Gothenburg, Sweden
Gothenburg, Sweden

The University of Gothenburg is a university in Sweden's second largest city, Gothenburg.The University of Gothenburg is the third-oldest of the current Swedish universities, and with 24,900 full-time students it is also among the largest universities in the Nordic countries. Wikipedia.


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Ronnback K.,Gothenburg University
Environment and History | Year: 2017

The paper studies the case of water pollution in Sweden, and how the city of Gothenburg had to struggle with this issue in order to secure a source of fresh water to satisfy its demand for drinking water. It is argued in the paper that the city employed a wide variety of strategies, ranging from water treatment to acquiring property rights over the watershed that provides its water. Most importantly, the city was interested in reducing the levels of pollution in the river, and consequently became a key stakeholder in the enforcement and implementation of effective environmental legislation. © 2017 The White Horse Press.


Andersson M.,Gothenburg University
American Naturalist | Year: 2017

Costly help can raise a relative’s reproduction, survival, and reproductive value and increase the inclusive fitness of the donor of help. Donor fitness is explored here in conspecific brood parasitism. In this alternative reproductive tactic, some females, “parasites,” lay eggs in nests of other females of the same species, “hosts,” suppliers of help that alone take care of the offspring. Modeling shows that hosts can gain inclusive fitness if parasitized by relatives whose reproduction or survival is thereby increased. These predictions are explored in waterfowl with frequent brood parasitism, female-biased philopatry, and neighbor relatedness. Approximate estimates based on waterfowl reproductive and life-history data show that host inclusive-fitness gain is often possible with related parasites. The largest gains can be achieved through increased reproduction, but gain is also possible through higher survival of parasites that avoid increased predation and other risks of nesting. Inclusive fitness depends on parasite reproductive value and can be highest for a host parasitized by her mother and for old, senescent hosts with low fecundity, helping young related parasites. These results and observed levels of host-parasite relatedness suggest that being “parasitized” in waterfowl is sometimes neutral or even advantageous because of inclusive-fitness benefits, contributing to evolution of frequent conspecific brood parasitism in this group. © 2016 by The University of Chicago.


Gottschling D.E.,Calico Life science | Nystrom T.,Gothenburg University
Cell | Year: 2017

Interconnectivity and feedback control are hallmarks of biological systems. This includes communication between organelles, which allows them to function and adapt to changing cellular environments. While the specific mechanisms for all communications remain opaque, unraveling the wiring of organelle networks is critical to understand how biological systems are built and why they might collapse, as occurs in aging. A comprehensive understanding of all the routes involved in inter-organelle communication is still lacking, but important themes are beginning to emerge, primarily in budding yeast. These routes are reviewed here in the context of sub-system proteostasis and complex adaptive systems theory. © 2017 Elsevier Inc.


Gustafsson D.R.,University of Utah | Olsson U.,Gothenburg University
Systematic Entomology | Year: 2017

The louse genus Carduiceps Clay & Meinertzhagen, 1939 is widely distributed on sandpipers and stints (Calidrinae). The current taxonomy includes three species on the Calidrinae (Carduiceps meinertzhageni, Carduiceps scalaris, Carduiceps zonarius) and four species on noncalidrine hosts. We estimated a phylogeny of four of the seven species of Carduiceps (the three mentioned above and Carduiceps fulvofasciatus) from 13 of the 29 hosts based on three mitochondrial loci, and evaluated the relative importance of flyway differentiation (same host species has different lice along different flyways) and flyway homogenization (different host species have the same lice along the same flyway). We found no evidence for either process. Instead, the present, morphology-based, taxonomy of the genus corresponds exactly to the gene-based phylogeny, with all four included species monophyletic. Carduiceps zonarius is found both to inhabit a wider range of hosts than wing lice of the genus Lunaceps occurring on the same group of birds, and to occur on Calidris sandpipers of all sizes, both of which are unexpected for a body louse. The previously proposed family Esthiopteridae is found to be monophyletic with good support. The concatenated dataset suggests that the pigeon louse genus Columbicola may be closely related to the auk and diver louse genus Craspedonirmus. These two genera share some morphological characters with Carduiceps, but no support was obtained for grouping these three genera together. Based on mitochondrial data alone, the relationships among genera within this proposed family cannot be properly assessed, but some previously suggested relationships within this proposed family are confirmed. © 2017 The Royal Entomological Society.


There is considerable variability in attitudes towards climate change between citizens of different countries. By using individual-level and country-level data, I examine if this variability in public opinion is partially caused by political party elites. The results show that when elites are united in their support for environmental issues, the perceived threat of climate change is higher than in countries where party elites are divided. The results also demonstrate that the perceived threat influences behavior related to climate change, and that threat mediates the effect of party positions. Consequently, the effect of party elites is stronger than previously acknowledged. The models rely on Generalized Method of Moments estimation and instrumental variables with clustering on EU member-states. © 2017 by the authors.


Hallberg B.,Gothenburg University | Palmer R.H.,Gothenburg University
Annals of Oncology | Year: 2016

A vast array of oncogenic variants has been identified for anaplastic lymphoma kinase (ALK). Therefore, there is a need tobetter understand the role of ALK in cancer biology in order to optimise treatment strategies. This review summarises thelatest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients withcancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, includingpoint mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK andthe amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associatedprotein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusionproteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substratespecificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe foruse in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within theATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutationpatterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature ofeach patient. Research into the oncogenic functions of ALK, and fast paced development of ALK inhibitors, has substantiallyimproved outcomes for patients with ALK-positive NSCLC. Limited data are available surrounding the physiologicalligand-stimulated activation of ALK signalling and further research is needed. Understanding the role of ALK in tumourbiology is key to further optimising therapeutic strategies for ALK-positive disease. © The Author 2016.


Brannstrom M.,Gothenburg University
Journal of Materials Science: Materials in Medicine | Year: 2017

Uterus transplantation is today the only available treatment for absolute uterine factor infertility which is caused by either congenital/surgical uterine absence or that a present uterus is non-functioning. Structured animal-based research, from rodents to nonhuman primates, was the scientific basis for a successful introduction of uterus transplantation as a clinical procedure. The patient groups for uterus transplantation, the preclinical research and data from the published human cases will be covered herein. During recent years the concept of bioengineering of organs and tissues has emerged. Creation of a bioengineered uterus is in the initial research state, with experiments performed in rodents. The research that has been performed to create a bioengineered uterus will be summarized. In conclusion, uterus transplantation is now a clinical experimental procedure for treatment of uterine factor infertility. In parallel to the establishment of this combined assisted reproduction technique and transplantation procedure as a routine clinical procedure, we predict that uterus bioengineering will develop further towards introduction within the human setting, but that this process will take several years. © 2017, The Author(s).


Paerregaard K.,Gothenburg University
Climate and Development | Year: 2017

What are the lessons from development practice that adaptation interventions can use to engage vulnerable people? To answer this question, the paper reviews field data on perceptions of environmental and climatic change in a Peruvian mountain community and discusses the possibilities and limitations of using local climate voices to prepare for climate change adaptation. The data comprise two complementary household surveys. The first survey provides information on the community’s socio-economic situation, whilst the second survey documents the villagers’ climate perception. The data reveal a paradox in the way the community understands global climate change. The villagers who live on the margin of the global world and belong to the poorest economic strata in Peru are deeply concerned about global climate change that is impacting their environment. Yet when locating the cause of climate change they point to their own community rather the industrialized world and suggest mitigation actions rather than adaptation initiatives as answer to the problems it entails. The paper suggests that adaptation initiatives must understand this paradox within the larger socio-economic and discursive context that shapes the villagers’ agency and climate perceptions. It proposes an informed participation approach that listens to the local voices but that also informs them about the global dimensions of climate change and engages them in a critical dialogue about the importance of sustainable development and the possibilities of taking advantage of the new opportunities that the changing environment offers. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Zhang C.,CAS Beijing Institute of Geographic Sciences and Nature Resources Research | Tang Q.,CAS Beijing Institute of Geographic Sciences and Nature Resources Research | Chen D.,Gothenburg University
Journal of Climate | Year: 2017

Evidence has suggested a wetting trend over part of the Tibetan Plateau (TP) in recent decades, although there are large uncertainties in this trend due to sparse observations. Examining the change in the moisture source for precipitation over a region in the TP with the most obvious increasing precipitation trend may help understand the precipitation change. This study applied the modified Water Accounting Model with two atmospheric reanalyses, ground-observed precipitation, and evaporation froma land surfacemodel to investigate the change inmoisture source of the precipitation over the targeted region. The study estimated that on average more than 69%andmore than 21%of the moisture supply to precipitation over the targeted region came from land and ocean, respectively. The moisture transports from the west of the TP by the westerlies and from the southwest by the Indian summermonsoon likely contributed themost to precipitation over the targeted region. The moisture from inside the region may have contributed about 18% of the total precipitation. Most of the increasedmoisture supply to the precipitation during 1979-2013 was attributed to the enhanced influx fromthe southwest and the local moisture supply. The precipitation recycling ratio over the targeted region increased significantly, suggesting an intensified hydrological cycle. Further analysis at monthly scale and with wet-dryyear composites indicates that the increased moisture contribution was mainly from the southwest and the targeted region duringMay and September. The enhanced water vapor transport from the IndianOcean during July and September and the intensified local hydrological recycling seem to be the primary reasons behind the recent precipitation increase over the targeted region. © 2017 American Meteorological Society.


