACL injuries in skeletally immature children. Methods: We performed a literature search with use of PubMed to identify prospective or retrospective studies whose primary aim was to assess the outcome after operative or nonoperative treatment of ACL injuries in skeletally immature children. To be included in the analysis, a study had to have amean duration of follow-up of at least two years and aminimum of ten children in the study had to be verified to be skeletally immature. The methodological quality of the included studies was evaluated with use of the Coleman Methodology Score. Results: No randomized controlled trials, two prospective cohort studies, and twenty-nine retrospective studies met the inclusion criteria. The Coleman Methodology Score averaged 44.7 ± 9.2 out of 100 (range, 28 to 62). The methodological deficiencies were most evident with regard to the number of included children, the study design, and the description of rehabilitation protocols, outcome criteria, and outcome assessments. Conclusions: Caution is necessary when interpreting the results of studies on the treatment of ACL injuries in skeletally immature children because of widespread methodological deficiencies. There is a need for appropriately sized prospective studies and detailed descriptions of rehabilitation programs. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2012 by The Journal of Bone and Joint Surgery, Incorporated.


Myrelid P.,Linkoping University | Oresland T.,University of Oslo
Journal of Crohn's and Colitis | Year: 2015

Colectomy is still frequently required in the care of ulcerative colitis. The most common indications are either non-responding colitis in the emergency setting, chronic active disease, steroid-dependent disease or neoplastic change like dysplasia or cancer. The use of the ileal pouch anal anastomosis has internationally been the gold standard, substituting the rectum with a pouch. Recently the use of the ileorectal anastomosis has increased in frequency as reconstructive method after subtotal colectomy. Data from centres using ileorectal anastomosis have shown the method to be safe, with functionality and risk of failure comparable to the ileal pouch anal anastomosis. The methods have different advantages as well as disadvantages, depending on a number of patient factors and where in life the patient is at time of reconstruction. The ileorectal anastomosis could, together with the Kock continent ileostomy, in selected cases be a complement to the ileal pouch anal anastomosis in ulcerative colitis and should be discussed with the patient before deciding on reconstructive method. Copyright © 2015 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.


Lifjeld J.T.,University of Oslo
Molecular Ecology | Year: 2015

Taxonomy is being increasingly informed by genomics. Traditionally, taxonomy has relied extensively on phenotypic traits for the identification and delimitation of species, though with a growing influence from molecular phylogenetics in recent decades. Now, genomics opens up new and more powerful tools for analysing the evolutionary history and relatedness among species, as well as understanding the genetic basis for phenotypic traits and their role in reproductive isolation. New insights gained from genomics will therefore have major effects on taxonomic classifications and species delimitation. How a genomics approach can inform a flawed taxonomy is nicely exemplified by Mason & Taylor () in this issue of Molecular Ecology. They studied redpolls, which comprise a genus (Acanthis) of fringillid finches with a wide distribution in the Holarctic region, and whose species taxonomy has been a matter of much controversy for decades (Fig.). Current authoritative checklists classify them into one, two or three species, and five or six subspecies, based largely on geographical differences in phenotypic traits. Previous studies, including a recent one of the subspecies on Iceland (Amouret et al.), have found no evidence of differentiation between these taxa in conventional molecular markers. The lack of genetic structure has been interpreted as incomplete lineage sorting among rapidly evolving lineages. Now Mason & Taylor (), using a large data set of genomewide SNPs, verify that they all belong to a single gene pool with a common evolutionary history, and with little or no geographical structuring. They also show that phenotypic traits used in taxonomic classifications (plumage and bill morphology) are closely associated with polygenic patterns of gene expression, presumably driven by ecological selection on a few regulatory genes. Several lessons can be learned from this study. Perhaps the most important one for taxonomy is the risk of taxonomic inflation resulting from overemphasizing phenotypic traits under local adaptation and ignoring a lack of phylogenetic signal in molecular markers. © 2015 John Wiley & Sons Ltd.


Malavasi L.,University of Pavia | Margadonna S.,University of Oslo
Chemical Society Reviews | Year: 2012

The focus of this review article is on the PbO-type Fe chalcogenides that recently emerged as a new class of superconductors. The fundamental correlations between structural details and chemical compositions are discussed together with their influence on the electronic properties. © 2012 The Royal Society of Chemistry.


Helgaker T.,University of Oslo | Coriani S.,University of Trieste | Jorgensen P.,University of Aarhus | Kristensen K.,University of Aarhus | And 2 more authors.
Chemical Reviews | Year: 2012

Developments in computational molecular electronic structure theory are discussed, emphasizing on molecular response theory based on construction of a many-electron wave function. To establish a variation principle for the quasi-energy in the intermediate normalization, the quasi-energy is calculated subject to the constraint that the intermediately normalized state satisfies the projected Schrödinger equation. The equations of motion for the response functions is used to obtain relations between transition-matrix elements. The studies have also found that eigenvalues are not encountered for electronic systems dominated by a single determinant and may always be removed by extending the excitation manifold. In the formulation by Olsen and Jørgensen, response functions are obtained by applying the Ehrenfest theorem to determine the time evolution of an expectation value for the Hartree-Fock and multi-configurational self-consistent field (MCSCF) states.


Eriksen E.F.,University of Oslo
Minerva Ginecologica | Year: 2012

Replacement therapy with estrogen and progestogen (HT) or estrogen alone (ET) and selective estrogen receptor modulators (SERMS) still constitute valuable additions to the range of osteoporosis treatments available. Due to the diverse action on a wide variety of organs, HT/ET has the capacity to improve quality of life in most postmenopausal women,- more than other more specific osteoporosis treatments. The initial optimism associated with HRT 20-30 years ago was reduced considerably after the HT arm of WHI was stopped prematurely due to safety concerns. Later analyses of the WHI study have, however, tempered the negative messages emerging from the first publication in 2002. HT/ET still constitutes a first line choice for prevention of bone loss and fracture in the early postmenopausal period for a period of 5 years. However, in women with low risk of adverse events classically associated with HT/ET newer analyses show that treatment can be continued with an acceptable risk benefit ratio. These analyses have also high-lighted the negative impact of progestogens on breast cancer risk an adverse effects on the cardiovascular system. Newer guidelines therefore suggest that a combination of a progestogen IUD and transdermal estrogen seems to be the best alternative for long term treatment. This combination minimizes cardiovascular safety concerns by avoiding the negative impact of first pass metabolism in the liver seen with oral compounds and minimizes exposure to progestogens. SERMS are valuable alternatives, particularly in osteopenic women (t-score -1,0 to -2,5) at increased risk of breast cancer, but their general lack of anti fracture efficacy towards non vertebral fractures limits their use in women at high risk of osteoporotic fracture.


Larsen A.C.,University of Oslo | Goriely S.,Free University of Colombia
Physical Review C - Nuclear Physics | Year: 2010

A low-energy enhancement of the γ-ray strength function in several light and medium-mass nuclei has been observed recently in He3-induced reactions. The effect of this enhancement on (n,γ) cross sections is investigated for stable and unstable neutron-rich Fe, Mo, and Cd isotopes. Our results indicate that the radiative neutron capture cross sections may increase considerably due to the low-energy enhancement when approaching the neutron drip line. This could have non-negligible consequences on r-process nucleosynthesis calculations. © 2010 The American Physical Society.


Aim. The purpose of the present study was to analyze sagittal and vertical cephalometric changes in 41 men and 52 women from 22-43 years of age and to examine differences between the periods 22-33 years (T1-T2) and 33-43 years (T2-T3) as well as gender differences in the changes during the two periods.Materials and methods. Our study data derived from three cephalograms of each individual. Very few subjects had undergone orthodontic treatment in childhood, and none had used retainers during the 5 years before the first cephalogram (T1). Neither had any undergone orthodontic treatment or orthognathic surgery during the observation periods. All cephalograms were taken with the same cephalostat, and all subjects were aged between 20 and 26 years, with a mean age of 22.6 and 22.5 years for women and men, respectively, when the first cephalogram was taken. The measurements were taken using a modified Dentofacial Planner SHORT software program.Results. At 22 years of age, all linear parameters (S-N, N-Me, S-tGo, Co-Me, Ar-Me) were larger in men. Of the anteroposterior parameters, S-N increased more in women, while Co-Gn and Ar-Gn increased more in men. This increase was largest in the first period in both genders. The vertical N-Me increased in both genders in both periods, but more in the women. The posterior S-tGo increased more in men in both periods. The lower parts of the vertical parameters increased more than the upper parts. The ML-NSL angle increased during both periods in women, while in men no statistically significant change was revealed. The S-N-A angle decreased in both genders in the first period and continued to decrease in the second in women, while in men an increase in the second period was demonstrated. Angles related to the anteroposterior position of the mandible (S-N-B and S-N-Po) decreased during both periods in women while the angles in men did not change. The incisors retroclined during both periods in both genders. Overall changes were larger in the first period than in the second. Conclusion. Changes of the human facial skeleton continue in the third and forth decade of life and are significant. However, the mandibular growth rate decreases between the third and fourth decade. Men generally have a larger anterior cranial base and a larger face. These gender differences continue to increase with advanced age. The sagittal position of the jaw bases became more retrognathic in women. The reason for the altered mandibular position is also a posterior rotation of the lower jaw. In men, the mandibular inclination remains more stable. © Springer-Verlag.


To review recent data on objectively measured overweight/obesity in national representative samples of European adolescents (aged 10-18 years), as well as availability of studies assessing trends in overweight/obesity in this target group. Attention was paid to the ability of the data to describe the obesity epidemic, especially in sociodemographic subgroups. Data on prevalence and trends in overweight/obesity among adolescents in the twenty-seven European Community member states, Iceland, Norway and Switzerland, available as scientific publications as well as reports or unpublished data by the end of 2009, were retrieved. Reports on the most recent objectively measured data from national representative samples were selected and described with regard to the years of data collection, sample sizes, response rates, age ranges included, trends by age, type of measures of overweight/obesity, sociodemographic variables and the sources of information. Objectively measured data on national representative samples were identified for only half of the countries, and the trend studies were mainly conducted applying subnational samples. Most studies used the criteria from the International Obesity Task Force (IOTF) to define overweight/obesity, but the age ranges studied and the years of data collection varied, and information on sample sizes and response rates were often not presented. Data on trends of overweight/obesity over time are increasing, and the most recent studies indicate that the prevalence rate of overweight/obesity has stabilized. Few studies reported data by sociodemographic subgroups other than gender and age. Objectively measured data on national representative samples of adolescents appear scattered, and there is a large heterogeneity with respect to the quality and comparability of available data. Increasing use of the IOTF criteria for overweight/obesity contributes to improved comparability across studies. Data by sociodemographic subgroups, and in particular by socio-economic status, are scarce.


Waters D.D.,San Francisco General Hospital | Ho J.E.,U.S. National Institutes of Health | Boekholdt S.M.,University of Amsterdam | Demicco D.A.,Pfizer | And 4 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives: The purpose of this study was to compare the incidence of new-onset diabetes (NOD) with cardiovascular (CV) event reduction at different levels of NOD risk. Background: Statins reduce the number of CV events but increase the incidence of NOD. We previously reported that 4 factors independently predicted NOD: fasting blood glucose >100 mg/dl, fasting triglycerides >150 mg/dl, body mass index >30 kg/m2, and history of hypertension. Methods: We compared NOD incidence with CV event reduction among 15,056 patients with coronary disease but without diabetes at baseline in the TNT (Treating to New Targets) (n = 7,595) and IDEAL (Incremental Decrease in Endpoints Through Aggressive Lipid Lowering) (n = 7,461) trials. CV events included coronary heart disease death, myocardial infarction, stroke, and resuscitated cardiac arrest. Results: Among 8,825 patients with 0 to 1 of the aforementioned NOD risk factors at baseline, NOD developed in 142 of 4,407 patients in the atorvastatin 80 mg group and in 148 of 4,418 in the atorvastatin 10 mg and simvastatin 20 to 40 mg groups (3.22% vs. 3.35%; hazard ratio [HR]: 0.97; 95% confidence intervals [CI]: 0.77 to 1.22). Among the remaining 6,231 patients with 2 to 4 NOD risk factors, NOD developed in 448 of 3,128 in the atorvastatin 80 mg group and in 368 of 3,103 in the lower-dose groups (14.3% vs. 11.9%; HR: 1.24; 95% CI: 1.08 to 1.42; p = 0.0027). The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups. Conclusions: Compared with lower-dose statin therapy, atorvastatin 80 mg/day did not increase the incidence of NOD in patients with 0 to 1 NOD risk factors but did, by 24%, among patients with 2 to 4 NOD risk factors. The number of CV events was significantly reduced with atorvastatin 80 mg in both NOD risk groups. © 2013 American College of Cardiology Foundation.


Hallen J.,University of Oslo | Hallen J.,Boehringer Ingelheim
Cardiology | Year: 2012

In acute myocardial infarction (AMI), the extent of myocardial damage is closely linked to prognosis. Early determination of infarct size is therefore key to assessing the future risk of patients and instructive for optimization of therapeutic strategies. The cardiac troponins, by allowing the physician to track the extent of injury suffered by the myocardium, provide a window into the heart. This article addresses the relationship between the cardiac troponins and the infarct size in AMI. Taken together, the data suggest that the cardiac troponins provide very useful information in this respect and especially in patients with ST elevation myocardial infarction. More studies are needed to understand how cardiac troponin-estimated infarct size may be integrated with other prognostic assessments and employed systematically in risk stratification. Early data are promising and indicate that cardiac troponins could provide useful information for early risk assessment that is complementary to the determination of cardiac function and volumes. Copyright © 2012 S. Karger AG, Basel.


Djupesland P.G.,OptiNose | Skretting A.,University of Oslo
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2012

Background: Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines. This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device (Opt-Powder; OptiNose US Inc., Yardley, PA, USA) to that of liquid aerosol administered via a traditional hand-actuated liquid spray pump (Rexam SP270, Rexam Pharma, France). Methods: The study was an open-label, crossover design in seven healthy subjects (five females, two males). The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either 99mTc-labeled lactose powder or liquid 99mTc- diethelyne triamine pentaacetic acid-aerosol. The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions. Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated. Results: Both powder and spray were distributed to all of the nasal regions. The Opt-Powder device, however, achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray (upper posterior region; Opt-Powder 18.3%±11.5 vs. Spray 2.4%±1.8, p<0.02; sum of upper and middle posterior regions; Opt-Powder 53.5%±18.5 vs. Spray 15.7%±13.8, p<0.02). The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder (Opt-Powder 17.4%±24.5 vs. Spray 59.4%±18.2, p<0.04). OptiNose powder delivery resulted in more rapid overall nasal clearance. No lung deposition was observed. Conclusions: The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior nonciliated regions the overall nasal clearance after spray was slower. © Copyright 2012, Mary Ann Liebert, Inc. 2012.


Fagerland M.W.,University of Oslo
BMC Medical Research Methodology | Year: 2012

Background: During the last 30 years, the median sample size of research studies published in high-impact medical journals has increased manyfold, while the use of non-parametric tests has increased at the expense of t-tests. This paper explores this paradoxical practice and illustrates its consequences. Methods: A simulation study is used to compare the rejection rates of the Wilcoxon-Mann-Whitney (WMW) test and the two-sample t-test for increasing sample size. Samples are drawn from skewed distributions with equal means and medians but with a small difference in spread. A hypothetical case study is used for illustration and motivation. Results: The WMW test produces, on average, smaller p-values than the t-test. This discrepancy increases with increasing sample size, skewness, and difference in spread. For heavily skewed data, the proportion of p < 0.05 with the WMW test can be greater than 90% if the standard deviations differ by 10% and the number of observations is 1000 in each group. The high rejection rates of the WMW test should be interpreted as the power to detect that the probability that a random sample from one of the distributions is less than a random sample from the other distribution is greater than 50%. Conclusions: Non-parametric tests are most useful for small studies. Using non-parametric tests in large studies may provide answers to the wrong question, thus confusing readers. For studies with a large sample size, t-tests and their corresponding confidence intervals can and should be used even for heavily skewed data. © 2012 Fagerland.


Krokan H.E.,Norwegian University of Science and Technology | Bjoras M.,University of Oslo
Cold Spring Harbor Perspectives in Biology | Year: 2013

Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to theDNA helix structure. BER is initiated bya DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or long-patch repair that largely uses different proteins to complete BER. At least 11 distinct mammalian DNA glycosylases are known, each recognizing a few related lesions, frequently with some overlap in specificities. Impressively, the damaged bases are rapidly identified in a vast excess of normal bases, without a supply of energy. BER protects against cancer, aging, and neurodegeneration and takes place both in nuclei and mitochondria. More recently, an important role of uracil-DNA glycosylaseUNG2in adaptive immunitywas revealed. Furthermore, otherDNAglycosylases may have important roles in epigenetics, thus expanding the repertoire of BER proteins. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.


Olsen I.,University of Oslo | Amano A.,Osaka University
Journal of Oral Microbiology | Year: 2015

Outer membrane vesicles (OMVs) from Gram-negative bacteria were first considered as artifacts and were followed with disbelief and bad reputation. Later, their existence was accepted and they became characterized as bacterial bombs, virulence bullets, and even decoys. Today, we know that OMVs also can be involved in cell-cell signaling/communication and be mediators of immune regulation and cause disease protection. Furthermore, OMVs represent a distinct bacterial secretion pathway selecting and protecting their cargo, and they can even be good Samaritans providing nutrients to the gut microbiota maintaining commensal homeostasis beneficial to the host. The versatility in functions of these nanostructures is remarkable and includes both defense and offense. The broad spectrum of usability does not stop with that, as it now seems that OMVs can be used as vaccines and adjuvants or vehicles engineered for drug treatment of emerging and new diseases not only caused by bacteria but also by virus. They may even represent new ways of selective drug treatment. © 2015 Ingar Olsen and Atsuo Amano.


Strandlie A.,Gjovik University College | Strandlie A.,University of Oslo | Fruhwirth R.,Austrian Academy of Sciences | Fruhwirth R.,Vienna University of Technology
Reviews of Modern Physics | Year: 2010

This paper reviews classical and adaptive methods of track and vertex reconstruction in particle physics experiments. Adaptive methods have been developed to meet the experimental challenges at high-energy colliders, in particular, the CERN Large Hadron Collider. They can be characterized by the obliteration of the traditional boundaries between pattern recognition and statistical estimation, by the competition between different hypotheses about what constitutes a track or a vertex, and by a high level of flexibility and robustness achieved with a minimum of assumptions about the data. The theoretical background of some of the adaptive methods is described, and it is shown that there is a close connection between the two main branches of adaptive methods: neural networks and deformable templates, on the one hand, and robust stochastic filters with annealing, on the other hand. As both classical and adaptive methods of track and vertex reconstruction presuppose precise knowledge of the positions of the sensitive detector elements, the paper includes an overview of detector alignment methods and a survey of the alignment strategies employed by past and current experiments. © 2010 The American Physical Society.


Diekert F.K.,University of Oslo
Environmental and Resource Economics | Year: 2012

The gravity of growth overfishing is increasingly recognized. The size-distribution of fish stocks is often severely truncated, even when the overall biomass is reasonably well managed. In a first part of this article, I show how the "race to fish" extends to the dimension of size: Akin to the classical Bertrand competition in prices, each agent has an incentive to target fish at a smaller size. In fact, for perfect selectivity, competition between two agents is sufficient to dissipate all rents. In a second part of this article, I explore the implications of size-differentiated harvesting for ITQ regulation. I show that quotas specified in terms of numbers are far superior to those specified in terms of weight or value. © 2012 The Author(s).


Lund D.,University of Oslo
Energy Strategy Reviews | Year: 2014

Starting around 1970, Norway's system of state participation and taxation in petroleum had important asymmetries, known as distortionary in tax theory. Moreover, tax rates were tailored to oil price changes. From 1986 onwards this has been reformed gradually into a stable and symmetric system, recognized as close to neutral, inducing companies to maximize pre-tax values. But the system is costly and risky for the state. If countries are unable or unwilling to bear costs and risks, they cannot implement the neutral system. Neither did Norway from the beginning. In that case a country faces important trade-offs between risk and the maximization of pre-tax value or state revenue. This may be partly circumvented by slowing the pace of licensing. © 2014 Elsevier Ltd.


Lempa J.,University of Oslo
Operations Research Letters | Year: 2010

We consider a class of optimal stopping problems of diffusions with a two-sided optimal rule. We propose an approach for finding and characterizing the solution. We establish that the optimal stopping rule can be associated with the unique fixed point of an auxiliary function. The results are illustrated with an explicit example. © 2009 Elsevier B.V. All rights reserved.


Reas D.L.,University of Oslo | Grilo C.M.,Yale University
Expert Opinion on Pharmacotherapy | Year: 2015

Introduction: Binge eating disorder (BED), a formal eating disorder diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is characterized by recurrent binge eating, marked distress about binge eating, and the absence of extreme weight compensatory behaviors. BED is more prevalent than other eating disorders, with broader distribution across age, sex and ethnic/racial groups, and is associated strongly with obesity and heightened risk for psychiatric/medical comorbidities.Areas covered: This article provides an overview of pharmacotherapy for BED with a focus on Phase III randomized controlled trials (RCTs). The search with minimal methodological inclusion requirements yielded 22 RCTs investigating several different medication classes; most were pharmacotherapy-only trials with 8 trials testing combination approaches with psychological-behavioral methods.Expert opinion: The evidence base regarding pharmacotherapy for BED remains limited, although this year the FDA approved the first medication (i.e., lisdexamfetamine dimesylate; LDX) specifically for moderate-to-severe BED. Data from RCTs suggest certain medications are superior to placebos for reducing binge eating over the short term; almost no data exist regarding longer-term effects of pharmacotherapy for BED. Except for topiramate, which significantly reduces both binge eating and weight, tested medications yield minimal weight loss and LDX is not indicated for weight loss. Psychological-behavioral and combination approaches with certain medications yield superior outcomes to pharmacotherapy-only acutely and over longer-term follow-up. © 2015 Informa UK, Ltd.


Raeder J.,University of Oslo
Expert Opinion on Pharmacotherapy | Year: 2014

New approved options with opioids in the postoperative setting may include new ways of administration, new combinations with other drugs and new opioid drugs. Newly approved devices for administration include sublingual sufentanil dispenser and transdermal iontophoretic fentanyl, with the purpose of almost mimicking the rapid and reliable onset of intravenous (IV) administration, without the problems of an ongoing IV cannula and cumbersome equipment. Still, potential problems of overdosing and misuse must be in focus when these devices come into use. Tapentadol is a new partial µ-receptor opioid agonist with a combined action on norepinephrine-induced analgesia, representing a promising drug in terms of less side effects at equianalgesic doses compared with pure agonists. The mixture of different opioids given together, such as oxycodone and morphine, for oral use may also have some analgesic synergy with an improved side-effect profile, although more studies are needed. Oral oxycodone is a reliable oral opioid option, but when combined with paracetamol in the same tablet or mixture, care should also be taken to avoid serious side effects from inadvertent paracetamol overdose. © 2014 Informa UK, Ltd.


