Oslo, Norway
Oslo, Norway

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.


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Patent
NewSouth Innovations Pty Ltd and University of Oslo | Date: 2016-12-06

The invention generally relates to the field of saxitoxins and the identification of microorganisms capable of producing them. More specifically, the invention relates to the identification of genes encoding saxitoxin in dinoflagellates, and methods for the specific detection of dinoflagellates that are producers of saxitoxins.


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.


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.


Houle D.,Florida State University | Govindaraju D.R.,Harvard University | Omholt S.,Norwegian University of Life Sciences | Omholt S.,University of Oslo
Nature Reviews Genetics | Year: 2010

A key goal of biology is to understand phenotypic characteristics, such as health, disease and evolutionary fitness. Phenotypic variation is produced through a complex web of interactions between genotype and environment, and such a 'genotype-phenotype' map is inaccessible without the detailed phenotypic data that allow these interactions to be studied. Despite this need, our ability to characterize phenomes- the full set of phenotypes of an individual- lags behind our ability to characterize genomes. Phenomics should be recognized and pursued as an independent discipline to enable the development and adoption of high-throughput and high-dimensional phenotyping. © 2010 Macmillan Publishers Limited. 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.


Moskvinite-(Y), Na2K(Y,REE)Si6O15, is a rare mineral, which until now has only been described from its type locality Dara-i-Pioz, Tajikistan. At Ilímaussaq moskvinite-(Y) was discovered in a drill core from Kvanefjeld, where it occurs as a replacement mineral associated with a mineral belonging to the britholite group. The composition was determined by a combination of electron probe microanalysis and laser ablation inductively coupled plasma mass spectrometry analyses. The empirical formula based on 15 oxygens is Na1.94K0.99(Y0.94Yb0.03Er0.03Dy0.03Ho0.01Gd0.01)λ1.05Si5.98O15. The coexistence of an almost pure Yand a light rare-earth element (REE) mineral is interpreted as fractionation of REE and Y during the replacement of an earlier formed REE mineral. Theoretical calculations of the observed replacement of feldspathoids by natrolite show that the generated fluid would have pH > 8, which inhibits large scale mobility of REE. In addition, a K-Fe sulfide member of the chlorbartonite-bartonite group is for the first time observed in Ilímaussaq where it occurs where sodalite is replaced by natrolite and arfvedsonite by aegirine. The sulfide incorporates the S and some of the Cl generated by the alteration of sodalite, whereas the K and Fe originates from the replacement of arfvedsonite by aegirine. © 2016 by Walter de Gruyter Berlin/Boston 2016.


Malmstrom M.,University of Oslo
Nature Genetics | Year: 2016

Teleost fishes constitute the most species-rich vertebrate clade and exhibit extensive genetic and phenotypic variation, including diverse immune defense strategies. The genomic basis of a particularly aberrant strategy is exemplified by Atlantic cod, in which a loss of major histocompatibility complex (MHC) II functionality coincides with a marked expansion of MHC I genes. Through low-coverage genome sequencing (9–39×), assembly and comparative analyses for 66 teleost species, we show here that MHC II is missing in the entire Gadiformes lineage and thus was lost once in their common ancestor. In contrast, we find that MHC I gene expansions have occurred multiple times, both inside and outside this clade. Moreover, we identify an association between high MHC I copy number and elevated speciation rates using trait-dependent diversification models. Our results extend current understanding of the plasticity of the adaptive immune system and suggest an important role for immune-related genes in animal diversification. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Fang E.F.,U.S. National Institute on Aging | Scheibye-Knudsen M.,U.S. National Institute on Aging | Brace L.E.,Harvard University | Kassahun H.,University of Oslo | And 6 more authors.
Cell | Year: 2014

Mitochondrial dysfunction is a common feature in neurodegeneration and aging. We identify mitochondrial dysfunction in xeroderma pigmentosum group A (XPA), a nucleotide excision DNA repair disorder with severe neurodegeneration, in silico and in vivo. XPA-deficient cells show defective mitophagy with excessive cleavage of PINK1 and increased mitochondrial membrane potential. The mitochondrial abnormalities appear to be caused by decreased activation of the NAD+-SIRT1-PGC-1α axis triggered by hyperactivation of the DNA damage sensor PARP-1. This phenotype is rescued by PARP-1 inhibition or by supplementation with NAD+ precursors that also rescue the lifespan defect in xpa-1 nematodes. Importantly, this pathogenesis appears common to ataxia-telangiectasia and Cockayne syndrome, two other DNA repair disorders with neurodegeneration, but absent in XPC, a DNA repair disorder without neurodegeneration. Our findings reveal a nuclear-mitochondrial crosstalk that is critical for the maintenance of mitochondrial health. © 2014 Elsevier Inc.


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.


Raiborg C.,University of Oslo | Wenzel E.M.,University of Oslo | Stenmark H.,University of Oslo | Stenmark H.,Norwegian University of Science and Technology
EMBO Journal | Year: 2015

Recent studies have revealed the existence of numerous contact sites between the endoplasmic reticulum (ER) and endosomes in mammalian cells. Such contacts increase during endosome maturation and play key roles in cholesterol transfer, endosome positioning, receptor dephosphorylation, and endosome fission. At least 7 distinct contact sites between the ER and endosomes have been identified to date, which have diverse molecular compositions. Common to these contact sites is that they impose a close apposition between the ER and endosome membranes, which excludes membrane fusion while allowing the flow of molecular signals between the two membranes, in the form of enzymatic modifications, or ion, lipid, or protein transfer. Thus, ER-endosome contact sites ensure coordination of molecular activities between the two compartments while keeping their general compositions intact. Here, we review the molecular architectures and cellular functions of known ER-endosome contact sites and discuss their implications for human health. Membrane contact sites, defined as sites of close apposition between two membranes, are crucial for the direct exchange of information between distinct endomembrane compartments. This review highlights the diverse functions of ER-endosome contact sites. © 2015 The Authors.


Lobert V.H.,University of Oslo
Physiology (Bethesda, Md.) | Year: 2011

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.


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.


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


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.


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.


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.


Butenko M.A.,University of Oslo | Simon R.,Heinrich Heine University Düsseldorf
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.


Background:Histone deacetylase inhibitors (HDACis) like vorinostat are promising radiosensitisers in prostate cancer, but their effect under hypoxia is not known. We investigated gene expression associated with radiosensitisation of normoxic and hypoxic prostate cancer cells by vorinostat.Methods:Cells were exposed to vorinostat under normoxia or hypoxia and subjected to gene expression profiling before irradiation and clonogenic survival analysis.Results:Pretreatment with vorinostat led to radiosensitisation of the intrinsically radioresistant DU 145 cells, but not the radiosensitive PC-3 and 22Rv1 cells, and was independent of hypoxia status. Knockdown experiments showed that the sensitisation was not caused by repression of hypoxia-inducible factor HIF1 or tumour protein TP53. Global deregulation of DNA repair and chromatin organisation genes was associated with radiosensitisation under both normoxia and hypoxia. A radiosensitisation signature with expression changes of 56 genes was generated and valid for both conditions. For eight signature genes, baseline expression also correlated with sensitisation, showing potential as pretreatment biomarker. The hypoxia independence of the signature was confirmed in a clinical data set.Conclusions:Pretreatment with HDACi may overcome radioresistance of hypoxic prostate tumours by similar mechanisms as under normoxia. We propose a gene signature to predict radiosensitising effects independent of hypoxia status.British Journal of Cancer advance online publication 6 September 2016; doi:10.1038/bjc.2016.278 www.bjcancer.com. © 2016 Cancer Research UK


Pedersen W.,University of Oslo | Sandberg S.,University of Oslo
Sociology of Health and Illness | Year: 2013

In a qualitative study, we investigated the medical motives of 100 Norwegian cannabis users, none of whom had legal access to medical cannabis. Cannabis was used therapeutically for conditions such as multiple sclerosis, attention deficit hyperactivity disorder and rheumatism, as well as for quality of life conditions such as quality of sleep, relaxation and wellbeing. The borders between medical and recreational cannabis use were blurred. This article identifies strategies of medical cannabis users to gain social acceptance. Several respondents downplayed effects such as intoxication and euphoria. Others used the language of medicine and knowledge of current research in psychopharmacology. Cannabis was contrasted with the potential for abuse of prescription medicines. The medical cannabis movement has had little success in Norway. Medical professionals are unable to accept that users may be more knowledgeable than experts and medical users cannot discard the values of traditional cannabis culture. Calls for medical cannabis use are thus perceived as a gambit in attempts to have cannabis legalised. We argue that, despite having had little effect on health authorities, the medical cannabis movement may be having the unintended effect of medicalising cannabis use and using it as a cure for everyday problems. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.


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.


O'Brien K.,University of Oslo | Barnett J.,University of Melbourne
Annual Review of Environment and Resources | Year: 2013

This article reviews research on global environmental change and human security, providing retrospective and tentative prospective views of this field. It explains the roles that the concept of human security has played in research on environmental change, as well as the knowledge that it has contributed. It then discusses the Global Environmental Change and Human Security (GECHS) project as an example of how this research has encouraged a more politicized understanding of the problem of global environmental change, drawing attention to the roles of power, agency, and knowledge. Finally, the article considers new research frontiers that have emerged from this field, including research on social transformations as a means of promoting, sustaining, and enhancing human security in response to complex global environmental challenges. The potential contributions of human security approaches to the next generation of global change research are discussed. © 2013 by Annual Reviews. All rights reserved.


Nezis I.P.,University of Oslo | Stenmark H.,University of Oslo
Antioxidants and Redox Signaling | Year: 2012

Significance: Sequestosome 1 (p62/SQSTM1) is a multifunctional adapter protein implicated in selective autophagy, cell signaling pathways, and tumorigenesis. Recent Advances: Recent evidence has revealed that p62/SQSTM1 has a critical role in an oxidative stress response pathway by its direct interaction with the ubiquitin ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), which results in constitutive activation of the transcription factor NF-E2-related factor 2 (NRF2). Critical Issues: Both NRF2 and KEAP1 are frequently mutated in cancer. The findings just cited uncover a link between p62/SQSTM1, autophagy, and the KEAP1-NRF2 stress response pathway in tumorigenesis and shed light on the interplay between autophagy and cancer. Future Directions: Here, we review the mechanisms by which p62/SQSTM1 implements its multiple roles in the regulation of tumorigenesis with emphasis on the KEAP1-NRF2 stress response signaling pathway. Uncovering the molecular mechanisms of p62/SQSTM1 function in oxidative stress signaling might contribute to elucidating its role in tumorigenesis. Antioxid. Redox Signal. © 2012 Mary Ann Liebert, Inc.


Robertson A.B.,University of Oslo | Dahl J.A.,University of Oslo | Ougland R.,University of Oslo | Klungland A.,University of Oslo
Nature Protocols | Year: 2012

We describe a method for the efficient and selective identification of DNA containing the 5-hydroxymethylcytosine (5-hmC) modification. This protocol takes advantage of two proteins: T4 β-glucosyltransferase (β-gt), which converts 5-hmC to β-glucosyl-5-hmC (β-glu-5-hmC), and J-binding protein 1 (JBP1), which specifically recognizes and binds to β-glu-5-hmC. We describe the steps necessary to purify JBP1 and modify this protein such that it can be fixed to magnetic beads. Thereafter, we detail how to use the JBP1 magnetic beads to obtain DNA that is enriched with 5-hmC. This method is likely to produce results similar to those of other 5-hmC pull-down assays; however, all necessary components for the completion of this protocol are readily available or can be easily and rapidly synthesized using basic molecular biology techniques. This protocol can be completed in less than 2 weeks and allows the user to isolate 5-hmC-containing genomic DNA that is suitable for analysis by quantitative PCR (qPCR), sequencing, microarray and other molecular biology assays. © 2012 Nature America, Inc. All rights reserved.


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.


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).


Asheim G.B.,University of Oslo
Environmental and Resource Economics | Year: 2010

Strategic use of environmental information may have as consequence that a benevolent environmental agency will choose not to disclose information leading to reduced moral motivation. Thus, decision makers will not have access to such information, implying that they will not be able to adjust their decisions to available information on the state of the environment. In contrast, if the benevolent environmental agency instead bases its regulation on standard economic instruments, these instruments will incorporate all available information. © 2010 Springer Science+Business Media B.V.


Many mechanisms control the state of stress within Earth plates. First-order well-known mechanisms include stresses induced by lateral variations of lithospheric density structure, sublithospheric tractions, ridge push and subduction pull. In this study, we attempt to quantify the influence of these mechanisms to understand the origin of stresses in the lithosphere, choosing the African plate (TAP) as an example. A finite-element based suite, Proshell, was developed to combine several data sets, to estimate the gravitational potential energy (GPE) of the lithosphere and to calculate stresses acting on the real (non-planar) geometry of TAP. We introduce several quantitative parameters to measure the degree of fit between the model and observations. Our modelling strategy involves nine series of numerical experiments. We start with the simplest possible model and then, step by step, build it up to be a more physically realistic model, all the while discussing the influence of each additional component. The starting (oversimplified) model series (1) is based on the CRUST2 data set for the crust and a half-space-cooling approximation of the lithospheric mantle. We then describe models (series 2-5) that account for lithospheric mantle density heterogeneities to build a more reliable GPE model. The consecutive series involve basal traction from the convective mantle (series A, C) and the rheological heterogeneity of the TAP via variations in its effective elastic thickness (series B, C). The model quality reflects the increase in complexity between series with an improving match to observed stress regimes and directions. The most complex model (series D) also accounts for the bending stresses in the elastic lithosphere and achieves a remarkably good fit to observations. All of our experiments were based on the iteration of controlling parameters in order to achieve the best fit between modelled and observed stresses, always considering physically feasible values. This gives us confidence that our methodology appropriately models the stress pattern of Africa, and that it may be further applied to other plates on Earth. Our modelling approach allows us to quantify several important features controlling the lithospheric stress pattern. Even though the initial oversimplified model does not fit the observations satisfactorily, it shows how ridge push may create significant compressive stresses in the lithosphere. More complex models show the importance of the density structure of the lithosphere, specifically in the subcrustal lithosphere. The stress regime within the TAP mainly results from a global balance of masses and mass moments between continental and oceanic parts of the plate. The orientation of stresses, in turn, is influenced more by local features expressed by topographic and crustal density variations, whereas existent subcrustal density variations appear to be smoothed by the crust above. The models show that accounting separately for either basal tractions or rheological heterogeneities brings moderate improvement, but the combination of these two mechanisms results in a substantially better match between model and observations. The bending stresses caused by isostatical readjustment improve the model match, but they have to be analysed with caution because of their depth-dependent nature. © The Author 2016.


Mesiti F.,Norwegian University of Science and Technology | Balasingham I.,University of Oslo
IEEE Journal on Selected Areas in Communications | Year: 2013

The recent advancements in nanotechnology have been instrumental in initiating research and development of intelligent nanomachines, in a variety of different application domains including healthcare. The stimulation of the cerebral cortex to assist the treatment of brain diseases have been investigated with growing interest in the past, where nanotechnology offers a dramatic breakthrough. In this paper, we discuss the feasibility of a nanomachine-to-neuron interface to design a nanoscale stimulator device called synaptic nanomachine (SnM), compatible with the neuronal communication paradigm. An equivalent neuron-nanomachine model (EqNN) is proposed to describe the behavior of neurons excited by a network of SnMs. Sample populations of neurons are simulated under different stimulation scenarios. The assessment of the existing correlation between SnM stimulus and response, as well as between neurons and clusters of neurons, has been performed using statistical methods. The obtained results reveal that a controlled nanoscale stimulation induces apparently an oscillatory behavior in the neuronal activity and localized synchronization between neurons. Both effects are expected to have the basis of important cognitive and behavioral functions such as learning and brain plasticity. © 1983-2012 IEEE.


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.


Bo K.,University of Oslo | Hilde G.,University of Oslo
Neurourology and Urodynamics | Year: 2013

Aims: There is level 1, grade A evidence that pelvic floor muscle training (PFMT) is effective in treatment of stress urinary incontinence (SUI), but long-term outcome has been questioned. The aim of this systematic review was to evaluate the long-term outcome of PFMT for female SUI. Methods: Computerized search on PubMed up to year 2012 was undertaken with the search strategy: pelvic floor AND (urinary incontinence OR stress urinary incontinence) AND (training OR exercise OR physical activity) AND (follow-up OR long-term). Limitations were: humans, female, clinical trial, English, and adults. Inclusion criteria were: studies on SUI using PFMT with or without biofeedback as the intervention, follow-up period of ≥1 year. Exclusion criteria were studies using electrical stimulation alone and studies in the peripartum period. Results: Nineteen studies were included (1,141 women followed between 1 and 15 years). Statistical meta-analysis was not performed due to high heterogeneity. Only two studies provided follow-up interventions. Losses to follow-up during the long-term period ranged between 0% and 39%. Long-term adherence to PFMT varied between 10% and 70%. Five studies reported that the initial success rate on SUI and MUI was maintained at long-term. Long-term success based on responders to the original trial varied between 41% and 85%. Surgery rates at long term varied between 4.9% and 58%. Conclusions: Short-term outcome of PFMT can be maintained at long-term follow-up without incentives for continued training, but there is a high heterogeneity in both interventional and methodological quality in short-and long-term pelvic floor muscle training studies. © 2012 Wiley Periodicals, Inc.


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).


Scheibert J.,University of Oslo | Dysthe D.K.,University of Oslo
Europhysics Letters | Year: 2010

We present a minimal quasistatic 1D model describing the kinematics of the transition from static friction to stick-slip motion of a linear elastic block on a rigid plane. We show how the kinematics of both the precursors to frictional sliding and the periodic stick-slip motion are controlled by the amount of friction-induced torque at the interface. Our model provides a general framework to understand and relate a series of recent experimental observations, in particular the nucleation location of micro-slip instabilities and the build-up of an asymmetric field of real contact area. Copyright © EPLA, 2010.


Strandlie A.,Gjøvik 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.


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.


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).


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.


Alvik A.,University of Oslo
Scandinavian Journal of Public Health | Year: 2014

Aim: To explore variables predicting low developmental scores in 6-month-old infants in a population-based study. Methods: In a longitudinal study representative of pregnant women in Oslo, Norway, questionnaires were answered at 17 and 30 weeks of pregnancy and 6 months after term; N = 1053 after exclusions (women with non-Scandinavian ethnicity, twin births, infants <5.0 or >7.0 months corrected age, and birth weight <2.5 kg), and data were collected from the Norwegian Birth Registry. Measures included sociodemographic variables, maternal mental health and pregnancy life style, data concerning the birth/newborn, and the Ages and Stages Questionnaires (ASQ) for 6-month-olds. Logistic regression analyses were used to identify variables predicting an ASQ score ≤15th percentile. Results: In adjusted analyses, only increasing maternal age and infant having older siblings predicted a low score on ASQ Total. These variables also predicted low scores on several ASQ areas (i.e. Communication, Gross motor, Fine motor, Problem-solving and Personal social), together with maternal major lifetime depression and feeling lonely. Protective variables were increasing infant birth weight (Gross motor) and pregnancy smoking (Communication). Other maternal sociodemographic variables, and infant sex, had no predictive power. Already at a maternal age of 31, the mean age of the pregnant women, the possibility of a low infant score increased significantly. Conclusions: In this population-based study, higher maternal age, having older siblings, and a history of maternal major lifetime depression, mainly predicts low developmental scores in 6-month-old infants. © 2013 the Nordic Societies of Public Health.


Brustugun O.T.,University of Oslo | Helland A.,University of Oslo
Acta Oncologica | Year: 2014

Background. Cancer of unknown primary (CUP) carries a dismal prognosis due to the two hallmarks of 1) being metastatic with 2) no known specific treatment. An organ-labeled diagnosis of cancer should therefore be sought. In this study, we have analyzed population-based incidence and survival data of CUP over the latest 40 years. Material and methods. Complete national data on 23 004 CUP-patients from the Cancer Registry of Norway sampled from 1971 to 2010 are presented, with absolute and age-adjusted incidence rates correlated to the total cancer incidence. One-year relative survival rates were calculated. Results. The incidence of CUP increased both in absolute numbers and as a fraction of total cancer incidence during the first half of the period. There has been a substantial decrease in incidence over the latest 20 years, now being responsible of only 1.7% and 1.2% of the total cancer incidence in females and males, respectively, with an age-adjusted incidence rate of 3.5 and 3.8, respectively. The one-year relative survival rate has increased and was slightly below 20% for both sexes in 2010. Conclusion. Better diagnostics, both radiological and pathological, is probably responsible for a substantially lower incidence. Improved treatment for cancers in general also benefits the CUP-group. © 2014 Informa Healthcare.


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.


OBJECTIVE: To review our experience of managing idiopathic normal pressure hydrocephalus (iNPH) during the 6-year period from 2002 to 2007, when intracranial pressure (ICP) monitoring was part of the diagnostic workup. METHODS: The review includes all iNPH patients undergoing diagnostic ICP monitoring during the years 2002 to 2007. Clinical grading was done prospectively using a normal pressure hydrocephalus (NPH) grading scale (scores from 3 to 15). The selection of patients for surgery was based on clinical symptoms, enlarged cerebral ventricles, and findings on ICP monitoring. The median follow-up time was 2 years (range, 0.3-6 years). Both static ICP and pulsatile ICP were analyzed. RESULTS: A total of 214 patients underwent the diagnostic workup, of whom 131 went on to surgery. Although 1 patient died shortly after treatment, 103 of the 130 patients (79%) improved clinically. This improvement lasted throughout the observation period. The static ICP observed during ICP monitoring was a poor predictor of the response to surgery. In contrast, among 109 of 130 patients with increased ICP pulsatility (ie, ICP wave amplitude >4 mm Hg on average and >5 mm Hg in >10% of recording time), 101 (93%) were responders (ie, increase in the NPH score of >2). Correspondingly, only 2 of 21 (10%) without increased ICP pulsatility were responders. Superficial wound infection was the only complication of ICP monitoring and occurred in 4 (2%) patients. CONCLUSION: Surgical results in iNPH were good with almost 80% of patients improving after treatment. The data indicate that improvement after surgery can be anticipated in 9 of 10 iNPH patients with abnormal ICP pulsatility, but in only 1 of 10 with normal ICP pulsatility. Diagnostic ICP monitoring had a low complication rate. Copyright © 2010 by the Congress of Neurological Surgeons.