Leposa N.,Gothenburg University
Journal of Cleaner Production | Year: 2017

Through a case study of leisure boating along the Swedish West Coast, this study explores how two conflicting roles – consumers and environmental citizens – produce and are produced by a highly ambivalent neoliberal discourse. On the one hand, this discourse supports economic growth and increasing consumption, while on the other hand it expects consumers to consider the environmental impacts of their actions and make pro-environmental choices. Through a mixed-method approach based on the application of consumer value theory (CVT) in combination with a motivation-opportunity-ability (MOA) model, this study demonstrates how the consumer role is predominantly produced and reproduced through social pressure and market forces as well as emotional and habitual attachment to boat-life and boating. This (re)production of the consumer role conflicts with the environmental citizenship role, as boaters agree that protection is needed while they also put high value on the sea as a place of freedom. The study suggests that there is a need for an environmental policy that recognises how the consumer role is produced and reproduced. Such policy should move beyond the assumption of the sovereignty of the individual and focus more closely on the interaction between humans and the sea. © 2017 Elsevier Ltd


Dupont S.,Gothenburg University
Journal of the Marine Biological Association of the United Kingdom | Year: 2017

Recent events in world politics demonstrate that a part of society has lost faith in their institutions. The importance of facts and evidence in citizens’ decision making is weakened by opinions and belief systems. This post-fact or alternate facts era is a new challenge in the field of science communication as we urgently need to tackle global environmental challenges. Not only do scientists need to better communicate their work, they also need to explore alternative ways of transferring knowledge to help citizens reconnect with nature and actively take responsible decisions to protect it. The activity ‘I am the Ocean’ has been developed by an artist and a scientist with the goal to help students understand, connect and be equipped to take actions on marine global changes. The activity was a mix of field trips, open discussions and sensory immersion. It illustrates how art and metaphors can add an emotional and physical dimension to science communication, allowing a better understanding of otherwise invisible threats, and move from knowledge to passion. Copyright © Marine Biological Association of the United Kingdom 2017


Interdisciplinary collaboration, particularly between natural and social sciences, is perceived as crucial to solving the significant challenges facing humanity. However, despite the need for such collaboration being expressed more frequently and intensely, it remains unclear to what degree such collaboration actually takes place, what trends and developments there are and which actors are involved. Previous studies, often based on bibliometric analysis of large bodies of literature, partly observed an increase in interdisciplinary collaboration in general, but in particular, the collaboration among distant fields was less explored. Other more qualitative studies found that interdisciplinary collaboration, particularly between natural and social scientists was not well developed, and obstacles abounded. To shed some light on the actual status and developments of this collaboration, we performed an analysis based on a sample of articles on groundwater research. We first identified journals and articles therein that potentially combined natural and social science aspects of groundwater research. Next, we analysed the disciplinary composition of their authors' teams, cited references, titles and keywords, making use of our detailed personal expertise in groundwater research and its interdisciplinary aspects. We combined several indicators developed from this analysis into a final classification of the degree of multidisciplinarity of each article. Covering the period between 1990 and 2014, we found that the overall percentage of multidisciplinary articles was in the low single-digit range, with only slight increases over the past decades. The interdisciplinarity of individuals plays a major role compared to interdisciplinarity involving two or more researchers. If collaboration with natural sciences takes place, social science is represented most often by economists. As a side result, we found that journals publishing multidisciplinary research had lower impact factors on average, and multidisciplinary papers were cited much less than mono-disciplinary ones. © 2017 Barthel, Seidl. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Svahn F.,Gothenburg University | Mathiassen L.,Georgia State University | Lindgren R.,Gothenburg University | Lindgren R.,University of Borås
MIS Quarterly: Management Information Systems | Year: 2017

Past research provides instructive yet incomplete answers as to how incumbent firms can address competing concerns as they embrace digital innovation. In particular, it offers only partial explanations of why different concerns emerge, how they manifest, and how firms can manage them. In response, we present a longitudinal case study of Volvo Cars'connected car initiative. Combining extant literature with insights from the case, we argue that incumbent firms face four competing concerns-capability (existing versus requisite), focus (product versus process), collaboration (internal versus external), and governance (control versus flexibility)- and that these concerns are systemically interrelated. Firms must therefore manage these concerns cohesively by continuously balancing new opportunities and established practices.


Themistocleous C.,Gothenburg University
Phonetica | Year: 2017

This study investigates the acoustic properties of vowels in 2 Modern Greek varieties: Standard Modern Greek (SMG) and Cypriot Greek (CG). Both varieties contain in their phonetic inventories the same 5 vowels. Forty-five female speakers between 19 and 29 years old participated in this study: 20 SMG speakers and 25 CG speakers, born and raised in Athens and Nicosia, respectively. Stimuli consisted of a set of nonsense CVCV and VCV words, each containing 1 of the 5 Greek vowels in stressed and unstressed position. Gaining insights from the controlled experimental design, the study sheds light on the gradient effects of vowel variation in Modern Greek. It shows that (1) stressed vowels are more peripheral than unstressed vowels, (2) SMG unstressed /i a u/ vowels are more raised than the corresponding CG vowels, (3) SMG unstressed vowels are shorter than CG unstressed vowels, and (4) SMG /i·u/ are more rounded than the corresponding CG vowels. Moreover, it shows that variation applies to specific subsystems, as it is the unstressed vowels that vary cross-varietally whereas the stressed vowels display only minor differences. The implications of these findings with respect to vowel raising and vowel reduction are discussed. © 2017 S. Karger AG, Basel


Shelke G.V.,Gothenburg University | Lasser C.,Gothenburg University | Gho Y.S.,Pohang University of Science and Technology | Lotvall J.,Gothenburg University
Journal of Extracellular Vesicles | Year: 2014

Extracellular vesicles (EVs), including the nano-sized exosomes, have the capacity to transfer multiple functional molecules between cells. In cell culture experiments, fetal bovine serum (FBS) is often used to supplement cell culture medium as a nutrient, but it is important to know that the FBS also contain significant quantities of EVs. The aim of the current study was to determine whether the FBS EVs can influence cultured cell phenotype, and secondly to determine the efficiency of FBS-EVelimination protocols. Firstly, FBS that had not been depleted of EVs induced a migratory phenotype in a lung cancer epithelial cell line (A549 cells), an effect that could be mimicked by isolated FBS EVs alone. FBS-derived EVs also contained RNA, which was protected from consecutive proteinase K and RNase A treatment. Comparison of common isolation protocols suggested that an 18-hour centrifugation period eliminates approximately 95% of RNA-containing FBS EVs, whereas a 1.5-hour protocol is insufficient. In conclusion, this study shows that FBS EVs substantially influence cultured cell behaviour, but also that they can be virtually removed by an 18-hour ultracentrifugation protocol. © 2014 Ganesh Vilas Shelke et al.


Fandriks L.,Gothenburg University
Journal of Internal Medicine | Year: 2017

The metabolic syndrome is a cluster of risk factors (central obesity, hyperglycaemia, dyslipidaemia and arterial hypertension), indicating an increased risk of diabetes, cardiovascular disease and premature mortality. The gastrointestinal tract is seldom discussed as an organ system of principal importance for metabolic diseases. The present overview connects various metabolic research lines into an integrative physiological context in which the gastrointestinal tract is included. Strong evidence for the involvement of the gut in the metabolic syndrome derives from the powerful effects of weight-reducing (bariatric) gastrointestinal surgery. In fact, gastrointestinal surgery is now recommended as a standard treatment option for type 2 diabetes in obesity. Several gut-related mechanisms that potentially contribute to the metabolic syndrome will be presented. Obesity can be caused by hampered release of satiety-signalling gut hormones, reduced meal-associated energy expenditure and microbiota-assisted harvest of energy from nondigestible food ingredients. Adiposity per se is a well-established risk factor for hyperglycaemia. In addition, a leaky gut mucosa can trigger systemic inflammation mediating peripheral insulin resistance that together with a blunted incretin response aggravates the hyperglycaemic state. The intestinal microbiota is strongly associated with obesity and the related metabolic disease states, although the mechanisms involved remain unclear. Enterorenal signalling has been suggested to be involved in the pathophysiology of hypertension and postprandial triglyceride-rich chylomicrons; in addition, intestinal cholesterol metabolism probably contributes to atherosclerosis. It is likely that in the future, the metabolic syndrome will be treated according to novel pharmacological principles interfering with gastrointestinal functionality. © 2016 The Association for the Publication of the Journal of Internal Medicine


Lunde C.,Gothenburg University | Gattario K.H.,Gothenburg University
Body Image | Year: 2017

The aim of this qualitative study was to examine young female sport participants’ experiences and thoughts in terms of sport, their bodies, and social appearance norms. Six focus groups with female sport participants (N = 25) from Sweden were conducted. Participants raised many positive experiences in relation to their sport participation, but they also witnessed a conflict in the intersection between the culture within their sport (emphasizing physical performance) and the culture outside their sport (emphasizing physical appearance). Through thematic analysis, four themes illustrating the balancing act between these two cultures were formed: (a) the performing body versus the objectified body, (b) food as fuel versus source of shame, (c) appreciation of body type diversity versus appearance prejudice, and (d) empowerment and agency versus disempowerment and restraints. The findings of this study indicate that young women who engage in sport have to face complex, ambiguous, and restricting norms and notions. © 2017 Elsevier Ltd


Jeppsson H.,Gothenburg University
Journal of Commercial Biotechnology | Year: 2016

This study examines a large sample of venture investments in public equities (VIPEs) in the biotechnology and pharmaceutical industry over the period 1995-2014. The results of the study are threefold. First, and contrary to widely held beliefs, there has been no significant increase in the number of VIPEs over time. In fact, both in terms of dollar amount as well as the number of VIPE transactions have actually went down post the record year in 2009. Second, this study documents that returns profiles from the public venture capital market share many similarities to the returns in the private VC market: few big winners, but overall a high loss rate. Approximately seven investments out of ten in public firms generate a loss. Third, the analysis of private investments in public equities shows that venture capitalists outperform other competitors, such as hedge funds and mutual funds. From a management perspective, venture investments in public equity provide several benefits including providing an additional source of potential funding, aligning the investment horizon of venture capitalists with other long-term investors, certifying the quality of the firm and contributing to the long-term success.


Jeppsson H.,Gothenburg University
Journal of Commercial Biotechnology | Year: 2016

This study analyzes first-day returns (underpricing) for venture-backed biotechnology IPOs during 1980 through 2015. The result of this study shows that the average first-day return was 17.5 percent, which translates into an amount equal to $6.3 billion that was left on the table-nearly triple the $2.2 billion in underwriter fees. The study provides different theoretical explanations to the underpricing phenomenon and discusses why venture capitalists may be willing to accept leaving money on the table. The analysis also shows that IPOs with a large degree of underpricing are concentrated in hot IPO markets such as during 1999-2000 and more recently in the years 2014-2015. Notable, eight of the thirteen venture-backed biotechnology IPOs with the largest amount of money left on the table in the history of biotechnology went public during 2014-2015. From an investor perspective, if the degree of underpricing is an indicator of a pricing bubble, as was the case in 1999-2000, rational investors should at least be a little bit concerned about the state of the biotechnology equity market. From a management and venture capitalist perspective, issuing firms should at least consider using auctions as opposed to book-building to price and allocate IPOs to decrease the degree of underpricing and thereby the amount of money left on the table.