Karen P.,University of Oslo
Angewandte Chemie - International Edition | Year: 2015

What is an oxidation state? Oxidation state has defining algorithms but lacks a comprehensive definition. Results of an IUPAC project to find such a definition have recently been published in an extensive Technical Report. A summary in this Essay is illustrated with applications on Lewis, bond-graph, and summary formulas of molecules, ions, or solids, together with the most recent information regarding tricky cases. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.


Torgalsboen A.-K.,University of Oslo
Clinical Schizophrenia and Related Psychoses | Year: 2012

The main purpose of this study was to follow up a group of persons who, fifteen years ago were considered to be fully recovered from schizophrenia, in order to examine how many have sustained their recovery and to investigate the role of resilience in recovery. A semi-structured interview was designed for this 15-year follow-up study based on previous research related to the course and prognosis of schizophrenia. In addition to the interview, measures of psychosocial functioning and the degree of positive and negative symptoms were used. Remission and recovery were evaluated by consensus-based criteria. The Connor-Davidson Resilience Scale was chosen to assess resilience. The results show a significant correlation between resilience and present psychosocial functioning. There is also a significant difference between fully recovered subjects and those in remission regarding their resilience score. These results show that the majority of the subjects had maintained their recovery, and that subjects who are still fully recovered have not used medication for seventeen years and are more resilient. Thus, a sustained, full recovery without medication seems possible for a subgroup of schizophrenia patients characterized by high resilience.


Jorgensen M.,University of Oslo
Information and Software Technology | Year: 2013

Context: A potentially important, but neglected, reason for effort overruns in software projects is related to selection bias. Selection bias-induced effort overruns occur when proposals are more likely to be accepted and lead to actual projects when based on effort estimates that are too low rather than on realistic estimates or estimates that are too high. The effect of this bias may be particularly important in bidding rounds, but is potentially relevant in all situations where there is effort or cost-based selection between alternatives. Objective: To better understand the relevance and management of selection bias effects in software development contexts. Method: First, we present a statistical model illustrating the relation between selection bias in bidding and other contexts and effort overruns. Then, we examine this relation in an experiment with software professionals who estimated and completed a set of development tasks and examine relevant field study evidence. Finally, we use a selection bias scenario to assess awareness of the effect of selection bias among software providers. Results: The results from the statistical model and the experiment demonstrated that selection bias is capable of explaining much of the effort overruns. The field evidence was also consistent with a substantial effect of selection bias on effort overruns, although there are alternative explanations for the findings. We found a low awareness of selection bias among the software providers. Conclusion: Selection bias is likely to be an important source of effort overruns and should be addressed to reduce problems related to over-optimistic effort estimates. © 2013 Elsevier B.V. All rights reserved.


de raav G.N.,University of Oslo
Therapeutic Drug Monitoring | Year: 2014

ABSTRACT: Belatacept is a novel immunosuppressive drug that inhibits the co-stimulatory signal required for T-cell activation and has been approved for the prevention of acute rejection after kidney transplantation. In this paper, the need for and possibility of therapeutic drug monitoring (TDM) of belatacept is reviewed. Clinical studies have defined the upper limit of the therapeutic window, but the lower limit is unknown. The pharmacokinetics and pharmacodynamics of belatacept display only limited inter-patient variability but no data are available on the intra-patient variability of these parameters. Several assays to measure serum belatacept concentrations and its in vitro immunologic effects have been developed, but these are not commercially available and require validation. Importantly, pharmacodynamic assays have not been correlated with clinical outcomes (both efficacy and safety) and have only used surrogate laboratory read-outs. TDM is likely to become feasible in the near future if these assays are developed further. However, because its pharmacokinetics and pharmacodynamics appear to vary little between individual patients, it may not be necessary to perform TDM for this drug. There could be a role for such an approach if one seeks to lower the belatacept doses further in an attempt to minimize adverse events. A future, prospective, concentration-ranging study that defines the lower end of the belatacept therapeutic window should however, be conducted first to provide the rationale for performing TDM of this novel immunosuppressant. © 2014 by Lippincott Williams & Wilkins


Skotland T.,University of Oslo | Skotland T.,Institute of Cancer Research
Contrast Media and Molecular Imaging | Year: 2012

Molecular imaging (MI) takes advantage of several new techniques to detect biomarkers or biochemical and cellular processes, with the goal of obtaining high sensitivity, specificity and signal-to-noise ratio imaging of disease. The imaging modalities bearing the most promise for MI are positron emission tomography (PET), single photon emission computer tomography (SPECT) and different optical imaging techniques with high sensitivity. Also magnetic resonance imaging (MRI) with contrast agents like ultra-small superparamagnetic iron oxide particles (USPIO), magnetic resonance spectroscopy and ultrasound imaging with contrast agents may be useful approaches. MI techniques have been used in the clinic for many years, i.e. PET imaging using 18F-labeled fluorodeoxyglucose. Animal studies have during the last years revealed great potential for MI also with several other agents. The focus of the present article is the challenges of clinical imaging of intracellular targets following intravenous injection of the agents. Thus, the great challenge of getting enough contrast agent into the cytosol and at the same time obtaining a low signal from tissue just outside the diseased area is discussed. © 2012 John Wiley & Sons, Ltd.


Finset A.,University of Oslo
Journal of Evaluation in Clinical Practice | Year: 2011

Rationale, aims and objectives: To give a selective review of empirical studies on person-centred clinical care, in particular concerning communication patterns between patients and providers. Methods: Descriptive and selective review of relevant literature. Results: Person-centred clinical care may have positive effects on patient satisfaction, patient adherence, health care utilization, malpractice litigation and health outcome. Person-centred communication skills may be promoted by way of communication skills training. Conclusion: The concept of person-centred care is rare in the empirical literature. Future research should operationalize the concept and design studies of the impact of patient-centred clinical care. © 2011 Blackwell Publishing Ltd.


Lappegard T.,Medical Clinic of Ringerike General Hospital | Hjortdahl P.,University of Oslo
Social Science and Medicine | Year: 2014

There is growing international interest in the geography of health care provision, with health care providers searching for alternatives to acute hospitalization. In Norway, the government has recently legislated for municipal authorities to develop local health services for a selected group of patients, with a quality equal to or better than that provided by hospitals for emergency admissions. General practitioners in Hallingdal, a rural district in southern Norway, have for several years referred acutely somatically ill patients to a community hospital, Hallingdal sjukestugu (HSS). This article analyzes patients' perceived quality of HSS to demonstrate factors applicable nationally and internationally to aid in the development of local alternatives to general hospitals. We used a mixed-methods approach with questionnaires, individual interviews and a focus group interview. Sixty patients who were taking part in a randomized, controlled study of acute admissions at HSS answered the questionnaire. Selected patients were interviewed about their experiences and a focus group interview was conducted with representatives of local authorities, administrative personnel and health professionals. Patients admitted to HSS reported statistically significant greater satisfaction with several care aspects than those admitted to the general hospital. Factors highlighted by the patients were the quiet and homelike atmosphere; a small facility which allowed them a good overall view of the unit; close ties to the local community and continuity in the patient-staff relationship. The focus group members identified some overarching factors: an interdisciplinary and holistic approach, local ownership, proximity to local general practices and close cooperation with the specialist health services at the hospital. Most of these factors can be viewed as general elements relevant to the development of local alternatives to acute hospitalization both nationally and internationally. This study indicates that perceived quality should be one of the main motivations for developing alternatives to general hospital admissions. © 2014 Elsevier Ltd.


Hofmann B.,Gjovik University College | Hofmann B.,University of Oslo
BMC Medical Ethics | Year: 2013

Background: Bariatric surgery for children and adolescents is becoming widespread. However, the evidence is still scarce and of poor quality, and many of the patients are too young to consent. This poses a series of moral challenges, which have to be addressed both when considering bariatric surgery introduced as a health care service and when deciding for treatment for young individuals. A question based (Socratic) approach is applied to reveal underlying moral issues that can be relevant to an open and transparent decision making process. Discussion. A wide range of moral issues with bariatric surgery for children and adolescents is identified in the literature. There is a moral imperative to help obese minors avoiding serious health problems, but there is little high quality evidence on safety, outcomes, and cost-effectiveness for bariatric surgery in this group. Lack of maturity and family relations poses a series of challenges with autonomy, informed consent, assent, and assessing the best interest of children and adolescents. Social aspects of obesity, such as medicalization, prejudice, and discrimination, raise problems with justice and trust in health professionals. Conceptual issues, such as definition of obesity and treatment end-points, present moral problems. Hidden interests of patients, parents, professionals, industry, and society need to be revealed. Summary. Performing bariatric surgery for obese children and adolescents in order to discipline their behavior warrants reflection and caution. More evidence on outcomes is needed to be able to balance benefits and risks, to provide information for a valid consent or assent, and to advise minors and parents. © 2013 Hofmann; licensee BioMed Central Ltd.


BACKGROUND: The choice of different graft types and surgical techniques used when reconstructing a torn anterior cruciate ligament may influence the long-term prevalence of osteoarthritis and functional outcomes. HYPOTHESIS: There are no differences in the prevalence of knee osteoarthritis or knee function in patients undergoing reconstruction of a torn anterior cruciate ligament with 4-strand hamstring autograft versus patellar tendon-bone autograft. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Seventy-two patients with subacute or chronic rupture of the anterior cruciate ligament were randomly assigned to autograft reconstruction with 4-strand gracilis and semitendinosus tendon (HAM) (N = 37) or with patellar tendon-bone (PTB) (N = 35) from the ipsilateral side. Outcome measurements were the Cincinnati knee score, single-legged hop tests, isokinetic muscle strength tests, pain, knee joint laxity test (KT-1000 arthrometer), and a radiologic evaluation (Kellgren and Lawrence) at 10-year follow-up. RESULTS: At 10 years, 57 patients (79%) were eligible for evaluation-29 in the HAM group and 28 in the PTB group. No differences were found between the 2 graft groups with respect to the Cincinnati knee score, the single-legged hop tests, pain, muscle strength measurements, or knee joint laxity. Fifty-five percent and 64% of the patients had osteoarthritis corresponding to Kellgren and Lawrence grade 2 or more in the HAM and the PTB groups, respectively (P =.27). For the uninvolved knee, the corresponding numbers were 28% and 22% (P = .62). CONCLUSION: At 10 years postoperatively, no statistically significant differences in clinical outcome between the 2 graft types were found. The prevalence of osteoarthritis was significantly higher in the operated leg than in the contralateral leg, but there were no significant differences between the 2 groups. The results indicate that the choice of graft type after an anterior cruciate ligament injury has minimal influence on the prevalence of osteoarthritis 10 years after surgery.


Damsa C.I.,University of Oslo
International Journal of Computer-Supported Collaborative Learning | Year: 2014

This article presents a study of small-group interaction in the context of collaborative learning in undergraduate education. The student groups participated in collaborative projects, which involved setting-up, conducting, and reporting on empirical research studies. This study sheds light on the nature of productive interactions, the joint efforts to co-construct knowledge and the shared epistemic agency expected to emerge when groups are addressing ill-structured, complex problems in a collaboration over time. In-depth qualitative analysis and descriptive statistics were used to analyze and interpret interaction data and developing knowledge objects (i.e., research reports) collected during a 20-week project period. The findings show that productive interactions can take different forms, with discourse-based and object-oriented being the most relevant patterns arising. In the latter case, the emergent knowledge objects also influence the course and productivity of the interaction. Finally, groups manifesting shared epistemic agency produce knowledge objects more complex and suitable to the problems addressed. These findings contribute to a better understanding of the collaborative learning process that includes work on knowledge objects over time. The implications for the educational practice and further research point towards the need for a better understanding of the way groups function when challenged to address complex problems and to participate in knowledge production, how these processes can benefit learning, and what is needed in terms of pedagogical and technological support, to enable students to be more than mere course-takers, but also producers of knowledge. © 2014, The Author(s).


Armstrong Oma K.,University of Oslo
World Archaeology | Year: 2010

Tim Ingold's seminal article 'From trust to domination' introduces a hypothesis in which there is a shift from hunter-gatherer cultures to agro-pastoral cultures regarding perceptions of, and engagements with, animals. Whereas hunters regard prey as kindred brothers, farmers regard, and treat, their domestic livestock as slaves. On the basis of this hypothesis, archaeologists frequently take this to be a universal given. In this article, Ingold's hypothesis is critiqued via an in-depth discussion of the concepts of trust, reciprocity and intimacy. The author suggests an alternative model to the dualism of either trust or domination, namely the notion of a social contract between humans and animals. The uses of this model are explored through Bronze Age case studies from southern Scandinavia © 2010 Taylor & Francis.


Grundetjern H.,University of Oslo
Criminology | Year: 2015

Based on interviews with 32 female drug dealers in Norway, this study investigates different gender performances among women situated in the illegal hard drug economy-a context with strong gendered "rules of the game." Using grounded theory methods, I have identified four predominant patterns in which women enact their gendered identities being part of the drug economy: performing emphasized femininity in the context of marginalization; performing street masculinity; employing a feminine business model; and last, flexible use of cultural repertoires. The findings suggest that different gender performances among dealers are rooted in variations in the cultural tool kits they have at their disposal. I find that the content of women's cultural tool kits varied with three sociodemographic factors: 1) age, 2) time of entrée to the drug economy, and 3) educational and employment history. Combined, these influenced the type of gender performances the dealers tended to use as well as their position in the drug market hierarchy. The research suggests that those dealers using cultural repertoires flexibly are the most successful as they skillfully employed the model best suited for the context they were in. © 2015 American Society of Criminology.


Hatlevik O.E.,Norwegian Center for in Education | Christophersen K.-A.,University of Oslo
Computers and Education | Year: 2013

During the last decade, information and communication technology has been given an increasingly large importance in our society. There seems to be a consensus regarding the necessity of supporting and developing school-based digital competence. In order to sustain digital inclusion, schools need to identify digital deficiencies and digital achievements. The concept of digital competence is scrutinized and discussed. This paper presents a research study including 4087 students from 24 upper secondary schools. The aim of the study was to scrutinize factors predicting students' digital competence, here operationalised as Digital judgements, To acquire and process digital information and To produce digital information. Analysis revealed substantial variation in digital competence between schools and within schools. The conditions at home, i.e. language integration and cultural capital, together with mastery orientation and academic aspirations did predict digital competence, and explained a substantial share of the total variation in digital competence. There are differences in what students mastered with ICT, and therefore, the students have various requirements. Further, the students attend heterogenic schools facing different kinds of challenges. Hopefully, the schools and teachers are willing to use the results from the test, and moreover, the test results can contribute to needs-based interventions and follow-ups. © 2012 Elsevier Ltd. All rights reserved.


Melberg H.O.,University of Oslo
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2014

The debate about whether health expenditures will increase more or less for the old is conceptually confused because the participants focus on different factors, use different assumptions and, finally, do not connect the predictions to more general theories of demand for health services. Some focus on increases in life expectancy and how this will change the distribution of end-of-life costs. Others focus on how changes in income and technology will affect the relationship between age and health spending. Higher income, and a larger share of the population, will make it more profitable to invest in treatments aimed at old people, which will lead to steepening in some age groups, but a flattening in other age groups. © Informa UK, Ltd.


Tenke P.,South Pest Hospital | Koves B.,South Pest Hospital | Johansen T.E.B.,University of Oslo
Current Opinion in Infectious Diseases | Year: 2014

PURPOSE OF REVIEW: Catheter-related urinary tract infections (UTIs) are among the most important nosocomial infections. This review summarizes the latest advances in the field of catheter care and the management of catheter-associated UTIs. RECENT FINDINGS: The most efficient methods to prevent catheter-associated UTIs are to avoid unnecessary catheterizations and to remove catheters as soon as possible. The use of different reminder systems and implementation of infection control programs can effectively decrease catheter-associated UTIs, although their introduction can be challenging. There is still no evidence to support the routine use of antimicrobial-impregnated catheters, but the use of hydrophilic-coated catheters for clean intermittent catheterization can effectively reduce infections. Preliminary results with chlorhexidine-coated catheters are promising. In cases of serious catheter-associated UTI in patients with a history of previous antibiotic therapy or healthcare-associated bacteraemia, empirical antibiotic treatment should be initiated with activity against multiresistant uropathogens. Suprapubic catheterization is not superior to urethral catheters in terms of reducing the rate of catheter-related bacteriuria. SUMMARY: A technology to prevent catheter-associated UTIs is still not available; however, there are promising results with new approaches such as the use of reminder systems and infection control programs, which can effectively decrease the rate of catheter-associated UTIs. There is evidence supporting the use of hydrophilic coated catheters for clean intermittent catheterization, but an optimal catheter material or coating still has to be developed. Evidence-based catheter management is crucial for every patient in need of a catheter.


Alve E.,University of Oslo | Goldstein S.T.,University of Georgia
Journal of Sea Research | Year: 2010

New data support our previously published propagule dispersal hypothesis and show that propagules of some benthic foraminiferal species can survive for two years before growth commences. Following exposure to simulated shallow-water conditions, shallow-water species of benthic foraminifera appeared and grew in large numbers (commonly >100 ind/12 ml sediment) in the <32 μm-size sediment fraction collected from 320 m water depth in the Skagerrak basin (North Sea). None of the shallow-water species that grew abundantly (Planorbulina mediterranensis, Morulaeplecta bulbosa, Bolivina pseudoplicata, Cuneata arctica, Eggerelloides scaber, Gavelinopsis praegeri) seem to grow or reproduce at or in the vicinity of the sampling site. Consequently, they must have been transported there as <32 μm-sized individuals. Their sudden appearance when exposed to shallow-water conditions suggests that they had been transported to the sampling site as propagules and that they could survive in the sediments until conditions became suitable for growth and, for some, reproduction. The lack of agglutination on the proloculi of the agglutinated taxa that appeared in the growth-chambers may enhance their passive transport via currents and, thereby, dispersal. Of all the indigenous foraminiferal species that occur at the sampling site, only Textularia earlandi and Bolivinellina pseudopunctata continued to grow and reproduce when transferred from bathyal (320 m) to simulated shallow-water (0 m) conditions. The former is considered a highly opportunistic species. According to the literature, most of the morphospecies which grew in the experiments are cosmopolitan. Our results indicate substantial inter-specific differences in dispersal potential and support previous suggestions that among free-living species, some serial forms have the potential for long-distance dispersal. Still, oceanographic, physical and ecological boundaries and barriers constrain the distribution of most species. In addition to benthic foraminifera, Gromia spp. (rhizarian protists related to the foraminifera) grew in >60% of the experimental growth-chambers. © 2009 Elsevier B.V. All rights reserved.


Hartmann W.K.,Planetary Science Institute | Werner S.C.,University of Oslo
Earth and Planetary Science Letters | Year: 2010

Recent controversies about systems of crater-count dating have been largely resolved, and with continuing refinements, crater counts will offer a fundamental geological tool to interpret not only ages, but also the nature of geological processes altering the surface of Mars. As an example of the latter technique, we present data on two debris aprons east of Hellas. The aprons show much shorter survival times of small craters than do the nearby contiguous plains. The order-of-magnitude depths of layers involved in the loss process can be judged from the depths of the affected craters. We infer that ice-rich layers in the top tens of meters of both aprons have lost crater topography within the last few 108yr, probably due to flow or sublimation of ice-rich materials. Mantling by ice-rich deposits, associated with climate change cycles of obliquity change, has probably also affected both the aprons and the plains. The crater-count tool thus adds chronological and vertical dimensional information to purely morphological studies. © 2009 Elsevier B.V.


Butenko M.A.,University of Oslo | Simon R.,Heinrich Heine University Dusseldorf
Journal of Experimental Botany | Year: 2015

Plants form new organs throughout their lives; this requires a balance between cell proliferation and differentiation, and between the generation and loss of organs. To do this, plants must maintain a population of stem cells within the meristems, and at the same time, closely control the identity and position of cells at the meristem boundaries as they differentiate to new leaf or flower primordia. Once developed, organs may need to be shed, either as a controlled developmental decision-such as floral abscission after pollination, or as a response to disease, environmental stress, and predators. Cell wall degradation at specialized abscission zone (AZ) cells needs to occur for this to take place, but since there is little cell rearrangement in plants, cell separation events are also important for plant architecture. In this Opinion paper we discuss the role of two peptide ligand signalling systems that control stem cell homeostasis and cell separation, respectively. We draw parallels between the signalling pathways and explore on the commonalities of the downstream components activated and controlled by the signalling peptides. We provide evidence for AZ cells having a meristem identity and discuss the role of identical KNOTTED-LIKE HOMEOBOX (KNOX) transcription factors in meristem maintenance and abscission. Lastly we explore the evolutionary relationship between the pathways. © 2015 The Author.


Sioud M.,University of Oslo
Methods in molecular biology (Clifton, N.J.) | Year: 2015

The ability to inhibit gene expression via RNA interference (RNAi) has a broad therapeutic potential for various human diseases such as infections and cancers. Recent advances in mechanistic understanding of RNAi have improved the design of functional small interfering (si) RNAs with superior potency and specificity. With respect to delivery, new developments in delivery strategies have facilitated preclinical and clinical siRNA applications. This review provides valuable insights to guide the design and delivery of therapeutic siRNAs.


Archontis V.,University of St. Andrews | Hansteen V.,University of Oslo
Astrophysical Journal Letters | Year: 2014

We report on the formation of small solar flares produced by patchy magnetic reconnection between interacting magnetic loops. A three-dimensional (3D) magnetohydrodynamic (MHD) numerical experiment was performed, where a uniform magnetic flux sheet was injected into a fully developed convective layer. The gradual emergence of the field into the solar atmosphere results in a network of magnetic loops, which interact dynamically forming current layers at their interfaces. The formation and ejection of plasmoids out of the current layers leads to patchy reconnection and the spontaneous formation of several small (size ≈1-2 Mm) flares. We find that these flares are short-lived (30 s-3 minutes) bursts of energy in the range O(1025-1027) erg, which is basically the nanoflare-microflare range. Their persistent formation and co-operative action and evolution leads to recurrent emission of fast EUV/X-ray jets and considerable plasma heating in the active corona. © 2014. The American Astronomical Society. All rights reserved.


Adipose tissue (AT) distribution is closely related to metabolic disease risk. GH reduces visceral and total body fat mass and induces whole body insulin resistance. Aims: To assess the effects of total and visceral adipose tissue (VAT) distribution and derived adipokines on systemic insulin resistance and lipid metabolism in acromegaly. Patients: Seventy adult patients with active acromegaly (43 males, age 49 ± 14 years) were evaluated before and a subset (n = 30, 20 males) was evaluated after treatment. Outcome Measures: Body composition and VAT, glucose metabolism parameters, lipids, C-reactive protein, and selected adipokines (vaspin, omentin, adiponectin, and leptin) were measured. Results: At baseline VAT was positively associated with glucose metabolism parameters, and with lipids. GH, but not IGF-I, was negatively associated with all AT depots (visceral, trunk, limbs, and total) (0.41 ≤ r ≤ 0.61, p < 0.001 for all) and positively associated with vaspin (r = 0.31, p = 0.013). Fat deposition after treatment was predominantly located on trunk and visceral depots. The lipid profile partially improved, with increases in HDL and ApoA-I and a decrease in Lp(a). Vaspin decreased and omentin increased. Adiponectin and leptin did not significantly change. The improvement in HOMA-IR was best predicted by the decreases in IGF-I and vaspin and the lack of trunk fat increase (R2 = 0.59, p = 0.001). Conclusions: (1) VAT was a metabolic risk factor for patients with active acromegaly; (2) vaspin and omentin were influenced by the disease activity but were not associated with VAT mass; (3) fat deposition after treatment was predominantly on the trunk and visceral depots; and (4) insulin resistance decreased and the lipid profile partially improved with treatment. © 2015 S. Karger AG, Basel Copyright © 2015, S. Karger AG. All rights reserved.