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.


Lervag A.,University of Oslo | Aukrust V.G.,University of Oslo
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2010

Background: This study examines the role of decoding and vocabulary skills as longitudinal predictors of reading comprehension in young first (L1) and second (L2) language learners. Methods: Two-group latent growth models were used to assess differences in growth and predictions of growth between the 198 L1 and 90 L2 language learners. Results: L1 learners had better initial reading comprehension skills and faster growth in these skills over time. Individual differences in decoding and vocabulary predicted initial reading comprehension skills, but only vocabulary predicted the subsequent growth of reading comprehension skills. Vocabulary seemed to be a stronger predictor of growth in reading comprehension among the L2 learners than among the L1 learners. Conclusions: Vocabulary appears to be a critical predictor of the early development of reading comprehension skills in both L1 and L2 learners. The limitations in vocabulary skills in the L2 learners seemed sufficient to explain their lag in developing reading comprehension skills, and this suggests that oral vocabulary training should be given a high priority in this group. © 2009 Association for Child and Adolescent Mental Health.


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.


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.


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.


Russell M.B.,University of Oslo | Ducros A.,Center dUrgences Cephalees
The Lancet Neurology | Year: 2011

Hemiplegic migraine is a rare form of migraine with aura that involves motor aura (weakness). This type of migraine can occur as a sporadic or a familial disorder. Familial forms of hemiplegic migraine are dominantly inherited. Data from genetic studies have implicated mutations in genes that encode proteins involved in ion transportation. However, at least a quarter of the large families affected and most sporadic cases do not have a mutation in the three genes known to be implicated in this disorder, suggesting that other genes are still to be identified. Results from functional studies indicate that neuronal hyperexcitability has a pivotal role in the pathogenesis of hemiplegic migraine. The clinical manifestations of hemiplegic migraine range from attacks with short-duration hemiparesis to severe forms with recurrent coma and prolonged hemiparesis, permanent cerebellar ataxia, epilepsy, transient blindness, or mental retardation. Diagnosis relies on a careful patient history and exclusion of potential causes of symptomatic attacks. The principles of management are similar to those for common varieties of migraine, except that vasoconstrictors, including triptans, are historically contraindicated but are often used off-label to stop the headache, and prophylactic treatment can include lamotrigine and acetazolamide. © 2011 Elsevier Ltd.


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.


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.


Debella-Gilo M.,University of Oslo | Kaab A.,University of Oslo
ISPRS Journal of Photogrammetry and Remote Sensing | Year: 2012

This paper presents an algorithm for locally adaptive template sizes in normalized cross-correlation (NCC) based image matching for measuring horizontal surface displacements of mass movements. After adaptively identifying candidate templates based on the image signal-to-noise ratio (SNR), the algorithm iteratively looks for the size at which the maximum cross-correlation coefficient attains a local peak and the matching position gets fixed. The algorithm is tested on modeled (deformed) images and applied to real bi-temporal images of different Earth surface mass movements. It is evaluated in comparison with globally (image-wide) fixed template sizes ranging from 11 to 101. pixels based on the improvement in the accuracy of displacement estimation and the SNR of image reconstruction. The results show that the algorithm could reduce the error of displacement estimation by up to over 90% (in the modeled case) and improve the SNR of the matching by up to over four times compared to the globally fixed template sizes highly reducing the effects of geometric distortion and noise. The algorithm pushes terrain displacement measurement from repeat images one step forward towards full automation. © 2012 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS).


Inngjerdingen M.,University of Oslo
Nature Methods | Year: 2016

We report a tool for the analysis of subcellular proteomics data, called MetaMass, based on the use of standardized lists of subcellular markers. We analyzed data from 11 studies using MetaMass, mapping the subcellular location of 5,970 proteins. Our analysis revealed large variations in the performance of subcellular fractionation protocols as well as systematic biases in protein annotation databases. The Excel and R versions of MetaMass should enhance transparency and reproducibility in subcellular proteomics. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Hessen D.O.,University of Oslo | Daufresne M.,IRSTEA | Leinaas H.P.,University of Oslo
Biological Reviews | Year: 2013

A family of empirically based ecological 'rules', collectively known as temperature-size rules, predicts larger body size in colder environments. This prediction is based on studies demonstrating that a wide range of ectotherms show increased body size, cell size or genome size in low-temperature habitats, or that individuals raised at low temperature become larger than conspecifics raised at higher temperature. There is thus a potential for reduction in size with global warming, affecting all levels from cell volume to body size, community composition and food webs. Increased body size may be obtained either by increasing the size or number of cells. Processes leading to changed cell size are of great interest from an ecological, physiological and evolutionary perspective. Cell size scales with fundamental properties such as genome size, growth rate, protein synthesis rates and metabolic activity, although the causal directions of these correlations are not clear. Changes in genome size will thus, in many cases, not only affect cell or body size, but also life-cycle strategies. Symmetrically, evolutionary drivers of life-history strategies may impact growth rate and thus cell size, genome size and metabolic rates. Although this goes to the core of many ecological processes, it is hard to move from correlations to causations. To the extent that temperature-driven changes in genome size result in significant differences among populations in body size, allometry or life-cycle events such as mating season, it could serve as a fast route to speciation. We offer here a novel perspective on the temperature-size rules from a 'bottom-up' perspective: how temperature may induce changes in genome size, and thus implicitly in cell size and body size of metazoans. Alternatively: how temperature-driven enlargement of cells also dictates genome-size expansion to maintain the genome-size to cell-volume ratio. We then discuss the different evolutionary drivers in aquatic versus terrestrial systems, and whether it is possible to arrive at a unifying theory that also may serve as a predictive tool related to temperature changes. This, we believe, will offer an updated review of a basic concept in ecology, and novel perspectives on the basic biological responses to temperature changes from a genomic perspective. © 2012 Cambridge Philosophical Society.


Slagsvold T.,University of Oslo | Wiebe K.L.,University of Saskatchewan
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

We briefly review the literature on social learning in birds, concluding that strong evidence exists mainly for predator recognition, song, mate choice and foraging. The mechanism of local enhancement may be more important than imitation for birds learning to forage, but the former mechanism may be sufficient for faithful transmission depending on the ecological circumstances. To date, most insights have been gained from birds in captivity. We present a study of social learning of foraging in two passerine birds in the wild, where we cross-fostered eggs between nests of blue tits, Cyanistes caeruleus and great tits, Parus major. Early learning causes a shift in the foraging sites used by the tits in the direction of the foster species. The shift in foraging niches was consistent across seasons, as showed by an analysis of prey items, and the effect lasted for life. The fact that young birds learn from their foster parents, and use this experience later when subsequently feeding their own offspring, suggests that foraging behaviour can be culturally transmitted over generations in the wild. It may therefore have both ecological and evolutionary consequences, some of which are discussed. © 2011 The Royal Society.


Bull V.H.,University of Oslo | Thiede B.,University of Oslo
Electrophoresis | Year: 2012

Endoplasmic reticulum (ER) stress occurs upon increased levels of unfolded proteins and results in activation of cellular responses such as the unfolded protein response (UPR) and ER-associated protein degradation (ERAD). To examine ER stress, we performed a quantitative proteome analysis of human neuroblastoma cells using stable isotope labeling with amino acids in cell culture (SILAC) in combination with SDS-PAGE and LC-MS/MS. Proteins associated with the ER were overrepresented in the dataset of altered proteins. In particular, ER chaperones responsible for protein folding were significantly upregulated in response to ER stress. The important ER stress regulator 78 kDa glucose-regulated protein (GRP-78 or BiP) was highly upregulated together with several proteins that have been found to form a multiprotein complex with BiP including cyclophilin B, DnaJ homolog subfamily B member 11, endoplasmin, hypoxia upregulated protein 1, protein disulfide isomerase and protein disulfide isomerase A4 upon tunicamycin-induced ER stress. Furthermore, seven aminoacyl-tRNA synthetases and five proteins belonging to the Sec61 complex were increased in response to tunicamycin-induced ER stress. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


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.


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.


Starrfelt J.,University of Oslo | Liow L.H.,University of Oslo
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

The fossil record is a rich source of information about biological diversity in the past. However, the fossil record is not only incomplete but has also inherent biases due to geological, physical, chemical and biological factors. Our knowledge of past life is also biased because of differences in academic and amateur interests and sampling efforts. As a result, not all individuals or species that lived in the past are equally likely to be discovered at any point in time or space. To reconstruct temporal dynamics of diversity using the fossil record, biased sampling must be explicitly taken into account. Here, we introduce an approach that uses the variation in the number of times each species is observed in the fossil record to estimate both sampling bias and true richness. We term our technique TRiPS (True Richness estimated using a Poisson Sampling model) and explore its robustness to violation of its assumptions via simulations. We then venture to estimate sampling bias and absolute species richness of dinosaurs in the geological stages of the Mesozoic. Using TRiPS, we estimate that 1936 (1543–2468) species of dinosaurs roamed the Earth during the Mesozoic. We also present improved estimates of species richness trajectories of the three major dinosaur clades: the sauropodomorphs, ornithischians and theropods, casting doubt on the Jurassic–Cretaceous extinction event and demonstrating that all dinosaur groups are subject to considerable sampling bias throughout the Mesozoic. © 2016 The Authors.


Jenssen T.,University of Tromsø | 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.


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.


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.


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.


Isakson P.,University of Oslo | Bjoras M.,University of Oslo | Boe S.O.,University of Oslo | Simonsen A.,University of Oslo
Blood | Year: 2010

Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid and/or arsenic trioxide represents a paradigm in targeted cancer therapy because these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). The authors of previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy-induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both all-trans retinoic acid and arsenic trioxide induce autophagy via the mammalian target of rapamycin pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy-induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease. © 2010 by The American Society of Hematology.


Buildings generally need serious attention in order to reduce global energy consumption and greenhouse gas emissions. Phase Change Materials (PCMs) that change phase just above normal room temperature are a promising means of reducing coolingenergy demand, and improving thermal comfort in buildings. This paper reviews the literature from studies of the thermal performance of different types of PCM and different ways of integrating them into buildings. Based on this review, the paper closes with an investigation of the potential for application of PCMs in passive-house standard dwellings and office buildings in the Nordic climate. © 2014 The Author.


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

Nandrolone or nortestosterone, an anabolic-androgenic steroid, has been prohibited by doping control regulations for more than 30 years. Although its main metabolism in the human body was already known at that time, and detection of its misuse by gas or liquid chromatographic separation with mass spectrometric detection is straightforward, many interesting aspects regarding this doping agent have appeared since. Over the years, nandrolone preparations have kept their position among the prohibited substances that are most frequently detected in WADA-accredited laboratories. Their forms of application range from injectable fatty acid esters to orally administered nandrolone prohormones. The long detection window for nandrolone ester preparations and the appearance of orally available nandrolone precursors have changed the pattern of misuse. At the same time, more refined analytical methods with lowered detection limits led to new insights into the pharmacology of nandrolone and revelation of its natural production in the body. Possible contamination of nutritional supplements with nandrolone precursors, interference of nandrolone metabolism by other drugs and rarely occurring critical changes during storage of urine samples have to be taken into consideration when interpreting an analytical finding. A set of strict identification criteria, including a threshold limit, is applied to judge correctly an analytical finding of nandrolone metabolites. The possible influence of interfering drugs, urine storage or natural production is taken into account by applying appropriate rules and regulations. © 2009 Springer-Verlag Berlin Heidelberg.


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.


Lin H.-H.,University of Oslo | Carlsson M.,University of Oslo
Astrophysical Journal | Year: 2015

The O I 135.56 nm line is covered by NASA's Interface Region Imaging Spectrograph (IRIS) small explorer mission which studies how the solar atmosphere is energized. We study here the formation and diagnostic potential of this line by means of non-local thermodynamic equilibrium modeling employing both 1D semi-empirical and 3D radiation magnetohydrodynamic models. We study the basic formation mechanisms and derive a quintessential model atom that incorporates essential atomic physics for the formation of the O I 135.56 nm line. This atomic model has 16 levels and describes recombination cascades through highly excited levels by effective recombination rates. The ionization balance O I/ O II is set by the hydrogen ionization balance through charge exchange reactions. The emission in the O I 135.56 nm line is dominated by a recombination cascade and the line is optically thin. The Doppler shift of the maximum emission correlates strongly with the vertical velocity in its line forming region, which is typically located at 1.0-1.5 Mm height. The total intensity of the line emission is correlated with the square of the electron density. Since the O I 135.56 nm line is optically thin, the width of the emission line is a very good diagnostic of non-thermal velocities. We conclude that the O I 135.56 nm line is an excellent probe of the middle chromosphere, and compliments other powerful chromospheric diagnostics of IRIS such as the Mg ii h & k lines and the C ii lines around 133.5 nm. © 2015. The American Astronomical Society. All rights reserved.


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.


Knaevelsrud H.,University of Oslo | Simonsen A.,University of Oslo
FEBS Letters | Year: 2010

Ubiquitinated protein aggregates are hallmarks of a range of human diseases, including neurodegenerative, liver and muscle disorders. These protein aggregates are typically positive for the autophagy receptor p62. Whereas the ubiquitin-proteasome system (UPS) degrades shortlived and misfolded ubiquitinated proteins that are small enough to enter the narrow pore of the barrel-shaped proteasome, the lysosomal pathway of autophagy can degrade larger structures including entire organelles or protein aggregates. This degradation requires autophagy receptors that link the cargo with the molecular machinery of autophagy and is enhanced by certain posttranslational modifications of the cargo. In this review we focus on how autophagy clears aggregate-prone proteins and the relevance of this process to protein aggregate associated diseases. © 2010 Federation of European Biochemical Societies.


Sagona A.P.,University of Oslo | Stenmark H.,University of Oslo
FEBS Letters | Year: 2010

Cytokinesis is the final stage of cell division during which the two daughter cells separate completely. Although less well understood than some of the earlier phases of the cell cycle, recent discoveries have shed light on the mechanisms that orchestrate this process, including cleavage furrow formation, midbody maturation and abscission. One of the reasons why research on cytokinesis has been attracting increasing attention is the concept that failure of this process in mammals is associated with carcinogenesis. In this minireview, we will discuss the possible links between cytokinesis and cancer, and highlight key mechanisms that connect these processes. © 2010 Federation of European Biochemical Societies.


Eriksen E.F.,University of Oslo
Reviews in Endocrine and Metabolic Disorders | Year: 2010

Bone remodeling is a tightly regulated process securing repair of microdamage (targeted remodeling) and replacement of old bone with new bone through sequential osteoclastic resorption and osteoblastic bone formation. The rate of remodeling is regulated by a wide variety of calcitropic hormones (PTH, thyroid hormone, sex steroids etc.). In recent years we have come to appreciate that bone remodeling proceeds in a specialized vascular structure, - the Bone Remodeling Compartment (BRC). The outer lining of this compartment is made up of flattened cells, displaying all the characteristics of lining cells in bone including expression of OPG and RANKL. Reduced bone turnover leads to a decrease in the number of BRCs, while increased turnover causes an increase in the number of BRCs. The secretion of regulatory factors inside a confined space separated from the bone marrow would facilitate local regulation of the remodeling process without interference from growth factors secreted by blood cells in the marrow space. The BRC also creates an environment where cells inside the structure are exposed to denuded bone, which may enable direct cellular interactions with integrins and other matrix factors known to regulate osteoclast/osteoblast activity. However, the denuded bone surface inside the BRC also constitutes an ideal environment for the seeding of bone metastases, known to have high affinity for bone matrix. Circulating osteoclast- and osteoblast precursor cells have been demonstrated in peripheral blood. The dominant pathway regulating osteoclast recruitment is the RANKL/OPG system, while many different factors (RUNX, Osterix) are involved in osteoblast differentiation. Both pathways are modulated by calcitropic hormones. © The Author(s) 2010.


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).


Walhovd K.B.,University of Oslo | Tamnes C.K.,University of Oslo | Fjell A.M.,University of Oslo
Current Opinion in Neurology | Year: 2014

Purpose of review: Thorough knowledge of normal neural foundations for cognitive behavioral development is fundamental to understand the mechanisms of both neurodevelopmental disorders and normal adaptation. This review aims at identifying the trends in MRI studies published within the last 18 months illuminating maturational structural brain foundations for normal cognitive behavioral development. Recent findings: Development is coordinated within neurocognitive systems, with predictable functional correlates. There is great individual variability within the normal range. Relationships between brain and cognitive variance at any given age are moderate, and appear to be of a complex and dynamic nature. Importantly, current studies point to a dimensional component to cognitive and behavioral psychopathology in which differences among healthy and clinical developmental groups exist along a continuum. Finally, factors influencing and detectable in early development are likely to have lifespan consequences. Summary: Brain development is highly coordinated, but the normal individual variation at any given age is substantial. Relationships between brain and cognitive measures are typically moderate and may fluctuate with age. A dimensional component to neural foundations for multiple developmental disorders makes the study of normal individual brain differences in development even more important to understand both normal and clinical cognitive behavioral outcomes throughout life.


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.


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.


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.


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.


Pedersen T.R.,University of Oslo
Circulation Research | Year: 2016

We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 The Authors.


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.


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.


With the occurrence of global change, research aimed at estimating the performance of marine ectotherms in a warmer and acidified future has intensified. The concept of oxygen- and capacity-limited thermal tolerance, which is inspired by the Fry paradigm of a bell-shaped increase-optimum-decrease-type response of aerobic scope to increasing temperature, but also includes proposed negative and synergistic effects of elevated CO2 levels, has been suggested as a unifying framework. The objectives of this meta-analysis were to assess the following: (i) the generality of a bell-shaped relationship between absolute aerobic scope (AAS) and temperature; (ii) to what extent elevated CO2 affects resting oxygen uptake MO2rest and AAS; and (iii) whether there is an interaction between elevated temperature and CO2. The behavioural effects of CO2 are also briefly discussed. In 31 out of 73 data sets (both acutely exposed and acclimated), AAS increased and remained above 90% of the maximum, whereas a clear thermal optimum was observed in the remaining 42 data sets. Carbon dioxide caused a significant rise in MO2rest in only 18 out of 125 data sets, and a decrease in 25, whereas it caused a decrease in AAS in four out of 18 data sets and an increase in two. The analysis did not reveal clear evidence for an overall correlation with temperature, CO2 regime or duration of CO2 treatment. When CO2 had an effect, additive rather than synergistic interactions with temperature were most common and, interestingly, they even interacted antagonistically on MO2rest and AAS. The behavioural effects of CO2 could complicate experimental determination of respiratory performance. Overall, this meta-analysis reveals heterogeneity in the responses to elevated temperature and CO2 that is not in accordance with the idea of a single unifying principle and which cannot be ignored in attempts to model and predict the impacts of global warming and ocean acidification on marine ectotherms. © The Author 2016.


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.


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.


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.


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).


Mills I.G.,University of Oslo | Mills I.G.,University of Cambridge
Nature Reviews Cancer | Year: 2014

Prostate cancer treatment is dominated by strategies to control androgen receptor (AR) activity. AR has an impact on prostate cancer development through the regulation of not only transcription networks but also genomic stability and DNA repair, as manifest in the emergence of gene fusions. Whole-genome maps of AR binding sites and transcript profiling have shown changes in the recruitment and regulatory effect of AR on transcription as prostate cancer progresses. Defining other factors that are involved in this reprogramming of AR function gives various opportunities for cancer detection and therapeutic intervention. © 2014 Macmillan Publishers Limited.


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.


Stene L.C.,Norwegian Institute of Public Health | Stene L.C.,University of Oslo | Gale E.A.M.,Southmead Hospital
Diabetologia | Year: 2013

There is ample evidence that environmental factors are involved in the aetiology of type 1 diabetes, but the nature and timing of the interactions are poorly understood. The intrauterine environment is known to play a role in the later development of type 2 diabetes, and this review considers a possible role in type 1 diabetes. Autoimmune type 1 diabetes is rare in those diagnosed before 6 months of age, but endogenous autoantibodies predictive of future type 1 diabetes may be detectable by 6-12 months of age, suggesting that environmental factors may operate before this age in some cases. Indirect evidence of a protective effect for the intrauterine environment comes from the observation that mothers with type 1 diabetes are less likely than affected fathers to transmit diabetes to their offspring, although the precise role (if any) is unclear. The risk of childhood-onset type 1 diabetes increases with maternal age at delivery, and with high birthweight, but these associations are weak and heterogeneous, and these factors are unlikely to be directly causally related to type 1 diabetes. No firm conclusion can be drawn from studies of maternal enteroviral infection or from various nutritional exposures. The birth process itself may play a role, as suggested by the slightly increased risk in children born by Caesarean section; lack of contact with maternal bacteria is one suggested mechanism. In sum, there is circumstantial evidence, but no proof of principle, that maternal or intrauterine conditions may modulate genetic risk of type 1 diabetes. The disease process culminating in type 1 diabetes typically begins in early life, but it is not clear whether the trail begins before or after birth. © 2013 Springer-Verlag Berlin Heidelberg.


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.


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.