Martinsson S.,Gothenburg University
Australian Field Ornithology | Year: 2016

An aberrantly coloured male Golden Whistler Pachycephala pectoralis, lacking yellow pigment, is reported from the Bellarine Peninsula, Victoria. This could be the first documented case of this colour aberration in the species. © 2016, Bird Observers Club of Australia (BOCA). All rights reserved.


Martinsson S.,Gothenburg University | Erseus C.,Gothenburg University
Molecular Phylogenetics and Evolution | Year: 2017

Cryptic mitochondrial (mt) lineages are known to exist in the earthworm morphospecies Lumbricus rubellus and L. terrestris. The latter was recently split into two species, L. terrestris and L. herculeus, based on large genetic distances and a statistical difference in body size. There is support for the separation of some lineages in L. rubellus into species, whereas other lineages, separated by similar mt genetic distances, have been found to be part of the same species. However, no study has evaluated the status of the cryptic mt lineages in L. terrestris-L. herculeus and L. rubellus using nuclear genes. We use a combination of methods to reveal extensive cryptic speciation and limited hybridization in Lumbricus, based on one nuclear (H3) and one mitochondrial (COI) marker. Using a Bayesian multi-locus species delimitation method, as well as single gene haplotype networks and gene trees, we delimit seven well supported cryptic species within the morphospecies L. rubellus, and confirm the split within the species-pair L. terrestris-L. herculeus. Limited hybridization was found between the most common species of L. rubellus (A) in northern Europe and two other species (B and H) in this complex, as well as between L. terrestris and L. herculeus. Deep mt divergence was found within L. terrestris s.str. but no support for further splitting of this taxon was found. Both L. rubellus and L. terrestris are well studied model organisms, and considering that cryptic species and hybridization were found within them, it is important that they are properly identified in future studies. © 2016 Elsevier Inc.


Aziz I.,Gothenburg University
Current Opinion in Gastroenterology | Year: 2017

PURPOSE OF REVIEW: Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. RECENT FINDINGS: Case–control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. SUMMARY: The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host–gut microbiota interaction. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Persson R.A.X.,Gothenburg University
Journal of Informetrics | Year: 2017

The rising trend of coauthored academic works obscures the credit assignment that is the basis for decisions of funding and career advancements. In this paper, a simple model based on the assumption of an unvarying “author ability” is introduced. With this assumption, the weight of author contributions to a body of coauthored work can be statistically estimated. The method is tested on a set of some more than five-hundred authors in a coauthor network from the CiteSeerX database. The ranking obtained agrees fairly well with that given by total fractional citation counts for an author, but noticeable differences exist. © 2017 Elsevier Ltd


Schuelke M.,Charité - Medical University of Berlin | Oien N.C.,Charité - Medical University of Berlin | Oien N.C.,Max Delbrück Center for Molecular Medicine | Oldfors A.,Gothenburg University
Neuropathology and Applied Neurobiology | Year: 2017

The advent of Next Generation Sequencing (NGS) technologies has accelerated the rate of novel disease gene discovery. Analysis of the large datasets generated by whole exome sequencing, whole genome sequencing, and other NGS approaches poses a challenge to physicians and pathologists searching for disease causing variants amongst the 50 000—3 million polymorphisms typically seen in these datasets. This review describes strategies that successfully combine classical neuropathological investigation (e.g. histology, immunostaining and electron microscopy) with modern NGS technologies to pinpoint the underlying genetic cause of a disease. We describe filtering techniques and free online bioinformatic tools that can help physicians and researchers establish a molecular diagnosis from NGS data. The ethical issues raised by NGS data are outlined. We provide specific examples that illustrate how traditional and contemporary approaches integrate to solve a difficult diagnosis or to correct initially wrong assumptions based on data generated from one method alone. © 2016 British Neuropathological Society


Chen L.,Gothenburg University | Liu B.,Gothenburg University
Oxidative Medicine and Cellular Longevity | Year: 2017

Cytoplasmic stress granules (SGs) are critical for facilitating stress responses and for preventing the accumulation of misfolded proteins. SGs, however, have been linked to the pathogenesis of neurodegenerative diseases, in part because SGs share many components with neuronal granules. Oxidative stress is one of the conditions that induce SG formation. SGs regulate redox levels, and SG formation in turn is differently regulated by various types of oxidative stress. These associations and other evidences suggest that SG formation contributes to the development of neurodegenerative diseases. In this paper, we review the regulation of SG formation/assembly and discuss the interactions between oxidative stress and SG formation. We then discuss the links between SGs and neurodegenerative diseases and the current therapeutic approaches for neurodegenerative diseases that target SGs. © 2017 Lihua Chen and Beidong Liu.


Qadri F.,Center for Vaccine science | Bhuiyan T.R.,Center for Vaccine science | Svennerholm A.-M.,Gothenburg University
Vaccine | Year: 2013

Oral mucosal vaccines have great promise for generating protective immunity against intestinal infections for the benefit of large numbers of people especially young children. There however appears to be a caveat since these vaccines have to overcome the inbuilt resistance of mucosal surfaces and secretions to inhibit antigen stimulation and responses. Unfortunately, these vaccines are not equally immunogenic nor protective in different populations. When compared to industrialized countries, children living in developing countries appear to have lower responses, but the reasons for these lowered responses are not clearly defined. The most likely explanations relate to undernutrition, micronutrient deficiencies, microbial overload on mucosal surfaces, alteration of microbiome and microbolom and irreversible changes on the mucosa as well as maternal antibodies in serum or breast milk may alter the mucosal pathology and lower immune responses to interventions using oral vaccines. The detrimental effect of adverse environment and malnutrition may bring about irreversible changes in the mucosa of children especially in the first 1000 days of life from conception to after birth and up to two years of age. This review aims to summarize the information available on lowered immune responses to mucosal vaccines and on interventions that may help address the constraints of these vaccines when they are used for children living under the greatest stress and under harmful adverse circumstances. © 2012 Elsevier Ltd.


Ambec S.,French National Institute for Agricultural Research | Ambec S.,Gothenburg University | Cohen M.A.,Vanderbilt University | Elgie S.,University of Ottawa | Lanoie P.,HEC Montréal
Review of Environmental Economics and Policy | Year: 2013

Some twenty years ago, Harvard Business School economist and strategy professor Michael Porter challenged conventional wisdom about the impact of environmental regulation on business by declaring that well-designed regulation could actually enhance competitiveness. The traditional view of environmental regulation held by virtually all economists until that time was that requiring firms to reduce an externality like pollution necessarily restricted their options and thus by definition reduced their profits. After all, if profitable opportunities existed to reduce pollution, profit-maximizing firms would already be taking advantage of them. Over the past twenty years, much has been written about what has since become known simply as the Porter Hypothesis. Yet even today, we continue to find conflicting evidence concerning the Porter Hypothesis, alternative theories that might explain it, and oftentimes a misunderstanding of what the Porter Hypothesis does and does not say. This article examines the key theoretical foundations and empirical evidence concerning the Porter Hypothesis, discusses its implications for the design of environmental regulations, and outlines directions for future research on the relationship between environmental regulation, innovation, and competitiveness. © The Author 2013. Published by Oxford University Press on behalf of the Association of Environmental and Resource Economists. All rights reserved.


Heister D.,University of California at San Diego | Brewer J.B.,University of California at San Diego | Magda S.,CorTechs Labs | Blennow K.,Gothenburg University | McEvoy L.K.,University of California at San Diego
Neurology | Year: 2011

Objective: To determine the ability of clinically available volumetric MRI (vMRI) and CSF biomarkers, alone or in combination with a quantitative learning measure, to predict conversion to Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). Methods: We stratified 192 MCI participants into positive and negative risk groups on the basis of 1) degree of learning impairment on the Rey Auditory Verbal Learning Test; 2) medial temporal atrophy, quantified from Food and Drug Administration-approved software for automated vMRI analysis; and 3) CSF biomarker levels. We also stratified participants based on combinations of risk factors. We computed Cox proportional hazards models, controlling for age, to assess 3-year risk of converting to AD as a function of risk group and used Kaplan-Meier analyses to determine median survival times. Results: When risk factors were examined separately, individuals testing positive showed significantly higher risk of converting to AD than individuals testing negative (hazard ratios [HR] 1.8- 4.1). The joint presence of any 2 risk factors substantially increased risk, with the combination of greater learning impairment and increased atrophy associated with highest risk (HR 29.0): 85% of patients with both risk factors converted to AD within 3 years, vs5%of those with neither. The presence of medial temporal atrophy was associated with shortest median dementia-free survival (15 months). Conclusions: Incorporating quantitative assessment of learning ability along with vMRI or CSF biomarkers in the clinical workup of MCI can provide critical information on risk of imminent conversion to AD. Copyright © 2011 by AAN Enterprises, Inc.


Swedberg K.,Gothenburg University | Zannad F.,University of Lorraine | McMurray J.J.V.,University of Glasgow | Krum H.,Monash University | And 4 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database. Background: Aldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study. Methods: Patients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event. Results: New onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33). Conclusions: In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline. © 2012 American College of Cardiology Foundation.


Samokhvalov A.V.,RAS Institute for Physics of Microstructures | Shekhter R.I.,Gothenburg University | Buzdin A.I.,Institut Universitaire de France
Scientific Reports | Year: 2014

Josephson junctions with a ferromagnetic metal weak link reveal a very strong decrease of the critical current compared to a normal metal weak link. We demonstrate that in the ballistic regime the presence of a small region with a non-collinear magnetization near the center of a ferromagnetic weak link restores the critical current inherent to the normal metal. The above effect can be stimulated by additional electrical bias of the magnetic gate which induces a local electron depletion of ferromagnetic barrier. The underlying physics of the effect is the interference phenomena due to the magnetic scattering of the Cooper pair, which reverses its total momentum in the ferromagnet and thus compensates the phase gain before and after the spin-reversed scattering. In contrast with the widely discussed triplet long ranged proximity effect we elucidate a new singlet long ranged proximity effect. This phenomenon opens a way to easily control the properties of SFS junctions and inversely to manipulate the magnetic moment via the Josephson current.