Abadie V.,University of Chicago | Sollid L.M.,University of Oslo | Barreiro L.B.,University of Chicago | Jabri B.,University of Chicago
Annual Review of Immunology | Year: 2011

Celiac disease (CD) is a gluten-sensitive enteropathy that develops in genetically susceptible individuals by exposure to cereal gluten proteins. This review integrates insights from immunological studies with results of recent genetic genome-wide association studies into a disease model. Genetic data, among others, suggest that viral infections are implicated and that natural killer effector pathways are important in the pathogenesis of CD, but most prominently these data converge with existing immunological findings that CD is primarily a T cellâ€"mediated immune disorder in which CD4 + T cells that recognize gluten peptides in the context of major histocompatibility class II molecules play a central role. Comparison of genetic pathways as well as genetic susceptibility loci between CD and other autoimmune and inflammatory disorders reveals that CD bears stronger resemblance to T cellâ€"mediated organ-specific autoimmune than to inflammatory diseases. Finally, we present evidence suggesting that the high prevalence of CD in modern societies may be the by-product of past selection for increased immune responses to combat infections in populations in which agriculture and cereals were introduced early on in the post-Neolithic period. © 2011 by Annual Reviews. All rights reserved.


Bruins Slot K.M.,University of Oslo
The Cochrane database of systematic reviews | Year: 2013

Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1950 to April 2013) and EMBASE (1980 to April 2013). In an effort to identify further published, unpublished and ongoing trials we searched trials registers and Google Scholar (July 2012). We also screened reference lists and contacted pharmaceutical companies, authors and sponsors of relevant published trials. Randomised controlled trials that directly compared the effects of long-term treatment (more than four weeks) with factor Xa inhibitors and VKAs for the prevention of cerebral and systemic embolism in patients with AF. We included patients with and without a previous stroke or TIA. The primary efficacy outcome was the composite endpoint of all strokes and other systemic embolic events. Two authors independently assessed trial quality and the risk of bias, and extracted data. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. However, in the case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects and performed a pre-specified sensitivity analysis excluding any fully open-label studies. We included data from 42,084 participants randomised into 10 trials. All participants had a confirmed diagnosis of AF (or atrial flutter) and were deemed by the randomising physician to be eligible for long-term anticoagulant treatment with a VKA (warfarin) with a target International Normalised Ratio (INR) of 2.0 to 3.0 in most patients. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux or rivaroxaban. Four trials were double-masked, five partially-masked (that is different doses of factor Xa inhibitor administered double-masked and warfarin administered open-label) and one was open-label. Median duration of follow-up ranged from 12 weeks to 1.9 years.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in nine of the included studies (40,777 participants). Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin (OR 0.81, 95% CI 0.72 to 0.91). We also analysed both components of this composite endpoint separately: treatment with a factor Xa inhibitor significantly decreased both the number of ischaemic and haemorrhagic strokes (OR 0.78, 95% CI 0.69 to 0.89) and the number of systemic embolic events (OR 0.53, 95% CI 0.32 to 0.87).All of the included studies (42,078 participants) reported the number of major bleedings. Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.89, 95% CI 0.81 to 0.98). There was, however, statistically significant and high heterogeneity (I2 = 81%) and an analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings (OR 0.92, 95% CI 0.63 to 1.34). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.84, 95% CI 0.76 to 0.92) but moderate heterogeneity was still observed (I2 = 65%). A similar sensitivity analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings in patients treated with factor Xa inhibitors (OR 0.78, 95% CI 0.57 to 1.05). Part of the observed heterogeneity can thus be explained by the increased risk of major bleedings in the factor Xa treatment arm in the single included open-label study, which studied idraparinux. Other heterogeneity might be explained by differences in baseline bleeding risks in the two largest trials of apixaban and rivaroxaban that we included in this review.Data on intracranial haemorrhages (ICHs) were reported in eight studies (39,638 participants). Treatment with a factor Xa inhibitor significantly reduced the risk of ICH compared with warfarin (OR 0.56, 95% CI 0.45 to 0.70). Again, we observed statistically significant heterogeneity (I2 = 60%). The pre-specified sensitivity analysis excluding the open-label study showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.51, 95% CI 0.41 to 0.64), without any sign of statistical heterogeneity (I2 = 0%).The number of patients who died from any cause was reported in six studies (38,924 participants). Treatment with a factor Xa inhibitor significantly reduced the number of all-cause deaths compared with warfarin (OR 0.88, 95% 0.81 to 0.97). Factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in patients with AF. Factor Xa inhibitors also seem to reduce the number of major bleedings and ICHs compared with warfarin, though the evidence for a reduction of major bleedings is somewhat less robust. There is currently no conclusive evidence to determine which factor Xa inhibitor is more effective and safer for long-term anticoagulant treatment of patients with AF as head-to-head studies of the different factor Xa inhibitors have not yet been performed.


Pedersen W.,University of Oslo | Skardhamar T.,Statistics Norway
Addiction | Year: 2010

Aim To examine the association between cannabis use during adolescence and young adulthood, and subsequent criminal charges. Methods Data were obtained from the Young in Norway Longitudinal Study. A population-based sample (n = 1353) was followed from 13 to 27 years of age. Data were gathered on cannabis use, alcohol consumption and alcohol problems, and use of other illegal substances such as amphetamines, cocaine and opiates. In addition, extensive information on socio-demographic, family and personal factors was collected. This data set was linked to individual-level information from official Norwegian crime statistics. Findings We found robust associations between cannabis use and later registered criminal charges, both in adolescence and in young adulthood. These associations were adjusted for a range of confounding factors, such as family socio-economic background, parental support and monitoring, educational achievement and career, previous criminal charges, conduct problems and history of cohabitation and marriage. In separate models, we controlled for alcohol measures and for use of other illegal substances. After adjustment, we still found strong associations between cannabis use and later criminal charges. However, when eliminating all types of drug-specific charges from our models, we no longer observed any significant association with cannabis use. Conclusions The study suggests that cannabis use in adolescence and early adulthood may be associated with subsequent involvement in criminal activity. However, the bulk of this involvement seems to be related to various types of drug-specific crime. Thus, the association seems to rest on the fact that use, possession and distribution of drugs such as cannabis is illegal. The study strengthens concerns about the laws relating to the use, possession and distribution of cannabis. © 2009 Society for the Study of Addiction.


Hessen D.O.,University of Oslo
Water (Switzerland) | Year: 2013

The pronounced increase in the cycling and deposition of biologically reactive dissolved inorganic nitrogen (DIN) over large areas globally not only cause increased concentrations of DIN in surface waters, but it will also affect nutrient ratios in rivers, lakes and coastal areas. This review addresses the flux and fate of DIN, focusing NO3 in lakes of boreal and alpine catchments. Not only DIN-deposition, but also catchment properties strongly affect the concentrations of NO3 in lakes, as well as NO3:total P (TP) ratios. This ratio displays an extreme variability, and does also serve as an indicator of shift between N and P-limitation of aquatic autotrophs. A high share of forests and bogs in the catchment generally decreases NO3:total P ratios, while alpine and subalpine catchments with sparse vegetation cover may have high NO3:total P ratios, especially in regions with high DIN-deposition. Several empirical and experimental studies indicate a shift from an initial N to P-limitation, but for N-limited lakes, an increased growth of phytoplankton, periphytes and macrophytes may be accredited to elevated inputs of DIN. An intensified P-limitation may also be a consequence of elevated DIN-deposition. This P-limitation may again yield higher C:P-ratios in autotrophs with negative impacts on grazers and higher trophic levels. © 2013 by the authors.


Exposed High Pressure (HP) and Ultra High Pressure (UHP) metamorphic terrains have been studied in order to assess the metamorphic processes and their role in changing petrophysical properties near Moho depth in continental root zones. The investigation points to a critical role of fluid and deformation in metamorphic transformation in the deep crust and upper mantle. This applies to a) formation of granulite facies areas, b) transformation of granulites to eclogites, c) retrogression of eclogite facies rocks to amphibolite and green schist facies rocks and d) the spinel lherzolite to garnet lherzolite transition. Dry rocks both feldspar bearing and ultramafic remain with their Pre-HP and UHP structures and anhydrous mineralogy preserved while reactions occur where fluid has been introduced along deformation zones. A mixture of metamorphic facies formed at widely variable times on metre to km scale will be present throughout the crust and upper mantle. Pseudotachylytes (frictional melts or ultracomminuted material) are observed in both ultramafic and feldspar bearing lithologies spatially associated with HP and UHP rocks suggesting that rock properties at Moho depth allow earthquakes. Seismicity enhances the metamorphic and metasomatic transitions through fragmentation and by opening the rock for fluid influx. Ductile eclogite facies shear zones nucleate along the brittle structures. These observations point to Moho as a rock processing zone with the following facets: 1. A metastable dry and strong lower crust and upper mantle. 2. Earthquakes and tremors result in fluid flow and HP metamorphism. 3. A pronounced weakening of the hydrated and transformed rocks allows flow of material and the development of new fabrics (LPO) in the transformed rocks. Deep tremor and earthquakes at Moho depth may record ongoing metamorphic transitions. © 2013 Elsevier B.V.


Gorbitz C.H.,University of Oslo
Journal of Physical Chemistry B | Year: 2011

The amino acid dl-norvaline undergoes two solid-solid phase transitions between room temperature and -180 °C. Single-crystal X-ray diffraction studies show that the first of these transitions, taking place around -80 °C, is completely reversible with respect to crystal quality, whereas the second, taking place below -100 °C, is not due to crystal delamination. High-quality crystal structures were obtained for the higher temperature phase β (at -70 °C) and the intermediate temperature phase α (at -90 °C). They show that although side-chain disorder is present for both forms, the β-to-α phase transition induces significant side-chain rearrangements, which are accompanied by a substantial reduction in molecular volume. The observed polymorphs are compared with those found for dl-aminobutyric acid, dl-norleucine, and dl-methionine. © 2011 American Chemical Society.


Baker T.,University of Oxford | Bull P.,University of Oslo
Astrophysical Journal | Year: 2015

Extremely large surveys with future experiments like Euclid and the SKA will soon allow us to access perturbation modes close to the Hubble scale, with wavenumbers If a modified gravity (MG) theory is responsible for cosmic acceleration, then the Hubble scale is a natural regime for deviations from General Relativity (GR) to become manifest. However, the majority of studies to date have concentrated on the consequences of alternative gravity theories for the subhorizon, quasi-static regime. In this paper, we investigate how modifications to the gravitational field equations affect perturbations around the Hubble scale. We choose functional forms to represent the generic scale-dependent behavior of gravity theories that modify GR at long wavelengths, and study the resulting deviations of ultra-large-scale relativistic observables from their GR behavior. We find that these are small unless modifications to the field equations are drastic. The angular dependence and redshift evolution of the deviations is highly parameterization- and survey-dependent, however, and so they are possibly a rich source of MG phenomenology if they can be measured. © 2015. The American Astronomical Society. All rights reserved..


Miloch W.J.,University of Oslo | Block D.,University of Kiel
Physics of Plasmas | Year: 2012

The charging of dust grain in the wake of another grains in sonic and supersonic collisionless plasma flows is studied by numerical simulations. We consider two grains aligned with the flow, as well as dust chains and multiple grain arrangements. It is found that the dust charge depends significantly on the flow speed, distance between the grains, and the grain arrangement. For two and three grains aligned, the charges on downstream grains depend linearly on the flow velocity and intergrain distance. The simulations are carried out with DiP3D, a three dimensional particle-in-cell code with both electrons and ions represented as numerical particles [W. J. Miloch et al., Phys. Plasmas 17, 103703 (2010)]. © 2012 American Institute of Physics.


Corfu F.,University of Oslo
Bulletin of the Geological Society of America | Year: 2013

The U-Pb system is a prime geochronometer, mainly due to its occurrence as a pair of isotopically distinct but chemically identical decay systems with 235U decaying to 207Pb and 238U to 206Pb, respectively. In addition, U has suitable half-lives and is hosted in some very convenient minerals, such as the widespread and robust mineral zircon. These twin decay systems, running at different speeds, allow an immediate verification of the validity of their ages, which must be concordant to be considered valid, although under favorable circumstances, discordant data can be extrapolated to the correct age. In detail, the degree of discordance can vary greatly, and discordance can have many different causes. The progress in developments of the U-Pb method is both a history of technical discoveries and advances, as well as a history of a long struggle toward concordance, toward an understanding of the causes of discordance, and toward ways to eliminate it. Despite the enormous progress achieved in this field, the problems of U-Pb discordance have not yet been completely resolved and will be one of the main hurdles to overcome in the future. This paper reviews some of the main stages in the evolution of the method, focusing especially on the style, causes, andimplications of U-Pb discordance in moderngeochronology. © 2013 Geological Society of America.


Berentsen S.,Haugesund Hospital | Tjonnfjord G.E.,University of Oslo
Blood Reviews | Year: 2012

Exact diagnosis of the subtype has essential therapeutic consequences in autoimmune hemolytic anemia. Cold-antibody types include primary chronic cold agglutinin disease (CAD) and rare cases of cold agglutinin syndrome (CAS) secondary to cancer or acute infection. Primary CAD is a clonal lymphoproliferative disorder. Not all patients require pharmacological therapy, but treatment seems indicated more often than previously thought. Corticosteroids should not be used to treat primary CAD. Half of the patients respond to rituximab monotherapy; median response duration is 11. months. The most efficient treatment to date is fludarabine and rituximab in combination, resulting in responses in 75%, complete responses in 20% and median response duration of more than 66. months. Toxicity may be a concern, and an individualized approach is discussed. Erythrocyte transfusions can be given provided specific precautions are undertaken. No evidence-based therapy exists in secondary CAS, but optimal treatment of the underlying disorder is essential when feasible. © 2012 Elsevier Ltd.


Cramer E.R.A.,Cornell University | Cramer E.R.A.,University of Oslo
PLoS ONE | Year: 2013

Physically challenging signals are likely to honestly indicate signaler quality. In trilled bird song two physically challenging parameters are vocal deviation (the speed of sound frequency modulation) and trill consistency (how precisely syllables are repeated). As predicted, in several species, they correlate with male quality, are preferred by females, and/or function in male-male signaling. Species may experience different selective pressures on their songs, however; for instance, there may be opposing selection between song complexity and song performance difficulty, such that in species where song complexity is strongly selected, there may not be strong selection on performance-based traits. I tested whether vocal deviation and trill consistency are signals of male quality in house wrens (Troglodytes aedon), a species with complex song structure. Males' singing ability did not correlate with male quality, except that older males sang with higher trill consistency, and males with more consistent trills responded more aggressively to playback (although a previous study found no effect of stimulus trill consistency on males' responses to playback). Males singing more challenging songs did not gain in polygyny, extra-pair paternity, or annual reproductive success. Moreover, none of the standard male quality measures I investigated correlated with mating or reproductive success. I conclude that vocal deviation and trill consistency do not signal male quality in this species. © 2013 Emily Rebecca Alison Cramer.


Hansteen V.H.,University of Oslo | Velli M.,Jet Propulsion Laboratory
Space Science Reviews | Year: 2012

Recent models of the fast solar wind are characterized by low coronal electron temperatures while proton, α-particle, and minor ion temperatures are expected to be quite high and generally anisotropic, including large temperatures perpendicular to the magnetic field and parallel beams. This entails that the electric field should be relatively unimportant and that solar wind outflows with both high asymptotic flow speeds but maintaining a low mass flux should be a natural outcome of plasma expansion along open polar magnetic field lines. In this chapter we will explain why such changes with respect to the classical, electron thermally driven solar wind have come about and outline the most important remaining concerning the astrophysics of coronal winds. The progress we have seen in the last decade is largely due observations made with instruments onboard Ulysses (McComas et al. in Space Sci. Rev. 72:93, 1995) and SOHO (Fleck et al. in The SOHO Mission, Kluwer, Dordrecht, 1995). These observations have spawned a new understanding of solar wind energetics, and the consideration of the chromosphere, corona, and solar wind as a unified system. We will begin by giving our own, highly biased, "pocket history" of solar wind theory highlighting the problems that had to be resolved in order to make the original Parker formulation of thermally driven winds conform with observational results. Central to this discussion are questions of how the wind's asymptotic flow speed and mass flux are set, but we will also touch upon higher order moments such as the ion and electron temperatures and heat fluxes as well as the possible role of Alfvén waves and particle effects in driving the solar wind outflow. Solar wind scaling laws will be discussed in the context of the origin of slow and fast wind streams. © 2012 Springer Science+Business Media B.V.


Lehtio L.,University of Oulu | Chi N.-W.,University of California at San Diego | Krauss S.,University of Oslo
FEBS Journal | Year: 2013

Tankyrase 1 and tankyrase 2 are poly(ADP-ribosyl)ases that are distinguishable from other members of the enzyme family by the structural features of the catalytic domain, and the presence of a sterile α-motif multimerization domain and an ankyrin repeat protein-interaction domain. Tankyrases are implicated in a multitude of cellular functions, including telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt-β-catenin signaling, and viral replication. In these processes, tankyrases interact with target proteins, catalyze poly(ADP-ribosyl)ation, and regulate protein interactions and stability. The proposed roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified. The selectivity and potency of these small molecules can be rationalized by how they fit within the NAD+-binding groove of the catalytic domain. Some molecules bind to the nicotinamide subsite, such as generic diphtheria toxin-like ADP-ribosyltransferase inhibitors, whereas others bind to a distinct adenosine subsite that diverges from other diphtheria toxin-like ADP-ribosyltransferases and confers specificity. A highly potent dual-site inhibitor is also available. Within the last few years, tankyrase inhibitors have proved to be useful chemical probes and potential lead compounds, especially for specific cancers. This review describes the biochemical and cellular functions of the tankyrase subfamily of human ADP-ribosyltransferases. Tankyrases use NAD+ as a substrate to covalently modify acceptor proteins leading to dissociation of macromolecular complexes and protein degradation. Existing tankyrase inhibitors target the nicotinamide and/or the adenine pocket of the donor NAD+-binding cleft of the catalytic domain. © 2013 FEBS.


Olsen I.,University of Oslo
Journal of Oral Microbiology | Year: 2014

The objective of the present review is to discuss if the yeast vacuole can be used as a target for attenuation of Candida albicans virulence. Literature searches were made electronically using predetermined inclusion criteria. The main searches were made through a systematic strategy in PubMed and authoritative journals in microbiology. It appeared that C. albicans virulence may be reduced by inhibiting vacuolar protontranslocating ATPase (V-ATPase) functions and acidification of the yeast vacuole by V-ATPase inhibitors, by seeking the synergistic effect of antifungals and non-antifungals affecting yeast vacuolar functions, and by inhibiting filament production - also regulated by the vacuole. Accordingly, we may impair C. albicans virulence by inhibiting functions of its vacuole, which plays essential roles during colonization and invasion of the host. Except for drugs where indications for clinical use can be redefined, such interventions may be closer to theory than to reality at the moment. But since the yeast is so difficult to eradicate by antifungal treatment, it could be rewarding to seek new strategies for reducing its virulence rather than trying to eradicate it completely from the microbiota, which often turns out to be impossible. © 2014 Ingar Olsen.


The rise in Infantile Autism, learning problems, cognitive decline with age, Alzheimer's, Parkinson's Diseases and the SIDS epidemic, has a common cause in the rising dietary deficit in Omega-3 brain-food. This paper suggests that aside from the wider concept of Autism Spectrum Disorders (ASD) and Pervasive Developmental Disorders (PDD), the rise in Infantile Autism (IA) in the last decade is the effect ofdeficient brain-food (Omega-3). The consequent delay of development, prolongs the 2nd regressive event in infancy to pruning of the centre in the Medial Frontal Lobe System that connects Hippocampus and Singulum. With a consequently defective Supplementary Motor Area (SMA), the Delayed Response Function is affected leading to persistent psychosis. Post-Pubertal Episodic Psychoses are associated with acute reduction of excitation, a risk of breakdown of circuitry, insufficient fill-in mechanisms, and silent spots. An acute psychosis occurs if the silent spots compromise SMA. Only two brain areas have continuous neurogenesis, indicating their important functions: the Hippocampus and Olfactory Bulb that belongs to the Lateral Frontal Lobe System essential to survival. Concerned with necessity of action in response to the environment, it relies upon short-term memory and Acute Feedback Mechanisms influenced by emotion and motivation from the external world. In contrast, the Medial Frontal Lobe network is controlled by Feed-Forward Predictive Mechanisms related to storage of information The Delayed Response Function is mastered at 7 months, when 2nd event occurs with pruning of axons and dendrites. An abolished or defective Delayed Response Function seriously incapacitates an individual: A defective "Social Brain" with an inability for conscious action and to communicate, predominates in IA. There is a near lack of speech, despite normal vision and hearing in the minority without marked adversity in pregnancy, at delivery or in infancy. The recent rise in IA despite no rise in adversity signifies a rising deficiency in brain-food. This is suggested by a changing clinical picture: no Mental Retardation in an IA majority. Deficit in Olfaction is pathognomonic in schizophrenia since 30yrs and distinguishes the Asperger Syndrome. If brain-food deficiency alone sufficiently prolongs pruning to cause absent activity in SMA in infancy, less mentally retarded IA from other causes might be observed. Deficit in brain-food was evident in the Sudden Infant Death Syndrome: birthweight averaged 200-300g lower than sibs, Omega-3 levels in brainstem were lower than controls. Only 20% SIDS died in first hypoxic episode, suggesting such episodes are more frequent than we imagined. Children with learning-behaviour problems have similarly depressed birthweight. A general deficiency in Omega-3 contributes to the lacking reduction in Schizophrenia, despite early puberty predominates. Olfactory Bulb is first affected in the Alzheimer's and Parkinson's Disease. Cognitive decline with age, hippocampal dysfunctions rises markedly irrespective of disease, but the major mental illnesses and Infantile Autism in particular, benefit from brainfood that might also prevent a development of these disorders. To secure optimal brain function in the coming generations, there is aneed to change the diet now from its emphasis on protein for body growth to food for the brain. This means there is a need to increase fish and sea food consumption. © 2011 A B Academic Publishers.