Gredeback G.,University of Oslo | Melinder A.,University of Oslo
Cognition | Year: 2010

Six- and 12-month-old infant's eye movements were recorded as they observed feeding actions being performed in a rational or non-rational manner. Twelve-month-olds fixated the goal of these actions before the food arrived (anticipation); the latency of these gaze shifts being dependent (r = .69) on infants life experience being feed. In addition, 6- and 12-month-olds dilated their pupil during observation of non-rational feeding actions. This effect could not be attributed to light differences or differences in familiarity, but was interpreted to reflect sympathetic-like activity and arousal caused by a violation of infant's expectations about rationality. We argue that evaluation of rationality requires less experience than anticipations of action goals, suggesting a dual process account of preverbal infants' everyday action understanding. © 2009 Elsevier B.V. All rights reserved.


Oksvold M.P.,University of Oslo
Science and Engineering Ethics | Year: 2016

Since the solution to many public health problems depends on research, it is critical for the progress and well-being for the patients that we can trust the scientific literature. Misconduct and poor laboratory practice in science threatens the scientific progress, leads to loss of productivity and increased healthcare costs, and endangers lives of patients. Data duplication may represent one of challenges related to these problems. In order to estimate the frequency of data duplication in life science literature, a systematic screen through 120 original scientific articles published in three different cancer related journals [journal impact factor (IF) <5, 5–10 and >20] was completed. The study revealed a surprisingly high proportion of articles containing data duplication. For the IF < 5 and IF > 20 journals, 25 % of the articles were found to contain data duplications. The IF 5–10 journal showed a comparable proportion (22.5 %). The proportion of articles containing duplicated data was comparable between the three journals and no significant correlation to journal IF was found. The editorial offices representing the journals included in this study and the individual authors of the detected articles were contacted to clarify the individual cases. The editorial offices did not reply and only 1 out of 29 cases were apparently clarified by the authors, although no supporting data was supplied. This study questions the reliability of life science literature, it illustrates that data duplications are widespread and independent of journal impact factor and call for a reform of the current peer review and retraction process of scientific publishing. © 2015, Springer Science+Business Media Dordrecht.


Smalo H.S.,University of Oslo | Uggerud E.,University of Oslo
Chemical Communications | Year: 2012

Density functional theory calculations show that both ring opening and chain dissociation of polymeric triazoles are facilitated by mechanical stretching of the molecules - the latter more than the former. Experimentally observed ring opening upon sonication can therefore not be explained by a mechanical stretching mechanism alone. © 2012 The Royal Society of Chemistry.


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.


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.


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.


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.


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.


Gronke M.,University of Oslo | Dijkstra M.,University of Oslo
Monthly Notices of the Royal Astronomical Society | Year: 2014

We quantify the directional dependence of the escape fraction of Lyman α (Lyα) and nonionizing UV-continuum photons from a multiphase medium, and investigate whether there exist directional enhancements in the Lyα equivalent width (EW). Our multiphase medium consists of spherically symmetric distributions of cold, dusty clumps embedded within a hot dust-free medium. We focus on three models from the analysis presented by Laursen et al. We find that for a Lyα and UV-continuum point source, it is possible to find an EW boost b(θ,ϕ) > 5b¯ in a few per cent of sight lines, where b¯ denotes the boost averaged over all photons. For spatially extended sources this directional dependence vanishes quickly when the size of the UV emitting region exceeds the mean distance between cold dusty clumps. Our analysis suggests that directional EW boosting can occur, and that this is mostly driven by reduced escape fractions of UV photons (which gives rise to UV-continuum 'shadows'), and less due to an enhanced Lyα escape fraction (or beaming), in certain directions. © 2014 The Authors.


Duggal S.,University of Oslo | Brinchmann J.E.,University of Oslo
Journal of Cellular Physiology | Year: 2011

Human mesenchymal stem cells (hMSCs) may be used for therapeutic applications. Culture conditions such as the serum source may impact on cell quality and the onset of replicative senescence. We have examined the effect of culturing hMSCs in autologous serum (AS) versus fetal bovine serum (FBS) on factors involved in in vitro replicative senescence. hMSCs from four donors were cultured in 10% FBS or 10% AS until they reached senescence. Cells were harvested at early passage and near senescence to study factors known to be involved in cellular senescence. The number of population doublings till senescence was similar for cells cultured in FBS, but varied greatly for hMSCs cultured in AS. FBS cells accumulated in S phase of cell cycle. This could not be explained by increased expression of cell cycle inhibitor proteins. Heat shock proteins were upregulated in AS compared to FBS cells. Reactive oxygen species and nitric oxide were upregulated in senescent FBS cells. Telomeres were shorter in senescent cells, more significantly in FBS cells. The source of serum was a determinant for the time till senescence in cultured hMSC. Serum source affected aspects of cell cycle regulation and the levels of heat shock proteins. Several mechanisms are likely to be responsible for replicative senescence in hMSC. Insight into the molecular details of how serum factors impacts on these mechanisms is important for the safe use of hMSCs in clinical applications. © 2011 Wiley-Liss, Inc.


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.


Jorde P.E.,University of Oslo | Jorde P.E.,Norwegian Institute of Marine Research
Molecular Ecology Resources | Year: 2012

A general expression for the covariance of allele frequencies among cohorts in age-structured populations is derived. The expression is used to extend the so-called temporal method for estimating effective population size from allele frequency shifts among samples from cohorts born any number of years apart. Computer simulations are used to check on the accuracy and precision of the method, and an application to coastal Atlantic cod is presented. © 2012 Blackwell Publishing Ltd.


Antolin P.,University of Oslo | Verwichte E.,University of Warwick
Astrophysical Journal | Year: 2011

The condensations composing coronal rain, falling down along loop-like structures observed in cool chromospheric lines such as Hα and Ca II H, have long been a spectacular phenomenon of the solar corona. However, considered a peculiar sporadic phenomenon, it has not received much attention. This picture is rapidly changing due to recent high-resolution observations with instruments such as the Hinode/Solar Optical Telescope (SOT), CRISP of the Swedish 1-m Solar Telescope, and the Solar Dynamics Observatory. Furthermore, numerical simulations have shown that coronal rain is the loss of thermal equilibrium of loops linked to footpoint heating. This result has highlighted the importance that coronal rain can play in the field of coronal heating. In this work, we further stress the importance of coronal rain by showing the role it can play in the understanding of the coronal magnetic field topology. We analyze Hinode/SOT observations in the Ca II H line of a loop in which coronal rain puts in evidence in-phase transverse oscillations of multiple strand-like structures. The periods, amplitudes, transverse velocities, and phase velocities are calculated, allowing an estimation of the energy flux of the wave and the coronal magnetic field inside the loop through means of coronal seismology. We discuss the possible interpretations of the wave as either standing or propagating torsional Alfvén or fast kink waves. An estimate of the plasma beta parameter of the condensations indicates a condition that may allow the often observed separation and elongation processes of the condensations. We also show that the wave pressure from the transverse wave can be responsible for the observed low downward acceleration of coronal rain. © 2011. The American Astronomical Society. All rights reserved.


When PET image volumes are reconstructed with ordered subset expectation-maximization (OSEM) and subjected to filtration with a 3D Gaussian filter the effective spatial resolution is a function of both the intrinsic scanner resolution and the user-selectable spatial width of the filter. A method was developed to derive the effective spatial resolution from such volumes obtained after acquisitions with a line source on a Siemens Biograph 64 PET/CT scanner. Assuming Gaussian distributions, the full widths at half maximum (FWHM) were derived from probit plots of cumulative spatial distributions across the line source. The effective FWHM values were also used to estimate the FWHM of the intrinsic resolution by extrapolation to a zero filter width. © The Author 2010. Published by Oxford University Press.


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.


Mota D.F.,University of Oslo | Winther H.A.,University of Oslo
Astrophysical Journal | Year: 2011

In chameleon field theories, a scalar field can couple to matter with gravitational strength and still evade local gravity constraints due to a combination of self-interactions and the couplings to matter. Originally, these theories were proposed with a constant coupling to matter; however, the chameleon mechanism also extends to the case where the coupling becomes field dependent. We study the cosmology of chameleon models with power-law couplings and power-law potentials. It is found that these generalized chameleons, when viable, have a background expansion very close to ΛCDM, but can in some special cases enhance the growth of the linear perturbations at low redshifts. For the models we consider, it is found that this region of the parameter space is ruled out by local gravity constraints. Imposing a coupling to dark matter only, the local constraints are avoided, and it is possible to have observable signatures on the linear matter perturbations. © 2011. The American Astronomical Society. All rights reserved..


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.


Miloch W.J.,University of Oslo
Procedia Computer Science | Year: 2015

Interaction of plasma with finite-sized objects is one of central problems in the physics of plasmas. Since object charging is often nonlinear and involved, it is advisable to address this problem with numerical simulations. First-principle simulations allow studying trajectories of charged plasma particles in self-consistent force fields. One of such approaches is the particlein-cell (PIC) method, where the use of spatial grid for the force calculation significantly reduces the computational complexity. Implementing finite-sized objects in PIC simulations is often a challenging task. In this work we present simulation results and discuss the numerical representation of objects in the DiP3D code, which enables studies of several independent objects in various plasma environments. © The Authors. Published by Elsevier B.V.


van der Velden M.,University of Oslo | El Emam K.,Ottawa Hospital Research Institute | El Emam K.,University of Ottawa
Journal of the American Medical Informatics Association | Year: 2013

Background: The literature describes teenagers as active users of social media, who seem to care about privacy, but who also reveal a considerable amount of personal information. There have been no studies of how they manage personal health information on social media. Objective: To understand how chronically ill teenage patients manage their privacy on social media sites. Design: A qualitative study based on a content analysis of semistructured interviews with 20 hospital patients (12e18 years). Results: Most teenage patients do not disclose their personal health information on social media, even though the study found a pervasive use of Facebook. Facebook is a place to be a "regular", rather than a sick teenager. It is a place where teenage patients stay up-to-date about their social lifedit is not seen as a place to discuss their diagnosis and treatment. The majority of teenage patients don't use social media to come into contact with others with similar conditions and they don't use the internet to find health information about their diagnosis. Conclusions: Social media play an important role in the social life of teenage patients. They enable young patients to be "regular" teenagers. Teenage patients' online privacy behavior is an expression of their need for self-definition and self-protection.


Koivisto T.S.,University of Oslo | Mota D.F.,University of Oslo | Zumalacarregui M.,University of Oslo | Zumalacarregui M.,University of Barcelona
Physical Review Letters | Year: 2012

It is shown that extensions to general relativity, which introduce a strongly coupled scalar field, can be viable if the interaction has a nonconformal form. Such disformal coupling depends upon the gradients of the scalar field. Thus, if the field is locally static and smooth, the coupling becomes invisible in the Solar System: this is the disformal screening mechanism. A cosmological model is considered where the disformal coupling triggers the onset of accelerated expansion after a scaling matter era, giving a good fit to a wide range of background observational data. Moreover, the interaction leaves signatures in the formation of large-scale structure that can be used to probe such couplings. © 2012 American Physical Society.


Rohr A.K.,University of Oslo | Hersleth H.-P.,University of Oslo | Kristoffer Andersson K.,University of Oslo
Angewandte Chemie - International Edition | Year: 2010

Damaged goods? Detailed knowledge of the cofactor conformation is essential for the functional analysis of flavoenzyme crystal structures. However, photoelectrons generated by X-rays during crystaldata collection can reduce the flavin cofactor and thus change its geometry (see picture). Monitoring of the flavin vibrational modes by Raman spectroscopy during X-ray crystal-data collection provided important information on the actual flavin state. (Figure Presented) © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


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.


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).


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.


How to differentiate between scale-free space use like Lévy walk and a two-level scale-specific process like composite random walk (mixture of intra- and inter-patch habitat movement) is surrounded by controversy. Composite random walk may under some parameter conditions appear Lévy walk-like from the perspective of the path's distribution of step lengths due to superabundance of very long steps relative to the expectation from a classic (single-level) random walk. However, a more explicit focus on the qualitative differences between studying movement at a high resolution mechanistic (behavioral) level and the more coarse-grained statistical mechanical level may contribute to resolving both this and other issues related to scaling complexity. Specifically, a re-sampling of a composite random walk at larger time lags than the micro-level unit time step for the simulation makes a Lévy-look-alike step length distribution re-shaping towards a Brownian motion-like pattern. Conversely, a true Levy walk maintains its scaling characteristics upon re-sampling. This result illustrates how a confusing pattern at the mechanistic level may be resolved by changing observational scale from the micro level to the coarser statistical mechanical meso- or macro-scale. The instability of the composite random walk pattern under rescaling is a consequence of influence of the central limit theorem. I propose that a coarse-graining test - studying simulated animal paths at a coarsened temporal scale by re-sampling a series - should be routinely performed prior to comparing theoretical results with those patterns generated from GPS data describing animal movement paths. Fixes from terrestrial mammals are often collected at hourly intervals or larger, and such a priori coarse-grained series may thus comply better with the statistical mechanical meso- or macro-level of analysis than the behavioral mechanics observed at finer resolutions typically in the range of seconds and minutes. If fixes of real animals are collected at this high frequency, coarse graining both the simulated and real series is advised in order to bring the analysis into a temporal scale domain where analytical methods from statistical mechanics can be applied. © 2012 The Authors. Oikos © 2012 Nordic Society Oikos.


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.


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).


Brustugun O.T.,University of Oslo | Moller B.,Institute of Population Based Cancer Research | Helland A.,University of Oslo
British Journal of Cancer | Year: 2014

Background: The severity of cancers is often measured in number of deaths. However, number of years of life lost (YLL) may be a more appropriate indicator of impact on society. Here we have calculated the YLL of adult cancers in Norway for the year 2012, as well as for the previous 15-year period. Methods: Data on age composition, expected remaining years of life, total numbers of deaths and deaths due to cancer were retrieved from the National Census Agency Statistics Norway. YLL were calculated for both sexes aged 25-99 years based on each individual's age at death, and the expected remaining years of life at that age. Results: Cancer deaths represented 25.8% of all adult deaths in 2012, with a lower fraction of females (28.7% in men and 23.1% in women), whereas cancer represented 35.2% of all YLL, with a higher fraction of females (32.8% in men and 37.8% in women). Females loose on average more life years to cancer than men (14.9 vs 12.7 years). Average YLL varied from 23.7 (cervical cancer) to 7.9 (prostate cancer). Lung cancer caused almost as many YLL alone (22.1% of cancer-caused YLL) as colon, prostate and breast cancer combined (23.1%). From 1997 to 2012, cancer-caused YLL as a fraction of all YLL increased from 32.5% to 35.2%, but with major differences among diagnoses. Conclusions: Cancer is a major and increasing cause of premature deaths, and YLL may be a more accurate measure than number of deaths. Public health efforts and research funding should be explicitly directed at preventing premature deaths. © 2014 Cancer Research UK.


Gradmann C.,University of Oslo
Social History of Medicine | Year: 2013

The paper assesses the development of antibiotic resistance diagnostics after 1945. In the 1950s, demand for such testing led to the adaptation of procedures from experimental pharmacology and bacterial genetics to the needs of clinical microbiology. Further developments were influenced by stakeholders in clinical medicine, public health and industry. These changes are viewed through the lens of a 1960s World Health Organisation (WHO)-initiated research project, and the ways in which it developed over time. Driven forward by the Swedish medical microbiologist Hans Ericsson, this project attempted to frame resistance diagnostics in relation to the needs of public health, a standardisation of diagnostic tools and with regard to therapeutic rationalism. These objectives were swiftly combined with that of raising the professional status of clinical microbiology. Such aspirations, however, ran counter to industrial interest. Early in the 1970s standardisation instead remained confined to a single element in the diagnostic process: a small paper disc containing antibiotics. Ironically, Ericsson, who had pushed for a broader standardisation of diagnostic processes, ultimately found himself embarking on a career as a commercial producer of those discs. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for the Social History of Medicine. All rights reserved.


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.


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.


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.


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.


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.


Waldminghaus T.,University of Oslo | Waldminghaus T.,University of Marburg | Weigel C.,HTW Berlin University of Applied Sciences | Skarstad K.,University of Oslo
Nucleic Acids Research | Year: 2012

In Escherichia coli, the SeqA protein binds specifically to GATC sequences which are methylated on the A of the old strand but not on the new strand. Such hemimethylated DNA is produced by progression of the replication forks and lasts until Dam methyltransferase methylates the new strand. It is therefore believed that a region of hemimethylated DNA covered by SeqA follows the replication fork. We show that this is, indeed, the case by using global ChIP on Chip analysis of SeqA in cells synchronized regarding DNA replication. To assess hemimethylation, we developed the first genome-wide method for methylation analysis in bacteria. Since loss of the SeqA protein affects growth rate only during rapid growth when cells contain multiple replication forks, a comparison of rapid and slow growth was performed. In cells with six replication forks per chromosome, the two old forks were found to bind surprisingly little SeqA protein. Cell cycle analysis showed that loss of SeqA from the old forks did not occur at initiation of the new forks, but instead occurs at a time point coinciding with the end of SeqA-dependent origin sequestration. The finding suggests simultaneous origin de-sequestration and loss of SeqA from old replication forks. © The Author(s) 2012. Published by Oxford University Press.


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.


Karlsen T.A.,University of Oslo | Brinchmann J.E.,University of Oslo
Molecular Therapy | Year: 2013

Synthetic microRNAs regulate gene expression when transfected into cells, and may be used in strategies for molecular therapy both in vitro and in vivo. Liposomal transfection reagents are frequently used as delivery vehicles in both settings. Here, we report on the immunological off-target effects observed following liposome transfection of synthetic microRNA-145 into human mesenchymal stem cells and human articular chondrocytes (hAC). The immune response was independent on endosome delivery and toll-like receptors (TLRs) but was mediated by retinoic acid inducible-gene 1 (RIG-I). Upregulation of immune genes required liposomal delivery, as no immune response was observed after electroporation of smiR-145 directly in to the cytosol, suggesting a new role of RIG-I. Immune response was seen both with blunt ended and 2-nucleotide 3′ overhang versions of synthetic miR-145, and occurred in the absence of a 5′ppp cap. Mutations in a centrally placed poly (UUUU) sequence reduced, but did not abolish the immune response. Interestingly, exposure to liposomes alone led to upregulation of several immune genes, including RIG-I mRNA. However, this process was not mediated by RIG-I. This insight is important for researchers to avoid unexpected results from gene transfer experiments in vitro and unwanted immune responses following the use of lipid-based transfection reagents in vivo. © The American Society of Gene & Cell Therapy.


Arcuri A.,Simula Research Laboratory | Briand L.,University of Oslo
Proceedings - International Conference on Software Engineering | Year: 2011

Randomized algorithms have been used to successfully address many different types of software engineering problems. This type of algorithms employ a degree of randomness as part of their logic. Randomized algorithms are useful for difficult problems where a precise solution cannot be derived in a deterministic way within reasonable time. However, randomized algorithms produce different results on every run when applied to the same problem instance. It is hence important to assess the effectiveness of randomized algorithms by collecting data from a large enough number of runs. The use of rigorous statistical tests is then essential to provide support to the conclusions derived by analyzing such data. In this paper, we provide a systematic review of the use of randomized algorithms in selected software engineering venues in 2009. Its goal is not to perform a complete survey but to get a representative snapshot of current practice in software engineering research. We show that randomized algorithms are used in a significant percentage of papers but that, in most cases, randomness is not properly accounted for. This casts doubts on the validity of most empirical results assessing randomized algorithms. There are numerous statistical tests, based on different assumptions, and it is not always clear when and how to use these tests. We hence provide practical guidelines to support empirical research on randomized algorithms in software engineering © 2011 ACM.


Norum J.H.,University of Oslo | Andersen K.,Institute of Cancer Research | Sorlie T.,University of Oslo
British Journal of Surgery | Year: 2014

Background Wide variability in breast cancer, between patients and within each individual neoplasm, adds confounding complexity to the treatment of the disease. In clinical practice, hormone receptor status has been used to classify breast tumours and to guide treatment. Modern classification systems should take the wide tumour heterogeneity into account to improve patient outcome. Methods This article reviews the identification of the intrinsic molecular subtypes of breast cancer, their prognostic and therapeutic implications, and the impact of tumour heterogeneity on cancer progression and treatment. The possibility of functionally addressing tumour-specific characteristics in in vivo models to inform decisions for precision therapies is also discussed. Results Despite the robust breast tumour classification system provided by gene expression profiling, heterogeneity is also evident within these molecular portraits. A complicating factor in breast cancer classification is the process of selective clonality within developing neoplasms. Phenotypically and functionally distinct clones representing the intratumour heterogeneity might confuse molecular classification. Molecular portraits of the heterogeneous primary tumour might not necessarily reflect the subclone of cancer cells that causes the disease to relapse. Studies of reciprocal relationships between cancer cell subpopulations within developing tumours are therefore needed, and are possible only in genetically engineered mouse models or patient-derived xenograft models, in which the treatment-induced selection pressure on individual cell clones can be mimicked. Conclusion In the future, more refined classifications, based on integration of information at several molecular levels, are required to improve treatment guidelines. Large-scale translational research efforts paved the way for identification of the intrinsic subtypes, and are still fundamental for ensuring future progress in cancer care. Molecular subtypes aid in decision making © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.


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.


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.


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.