Fagman H.,Instituto Of Ricerche Genetiche Gaetano Salvatore Irgs | Nilsson M.,Gothenburg University
Molecular and Cellular Endocrinology | Year: 2010

Congenital hypothyroidism is mainly due to structural defects of the thyroid gland, collectively known as thyroid dysgenesis. The two most prevalent forms of this condition are abnormal localization of differentiated thyroid tissue (thyroid ectopia) and total absence of the gland (athyreosis). The clinical picture of thyroid dysgenesis suggests that impaired specification, proliferation and survival of thyroid precursor cells and loss of concerted movement of these cells in a distinct spatiotemporal pattern are major causes of malformation. In normal development the thyroid primordium is first distinguished as a thickening of the anterior foregut endoderm at the base of the prospective tongue. Subsequently, this group of progenitors detaches from the endoderm, moves caudally and ultimately differentiates into hormone-producing units, the thyroid follicles, at a distant location from the site of specification. In higher vertebrates later stages of thyroid morphogenesis are characterized by shape remodeling into a bilobed organ and the integration of a second type of progenitors derived from the caudal-most pharyngeal pouches that will differentiate into C-cells. The present knowledge of thyroid developmental dynamics has emerged from embryonic studies mainly in chicken, mouse and more recently also in zebrafish. This review will highlight the key morphogenetic steps of thyroid organogenesis and pinpoint which crucial regulatory mechanisms are yet to be uncovered. Considering the co-incidence of thyroid dysgenesis and congenital heart malformations the possible interactions between thyroid and cardiovascular development will also be discussed. © 2009 Elsevier Ireland Ltd.


Lind M.,Gothenburg University | Lind M.,NU Hospital Organisation | Bounias I.,NU Hospital Organisation | Olsson M.,Chalmers University of Technology | And 2 more authors.
The Lancet | Year: 2011

Poor glycaemic control is associated with microvascular and macrovascular complications in type 1 diabetes, but whether glycaemic control is associated with heart failure in such patients is not known. We aimed to assess this association in a large cohort of patients with type 1 diabetes identified from the Swedish national diabetes registry. We identified all patients (aged ≥18 years) with type 1 diabetes and no known heart failure who were registered in the national diabetes registry between January, 1998, and December, 2003. These patients were followed up until hospital admission for heart failure, death, or end of follow-up on Dec 31, 2009. We calculated incidence categorised by glycated haemoglobin A1c (HbA1c) values, and we assessed the association between patients' characteristics, including HbA1c, and heart failure. In a cohort of 20 985 patients with mean age of 38·6 years (SD 13·3) at baseline, 635 patients (3) were admitted to hospital with a primary or secondary diagnosis of heart failure during a median follow-up of 9·0 years (IQR 7·3-11·0), with an incidence of 3·38 events per 1000 patient-years (95 CI 3·12-3·65). Incidence increased monotonically with HbA1c, with a range of 1·42-5·20 per 1000 patient-years between patients in the lowest (<6·5) and highest (≥10·5) categories of HbA1c. In a Cox regression analysis, with adjustment for age, sex, duration of diabetes, cardiovascular risk factors, and baseline or intervening acute myocardial infarction and other comorbidities, the hazard ratio for development of heart failure was 3·98 (95 CI 2·23-7·14) in patients with HbA1c of 10·5 or higher compared with a reference group of patients with HbA1c of less than 6·5. Risk of heart failure increased with age and duration of diabetes. Other modifiable factors associated with increased risk of heart failure were smoking, high systolic blood pressure, and raised body-mass index. In a subgroup of 18 281 patients (87) with data for blood lipids, higher HDL cholesterol was associated with lower risk of heart failure, but there was no association with LDL cholesterol. The positive association between HbA1c and risk of heart failure in fairly young patients with type 1 diabetes indicates a potential for prevention of heart failure with improved glycaemic control. AstraZeneca, Novo Nordisk Scandinavia, Swedish Heart and Lung Foundation, and Swedish Research Council. © 2011 Elsevier Ltd.


Strom A.,Gothenburg University | Johannesson H.,Gothenburg University | Japaridze G.I.,Andronikashvili Institute of Physics | Japaridze G.I.,Ilia State University
Physical Review Letters | Year: 2010

We analyze the dynamics of the helical edge modes of a quantum spin Hall state in the presence of a spatially nonuniform Rashba spin-orbit (SO) interaction. A randomly fluctuating Rashba SO coupling is found to open a scattering channel which causes localization of the edge modes for a weakly screened electron-electron (e-e) interaction. A periodic modulation of the SO coupling, with a wave number commensurate with the Fermi momentum, makes the edge insulating already at intermediate strengths of the e-e interaction. We discuss implications for experiments on edge state transport in a HgTe quantum well. © 2010 The American Physical Society.


Friberg L.,Danderyd Hospital | Bergfeldt L.,Gothenburg University
Stroke | Year: 2013

Background and Purpose: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. This study aims to update the knowledge about AF and associated stroke risk and benefits of anticoagulation. Methods: We extracted data from the hospital, specialized outpatient, and primary healthcare and drug registries in a Swedish region with 1.56 million residents. We identified all individuals who had received an AF diagnosis during the previous 5 years; all stroke events during 2010; and patients with AF aged ≥50 years who had received warfarin during 2009. Results: AF had been diagnosed in 38 446 subjects who were alive at the beginning of 2010 (prevalence of 3.2% in the adult [≥20 years] population); ≈46% received warfarin therapy. In 2010, there were 4565 ischemic stroke events and 861 intracranial hemorrhages. AF had been diagnosed in 38% of ischemic events (≥50% among those aged ≥80 years) and in 23% of intracranial hemorrhages. An AF diagnosis was often lacking in hospital discharge records after stroke events. Warfarin therapy was associated with an odds ratio of 0.50 (confidence interval, 0.43-0.57) for ischemic stroke and, despite an increased risk of intracranial hemorrhage, an odds ratio of 0.57 (confidence interval, 0.50-0.64) for the overall risk for stroke. Conclusions: AF is more common than present guidelines suggest. The attributable risk of AF for ischemic stroke increases with age and is close to that of hypertension in individuals aged ≥80 years. Because a majority of patients with AF with increased risk for stroke had not received anticoagulation therapy, there is a large potential for improvement. © 2013 American Heart Association, Inc.


Swedberg K.,Gothenburg University | Komajda M.,University Pierre and Marie Curie | Bohm M.,Universitatskliniken des Saarlandes | Borer J.,New York University | And 3 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: This study used the SHIFT (Systolic Heart failure treatment with the I f inhibitor ivabradine Trial) database to assess the impact of background beta-blocker dose on response to ivabradine. Background: In systolic heart failure, reduction in relatively high heart rates improves clinical outcomes when achieved with beta-blockers and even more so when the sinus node inhibitor ivabradine also is added. Methods: Among patients with systolic heart failure, sinus rhythm, and heart rate <70 beats/min on recommended background therapy, maximally tolerated beta-blocker doses were subgrouped as no beta-blocker, <25%, 25% to <50%, 50% to <100%, and 100% of European Society of Cardiology-suggested target doses. The impact of ivabradine on cardiovascular death or heart failure hospitalization (primary endpoint) was analyzed in each subgroup as time-to-first event using Cox models adjusted for heart rate. The statistical models assessed heterogeneity and trend of the treatment effect across subgroups, and an additional analysis was made adjusting for the interaction of randomized treatment with baseline heart rate. Results: The primary endpoint and heart failure hospitalizations were significantly reduced by ivabradine in all subgroups with <50% of target beta-blocker dose, including no beta-blocker (p = 0.012). Despite an apparent trend to reduction in treatment-effect magnitude with increasing beta-blocker dose, no variation in treatment effect was seen in general heterogeneity interaction tests (p = 0.35). Across beta-blocker subgroups, treatment effect was borderline nonsignificant only for the primary endpoint (p = 0.056), and significance was further lost after adjusting for interaction between baseline heart rate and ivabradine effect (p = 0.14). Conclusions: The magnitude of heart rate reduction by beta-blocker plus ivabradine, rather than background beta-blocker dose, primarily determines subsequent effect on outcomes. (Effects of ivabradine on cardiovascular events in patients with moderate to severe chronic heart failure and left ventricular systolic dysfunction. A three-year randomised double-blind placebo-controlled international multicentre study; ISRCTN70429960) © 2012 American College of Cardiology Foundation.


Waterhouse L.,The College of New Jersey | Gillberg C.,Gothenburg University
Journal of Autism and Developmental Disorders | Year: 2014

Although accumulated evidence has demonstrated that autism is found with many varied brain dysfunctions, researchers have tried to find a single brain dysfunction that would provide neurobiological validity for autism. However, unitary models of autism brain dysfunction have not adequately addressed conflicting evidence, and efforts to find a single unifying brain dysfunction have led the field away from research to explore individual variation and micro-subgroups. Autism must be taken apart in order to find neurobiological treatment targets. Three research changes are needed. The belief that there is a single defining autism spectrum disorder brain dysfunction must be relinquished. The noise caused by the thorny brain-symptom inference problem must be reduced. Researchers must explore individual variation in brain measures within autism. © 2014 Springer Science+Business Media.


Guerreiro R.J.,U.S. National Institutes of Health | Guerreiro R.J.,University of Coimbra | Gustafson D.R.,Gothenburg University | Gustafson D.R.,SUNY Downstate Medical Center | Hardy J.,University College London
Neurobiology of Aging | Year: 2012

Alzheimer's disease (AD) is a complex disorder with a clear genetic component. Three genes have been identified as the cause of early onset familial AD (EOAD). The most common form of the disease, late onset Alzheimer's disease (LOAD), is, however, a sporadic one presenting itself in later stages of life. The genetic component of this late onset form of AD has been the target of a large number of studies, because only one genetic risk factor (APOE4) has been consistently associated with the disease. However, technological advances allow new approaches in the study of complex disorders. In this review, we discuss the new results produced by genome wide association studies, in light of the current knowledge of the complexity of AD genetics. © 2012.


Zannad F.,French Institute of Health and Medical Research | Zannad F.,University of Lorraine | McMurray J.J.V.,University of Glasgow | Krum H.,Monash University | And 6 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS: In this randomized, double-blind trial, we randomly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS: The trial was stopped prematurely, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P = 0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001). CONCLUSIONS: Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.) Copyright © 2010 Massachusetts Medical Society.