Jeppesen E.,University of Oslo
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

High prevalence of psychosocial problems has been observed in clinical studies of teenagers who have a parent with cancer. In contrast, we used a population-based design to study such problems in teenagers who have a parent with cancer (cases) compared with matched teenagers with cancer-free parents (controls). We hypothesized that higher prevalence of psychosocial problems would be observed in cases compared with controls and that sex differences would be observed between cases and controls. We used data from a cross-sectional population-based survey of teenagers (Young-HUNT study). Among 8,986 teenage participants, 120 of their parents had invasive cancer before the Young-HUNT study according to the Norwegian Cancer Registry. These parents had 143 teenagers (cases) participating in the Young-HUNT study. Matched on sex, age, and municipality, 429 control teenagers with cancer-free parents were drawn from the Young-HUNT study. Six psychosocial problems were studied. No significant differences in psychosocial problems were observed between cases and controls in the total sample. Fewer case daughters reported eating problems compared with control daughters, and more case sons reported eating problems compared with control sons. More case daughters than case sons reported somatic stress symptoms and low self-esteem and displayed more caseness of anxiety/depression. These three sex differences were also observed among controls, indicating that they were general sex differences. In this population-based study, teenagers who had a parent with cancer did not have higher prevalence of psychosocial problems than controls. Sex differences observed in previous clinically based studies were confirmed but may simply reflect sex differences observed among teenagers in general.


Olsen I.,University of Oslo
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2015

Biofilms are heterogeneous structures composed of bacterial cells surrounded by a matrix and attached to solid surfaces. The bacteria here are 100 to 1,000 times more tolerant to antimicrobials than corresponding planktonic cells. Biofilms can be difficult to eradicate when they cause biofilm-related diseases, e.g., implant infections, cystic fibrosis, urinary tract infections, and periodontal diseases. A number of phenotypic features of the biofilm can be involved in biofilm-specific tolerance and resistance. Little is known about the molecular mechanisms involved. The current review deals with both phenotypic and molecular mechanisms of biofilm-specific antibiotic tolerance and resistance. © 2015, Springer-Verlag Berlin Heidelberg.


Buil A.,Swiss Institute of Bioinformatics | Buil A.,University of Oslo | Buil A.,Kings College London
Nature genetics | Year: 2015

Understanding the genetic architecture of gene expression is an intermediate step in understanding the genetic architecture of complex diseases. RNA sequencing technologies have improved the quantification of gene expression and allow measurement of allele-specific expression (ASE). ASE is hypothesized to result from the direct effect of cis regulatory variants, but a proper estimation of the causes of ASE has not been performed thus far. In this study, we take advantage of a sample of twins to measure the relative contributions of genetic and environmental effects to ASE, and we find substantial effects from gene × gene (G×G) and gene × environment (G×E) interactions. We propose a model where ASE requires genetic variability in cis, a difference in the sequence of both alleles, but where the magnitude of the ASE effect depends on trans genetic and environmental factors that interact with the cis genetic variants.


To study the association between self-reported physical activity (PA) and objectively measured PA, resting heart rate, and physical fitness. During 2007-08, 5017 men and 5607 women aged 30-69 years attended the sixth survey of the Tromsø study. Self-reported PA during leisure-time and work were assessed and resting heart rate was measured. In a sub-study, the activity study, PA (Actigraph LLC) and physical fitness (VO&x2082;(max)) were objectively measured among 313 healthy men and women aged 40-44 years. Self-reported leisure PA was significantly correlated with VO&x2082;(max) (ml/kg/min) (women 0.40, p < 0.001, men 0.44 p < 0.001) and moderate-to-vigorous PA (>2000 counts/min) (women 0.28, p < 0.01, men 0.25, p < 0.01). The intra-class correlation coefficient between self-reported leisure PA and overall PA (counts/min) measured by accelerometer was 0.62 (95% CI 0.51, 0.71) for women and 0.59 (95% CI 0.47, 0.69) for men, and for VO&x2082;(max) the intra-class correlation coefficient was 0.86 (95% CI 0.81, 0.90) for both sexes.


Background Earlier investigations have shown mortality effects of community socio-economic resources. However, the sex differences have not been clear, and the estimates may well have been biased because of inadequate control for community factors affecting both the socio-economic resources and mortality. The objective of this study was to see whether any effects appeared when time-invariant community characteristics were controlled by including community dummies (fixed effects) and whether there were any differences between women and men. Methods Discrete-time hazard models for all-cause mortality were estimated for 1981e2002 for all Norwegians aged 60e89, using register data. There were 730 000 deaths among 1.7 million people observed during 19 million person-years. Average education was measured for 433 municipalities for each of the 22 years. Results According to the simplest models, a high average education in the municipality is associated with increased mortality. Control for population size (timeaveraged) reversed the effects. Inclusion of municipality dummies instead of population size, to control also for additional unobserved time-invariant municipality characteristics, gave very different results: the effects were even stronger for men, while those for women were no longer significant. The results were quite robust to alternative specifications, including the use of a lagged average-education variable. Conclusion The study supports the idea that community socio-economic resources may affect mortality and suggests that sex differentials may deserve more attention. It also illustrates the importance of controlling for time-invariant community factors. Unless these can be easily measured, in future investigations one may consider establishing longitudinal data and using a fixedeffects approach such as that used here.


The aim of this study was to investigate the incidence of dysplasia in the 'normal' contralateral hip in patients with unilateral developmental dislocation of the hip (DDH) and to evaluate the long-term prognosis of such hips. A total of 48 patients (40 girls and eight boys) were treated for late-detected unilateral DDH between 1958 and 1962. After preliminary skin traction, closed reduction was achieved at a mean age of 17.8 months (4 to 65) in all except one patient who needed open reduction. In 25 patients early derotation femoral osteotomy of the contralateral hip had been undertaken within three years of reduction, and later surgery in ten patients. Radiographs taken during childhood and adulthood were reviewed. The mean age of the patients was 50.9 years (43 to 55) at the time of the latest radiological review. In all, eight patients (17%) developed dysplasia of the contralateral hip, defined as a centre-edge (CE) angle < 20° during childhood or at skeletal maturity. Six of these patients underwent surgery to improve cover of the femoral head; the dysplasia improved in two after varus femoral osteotomy and in two after an acetabular shelf operation. During longterm follow-up the dysplasia deteriorated to subluxation in two patients (CE angles 4° and 5°, respectively) who both developed osteoarthritis (OA), and one of these underwent total hip replacement at the age of 49 years. In conclusion, the long-term prognosis for the contralateral hip was relatively good, as OA occurred in only two hips (4%) at a mean follow-up of 50 years. Regular review of the 'normal' side is indicated, and corrective surgery should be undertaken in those who develop subluxation. © 2014 The British Editorial Society of Bone & Joint Surgery.


Moosmayer S.,Martina Hansens Hospital | Tariq R.,Unilabs Diagnostics | Stiris M.,Unilabs Radiology and Laboratory Services | Smith H.-J.,University of Oslo
Journal of Bone and Joint Surgery - Series A | Year: 2013

Background: Little is known about the clinical and anatomic progression of asymptomatic rotator cuff tears. The purpose of our study was to assess if deterioration in rotator cuff tear anatomy would be correlated to the development of symptoms. Methods: Fifty patients with initially asymptomatic full-thickness rotator cuff tears were followed clinically, sonographically, and bymagnetic resonance imaging over three years. Changes of tear size, muscle atrophy, fatty degeneration, and condition of the long head of the biceps tendon were compared between tears that developed symptoms and those that did not. Results: Eighteen of fifty tears developed symptoms during follow-up. There was a significantly larger increase (p = 0.02) in the mean tear size in the newly symptomatic group (10.6 mm) when compared with the still-asymptomatic group (3.3 mm). The rate of progressing to advanced muscle atrophy was higher (p = 0.08) in the newly symptomatic group (35% [six of seventeen subjects]) when compared with the still-asymptomatic group (12% [three of twenty-five subjects]). The rate of fatty degeneration was significantly higher (p = 0.02) in the newly symptomatic group (35% [six of seventeen subjects]) when compared with the still-asymptomatic group (4% [one of twenty-five subjects]). The rate of pathology of the long head of the biceps tendon was significantly higher (p = 0.02) in the newly symptomatic group (33% [six of eighteen subjects]) when compared with the still-asymptomatic group (6% [two of thirty-two subjects]). Conclusions: During a relatively short-term follow-up, a substantial percentage of asymptomatic rotator cuff tears became symptomatic and underwent anatomic deterioration. Increase in tear size and decrease of muscle quality were correlated to the development of symptoms. Subjects diagnosed with an asymptomatic rotator cuff tear should be informed about the natural history of the condition and follow-up with repeated imaging may be indicated to monitor tear progression. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2013 by The Journal of Bone and Joint Surgery, Incorporated.


Gourraud P.-A.,University of California at San Francisco | Harbo H.F.,University of California at San Francisco | Harbo H.F.,University of Oslo | Hauser S.L.,University of California at San Francisco | Baranzini S.E.,University of California at San Francisco
Immunological Reviews | Year: 2012

Multiple sclerosis (MS) is a prevalent inflammatory disease of the central nervous system that often leads to disability in young adults. Treatment options are limited and often only partly effective. The disease is likely caused by a complex interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration. A series of genomic studies have confirmed a central role for the immune system in the development of MS, including genetic association studies that have now dramatically expanded the roster of MS susceptibility genes beyond the longstanding human leukocyte antigen (HLA) association in MS first identified nearly 40years ago. Advances in technology together with novel models for collaboration across research groups have enabled the discovery of more than 50 non-HLA genetic risk factors associated with MS. However, with a large proportion of the disease heritability still unaccounted for, current studies are now geared towards identification of causal alleles, associated pathways, epigenetic mechanisms, and gene-environment interactions. This article reviews recent efforts in addressing the genetics of MS and the challenges posed by an ever increasing amount of analyzable data, which is spearheading development of novel statistical methods necessary to cope with such complexity. © 2012 John Wiley & Sons A/S.


King H.E.,University of Munster | Plumper O.,University of Oslo | Putnis A.,University of Munster
Environmental Science and Technology | Year: 2010

Large-scale olivine carbonation has been proposed as a potential method for sequestering CO2 emissions. For in situ carbonation techniques, understanding the relationship between the formation of carbonate and other phases is important to predict the impact of possible passivating layers on the reaction. Therefore, we have conducted reactions of olivine with carbonated saline solutions in unstirred batch reactors. Altering the reaction conditions changed the Mg-carbonate morphology. We propose that this corresponded to changes in the ability of the system to precipitate hydromagnesite or magnesite. During high-temperature reactions (200 °C), an amorphous silicaenriched phase was precipitated that was transformed to lizardite as the reaction progressed. Hematite was also precipitated in the initial stages of these reactions but dissolved as the reaction proceeded. Comparison of the experimental observations with reaction models indicates that the reactions are governed by the interfacial fluid composition. The presence of a new Mgsilicate phase and the formation of secondary products at the olivine surface are likely to limit the extent of olivine to carbonate conversion. © 2010 American Chemical Society.


Olsen I.,University of Oslo
Acta odontologica Scandinavica | Year: 2015

OBJECTIVE: To give an overview of the periodontal-systemic connection seen from a microbiologist.METHODS: Original research papers, review articles and workshop proceedings were consulted.RESULTS: Periodontal bacteria can cross epithelial cells, enter the circulation, invade endothelial cells, induce endothelial cell dysfunction and activate inflammatory and immune responses. Several studies support the association between periodontitis (PD) and cardiovascular disease. Severe PD involves a risk for development of type 2 diabetes. Maternal PD is moderately associated with adverse pregnancy outcome and pre-eclampsia. Dental plaque can contain respiratory pathogens able to promote chronic obstructive pulmonary disease and pneumonia. Periodontal bacterial DNA has been detected in synovial fluid of patients with rheumatoid arthritis. Minor evidence exists for associations between PD and chronic kidney disease, obesity, cancer, metabolic syndrome and cognitive impairment. Concerns can be raised as to the interpretation of some study results due to heterogeneity in definitions used for PD, too much weight upon in vitro studies with a few selected organisms and failing recognition that the majority of the periodontal microbiota is not yet cultivated.CONCLUSION: Periodontal bacteria may participate in extra-oral infections such as CVD, diabetes, APO, pre-eclampsia, COPD, pneumonia, RA, CKD, obesity, cancer, MetS and cognitive impairment. Most knowledge is based on associations which do not necessarily imply causality. Future studies should reach consensus on the definition of PD and systemic disease outcomes, recognize the full spectrum of the microbiota in PD and bacteremia, including not-yet-cultivated organisms and delineate the clinical significance of genetic strain variations and the role of periodontopathogenic vs gut organisms within atheromatous lesions. For demonstration of causality, large, long-term clinical studies should use well-defined criteria for PD and robust disease outcomes to elucidate the importance of PD intervention and prevention.


Abbas N.,University of Oslo
Current radiopharmaceuticals | Year: 2013

The aim of the present study was to compare the biodistribution, normal tissue toxicity and therapeutic effect of the alpha-particle emitting 227Th-trastuzumab and the beta-particle emitting 177Lu-trastuzumab in mice with HER2- expressing SKBR-3 breast cancer xenografts. Biodistributions of the two radioimmunoconjugates were determined at different time points after i.v. injection. Inhibition of tumor growth was measured after single injection of 227Th-trastuzumab (200, 400, 600 or 1000 kBq/kg), 177Lu-trastuzumab (40 or 200 MBq/kg) or saline. The toxicity profiles were compared by measurements of body weight,clinical chemistry and hematological parameters, as well as histological examination of tissue specimens. 400 kBq/kg of 227Th-trastuzumab and 40 MBq/kg of 177Lu-trastuzumab both resulted in an absorbed radiation dose to tumor of approximately 3 Gy. A significant anti-tumor effect and increased survival were observed at injected dosages of 400-1000 kBq/kg of 227Th-trastuzumab and 200 MBq/kg of 177Lu-trastuzumab as compared to the saline control. When compared at the same therapeutic effect level (100% prolonged growth delay as compared to control) the absorbed radiation dose of 227Th-trastuzumab was 3 times lower than with 177Lu-trastuzumab, indicating a relative biological effect (RBE) of 2.8 for 227Th-trastuzumab. In contrast, when compared at the same temporary decrease of WBC count (50% decrease in number of white blood cells as compared to control), the growth delay was 3 times longer with 177Lutrastuzumab than with 227Th-trastuzumab, which indicates that the therapeutic index was three times higher for 177Lutrastuzumab than for 227Th-trastuzumab. In this xenograft model the RBE was higher for 227Th-trastuzumab than for 177Lu-trastuzumab, while the therapeutic index of 177Lu-trastuzumab was superior to that of 227Th-trastuzumab.


Heyerdahl H.,University of Oslo
Current radiopharmaceuticals | Year: 2013

The aim of the current study was to investigate the therapeutic effect of 227Th-radioimmunotherapy on intraperitoneally growing human bioluminescent HER2 positive ovarian cancer cells. In vitro toxicity of 227Th-trastuzumab in bioluminescent SKOV3-luc-D3 ovarian cancer cells was assessed in a growth assay. The biodistribution of intraperitoneally administrated 227Th-trastuzumab in athymic nude mice without tumor cells was determined. For in vivo therapy, seventy female athymic nude mice were intraperitoneally inoculated with tumor cells 17 days prior to injection of single 227Th-trastuzumab doses of 1000 kBq/kg, 600 kBq/kg or 400 kBq/kg, or three injections with 400 kBq/kg 227Th-trastuzumab separated by 4 weeks. Two control groups were given either 20 μg unlabeled trastuzumab or 0.9% NaCl. In vivo bioluminescence imaging was performed weekly before and after onset of therapy. Tumor growth, survival and toxicity were compared. There was a statistically significant therapeutic effect of the 227Th-trastuzumab treatment both with respect to survival and tumor growth. The maximum tolerated dosage was 600 kBq/kg 227Th-trastuzumab. In the in vitro study, two hours incubation with 20 kBq/ml of 227Th-trastuzumab, followed by washing, and subsequent culture of the cells resulted in an average absorbed radiation dose of 6 Gy after 11 days and complete growth inhibition. Targeted alpha therapy with 227Th-trastuzumab of human SKOV3-luc-D3 cells growing intraperitoneally in nude mice was clearly superior to unlabeled trastuzumab therapy. The results warrant further studies of 227Th-radioimmunotherapy used as adjuvant treatment and for metastatic cancer.


Vento M.,University of Valencia | Saugstad O.D.,University of Oslo
Journal of Pediatrics | Year: 2011

Resuscitation is the most common procedure performed in neonatology. However, new contributions based on scientific evidence challenge the traditional procedures. Of these new contributions, the use of room-air instead of 100% oxygen and titration of the oxygen inspiratory fraction according to oximetry and heart rate represent a new approach in the resuscitation of both term and preterm newborns. © 2011 Mosby Inc. All rights reserved.


Hirschfield G.M.,University of Birmingham | Karlsen T.H.,University of Oslo | Karlsen T.H.,University of Bergen | Lindor K.D.,Arizona State University | Adams D.H.,University of Birmingham
The Lancet | Year: 2013

Primary sclerosing cholangitis is the classic hepatobiliary manifestation of inflammatory bowel disease and is generally chronic and progressive. Patients frequently present with asymptomatic, anicteric cholestasis, but many develop progressive biliary strictures with time, leading to recurrent cholangitis, biliary cirrhosis, and end-stage liver disease. Medical treatment does not slow the progression of disease, and many patients need liver transplantation, after which recurrent disease is a risk. The increased incidence of hepatobiliary cancer, which is not related to the underlying severity of biliary fibrosis, is of particular concern. Risk of colorectal cancer is also increased in patients with coexistent inflammatory bowel disease. Mechanistic insights have arisen from studies of secondary sclerosing cholangitis, in which a similar clinical profile is associated with a specific cause, and genomic studies have elucidated potential disease-initiating pathways in the primary form. The close association between inflammatory bowel disease and primary sclerosing cholangitis underscores the need to further understand the role of environmental factors in generation of lymphocytes that are postulated to be retargeted, deleteriously, to the biliary tree. Treatment of primary sclerosing cholangitis is confined to supportive measures, but advances in pathobiology suggest that new stratified approaches will soon be available.


Vanem E.,University of Oslo | Bitner-Gregersen E.M.,DNV GL
Applied Ocean Research | Year: 2012

This paper presents a stochastic model in space and time for significant wave height, a Bayesian hierarchical space-time model. The model consists of different components in a hierarchical manner including a component to model the contribution from long-term trends in the wave climate. As far as the authors are aware, no such model of significant wave height to date exploits the flexible framework of Bayesian hierarchical space-time models, which allow modelling of complex dependence structures in space and time and incorporation of physical features and prior knowledge, yet at the same time remains intuitive and easily interpreted. Furthermore, including a trend component in the model is a novel feature.The model presented in this paper has been fitted to significant wave height data for monthly maxima over an area in the North Atlantic ocean, and aims at describing the temporal and spatial variability of the data over a period of more than 44 years for the chosen area. In particular, the model identifies long-term trends present in the data. Subsequently, it will be explored how the results from the model can be linked to structural loads and response calculations. The proposed approach is illustrated by an example showing the potential impact of the estimated long-term trends of significant wave height on the wave-induced structural loads of an oil tanker. © 2012 Elsevier Ltd.


Pedersen T.R.,University of Oslo
American journal of cardiovascular drugs : drugs, devices, and other interventions | Year: 2010

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are extremely effective at reducing low-density lipoprotein (LDL) cholesterol and have been demonstrated to reduce mortality and the risk of major cardiovascular events in a number of large primary and secondary prevention studies. The linear relationship between LDL-cholesterol and cardiovascular risk suggests statins work solely by reducing LDL-cholesterol, and that ancillary properties do not contribute to cardiovascular risk reduction. In recent years, however, a number of additional non-lipid-lowering, or 'pleiotropic', effects of statins have been suggested to contribute to their efficacy in cardiovascular disease. The first data to suggest that statins may have benefits beyond lipid lowering came from the Heart Protection Study, in which simvastatin reduced mortality and morbidity even in patients with 'normal' LDL-cholesterol levels (2.6mmol/L or 100mg/dL). It has since been demonstrated, however, that cardiovascular risk remains high at this LDL concentration, but is substantially reduced in those achieving levels below 2.0mmol/L (77mg/dL). Evidence for the pleiotropic effects of statins in heart failure comes largely from retrospective and subgroup analyses of large studies. When statin therapy is compared with placebo, or when high-dose statin therapy is compared with low-dose treatment, a lower incidence of heart failure or hospitalization is observed. Despite promising retrospective data, however, two prospective studies of rosuvastatin in the treatment of patients with New York Heart Association class II-IV heart failure showed no impact on the primary endpoint and only one of the studies showed a lower rate of hospitalization favouring rosuvastatin. A number of small studies has shown evidence for mechanisms of action of statins outside of LDL-cholesterol lowering, including improvements in endothelial function, halting or retardation of atheroma development, reduction in inflammation and antithrombotic effects. The linear relationship between LDL-cholesterol lowering and reduction in coronary heart disease risk, as well as a lack of conclusive evidence for other mechanisms of action raise the question of whether any cholesterol-lowering agent is equally effective for reducing cardiovascular risk, but recent data from the torcetrapib clinical trial programme suggest this is not the case. Future cholesterol-lowering modalities must be able to demonstrate efficacy and good tolerability in large-scale clinical trials.


Berg T.,University of Oslo
Frontiers in Physiology | Year: 2014

Here, the influence of ß3-adrenoceptors on catecholamine release in normotensive and spontaneously hypertensive rats was analyzed. Blood pressure was recorded through a femoral artery catheter, and cardiac output by ascending aorta flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated with tyramine, which allowed presynaptic release-control to be reflected as changes in the plasma norepinephrine concentration. ß3-adrenoceptor agonist (BRL37344) reduced baseline vascular resistance, the tyramine-stimulated norepinephrine overflow and the positive inotropic response to tyramine in hypertensive but not normotensive rats. ß3-adrenoceptor antagonist (SR59230A) reduced tyramine-stimulated norepinephrine release in both strains and the secretion of epinephrine in hypertensive rats. SR59230A reduced tyramine-induced tachycardia in normotensive rats, and prevented down-regulation of the tyramine-induced rise in resistance in hypertensive rats. It was concluded that the contradicting results obtained by agonist vs. antagonist, could be explained by their interaction with two different ß-adrenoceptors: The BRL37344-dependent inhibition of stimulated norepinephrine release and positive inotropic response to tyramine was compatible with stimulation of ß3-adrenoceptor coupling to inhibitory G-protein. This was observed only in hypertensive rats during stimulated, high levels of circulating catecholamines. The effect of BRL37344 on baseline vascular resistance was compatible with activation of ß3-adrenoceptor coupling to endothelial nitric oxide synthase. The inhibitory effect of SR59230A on tyramine-stimulated norepinephrine release in both strains, the increased TPR-response to tyramine in hypertensive rats and tachycardia in normotensive rats may result from inhibition of the low-affinity-state ß1-adrenoceptor, also known as the putative ß4-adrenoceptor. © 2014 Berg.