Andersen T.,University of Oslo
Precambrian Research | Year: 2014

The interpretation of detrital zircon data is facing some important and potentially damaging inconsistencies that are commonly overlooked: combined U-Pb and Lu-Hf data from detrital zircon in sedimentary rocks have been used successfully to study global processes such as the extraction, growth and preservation of continental crust, suggesting generally similar patterns of evolution in different continents. Yet at the same time, such data are increasingly used to identify the source-rocks of individual clastic deposits, based on the implicit assumption that material from different source terranes carry distinct provenance signatures.For example, Precambrian detrital zircon age-fractions from late Mesoproterozoic to Recent sediments in Laurentia show patterns of U-Pb ages and initial Hf isotope composition indistinguishable from that of zircon from granitoids in Fennoscandia. This is perhaps not too surprising, as Fennoscandia and Laurentia have been near neighbours in three supercontinents (Nuna, Rodinia, Pangea). Transport and homogenization of clastic material in intracontinental basins and along a common continental margin would smooth out differences, and the two neighbouring continents may have closely parallel histories of internal growth.A stronger reason for concern is that Precambrian age fractions in detrital zircon suites from areas as distant as Australia and South Africa also show distribution patterns that cannot be distinguished with confidence from sources in Fennoscandia. These continents have not been near neighbours in post-Archaean supercontinents. Since exchange of detritus between such distant blocks is improbable, one is left with the alternative explanations of pronounced parallel evolution (perhaps related to the assembly of supercontinents in the geological past), or pure coincidence.Whatever the explanation: exchange, parallelism or coincidence, observations such as these challenge the main assumptions underlying the use of zircon as an indicator of sedimentary provenance: That a given age and initial Hf isotopic pattern of a population of detrital zircons can be unequivocally related to a specific first-generation source. © 2013 Elsevier B.V.


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.


Rofstad E.K.,University of Oslo | Mathiesen B.,University of Oslo
Neoplasia | Year: 2010

The development of metastases has been shown to be associated with the microvascular density of the primary tumor in some clinical studies and with the extent of hypoxia in others. The aim of this study was to investigate the validity of these apparently inconsistent observations and to reveal possible links between them. Xenografted tumors of nine melanoma cell lines established from patients with diseases differing in aggressiveness were studied. The aggressiveness of the cell lines was assessed by measuring their lung colonization potential, invasiveness, angiogenic potential, and tumorigenicity. Spontaneous metastasis was assessed in untreated mice and mice treated with neutralizing antibody against vascular endothelial growth factor A (VEGF-A) or interleukin 8 (IL-8). Microvascular density was scored in histologic preparations. Hypoxic fractions were measured by using a radiobiologic assay and a pimonidazole-based immunohistochemical assay. The aggressiveness of the melanoma lines reflected the aggressiveness of the donor patients' tumors. The metastatic propensity was associated with the microvascular density but not with the hypoxic fraction. Anti-VEGF-A and anti-IL-8 treatments resulted in decreased microvascular density and reduced incidence of metastases in all lines. Large hypoxic fractions were not a secondary effect of high cellular aggressiveness, whereas the microvascular density was associated with the cellular aggressiveness. The metastatic propensity was governed by the angiogenic potential of the tumor cells. The differences in microvascular density among the lines were most likely a consequence of differences in the constitutive angiogenic potential rather than differences in hypoxia-induced angiogenesis. VEGF-A and IL-8 may be important therapeutic targets for melanoma. © 2010 Neoplasia Press, Inc. All rights reserved.


Werner S.C.,University of Oslo
Earth and Planetary Science Letters | Year: 2014

Basin formation ages for Moon, Mars and Mercury are determined by cratering statistics, compared and evaluated with respect to their maximum surface ages and available isotope ages, and two possible Solar System evolution models. Both Mars and Mercury appear to have undergone significant resurfacing, so that at least the first 200-400 million years are not recorded on their surfaces. Basin frequency and crater frequencies below 150 km indicate that the Moon has the oldest surface, Mercury has an intermediate age, and Mars has the youngest preserved terrain. An offset between the basin size-frequency distribution, the smaller crater size-frequency distribution and the main belt asteroid size-frequency distribution is observed in all three cases, suggesting an age difference of about 150 Ma between basin and smaller crater distribution-based ages. I interpreted this in terms of lack of understanding of the basin formation process, and suggest that one possible explanation for the apparently under-representative basin frequency could be a different (lower) average impact velocity compatible with the 'Nice' flux model. The basin formation pattern derived with the standard monotonically decaying or the sawtooth-like Nice-model flux does not reveal a coherent picture according to the late heavy bombardment idea. This is here attributed to an incomplete understanding of the cratering rate ratios between the planetary bodies considered here. Because of the Moon's unique formation history, I also suggest that it is questionable whether the Moon is a suitable analogue for the formation, evolution and cratering record of the other terrestrial bodies. © 2014 Elsevier B.V.


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.


Have changes in culture media used for IVF resulted in changes in offspring birthweight or placental weight that differed from the trends in offspring from spontaneous conceptions during the corresponding time periods? Changes in culture media used for IVF were associated with significant differences in offspring birthweight and in placental weight to birthweight ratio when compared with the trend in offspring from spontaneous conceptions during the time periods. The effect of culture media used for IVF on offspring birthweight has varied between studies. There is a large variation in birthweight between newborns, and birthweight may vary across populations and over time. Such variations may therefore have influenced previous results. We included all singleton births from IVF at one treatment center in Norway during the years 1999-2011(n = 2435) and all singleton births from spontaneous conceptions in Norway during the same years (n = 698 359). Three different media were used for embryo culture; Medicult Universal IVF (1999 through 2007, n = 1584), Medicult ISM1 (2008 until 20 September 2009, n = 402) and Vitrolife G-1 PLUS (21 September 2009 through 2011, n = 449). We estimated mean birthweight and placental weight in IVF pregnancies by culture media. We also estimated mean weights in IVF and in spontaneous pregnancies by year of birth. Thereafter, we studied whether the changes in mean weights in IVF pregnancies differed from the changes in weight in spontaneous pregnancies in the periods corresponding to culture media changes by applying a grouped difference-in-difference analysis. Adjustments were made for parity, maternal age and gestational age at birth. In singleton offspring from IVF the mean birthweight was 3447.6 g with Medicult Universal, 3351.7 g with Medicult ISM1 and 3441.4 g with Vitrolife G-1 PLUS (P < 0.05). The corresponding mean placental weights were 684.1, 693.4 and 704.3 g (P < 0.05). In offspring from spontaneous conceptions the mean birthweight decreased (56.9 g) and the placental weight increased (9.3 g) during the study period. The adjusted difference in birthweight in offspring from IVF decreased with 35.0 g by the change from Medicult Universal to Medicult ISM1 (P = 0.16) and increased with 79.9 g by the change from Medicult ISM1 to Vitrolife G-1 PLUS (P = 0.01) when compared with changes in offspring after spontaneous conceptions, We also found a significant increase in placental weight in relation to birthweight by the change from Medicult ISM1 to Vitrolife G-1 PLUS (P = 0.02). There may be underlying factors that have influenced both birthweight and the use of culture media in IVF pregnancies. Lack of adjustment for such possible factors may have biased our results. We found a significant effect of culture media used for IVF on birthweight and on placental weight in relation to birthweight. Also the population changes over time should encourage identification of factors in very early embryonic life that may influence birthweight and placental weight. We received funding from the South-Eastern Regional Health Authority in Norway for this study (2011136-2012). None of the authors has any conflicts of interest to declare.


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.


Lone A.M.,University of Oslo | Tasken K.,University of Oslo
Frontiers in Immunology | Year: 2013

Eicosanoids are inflammatory mediators primarily generated by hydrolysis of membrane phospholipids by phospholipase A2 to ω-3 and ω-6 C20 fatty acids that next are converted to leukotrienes (LTs), prostaglandins (PGs), prostacyclins (PCs), and thromboxanes (TXAs). The rate-limiting and tightly regulated lipoxygenases control synthesis of LTs while the equally well-controlled cyclooxygenases 1 and 2 generate prostanoids, including PGs, PCs, and TXAs. While many of the classical signs of inflammation such as redness, swelling, pain, and heat are caused by eicosanoid species with vasoactive, pyretic, and pain-inducing effects locally, some eicosanoids also regulate T cell functions. Here, we will review eicosanoid production in T cell subsets and the inflammatory and immunoregulatory functions of LTs, PGs, PCs, and TXAs in T cells. © 2013 Lone and Taskén.


Stuken A.,University of Oslo | Jakobsen K.S.,University of Oslo
Microbiology | Year: 2010

Cylindrospermopsin (CYN), a potent hepatoxin, occurs in freshwaters worldwide. Several cyanobacterial species produce the toxin, but the producing species vary between geographical regions. Aphanizomenon flos-aquae, a common algae species in temperate fresh and brackish waters, is one of the three well-documented CYN producers in European waters. So far, no genetic information on the CYN genes of this species has been available. Here, we describe the complete CYN gene cluster, including flanking regions from the German Aphanizomenon sp. strain 10E6 using a full genome sequencing approach by 454 pyrosequencing and bioinformatic identification of the gene cluster. In addition, we have sequenced a ∼7 kb fragment covering the genes cyrC (partially), cyrA and cyrB (partially) of the same gene cluster in the CYN-producing Aphanizomenon sp. strains 10E9 and 22D11. Comparisons with the orthologous gene clusters of the Australian Cylindrospermopsis raciborskii strains AWT205 and CS505 and the partial gene cluster of the Israeli Aphanizomenon ovalisporum strain ILC-146 revealed a high gene sequence similarity, but also extensive rearrangements of gene order. The high sequence similarity (generally higher than that of 16S rRNA gene fragments from the same strains), atypical GC-content and signs of transposase activities support the suggestion that the CYN genes have been horizontally transferred. © 2010 SGM.


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.


Ose L.,University of Oslo
Clinical Lipidology | Year: 2010

Addressing dyslipidemia is crucial to reducing the burden imposed by cardiovascular disease. However, many current statins have major limitations. Moreover, innovative treatments need to address non-LDL-C residual risk (which may be marked by high triglycerides, low HDL-C concentrations or raised ApoB:ApoA1 ratio) and increase the proportion of patients attaining treatment targets. Pitavastatin is a novel statin that induces plaque regression and is non-inferior to atorvastatin and, on some measures, superior to simvastatin and to pravastatin in the elderly. Pitavastatin addresses non-LDL-C risk factors, including producing reproducible and sustained increases in HDL-C levels. Both the pitavastatin molecule and the lactone metabolite undergo very little metabolism by CYP3A4 and, therefore, unlike some other statins, does not interact with CYP3A4 substrates. Pitavastatin is well tolerated. As such, pitavastatin shows distinctive pharmacokinetic and clinical profiles that should help a greater proportion of dyslipidemic patients attain their treatment goals. © 2010 Future Medicine Ltd.


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.


After the discovery of X-ray diffraction by crystals, amino acids were among the first organic compounds to have their solid-state structures investigated. The Cambridge Structural Database now contains more than 3500 entries for -amino acids alone. After a short introduction dealing with the early history of X-ray structure determination, this review provides a classification of amino acid structures, describes essential structural elements, especially hydrogen bonding preferences and coordination to metal ions, and considers recent investigations on phase transitions as the result of extreme temperatures or pressure. © 2015 Taylor & Francis.


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.


Seligmann H.,University of Oslo | Seligmann H.,Hebrew University of Jerusalem
Biology Direct | Year: 2010

Background: The hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Antisense tRNA expression is plausible because tRNA punctuation signals mt sense RNA maturation: both sense and antisense tRNAs form secondary structures potentially signalling processing. Sense RNA maturation processes by default 11 antisense tRNAs neighbouring sense genes. If antisense tRNAs are expressed, processed antisense tRNAs should have adapted more for translational activity than unprocessed ones. Four tRNA properties are examined: antisense tRNA 5' and 3' end processing by sense RNA maturation and its accuracy, cloverleaf stability and misacylation potential.Results: Processed antisense tRNAs align better with standard tRNA sequences with the same cognate than unprocessed antisense tRNAs, suggesting less misacylations. Misacylation increases with cloverleaf fragility and processing inaccuracy. Cloverleaf fragility, misacylation and processing accuracy of antisense tRNAs decrease with genome-wide usage of their predicted cognate amino acid.Conclusions: These properties correlate as if they adaptively coevolved for translational activity by some antisense tRNAs, and to avoid such activity by other antisense tRNAs. Analyses also suggest previously unsuspected particularities of aminoacylation specificity in mt tRNAs: combinations of competition between tRNAs on tRNA synthetases with competition between tRNA synthetases on tRNAs determine specificities of tRNA amino acylations. The latter analyses show that alignment methods used to detect tRNA cognates yield relatively robust results, even when they apparently fail to detect the tRNA's cognate amino acid and indicate high misacylation potential.Reviewers: This article was reviewed by Dr Juergen Brosius, Dr Anthony M Poole and Dr Andrei S Rodin (nominated by Dr Rob Knight). © 2010 Seligmann; licensee BioMed Central Ltd.


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.


Pedersen G.,University of Oslo | Karterud S.,University of Oslo
Comprehensive Psychiatry | Year: 2012

Objective: The objective was to investigate the validity and clinical impact of the symptom and function dimensions of the Global Assessment of Functioning (GAF) in the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fourth Edition. Is there any need for revision with respect to the DSM, Fifth Edition? Material: The sample comprised 2695 patients consecutively admitted to 14 different treatment units participating in the Norwegian Network of Personality-Focused Treatment Programs from 1998 to 2007. Methods: Convergent and discriminant validity of the symptom and function dimensions of GAF was analyzed by their associations with demographic variables, diagnostic status, and other self-reported variables assessing symptom distress, interpersonal problems, work and social impairment, and quality of life. Results: The validity of the separate GAF dimensions was confirmed by discriminant and concurrent associations to other relevant clinical measures. However, the traditional GAF measure based on the lower score of either symptom or function level was found to serve well as a global indicator of symptom distress and social dysfunction. A substantial difference between the symptom and function score of GAF was found in about 10% of the cases; and when differences were found, functional impairment was most often more severe. Conclusion: This study confirms the validity of the 2 GAF dimensions. However, substantial differences between these dimensions are rarely occurring. We therefore recommend that the GAF scale be prolonged in the DSM, Fifth Edition, roughly in the same shape as in the DSM, Fourth Edition. © 2012 Elsevier Inc. All rights reserved.


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.


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.


Espelund M.,Norwegian Defence Research Establishment | Klaveness D.,University of Oslo
Frontiers in Microbiology | Year: 2014

Clostridium botulinum comprises a diverse group of botulinum toxin-producing anaerobic rod-shaped spore-forming bacteria that are ubiquitously distributed in soils and aquatic sediments. Decomposition of plants, algae, and animals creates anaerobic environments that facilitate growth of C. botulinum, which may then enter into food webs leading to intoxication of animals. Via saprophytic utilization of nutrients, the bacteria rapidly sporulate, creating a reservoir of highly robust spores. In the present review, we focus on the occurrence of C. botulinum in non-clinical environments, and examine factors influencing growth and environmental factors associated with botulism outbreaks. We also outline cases involving specific environments and their biota. In wetlands, it has been found that some C. botulinum strains can associate with toxin-unaffected organisms-including algae, plants, and invertebrates-in which the bacteria appear to germinate and stay in the vegetative form for longer periods of time. We suggest the need for future investigations to resolve issues related to the environments in which C. botulinum spores may accumulate and germinate, and where the vegetative forms may multiply. © 2014 Espelund and Klaveness.


Holen O.H.,University of Oslo | Svennungsen T.O.,University of Oslo
American Naturalist | Year: 2012

Aposematic prey use conspicuous warning signals to advertise their defenses to predators. It has long been recognized that the efficiency of a warning signal may be reduced if poorly defended prey (automimics) are present in the population. The handicap principle suggests that the use of warning signals by poorly defended prey may be kept in check if signaling is costly. Three mechanisms that involve signal costs have been proposed to facilitate honest warning signals in prey: go-slow behavior in predators, resource allocation trade-offs, and costs of detection alone. We study all three in a unified game-theoretical framework. We find that the go-slow mechanism and the resource allocation mechanism can introduce differential benefits and differential costs of signaling, respectively, and can support honest signaling in accordance with the handicap principle. When honest signaling is maintained by the go slow mechanism, conspicuous prey will necessarily suffer more attacks on average than cryptic prey. In contrast, when honest signaling is maintained by the resource allocation mechanism, cryptic prey will suffer more attacks. The detection cost mechanism lacks differential costs and benefits, and its potential for maintaining honest signaling equilibria is limited. We relate our results to intra- and inter specific correlations between conspicuousness and defense. © 2012 by The University of Chicago.


To evaluate the impact of mass vaccination with adjuvanted vaccines (eventually 40% population coverage) and antivirals during the 2009 influenza pandemic in Norway, we fitted an age-structured SEIR model using data on vaccinations and sales of antivirals in 2009/10 in Norway to Norwegian ILI surveillance data from 5 October 2009 to 4 January 2010. We estimate a clinical attack rate of approximately 30% (28.7-29.8%), with highest disease rates among children 0-14 years (43-44%). Vaccination started in week 43 and came too late to have a strong influence on the pandemic in Norway. Our results indicate that the countermeasures prevented approximately 11-12% of potential cases relative to an unmitigated pandemic. Vaccination was found responsible for roughly 3 in 4 of the avoided infections. An estimated 50% reduction in the clinical attack rate would have resulted from vaccination alone, had the campaign started 6 weeks earlier. Had vaccination been prioritized for children first, the intervention should have commenced approximately 5 weeks earlier in order to achieve the same 50% reduction. In comparison, we estimate that a non-adjuvanted vaccination program should have started 8 weeks earlier to lower the clinical attack rate by 50%. In conclusion, vaccination timing was a critical factor in relation to the spread of the 2009 A(H1N1) influenza. Our results also corroborate the central role of children for the transmission of A(H1N1) pandemic influenza.


Berthling I.,Norwegian University of Science and Technology | Etzelmuller B.,University of Oslo
Quaternary Research | Year: 2011

Recent accounts suggest that periglacial processes are unimportant for large-scale landscape evolution and that true large-scale periglacial landscapes are rare or non-existent. The lack of a large-scale topographical fingerprint due to periglacial processes may be considered of little relevance, as linear process-landscape development relationships rarely can be substantiated. Instead, periglacial landscapes may be classified in terms of specific landform associations. We propose "cryo-conditioning", defined as the interaction of cryotic surface and subsurface thermal regimes and geomorphic processes, as an overarching concept linking landform and landscape evolution in cold regions. By focusing on the controls on processes, this concept circumvents scaling problems in interpreting long-term landscape evolution derived from short-term processes. It also contributes to an unambiguous conceptualization of periglacial geomorphology. We propose that the development of several key elements in the Norwegian geomorphic landscape can be explained in terms of cryo-conditioning. © 2010 University of Washington.


Nuth C.,University of Oslo | Kaab,University of Oslo
Cryosphere | Year: 2011

There are an increasing number of digital elevation models (DEMs) available worldwide for deriving elevation differences over time, including vertical changes on glaciers. Most of these DEMs are heavily post-processed or merged, so that physical error modelling becomes difficult and statistical error modelling is required instead. We propose a three-step methodological framework for assessing and correcting DEMs to quantify glacier elevation changes: (i) remove DEM shifts, (ii) check for elevation-dependent biases, and (iii) check for higher-order, sensor-specific biases. A simple, analytic and robust method to co-register elevation data is presented in regions where stable terrain is either plentiful (case study New Zealand) or limited (case study Svalbard). The method is demonstrated using the three global elevation data sets available to date, SRTM, ICESat and the ASTER GDEM, and with automatically generated DEMs from satellite stereo instruments of ASTER and SPOT5-HRS. After 3-D co-registration, significant biases related to elevation were found in some of the stereoscopic DEMs. Biases related to the satellite acquisition geometry (along/cross track) were detected at two frequencies in the automatically generated ASTER DEMs. The higher frequency bias seems to be related to satellite jitter, most apparent in the back-looking pass of the satellite. The origins of the more significant lower frequency bias is uncertain. ICESat-derived elevations are found to be the most consistent globally available elevation data set available so far. Before performing regional-scale glacier elevation change studies or mosaicking DEMs from multiple individual tiles (e.g. ASTER GDEM), we recommend to co-register all elevation data to ICESat as a global vertical reference system. © Author(s) 2011.


Kaab A.,University of Oslo | Prowse T.,University of Victoria
Geophysical Research Letters | Year: 2011

Knowledge of water-surface velocities in rivers is useful for understanding a wide range of lotic processes and systems, such as water and ice fluxes and forces, mixing, solute and sediment transport, bed and bank stability, aquatic and riparian ecology, and extreme hydrologic events. In cold regions, river-ice break up and the associated downstream transport of ice debris is often the most important hydrological event of the year, producing flood levels that commonly exceed those for the open-water period and dramatic consequences for river infrastructure and ecology. Quantification of river surface velocity and currents has relied mostly on very scarce in situ measurements or particle tracking in laboratory models, with few attempts to cover entire river reaches. Accurate and complete surface-velocity fields on rivers have rarely been produced. Here, we use river-ice debris as an index of surface water velocity, and track it over a time period of about one minute, which is the typical time lapse between the two or more images that form a stereo data set in spaceborne, alongtrack optical-stereo mapping. In this way, we measure and visualize for the first time, the almost complete surface velocity field of a river. Examples are used from approximately 80 km and 40 km long reaches of the St. Lawrence and Mackenzie rivers, respectively. The methodology and results will be valuable to a number of disciplines requiring detailed information about river flow, such as hydraulics, hydrology, river ecology and natural-hazard management. Copyright 2011 by the American Geophysical Union.


Stjern C.W.,University of Oslo
Atmospheric Chemistry and Physics | Year: 2011

Weekly cycles in aerosol concentration and corresponding cycles in precipitation have been reported over Europe, but results are conflicting. To obtain a large potential effect of aerosols on precipitation the focus will here be on a highly polluted region on the borders between Germany, Poland and the Czech Republic. Meteorological parameters from 30 surface stations in a mix of urban, rural and remote locations were analyzed for the time period 1983-2008, using three different tests: the Kruskal-Wallis test, a spectral analysis and a comparison of the regular 7-day week to constructed 6- and 8-day weeks. A clear and statistically significant weekly cycle will be expected to pass all three tests. Precipitation amount as well as meteorological variables associated with convective conditions, such as the frequency of heavy precipitation events and observations of rain showers, showed two-peak weekly cycles with maxima on Tuesdays and during weekends. The amplitudes of the weekly cycles were in many cases larger for the heavily polluted 1983-1987 period than for the cleaner 2004-2008 period, but were equally often largest in the cleaner period. Moreover, of all the variables, periods and seasons investigated, the weekly cycles were statistically significant only for summertime values of light precipitation frequency and cloud amount, and only by one of the three tests applied (the Kruskal-Wallis test). Conclusively, clear weekly cycles in meteorological variables were not found in this polluted region of Europe. © 2011 Author(s).