Sein M.K.,University of Agder | Henfridsson O.,Viktoria Institute | Henfridsson O.,University of Oslo | Purao S.,Pennsylvania State University | And 3 more authors.
MIS Quarterly: Management Information Systems | Year: 2011

Design research (DR) positions information technology artifacts at the core of the Information Systems discipline. However, dominant DR thinking takes a technological view of the IT artifact, paying scant attention to its shaping by the organizational context. Consequently, existing DR methods focus on building the artifact and relegate evaluation to a subsequent and separate phase. They value technological rigor at the cost of organizational relevance, and fail to recognize that the artifact emerges from interaction with the organizational context even when its initial design is guided by the researchers' intent. We propose action design research (ADR) as a new DR method to address this problem. ADR reflects the premise that IT artifacts are ensembles shaped by the organizational context during development and use. The method conceptualizes the research process as containing the inseparable and inherently interwoven activities of building the IT artifact, intervening in the organization, and evaluating it concurrently. The essay describes the stages of ADR and associated principles that encapsulate its underlying beliefs and values. We illustrate ADR through a case of competence management at Volvo IT.


Bonjer H.J.,VU University Amsterdam | Deijen C.L.,VU University Amsterdam | Abis G.A.,VU University Amsterdam | Cuesta M.A.,VU University Amsterdam | And 9 more authors.
New England Journal of Medicine | Year: 2015

Background: Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer. Methods: In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio. The primary end point was locoregional recurrence 3 years after the index surgery. Secondary end points included disease-free and overall survival. Results: A total of 1044 patients were included (699 in the laparoscopic-surgery group and 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was 5.0% in the two groups (difference, 0 percentage points; 90% confidence interval [CI], -2.6 to 2.6). Disease-free survival rates were 74.8% in the laparoscopic-surgery group and 70.8% in the open-surgery group (difference, 4.0 percentage points; 95% CI, -1.9 to 9.9). Overall survival rates were 86.7% in the laparoscopic-surgery group and 83.6% in the open-surgery group (difference, 3.1 percentage points; 95% CI, -1.6 to 7.8). Conclusions: Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery. Copyright © 2015 Massachusetts Medical Society. All rights reserved.


Lind M.,NUHospital Organization | Lind M.,Gothenburg University | Kosiborod M.,Saint Lukes Mid America Heart Institute | Kosiborod M.,University of Missouri - Kansas City | And 9 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: The excess risk of death from any cause and of death from cardiovascular causes is unknown among patients with type 1 diabetes and various levels of glycemic control. We conducted a registry-based observational study to determine the excess risk of death according to the level of glycemic control in a Swedish population of patients with diabetes. METHODS: We included in our study patients with type 1 diabetes registered in the Swedish National Diabetes Register after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. Patients and controls were followed until December 31, 2011, through the Swedish Register for Cause-Specific Mortality. RESULTS: The mean age of the patients with diabetes and the controls at baseline was 35.8 and 35.7 years, respectively, and 45.1% of the participants in each group were women. The mean follow-up in the diabetes and control groups was 8.0 and 8.3 years, respectively. Overall, 2701 of 33,915 patients with diabetes (8.0%) died, as compared with 4835 of 169,249 controls (2.9%) (adjusted hazard ratio, 3.52; 95% confidence interval [CI], 3.06 to 4.04); the corresponding rates of death from cardiovascular causes were 2.7% and 0.9% (adjusted hazard ratio, 4.60; 95% CI, 3.47 to 6.10). The multivariable-adjusted hazard ratios for death from any cause according to the glycated hemoglobin level for patients with diabetes as compared with controls were 2.36 (95% CI, 1.97 to 2.83) for a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole), 2.38 (95% CI, 2.02 to 2.80) for a level of 7.0 to 7.8% (53 to 62 mmol per mole), 3.11 (95% CI, 2.66 to 3.62) for a level of 7.9 to 8.7% (63 to 72 mmol per mole), 3.65 (95% CI, 3.11 to 4.30) for a level of 8.8 to 9.6% (73 to 82 mmol per mole), and 8.51 (95% CI, 7.24 to 10.01) for a level of 9.7% or higher (≥83 mmol per mole). Corresponding hazard ratios for death from cardiovascular causes were 2.92 (95% CI, 2.07 to 4.13), 3.39 (95% CI, 2.49 to 4.61), 4.44 (95% CI, 3.32 to 5.96), 5.35 (95% CI, 3.94 to 7.26), and 10.46 (95% CI, 7.62 to 14.37). CONCLUSIONS: In our registry-based observational study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that was twice as high as the risk for matched controls. Copyright © 2014 Massachusetts Medical Society. All rights reserved.


Rodriguez-Calvo T.,La Jolla Institute for Allergy and Immunology | Ekwall O.,La Jolla Institute for Allergy and Immunology | Ekwall O.,Gothenburg University | Amirian N.,La Jolla Institute for Allergy and Immunology | And 3 more authors.
Diabetes | Year: 2014

Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors that have been implicated in the pathogenesis of disease both as triggers and potentiators of β-cell destruction. CD8 T cells are the main cell type found in human islets, and they have been shown in vitro to be capable of killing β-cells overexpressing MHC class I. In this study, we report that CD8 T cells infiltrate the exocrine pancreas of diabetic subjects in high numbers and not only endocrine areas. T1D subjects present significantly higher CD8 T cell density in the exocrine tissue without the presence of prominent insulitis. Even T1D donors without remaining insulin-containing islets and long disease duration show elevated levels of CD8 T cells in the exocrine compartment. In addition, higher numbers of CD4+ and CD11c+ cells were found in the exocrine tissue. Preliminary data in type 2 diabetic (T2D) subjects indicate that overall, there might be a spontaneous inflammatory infiltration of the exocrine tissue, common to both T1D and T2D subjects. Our study provides the first information on the precise tissue distribution of CD8 T cells in pancreata from T1D, T2D, autoantibody-positive, and healthy control subjects. © 2014 by the American Diabetes Association.


Su F.,CAS Institute of Tibetan Plateau Research | Duan X.,CAS Institute of Tibetan Plateau Research | Chen D.,Gothenburg University | Hao Z.,Hohai University | Cuo L.,CAS Institute of Tibetan Plateau Research
Journal of Climate | Year: 2013

The performance of 24 GCMs available in the fifth phase of the Coupled Model Intercomparison Project (CMIP5) is evaluated over the eastern Tibetan Plateau (TP) by comparing the model outputs with ground observations for the period 1961-2005. The twenty-first century trends of precipitation and temperature based on the GCMs' projections over the TP are also analyzed. The results suggest that for temperature most GCMs reasonably capture the climatological patterns and spatial variations of the observed climate. However, the majority of the models have cold biases, with a mean underestimation of 1.1°-2.5°C for the months December-May, and less than 1°C for June-October. For precipitation, the simulations of all models overestimate the observations in climatological annual means by 62.0%-183.0%, and only half of the 24 GCMsare able to reproduce the observed seasonal pattern, which demonstrates a critical need to improve precipitationrelated processes in these models. All models produce a warming trend in the twenty-first century under the Representative Concentration Pathway 8.5 (rcp8.5) scenario; in contrast, the rcp2.6 scenario predicts a lower average warming rate for the near term, and a small cooling trend in the long-term period with the decreasing radiative forcing. In the near term, the projected precipitation change is about 3.2% higher than the 1961-2005 annual mean, whereas in the long term the precipitation is projected to increase 6.0% under rcp2.6 and 12.0% under the rcp8.5 scenario. Relative to the 1961-2005 mean, the annual temperature is projected to increase by 1.2°-1.3°C in the short term; the warmings under the rcp2.6 and rcp8.5 scenarios are 1.8° and 4.1°C, respectively, for the long term. © 2013 American Meteorological Society.


Powell A.,University of Swansea | Eriksson S.P.,Gothenburg University
Advances in Marine Biology | Year: 2013

Nephrops norvegicus represents a very valuable fishery across Europe, and the species possesses a relatively complex life cycle and reproductive biology across spatial and temporal scales. Insights into embryonic and larval biology, and associated abiotic and biotic factors that influence recruitment, are important since this will affect population and species success. Much of the fishery, and indeed scientific sampling, is reliant on trawling, which is likely to cause direct and indirect stresses on adults and developing embryos. We have collated evidence, including that garnered from laboratory studies, to assess the likely effects on reproduction and population. Using know-how from hatchery operations in similar species such as Homarus sp., we also seek to optimise larviculture that could be commercialised to create a hatchery and thus assist stock remediation. This review chapter is therefore divided into three sections: (1) general N. norvegicus reproductive biology, (2) life cycle and larval biology and (3) a comprehensive review of all rearing attempts for this species to date, including a likely way forward for pilot scale and hence commercial restocking operations. © 2013 Elsevier Ltd.


Abrahams N.,Gender and Health Research Unit | Devries K.,London School of Hygiene and Tropical Medicine | Watts C.,London School of Hygiene and Tropical Medicine | Petzold M.,Gothenburg University | And 2 more authors.
The Lancet | Year: 2014

Background: Several highly publicised rapes and murders of young women in India and South Africa have focused international attention on sexual violence. These cases are extremes of the wider phenomenon of sexual violence against women, but the true extent is poorly quantified. We did a systematic review to estimate prevalence. Methods: We searched for articles published from Jan 1, 1998, to Dec 31, 2011, and manually search reference lists and contacted experts to identify population-based data on the prevalence of women's reported experiences of sexual violence from age 15 years onwards, by anyone except intimate partners. We used random effects meta-regression to calculate adjusted and unadjusted prevalence for regions, which we weighted by population size to calculate the worldwide estimate. Findings: We identified 7231 studies from which we obtained 412 estimates covering 56 countries. In 2010 7·2% (95% CI 5·2-9·1) of women worldwide had ever experienced non-partner sexual violence. The highest estimates were in sub-Saharan Africa, central (21%, 95%CI 4·5-37·5) and sub-Saharan Africa, southern (17·4%, 11·4-23·3). The lowest prevalence was for Asia, south (3·3%, 0-8·3). Limited data were available from sub-Saharan Africa, central, North Africa/Middle East, Europe, eastern, and Asia Pacific, high income. Interpretation: Sexual violence against women is common worldwide, with endemic levels seen in some areas, although large variations between settings need to be interpreted with caution because of differences in data availability and levels of disclosure. Nevertheless, our findings indicate a pressing health and human rights concern. © 2014 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved.