Rindal E.,University of Oslo | Brower A.V.,Middle Tennessee State University
Cladistics | Year: 2011

The use of model-based methods to infer a phylogenetic tree from a given data set is frequently motivated by the truism that under certain circumstances the parsimony approach (MP) may produce incorrect topologies, while explicit model-based approaches are believed to avoid this problem. In the realm of empirical data from actual taxa, it is not known (or knowable) how commonly MP, maximum-likelihood or Bayesian inference are inaccurate. To test the perceived need for "sophisticated" model-based approaches, we assessed the degree of congruence between empirical phylogenetic hypotheses generated by alternative methods applied to DNA sequence data in a sample of 1000 recently published articles. Of 504 articles that employed multiple methods, only two exhibited strongly supported incongruence among alternative methods. This result suggests that the MP approach does not produce deviant hypotheses of relationship due to convergent evolution in long branches. Our finding therefore indicates that the use of multiple analytical methods is largely superfluous. We encourage the use of analytical approaches unencumbered by ad hoc assumptions that sap the explanatory power of the evidence. © The Willi Hennig Society 2010.


Graetz J.,HRL Laboratories | Hauback B.C.,University of Oslo
MRS Bulletin | Year: 2013

Aluminum hydride (AlH3), and the complex aluminum hydrides (e.g., M 3AlH6, MAlH5, M2AlH 7, M(AlH4) n), make up a fascinating class of materials that have received considerable attention over the past 60 years for their use as explosives, reducing agents, solid rocket propellants, as well as a hydrogen source for portable power systems. The recent renaissance in hydrogen storage research, particularly for automotive applications, has generated renewed interest in aluminum-based hydrides due to their capacity to store up to 11 wt% hydrogen with volumetric capacities up to 150 g H2/L (more than twice that of liquid hydrogen). In addition, hydrogen can be released from these materials by low temperature thermolysis (<100°C), making them well-suited for proton exchange membrane fuel cells and other low temperature applications. This article covers recent research on aluminum-based hydrides, including crystal structures, thermodynamics, kinetics, hydrogenation conditions, and regeneration methods. © 2013 Materials Research Society.


Bakland G.,University of Tromso | Gran J.T.,University of Oslo | Nossent J.C.,University of Tromso
Annals of the Rheumatic Diseases | Year: 2011

Background: The onset of disease in ankylosing spondylitis (AS) is generally earlier than in other joint diseases, exposing patients to a prolonged burden of disease. Whether this is associated with excess mortality is still uncertain. Radiation therapy for AS has previously been shown to increase mortality. The present study investigated standardised mortality ratios, causes of death and survival predictors in a large regional cohort of patients with AS. Method: A total of 677 patients with AS followed at our hospital since 1977 were matched by gender, age and postal area to three controls from the general population and standardised mortality rates (SMRs) were calculated. Cause of death was established using patients' hospital records. In a subset of 360 patients, clinical and demographic data collected during an earlier research visit (1998-2000) were used in a prospective multivariate analysis of predictors for mortality in AS. Results: The crude mortality among patients with AS in this study was 14.5% (98 patients); SMR was only significantly increased among male patients compared with female patients (1.63 vs 1.38, p<0.001). Circulatory disease was the most frequent cause of death (40.0%), followed by malignant (26.8%) and infectious (23.2%) diseases. Factors independently associated with reduced survival were diagnostic delay (OR 1.05), increasing levels of C-reactive protein (OR 2.68), work disability (OR 3.65) and not using any non-steroidal anti-inflammatory drugs (OR 4.35). Conclusions: Mortality is increased in patients with AS and circulatory disease is the most frequent cause of death. Parameters reflecting the duration and intensity of inflammation are associated with reduced survival. These results indicate that, to improve long-term survival in AS, there is a need for early detection and anti-inflammatory treatment as well as a vigilant approach for cardiovascular risk factors.


Koivisto T.S.,University of Oslo | Urban F.R.,University of British Columbia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

A completely new mechanism to generate the observed amount of large-scale cosmological magnetic fields is introduced in the context of three-form inflation. The amplification of the fields occurs via fourth order dynamics of the vector perturbations and avoids the backreaction problem that plagues most previously introduced mechanisms. © 2012 American Physical Society.


Schwengner R.,Helmholtz Center Dresden | Frauendorf S.,University of Notre Dame | Larsen A.C.,University of Oslo
Physical Review Letters | Year: 2013

Magnetic dipole strength functions are deduced from averages of a large number of M1 transition strengths calculated within the shell model for the nuclides Zr90, Mo94, Mo95, and Mo96. An enhancement of M1 strength toward low transition energy is found for all nuclides considered. Large M1 strengths appear for transitions between close-lying states with configurations including proton as well as neutron high-j orbits that recouple their spins and add up their magnetic moments coherently. The M1 strength function deduced from the calculated M1 transition strengths is compatible with the low-energy enhancement found in (He3, He′3) and (d, p) experiments. The Letter presents an explanation of the experimental findings. © 2013 American Physical Society.


Johannessen A.,University of Oslo
Bioanalysis | Year: 2010

By the end of 2008, 4 million people were receiving antiretroviral treatment for HIV/AIDS in low-and middle-income countries. In industrialized countries, monitoring of treatment with viral load measurements and drug resistance testing is the standard of care to ensure early detection of treatment failure and a prompt switch to a fully active second-line regimen, before drug-resistant mutations accumulate. These tests, however, require highly specialized laboratories and stringent procedures for storage and shipment of plasma, and are rarely available in resource-limited settings. Therefore, treatment failure in such settings is usually not detected until patients develop severe immunodeficiency, at which stage widespread resistance is likely. Dried blood spots (DBS) are easy to collect and store, and can be a convenient alternative to plasma in settings with limited laboratory capacity. This review provides an overview of possible applications of DBS technologies in the monitoring of HIV treatment, with the main focus on viral load quantification and drug resistance testing. © 2010 Future Science Ltd.


Halvorsen T.G.,Norwegian University of Science and Technology | Sorensen T.M.,University of Oslo
Nuclear Physics B | Year: 2012

We propose a general formulation of simplicial lattice gauge theory inspired by the finite element method. Numerical tests of convergence towards continuum results are performed for several SU(2) gauge fields. Additionally, we perform simplicial Monte Carlo quantum gauge field simulations involving measurements of the action as well as differently sized Wilson loops as functions of β. © 2011 Elsevier B.V.


Moen J.,University of Oslo
Philosophy, Psychiatry and Psychology | Year: 2015

The debate concerning evidence-based medicine (EBM) is often articulated in dichotomous terms. For example, it has been claimed that EBM is linked epistemologically to the theory of foundationalism and that important critics of EBM emerge from antifoundationalist epistemologies. This may leave us stuck in an overly general and fruitless debate concerning how different kinds of knowledge should be ranked. By contrast, when framed in less dichotomous terms, opposing positions of EBM might be brought to agree that the different perspectives they represent are both relevant and important for psychiatric practice. Disagreement would then focus on how the perspectives should be related and weighted. In this paper, I use contemporary pragmatism’s conception of a vocabulary to bypass the realism–relativism dichotomy and to make a rethinking of EBM’s role in psychiatry. According to this approach, scientific evidence as well as narrative perspectives should always be evaluated in specific contexts, according to how well they serve our concrete, particular ends. Although the role of scientific evidence in the formation of psychiatric practice is indisputably important, that role is not to provide a basis, in any meaningful, nonambiguous sense, for psychiatry as such. This point is illustrated by a pragmatist approach to Straus et al.’s operationalized version of EBM. © 2015 by The Johns Hopkins University Press


Seligmann H.,University of Oslo
BioSystems | Year: 2010

Protein synthesis (translation) stops at stop codons, codons not complemented by tRNA anticodons. tRNAs matching stops, antitermination (Ter) tRNAs, prevent translational termination, producing dysfunctional proteins. Genomes avoid tRNAs with anticodons whose complement (the anticodon of the 'antisense' tRNA) matches stops. This suggests that antisense tRNAs, which also form cloverleaves, are occasionally expressed. Mitochondrial antisense tRNA expression is plausible, because both DNA strands are transcribed as single RNAs, and tRNA structures signal RNA maturation. Results describe potential antisense Ter tRNAs in mammalian mitochondrial genomes detected by tRNAscan-SE, and evidence for adaptations preventing translational antitermination: genomes possessing Ter tRNAs use less corresponding stop codons; antisense Ter tRNAs form weaker cloverleaves than homologuous non-Ter antisense tRNAs; and genomic stop codon usages decrease with stabilities of codon-anticodon interactions and of Ter tRNA cloverleaves. This suggests that antisense tRNAs frequently function in translation. Results suggest that opposite strand coding is exceptional in modern genes, yet might be frequent for mitochondrial tRNAs. This adds antisense tRNA templating to other mitochondrial tRNA functions: sense tRNA templating, formation and regulation of secondary (light strand DNA) replication origins. Antitermination probably affects mitochondrial degenerative diseases and ageing: pathogenic mutations are twice as frequent in tRNAs with antisense Ter anticodons than in other tRNAs, and species lacking mitochondrial antisense Ter tRNAs have longer mean maximal lifespans than those possessing antisense Ter tRNAs. © 2010 Elsevier Ireland Ltd.


Hellesland J.,University of Oslo
Engineering Structures | Year: 2012

The paper deals with approximate effective length formulas, and how such formulas may be applied in system instability analysis of frames. End restraint assessments in a system instability perspective are discussed, and available formulas are reviewed. The overview is limited to the important class of compression members that are either completely unbraced (free-to-sway, zero shear) or fully braced against lateral translation of one end relative to the other. Whereas most approximate effective length formulas have been developed for positive end restraints, buckling modes of compression members in a frame can be associated with both positive and negative end restraints. It is a main concern of the study to identify the applicability of the various approximate formulas for a reasonable wide range of positive and negative restraint combinations. Extensive comparisons with exact effective length results have been carried out for isolated members, and applications in system instability analyses are demonstrated. © 2012 Elsevier Ltd.


Dal L.A.,University of Oslo | Kachelriess M.,Norwegian University of Science and Technology
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We calculate the antideuteron yield in dark matter annihilations on an event-by-event basis using the herwig++ MonteCarlo generator. We present the resulting antideuteron fluxes for quark and gauge boson final states. As deuteron production in the coalescence model depends on momentum differences between nucleons that are small compared to Λ QCD, it is potentially very sensitive to the hadronization model employed. We therefore compare our antideuteron yields to earlier results based on pythia, thereby estimating their uncertainties. We also briefly discuss the importance of n>2 final states for annihilations of heavy dark matter particles. © 2012 American Physical Society.


Ohlberger J.,University of Oslo
Functional Ecology | Year: 2013

Accumulating evidence suggests that the average body size of many organisms is declining in response to climate warming. This phenomenon has been suggested to represent a universal response to warming that may impose significant adverse effects on ecosystem functioning and services. However, we do not have a thorough understanding of why body sizes are commonly declining, and why some organisms show the opposite response. Because ectotherms constitute the vast majority of organism biomass and about 99% of species worldwide, it is particularly important to understand how ectotherms respond to a warming climate. This review discusses the underlying physiological mechanisms of changes in ectotherm body size and addresses observed responses within a broad ecological context at different levels of organization, from individuals to communities, particularly in aquatic systems. Warming-induced responses in average body size are not only determined by changes in rates of individual growth and development, but also mediated through size-dependent feedbacks at the population level, as well as competitive and predatory interactions within the community. Emergent properties at higher organizational levels have already been observed in both experimental and natural systems. Various approaches will be required for enhancing our knowledge about the importance of such processes in natural systems. These include controlled semi-natural experiments and phylogenetic comparisons as well as statistical models of time-series data and theoretical models linking climate effects at the individual, population and community levels. Understanding causes of observed changes in organism body sizes and how these depend on the ecological context is essential for improving our predictions and the management of ecosystems in the face of a warming climate. © 2013 British Ecological Society.


Solberg A.H.S.,University of Oslo
Proceedings of the IEEE | Year: 2012

Oil spills on the sea surface are observed relatively often. Pollution due to either accidents or deliberate oily discharges from ships represents a serious threat to the marine environment. Operational oil spill monitoring is currently done using a combination of satellite monitoring and aircraft surveillance. The combined use of satellite-based synthetic aperture radar (SAR) images and aircraft surveillance flights is a cost-effective way to monitor oil spills in large ocean areas and catch the polluters. SAR images enable covering large areas, but aircraft observations are needed to prosecute the polluter, and in certain cases to verity the oil spill. Traditionally, oil spill detection is based on single polarization SAR images. Oil spills can be discriminated from look-alikes based on a set of features describing the contrast, shape, homogeneity, source, and surroundings of the slick. Good performance is reported for single-polarization oil spill detection, but in certain cases the oil slicks cannot be discriminated from biogenic films. In the recent years, a number of studies have shown that polarimetric SAR can improve the discrimination between oil slicks and biogenic films. Several features computed from dual-pol or quad-pol images have been proposed. These include both quad-pol features like polarimetric entropy and anisotropy, mean scattering angle, polarimetric span, conformity coefficient, as well as the dual-pol features standard deviation of the copolarized phase difference and the copolarized correlation coefficient. As dual-pol SAR imagery is now available on a regular basis from Cosmo Skymed and TerraSAR-X, and quad-pol data are available from RADARSAT-2, polarimetric SAR can now be utilized on a more regular basis. Optical data from sensors like Aqua MODIS and ENVISAT MERIS can be a useful supplement under certain cloud-free conditions. © 2012 IEEE.


Wohlfahrt J.C.,University of Oslo
The International journal of oral & maxillofacial implants | Year: 2012

Porous titanium granules (PTG) may have potential as an osteoconductive bone graft substitute to treat peri-implant osseous defects. The aim of this study was to analyze clinical and radiographic outcomes of peri-implant osseous defects after treatment with PTG. This prospective, randomized, case-control, clinical 12-month study compared open-flap debridement and surface decontamination with titanium curettes and 24% ethylenediaminetetraacetic acid gel (n = 16) to the same protocol but with the addition of PTG (n = 16). One-, two-, and three-wall infrabony defects were included. Patients were given amoxicillin and metronidazole 3 days before surgery and for 7 days afterwards. Implants were submerged and allowed to heal for 6 months. Probing pocket depths, bleeding on probing, implant stability using resonance frequency analysis, and radiographic evaluation were performed at baseline and at 12 months. The threshold for significance was set at .05. Change in radiographic defect height and percent fill of the peri-implant osseous defect significantly favored patients treated with PTG. Both treatment modalities demonstrated significant improvements in probing pocket depth, but significant differences between groups were not observed. The PTG-treated implants showed an increase in implant stability quotient (ISQ) of 1.6 units, compared with a decrease of 0.7 ISQ for the control group. No adverse effects were associated with PTG treatment. Reconstruction with PTG resulted in significantly better radiographic peri-implant defect fill compared with controls; however, the results do not necessarily imply reosseointegration or osseointegration of PTG particles. Improvements in clinical parameters were seen in both groups, but no differences between groups were demonstrated.


Hansen T.F.,University of Oslo | Pelabon C.,Norwegian University of Science and Technology | Houle D.,Florida State University
Evolutionary Biology | Year: 2011

Short-term evolutionary potential depends on the additive genetic variance in the population. The additive variance is often measured as heritability, the fraction of the total phenotypic variance that is additive. Heritability is thus a common measure of evolutionary potential. An alternative is to measure evolutionary potential as expected proportional change under a unit strength of selection. This yields the mean-scaled additive variance as a measure of evolvability. Houle in Genetics 130:195-204, (1992) showed that these two ways of scaling additive variance are often inconsistent and can lead to different conclusions as to what traits are more evolvable. Here, we explore this relation in more detail through a literature review, and through theoretical arguments. We show that the correlation between heritability and evolvability is essentially zero, and we argue that this is likely due to inherent positive correlations between the additive variance and other components of phenotypic variance. This means that heritabilities are unsuitable as measures of evolutionary potential in natural populations. More generally we argue that scaling always involves non-trivial assumptions, and that a lack of awareness of these assumptions constitutes a systemic error in the field of evolutionary biology. © 2011 Springer Science+Business Media, LLC.


A class of rigid isoreticular metal-organic frameworks (A-IRMOF-M0, A = Zn, Cd, alkaline-earth metals) were systematically investigated using DFT calculations. The calculated lattice parameters supplement the incomplete available theoretical structural parameters for Zn-IRMOF-M0, and extends the prediction to the remaining members of this series. The estimated bulk moduli of A-IRMOF-M0 series range from 16.4 to 45.3 GPa indicating relatively soft materials, but still rank the most rigid ones in the IRMOF series. The electronic structure calculations demonstrated that the band gap for A-IRMOF-M0 series is ca. 3.2-3.7 eV, indicating all are semiconductors. The large magnitude of estimated formation energies (-53 to -88 kJ/mol), indicative of very high stabilities of IRMOF-M0 series. The linear optical properties of these materials were systematically investigated, which demonstrated that A-IRMOF-M0 series have much stronger optical responses than that of MOF-5 (e.g., using the lower photon energy can obtain responses as strong as that of MOF-5). This provides very useful and detailed information for the experimental confirmation and the potential application of A-IRMOF-M0 series as solar cell materials and optoelectronic devices. The detailed analysis of chemical bonding in the A-IRMOF-M0 series reveals the nature of the A-O, O-C, and C-C bonds, i.e., the A-O bond has mainly ionic interaction whereas O-C and C-C exhibit mainly covalent interactions. The findings in this paper might contribute to a comprehensive understanding about this kind of material and shed insight into the synthesis and application of novel and robust MOFs. ©2013 Elsevier Inc. All rights reserved.


Sedimentology, sequence stratigraphy and facies analysis have for many years been disciplines rather separate from diagenesis which is concerned with processes occurring after deposition. Prediction of rock properties as a function of burial depth in sedimentary basins requires that these disciplines become more integrated. Compaction of sedimentary rocks is driven towards increased density (lower porosity) and higher rock velocity as functions of burial depth (effective stress) and temperature. Both the mechanical and chemical compaction of sedimentary rocks are functions of the primary textural and mineralogical composition of the sediments at the time of deposition and after shallow burial diagenesis. This is controlled by the provenance, transport and depositional environment. Many published sedimentological studies, however, contain little information about the mineralogical and textural composition of the sedimentary sequences.Near the surface, sediments are in an open geochemical system due to groundwater flow, diffusion and evaporation. Here their composition may be changed by mineral dissolution and transport of the dissolved components. At greater depth, below the reach of significant meteoric water flow, the porewater has an exceedingly low mobility and capacity to transport solids in solution. The porewater will gradually approach equilibrium with the minerals present, reducing the concentration gradients in the porewater and the potential for both advective and diffusive transport of solids in solution. Significant increased porosity (secondary porosity) is dependent on the dissolution and removal of solids in solution which may occur during freshwater flushing at shallow depth dissolving feldspar and precipitating kaolinite. Below the reach of freshwater the porewater flow is limited and represents a geochemically nearly closed system. The porewater will in most marine sediments be in equilibrium with calcite, even if it occurs in small amounts. Prediction of rock properties such as porosity and seismic velocity at a certain depth in a sedimentary basin must be based on the burial history (effective stress and temperature), but the primary mineralogical and textural composition of the sediments is equally important. Studies of depositional environments and provenance should therefore be integrated with diagenesis and be a part of basin analysis which is used for basin modelling. © 2013 Elsevier B.V.


Domeier M.,University of Oslo
Gondwana Research | Year: 2015

The tectonics, dynamics, and biogeographic landscape of the early Paleozoic were dominated by the opening and expansion of one large ocean-the Rheic-and the diminution to terminal closure of another-Iapetus. An understanding of the evolution of these oceans is thus central to an understanding of the early Paleozoic, but their chronicle also presents a rich temporal profile of the Wilson cycle, illustrating continental-scale rifting, microcontinent formation, ocean basin development, arc accretion, and continent-continent collision. Nevertheless, contemporary paleogeographic models of the Iapetus and Rheic oceans remain mostly schematic or spatiotemporally disjointed, which limits their utility and hinders their testing. Moreover, many of the important kinematic and dynamic aspects of the evolution of these oceans are impossible to unambiguously resolve from a conceptual perspective and the existing models unsurprisingly present a host of contradictory scenarios. With the specific aim to resolve some of the uncertainties in the evolution of this early Paleozoic domain, and a broader aim to instigate the application of quantitative kinematic models to the early Paleozoic, I present a new plate tectonic model for the Iapetus and Rheic oceans. The model has realistic tectonic plates, which include oceanic lithosphere, that are defined by explicit and rigorously managed plate boundaries, the nature and kinematics of which are derived from geological evidence and plate tectonic principles. Accompanying the presentation and discussion of the plate model, an extensive review of the underlying geological and paleogeographic data is also presented. © 2015 International Association for Gondwana Research.


Dyba T.,University of Oslo
IEEE Software | Year: 2013

An overview of how context affects empirical software engineering research and how to better contextualize empirical evidence proposes a contextual framework that answers journalism's 'Five Ws': What, Who, Where, When, and Why. © 1984-2012 IEEE.


Mengshoel A.M.,University of Oslo
Arthritis Care and Research | Year: 2010

Objective. To examine the nature of fatigue and how it is managed in daily life situations by individuals with ankylosing spondylitis (AS). Methods. Twelve informants, 8 women and 4 men ages 30-59 years, who had lived with the diagnosis of AS for 6 months to 36 years, participated in qualitative interviews. They were asked to describe their daily life during good and bad days of AS, and to give examples of everyday situations where they experienced fatigue and what they did to recover. The text analysis consisted of identifying and coding meaningful statements, sorting the codes into categories, and condensing themes. Results. Two separate conditions of fatigue were identified. One consisted of comprehensible, manageable tiredness related to a life strain that was exacerbated by having AS. Life strain-related tiredness indicated to the respondents that they should rest or temporarily slow down, and this protected them from overexertion. The other condition was an unfamiliar and unmanageable fatigue that was related to their illness. Illness-related fatigue was accompanied by unbearable pain, severe stiffness, and heaviness of the body that could not be alleviated by the individual. This condition was considered a sign of the onset or a flare up of inflammation. Conclusion. Fatigue in the individuals with AS varied over time, and took the form of 2 different conditions. Life strain-related tiredness had a positive aspect in that it protected against overstrain and guided life strain regulation. In contrast, illness-related fatigue was nonpurposive for the individuals and seems to call for medical therapy. © 2010, American College of Rheumatology.


Mainini R.,National institute for astrophysics | Mota D.F.,University of Oslo
Astrophysical Journal | Year: 2012

We provide an exhaustive analysis of the Integrated Sachs-Wolfe (ISW) effect in the context of coupled dark energy cosmologies where a component of massive neutrinos is also present. We focus on the effects of both the coupling between dark matter and dark energy and of the neutrino mass on the cross-correlation between galaxy/quasar distributions and ISW effect. We provide a simple expression to appropriately rescale the galaxy bias when comparing different cosmologies. Theoretical predictions of the cross-correlation function are then compared with observational data. We find that, while it is not possible to distinguish among the models at low redshifts, discrepancies between coupled models and ΛCDM increase with z. In spite of this, current data alone does not seem able to distinguish between coupled models and ΛCDM. However, we show that upcoming galaxy surveys will permit tomographic analysis that will allow us to better discriminate among the models. We discuss the effects on cross-correlation measurements of ignoring galaxy bias evolution, b(z), and magnification bias correction and provide fitting formulae for b(z) for the cosmologies considered. We compare three different tomographic schemes and investigate how the expected signal-to-noise ratio, S/N, of the ISW-LSS cross-correlation changes when increasing the number of tomographic bins. The dependence of S/N on the area of the survey and the survey shot noise is also discussed.