Maupin V.,University of Oslo
Geophysical Journal International | Year: 2011

A model for the upper mantle SV-wave velocity under southern Norway is obtained by depth inversion of the average phase velocity of the Rayleigh wave fundamental mode in the area. The average dispersion curve is obtained in the period range 22-200s by beamforming of 190 Rayleigh waves recorded by the MAGNUS network, a temporary regional network of 41 broad-band stations. Resolution of the beamforming procedure is increased by deconvolving the original beams from the array response function using the Lucy-Richardson algorithm. In addition to an average phase velocity, beamforming gives us some information concerning the nature of the incoming wavefield. We detect deviations of the wave propagation direction from the great-circle paths which commonly reach 10° at a period of 25 s for the teleseismic events. The amplitude of the deviations decreases with increasing period and with decreasing epicentral distance, as expected. The phase velocity measured by beamforming does not show any correlation with the deviation from great circle path, suggesting that deviation does not bias phase velocity measurements. We detect also significant multipathing with characteristics that vary rapidly with frequency. The obtained SV-wave velocity profile clearly shows that southern Norway is underlain by a low-velocity zone in the upper mantle and does not have shield-like characteristics, despite its location in the Baltic shield. These findings support the hypothesis that the high topography of southern Norway is sustained by anomalous upper-mantle material. © 2011 The Author Geophysical Journal International © 2011 RAS.


Schmalholz S.M.,University of Lausanne | Fletcher R.C.,University of Oslo
Geophysical Journal International | Year: 2011

The uniaxial exponential law, has been applied to experimental results for steady-state creep, including that of wet and dry olivine, pyroxenite and carbonates, at a deviatoric stress greater than ~100 MPa. Such stress levels likely occur in the upper-mantle lithosphere and middle crust. In a layered rock, in layer-parallel extension or shortening, high deviatoric stress can occur in the stiffest layers, for example, a dolomite layer in fine-grained marble. Under assumptions of isotropy and incompressibility, the uniaxial law yields where J2=sijsij/2 is an invariant of the deviatoric stress tensor, sij. Linearization about a homogeneous basic-state of flow yields equations identical in form to those obtained for the familiar power law. This establishes expressions for an effective viscosity, and stress exponent, where is an invariant of the basic-state deformation rate, These results allow application of existing analytical folding and necking solutions for a rock layer of power-law fluid to a rock layer with an exponential flow law. The effective stress exponent for the exponential flow law increases with decreasing temperature, through the dependence of C on the latter and, weakly, with increasing deformation rate. For dry olivine, effective stress exponents are between 10 and 30 for temperatures between 400 and 600°C with little dependence on deformation rate. Finite element simulations employing full non-linear forms of the flow laws show that large strain necking is nearly identical for power law and exponential flow laws. The results suggest that the instability in necking and folding in ductile rock layers can be considerably stronger than inferred from results based on flow laws representing diffusion and dislocation creep. The large values of the effective stress exponent, ne > ~15, that may be attained for exponential flow laws can account for observed outcrop-scale ductile necking. © 2010 The Authors Geophysical Journal International © 2010 RAS.


Debella-Gilo M.,University of Oslo | Kaab A.,University of Oslo
Remote Sensing of Environment | Year: 2011

This study evaluates the performance of two fundamentally different approaches to achieve sub-pixel precision of normalised cross-correlation when measuring surface displacements on mass movements from repeat optical images. In the first approach, image intensities are interpolated to a desired sub-pixel resolution using a bi-cubic interpolation scheme prior to the actual displacement matching. In the second approach, the image pairs are correlated at the original image resolution and the peaks of the correlation coefficient surface are then located at the desired sub-pixel resolution using three techniques, namely bi-cubic interpolation, parabola fitting and Gaussian fitting. Both principal approaches are applied to three typical mass movement types: rockglacier creep, glacier flow and land sliding. In addition, the influence of pixel resolution on the accuracies of displacement measurement using image matching is evaluated using repeat images resampled to different spatial resolutions. Our results show that bi-cubic interpolation of image intensity performs best followed by bi-cubic interpolation of the correlation surface. Both Gaussian and parabolic peak locating turn out less accurate. By increasing the spatial resolution (i.e. reducing the ground pixel size) of the matched images by 2 to 16 times using intensity interpolation, 40% to 80% reduction in mean error in reference to the same resolution original image could be achieved. The study also quantifies how the mean error, the random error, the proportion of mismatches and the proportion of undetected movements increase with increasing pixel size (i.e. decreasing spatial resolution) for all of the three mass movement examples investigated. © 2010 Elsevier Inc.


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.


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.


Linden A.,University of Oslo
Boreal Environment Research | Year: 2011

Understanding phenological responses to climate change requires explicit quantitative estimation of phenological distributions. First arrival dates (FAD) are frequently used, but biased, noisy and qualitative metrics of migration phenology. Despite critique against the use of FAD, better understanding of the risks and possible usefulness of this readily available data type is needed. I here present a stochastic model for the number of observed migrating birds during a given season. Firstly, I simulate data according to the model to quantify and describe how FAD are affected by population size, observation effort and observability, and provide some guidelines for interpreting earlier results and doing statistical correction. Secondly, I describe principles for how FAD and complementary daily migration data can be combined to fit phenological distribution functions, providing coherent quantitative measures of phenology. Using data on tree pipits (Anthus trivialis) I demonstrate how this can be done using generalized linear models. © 2011.


Henne W.M.,Cornell University | Stenmark H.,University of Oslo | Emr S.D.,Cornell University
Cold Spring Harbor Perspectives in Medicine | Year: 2013

The endosomal sorting complexes required for transport (ESCRT) drive multivesicular body (MVB) biogenesis and cytokinetic abscission. Originally identified through genetics and cell biology, more recent work has begun to elucidate the molecular mechanisms of ESCRT-mediated membrane remodeling, with special focus on the ESCRT-III complex. In particular, several light and electron microscopic studies provide high-resolution imaging of ESCRT-III rings and spirals that purportedly drive MVB morphogenesis and abscission. These studies highlight unifying principles to ESCRT-III function, in particular: (1) the ordered assembly of the ESCRT-III monomers into a heteropolymer, (2) ESCRT-III as a dynamic complex, and (3) the role of the AAA ATP asVps4 as a contributing factor in membrane scission. Mechanistic comparisons of ESCRT-III function in MVB morphogenesis and cytokinesis suggest common mechanisms in membrane remodeling. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.


Josang A.,University of Oslo
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Dangers exist on the Internet in the sense that there are attackers who try to break into our computers or who in other ways try to trick us when we engage in online activities. In order to steer away from such dangers people tend to look for signals of security and trustworthiness when navigating the Internet and accessing remote hosts. Seen from an online service provider's perspective it therefore is an essential marketing requirement to appear trustworthy, especially when providing sensitive or professional services. Said more directly, any perception of weak security or low trustworthiness could be disastrous for an otherwise secure and honest online service provider. In this context many security vendors offer solutions for strengthening security and trustworthiness. However there is also a risk that security vendors through their marketing strategy create an illusion that an online service provider which does not implement their solutions might therefore be insecure or untrustworthy. This would represent what we call trust extortion, because service providers are forced to implement specific security solutions to appear trustworthy although there might be alternative security solutions that provide equal or better security. We describe real examples where this seems to be the case. Trust extortion as a marketing strategy does not have to be explicit, but can be done very subtly e.g. through standardisation and industry fora, which then gives it a veil of legitimacy. © 2012 Springer-Verlag Berlin Heidelberg.


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.


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.


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.


Winther H.A.,University of Oslo
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The Layzer-Irvine equation describes energy conservation for a pressure less fluid interacting though quasi-Newtonian gravity in an expanding Universe. We here derive a Layzer-Irvine equation for scalar field theories where the scalar field is coupled to the matter fields, and show applications of this equation by applying it to N-body simulations of modified gravity theories. There it can be used as both a dynamical test of the accuracy of the solution and the numerical implementation when solving the equation of motion. We also present an equation that can be used as a new static test for an arbitrary matter distribution. This allows us to test the N-body scalar field solver using a matter distribution which resembles what we actually encounter in numerical simulations. © 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.


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.


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.


Diabetes with onset in childhood and adolescence has consequences for the family and the child, and the negative health effects and burden of daily disease management are well known. Less is known about the socioeconomic consequences of the disease and how it impacts on school performance. In this issue of Diabetologia, Persson et al report from a Swedish study regarding the impact of childhood-onset type 1 diabetes on school performance (doi: 10.1007/s00125-013-2870-8). Results indicate that onset of type 1 diabetes in childhood has adverse effects on school achievement and potentially on future successful employment. The authors suggest that attention must be paid in school to the particular needs of children with diabetes, although the question needs to be raised as to whether the differences are of such a magnitude that they matter and are relevant for healthcare and school personnel. The study provides a novel addition and is important because of the limited information available on educational performance among children and adolescents with diabetes. However, the results should be interpreted with caution because of the limitations of the study design, the relatively small differences detected and the fact that results from one country are not transferable to other countries without further research. The challenge is to find the resources to set up population-based studies in countries where appropriate data are available to investigate the long-term effects of type 1 diabetes on education and employment in different settings. © 2013 Springer-Verlag Berlin Heidelberg.


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.


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.


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.


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.


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.


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.


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.


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.


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.


Stensrud M.J.,University of Oslo | Puchades M.,University of Oslo | Gundersen V.,University of Oslo
Brain structure & function | Year: 2014

Recently, electrophysiological evidence was given for inhibitory postsynaptic responses at dopaminergic striatal synapses. These responses were independent of the vesicular GABA transporter, VGAT, but dependent on the vesicular dopamine transporter VMAT2. The identity and the exact source of the released molecule, as well as the presence of the putative inhibitory transmitter in VMAT2 containing synaptic vesicles remain to be shown. To clarify this, in particular to determine whether GABA is responsible for the inhibitory response at dopaminergic synapses, we used the electron microscopic immunogold method to label in vivo perfusion fixed striatal tissue with antibodies recognising GABA, VGAT, VMAT2 and tyrosine hydroxylase. We show that about 13 % of tyrosine hydroxylase positive and 11 % of VMAT2 axonal terminals in the caudo-putamen contain significant labelling for GABA. Immunogold signals for tyrosine hydroxylase and VGAT was totally segregated into different pools of nerve terminals. Quantitative analyses of the distance between gold particles signalling GABA and synaptic vesicles showed that GABA was as closely associated with synaptic vesicles in tyrosine hydroxylase positive as in tyrosine hydroxylase negative nerve terminals. Likewise, in dopaminergic terminals GABA and VMAT2 immunogold particles showed a close spatial localization, strongly suggesting the presence of GABA in VMAT2 positive synaptic vesicles. Our results suggest that GABA is exocytosed together with dopamine from dopaminergic nerve terminals in the caudo-putamen through VGAT negative and VMAT2 positive synaptic vesicles.


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.


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.


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.


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.


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.


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.


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.


Thorstensen T.,University of Oslo | Grini P.E.,University of Oslo | Aalen R.B.,University of Oslo
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2011

Post-translational methylation of lysine residues on histone tails is an epigenetic modification crucial for regulation of chromatin structure and gene expression in eukaryotes. The majority of the histone lysine methyltransferases (HKMTases) conferring such modifications are proteins with a conserved SET domain responsible for the enzymatic activity. The SET domain proteins in the model plant Arabidopsis thaliana can be assigned to evolutionarily conserved classes with different specificities allowing for different outcomes on chromatin structure. Here we review the present knowledge of the biochemical and biological functions of plant SET domain proteins in developmental processes. This article is part of a Special Issue entitled: Epigenetic control of cellular and developmental processes in plants. © 2011 Elsevier B.V.


Abrahamsen H.,University of Oslo | Stenmark H.,University of Oslo | Platta H.W.,Ruhr University Bochum
FEBS Letters | Year: 2012

The class III phosphatidylinositol 3-kinase (PI3K-III) complex and its phosphorylated lipid product phosphatidylinositol 3-phosphate (PtdIns3P) control the three topologically related membrane-involution processes autophagy, endocytosis, and cytokinesis. The activity of the catalytic unit of PI3K-III complex, the Vacuolar sorting protein 34 (VPS34), depends on the membrane targeting unit Vacuolar sorting protein 15 (VPS15), and the tumor suppressor protein Beclin 1. It is established that the overall activity of VPS34 is positively regulated by Beclin 1, whose positive influence is further controlled through the association with a set of Beclin1 interacting components, which stimulate or inhibit VPS34. The interaction between Beclin 1 and Beclin 1-associated components are controllable and is regulated by phosphorylation in a context-dependent manner. Here, we focus on an emerging concept whereby the activity of the PI3K-III complex is controlled by ubiquitination of Beclin 1 or Beclin 1-associated molecules. In summary, at least three different ubiquitin ligases can affect the positive regulatory function of Beclin 1 towards VPS34, suggesting that ubiquitination is an important and physiologically relevant event in tuning the tumor suppressor function of Beclin 1. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Rusten T.E.,University of Oslo | Vaccari T.,Instituto Firc Of Oncologia Molecolare | Stenmark H.,University of Oslo
Nature Cell Biology | Year: 2012

Originally identified for their involvement in endosomal sorting and multivesicular endosome (MVE) biogenesis, components of the endosomal sorting complex required for transport (ESCRT) are now known to control additional cellular functions such as receptor signalling, cytokinesis, autophagy, polarity, migration, miRNA activity and mRNA transport. The diverse cell biological functions of ESCRT proteins are translated into a pleiotropic set of developmental trajectories that reflect the wide repertoire of these evolutionarily conserved proteins.


Antolin P.,University of Oslo | Rouppe Van Der Voort L.,University of Oslo
Astrophysical Journal | Year: 2012

Observed in cool chromospheric lines, such as Hα or Ca II H, coronal rain corresponds to cool and dense plasma falling from coronal heights. Considered as a peculiar sporadic phenomenon of active regions, it has not received much attention since its discovery more than 40 years ago. Yet, it has been shown recently that a close relationship exists between this phenomenon and the coronal heating mechanism. Indeed, numerical simulations have shown that this phenomenon is most likely due to a loss of thermal equilibrium ensuing from a heating mechanism acting mostly toward the footpoints of loops. We present here one of the first high-resolution spectroscopic observations of coronal rain, performed with the CRisp Imaging Spectro Polarimeter (CRISP) instrument at the Swedish Solar Telescope. This work constitutes the first attempt to assess the importance of coronal rain in the understanding of the coronal magnetic field in active regions. With the present resolution, coronal rain is observed to literally invade the entire field of view. A large statistical set is obtained in which dynamics (total velocities and accelerations), shapes (lengths and widths), trajectories (angles of fall of the blobs), and thermodynamic properties (temperatures) of the condensations are derived. Specifically, we find that coronal rain is composed of small and dense chromospheric cores with average widths and lengths of 310km and 710km, respectively, average temperatures below 7000K, displaying a broad distribution of falling speeds with an average of 70kms-1, and accelerations largely below the effective gravity along loops. Through estimates of the ion-neutral coupling in the blobs we show that coronal rain acts as a tracer of the coronal magnetic field, thus supporting the multi-strand loop scenario, and acts as a probe of the local thermodynamic conditions in loops. We further elucidate its potential in coronal heating. We find that the cooling in neighboring strands occurs simultaneously in general suggesting a similar thermodynamic evolution among strands, which can be explained by a common footpoint heating process. Constraints for coronal heating models of loops are thus provided. Estimates of the fraction of coronal volume with coronal rain give values between 7% and 30%. Estimates of the occurrence time of the phenomenon in loops set times between 5 and 20hr, implying that coronal rain may be a common phenomenon, in agreement with the frequent observations of cool downflows in extreme-ultraviolet lines. The coronal mass drain rate in the form of coronal rain is estimated to be on the order of 5 × 109gs-1, a significant quantity compared to the estimate of mass flux into the corona from spicules. © 2012. The American Astronomical Society. All rights reserved.


Sekse D.H.,University of Oslo | Rouppe Van Der Voort L.,University of Oslo | De Pontieu B.,Lockheed Martin
Astrophysical Journal | Year: 2012

Spicules were recently found to exist as two different types when a new class of so-called typeII spicules was discovered at the solar limb with the Solar Optical Telescope on board the Hinode spacecraft. These typeII spicules have been linked with on-disk observations of rapid blueshifted excursions (RBEs) in the Hα and Ca II 8542 lines. Here we analyze observations optimized for the detection of RBEs in both Hα and Ca II 8542 lines simultaneously at a high temporal cadence taken with the Crisp Imaging Spectropolarimeter at the Swedish Solar Telescope on La Palma. In this study, we used a high-quality time sequence for RBEs at different blueshifts and employed an automated detection routine to detect a large number of RBEs in order to expand on the statistics of RBEs. We find that the number of detected RBEs is strongly dependent on the associated Doppler velocity of the images on which the search is performed. Automatic detection of RBEs at lower velocities increases the estimated number of RBEs to the same order of magnitude expected from limb spicules. This shows that RBEs and typeII spicules are indeed exponents of the same phenomenon. Furthermore, we provide solid evidence that Ca II 8542 RBEs are connected to Hα RBEs and are located closer to the network regions with the Hα RBEs being a continuation of the Ca II 8542 RBEs. Our results show that RBEs have an average lifetime of 83.9s when observed in both spectral lines and that the Doppler velocities of RBEs range from 10 to 25kms-1 in Ca II 8542 and 30 to 50kms-1 in Hα. In addition, we automatically determine the transverse motion of a much larger sample of RBEs than previous studies, and find that, just like typeII spicules, RBEs undergo significant transverse motions of the order of 5-10kms-1. Finally, we find that the intergranular jets discovered at Big Bear Solar Observatory are a subset of RBEs. © 2012. The American Astronomical Society. All rights reserved..


Vissers G.,University of Oslo | Rouppe Van Der Voort L.,University of Oslo
Astrophysical Journal | Year: 2012

High-quality imaging spectroscopy in the Hα line, obtained with the CRisp Imaging SpectroPolarimeter (CRISP) at the Swedish 1-m solar Telescope (SST) at La Palma and covering a small sunspot and its surroundings, is studied. They exhibit ubiquitous flows both along fibrils making up the chromospheric canopy away from the spot and in the superpenumbra. We term these flows "flocculent" to describe their intermittent character, that is, morphologically reminiscent of coronal rain. The flocculent flows are investigated further in order to determine their dynamic and morphological properties. For the measurement of their characteristic velocities, accelerations, and sizes, we employ a new versatile analysis tool, the CRisp SPectral EXplorer (CRISPEX), which we describe in detail. Absolute velocities on the order of 7.2-82.4kms-1 are found, with an average value of 36.5 ± 5.9kms-1 and slightly higher typical velocities for features moving toward the sunspot than away. These velocities are much higher than those determined from the shift of the line core, which shows patches around the sunspot with velocity enhancements of up to 10-15kms-1 (both red- and blueshifted). Accelerations are determined for a subsample of features that show clear accelerating or decelerating behavior, yielding an average of 270 ± 63ms-2 and 149± 63ms-2 for the accelerating and decelerating features, respectively. Typical flocculent features measure 627± 44km in length and 304 ± 30km in width. On average, 68 features are detected per minute, with an average lifetime of 67.7 ± 8.8s. The dynamics and phenomenology of the flocculent flows suggest they may be driven by a siphon flow, where the flocculence could arise from a density perturbation close to one of the footpoints or along the loop structure. © 2012. The American Astronomical Society. All rights reserved.


Tungen J.E.,University of Oslo | Nolsoe J.M.J.,University of Oslo | Hansen T.V.,University of Oslo
Organic Letters | Year: 2012

Asymmetric iodolactonization of γ- and δ-unsaturated carboxylic acids has been explored in the presence of six different chiral organocatalysts 5-8. The catalyst 6b was found to facilitate the cyclization of 5-arylhex-5-enoic acids 1 to the corresponding iodolactones 2 with up to 96% ee. By this protocol, unsaturated carboxylic acids are converted enantioselectively to synthetically useful δ-lactones in high yields using commercially available NIS. Apparently, both hydrogen bonding and aryl/aryl interactions are important for efficient stereodifferentiation. © 2012 American Chemical Society.


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.


Sandset P.M.,University of Oslo
Thrombosis Research | Year: 2013

There is now compelling evidence that use of oral contraceptives and postmenopausal hormonal therapies containing various estrogens is associated with a weak, but clinically relevant risk of both arterial and venous thrombosis. The increased risk is related to type and dose of both estrogen and combined progestagen and mode of delivery. Treatment induces mainly subtle changes in individual components of the coagulation and fibrinolytic systems, but the overall effect is the induction of a prothrombotic phenotype. This brief review summarizes some of the mechanisms responsible the prothrombotic effects of such treatment. © 2013 Elsevier Ltd. All rights reserved.


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.


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.


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.


Karlsen T.H.,University of Oslo | Karlsen T.H.,University of Bergen | Boberg K.M.,University of Oslo
Journal of Hepatology | Year: 2013

Primary sclerosing cholangitis (PSC) remains one of the most challenging conditions of clinical hepatology. There has been a steady growth in research to overcome this fact and the present review aims at summarizing the most recently published literature. The main emphasis will be put on the link of recent pathogenetic insights to clinical characteristics and patient management. With regard to pathogenesis, there is no consensus yet as to whether immune mediated injury or factors related to bile acid physiology are the most important. It also remains to be clarified whether PSC is a mixed bag of various secondary etiologies yet to be defined, or a disease entity predominantly represented by sclerosing cholangitis in the context of inflammatory bowel disease. Most important, there is no available medical therapy with proven influence on clinical end points, and timing of liver transplantation and patient follow-up are challenging due to the unpredictable and high risk of cholangiocarcinoma. © 2013 European Association for the Study of the Liver.