Godhe A.,Gothenburg University | Godhe A.,Carl von Ossietzky University | Godhe A.,Swedish Meteorological and Hydrological Institute
Proceedings. Biological sciences / The Royal Society | Year: 2013

We investigated the gene flow of the common marine diatom, Skeletonema marinoi, in Scandinavian waters and tested the null hypothesis of panmixia. Sediment samples were collected from the Danish Straits, Kattegat and Skagerrak. Individual strains were established from germinated resting stages. A total of 350 individuals were genotyped by eight microsatellite markers. Conventional F-statistics showed significant differentiation between the samples. We therefore investigated whether the genetic structure could be explained using genetic models based on isolation by distance (IBD) or by oceanographic connectivity. Patterns of oceanographic circulation are seasonally dependent and therefore we estimated how well local oceanographic connectivity explains gene flow month by month. We found no significant relationship between genetic differentiation and geographical distance. Instead, the genetic structure of this dominant marine primary producer is best explained by local oceanographic connectivity promoting gene flow in a primarily south to north direction throughout the year. Oceanographic data were consistent with the significant FST values between several pairs of samples. Because even a small amount of genetic exchange prevents the accumulation of genetic differences in F-statistics, we hypothesize that local retention at each sample site, possibly as resting stages, is an important component in explaining the observed genetic structure.


Swedberg K.,Gothenburg University | Komajda M.,University Pierre and Marie Curie | Bohm M.,Universitatskliniken des Saarlandes | Borer J.S.,New York University | And 4 more authors.
The Lancet | Year: 2010

Background Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure. Methods Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35 or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a β blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7·5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960. Findings 6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22·9 (IQR 18-28) months. 793 (24) patients in the ivabradine group and 937 (29) of those taking placebo had a primary endpoint event (HR 0·82, 95 CI 0·75-0·90, p<0·0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 [21] placebo vs 514 [16] ivabradine; HR 0·74, 0·66-0·83; p<0·0001) and deaths due to heart failure (151 [5] vs 113 [3]; HR 0·74, 0·58-0·94, p=0·014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0·025). 150 (5) of ivabradine patients had symptomatic bradycardia compared with 32 (1) of the placebo group (p<0·0001). Visual side-effects (phosphenes) were reported by 89 (3) of patients on ivabradine and 17 (1) on placebo (p<0·0001). Interpretation Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder. Funding Servier, France. © 2010 Elsevier Ltd.


Sterner T.,Gothenburg University | Sterner T.,University Fellow
Energy Policy | Year: 2012

This paper. 11Thanks for excellent research assistance for this paper to Emmanuel Carlsson. Valuable comments from Francisco Alpizar, Ashokankur Datta and an anonymous referee are gratefully acknowledged as is financial support from the Swedish International Development Cooperation Agency (Sida) to the Environmental Economics Unit at the University of Gothenburg. takes as its starting point the observation that fuel prices - and thus taxes - are important for good management of climate change and other environmental problems. To economists this should be no surprise yet it seems that the role of fuel taxation as an instrument of climate policy has not been fully appreciated. It is however one of the few policy instruments that, since several decades, has actually reduced fuel consumption appreciably. Thanks to taxation (mainly in Europe and Japan), carbon emissions are considerably lower than they would have been otherwise. In future where carbon emissions are to be cut drastically, this instrument will be crucial. There is however much opposition to the instrument. This opposition uses various arguments, for instance that fuel taxes hurt the poor since they are strongly regressive. We however find that the choice of country and methodology turns out to be of great consequence. We study seven European countries-France, Germany, United Kingdom, Italy, Serbia, Spain and Sweden and do find some evidence of regressivity but the evidence is very weak. It does not apply when lifetime income is used and it does not apply to the poorest country in the group. The best one-line summary is probably that the tax is approximately proportional. © 2010 Elsevier Ltd.


News Article | November 21, 2016
Site: www.techtimes.com

Nanotechnology - What You Should Know Concerns are out that antibiotic-resistant bacteria are spreading fast through polluted air in cities. This follows a study conducted by researchers at the Gothenburg University. The results showed Beijing City's air pollution had been a carrier of DNA from genes that turn bacteria resistant even to the strongest of antibiotics. "This may be a more important means of transmission than previously thought," commented Joakim Larsson, Director of the Centre for Antibiotic Resistance Research at the University of Gothenburg. The study has been published in the Microbiome journal. During the study, the researchers probed genes that make bacteria resistant to antibiotics. They analyzed 864 samples of DNA extracted from animals, humans, and other environments. "The air samples we did analyze showed a wide mix of different resistance genes," said Larsson. They expressed high concern over the growth of genes that resist carbapenems — last resort antibiotics used in hard-to-treat bacterial infections. However, clarity was missing in the study whether the bacteria was alive in the air so as to pose a real threat. "It is reasonable to believe that there is a mixture of live and dead bacteria, based on experience from other studies of air," said Larsson. Larsson is known for his study on water-borne pollution caused by the discharge of antibiotics from pharmaceutical units in India as a factor that breeds resistant bacteria. Now, the research has turned attention to the role of European sewage treatment plants in spreading the contagious pathogens. "We're going to let treatment plant employees carry air samplers. We will also study their bacterial flora and flora of people who live very close and farther away, and see if there seems to be a connection to the treatment plants," Larsson added. Meanwhile, the menace of expanding antibiotic-resistant bacteria is harming more children who are coping with weak immune systems. Adding to the conundrum is the finding that antibiotics are losing power as revealed in a study on child patients. Soaring infection rates among children are putting pressure on scientists to develop new medicines that can overcome the antibiotic resistant bacteria. One example is P. aeruginosa — a common bacteria that causes skin rashes. It has become highly antibiotic resistant according to the Center for Disease Control and Prevention. Causing severe symptoms including death, the details of the bacteria are discussed in the Journal of the Pediatric Infectious Diseases Society. In the decade-long survey, the study examined child patients from 300 hospitals in the United States. Noting the alarming growth rate of P. aeruginosa bacteria, which in 1999 resisted three types of antibiotics, the study said the same has soared to 26 in 2012. More worrying was the surge in infections caused by P. aeruginosa in children. Though commonplace, P. aeruginosa is still "associated with significant morbidity and mortality," said the study's author Latania K. Logan, who is a doctor at the Rush University Medical Center. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


Baczyk M.,Academy of Physical Education in Poznan | Jankowska E.,Gothenburg University
Journal of Physiology | Year: 2014

The main aim of the present study was to examine to what extent long-lasting subcortical actions of transcranial direct current stimulation (tDCS) may be related to its presynaptic actions. This was investigated in the red nucleus, where tDCS was recently demonstrated to facilitate transmission between interpositorubral and rubrospinal neurons. Changes in the excitability of preterminal axonal branches of interpositorubral neurons close to rubrospinal neurons were investigated during and after tDCS (0.2 mA) applied over the sensorimotor cortical area in deeply anaesthetized rats and cats. As a measure of the excitability, we used the probability of antidromic activation of individual interpositorubral neurons by electrical stimuli applied in the red nucleus. Our second aim was to compare effects of weak (≤1 μA) direct current applied within the red nucleus with effects of tDCS to allow the use of local depolarization in a further analysis of mechanisms of tDCS instead of widespread and more difficult to control depolarization evoked by distant electrodes. Local cathodal polarization was found to replicate all effects of cathodal tDCS hitherto demonstrated in the rat, including long-lasting facilitation of trans-synaptically evoked descending volleys and trisynaptically evoked EMG responses in neck muscles. It also replicated all effects of anodal tDCS in the cat. In both species, it increased the excitability of preterminal axonal branches of interpositorubral neurons up to 1 h post-tDCS. Local anodal polarization evoked opposite effects. We thus show that presynaptic actions of polarizing direct current may contribute to both immediate and prolonged effects of tDCS. © 2014 The Physiological Society.


Stattin P.,Umeå University | Holmberg E.,Gothenburg University | Johansson J.-E.,Örebro University | Holmberg L.,King's College London | And 2 more authors.
Journal of the National Cancer Institute | Year: 2010

Background Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA). Methods In the National Prostate Cancer Register of Sweden Follow-up Study, a nationwide cohort, we identified 6849 patients aged 70 years or younger. Inclusion criteria were diagnosis with local clinical stage T1-2 prostate cancer from January 1, 1997, through December 31, 2002, a Gleason score of 7 or less, a serum PSA level of less than 20 ng/mL, and treatment with surveillance (including active surveillance and watchful waiting, n = 2021) or curative intent (including radical prostatectomy, n = 3399, and radiation therapy, n = 1429). Among the 6849 patients, 2686 had low-risk prostate cancer (ie, clinical stage T1, Gleason score 2-6, and serum PSA level of <10 ng/mL). The study cohort was linked to the Cause of Death Register, and cumulative incidence of death from prostate cancer and competing causes was calculated. Results For the combination of low-and intermediate-risk prostate cancers, calculated cumulative 10-year prostate cancer-specific mortality was 3.6% (95% confidence interval [CI] = 2.7% to 4.8%) in the surveillance group and 2.7% (95% CI = 2.1% to 3.45) in the curative intent group. For those with low-risk disease, the corresponding values were 2.4% (95% CI = 1.2% to 4.1%) among the 1085 patients in the surveillance group and 0.7% (95% CI = 0.3% to 1.4%) among the 1601 patients in the curative intent group. The 10-year risk of dying from competing causes was 19.2% (95% CI = 17.2% to 21.3%) in the surveillance group and 10.2% (95% CI = 9.0% to 11.4%) in the curative intent group. Conclusion A 10-year prostate cancer-specific mortality of 2.4% among patients with low-risk prostate cancer in the surveillance group indicates that surveillance may be a suitable treatment option for many patients with low-risk disease. © 2010 The Author. Published by Oxford University Press.


Achurra A.,University of the Basque Country | Erseus C.,Gothenburg University
Invertebrate Systematics | Year: 2013

Individuals of the aquatic oligochaete species Stylodrilus heringianus Clapar̀de, 1862 were collected across a part of this species' distribution range in Sweden, Estonia, Great Britain and Spain to test whether they represent a single metapopulation or several separately evolving lineages. Using sequences of the barcoding gene cytochrome c oxidase subunit I (COI) and two nuclear genes (internal transcribed spacer region and histone 3), three different approaches were conducted: pairwise distance-method, Bayesian inference and network analysis. Both the COI phylogeny and network analyses were concordant in recovering six haplotype clusters, which showed a maximum genetic distance of 7.7% (K2P) among each other. Nevertheless, nuclear genes failed to confirm any lineage separation, and we conclude that the sampled specimens all belong to the same species. A phylogeographic history with allopatric divergence and secondary contact is suggested to explain this intraspecific pattern of mitochondrial divergence and nuclear non-divergence. The study shows that a mitochondrial single-locus approach can be problematic for the accurate delimitation of species, and we emphasise the need for nuclear genes as supplementary markers, when taxonomic resolution is assessed with COI barcodes. © CSIRO 2011.