Asheim G.B.,University of Oslo
Environmental and Resource Economics | Year: 2013

This paper presents a distributional argument for the use of supply-side climate policies whereby carbon emissions are controlled through (i) depletion quotas or (ii) permanent confiscation of a fraction of the in situ carbon stocks. The modeling considers intertemporal competitive equilibria in the Cobb-Douglas version of the Dasgupta-Heal-Solow-Stiglitz model of capital accumulation and costless resource extraction. It is shown how policies (i) and (ii) preserve the functional distribution of income between capital owners and resource owners, compared to the case where no climate policy is needed, while suggested demand-side policies do not. Such observations are of interest as avoiding functional redistribution may facilitate climate change negotiations. The paper discusses policy implications of the analysis outside the simplified setting of the stylized model. © 2012 Springer Science+Business Media B.V.


Saugstad O.D.,University of Oslo | Aune D.,Norwegian University of Science and Technology | Aune D.,Imperial College London
Neonatology | Year: 2013

Background: The optimal oxygen saturation for extremely low birth weight infants in the postnatal period beyond the delivery room is not known. Objectives: To summarize and discuss the results of the randomized trials, constituting the NEOPROM (Neonatal Oxygenation Prospective Meta-analysis) collaborative study, examining the effect of low versus high functional oxygen saturation targets in the postnatal period in premature infants with gestational age <28 weeks. Methods: A meta-analysis of SUPPORT (Surfactant, Positive Pressure and Pulse Oximetry Randomized Trial), the three BOOST II (Benefits of Oxygen Saturation Targeting) studies and the COT (Canadian Oxygen Trial) was performed including a total of 4,911 infants randomized to either a low (85-89%) or high (91-95%) functional oxygen saturation (SpO2) within the first 24 h after birth. Results: Relative risks (RR; 95% CIs) comparing a low versus a high oxygen saturation target were 1.41 (1.14-1.74) for mortality at discharge or at follow-up, 0.74 (0.59-0.92) for severe retinopathy of prematurity, 0.95 (0.86-1.04) for physiologic bronchopulmonary dysplasia, 1.25 (1.05-1.49) for necrotizing enterocolitis, 1.02 (0.88-1.19) for brain injury, and 1.01 (0.95-1.08) for patent ductus arteriosus. RR >1.0 favors a high oxygen saturation. Conclusions: RRs for mortality and necrotizing enterocolitis are significantly increased and severe retinopathy of prematurity significantly reduced in low compared to high oxygen saturation target infants. There are no differences regarding physiologic bronchopulmonary dysplasia, brain injury or patent ductus arteriosus between the groups. Based on these results, it is suggested that functional SpO2 should be targeted at 90-95% in infants with gestational age <28 weeks until 36 weeks' postmenstrual age. However, there are still several unanswered questions in this field. © 2013 S. Karger AG, Basel.


Collins A.R.,University of Oslo
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The comet assay is a sensitive electrophoretic method for measuring DNA breaks at the level of single cells, used widely in genotoxicity experiments, biomonitoring, and in fundamental research. Its sensitivity and range of application are increased by the incorporation of an extra step, after lysis of agarose-embedded cells, in which the DNA is digested with lesion-specific endonucleases (DNA repair enzymes of bacterial or phage origin). Enzymes with specificity for oxidised purines, oxidised pyrimidines, alkylated bases, UV-induced cyclobutane pyrimidine dimers, and misincorporated uracil have been employed. The additional enzyme-sensitive sites, over and above the strand breaks detected in the standard comet assay, give a quantitative estimate of the number of specific lesions present in the cells.


Undheim K.,University of Oslo
Synthesis (Germany) | Year: 2014

The fundamental spirane framework consists of two monocyclic rings linked in an orthogonal relationship by a common ring atom. In spiranes with no annular heteroatom, four carbon atoms are bonded directly to the quaternary spirocarbon. The spirocarbon may be the site of a stereogenic centre and stereoisomerism. This review covers families of spiranes where one or both rings carry additional annular heteroatoms, mainly N, O or S. The heteroatoms are indicated by replacement prefixes. In general, the term 'hetera' denotes a nonspecified annulated heteroatom which may be N, O, or S. The presentation is arranged with preference for the size of the monocyclic rings and thereafter the nature of the annular heteroatoms. In general, rigid spirocyclic structures provide wide variations of spatial disposition of the functional groups. When the spirane skeleton consists of small- or medium-sized rings, a rigid structure results that also confers stiffness onto molecules in which the spirane may be embedded. The rigidity of such systems provides a stiff framework for the attachment of pharmacophoric groups, or a rigid framework for metal coordination. Reference is made to a limited number of studies of physico-chemical properties of small-ring systems. Nitrogen-containing systems are most common. 1 Introduction and Definitions 2 Heteraspiro[2.m]alkanes 3 Heteraspiro[3.m]alkanes 4 Heteraspiro[4.m]alkanes 5 Heteraspiro[5.m]alkanes. © Georg Thieme Verlag Stuttgart, New York.


Zachrisson A.,University of Oslo
International Journal of Psychoanalysis | Year: 2011

This paper presents a heuristic model for the dynamics of psychoanalytic supervision. It is not a manual for how to perform supervision, but a model for how to identify and think about the complex elements and forces influencing the supervisory process. The point of departure is that psychoanalysis is a composite craft in which seemingly contrary elements like strict rules and creative intuitions have their place and interact. Several aspects of supervision are discussed: aims, learning processes, teaching methods, relationship, emotional atmosphere and evaluation. Competence is given a pivotal place in the model. The main feature of the model is that these aspects of supervision are all seen as suspended in a field of dynamic tensions between phenomena in real or apparent opposition. One example of this is the tension in the supervisory relationship between supervisor as instructor acting as an authority for the candidate whilst being a mentor fostering autonomy in the candidate. It is argued that related kinds of dynamics characterize several aspects of psychoanalytic supervision and that these tensions are inherent in analytic work. In conclusion a key word picture of the model is presented. © 2011 Institute of Psychoanalysis.


Nortvedt P.,University of Oslo
Health Care Analysis | Year: 2011

This paper aims at addressing some questions considering the conflicting normative claims of partiality, i.e. to provide for the caring needs of the particular patient, and impartial claims of treating all patients with a relevant need equally. This ethical conflict between different conceptions of moral responsibilities within professional ethics relates to debates between an ethics of care and an ethics of justice. An ethics of care is a particularistic position that endorses some form of partiality, i.e. favouring persons to whom one stands in particular relationships. This paper argues that also a professional ethics must endorse some kind of partiality at the clinical level of health care. In fact, consideration of care for particular patients is a prerequisite for giving proper and attentive care towards the individual patient. This paper will discuss how partial concerns might be balanced against claims of distributive justice within the frame of the formal principle of justice. It is concluded that there is an urgent need for the recognition of the consequences of macro-level decisions for the possibility of the discharge of moral responsibility on a clinical level of health care. This would mean that health care institutions should adapt for the possibility of a basic standard of proper care and attention for the individual patient. © 2010 Springer Science+Business Media, LLC.


Leistedt B.,University College London | Peiris H.V.,University College London | Verde L.,University of Barcelona | Verde L.,University of Oslo
Physical Review Letters | Year: 2014

It has been claimed recently that massive sterile neutrinos could bring about a new concordance between observations of the cosmic microwave background, the large-scale structure of the Universe, and local measurements of the Hubble constant, H0. We demonstrate that this apparent concordance results from combining data sets which are in significant tension, even within this extended model, possibly indicating remaining systematic biases in the measurements. We further show that this tension remains when the cosmological model is further extended to include significant tensor modes, as suggested by the recent BICEP2 results. Using the Bayesian evidence, we show that the cold dark matter model with a cosmological constant is strongly favored over its neutrino extensions by various combinations of data sets. Robust data combinations yield stringent limits of ∑mν≳0.3eV and mν,sterileeff≳0.3eV at 95% C.L. for the sum of active and sterile neutrinos, respectively. © 2014 American Physical Society.


To evaluate if exercise programs in trials for patients with ankylosing spondylitis (AS) have the potential for effectiveness. A systematic literature search was performed and randomized trials examining the effectiveness of exercise programs for AS patients were analyzed according to 3 elements: whether the exercise programs were designed according to the American College of Sports Medicine (ACSM) recommendations for developing cardiorespiratory fitness, muscular strength, and flexibility; whether physiologic responses were properly measured; and whether adherence to programs was monitored. Twelve trials with a total of 826 AS patients were evaluated. Five trials included cardiorespiratory exercise as a part of the exercise programs. One of these met the ACSM recommendations for intensity, duration, frequency, and length of the exercise period. This trial showed the greatest within-group improvement in aerobic capacity (effect size [ES] 2.19). Five trials included muscular strength training, but none measured the physiologic responses nor met the recommendations for improving muscular strength. Eleven trials included flexibility training, but the programs were poorly described overall. Small improvements in spinal mobility (ES range 0.02-0.67) were reported in all trials. Finally, 4 trials reported on participants' adherence to the exercise programs, but only 1 provided sufficient information to evaluate the possible influence of the adherence. The quality of interventions in exercise trials for patients with AS can be improved. Future trials should also focus on measuring and reporting physiologic responses and adherence to exercise interventions. Copyright © 2011 by the American College of Rheumatology.


Furst E.L.',University of Oslo
Culture, Medicine and Psychiatry | Year: 2015

Struck by a cardiac arrest that lasted 3/4 of an hour, a 53-year-old man suddenly collapsed one day at work. The result was a serious anoxic brain damage that developed into dementia. This essay presents the process of ‘coming back to himself’ while it questions what this concept might imply. The descriptions and analyses rest upon an ethnographic study of his life, at hospitals and then at home, assisted by his wife, who is also the author of this article. Theoretically, the analysis depends on Merleau-Ponty’s phenomenology of perception and is also based on the therapeutic use of music in treating people with dementia championed by Oliver Sachs. It is argued that the field of medicine has much to learn from the anthropological method of long-term observation, as well as theories of embodiment that see the body as simultaneously being an object and a subject. © 2014, Springer Science+Business Media New York.


Agewall S.,University of Oslo
Current atherosclerosis reports | Year: 2014

Detection of a rise and/or fall of cardiac troponin (cTn) is the cornerstone in the diagnosis of myocardial infarction (MI). For the acute risk, it is hypothesized that cTn mirrors activated coagulation and platelet reactivity and indicates the presence of a ruptured plaque, which may help to identify patients at high risk who benefit particularly from aggressive pharmacological treatment and early invasive strategy. High-sensitivity assays using the 99th percentile as the threshold for positivity can achieve sensitivity at presentation of 90 % or more, and performance further improves with subsequent measurements within 3 to 6 h. By 3 h, negative predictive values of almost 100 % have been reported. However, use of assays with higher sensitivity lead ultimately to a loss of clinical specificity. Thus, other conditions than MI, such as stroke, pulmonary embolism, sepsis, acute perimyocarditis, Takotsubo, acute heart failure and tachycardia also can go with elevated troponin levels. The detection of brief rise and subsequent fall of troponin concentration in marathon runners, and even in healthy subjects, after a standardized exercise test has cast doubts on the hypothesis that troponin is released only upon irreversible damage. This kind of troponin leakage may originate from a cytosolic compartment of the cells and not from the necrosis of thin filaments.


Omholt S.W.,University of Oslo
Progress in Biophysics and Molecular Biology | Year: 2013

The genotype-phenotype relation is at the core of theoretical biology. It is argued why a mathematically based explanatory structure of this relation is in principle possible, and why it has to embrace both sequence to consequence and consequence to sequence phenomena. It is suggested that the primary role of DNA in the chain of causality is that its presence allows a living system to induce perturbations of its own dynamics as a function of its own system state or phenome, i.e. it capacitates living systems to self-transcend beyond those morphogenetic limits that exist for non-living open physical systems in general. Dynamic models bridging genotypes with phenotypic variation in a causally cohesive way are shown to provide explanations of genetic phenomena that go well beyond the explanatory domains of statistically oriented genetics theory construction. A theory originally proposed by Rupert Riedl, which implies that the morphospace that is reachable by the standing genetic variation in a population is quite restricted due to systemic constraints, is shown to provide a foundation for a mathematical conceptualization of numerous evolutionary phenomena associated with the phenotypic consequence to sequence relation. The paper may be considered a call to arms to mathematicians and the mathematically inclined to rise to the challenge of developing new formalisms capable of dealing with the deep defining characteristics of living systems. © 2012 Elsevier Ltd.


Zachrisson A.,University of Oslo
International Journal of Psychoanalysis | Year: 2013

In the Oedipus myth we find a dramatic representation of the child's passionate ties to its parents. In the play Oedipus the King, Sophocles relates the theme of the myth to the question of self-knowledge. This was the predominant reading in German 19th century thinking, and even as a student Freud was fascinated by Oedipus' character - not primarily as the protagonist of an oedipal drama, but as the solver of divine riddles and as an individual striving for self-knowledge. Inspired by Vellacott, Steiner has proposed an alternative reading of Oedipus the King as a play about a cover-up of the truth. The text supports both these arguments. The pivotal theme of the tragedy is Oedipus' conflict between his desire to know himself and his opposing wish to cover up the truth that will bring disaster. It is this complex character of Oedipus and the intensity of his conflict-ridden struggle for self-knowledge that has made the tragedy to a rich source of inspiration for psychoanalytic concept formation and understanding both of emotional and cognitive development up to our own time. Copyright © 2012 Institute of Psychoanalysis.


Saugstad O.D.,University of Oslo
Journal of Perinatal Medicine | Year: 2010

Aims: To summarize present knowledge regarding the relation between oxidative stress and development of bronchopulmonary dysplasia (BPD). Methods: Relevant literature searched at Pubmed and other sources. Results: Oxidative stress is generated in a number of conditions and by a number of causes such as inflammation and hyperoxia. Ontogenic aspects are discussed. Oxidative stress as physiological regulators, its relation to transcription factors and inflammation is summarized. The role of oxygen and antioxidant therapy and newborn resuscitation for development and prevention of BPD as well as new therapeutic modes especially the use of growth factors, gene therapy and stem cells, are briefly discussed. Conclusion: Oxidative stress and BPD are associated. A better understanding of this association is necessary in order to reduce the severity and the incidence of the condition. Copyright © by Walter de Gruyter, Berlin, New York.


Reine P.A.,University of Oslo
Scandinavian journal of clinical and laboratory investigation | Year: 2013

The pharmacokinetics of the immunosuppressant mycophenolic acid (MPA) demonstrates high inter- and intra-patient variability. Variation in the binding of MPA to albumin has been postulated to be an important factor in this variability, and monitoring of free MPA has been suggested to improve therapeutic drug monitoring (TDM) of MPA. Inosine monophosphate dehydrogenase (IMPDH) is the target enzyme for MPA, therefore the IMPDH activity in lymphocytes can serve as a marker of the MPA-specific response. This study aimed to explore how the albumin concentration influences the free concentration of MPA in liver transplant recipients and to assess whether alteration in the free MPA influences IMPDH activity in CD4 + cells. Blood samples were taken from 20 liver transplant recipients on two separate occasions (days 3-5 and 16-21). Total and free concentrations of MPA, and IMPDH activity were measured during the first 4 h of each dose interval. Albumin levels correlated with the free fraction of MPA. However, the total MPA and free MPA were equal predictors of the immunosuppressive response as defined by IMPDH activity. Total and free MPA are equally good predictors of the immunosuppressive effect exerted by MPA as defined by IMPDH activity. IMPDH activity measurements represent a promising approach to TDM in patients treated with MPA.


Ludvigsen S.R.,University of Oslo
Learning, Media and Technology | Year: 2012

In this article, I develop a perspective on learning as multilayered phenomena. I take a socio-genetic approach in order to understand human activity and to show how categories are a fundamental part of learning in a specific type of institutional practice. In the empirical section, student dialogue is analysed in relation to a set of categories taken from scientific discourse. The analysis illustrates how categories in the progressive inquiry model could guide students towards a more systematic orientation to problem solving. © 2012 Taylor and Francis Group, LLC.


Pathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.


Christensen J.O.,National Institute of Occupational Health | Christensen J.O.,University of Oslo | Knardahl S.,National Institute of Occupational Health
Pain | Year: 2014

The current study estimated the impact of psychological and social work factors over time on neck pain. A sample of Norwegian employees (n = 1250) was surveyed on 3 occasions spanning 4 years. Five exposures were studied: quantitative demands, decision control, social climate, empowering leadership, and role conflict. Group-based trajectory models suggested factors changed little over time - employees could be classified by mean levels of exposure into groups exhibiting stable "high", "middle", and "low" levels. The exception was decision control, for which a 4-level classification was derived: "high", "high-middle", "low-middle", and "low". Pain prevalence at the end of the study period was compared across groups. Risk and prognosis were also assessed separately by dividing the sample according to pain status at baseline. For all factors, distinct differences in risk were observed between exposure groups, controlled for pain at baseline, skill level, sex, and age. Statistically significant effects ranged from 0.38 (CI 0.20-0.73, P < 0.01) for high social climate to 3.00 (CI 1.63-5.50, P < 0.01) for high role conflict. The risk of new-onset pain was predicted by all factors. ORs ranged from 0.32 (CI 0.16-0.67, P < 0.01) for high empowering leadership to 2.61 (CI 1.09-6.21, P < 0.05) for high role conflict. Pain persistence was predicted by high role conflict (OR 3.26, CI 1.30-8.18, P < 0.05), high quantitative demands (odds ratio [OR] 3.66, CI 1.58-8.49, P < 0.01), and high-middle decision control (OR 0.45, CI 0.21-0.99, P < 0.05). Future studies should collect information at multiple time points to clarify the impact of prolonged and changing exposure on musculoskeletal pain. ©2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Gobel S.M.,University of York | Watson S.E.,University of York | Lervag A.,University of Oslo | Hulme C.,University College London
Psychological Science | Year: 2014

In this article, we present the results of an 11-month longitudinal study (beginning when children were 6 years old) focusing on measures of the approximate number sense (ANS) and knowledge of the Arabic numeral system as possible influences on the development of arithmetic skills. Multiple measures of symbolic and nonsymbolic magnitude judgment were shown to define a unitary factor that appears to index the efficiency of an ANS system, which is a strong longitudinal correlate of arithmetic skills. However, path models revealed that knowledge of Arabic numerals at 6 years was a powerful longitudinal predictor of the growth in arithmetic skills, whereas variations in magnitude-comparison ability played no additional role in predicting variations in arithmetic skills. These results suggest that verbal processes concerned with learning the labels for Arabic numerals, and the ability to translate between Arabic numerals and verbal codes, place critical constraints on arithmetic development. © The Author(s) 2014.


Lundin K.E.A.,University of Oslo | Wijmenga C.,University of Groningen
Nature Reviews Gastroenterology and Hepatology | Year: 2015

Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening - and subsequent treatment if coeliac disease is detected - could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed. © 2015 Macmillan Publishers Limited. All rights reserved.


Hansen T.F.,University of Oslo
Evolution | Year: 2013

Organisms are built from thousands of genes that interact in complex ways. Still, the mathematical theory of evolution is dominated by a gene-by-gene perspective in which genes are assumed to have the same effects regardless of genetic background. Gene interaction, or epistasis, plays a role in some theoretical developments such as the evolution of recombination, reproductive isolation, and canalization, but is strikingly missing from our standard accounts of phenotypic adaptation. This absence is most puzzling within the field of quantitative genetics, which, despite its polygenic perspective and elaborate statistical representation of epistasis, has not found a single important role for gene interaction in evolution. To the contrary, there is a widespread consensus that epistasis is evolutionary inert, and that all we need to know to predict evolutionary dynamics is the additive component of the genetic variance. This view may have roots in convenience, but also in theoretical results showing that the response to selection derived from epistatic variance components is not permanent and will decay when selection is relaxed. I show that these results are tied to a conceptual confusion, and are misleading as general statements about the significance of epistasis for the selection response and adaptation. © 2013 The Society for the Study of Evolution.


Biological diversity is, to a large extent, a matter of var-iation in size. Proportional (isometric) scaling, where large and small individuals are magnified versions of each other, is often assumed to be the most common way morphological traits scale relative to over-all size within species. However, the many traits showing nonpro-portional (allometric) scaling have motivated some of the most dis-cussed hypotheses on scaling relationships in biology, like the positive allometry hypothesis for secondary sexual traits and the negative allom-etry hypothesis for genitals. I evaluate more than 3,200 allometric pa-rameters from the literature and find that negative allometry, not isom-etry, is the expected scaling relationship of morphological traits within species. Slopes of secondary sexual traits are more often steeper com-pared with other traits, but slopes larger than unity are also common for traits not under sexual selection. The steepness of the allometric slope is accordingly a weak predictor of past and present patterns of se-lection. Scaling of genitals varies across taxonomic groups, but nega-tive allometry of genitals in insects and spiders is a consistent pattern. Finally, I find indications that terrestrial organisms may have a different scaling of morphological traits overall compared with aquatic species. © 2015 by The University of Chicago. 0003-0147/2016/18701-55987$15.00. All rights reserved.


Houle D.,Florida State University | Pelabon C.,Norwegian University of Science and Technology | Wagner G.P.,Yale University | Hansen T.F.,University of Oslo
Quarterly Review of Biology | Year: 2011

Measurement-the assignment of numbers to attributes of the natural world-is central to all scientific inference. Measurement theory concerns the relationship between measurements and reality; its goal is ensuring that inferences about measurements reflect the underlying reality we intend to represent. The key principle of measurement theory is that theoretical context, the rationale for collecting measurements, is essential to defining appropriate measurements and interpreting their values. Theoretical context determines the scale type of measurements and which transformations of those measurements can be made without compromising their meaningfulness. Despite this central role, measurement theory is almost unknown in biology, and its principles are frequently violated. In this review, we present the basic ideas of measurement theory and show how it applies to theoretical as well as empirical work. We then consider examples of empirical and theoretical evolutionary studies whose meaningfulness have been compromised by violations of measurement-theoretic principles. Common errors include not paying attention to theoretical context, inappropriate transformations of data, and inadequate reporting of units, effect sizes, or estimation error. The frequency of such violations reveals the importance of raising awareness of measurement theory among biologists. © 2011 by The University of Chicago Press.


Thorsby E.,University of Oslo
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

It is now generally accepted that Polynesia was first settled by peoples from southeast Asia. An alternative that eastern parts of Polynesia were first inhabited by Amerindians has found little support. There are, however, many indications of a 'prehistoric' (i.e. before Polynesia was discovered by Europeans) contact between Polynesia and the Americas, but genetic evidence of a prehistoric Amerindian contribution to the Polynesian gene pool has been lacking. We recently carried out genomic HLA (human leucocyte antigen) typing as well as typing for mitochondrial DNA (mtDNA) and Y chromosome markers of blood samples collected in 1971 and 2008 from reputedly non-admixed Easter Islanders. All individuals carried HLA alleles and mtDNA types previously found in Polynesia, and most of the males carried Y chromosome markers of Polynesian origin (a few had European Y chromosome markers), further supporting an initial Polynesian population on Easter Island. The HLA investigations revealed, however, that some individuals also carried HLA alleles which have previously almost only been found in Amerindians. We could trace the introduction of these Amerindian alleles to before the Peruvian slave trades, i.e. before the 1860s, and provide suggestive evidence that they were introduced already in prehistoric time. Our results demonstrate an early Amerindian contribution to the Polynesian gene pool on Easter Island, and illustrate the usefulness of typing for immunogenetic markers such as HLA to complement mtDNA and Y chromosome analyses in anthropological investigations.