Soland T.M.,University of Oslo | Brusevold I.J.,University of Oslo
Histopathology | Year: 2013

Despite the tremendous number of studies of prognostic molecular markers in cancer, only a few such markers have entered clinical practise. The lack of clinical prognostic markers clearly reflects limitations in or an inappropriate approach to prognostic studies. This situation should be of great concern for the research community, clinicians and patients. In the present review, we evaluate immunohistochemical prognostic marker studies in oral squamous cell carcinomas (OSCC) from 2006 to 2012. We comment upon general issues such as study design, assay methods and statistical methods, applicable to prognostic marker studies irrespective of cancer type. The three most frequently studied markers in OSCC are reviewed. Our analysis revealed that most new molecular markers are reported only once. To draw conclusions of clinical relevance based on the few markers that appeared in more than one study was problematic due to between-study heterogeneity. Currently, much valuable tissue material, time and money are wasted on irrelevant studies. © 2013 John Wiley & Sons Ltd.


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.


Koehler P.E.,University of Oslo | Guber K.H.,Oak Ridge National Laboratory
Physical Review C - Nuclear Physics | Year: 2013

192Pt is produced solely by the slow neutron capture (s) nucleosynthesis process and hence an accurate (n,γ) reaction rate for this nuclide would allow its use as an important calibration point near the termination of the s-process nucleosynthesis flow. For this reason, we have measured neutron capture and total cross sections for 192,194,195 ,196,natPt in the energy range from 10 eV to several hundred keV at the Oak Ridge Electron Linear Accelerator. Measurements on the other Pt isotopes were, in part, necessitated by the fact that only a relatively small 192Pt sample of modest enrichment was available. Astrophysical 192 ,194,195,196Pt(n,γ) reaction rates, accurate to approximately 3%-5%, were calculated from these data. No accurate reaction rates have been published previously for any of these isotopes. At s-process temperatures, previously recommended rates are larger (by as much as 35%) and have significantly different shapes as functions of temperature than our new rates. We used our new Pt results, together with 191,193Ir(n, γ) data, to calibrate nuclear statistical model calculations and hence obtain an improved rate for the unmeasured s-process branching-point isotope 192Ir. © 2013 American Physical Society.


Davidson B.,University of Oslo | Trope C.G.,University of Oslo | Reich R.,Hebrew University of Jerusalem
Gynecologic Oncology | Year: 2014

Objective MicroRNAs (miRNAs, miRs) are non-coding RNAs which post-transcriptionally regulate mRNA synthesis. Data regarding the expression and clinical relevance of miRNAs and the miRNA-regulating machinery in ovarian carcinoma has been rapidly expanding in recent years. This review presents current knowledge in this area. Methods PubMed search was undertaken using the terms 'ovarian' and 'microRNA'. Results A total of 492 papers were identified, of which approximately 100 were publications in English focusing exclusively or partly on clinical ovarian carcinoma specimens. These studies have identified multiple miRNAs with a potential role in the diagnosis, biology and progression of ovarian carcinoma, as well as on predicting chemoresponse and determining prognosis. Conclusions The presented data support a clinical role for miRNAs in ovarian carcinoma and suggest that miRNA-regulated pathways may be of relevance for novel therapeutics. Novel technologies offer new possibilities for wide-scale miRNA-based classification of OC. Further genomic research focusing on larger series of tumors of similar histological type in combination with experimental approaches is likely to expand our understanding of the role of miRNAs in this cancer. © 2014 Elsevier Inc.


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.


Fjell A.M.,University of Oslo | Walhovd K.B.,University of Oslo
Reviews in the Neurosciences | Year: 2010

The structure of the brain is constantly changing from birth throughout the lifetime, meaning that normal aging, free from dementia, is associated with structural brain changes. This paper reviews recent evidence from magnetic resonance imaging (MRI) studies about age-related changes in the brain. The main conclusions are that (1) the brain shrinks in volume and the ventricular system expands in healthy aging. However, the pattern of changes is highly heterogeneous, with the largest changes seen in the frontal and temporal cortex, and in the putamen, thalamus, and accumbens. With modern approaches to analysis of MRI data, changes in cortical thickness and subcortical volume can be tracked over periods as short as one year, with annual reductions of between 0.5% and 1.0% in most brain areas. (2) The volumetric brain reductions in healthy aging are likely only to a minor extent related to neuronal loss. Rather, shrinkage of neurons, reductions of synaptic spines, and lower numbers of synapses probably account for the reductions in grey matter. In addition, the length of myelinated axons is greatly reduced, up to almost 50%. (3) Reductions in specific cognitive abilities - for instance processing speed, executive functions, and episodic memory - are seen in healthy aging. Such reductions are to a substantial degree mediated by neuroanatomical changes, meaning that between 25% and 100% of the differences between young and old participants in selected cognitive functions can be explained by group differences in structural brain characteristics. © Freund & Pettman.


Corthay A.,University of Oslo
Frontiers in Immunology | Year: 2014

The importance of the immune system in conferring protection against pathogens like viruses, bacteria, and parasitic worms is well established. In contrast, there is a long-lasting debate on whether cancer prevention is a primary function of the immune system. The concept of immunological surveillance of cancer was developed by Lewis Thomas and Frank Macfarlane Burnet more than 50 years ago. We are still lacking convincing data illustrating immunological eradication of precancerous lesions in vivo. Here, I present eight types of evidence in support of the cancer immunosurveillance hypothesis. First, primary immunodeficiency in mice and humans is associated with increased cancer risk. Second, organ transplant recipients, who are treated with immunosuppressive drugs, are more prone to cancer development. Third, acquired immunodeficiency due to infection by human immunodeficiency virus (HIV-1) leads to elevated risk of cancer. Fourth, the quantity and quality of the immune cell infiltrate found in human primary tumors represent an independent prognostic factor for patient survival. Fifth, cancer cells harbor mutations in protein-coding genes that are specifically recognized by the adaptive immune system. Sixth, cancer cells selectively accumulate mutations to evade immune destruction ("immunoediting"). Seventh, lymphocytes bearing the NKG2D receptor are able to recognize and eliminate stressed premalignant cells. Eighth, a promising strategy to treat cancer consists in potentiating the naturally occurring immune response of the patient, through blockade of the immune checkpoint molecules CTLA-4, PD-1, or PD-L1. Thus, there are compelling pieces of evidence that a primary function of the immune system is to confer protection against cancer. © 2014 Corthay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).


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.


Waaktaar T.,Center for Child and Adolescent Mental Health | Torgersen S.,University of Oslo
Behavior Genetics | Year: 2012

The aim of this multi-informant twin study was to determine the relative role of genetic and environmental factors in explaining variation in trait resilience in adolescents. Participants were consenting families (N = 2,638 twins in 1,394 families), from seven national cohorts (age 12-18 years, both sexes) of monozygotic and dizygotic twins reared together. Questionnaire data on the adolescents' Ego-resilience (ER89) was collected from mothers, fathers and twins, and analysed by means of multivariate genetic modelling. Variance in trait resilience was best represented in an ADE common pathways model with sex limitation. Variance in the latent psychometric resilience factor was largely explained by additive genetic factors (77% in boys, 70% in girls), with the remaining variance (23 and 30%) attributable to non-shared environmental factors. Additive genetic sources explained more than 50% of the informant specific variation in mothers and fathers scores. In twins, additive and non-additive genetic factors together explained 40% and non-shared environmental factor the remaining 60% of variation. In the mothers' scores, the additive genetic effect was larger for boys than for girls. The non-additive genetic factor found in the twins' self ratings was larger in boys than in girls. The remaining sex differences in the specific factors were small. Trait resilience is largely genetically determined. Estimates based on several informants rather than single informants approaches are recommended. © The Author(s) 2011.


Hansen T.F.,University of Oslo | Bartoszek K.,Chalmers University of Technology
Systematic Biology | Year: 2012

Regressions of biological variables across species are rarely perfect. Usually, there are residual deviations from the estimated model relationship, and such deviations commonly show a pattern of phylogenetic correlations indicating that they have biological causes. We discuss the origins and effects of phylogenetically correlated biological variation in regression studies. In particular, we discuss the interplay of biological deviations with deviations due to observational or measurement errors, which are also important in comparative studies based on estimated species means. We show how bias in estimated evolutionary regressions can arise from several sources, including phylogenetic inertia and either observational or biological error in the predictor variables. We show how all these biases can be estimated and corrected for in the presence of phylogenetic correlations. We present general formulas for incorporating measurement error in linear models with correlated data. We also show how alternative regression models, such as major axis and reduced major axis regression, which are often recommended when there is error in predictor variables, are strongly biased when there is biological variation in any part of the model. We argue that such methods should never be used to estimate evolutionary or allometric regression slopes. © 2012 The Author(s).


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.


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.


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.


Berg K.,University of Oslo | Pedersen T.R.,University of Oslo | Sandvik L.,University of Oslo | Bragadottir R.,University of Oslo
Ophthalmology | Year: 2015

Purpose: To compare the efficacy and safety of bevacizumab versus ranibizumab when administered according to a treat-and-extend protocol for the treatment of neovascular age-related macular degeneration (AMD). Design: Multicenter, randomized, noninferiority trial with a noninferiority limit of 5 letters. Participants: Patients aged ≥50 years with previously untreated neovascular AMD in 1 eye and best-corrected visual acuity (BCVA) between 20/25 and 20/320. Methods: Patients were randomly assigned to receive ranibizumab 0.5 mg or bevacizumab 1.25 mg intravitreal injections. Monthly injections were given until inactive disease was achieved. The patients were then followed with a gradual extension of treatment interval by 2 weeks at a time up to a maximum of 12 weeks. If signs of recurrent disease appeared, the treatment interval was shortened by 2 weeks at a time. Main Outcome Measures: Change in visual acuity at 1 year. Results: Between March 2009 and July 2012, 441 patients were randomized at 10 ophthalmological centers in Norway. The 1-year visit was completed by 371 patients. In the per protocol analysis at 1 year, bevacizumab was equivalent to ranibizumab, with 7.9 and 8.2 mean letters gained, respectively (95% confidence interval [CI] of mean difference, -2.4 to 2.9; P = 0.845). The intention-to-treat analysis was concordant. There was no significant difference in measured central retinal thickness (CRT), with a mean decrease of -112 μm for bevacizumab and -120 μm for ranibizumab (95% CI of mean difference, -13 to 28; P = 0.460). There was a statistically significant difference (P = 0.001) between the drugs regarding the number of treatments: 8.9 for bevacizumab and 8.0 for ranibizumab. There were fewer arteriothrombotic events in the bevacizumab group (1.4%) than in the ranibizumab group (4.5%) (P = 0.050) and significantly more cardiac events in the ranibizumab group (P = 0.036). However, patients treated with ranibizumab more often had a history of myocardial infarction (P = 0.021). Conclusions: Bevacizumab and ranibizumab had equivalent effects on visual acuity at 1 year when administered according to a treat-and-extend protocol. The visual acuity results at 1 year were comparable to those of other clinical trials with monthly treatment. The numbers of serious adverse events were small. © 2015 by the American Academy of Ophthalmology.


Karlsen T.H.,University of Oslo | Lammert F.,Saarland University | Thompson R.J.,King's College London
Journal of Hepatology | Year: 2015

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. © 2015 European Association for the Study of the Liver.


Westgard Erichsen M.,University of Oslo | Svelle S.,University of Oslo | Olsbye U.,University of Oslo
Journal of Catalysis | Year: 2013

The methanol-to-hydrocarbons (MTH) reaction was studied over a moderately acidic zeotype material, H-SAPO-5, at 350-450°C and with WHSV = 0.3-5 h -1. C3-C5 alkenes were the main products of reaction, followed by C6+ aliphatics. Conversion-selectivity plots from experiments conducted at various contact times revealed that coking did not influence product selectivity significantly. Steady-state isotope transient experiments (12CH3OH//13CH3OH) were performed at 450°C. 13C incorporation was more rapid in the alkene products than in the polymethylated benzene molecules that were retained inside the catalyst after testing, suggesting that polymethylbenzenes contribute only to a minor extent to alkene formation in H-SAPO-5. Co-feed studies of methanol and benzene at 350°C revealed that benzene shifts the product selectivity towards ethene and aromatic products. Co-feeding 13CH3OH and benzene at 250°C, giving <2% conversion of both reactants, indicated that polymethylbenzenes, when present in excessive amounts, may contribute to ethene and propene, but not to C4+ alkene, formation. Furthermore, the isotopic labelling pattern of ethene provided the first direct experimental evidence for ethene formation by a paring-type reaction from polymethylated benzene intermediates. Overall, the results obtained in this study suggest that a lower acid strength promotes an alkene-mediated MTH reaction mechanism, and that acid strength is therefore an important design parameter for selectivity optimisation in zeotype catalysis. © 2012 Elsevier Inc. All rights reserved.


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.


Lund E.,University of Oslo | Oldenburg A.R.,University of Oslo | Collas P.,University of Oslo
Nucleic Acids Research | Year: 2014

Nuclear lamins contact the genome at the nuclear periphery through large domains and are involved in chromatin organization. Among broad peak calling algorithms available to date, none are suited for mapping lamin-genome interactions genome wide. We disclose a novel algorithm, enriched domain detector (EDD), for analysis of broad enrichment domains from chromatin immunoprecipitation (ChIP)-seq data. EDD enables discovery of genomic domains interacting with broadly distributed proteins, such as A-and B-type lamins affinity isolated by ChIP. The advantages of EDD over existing broad peak callers are sensitivity to domain width rather than enrichment strength at a particular site, and robustness against local variations. © 2014 The Author(s) 2014.


Andreassen O.A.,University of Oslo | Thompson W.K.,University of California at San Diego | Dale A.M.,University of California at San Diego
Schizophrenia Bulletin | Year: 2014

Genome-wide association studies (GWAS) have identified a large number of gene variants associated with schizophrenia, but these variants explain only a small portion of the heritability. It is becoming increasingly clear that schizophrenia is influenced by many genes, most of which have effects too small to be identified using traditional GWAS statistical methods. By applying recently developed Empirical Bayes statistical approaches, we have demonstrated that functional genic elements show differential contribution to phenotypic variance, with some elements (regulatory regions and exons) showing strong enrichment for association with schizophrenia. Applying related methods, we also showed abundant genetic overlap (pleiotropy) between schizophrenia and other phenotypes, including bipolar disorder, cardiovascular disease risk factors, and multiple sclerosis. We estimated the number of gene variants with effects in schizophrenia and bipolar disorder to be approximately 1.2%. By applying our novel statistical framework, we dramatically improved gene discovery and detected a large number of new gene loci associated with schizophrenia that have not yet been identified with standard GWAS methods. Utilizing independent schizophrenia substudies, we showed that these new loci have high replication rates in de novo samples, indicating that they likely represent true schizophrenia risk genes. The new statistical tools provide a powerful approach for uncovering more of the missing heritability of schizophrenia and other complex disorders. In conclusion, the highly polygenic architecture of schizophrenia strongly suggests the utility of research approaches that recognize schizophrenia neuropathology as a complex dynamic system, with many small gene effects integrated in functional networks. © 2013 The Author.


Bolstad N.,University of Oslo | Warren D.J.,University of Oslo | Nustad K.,University of Oslo
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

Immunometric assays are inherently vulnerable to interference from heterophilic antibodies, endogenous antibodies that bind assay antibodies. The consequences of such interference can be devastating. In this review, we discuss strategies that reduce the damage caused by heterophilic antibodies. Clinicians should only order blood tests that are indicated for the patient and clinical setting at hand, and have the confidence to question laboratory results discordant with the clinical picture. Laboratorians should familiarize themselves with the vulnerability of the assays they offer, and be able to perform and interpret adequate confirmatory measures correctly. When designing immunoassays, the immunoassay industry should invest the necessary resources in specific protective measures against heterophilic antibody interference. Examples include using antibody fragments and the addition of effective blockers to assay reagents. The increasing use of modified monoclonal mouse antibodies both in therapy and diagnostics could present a particular challenge in the future. © 2013 Elsevier Ltd. 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.


Nolsoe J.M.J.,University of Oslo | Hansen T.V.,University of Oslo
European Journal of Organic Chemistry | Year: 2014

The diversity entailed by halolactonization makes it a fundamental transformation, enabling the synthetic organic chemist to build up molecular complexity in a way that relates structural elements in a predictable manner. Due to practical aspects and the subsequent flexible manipulation of the installed halogen handle, iodolactonization takes precedence over the other variants. The asymmetry that can be conferred on the products by iodine-induced cyclization has been the subject of various approaches. For a long time stereoselectivity has been achieved by substrate-controlled reactions. However, lately, the reagent-controlled counterpart has surfaced as an alternative based on the action of a catalyst. Despite the fact that the current progress in catalytic asymmetric iodolactonization has happened only in the space of the last three years, a number of conceptually different approaches have already been applied to advance beyond the substrate-controlled reaction. Herein we describe the various strategies, which have propelled the development of asymmetric iodolactonization to its current state, putting an emphasis on catalysis. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


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.


Konijnenberg C.,University of Oslo | Melinder A.,University of Oslo
Addiction | Year: 2013

Aims: Opioid maintenance therapy (OMT) is generally recommended for pregnant opioid-dependent women. Previous studies investigating the long-term effects of OMT on children's cognitive development found that children of women in OMT have an increased risk of developing deficits in motor and visual perceptual skills, which are important aspects of the mirror neurone system (MNS), a complex neural circuit involved in learning and social interactions. The aim of the current study was to investigate aspects of the MNS in children of women in OMT. Design: A 2 (control group versus OMT group)×2 (human versus mechanic) mixed factorial design. Setting: The Cognitive Developmental Research Unit at the University of Oslo, Norway. Participants: Fifteen children of women in OMT and 15 non-exposed children participated. Measurements: Goal-directed eye movements were recorded using a Tobii 1750 eye tracker. Neurocognitive tests were employed to map children's cognitive development. Findings: The OMT group made fewer proactive goal-directed eye movements [mean=-37.73, standard deviation (SD)=208.56] compared to the control group (mean=181.47, SD=228.65), F(1,28)=7.53, P=0.01, η2=0.21. No differences were found on tests of visual perception or goal understanding. Conclusions: Use of opioid maintenance therapy during pregnancy appears to be associated with impaired goal-directed eye movements in the 4-year-old infant which may affect later social adjustment adversely. © 2012 Society for the Study of Addiction.


Root D.,University of Oslo | Root D.,Apt Therapeutics, Inc. | Corfu F.,University of Oslo
Contributions to Mineralogy and Petrology | Year: 2012

U-Pb geochronology for eclogites in two different areas of the Seve Nappe Complex (SNC) in Sweden confirms previous indications of discrete Ordovician high-pressure events affecting various parts of the complex. In Norrbotten, just north of the Arctic circle, eclogites from the Tsäkkok and Vaimok Lenses yield identical metamorphic zircon ages of 482 ± 1 Ma. Titanite in a metagabbro from the Vaimok Lens retains an older age of 607 ± 2 Ma, which may date a protolith coeval with mafic dikes in the overlying Sarek Lens; high-U zircon cores in one of the eclogites also indicate a similar age. Farther south, in Jämtland, the Tjeliken eclogite yields a significantly younger metamorphic age of 446 ± 1 Ma. Although they support the age discrepancy between the Norrbotten and Jämtland eclogites, the U-Pb ages of both eclogite suites are ca. 20 m. y. younger than previously reported Sm-Nd ages. The latter may either represent early prograde growth or be spuriously too old due to isotopic disequilibrium. The SNC has traditionally been taken to represent the outermost margin of Baltica, linking the Early Caledonian eclogite-forming events to subduction of Baltica below an offshore arc. Alternatively, the coincidence of these eclogite-forming events with orogenic phases recorded on the Laurentian margin may point to an origin from other regions of the Iapetus Ocean. © 2011 Springer-Verlag.


Lison P.,University of Oslo
Proceedings of the SIGDIAL 2011 Conference: 12th Annual Meeting of the Special Interest Group on Discourse and Dialogue | Year: 2011

We present a new approach to dialogue management based on the use of multiple, interconnected policies. Instead of capturing the complexity of the interaction in a single large policy, the dialogue manager operates with a collection of small local policies combined concurrently and hierarchically. The meta-control of these policies relies on an activation vector updated before and after each turn. © 2011 Association for Computational Linguistics.


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.


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.


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.


Allanach B.,University of Cambridge | Raklev A.,University of Oslo | Kvellestad A.,University of Oslo
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

ATLAS recently reported a 3σ excess in a leptonic-Z+ETmiss channel. This was interpreted in the literature in a simplified general gauge mediation model containing a gluino, a Higgsino next-to-lightest supersymmetric particle and a gravitino lightest supersymmetric particle. We test the consistency of this explanation in lieu of the results of the corresponding search in CMS, and other LHC searches for new physics. Due to nondecoupling effects from squarks the parameter space of these models is split into two regions; in one region additional leptons via top quark production are expected, while the other region sees a large probability for zero-lepton events. After combining the relevant constraints we find that these models cannot explain the ATLAS excess. © 2015 American Physical Society.


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.


The present review focuses on characteristics of lanthanum tungstate in the compositional region 25-30 mol% La2O3 in the La 2O3-WO3 phase diagram. These tungstates represent an interesting family of materials for technological applications being proton or mixed proton-electron conductors depending on conditions. The material family was traditionally identified as La6WO12. However, recent efforts have shown that lanthanum tungstate can more correctly be represented by the formula La28-xW4+xO 54+δ, where nearly one tungsten (x ∼ 1) dissolves in lanthanum sites to form a stable composition. In the present contribution, the importance of the crystal structure and the effect of the La/W ratio on stability, defect chemistry and, accordingly, transport properties of this material are reviewed. A revisited phase diagram in this compositional region is presented. Reported doping strategies on both the A- and B-sites are discussed in view of the applicability of these materials as dense ceramic H2 separation membranes. © 2014 the Partner Organisations.