Yilmaz A.,Gothenburg University | Price R.W.,University of California at San Francisco | Gisslen M.,Gothenburg University
Journal of Antimicrobial Chemotherapy | Year: 2012

The advent of combination antiretroviral treatment has had a profound impact on CNS HIV infection and its clinical complications, but neurological impairment still occurs in patients on systemically effective combination therapy, and in some patients it may be important to consider antiretroviral drug entry and effects within the CNS. There are now data on the CNS exposure for most antiretroviral drugs. This review focuses on the CNS pharmacokinetics and pharmacodynamics of antiretroviral drugs in humans, and also discusses controversies in this field. ©The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Malmstrom S.,Gothenburg University | Berglin-Enquist I.,Genentech
Journal of Clinical Microbiology | Year: 2010

Chronic infection with hepatitis B virus (HBV) is an important cause of cirrhosis and cancer of the liver. HBV is currently classified into eight genotypes, A to H. Accumulated evidence shows that the genotype influences both the clinical course of infection and the response to treatment. We describe a new method for genotyping based on TaqMan real-time PCR, which identifies all HBV genotypes without post-PCR processing. In this assay, each sample is processed in four multiplex real-time PCRs, each targeting two or three genotype-specific segments of HBV. By analyzing 185 samples representing all genotypes and different proportions of genotype mixtures, we could validate high accuracy of the assay. We conclude that this new assay represents a significant advancement for both diagnostics and clinical research because it is accurate, practical, and based on a technique that is well established in many virological laboratories. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Muduli P.K.,Gothenburg University | Heinonen O.G.,Argonne National Laboratory | Heinonen O.G.,Northwestern University | Akerman J.,Gothenburg University | Akerman J.,KTH Royal Institute of Technology
Physical Review Letters | Year: 2012

We discuss the coherence of magnetic oscillations in a magnetic tunnel junction based spin torque oscillator as a function of the external field angle. Time-frequency analysis shows mode hopping between distinct oscillator modes, which arises from linear and nonlinear couplings in the Landau-Lifshitz-Gilbert equation, analogous to mode hopping observed in semiconductor ring lasers. These couplings and, therefore, mode hopping are minimized near the current threshold for the antiparallel alignment of free-layer with reference layer magnetization. Away from the antiparallel alignment, mode hopping limits oscillator coherence. © 2012 American Physical Society.


Lanata N.,Gothenburg University | Strand H.U.R.,Gothenburg University | Dai X.,CAS Institute of Physics | Hellsing B.,Gothenburg University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We present a self-consistent numerical approach to solve the Gutzwiller variational problem for general multiband models with arbitrary on-site interaction. The proposed method generalizes and improves the procedure derived by Deng, overcoming the restriction to density-density interaction without increasing the complexity of the computational algorithm. Our approach drastically reduces the problem of the high-dimensional Gutzwiller minimization by mapping it to a minimization only in the variational density matrix, in the spirit of the Levy and Lieb formulation of density functional theory (DFT). For fixed density the Gutzwiller renormalization matrix is determined as a fixpoint of a proper functional, whose evaluation requires only ground-state calculations of matrices defined in the Gutzwiller variational space. Furthermore, the proposed method is able to account for the symmetries of the variational function in a controlled way, reducing the number of variational parameters. After a detailed description of the method we present calculations for multiband Hubbard models with full (rotationally invariant) Hund's rule on-site interaction. Our analysis shows that the numerical algorithm is very efficient, stable, and easy to implement. For these reasons this method is particularly suitable for first-principles studies (e.g., in combination with DFT) of many complex real materials, where the full intra-atomic interaction is important to obtain correct results. © 2012 American Physical Society.


Lindberg F.,King's College London | Lindberg F.,Gothenburg University | Grimmond C.S.B.,King's College London
Theoretical and Applied Climatology | Year: 2011

The solar and longwave environmental irradiance geometry (SOLWEIG) model simulates spatial variations of 3-D radiation fluxes and mean radiant temperature (Tmrt) as well as shadow patterns in complex urban settings. In this paper, a new vegetation scheme is included in SOLWEIG and evaluated. The new shadow casting algorithm for complex vegetation structures makes it possible to obtain continuous images of shadow patterns and sky view factors taking both buildings and vegetation into account. For the calculation of 3-D radiation fluxes and Tmrt, SOLWEIG only requires a limited number of inputs, such as global shortwave radiation, air temperature, relative humidity, geographical information (latitude, longitude and elevation) and urban geometry represented by high-resolution ground and building digital elevation models (DEM). Trees and bushes are represented by separate DEMs. The model is evaluated using 5 days of integral radiation measurements at two sites within a square surrounded by low-rise buildings and vegetation in Göteborg, Sweden (57°N). There is good agreement between modelled and observed values of Tmrt, with an overall correspondence of R2 = 0.91 (p > 0.01, RMSE = 3.1 K). A small overestimation of Tmrt is found at locations shadowed by vegetation. Given this good performance a number of suggestions for future development are identified for applications which include for human comfort, building design, planning and evaluation of instrument exposure. © 2011 Springer-Verlag.


Ahlquist M.S.G.,KTH Royal Institute of Technology | Norrby P.-O.,Gothenburg University
Angewandte Chemie - International Edition | Year: 2011

18e R.I.P. The apparent compliance of [Pd(PPh3)4] ("tetrakis") with the 18-electron rule is not due to an electronic preference on the central metal. Pd is valence-saturated already by two ligands. Further ligand addition gives a minor energy gain, and is only possible due to strong back-bonding. Dispersion corrections are needed for properly describing the interactions between the ligands. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Economou A.D.,King's College London | Ohazama A.,King's College London | Porntaveetus T.,King's College London | Sharpe P.T.,King's College London | And 5 more authors.
Nature Genetics | Year: 2012

We present direct evidence of an activator-inhibitor system in the generation of the regularly spaced transverse ridges of the palate. We show that new ridges, called rugae, that are marked by stripes of expression of Shh (encoding Sonic hedgehog), appear at two growth zones where the space between previously laid rugae increases. However, inter-rugal growth is not absolutely required: new stripes of Shh expression still appeared when growth was inhibited. Furthermore, when a ruga was excised, new Shh expression appeared not at the cut edge but as bifurcating stripes branching from the neighboring stripe of Shh expression, diagnostic of a Turing-type reaction-diffusion mechanism. Genetic and inhibitor experiments identified fibroblast growth factor (FGF) and Shh as components of an activator-inhibitor pair in this system. These findings demonstrate a reaction-diffusion mechanism that is likely to be widely relevant in vertebrate development. © 2012 Nature America, Inc. All rights reserved.


Gorjon S.P.,Research Center y Extension Forestal Andino Patagonico | Hallenberg N.,Gothenburg University
Mycological Progress | Year: 2013

Gloeocystidiellum rajchenbergii, Hypochnicium patagonicum, Pteridomyces valdivianus, and Stereum greslebinii are described as new species from the Chilean Patagonia. An annotated checklist of corticioid fungi from Chile, listing 94 species with notes on distribution and ecology, scheduled for regular update, is available from http://corticioids.webs.com/checklists.htm. © 2012 German Mycological Society and Springer.


Bende M.,Central Hospital | Millqvist E.,Gothenburg University
Frontiers in Physiology | Year: 2012

The aim of this study was to determine the prevalence of chronic cough in relation to upper airway symptoms, in a cross-sectional, population-based epidemiological study. Another aim was to relate coughing to other explanatory variables and risk factors. A random sample of 1900 inhabitants from the age of 20, stratified for age and gender, was recruited. Subjects were invited for clinical examinations that included questions about general odor intolerance, respiratory symptoms, and smoking habits, and a smell identification test. In total, 1387 volunteers (73% of the sample) were investigated. The overall prevalence of self-reported chronic cough was 6.3% [95% confidence interval (CI): 5.0-7.6%]. Female gender, age, height, BMI, and smoking were significantly related to cough. Furthermore, nasal blockage, nasal secretion, sneezing, asthma, odor and cold air sensitivity, and aspirin intolerance also related to cough with statistical significance, indicating a close connection between chronic cough and upper airway symptoms. In keeping with other studies, this study demonstrates that chronic cough is a widespread problem in society, and is about twice as common in women than in men. © 2012 Bende and Millqvist.


Blanc P.D.,University of California at San Francisco | Blanc P.D.,Gothenburg University
American Journal of Industrial Medicine | Year: 2015

Background: Very rapidly progressive "acute silicosis" was observed prior to the 1930 International Labour Office Conference on silicosis, but its clinical significance and pathologic relationship to classic silica caused pneumoconiosis were not settled. Methods: Textual analysis of the 1930 Conference proceedings identified data relevant to rapidly progressive silicosis. Standard bibliographic searches identified relevant biomedical literature dating from before and after the Conference. Results: The 1930 Johannesburg Conference contained descriptions of acute silicosis, especially in the abrasive powders industry, but acute silica-related lung disease did not conform to a three-stage disease model in which tuberculosis supra-infection caused advanced disease, a model accepted at the Conference. Over following decades, additional reports appeared of rapidly progressive silicosis, unrelated to tuberculosis. Pulmonary alveolar proteinosis was identified only in 1958. Conclusions: Adoption by the 1930 Johannesburg Conference of a classification scheme into which acute rapidly progressive disease unrelated to tuberculosis fitted poorly may have impeded the understanding of acute silicosis and its importance. © 2015 Wiley Periodicals, Inc.