Berg Y.,University of Oslo
Analog Integrated Circuits and Signal Processing | Year: 2012

Simple and symmetrical ultra low-voltage current mode analog circuits and autozeroing amplifiers are presented. The low-voltage analog circuits are based on low-voltage inverters resembling precharge digital logic. Ultra low-voltage analog circuits can be operated at supply voltages down to 250 mV with rail-to-rail input and output swing. The output current of the ultra low-voltage symmetrical transconductance amplifier can be quite large due to a current boost technique. Ultra low-voltage analog circuits can be operated at supply voltages down to 250 mV with rail- to-rail input and output swing. The current headroom is 3 μA and the supply voltage is 300 mV. For supply voltages down to 300 mV simulated data shows that the maximum clock frequency is approximately 600 MHz. © 2012 Springer Science+Business Media, LLC.


Kvernflaten B.,University of Oslo
Reproductive Health Matters | Year: 2013

In support of maternal health, disease-specific and target-oriented global policy initiatives, such as in Millennium Development Goal 5, have led to a prioritisation of narrow indicators at the expense of more comprehensive approaches. In line with global policy, Nicaragua has made skilled attendants and institutionalised delivery central to its efforts to achieving MDG5 on maternal health. Drawing on ethnographic fieldwork in Nicaragua, involving participant observation and interviews with hospital and community health workers, and women and their families, this paper critically discusses how target-oriented maternal health strategies were manifested in local realities. It shows that Nicaragua's brigadistas (community health workers) and parteras (traditional birth attendants) have been driven to narrowing their own roles to identifying pregnant women and advocating that they have an institutional delivery as one their most important tasks, making them agents of MDG 5 target achievement. This has engendered fear among brigadistas and parteras of being held individually responsible in the event of a maternal death, creating dissatisfaction with their role and reducing their motivation. While intended to improve maternal health, the pressure to reach targets has unintended negative implications for the relationship between women, the local volunteers and the formal health system, which needs to be addressed. © 2013 Reproductive Health Matters.


Behnke J.,University of Nottingham | Harris P.D.,University of Oslo
Trends in Parasitology | Year: 2010

A popular model system for exploring the host-parasite relationship of gastrointestinal nematodes is commonly known as Heligmosomoides polygyrus bakeri. Recently, this parasite was raised to full species level as H. bakeri, to distinguish it from a close relative, H. polygyrus sensu stricto, the dominant intestinal nematode of wood mice in Western Europe, which is unable to infect laboratory mice (Mus sp.) without the aid of powerful immunosuppressants. Herein, the argument is presented that it is necessary to rename this parasite, and that H. bakeri is the correct name for the species used widely throughout the world as a laboratory research model. Supporting this claim, key evidence is presented demonstrating that H. bakeri and H. polygyrus are two quite distinct species. © 2010.


Tamanini N.,University College London | Koivisto T.S.,University of Oslo
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Theories with a nonminimal coupling between the space-time curvature and matter fields introduce an extra force due to the nonconservation of the matter energy momentum. In the present work the theoretical consistency of such couplings is studied using a scalar field Lagrangian to model the matter content. The conditions that the coupling does not introduce ghosts, classical instabilities or superluminal propagation of perturbations are derived. These consistency conditions are then employed to rule out or severely restrict the forms of the nonminimal coupling functions considered in the previous literature. For example, a power-law coupling is viable only for sublinear positive power of the curvature scalar. © 2013 American Physical Society.


Koivisto T.S.,University of Oslo | Tamanini N.,University College London
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

In the first-order formalism of gravitational theories, the spacetime connection is considered as an independent variable to vary together with the metric. However, the metric still generates its Levi-Civita connection that turns out to determine the geodesics of matter. Recently, "hybrid" gravity theories have been introduced by constructing actions involving both the independent Palatini connection and the metric Levi-Civita connection. In this study a method is developed to analyze the field content of such theories, in particular to determine whether the propagating degrees of freedom are ghosts or tachyons. New types of second-, fourth- and sixth-order derivative gravity theories are investigated and the so-called f(X) theories are singled out as a viable class of "hybrid" extensions of general relativity. These are the theories in which the corrections to Einstein's theory are written in terms of the deviations from the usual trace equation X=R-κ2T. © 2013 American Physical Society.


Dahl A.A.,University of Oslo
Future Oncology | Year: 2010

Personality refers to an individuals enduring and pervasive personal motivation, emotion, interpersonal style, attitudes and behavior that are stable over a long time after young adulthood. In relation to the cancer trajectory, three basic and one other personality traits have been studied with some frequency, namely neuroticism, extraversion, conscientiousness and optimism. The considerable stability of personality over time makes it a potential long-acting etiological factor for the development of cancer. However, the studies performed so far do not give much support to personality as a causative factor for cancer. Some studies of cancer survival have found significant associations between lower optimism and higher neuroticism with shorter survival. More mental distress and fatigue and poorer quality of life is significantly associated with higher neuroticism and lower optimism at cancer screening, diagnosis and primary treatment, short- and long-term follow-up and towards the end of life. Neuroticism is a strong predictor of post-traumatic stress disorder triggered by cancer as a life-threatening experience eventually leading to negative personality changes. To what extent cancer leads to positive personality changes (post-traumatic growth) is currently unsettled. Basic personality traits are strongly associated with lifestyle, which is considered an important etiological factor for the development of cancer. The methodological problems in the study of personality and cancer are considerable, and many research designs used so far may have been too simplistic. Studies of potential biomarkers for personality traits combined with inflammation markers of cellular carcinogenesis in longitudinal designs could be promising for the future. High neuroticism is important for the clinical management of cancer patients and should gain more attention from oncologists in the future. © 2010 Future Medicine Ltd.


Buiter S.J.H.,Geological Survey of Norway | Buiter S.J.H.,University of Oslo
Tectonophysics | Year: 2012

Fold-and-thrust belts and accretionary wedges form by compression of sedimentary sequences and basement rocks into forward and backward thrusts, folds, nappes, and duplexes. For over a century, models have been used to investigate the essential characteristics of such brittle wedges. Here I review model studies of brittle thrust wedges in orthogonal compression, focussing on critical taper theory, analogue and numerical techniques for modelling brittle behaviour, and the most commonly investigated variations in wedge model studies, those in basal dip, basal strength, internal strength, and surface processes. Many model results can be placed in the context of critical taper theory, which provides analytical solutions for wedge taper angle and slip line orientations for a homogeneous material on the verge of failure throughout. Dynamic forward models have confirmed critical taper predictions of decreasing surface dip for increasing basal dip, wider wedges with steeper forward thrusts and shallower backward thrusts for decreasing basal strength, narrower wedges and enhanced exhumation for surface erosion, and decreasing surface dip for increasing internal strength. But analogue and numerical models have been able to take these results a step further by investigating the evolution of non-critical thrust wedges and the effects of non-homogeneous materials with décollement layers and strain-weakening shear zones. These results have highlighted the strong impact of heterogeneous materials on the internal structures of thrust wedges and raise the question whether the complexity of structures that are observed in many natural fold-and-thrust belts requires that lithological layering, inherited faults, or a wide range of rheologies need to be included in forward models of brittle thrust wedges. © 2011 Elsevier B.V.


Collas P.,University of Oslo
Methods in Molecular Biology | Year: 2011

Chromatin immunoprecipitation (ChIP) is a widely used technique to get a snap-shot of protein-DNA interactions in cells. ChIP has notably been used for mapping the location of modified histones, transcription factors, or chromatin remodeling enzymes in the genome, often in relation to transcription or differentiation. Conventional ChIP protocols however, have for a long time required large numbers of cells, which has limited the applicability of ChIP to rare or small cell samples. In recent years, ChIP assays for small cell numbers (in the 10,000-100,000 range) have been recently reported by us and others. This chapter describes a micro (μ)ChIP procedure for multiple parallel ChIPs from a single chromatin batch from 1,000 cells. © 2011 Springer Science+Business Media, LLC.


Srholec M.,University of Oslo
Regional Studies | Year: 2010

SRHOLEC M. A multilevel approach to geography of innovation, Regional Studies. The aim of this paper is to demonstrate how research on geography of innovation can benefit from multilevel modelling. Using micro-data from the third Community Innovation Survey in the Czech Republic, the hypothesis that regional framework conditions determine the innovative performance of firms and that this effect differs for different kinds of firms is quantitatively assessed. The results indicate that the quality of the regional innovation system directly influences the likelihood of a firm to innovate and that this effect decreases with the size of the firm. Also, broader social characteristics of the region are relevant explanatory factors of innovation. © 2010 Regional Studies Association.


Cromsigt J.P.G.M.,University of Oslo | Kuijper D.P.J.,Polish Academy of Sciences
Perspectives in Plant Ecology, Evolution and Systematics | Year: 2011

Browsing lawns, as an analogue of the influential grazing lawn concept, received increased recent interest. We revisit this concept and ask whether the underlying characteristics of a grazing lawn can indeed be generalized to browser-woody plant interactions. Based on previous studies, we define a lawn as a grazed or browsed patch in which intense foraging leads to increased resource availability and a proportional increase of palatable plant species in the patch. We then argue that present examples do not fully support a browsing lawn analogue. Although intense browsing can lead to increased resource availability, it generally reduces the share of palatable plant species in the community. We present an example that does seem to fit both lawn conditions; intensely browsed regeneration patches of palatable trees in Białowieża Primeval forest. Browsing not only prunes these regeneration patches into lawn-like structures, but also increases the share of palatable species in the tree community. Finally, we outline key open issues of the browsing lawn analogue and discuss the discrepancy between our example and the general understanding that browsing reduces the share of palatable tree species. We suggest that lawns are most likely to develop in relatively resource-rich environments where plants can invest in tolerance traits and in situations where herbivores show strong patch selection but are relatively unselective for individual plants within the patch. Although our example fits these conditions, many studies on browser-woody plant interactions come from relatively nutrient poor systems with strong selection for individual palatable trees. More studies in systems similar to our example might show that positive interactions between browsing and the proportion of palatable woody species in a community are not so rare. © 2011 Perspectives in Plant Ecology, Evolution and Systematics.


Molberg O.,University of Oslo
Current Opinion in Rheumatology | Year: 2016

PURPOSE OF REVIEW: Interstitial lung disease (ILD) is the major determinant of morbidity and mortality in systemic sclerosis (SSc). In highly selected SSc patients, it was recently shown that stem cell therapy early in the disease course improved survival and reduced the extent of ILD, providing a rationale for early ILD detection strategies in this disease. Here, we review recent progress on ILD screening and early diagnosis in SSc. RECENT FINDINGS: Two studies showed that over 60% of unselected SSc cases with ILD by high-resolution computer tomography (HRCT) had normal range pulmonary function tests (PFTs); indicating poor performance of PFTs for ILD screening purposes. Serial, paired HRCT and PFT analyses indicated that screening by HRCT at baseline predicted risk for lung fibrosis development, progression rate of fibrosis and PFT decline. Analyses of circulating biomarkers, like CCL18, and nonradiating lung imaging modalities, like ultrasound and MRI, showed promise as tools for early ILD detection; but further work is needed. SUMMARY: Prospective cohort data indicated poor performance of PFT as a stand-alone method for ILD screening. Lung HRCT appeared promising, but radiation is an issue. Promising biomarker data indicate the possibility of new ILD screening algorithms in SSc. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Langard S.,University of Oslo
Journal of Trace Elements in Medicine and Biology | Year: 2015

In the early 16th century Gregorius Agricola reported on Bergsucht (miner's consumption) in mine workers in the Erzgebirge. About 350 years later, Härting and Hesse reported on large numbers of lung cancers among the mine-workers in the same mine district, thus confirming that Bergsucht primarily was lung cancer, but could also have been pnumoconiosis or tuberculosis or a combination of both. Mining for bismuth continued another 75 years - through World War II. Bismuth mining was replaced by large scale uranium mining from the late 1940 through 1989, employing some 400-450,000 workers, resulting in the major local epidemic of work-related cancer larger than anywhere in the world, so far amounting to ±14-15,000 cases. Had the mine developers listened to the warnings by Agricola and Härting and Hesse, the epidemic could have been prevented. © 2014 Elsevier GmbH.


Brandtzaeg P.,University of Oslo
Current Opinion in Gastroenterology | Year: 2010

Purpose of review: To review recent findings dealing with the involvement of mucosal immunoglobulin A (IgA) in the gut barrier function and various gastrointestinal diseases. New information will be discussed in the context of previous knowledge in this field. Recent findinds: The epithelial barrier function seems to be central in many mucosal disorders because it is decisive for host-microbial interactions and penetration of soluble antigens into the lamina propria. Secretory IgA contributes to the barrier function and recent evidence strongly supports the notion that such antibodies are involved in immunological homeostasis. Summary: Inflammatory bowel disease involves a break of tolerance to the commensal microbiota. Aberrations in the mucosal IgA system may, therefore, be part of the inflammatory bowel disease pathogenesis. In gluten-induced enteropathy, however, it has been suggested that a mucosal IgA response may promote the progression of celiac disease and dermatitis herpetiformis by enhancing the uptake of gluten peptides and inhibiting the enzyme activity of tissue transglutaminase. A mucosal IgA response may also promote gastritis by protecting Helicobacter pylori from complement attack. In food allergy, several facets of the epithelial barrier function may show deficiency, including secretory IgA. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Collins A.R.,University of Oslo
Mutagenesis | Year: 2015

The contributions to this special issue of Mutagenesis have been selected to cover the main research areas served by the comet assay, namely genotoxicology, environmental toxicology, human biomonitoring and fundamental investigations into mechanisms of DNA damage and repair. Innovative methods are described, technical issues are explored, and guidelines are given for venturing into relatively new or unexploited areas of research. The popularity of the comet assay in a historical context is illustrated by a bibliometric survey. © 2014 The Author. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.


Brandtzaeg P.,University of Oslo
Nature Reviews Gastroenterology and Hepatology | Year: 2010

Numerous genes are involved in innate and adaptive immunity and these have been modified over millions of years. During this evolution, the mucosal immune system has developed two anti-inflammatory strategies: immune exclusion by the use of secretory antibodies to control epithelial colonization of microorganisms and to inhibit the penetration of potentially harmful agents; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens, such as food proteins. The latter strategy is called oral tolerance when induced via the gut. Homeostatic mechanisms also dampen immune responses to commensal bacteria. The mucosal epithelial barrier and immunoregulatory network are poorly developed in newborns. The perinatal period is, therefore, critical with regard to the induction of food allergy. The development of immune homeostasis depends on windows of opportunity during which innate and adaptive immunity are coordinated by antigen-presenting cells. The function of these cells is not only orchestrated by microbial products but also by dietary constituents, including vitamin A and lipids, such as polyunsaturated omega-3 fatty acids. These factors may in various ways exert beneficial effects on the immunophenotype of the infant. The same is true for breast milk, which provides immune-inducing factors and secretory immunoglobulin A, which reinforces the gut epithelial barrier. It is not easy to dissect the immunoregulatory network and identify variables that lead to food allergy. This Review discusses efforts to this end and outlines the scientific basis for future food allergy prevention. © 2010 Macmillan Publishers Limited. All rights reserved.


Collas P.,University of Oslo
Epigenetics | Year: 2010

Cell fate decisions are largely programmed by interactions between multiple layers of regulation of gene expression. Among these, epigenetic states have been extensively examined, mostly in the context of embryonic stem cell differentiation. Recent studies however have focused on understanding chromatin-based mechanisms of differentiation of adult progenitor cells into specific lineages but not others. The results point to the view that promoter DNA methylation patterns are not the primary determinant of gene activation potential and differentiation capacity of mesenchymal stem cells. Post-translational histone modifications on promoters contribute to establishing a permissive state of differentiation, but cannot, based on current knowledge, predict transcriptional activation outcome. Additional regulatory layers need to be examined to be able to explain cell fate commitment and ultimately predict cell fate. © 2010 Landes Bioscience.


There is a single-minded focus on events in survival analysis, and we often ignore longitudinal data that are collected together with the event data. This is due to a lack of methodology but also a result of the artificial distinction between survival and longitudinal data analyses. Understanding the dynamics of such processes is important but has been hampered by a lack of appreciation of the difference between confirmatory and exploratory causal inferences. The latter represents an attempt at elucidating mechanisms by applying mediation analysis to statistical data and will usually be of a more tentative character than a confirmatory analysis. The concept of local independence and the associated graphs are useful. This is related to Granger causality, an important method from econometrics that is generally undervalued by statisticians. This causality concept is different from the counterfactual one since it lacks lacks the intervention aspect. The notion that one can intervene at will in naturally occurring processes, which seems to underly much of modern causal inference, is problematic when studying mediation and mechanisms. It is natural to assume a stochastic process point of view when analyzing dynamic relationships. We present some examples to illustrate this. It is not clear how survival analysis must be developed to handle the complex life-history data that are increasingly being collected today. We give some suggestions. © 2012 John Wiley & Sons, Ltd.


Buer J.K.,University of Oslo
Inflammopharmacology | Year: 2014

This article is an historical investigation of the term non-steroidal anti-inflammatory drugs and its acronym NSAIDs. Drug names and categories tend to be taken at face value in everyday practice, as natural categories existing in their own right. The main argument of this article is that the term NSAID is a reminder that drug names and categories are complex cultural and social products that have been created by specific people, for specific purposes, through specific historical processes, and that this is relevant for their use today. The article locates the first appearances of the phrase non-steroidal at the entry to the 1960s, when the iatrogenic tragedies that followed from the introduction of corticosteroids had become apparent, and where a clear separation between these drugs and emerging anti-inflammatory alternatives was needed. The article then shows how both the phrase and the acronym appeared for the first time out of specific textual contexts in publications by Michael W. Whitehouse, before they were taken up by a wider community and transformed into concepts independent on the context of their first appearances. © 2014, Springer Basel.


It was in the 1940s that antibiotic resistance arose as an object of study for clinical medicine. Somewhat earlier it had become an important analytical tool for bacterial geneticists. However, the concept of antibiotic resistance as an induced and inheritable trait of microbial species was introduced a generation earlier in the years preceding the First World War. The paper reconstructs the concept that was put forward by the German immunologist Paul Ehrlich in 1907. He came across the phenomenon when trying to develop chemotherapies for trypanosomiasis, the best known of which is African sleeping sickness. However, resistance was studied by him for other than therapy-related purposes. It provided a productive laboratory model for the study of cell functions. Induced resistance to chemicals facilitated the development of ideas on the relation of a parasite's cellular metabolism and of drug action, i.e. by providing a negative proof for the existence of chemoreceptors on the surfaces of parasite cells. This approach does also serve to explain why British and German researchers continued to study the phenomenon of induced resistance in microbes for decades -despite it being absent from clinical medicine. After all, there existed very few chemotherapies of infectious diseases prior to the arrival of the sulfa drugs. Moreover, resistance to such medicines was rarely observed. However, being part and parcel of Ehrlich's theories, his views on resistance were also criticised together with these. It was in particular Henry Dale who would challenge Ehrlich's views of resistance being an inheritable and stable trait of microbes. Instead he insisted that understanding this «wholly mysterious phenomenon» required taking into account some host interaction. Induced resistance, which had come into being as a chance discovery on the chemotherapy of sleeping sickness, thus became one of the more important laboratory models of twentieth-century immunological research. Its early history is largely discontinuous with later work, and antimicrobial resistance as it evolved from 1900 to 1940 followed other trajectories than those which became relevant after 1940.


Henden E.,University of Oslo
Bioethics | Year: 2013

Does addiction to heroin undermine the voluntariness of heroin addicts' consent to take part in research which involves giving them free and legal heroin? This question has been raised in connection with research into the effectiveness of heroin prescription as a way of treating dependent heroin users. Participants in such research are required to give their informed consent to take part. Louis C. Charland has argued that we should not presume that heroin addicts are competent to do this since heroin addiction by nature involves a loss of ability to resist the desire for heroin. In this article, I argue that Charland is right that we should not presume that heroin addicts are competent to consent, but not for the reason he thinks. In fact, as Charland's critics correctly point out, there is plenty of evidence showing that heroin addicts can resist their desire for heroin. These critics are wrong, however, to conclude from this that we should presume that heroin addicts are competent to give their voluntary consent. There are, I shall argue, other conditions associated with heroin addiction that might constrain heroin addicts' choice in ways likely to undermine the voluntariness of their consent. In order to see this, we need to move beyond the focus on the addicts' desires for heroin and instead consider the wider social and psychological circumstances of heroin addiction, as well as the effects these circumstances may have on the addicts' beliefs about the nature of their options. © 2012 John Wiley & Sons Ltd.


Hasle G.,University of Oslo
Frontiers in Cellular and Infection Microbiology | Year: 2013

Birds, particularly passerines, can be parasitized by Ixodid ticks, which may be infected with tick-borne pathogens, like Borrelia spp., Babesia spp., Anaplasma, Rickettsia/Coxiella, and tick-borne encephalitis virus. The prevalence of ticks on birds varies over years, season, locality and different bird species. The prevalence of ticks on different species depends mainly on the degree of feeding on the ground. In Europe, the Turdus spp., especially the blackbird, Turdus merula, appears to be most important for harboring ticks. Birds can easily cross barriers, like fences, mountains, glaciers, desserts and oceans, which would stop mammals, and they can move much faster than the wingless hosts. Birds can potentially transport tick-borne pathogens by transporting infected ticks, by being infected with tick-borne pathogens and transmit the pathogens to the ticks, and possibly act as hosts for transfer of pathogens between ticks through co-feeding. Knowledge of the bird migration routes and of the spatial distribution of tick species and tick-borne pathogens is crucial for understanding the possible impact of birds as spreaders of ticks and tick-borne pathogens. Successful colonization of new tick species or introduction of new tick-borne pathogens will depend on suitable climate, vegetation and hosts. Although it has never been demonstrated that a new tick species, or a new tick pathogen, actually has been established in a new locality after being seeded there by birds, evidence strongly suggests that this could occur. © 2013 Hasle.


Recent research has highlighted how parental narratives can be important in the resistance against disabling processes. This article contains analyses of enabling language in narratives published by Scandinavian disability rights organizations. First, drawing on the work of Fisher and Goodley, I point out that the material constitute a threefold: normality narratives, resistance narratives, and narratives that demonstrate an appreciation of the present and the child's individual alterity. Second, I demonstrate that the last narrative draws on Romanticism rather than linguistic resources from disability culture. Third, I show that these narratives are hyperboles - texts that strengthen and emphasise the valuation to the point where the narrative structure transcends narrative consistency. Fourth, drawing on the work of Kristeva, I argue that this form of narration constitutes an intimate politics of love. © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.