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.


Brown B.A.,Michigan State University | Larsen A.A.C.,University of Oslo
Physical Review Letters | Year: 2014

A strong enhancement at low γ-ray energies has recently been discovered in the γ-ray strength function of Fe56,57. In this work, we have for the first time obtained theoretical γ decay spectra for states up to ≈8MeV in excitation for Fe56,57. We find large B(M1) values for low γ-ray energies that provide an explanation for the experimental observations. The role of mixed E2 transitions for the low-energy enhancement is addressed theoretically for the first time, and it is found that they contribute a rather small fraction. Our calculations clearly show that the high-(=f) diagonal terms are most important for the strong low-energy M1 transitions. As such types of 0ω transitions are expected for all nuclei, our results indicate that a low-energy M1 enhancement should be present throughout the nuclear chart. This could have far-reaching consequences for our understanding of the M1 strength function at high excitation energies, with profound implications for astrophysical reaction rates. © 2014 American Physical Society.


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.


Adger W.N.,University of Exeter | Barnett J.,University of Melbourne | Brown K.,University of Exeter | Marshall N.,James Cook University | O'Brien K.,University of Oslo
Nature Climate Change | Year: 2013

Society's response to every dimension of global climate change is mediated by culture. We analyse new research across the social sciences to show that climate change threatens cultural dimensions of lives and livelihoods that include the material and lived aspects of culture, identity, community cohesion and sense of place. We find, furthermore, that there are important cultural dimensions to how societies respond and adapt to climate-related risks. We demonstrate how culture mediates changes in the environment and changes in societies, and we elucidate shortcomings in contemporary adaptation policy. © 2013 Macmillan Publishers Limited. All rights reserved.


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..


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.


Raiborg C.,University of Oslo | Schink K.O.,University of Oslo | Stenmark H.,University of Oslo
FEBS Journal | Year: 2013

Endocytosis and subsequent membrane traffic through endosomes are cellular processes that are integral to eukaryotic evolution, and numerous human diseases are associated with their dysfunction. Consequently, it is important to untangle the molecular machineries that regulate membrane dynamics and protein flow in the endocytic pathway. Central in this context is class III phosphatidylinositol 3-kinase, an evolutionarily conserved enzyme complex that phosphorylates phosphatidylinositol into phosphatidylinositol 3-phosphate. Phosphatidylinositol 3-phosphate recruits specific effector proteins, most of which contain FYVE or PX domains, to promote endocytosis, endosome fusion, endosome motility and endosome maturation, as well as cargo sorting to lysosomes, the biosynthetic pathway or the plasma membrane. Here we review the functions of key phosphatidylinositol 3-phosphate effectors in regulation of endocytic membrane dynamics and protein sorting. Class III phosphatidylinositol 3-kinase (PI3K-III) and its catalytic product phosphatidylinositol 3-phosphate (PtdIns3P) are central regulators of endocytic membrane traffic. PtdIns3P recruits specific effector proteins, most of which contain FYVE or PX domains, to promote endocytosis, endosome fusion, endosome motility, and endosome maturation, as well as cargo sorting to lysosomes, the biosynthetic pathway or the plasma membrane. © 2013 The Authors Journal compilation © 2013 FEBS.


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.


Llinares C.,University of Oslo | Mota D.F.,University of Oslo
Physical Review Letters | Year: 2013

Several extensions of general relativity and high energy physics include scalar fields as extra degrees of freedom. In the search for predictions in the nonlinear regime of cosmological evolution, the community makes use of numerical simulations in which the quasistatic limit is assumed when solving the equation of motion of the scalar field. In this Letter, we propose a method to solve the full equations of motion for scalar degrees of freedom coupled to matter. We run cosmological simulations which track the full time and space evolution of the scalar field, and find striking differences with respect to the commonly used quasistatic approximation. This novel procedure reveals new physical properties of the scalar field and uncovers concealed astrophysical phenomena which were hidden in the old approach. © 2013 American Physical Society.


Llinares C.,University of Oslo | Mota D.F.,University of Oslo
Physical Review Letters | Year: 2013

Scalar fields are crucial components in high energy physics and extensions of general relativity. The fact that they are not observed in the Solar System may be due to a mechanism which screens their presence in high dense regions. We show how observations of the ellipticity of galaxy clusters can discriminate between models with and without scalar fields and even between different screening mechanisms. Using current x-ray observations we put novel constraints on the different models. © 2013 American Physical Society.


Friedman R.,Linnaeus University | Boye K.,University of Oslo | Flatmark K.,University of Oslo
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2013

The complexity of cancer and the vast amount of experimental data available have made computer-aided approaches necessary. Biomolecular modelling techniques are becoming increasingly easier to use, whereas hardware and software are becoming better and cheaper. Cross-talk between theoretical and experimental scientists dealing with cancer-research from a molecular approach, however, is still uncommon. This is in contrast to other fields, such as amyloid-related diseases, where molecular modelling studies are widely acknowledged. The aim of this review paper is therefore to expose some of the more common approaches in molecular modelling to cancer scientists in simple terms, illustrating success stories while also revealing the limitations of computational studies at the molecular level. © 2013 Elsevier B.V.


Bjerkan A.M.,University of Oslo
Journal of Risk Research | Year: 2010

A large cross-sectional survey was conducted amongst employees in the Norwegian offshore oil and gas industry as part of the 'Trends in Risk Level' project initiated by the Norwegian Petroleum Safety Authority in 1999/2000. The aim of the study was to examine the relationship between health, safety and (work) environment (HSE). Furthermore to examine the effect of HSE-related variables and occupational accidents amongst eight different offshore work groups on different installations and within different companies on the Norwegian continental shelf (NCS). The study is based on a large cross-sectional survey. The survey was distributed to all employees travelling offshore between December 2005 and March 2006 (N = 9945). The resulting sample consisted of employees employed within different companies on different installations, and working within different offshore work groups. The results showed that the correlations between health, safety and work environment were significant. Differences between the work groups were identified with regard to HSE-related variables, such as perceived work safety climate and perception of the psychosocial work environment. Perceived work safety climate along with perception of the physical and psychosocial work environment accounted for differing degrees of the explained variance in subjective health status and reported occupational accidents in the different offshore work groups. The study concludes that work group has to be taken into account when studying the effects of work safety climate and perception of the work environment on subjective health status as well as accident frequency. The results also suggest that HSE interventions should be targeted towards the work group level in addition to the organisation as a whole. © 2010 Taylor & Francis.


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.


Ravndal E.,University of Oslo | Amundsen E.J.,SIRUS Norwegian Institute for Alcohol and Drug Research
Drug and Alcohol Dependence | Year: 2010

Background: Drug users who are leaving/completing inpatient medication-free treatment may, like drug users released from prison, have an elevated risk of dying from fatal overdoses. This is mainly explained by their low drug tolerance. Methods: Two hundred and seventy-six drug users who had been admitted to 11 inpatient facilities in Norway, were followed prospectively after discharge from treatment during an 8-year period (1998-2006). The following instruments were used: EuropASI, SCL-25 and MCMI II. Information on deaths and causes of death were obtained from the National Death Register. Results: A total of 36 deaths were registered after discharge from treatment during the observation period, of which 24 were classified as overdose deaths. During the first 4 weeks after discharge six persons died, yielding an unadjusted excess mortality of 15.7 (rate ratio) in this period (CI 5.3-38.3). All were dropouts and all deaths were classified as opiate overdoses. There was no significant association between time in index treatment and mortality after discharge, nor did any background characteristics correlate significantly with elevated mortality shortly after discharge. Conclusions: The elevated risk of dying from overdose within the first 4 weeks of leaving medication-free inpatient treatment is so dramatic that preventive measures should be taken. More studies from similar inpatient programmes are needed in order to obtain systematic knowledge about determinants of overdose deaths shortly after leaving treatment, and possible preventive measures. © 2009 Elsevier Ireland Ltd. All rights reserved.


The optimal setting and content of primary health care rehabilitation of older people is not known. Our aim was to study independence, institutionalization, death and treatment costs 18 months after primary care rehabilitation of older people in two different settings. Eighteen months follow-up of an open, prospective study comparing the outcome of multi-disciplinary rehabilitation of older people, in a structured and intensive Primary care dedicated inpatient rehabilitation (PCDIR, n=202) versus a less structured and less intensive Primary care nursing home rehabilitation (PCNHR, n=100). Participants: 302 patients, disabled from stroke, hip-fracture, osteoarthritis and other chronic diseases, aged ≥65years, assessed to have a rehabilitation potential and being referred from general hospital or own residence. Outcome measures: Primary: Independence, assessed by Sunnaas ADL Index(SI). Secondary: Hospital and short-term nursing home length of stay (LOS); institutionalization, measured by institutional residence rate; death; and costs of rehabilitation and care. Statistical tests: T-tests, Correlation tests, Pearson's χ2, ANCOVA, Regression and Kaplan-Meier analyses. Overall SI scores were 26.1 (SD 7.2) compared to 27.0 (SD 5.7) at the end of rehabilitation, a statistically, but not clinically significant reduction (p=0.003 95%CI(0.3-1.5)). The PCDIR patients scored 2.2points higher in SI than the PCNHR patients, adjusted for age, gender, baseline MMSE and SI scores (p=0.003, 95%CI(0.8-3.7)). Out of 49 patients staying >28 days in short-term nursing homes, PCNHR-patients stayed significantly longer than PCDIR-patients (mean difference 104.9 days, 95%CI(0.28-209.6), p=0.05). The institutionalization increased in PCNHR (from 12%-28%, p=0.001), but not in PCDIR (from 16.9%-19.3%, p= 0.45). The overall one year mortality rate was 9.6%. Average costs were substantially higher for PCNHR versus PCDIR. The difference per patient was 3528€ for rehabilitation (p<0.001, 95%CI(2455-4756)), and 10134€ for the at-home care (p=0.002, 95%CI(4066-16202)). The total costs of rehabilitation and care were 18702€ (=1.6 times) higher for PCNHR than for PCDIR. At 18 months follow-up the PCDIR-patients maintained higher levels of independence, spent fewer days in short-term nursing homes, and did not increase the institutionalization compared to PCNHR. The costs of rehabilitation and care were substantially lower for PCDIR. More communities should consider adopting the PCDIR model. Clinicaltrials.gov ID NCT01457300.


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.


McQuarrie N.,University of Pittsburgh | Van Hinsbergen D.J.,University of Oslo | Van Hinsbergen D.J.,University Utrecht
Geology | Year: 2013

The Arabia-Eurasia collision has been linked to global cooling, the slowing of Africa, Mediterranean extension, the rifting of the Red Sea, an increase in exhumation and sedimentation on the Eurasian plate, and the slowing and deformation of the Arabian plate. Collision age estimates range from the Late Cretaceous to Pliocene, with most estimates between 35 and 20 Ma. We assess the consequences of these collision ages on the magnitude and location of continental consumption by compiling all documented shortening within the region, and integrating this with plate kinematic reconstructions. Shortening estimates across the orogen allow for ~350 km of Neogene upper crustal contraction, necessitating collision by 20 Ma. A 35 Ma collision requires additional subduction of ~400-600 km of Arabian continental crust. Using the Oman ophiolite as an analogue, ophiolitic fragments preserved along the Zagros suture zone permit ~180 km of subduction of the Arabian continental margin plus overlying ophiolites. Wholesale subduction of this more dense continental margin plus ophiolites would reconstruct ~400-500 km of postcollisional Arabia-Eurasia convergence, consistent with a ca. 27 Ma initial collision age. This younger Arabia-Eurasia collision suggests a noncollisional mechanism for the slowing of Africa, and associated extension. © 2013 Geological Society of America.


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.


Steponkiene S.,University of Oslo
International journal of nanomedicine | Year: 2011

In novel treatment approaches, therapeutics should be designed to target cancer stem cells (CSCs). Quantum dots (QDs) are a promising new tool in fighting against cancer. However, little is known about accumulation and cytotoxicity of QDs in CSCs. Accumulation and cytotoxicity of CdTe-MPA (mercaptopropionic acid) QDs in CSCs were assessed using flow cytometry and fluorescence-activated cell sorting techniques as well as a colorimetric cell viability assay. We investigated the expression of two cell surface-associated glycoproteins, CD44 and CD133, in four different cancer cell lines (glioblastoma, melanoma, pancreatic, and prostate adenocarcinoma). Only the melanoma cells were positive to both markers of CD44 and CD133, whereas the other cells were only CD44-positive. The QDs accumulated to a similar extent in all subpopulations of the melanoma cells. The phenotypical response after QD treatment was compared with the response after ionizing radiation treatment. The percentage of the CD44(high-)CD133(high) subpopulation decreased from 72% to 55%-58% for both treatments. The stem-like subpopulation CD44(high)CD133(low/-) increased from 26%-28% in the untreated melanoma cells to 36%-40% for both treatments. Treatment of melanoma cells with QDs results in an increase of stem-like cell subpopulations. The changes in phenotype distribution of the melanoma cells after the treatment with QDs are comparable with the changes after ionizing radiation.


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.


Skotland T.,University of Oslo | Skotland T.,Norwegian Radium Hospital
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.


Sert B.,University of Oslo
International Journal of Medical Robotics and Computer Assisted Surgery | Year: 2010

Background: Port-site metastasis (PSM) following minimally invasive surgery for gynaecological cancer has been recognized as a potential problem over the last two decades. Methods: A 60 year-old woman with stage Ib1 adenocarcinoma of the cervix was treated with radical hysterectomy, bilateral salpingo- oophorectomy and bilateral pelvic lymph node dissection, using robot-assisted laparoscopy. Results: Eighteen months after primary surgery, the patient developed a pelvic recurrence invading both the bladder mucosa and the parametrium. During the routine recurrence work-up, we found an 8 mm robotic port-site metastasis (PSM) on the abdominal computed tomography (CT) scan. Conclusion: This is the first case report emphasizing the risk of PSM and early pelvic recurrences in robot-assisted laparoscopic radical hysterectomy and bilateral pelvic lymph node dissection for an early-stage cervical adenocarcinoma patient with negative lymph nodes, histologically examined by immunohistochemical ultrastaging. Copyright © 2010 John Wiley & Sons, Ltd.


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.


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.


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.


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.


Saugstad O.D.,University of Oslo
Acta Paediatrica, International Journal of Paediatrics | Year: 2011

The 2010 International Liaison Committee on Resuscitation guidelines for newborn resuscitation represent important progress. The criteria for assessment are simplified based on heart rate and respiration only and there is no timing of stages after the first 60 sec. Instead of giving supplemental oxygen, the guidelines state that 'it is best to start with air'. However, the optimal oxygen concentration later in the process and for premature babies is not yet clear. A description of an adequate heart rate response is not given, and the cut-off of 100 bpm may be arbitrary. There are still no clear recommendations regarding ventilation, inspiratory time, use of positive end expiratory pressure or continuous positive airway pressure. The guidelines do not mention which paCO 2 level might be optimal. As colour pink assessment and routine suctioning of airways are not recommended anymore, there is an urgent need to obtain international consensus and create a new and revised Apgar score without these two variables. Conclusion: In spite of improved guidelines for newborn resuscitation, there is still a number of unanswered questions and a need for more delivery room studies. © 2011 The Author/Acta Pædiatrica.


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.


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.


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.


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.


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.


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.


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.


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.


Recent work has demonstrated that cardiomyocyte Ca2+release is desynchronized in several pathological conditions. Loss of Ca2+ release synchrony has been attributed to t-tubule disruption, but it is unknown if other factors also contribute. We investigated this issue in normal and failing myocytes by integrating experimental data with a mathematical model describing spatiotemporal dynamics of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). Heart failure development in postinfarction mice was associated with progressive t-tubule disorganization, as quantified by fast-Fourier transforms. Data from fast-Fourier transforms were then incorporated in the model as a dyadic organization index, reflecting the proportion of ryanodine receptors located in dyads. With decreasing dyadic-organization index, the model predicted greater dyssynchrony of Ca 2+ release, which exceeded that observed in experimental line-scan images. Model and experiment were reconciled by reducing the threshold for Ca2+ release in the model, suggesting that increased RyR sensitivity partially offsets the desynchronizing effects of t-tubule disruption in heart failure. Reducing the magnitude of SR Ca2+ content and release, whether experimentally by thapsigargin treatment, or in the model, desynchronized the Ca2+ transient. However, in cardiomyocytes isolated from SERCA2 knockout mice, RyR sensitization offset such effects. A similar interplay between RyR sensitivity and SR content was observed during treatment of myocytes with low-dose caffeine. Initial synchronization of Ca 2+ release during caffeine was reversed as SR content declined due to enhanced RyR leak. Thus, synchrony of cardiomyocyte Ca2+ release is not only determined by t-tubule organization but also by the interplay between RyR sensitivity and SR Ca2+ content. © 2013 Biophysical Society.


Iversen T.-G.,University of Oslo | Skotland T.,University of Oslo | Sandvig K.,University of Oslo
Nano Today | Year: 2011

During recent years there has been much interest in the use of nanoparticles for in vitro studies as well as for delivery of drugs and contrast agents in animals and humans. To this end it is necessary to increase our understanding of how these particles are taken up and transported within the cells, and to which extent they are metabolized and secreted. In this review we discuss the possibilities, challenges and pitfalls of studying endocytic pathways involved in cellular uptake of nanoparticles. Thus, the use of pharmacological inhibitors, expression of mutated proteins, use of siRNAs and colocalization experiments in such studies are critically evaluated. Although the main focus is on cellular uptake, also aspects of intracellular transport, recycling of nanoparticles to the cell exterior, disturbance of cellular functions, and metabolism of nanoparticles are discussed. © 2011 Elsevier Ltd. All rights reserved.


Nova A.,University of Oslo | Balcells D.,University of Oslo
Chemical Communications | Year: 2014

DFT and CCSD(T) calculations show that the weakest C-H bonds of N- and P-donor ligands are strengthened and deactivated upon metal-binding. The increase in C-H BDE and ΔG‡ for H abstraction ranges from ca. 1 to 15 kcal mol-1. This journal is © The Royal Society of Chemistry 2014.


Esayas S.Y.,University of Oslo
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

In recent years, businesses have faced large regulatory fines as a result of information security breaches. This signifies the need for businesses to account for legal issues when addressing their information security risks and to ensure that their day-to-day business operations do not violate legal norms of relevance to information security, such as data privacy laws. This paper offers a twofold contribution to this issue. First, it purposes that organizations' security risk analysis should be accompanied by an assessment of the legal implications of identified security risks. This enables organizations understand the associated legal risks they would face if the identified security risks were to materialize and prioritize the risks accordingly. Second, the paper underlines the need for security testing to support compliance checking. Particularly, the use of conformance testing would enhance organizations' level of assurance regarding their compliance with legal norms of relevance to information security. © 2014 Springer International Publishing Switzerland.


Knaevelsrud H.,University of Oslo | Simonsen A.,University of Oslo
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2012

The balance between protein and lipid biosynthesis and their eventual degradation is a critical component of cellular health. Autophagy, the catabolic process by which cytoplasmic material becomes degraded in lysosomes, can be induced by various physiological stimuli to maintain cellular homeostasis. Autophagy was for a long time considered a non-selective bulk process, but recent data have shown that unwanted components such as aberrant protein aggregates, dysfunctional organelles and invading pathogens can be selectively eliminated by autophagy. Recently, also intracellular lipid droplets were described as specific autophagic cargo, indicating that autophagy plays a role in lipid metabolism and storage (Singh et al., 2009 [1]). Moreover, over the past several years, it has become increasingly evident that lipids and lipid-modifying enzymes play important roles in the autophagy process itself, both at the level of regulation of autophagy and as membrane constituents required for formation of autophagic vesicles. In this review, we will discuss the interplay between lipids and autophagy, as well as the role of lipid-binding proteins in autophagy. We also comment on the possible implications of this mutual interaction in the context of disease. This article is part of a Special Issue entitled Lipids and Vesicular Transport. © 2012 Elsevier B.V.


Hahn C.,University of Oslo | Bachmann L.,University of Oslo | Chevreux B.,DSM Nutritional Products Ltd.
Nucleic Acids Research | Year: 2013

We present an in silico approach for the reconstruction of complete mitochondrial genomes of non-model organisms directly from next-generation sequencing (NGS) data - mitochondrial baiting and iterative mapping (MITObim). The method is straightforward even if only (i) distantly related mitochondrial genomes or (ii) mitochondrial barcode sequences are available as starting-reference sequences or seeds, respectively. We demonstrate the efficiency of the approach in case studies using real NGS data sets of the two monogenean ectoparasites species Gyrodactylus thymalli and Gyrodactylus derjavinoides including their respective teleost hosts European grayling (Thymallus thymallus) and Rainbow trout (Oncorhynchus mykiss). MITObim appeared superior to existing tools in terms of accuracy, runtime and memory requirements and fully automatically recovered mitochondrial genomes exceeding 99.5% accuracy from total genomic DNA derived NGS data sets in <24 h using a standard desktop computer. The approach overcomes the limitations of traditional strategies for obtaining mitochondrial genomes for species with little or no mitochondrial sequence information at hand and represents a fast and highly efficient in silico alternative to laborious conventional strategies relying on initial long-range PCR. We furthermore demonstrate the applicability of MITObim for metagenomic/pooled data sets using simulated data. MITObim is an easy to use tool even for biologists with modest bioinformatics experience. The software is made available as open source pipeline under the MIT license at https://github.com/chrishah/MITObim. © 2013 The Author(s) 2013. Published by Oxford University Press.


Verbeke C.S.,Karolinska University Hospital | Gladhaug I.P.,University of Oslo
British Journal of Surgery | Year: 2012

Background: Assessment of the origin of adenocarcinoma in pancreatoduodenectomy specimens (pancreatic, ampullary or biliary) and resection margin status is not performed in a consistent manner in different centres. The aim of this review was to identify the impact of such variations on patient outcome. Methods: A systematic literature search for articles on pancreatic, ampullary, distal bile duct and periampullary cancer was performed, with special attention to data on resection margin status, pathological examination and outcome. Results: The frequent reclassification of tumour origin following slide review, and the wide variation in published incidence of pancreatic (33-89 per cent), ampullary (5-42 per cent) and distal bile duct (5-38 per cent) cancers indicate that the histopathological distinction between the three cancer groups is less accurate than generally believed. Recent studies have shown that the wide range of rates of microscopic margin involvement (R1) in pancreatoduodenectomy specimens (18-85, 0-27 and 0-72 per cent respectively for pancreatic, ampullary and distal bile duct cancers) is mainly caused by differences in pathological assessment rather than surgical practice and patient selection. As a consequence of the existing inconsistency in reporting of these data items, the clinical significance of microscopic margin involvement in each of the three cancer groups remains unclear. Conclusion: Inaccurate and inconsistent distinction between pancreatic, ampullary and distal bile duct cancer, combined with inaccuracies in resection margin assessment, results in obfuscation of key clinicopathological data. Specimen dissection technique plays a key role in the quality of the assessment of both tumour origin and margin status. Unless the pathological examination is meticulous and standardized, comparison of results between centres and observations in multicentre trials will remain of limited value. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


van Hinsbergen D.J.J.,University of Oslo
Earth-Science Reviews | Year: 2010

This paper provides a review of the structure and metamorphism of the Menderes Massif in western Turkey, and subsequently a map-view restoration of its Neogene unroofing history. Exhumation of this massif - among the largest continental extensional provinces in the world - is generally considered to have occurred along extensional detachments with a NE-SW stretching direction. Restoration of the early Miocene history, however, shows that these extensional detachments can only explain part of the exhumation history of the Menderes Massif, and that NE-SW stretching can only be held accountable for half, or less, of the exhumation.Restoration back to ~ 15. Ma is relatively straightforward, and is mainly characterised by a previously reported 25-30° vertical axis rotation difference between the northern Menderes Massif, and the Southern Menderes Massif and overlying HP nappes, Lycian Nappes and Bey Daǧlari about a pivot point close to Denizli. To the west of this pole, the rotation was accommodated by exhumation of the Central Menderes core complex since middle Miocene times, and to the east probably by shortening.At the end of the early Miocene, the Menderes Massif formed a rectangular, NE-SW trending tectonic window of ~ 150 × 100km. Geochronology suggests unroofing between ~ 25 and 15Ma. The north-eastern Menderes Massif was exhumed along the early Miocene Simav detachment, over a distance of ~ 50. km. The accommodation of the remainder of the exhumation is enigmatic, but penetrative NE-SW stretching lineations throughout the Menderes Massif suggest a prominent role of NE-SW extension. This, however, requires that the eastern margin of the Menderes Massif, bordering a region without significant extension, is a transform fault with an offset of ~ 150. km, cutting through the Lycian Nappes. For this, there is no evidence.The Lycian Nappes - a non-metamorphic stack of sedimentary thrust slices and an overlying ophiolite and ophiolitic mélange - have been previously shown to thrust to the SE between 23 and 15. Ma over at least 75. km. This is contemporaneous with, and orthogonal to stretching along the Simav detachment. I here argue that the amount of SE-wards displacement of the Lycian Nappes was twice the minimum amount of 75km, which would restore them back on top of most of the Menderes Massif, apart from the ~ 50. km unroofed along the Simav detachment. A decollement was likely formed by a high-pressure, low-temperature metamorphosed nappe immediately underlying the Lycian Nappes in the north - the Ören unit. Latest Oligocene to early Miocene fission track ages of the Menderes Massif, as well as NE-SW trending lower Miocene grabens on the Massif are in line with this hypothesis.The main implications of this restoration are that 1) the eastern part of the Aegean back-arc accommodated not more than 50. km of NE-SW extension in the early Miocene, and 2) any pre-Miocene exhumation of the Menderes Massif cannot be attributed to the known extensional detachments. The restoration in this paper suggests that most of the Menderes Massif already resided at upper crustal levels at the inception of extensional detachment faulting, a situation reminiscent of the role of extensional detachments on the island of Crete. © 2010 Elsevier B.V.


Bergersen L.H.,University of Oslo | Bergersen L.H.,Copenhagen University
Journal of Cerebral Blood Flow and Metabolism | Year: 2015

Lactate acts as a 'buffer' between glycolysis and oxidative metabolism. In addition to being exchanged as a fuel by the monocarboxylate transporters (MCTs) between cells and tissues with different glycolytic and oxidative rates, lactate may be a 'volume transmitter' of brain signals. According to some, lactate is a preferred fuel for brain metabolism. Immediately after brain activation, the rate of glycolysis exceeds oxidation, leading to net production of lactate. At physical rest, there is a net efflux of lactate from the brain into the blood stream. But when blood lactate levels rise, such as in physical exercise, there is net influx of lactate from blood to brain, where the lactate is used for energy production and myelin formation. Lactate binds to the lactate receptor GPR81 aka hydroxycarboxylic acid receptor (HCAR1) on brain cells and cerebral blood vessels, and regulates the levels of cAMP. The localization and function of HCAR1 and the three MCTs (MCT1, MCT2, and MCT4) expressed in brain constitute the focus of this review. They are possible targets for new therapeutic drugs and interventions. The author proposes that lactate actions in the brain through MCTs and the lactate receptor underlie part of the favorable effects on the brain resulting from physical exercise. © 2015 ISCBFM All rights reserved.


Collas P.,University of Oslo | Lund E.G.,University of Oslo | Oldenburg A.R.,University of Oslo
BioEssays | Year: 2014

The nuclear envelope shapes the functional organization of the nucleus. Increasing evidence indicates that one of its main components, the nuclear lamina, dynamically interacts with the genome, including the promoter region of specific genes. This seems to occur in a manner that accords developmental significance to these interactions. This essay addresses key issues raised by recent data on the association of nuclear lamins with the genome. We discuss how lamins interact with large chromatin domains and with spatially restricted regions on gene promoters. We address the relationship between these interactions, chromatin modifications and gene expression outcomes. Lamin-genome contacts are redistributed after cell division and during stem cell differentiation, with evidence of lineage specificity. Thus, we also speculate on a developmental role of lamin interactions with specific genes. Finally, we highlight how concepts arising from this recent work lay the foundations of future challenges and investigations. © 2014 WILEY Periodicals, Inc.


OBJECTIVE: To compare systolic cardiac function in patients with juvenile dermatomyositis (JDM) with matched controls and examine associations between systolic and diastolic cardiac function and disease variables.METHODS: Fifty-nine patients, examined at follow-up, median 16.8 years (2-38 years) after disease onset, were compared with 59 age-matched and sex-matched controls. Echocardiography was performed and analysed blinded to patient information. We used mitral annulus displacement to assess the relative long-axis shortening of the left ventricle (long-axis strain) and early diastolic tissue velocity (e'), as markers for systolic and diastolic function, respectively. Disease activity and organ damage were assessed at follow-up by clinical examination and retrospectively by chart review.RESULTS: Long-axis strain was reduced in patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001), whereas no difference was seen between patients with active and inactive disease. Disease duration correlated with systolic and diastolic function (rsp=-0.50 and rsp=-0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=-0.36 and rsp=-0.46) and MDI at follow-up (rsp=-0.33 and rsp=-0.60), all p<0.01. High early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle, predicted systolic (standardised β=-0.28, p=0.011, R(2)=48%) and diastolic dysfunction (β=-0.36, p<0.001, R(2)=72%) at follow-up.CONCLUSIONS: Long-axis strain was reduced in JDM patients compared with controls, suggesting systolic dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1 year. This indicates a common pathway to two different cardiac manifestations in JDM, perhaps with similar pathogenesis as skin affection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.


Mills I.G.,University of Oslo
Seminars in Cell and Developmental Biology | Year: 2012

Cellular signal transduction in response to environmental signals involves a relay of precisely regulated signal amplifying and damping events. A prototypical signaling relay involves ligands binding to cell surface receptors and triggering the activation of downstream enzymes to ultimately affect the subcellular distribution and activity of DNA-binding proteins that regulate gene expression. These so-called signal transduction cascades have dominated our view of signaling for decades. More recently evidence has accumulated that components of these cascades can be multifunctional, in effect playing a conventional role for example as a cell surface receptor for a ligand whilst also having alternative functions for example as transcriptional regulators in the nucleus. This raises new challenges for researchers. What are the cues/triggers that determine which role such proteins play? What are the trafficking pathways which regulate the spatial distribution of such proteins so that they can perform nuclear functions and under what circumstances are these alternative functions most relevant? © 2011 Elsevier Ltd.


Sekse D.H.,University of Oslo | Van Der Voort L.R.,University of Oslo | De Pontieu B.,Lockheed Martin
Astrophysical Journal | Year: 2013

The newly established type II spicule has been speculated to provide enough hot plasma to play an important role in the mass loading and heating of the solar corona. With the identification of rapid blueshifted excursions (RBEs) as the on-disk counterpart of type II spicules we have analyzed three different high-quality timeseries with the CRisp Imaging SpectroPolarimeter (CRISP) at the Swedish Solar Telescope on La Palma and subjected to an automated detection routine to detect a large number of RBEs for statistical purposes. Our observations are of a quiet-Sun region at disk center and we find lower Doppler velocities, 15-40 km s-1, and Doppler widths, 2-15 km s-1, of RBEs than in earlier coronal hole studies, 30-50 km s-1 and 7-23 km s-1, respectively. In addition, we examine the spatial dependence of Doppler velocities and widths along the RBE axis and conclude that there is no clear trend to this over the field of view or in individual RBEs in the quiet Sun at disk center. These differences with previous coronal hole studies are attributed to the more varying magnetic field configuration in quiet-Sun conditions. Using an extremely high-cadence data set has allowed us to improve greatly on the determination of lifetimes of RBEs, which we find to range from 5 to 60 s with an average lifetime of 30 s, as well as the transverse motions in RBEs, with transverse velocities up to 55 km s-1 and averaging 12 km s-1. Furthermore, our measurements of the recurrence rates of RBEs provide important new constraints on coronal heating by spicules. We also see many examples of a sinusoidal wave pattern in the transverse motion of RBEs with periods averaging 54 s and amplitudes from 21.5 to 129 km which agrees well with previous studies of wave motion in spicules at the limb. We interpret the appearance of RBEs over their full length within a few seconds as the result of a combination of three kinds of motions as is earlier reported for spicules. Finally, we look at the temporal connection between Hα and Ca II 8542 RBEs and find that Ca II 8542 RBEs in addition to being located closer to the footpoint also appear before the Hα RBEs. This connection between Ca II 8542 and Hα supports the idea that heating is occurring in spicules and contributes more weight to the prominence of spicules as a source for heating and mass loading of the corona. © 2013. The American Astronomical Society. All rights reserved.


Bakland G.,University of Tromsø | Gran J.T.,University of Oslo | Nossent J.C.,University of Tromsø
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.


Larsson A.O.,University of Oslo
Journal of Broadcasting and Electronic Media | Year: 2013

Twitter is currently one of the most popular outlets of so-called social media, Internet services that allow their users to communicate and share content in a variety of ways. As with the Internet itself, Twitter has been heralded to hold interesting possibilities within the context of journalism-potentially bringing journalists and their respective audiences closer to each other through supposedly common Twitter practices like @ messages and retweeting. This article presents a large-scale empirical study on Twitter use in the journalistic context. The aim is to assess patterns of journalist-audience interaction on Twitter. Specifically, the article outlines a structural analysis of Twitter use pertaining to the first season of the current events talk show Hübinette, which aired on Swedish public service television during the fall of 2011. Employing state-of-the-art approaches for data collection and analysis, the article shows that while traditional patterns of journalist-reader relationships are most common, some users are employing the Twitter platform in somewhat unforeseen ways. © 2013 Copyright Taylor and Francis Group, LLC.


Nagelhus E.A.,University of Oslo | Ottersen O.P.,University of Oslo
Physiological Reviews | Year: 2013

Aquaporin-4 (AQP4) is one of the most abundant molecules in the brain and is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. While AQP4 has been implicated in a number of pathophysiological processes, its role in brain physiology has remained elusive. Only recently has evidence accumulated to suggest that AQP4 is involved in such diverse functions as regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, interstitial fluid resorption, waste clearance, neuroinflammation, osmosensation, cell migration, and Ca2+ signaling. AQP4 is also required for normal function of the retina, inner ear, and olfactory system. A review will be provided of the physiological roles of AQP4 in brain and of the growing list of data that emphasize the polarized nature of astrocytes. © 2013.


Schink K.O.,University of Oslo | Raiborg C.,University of Oslo | Stenmark H.,University of Oslo
BioEssays | Year: 2013

Phosphatidylinositol 3-phosphate (PtdIns3P) is generated on the cytosolic leaflet of cellular membranes, primarily by phosphorylation of phosphatidylinositol by class II and class III phosphatidylinositol 3-kinases. The bulk of this lipid is found on the limiting and intraluminal membranes of endosomes, but it can also be detected in domains of phagosomes, autophagosome precursors, cytokinetic bridges, the plasma membrane and the nucleus. PtdIns3P controls cellular functions through recruitment of specific protein effectors, many of which contain FYVE or PX domains. Cellular processes known to be controlled by PtdIns3P and its effectors include endosomal fusion, sorting and motility, autophagy, cytokinesis, regulated exocytosis and signal transduction. Here we discuss how Ptdins3P is generated on specific cellular membranes, how its localizations and functions can be studied, and how its effectors serve to control cellular functions. © 2013 WILEY Periodicals, Inc.


Linden A.,University of Oslo | Mantyniemi S.,University of Helsinki
Ecology | Year: 2011

A Poisson process is a commonly used starting point for modeling stochastic variation of ecological count data around a theoretical expectation. However, data typically show more variation than implied by the Poisson distribution. Such overdispersion is often accounted for by using models with different assumptions about how the variance changes with the expectation. The choice of these assumptions can naturally have apparent consequences for statistical inference. We propose a parameterization of the negative binomial distribution, where two overdispersion parameters are introduced to allow for various quadratic mean-variance relationships, including the ones assumed in the most commonly used approaches. Using bird migration as an example, we present hypothetical scenarios on how overdispersion can arise due to sampling, flocking behavior or aggregation, environmental variability, or combinations of these factors. For all considered scenarios, mean-variance relationships can be appropriately described bthe negative binomial distribution with two overdispersion parameters. To illustrate, we apply the model to empirical migration data with a high level of overdispersion, gaining clearly different model fits with different assumptions about mean-variance relationships. The proposed framework can be a useful approximation for modeling marginal distributions of independent count data in likelihood-based analyses. © 2011 by the Ecological Society of America..


Rouppe Van Der Voort L.,University of Oslo | De La Cruz Rodriguez J.,Uppsala University
Astrophysical Journal | Year: 2013

Sunspot chromospheres display vigorous oscillatory signatures when observed using chromospheric diagnostics such as the strong Ca II lines and Hα. New high-resolution sunspot observations from the Swedish 1 m Solar Telescope show the ubiquitous presence of small-scale, periodic, jet-like features that move up and down. This phenomenon has not been described before. The typical width of these features is about 0.″3 and they display clear parabolic trajectories in space-time diagrams. The maximum extension of the top of the jets is lowest in the umbra, a few 100 km, and progressively longer further away from the umbra in the penumbra, with the longest extending more than 1000 km. These jets resemble the dynamic fibrils found in plage regions but at smaller extensions. Local thermodynamic equilibrium inversion of spectropolarimetric Ca II 8542 observations enabled a comparison of the magnetic field inclination and properties of these short jets. We find that the most extended of these jets also have longer periods and tend to be located in regions with more horizontal magnetic fields. These results are direct observational confirmation of the mechanism of long-period waves propagating along inclined magnetic fields into the solar chromosphere. This mechanism was identified earlier as the driver of dynamic fibrils in plage, part of the mottles in the quiet Sun, and the type I spicules at the limb. The sunspot dynamic fibrils that we report here represent a new class of manifestation of this mechanism, distinct from the transient penumbral and umbral micro-jets reported earlier. © 2013. The American Astronomical Society. All rights reserved.


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.


Sioud M.,University of Oslo | Mobergslien A.,University of Oslo
Bioconjugate Chemistry | Year: 2012

Small interfering RNAs (siRNAs) have displayed considerable promise for the treatment of cancer. However, their delivery to the desired cell population remains a challenging task. Here we have covalently conjugated a siRNA against survivin to gastrin-releasing peptides (GRPs) to direct siRNA molecules to cancer cells that express the GRP receptor. The cellular uptake of the peptide-siRNA conjugates was tested in breast MDA-MB 231 cancer cells, which express the GRP receptor. Fluorescein-tagged GRP-siRNA conjugates were taken up by cancer cells but not normal mammary epithelial cells or human blood monocytes. By 120 min of incubation, most of the cells have taken up the conjugates. Excess free peptide inhibited uptake, implying dependence of uptake on GRP receptor. Moreover, bitargeting of siRNA molecules by GR and luteinizing hormone-releasing peptides accelerated the uptake kinetics by MDA-MB 231 cells when compared to monotargeted siRNAs. Peptide-siRNA conjugates, but not free siRNAs, inhibited the expression of survivin, an endogenous gene involved in cancer cell survival. None of the peptide-siRNA conjugates induced the expression of inflammatory cytokines or interferon α in human blood leukocytes. Overall, the data demonstrate the feasibility of GRP receptor-mediated targeted delivery of siRNAs to cancer cells, an important step for RNA interference therapy in humans. © 2012 American Chemical Society.


Bard S.,University of Oslo | Carlsson M.,University of Oslo
Astrophysical Journal | Year: 2010

We investigate the formation and evolution of the Ca ii H line in a sunspot. The aim of our study is to establish the mechanisms underlying the formation of the frequently observed brightenings of small regions of sunspot umbrae known as "umbral flashes." We perform fully consistent NLTE radiation hydrodynamic simulations of the propagation of acoustic waves in sunspot umbrae and conclude that umbral flashes result from increased emission of the local solar material during the passage of acoustic waves originating in the photosphere and steepening to shock in the chromosphere. To quantify the significance of possible physical mechanisms that contribute to the formation of umbral flashes, we perform a set of simulations on a grid formed by different wave power spectra, different inbound coronal radiation, and different parameterized chromospheric heating. Our simulations show that thewaves with frequencies in the range 4.5-7.0 mHz are critical to the formation of the observed blueshifts of umbral flashes while waves with frequencies below 4.5 mHz do not play a role despite their dominance in the photosphere. The observed emission in the Ca ii H core between flashes only occurs in the simulations that include significant inbound coronal radiation and/or extra non-radiative chromospheric heating in addition to shock dissipation. © 2010. The American Astronomical Society.


Nordal E.J.,University of Oslo | Guleng G.E.,University of Oslo
Journal of the European Academy of Dermatology and Venereology | Year: 2011

Background Only a few, small double-blind clinical trials have been reported for the treatment of vitiligo. Narrowband-ultraviolet B (NB-UVB) is an established form of treatment for this condition. Tacrolimus ointment is assumed to have an effect in some patients. Objectives To assess the additive effect of tacrolimus ointment (0.1%) once daily in vitiligo patients treated with NB-UVB. Methods In a randomized double-blind trial, patients with stable symmetrical vitiligo were treated half-side with tacrolimus ointment (0.1%) and half-side with placebo ointment. Whole body NB-UVB was given twice or thrice weekly for at least 3 months. As a morphometric device, Visitrak™ was used to measure the area of the vitiligo target lesions. Results Of 40 patients, 27 had a better effect on the tacrolimus side. The degree of improvement was significantly better on the tacrolimus side (P = 0.005). The median reduction in the target lesion areas was 42.1% on the tacrolimus side and 29% on the placebo side. There was a correlation between the effect and the number of topical tacrolimus applications (P = 0.044), but there was no correlation with the number of UV treatments given; neither any significance of gender, age, skin type, duration of disease, familial occurrence of vitiligo nor presence of other autoimmune disease or atopy was observed. We found a significant reduction in the patients' subjective disease impact during the treatment period (P < 0.001). Conclusion According to this study, the combination of NB-UVB and tacrolimus ointment (0.1%) is more effective than UV treatment alone in patients with vitiligo. The effect is tacrolimus total dose-dependent. © 2011 European Academy of Dermatology and Venereology.


Santos P.,University of Oslo
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

This paper aims to introduce a new parameterisation for the coupling Q in interacting dark matter and dark energy models by connecting said models with the Continuous Tower of Scalar Fields model. Based upon the existence of a dark matter and a dark energy sectors in the Continuous Tower of Scalar Fields, a simplification is considered for the evolution of a single scalar field from the tower, validated in this paper. This allows for the results obtained with the Continuous Tower of Scalar Fields model to match those of an interacting dark matter-dark energy system, considering that the energy transferred from one fluid to the other is given by the energy of the scalar fields that start oscillating at a given time, rather than considering that the energy transference depends on properties of the whole fluids that are interacting. © 2015 The Author.


Nilsson G.E.,University of Oslo | Lefevre S.,University of Oslo
Physiology | Year: 2016

With the projected levels of global warming and ocean acidification, fishes have to face warmer waters with CO2 levels that are the highest in over 30 million years. The resultant rise in body temperature means that metabolic rates of fish will increase, and some may become energetically compromised. No less worrying, and maybe more surprising, is that rising CO2 concentrations appear to trigger pH regulatory mechanisms that disrupts neural ion gradients, leading to altered neurotransmitter funct