Weber J.E.H.,University of Oslo
Wave Motion | Year: 2011

We investigate theoretically the effects of viscosity and surface films on small-amplitude Gerstner waves in deep water. The analysis is performed by using a Lagrangian formulation of fluid motion. For inviscid fluids with a free surface Gerstner waves of arbitrary amplitude are exact solutions of the nonlinear Lagrangian equations. These waves have a trochoidal surface shape. They possess vorticity, but have no mean wave momentum, i.e. induce no net drift in the fluid. By expanding the wave motion after the wave steepness as a small parameter, we demonstrate how Gerstner waves to second order in wave steepness change due to viscosity, leading to a mean drift near the surface and a backward drift beneath the surface layer, so that they conserve total (zero) mean wave momentum. In addition, if the surface is covered by a freely floating inextensible film, the mean drift at the surface (the film speed) increases dramatically. A comparison with experimental data for the drift of thin plastic sheets in wave tanks is made, showing that the presence of viscosity-modified Gerstner waves cannot be ruled out on the basis of these observations. © 2010 Elsevier B.V.


Hanseth O.,University of Oslo | Lyytinen K.,Case Western Reserve University
Journal of Information Technology | Year: 2010

We propose a design theory that tackles dynamic complexity in the design for Information Infrastructures (IIs) defined as a shared, open, heterogeneous and evolving socio-technical system of Information Technology (IT) capabilities. Examples of IIs include the Internet, or industry-wide Electronic Data Interchange (EDI) networks. IIs are recursively composed of other infrastructures, platforms, applications and IT capabilities and controlled by emergent, distributed and episodic forms of control. II's evolutionary dynamics are nonlinear, path dependent and influenced by network effects and unbounded user and designer learning. The proposed theory tackles tensions between two design problems related to the II design: (1) the bootstrap problem: IIs need to meet directly early users needs in order to be initiated; and (2) the adaptability problem: local designs need to recognize II's unbounded scale and functional uncertainty. We draw upon Complex Adaptive Systems theory to derive II design rules that address the bootstrap problem by generating early growth through simplicity and usefulness, and the adaptability problem by promoting modular and generative designs. We illustrate these principles by analyzing the history of Internet exegesis. © 2010 JIT Palgrave Macmillan All rights reserved.


Magraso A.,University of Oslo
Journal of Power Sources | Year: 2013

The partial protonic, oxide ion and electronic conductivities of lanthanum tungstate (La28-xW4+xO54+δ with x = 1, LWO54) and 30% molybdenum substituted lanthanum tungstate (Mo-LWO54) have been extracted using the EMF method. LWO54 is a relatively pure ionic conductor up to ∼800 C; above that temperature electrons start to contribute significantly (under reducing conditions). The maximum protonic conductivity is ∼2-3 × 10-3 S cm-1, and protonic conductivity dominates the ionic regime under wet conditions below ∼700 C. Above this temperature, oxide ion conductivity dominates the ionic contribution. The protonic and oxide ion conductivities for Mo-substituted LWO54 are quite similar to the Mo-free material, while the electronic conductivity is almost one order of magnitude higher for the former in wet 5% H2/Ar. From this report is clear that nominally undoped lanthanum tungstate is most suited for applications as electrolyte in proton conducting SOFCs, while Mo-LWO54 presents improved mixed proton-electron conductivity for use as dense membrane for hydrogen separation. © 2013 Elsevier B.V. All rights reserved.


Vanberg P.,University of Oslo
Handbook of Experimental Pharmacology | Year: 2010

Abuse of anabolic androgenic steroids (AAS) has been linked to a variety of different cardiovascular side effects. In case reports, acute myocardial infarction is the most common event presented, but other adverse cardiovascular effects such as left ventricular hypertrophy, reduced left ventricular function, arterial thrombosis, pulmonary embolism and several cases of sudden cardiac death have also been reported. However, to date there are no prospective, randomized, interventional studies on the long-term cardiovascular effects of abuse of AAS. In this review we have studied the relevant literature regarding several risk factors for cardiovascular disease where the effects of AAS have been scrutinized: (1) Echocardiographic studies show that supraphysiologic doses of AAS lead to both morphologic and functional changes of the heart. These include a tendency to produce myocardial hypertrophy (Fig. 3), a possible increase of heart chamber diameters, unequivocal alterations of diastolic function and ventricular relaxation, and most likely a subclinically compromised left ventricular contractile function. (2) AAS induce a mild, but transient increase of blood pressure. However, the clinical significance of this effect remains modest. (3) Furthermore, AAS confer an enhanced pro-thrombotic state, most prominently through an activation of platelet aggregability. The concomitant effects on the humoral coagulation cascade are more complex and include activation of both pro-coagulatory and fibrinolytic pathways. (4) Users of AAS often demonstrate unfavorable measurements of vascular reactivity involving endothelial-dependent or endothelial-independent vasodilatation. A degree of reversibility seems to be consistent, though. (5) There is a comprehensive body of evidence documenting that AAS induce various alterations of lipid metabolism. The most prominent changes are concomitant elevations of LDL and decreases of HDL, effects that increase the risk of coronary artery disease. And finally, (6) the use of AAS appears to confer an increased risk of life-threatening arrhythmia leading to sudden death, although the underlying mechanisms are still far from being elucidated. Taken together, various lines of evidence involving a variety of pathophysiologic mechanisms suggest an increased risk for cardiovascular disease in users of anabolicandrogenic steroids. © 2009 Springer-Verlag Berlin Heidelberg.


Fagerland M.W.,University of Oslo | Newcombe R.G.,University of Cardiff
Statistics in Medicine | Year: 2013

The inverse hyperbolic sine transformation can be used to shorten the standard delta logit interval for the odds ratio and the delta log interval for the relative risk. As it stands, this transformation does not provide sufficient coverage. A pseudo-frequency modification is suggested and evaluated. The modification achieves an improvement in coverage for both the odds ratio and the relative risk and a further improvement in interval width for the odds ratio. We also find that another closed form interval, called MOVER-R Wilson, which is based on the method of variance estimates recovery, performs well. When the more complex and software demanding intervals, such as the asymptotic score, are unavailable, the adjusted inverse sinh intervals and MOVER-R Wilson provide two simple approaches to interval estimation of the odds ratio and the relative risk. © 2012 John Wiley & Sons, Ltd.


Torlakovic L.,University of Oslo
The Angle orthodontist | Year: 2011

To describe the age-related changes of the soft tissue facial profile from the second to fourth decades of life. Cephalograms from the same subjects in their 20s, 30s, and 40s were analyzed. A coordinate system analysis based on stable landmarks is used. A line connecting Walker's point (W) and sphenoethmoidal (SE) created the x-axis. Walker's point was origin. Depending on data distribution, landmark displacements from T1 to T2, from T2 to T3, and from T1 to T3 were analyzed using the paired t-test or the Wilcoxon test for zero expected change versus a two-sided alternative. For each landmark the mean, standard deviation, P value, and lower and higher 95% confidence intervals were calculated. During T2-T1, for males, the whole profile was displaced anteriorly and slightly superiorly, and for females, the lower facial profile was displaced in a posterior and inferior direction. Greater changes occurred in the female profile than the male profile. During T3-T2, the female profile changed slightly while the male profile underwent great changes: the upper facial profile was displaced anteriorly, and the lower profile was displaced posteriorly. The whole profile was displaced in the inferior direction. Significant changes occurred in the soft tissue facial profile from the second to fourth decades. Aging of the male facial profile began 10 years later than for females; however, when the changes did occur, they were of greater magnitude. The upper facial profile was displaced in the anterior direction and the whole profile was displaced inferiorly for both sexes.


Samuelsen A.B.C.,University of Oslo | Schrezenmeir J.,Clinical Research Center Kiel | Knutsen S.H.,Norwegian Institute of Food
Molecular Nutrition and Food Research | Year: 2014

Yeast-derived beta-glucans (Y-BG) are considered immunomodulatory compounds suggested to enhance the defense against infections and exert anticarcinogenic effects. Specific preparations have received Generally Recognized as Safe status and acceptance as novel food ingredients by European Food Safety Authority. In human trials, orally administered Y-BG significantly reduced the incidence of upper respiratory tract infections in individuals susceptible to upper respiratory tract infections, whereas significant differences were not seen in healthy individuals. Increased salivary IgA in healthy individuals, increased IL-10 levels in obese subjects, beneficial changes in immunological parameters in allergic patients, and activated monocytes in cancer patients have been reported following Y-BG intake. The studies were conducted with different doses (7.5-1500 mg/day), using different preparations that vary in their primary structure, molecular weight, and solubility. In animal models, oral Y-BG have reduced the incidence of bacterial infections and levels of stress-induced cytokines and enhanced antineoplastic effects of cytotoxic agents. Protective effects toward drug intoxication and ischemia/reperfusion injury have also been reported. In conclusion, additional studies following good clinical practice principles are needed in which well-defined Y-BG preparations are used and immune markers and disease endpoints are assessed. Since optimal dosing may depend on preparation characteristics, dose-response curves might be assessed to find the optimal dose for a specific preparation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Brandtzaeg P.,University of Oslo
Journal of Pediatrics | Year: 2010

Mucosal immunity reduces the need for elimination of penetrating exogenous antigens by proinflammatory systemic immunity. The adult gut mucosa contains some 80% of the body's activated B cells-differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric immunoglobulin A (IgA), which, along with pentameric immunoglobulin M (IgM), can be exported by secretory epithelia expressing the polymeric immunoglobulin receptor. Immune exclusion of antigens is performed mainly by secretory IgA in cooperation with innate defenses, but, in newborns and in IgA deficiency, secretory IgM is important. In the gut, induction and regulation of mucosal immunity occurs primarily in gut-associated lymphoid tissue-particularly the Peyer's patches-and also in mesenteric lymph nodes. Terminal differentiation to PCs is accomplished in the lamina propria to which the activated memory/effector T and B cells home. Lactating mammary glands are part of the secretory immune system, and IgA antibodies in breast milk reflect antigenic stimulation of gut-associated lymphoid tissue and nasopharynx-associated lymphoid tissue such as the tonsils. Breast-milk antibodies are thus highly targeted against infectious agents and other exogenous antigens in the mother's environment, which are those likely to be encountered by the infant. Therefore breast-feeding represents an ingenious immunologic integration of mother and child. © 2010 Mosby, Inc. All rights reserved.


Aanestad M.,University of Oslo | Jensen T.B.,Copenhagen Business School
Journal of Strategic Information Systems | Year: 2011

Initiatives that seek to realize the vision of nation-wide information infrastructures (II) in healthcare have often failed to achieve their goals. In this paper, we focus on approaches used to plan, conduct, and manage the realization of such visions. Our empirical material describes two Danish initiatives, where a national project failed to deliver interoperable Electronic Patient Record (EPR) systems while a small, local solution grew and now offers a nation-wide solution for sharing patient record information. We apply II theory, specifically the five design principles proposed by Hanseth and Lyytinen, to contrast the organization and implementation strategies of the two projects. Our findings highlight how implementation strategies differ with respect to how stakeholders are mobilized. We argue that the realization of nation-wide IIs for healthcare not only requires a gradual transition of the installed base, which current II theory advocates. Here we articulate and exemplify a modular implementation strategy as an approach that also addresses the challenges related to mobilization and organization of multiple stakeholders. © 2011 Elsevier B.V. All rights reserved.


Ericsson K.,University of Oslo
Theoretical Criminology | Year: 2011

This article discusses how war rapes and consensual sexual relationships with enemy soldiers are framed and understood, with special emphasis on the consequences for the women involved. It war rapes in Bosnia-Herzegovina during the Balkan war and Danish and Norwegian women's sexual relationships with German occupant soldiers during the Second World War. I argue that the conception of women's sexuality as national property is central to understanding the attitudes towards both categories of women. To preserve their dignity, war rape victims may profit from a collective, political discourse. Women having had consensual relationships to enemy soldiers, however, have to extricate themselves from the collective and political discourse and interpret what happened to them as strictly personal. © The Author(s) 2010.


Nasholm S.P.,University of Oslo
Journal of the Acoustical Society of America | Year: 2013

Frequency-dependent acoustical loss due to a multitude of physical mechanisms is commonly modeled by multiple relaxations. For discrete relaxation distributions, such models correspond with causal wave equations of integer-order temporal derivatives. It has also been shown that certain continuous distributions may give causal wave equations with fractional-order temporal derivatives. This paper demonstrates analytically that if the wave-frequency ω satisfies ΩL ≪ ω ≪ ΩH, a continuous relaxation distribution populating only Ω [ΩL, ΩH] gives the same effective wave equation as for a fully populated distribution. This insight sparks the main contribution: the elaboration of a method to determine discrete relaxation parameters intended for mimicking a desired attenuation behavior for band-limited waves. In particular, power-law attenuation is discussed as motivated by its prevalence in complex media, e.g., biological tissue. A Mittag-Leffler function related distribution of relaxation mechanisms has previously been shown to be related to the fractional Zener wave equation of three power-law attenuation regimes. Because these regimes correspond to power-law regimes in the relaxation distribution, the idea is to sample the distribution's compressibility contributions evenly in logarithmic frequency while appropriately taking the stepsize into account. This work thence claims to provide a model-based approach to determination of discrete relaxation parameters intended to adequately model attenuation power-laws. © 2013 Acoustical Society of America.


Friestad C.,University of Oslo
International Journal of Offender Therapy and Comparative Criminology | Year: 2012

Most structured sex-offender programs are based on a cognitive-behavioural model of behaviour change. Within this overarching theoretical paradigm, extensive use of cognitive distortions is seen as a central core symptom among sex offenders. However, the literature on cognitive distortions lacks a clear and consistent definition of the term. It is unclear whether cognitive distortions are consciously employed excuses or unconscious processes serving to protect the offender from feelings of guilt or shame. In this article, the dominant cognitive-behavioural interpretation of cognitive distortions is contrasted with two alternative interpretations. One is based on an attributional perspective and the notion of attributional biases. The other explanation is based on a narrative approach focusing on the action elements of cognitive distortions, that is, as something people do rather than something they have. Clinical implications of these alternative conceptualizations are discussed and illustrated throughout by a case example. © The Author(s) 2012.


Hansson P.,Karolinska Institutet | Hansson P.,University of Oslo
Pain | Year: 2014

Activity-dependent C-fiber-induced CS is a state of neuronal hyperexcitability in the CNS. Detailed information is lacking regarding the spatial extension in the CNS of such hyperexcitability during challenging inputs from nociceptive afferents. This, in conjunction with a lack of criteria for how CS expresses itself in clinical phenomenology, suggests that CS currently cannot be recommended as a nomenclature when labeling regional and remote increased sensitivity in painful conditions. Unfortunately, a significant body of human experimental and clinical literature interprets a multitude of symptoms and signs as expressions of CS, to an extent that is not supported by current research evidence [12,14,15]. Some of those involved in the field of pain management have since long articulated the will to pursue a mechanism-based classification and treatment of pain. In the interest of this pursuit, translational aspects of pain medicine would benefit from more cautious interpretations of findings in humans than what is currently the case for activity-dependent CS. Repeated use in the clinical scenario of a concept only proved in preclinical settings has become commonplace in parts of the pain community. This may leave translational aspects of pain trivialized and members of the scientific and clinical community of pain open to challenge by those who know better. © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Lid I.M.,University of Oslo
Disability and Rehabilitation | Year: 2014

Purpose: To discuss Universal Design (UD) as an interdisciplinary topic with relevance for rehabilitation professions and planning and building professions. Significant for this topic is to discuss to what model of disability UD strategies correlates. The paper argues that the UN Convention on the Rights for Persons with Disabilities (CRPD) pre-supposes a relational model of disability. Method: This is a theoretical paper on the understanding of UD and the significance of UD as a subject of interdisciplinary research and teaching. The paper is based on literature and focuses on how to understand UD in interdisciplinary contexts. Both impairment effects and disabling barriers are important for understanding UD. Rehabilitation professions together with user-representatives provide knowledge on impairments as an aspect of human diversity; planning professionals provide knowledge on architecture and spatial planning. As an emerging field of knowledge, UD involves different knowledge; however, these differences may also lead to difficulties in communication. Results: Both theoretically and practically UD must correspond to an understanding of disability as relational, involving person, interaction and barriers. Implementing UD strategies ought to be linked to a concept of person that clearly includes impairments as a dimension of human plurality. Conclusion: In conclusion, the paper suggests that a common knowledge platform can prove productive for interdisciplinary work with UD.Implications for RehabilitationUniversal Design is a strategy to improve equal access for people with disabilities.A concept of the person and of disability is of importance for implementing Universal Design strategies.The interdisciplinary involvement in Universal Design must involve rehabilitation professions to attend to the individual dimension in Universal Design. © 2014 Informa UK Ltd.


Dembic Z.,University of Oslo
Current Pharmaceutical Design | Year: 2014

Over the past, progress has always been achieved in therapy of various human diseases with the introduction of novel methodologies from basic to clinical research. Recent advances in techniques, especially DNA sequencing and methylation analyses, faster miniaturized proteomics and live cellular stainings, are opening a new era in cancer research. Perhaps the difference this time can be envisaged as the beginning of the long-sought individualization of forthcoming cancer therapies. Cancer has complex genetic susceptibility that is wider than previously thought. Apart from genes encoding six functional capabilities of cancer – independent growth, avoidance of apoptosis, immortalization, multi-drug resistance, neovascularization, and invasiveness - predisposition includes four more factors that promote genome instability, inflammation, deregulation of metabolism as well as evasion of destruction by the immune system. The underlying genetic events, i.e. base-pair DNA mutations, are not the sole factors in cancer development. Additional novel controls of gene expression have been found in the epigenetic machinery, which has been increasingly important in assessing cancer risk in recent years. The predisposing factors, including their regulatory elements, are bona fide potential new targets in prospective cancer pharmacotherapy. © 2014 Bentham Science Publishers.


Schneider M.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hua T.A.,Novartis | Bohm M.,Saarland University | Wachtell K.,The Heart Center | And 2 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: The authors reviewed published clinical trial data on the effects of renin-angiotensin system (RAS) inhibition for the prevention of atrial fibrillation (AF), aiming to define when RAS inhibition is most effective. Background: Individual studies examining the effects of RAS inhibition on AF prevention have reported controversial results. Methods: All published randomized controlled trials reporting the effects of treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the primary or secondary prevention of AF were included. Results: A total of 23 randomized controlled trials with 87,048 patients were analyzed. In primary prevention, 6 trials in hypertension, 2 trials in myocardial infarction, and 3 trials in heart failure were included (some being post-hoc analyses of randomized controlled trials). In secondary prevention, 8 trials after cardioversion and 4 trials assessing the medical prevention of recurrence were included. Overall, RAS inhibition reduced the odds ratio for AF by 33% (p < 0.00001), but there was substantial heterogeneity among trials. In primary prevention, RAS inhibition was effective in patients with heart failure and those with hypertension and left ventricular hypertrophy but not in post-myocardial infarction patients overall. In secondary prevention, RAS inhibition was often administered in addition to antiarrhythmic drugs, including amiodarone, further reducing the odds for AF recurrence after cardioversion by 45% (p = 0.01) and in patients on medical therapy by 63% (p < 0.00001). Conclusions: This analysis supports the concept of RAS inhibition as an emerging treatment for the primary and secondary prevention of AF but acknowledges the fact that some of the primary prevention trials were post-hoc analyses. Further areas of uncertainty include potential differences among specific RAS inhibitors and possible interactions or synergistic effects with antiarrhythmic drugs. © 2010 American College of Cardiology Foundation.


In industrialized countries, female physicians have up to 10. h lower labor supply a week than male physicians. At the same time, the number of female physicians is increasing. The question analyzed in this article is whether these differences in labor supply for female and male hospital physicians persist in a modern welfare society, such as Norway, where comprehensive welfare reforms aim to reduce gender inequality are implemented. Information on weekly working hours from all hospital physicians in Norway during the period 2001-2007 was merged with economic variables (wages, income from other sources, net personal dept), demographic variables (age, sex, marital status, children born in the year, number of children), managerial positions and variables describing the hospital, specialty and time (year). The estimation method employed both random and fixed-effects models. Labor supply for women was 10-11 percent or 4-4.5. h per week lower than among men. The effects of children diverged strongly between the sexes. For instance, childbirth in a given year reduced the supply of working hours by women by approximately 80% but had no effects for men. After controlling for children and other factors, female physicians worked some 3-4% or 1-1.5 fewer hours than comparable male physicians. Although significant, variation in labor supply between female and male physicians is much lower in Norway then in other advanced industrialized countries. © 2012 Elsevier Ireland Ltd.


Li Z.,University of Oslo
International Journal of Hydrogen Energy | Year: 2012

Transcendental equations have to be solved in order to extract surface exchange and diffusion coefficients from transient techniques. In this work, numerical evaluations of the equation β ntanβ n = A, frequently used for a thin plane sheet geometry, have been studied in detail. Based on the Newton-Raphson method and the characteristics of the tangent function, a fast and stable algorithm was suggested to solve this equation for all values of A, which has so far not been the case in the literature. Moreover, a numerical approach to the transcendental equation used in a spherical geometry was also brought up. Copyright © 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.


Valberg M.,University of Oslo
American Journal of Epidemiology | Year: 2014

Using a 2-level hierarchical frailty model, we analyzed population-wide data on testicular germ-cell tumor (TGCT) status in 1,135,320 two-generational Norwegian families to examine the risk of TGCT in family members of patients. Follow-up extended from 1954 (cases) or 1960 (unaffected persons) to 2008. The first-level frailty variable was compound Poisson-distributed. The underlying Poisson parameter was randomized to model the frailty variation between families and was decomposed additively to characterize the correlation structure within a family. The frailty relative risk (FRR) for a son, given a diseased father, was 4.03 (95% confidence interval (CI): 3.12, 5.19), with a borderline significantly higher FRR for nonseminoma than for seminoma (P = 0.06). Given 1 affected brother, the lifetime FRR was 5.88 (95% CI: 4.70, 7.36), with no difference between subtypes. Given 2 affected brothers, the FRR was 21.71 (95% CI: 8.93, 52.76). These estimates decreased with the number of additional healthy brothers. The estimated FRRs support previous findings. However, the present hierarchical frailty approach allows for a very precise definition of familial risk. These FRRs, estimated according to numbers of affected/nonaffected family members, provide new insight into familial TGCT. Furthermore, new light is shed on the different familial risks of seminoma and nonseminoma. © The Author 2013.


Perreault M..-C.,Emory University | Glover J.C.,University of Oslo
Annals of the New York Academy of Sciences | Year: 2013

Subcortical descending glutamatergic neurons, such as reticulospinal (RS) neurons, play decisive roles in the initiation and control of many motor behaviors in mammals. However, little is known about the mechanisms used by RS neurons to control spinal motor networks because most of the neuronal elements involved have not been identified and characterized. In this review, we compare, in the embryonic mouse, the timing of developmental events that lead to the formation of synaptic connections between RS and spinal cord neurons. We then summarize our recent research in the postnatal mouse on the organization of synaptic connections between RS neurons and lumbar axial motoneurons (MNs), hindlimb MNs, and commissural interneurons. Finally, we give a brief account of some of the most recent studies on the intrinsic capabilities for plasticity of the mammalian RS system. The present review should give an updated insight into how functional specificity in RS motor networks emerges. © 2013 New York Academy of Sciences.


The behavioural response of nematodes to chemical stimuli has been