Muduli P.K.,Gothenburg University | Heinonen O.G.,Argonne National Laboratory | Akerman J.,KTH Royal Institute of Technology
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We have measured the bias voltage and field dependence of eigenmode frequencies in a magnetic tunnel junction with MgO barrier. We show that both free layer (FL) and reference layer (RL) modes are excited, and that a crossover between these modes is observed by varying external field and bias voltage. The bias voltage dependence of the FL and RL modes are shown to be dramatically different. The bias dependence of the FL modes is linear in bias voltage, whereas that of the RL mode is strongly quadratic. Using modeling and micromagnetic simulations, we show that the linear bias dependence of FL frequencies is primarily due to a linear dependence of the perpendicular spin torque on bias voltage, whereas the quadratic dependence of the RL on bias voltage is dominated by the reduction of exchange bias due to Joule heating, and is not attributable to a quadratic dependence of the perpendicular spin torque on bias voltage. © 2011 American Physical Society.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: REGIONS-1;REGIONS-2009-1 | Award Amount: 1.65M | Year: 2010

Water resource management is becoming an urgent challenge, for Europe and the world, as populations grow and requirements increase. Degradation of our coastal and estuarine waters is of particular concern to policy makers at regional, national, EU and international levels, and increasingly to the public at large. The EMSAC project will address this challenge by ensuring that Europes knowledge resource is effectively directed towards building the mix of solutions required. These include: advanced sensing and surveillance systems, improved operational management for resource extraction including renewable energy, better management of coastal ecosystems and protected areas, techniques to minimise impacts of flooding due to sea-level rise, and advances in resource-efficient desalination. EMSAC will help achieve this by working collaboratively with clusters of expertise in different regions of Europe, involving research institutions, businesses and public authorities. These new relationships will facilitate a shared action plan of priorities in RTD, innovation and their supporting infrastructure. Europe is fortunate to possess many world-class research bodies in the field of coastal and estuarine sciences, as well as a vibrant mix of companies operating in the coastal zone management, renewable energy & monitoring markets. However, this expertise is presently fragmented across disciplines, and investment in RTD lacks consistency between regional, national and EU levels. There is also inadequate coupling between the RTD base and this rapidly evolving market domain. By working with leading regional clusters of capability, and inviting other regions to engage during the project, EMSAC will stimulate an integrated investment portfolio of RTD priorities and innovation capacity. This will not only deliver improved resource management in coastal and estuarine waters, but will also position Europes businesses to exploit this commercial opportunities to the full.


Muth A.,Institute of Clinical science | Ragnarsson O.,Gothenburg University | Johannsson G.,Gothenburg University | Wangberg B.,Institute of Clinical science
British Journal of Surgery | Year: 2015

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension. The main aims of this paper were to review outcome after surgical versus medical treatment of PA and partial versus total adrenalectomy in patients with PA. Methods: Relevant medical literature from PubMed, the Cochrane Library and Embase OvidSP from 1985 to June 2014 was reviewed. Results: Of 2036 records, 43 articles were included in the final analysis. Twenty-one addressed surgical versus medical treatment of PA, four considered partial versus total adrenalectomy for unilateral PA, and 18 series reported on surgical outcomes. Owing to the heterogeneity of protocols and reported outcomes, only a qualitative analysis was performed. In six studies, surgical and medical treatment had comparable outcomes concerning blood pressure, whereas six showed better outcome after surgery. No differences were seen in cardiovascular complications, but surgery was associated with the use of fewer antihypertensive medications after surgery, improved quality of life, and (possibly) lower all-cause mortality compared with medical treatment. Randomized studies indicate a role for partial adrenalectomy in PA, but the high rate of multiple adenomas or adenoma combined with hyperplasia in localized disease is disconcerting. Surgery for unilateral dominant PA normalized BP in a mean of 42 (range 20-72) per cent and the biochemical profile in 96-100 per cent of patients. The mean complication rate in 1056 patients was 4.7 per cent. Conclusion: Recommendations for treatment of PA are hampered by the lack of randomized trials, but support surgical resection of unilateral disease. Partial adrenalectomy may be an option in selected patients. © 2015 BJS Society Ltd.


News Article | December 8, 2016
Site: www.eurekalert.org

Bacterial resistance does not come just through adaptation to antibiotics, sometimes the bacteria simply go to sleep. An international team of researchers is looking at compounds that attack bacteria's ability to go dormant and have found the first oxygen-sensitive toxin antitoxin system. "Antibiotics can only kill bacteria when they are actively growing and dividing," said Thomas K. Wood, professor of chemical engineering and holder of the Biotechnology Endowed Chair, Penn State. "But, environmental stress factors often turn on a bacterial mechanism that creates a toxin that makes the cell dormant and therefore antibiotic resistant." Bacteria that form biofilms are often difficult to kill. They can react to environmental signals and produce a toxin that makes the cells go dormant. Antibiotics cannot target dormant cells. One type of bacterium that does this lives in the gastrointestinal track. Bile, secreted by the liver and stored in the gall bladder, when released into the GI track can kill bacteria. In the presence of bile, these bacteria produce a protein that is a self-toxin and the bacteria go dormant. When the bile is gone, the bacteria produce another protein that destroys the inhibitor protein and the bacteria come alive. These toxin antitoxin systems are inherent in bacteria and serve to protect them against a variety of external, environmental insults. Wood and his colleagues characterized the first toxin antitoxin system in a biofilm. They report today (Dec. 8) in Nature Communications that this system also is the first known to be oxygen-dependent. The characterization was done at the molecular and atomic level by researchers at the Biomolecular NMR Laboratory at the University of Barcelona, Spain. They found that the E. coli antitoxin's structure had channels that are just large enough for oxygen to pass through. The toxin in this system is Hha and the antitoxin is TomB. However, unlike other toxin antitoxin pairs where the toxin makes the cell dormant and the antitoxin inactivates the toxin by binding, this system needs oxygen in the presence of the antitoxin to oxidize the toxin and wake up the bacteria. "If we understand the toxin antitoxin systems at a molecular or atomic level, we can make better antimicrobials," said Wood. "I would argue that the toxin antitoxin systems are fundamental to the physiology of all bacteria. We hope this will give us insight into how they survive the antibiotics." Free-swimming bacteria are usually easily targeted by antibodies or antibiotics, but bacteria that form biofilms are harder to kill. In tuberculosis, the bacteria have as many as 88 different toxin options to react to environmental stresses. According to Wood, this is one of the reasons that TB patients need to stay on antibiotics for months or years to clear the body of all the bacteria. Biofilms are involved in 80 percent of human infections and are one of the strongest contributors to the pressing antibiotic resistance problem. The researchers found that 10 percent oxygen is sufficient to wake up the bacteria, but in a biofilm, the problem becomes accessibility. The bacteria on the edges of the film can be easily exposed to oxygen, but those further inside the film might not come into contact with the oxygen. The channels that form in the E. coli biofilm allow the oxygen to penetrate into the biofilm, awaken the bacteria, break up the biofilm and disperse it. The researchers suggest that this type of toxin, one that is oxygen-dependent, could become the target for antibacterial treatments to inhibit the formation of biofilms. Also working on this project at Penn State were W.C. Soo, postdoctoral fellow, and Thammajun L. Wood, research associate in chemical engineering. Other researchers included Oriol Marimon, Joáo M.C. Teixeira, Tiago N. Cordeiro, Irene Amata, Jesús Garcia, Ainara Morera and Miquel Pons, all at Biomolecular NMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain; Maxim Mayzel, and Vladislave Yu. Orekhov, Swedish NMR Centre, Gothenburg University, Gothenburg, Sweden; and Marina Gay and Marta Vilaseca, Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain.


Saljo R.,Gothenburg University | Saljo R.,University of Turku
Journal of Computer Assisted Learning | Year: 2010

The purpose of this article is to offer some reflections on the relationships between digital technologies and learning. It is argued that activities of learning, as they have been practised within institutionalized schooling, are coming under increasing pressure from the developments of digital technologies and the capacities to store, access and manipulate information that such resources offer. Thus, the technologies do not merely support learning; they transform how we learn and how we come to interpret learning. The metaphors of learning currently emerging as relevant in the new media ecology emphasize the transformational and performative nature of such activities, and of knowing in general. These developments make the hybrid nature of human knowing and learning obvious; what we know and master is, to an increasing extent, a function of the mediating tools we are familiar with. At a theoretical and practical level, this implies that the interdependences between human agency, minds, bodies and technologies have to serve as foundations when attempting to understand and improve learning. Attempts to account for what people know without integrating their mastery of increasingly sophisticated technologies into the picture will lack ecological validity. © 2010 Blackwell Publishing Ltd.


Hallqvist A.,Gothenburg University | Bergman B.,Sahlgrenska University Hospital | Nyman J.,Gothenburg University
Radiotherapy and Oncology | Year: 2012

Background: In non-small cell lung cancer (NSCLC) stage III, data on patient reported health-related quality of life (HRQL) are scarce, especially regarding concurrent chemoradiotherapy. Aims: To evaluate HRQL in patients treated with high dose radiotherapy combined with concurrent chemotherapy or the antibody cetuximab. Methods: The study population comprised all patients enroled in either of two phase II trials in locally advanced NSCLC performed in Sweden 2002-2007. The RAKET trial investigated three different ways of increasing local control (accelerated hyperfractionated treatment or concurrent daily or weekly chemotherapy). The Satellite trial evaluated the addition of cetuximab to thoracic irradiation. HRQL was measured at four time points: At baseline, before radiotherapy, 4-6 weeks after radiotherapy and at 3 months follow-up, using the EORTC QLQ-C30 and LC14 set of questionnaires. Results: 154/220 patients (65%) who completed HRQL assessments at all time points were included in the longitudinal study. There was a significant decline over time regarding most functioning measures. Dyspnoea and fatigue gradually deteriorated without recovery after completed treatment. Chemotherapy related symptoms showed a transient deterioration, whereas radiotherapy related esophagitis had not fully recovered at 3 months. Patients with stage IIIA disease tended to recover better regarding global QL, fatigue and dyspnoea compared to patients with stage IIIB. Patients with WHO performance status (PS) 0 reported improved global QL and less fatigue over time compared with PS 1. Concurrent chemotherapy was associated with more pronounced fatigue and dysphagia, and worse global QL compared with concurrent cetuximab. Baseline physical functioning was an independent predictor of overall survival. Conclusion: Patients undergoing high dose thoracic radiotherapy combined with chemotherapy or cetuximab reported a gradual deterioration in functioning, dyspnoea and fatigue, while treatment related side effects were transient. Radiotherapy with concurrent cetuximab had less negative impact on HRQL than concurrent chemoradiation. © 2011 Elsevier Ireland Ltd. All rights reserved.


Lindkvist B.,Gothenburg University | Lindkvist B.,Sahlgrenska University Hospital
World Journal of Gastroenterology | Year: 2013

Pancreatic exocrine insufficiency is an important cause of maldigestion and a major complication in chronic pancreatitis. Normal digestion requires adequate stimulation of pancreatic secretion, sufficient production of digestive enzymes by pancreatic acinar cells, a pancreatic duct system without significant outflow obstruction and adequate mixing of the pancreatic juice with ingested food. Failure in any of these steps may result in pancreatic exocrine insufficiency, which leads to steatorrhea, weight loss and malnutrition-related complications, such as osteoporosis. Methods evaluating digestion, such as fecal fat quantification and the 13C-mixed triglycerides test, are the most accurate tests for pancreatic exocrine insufficiency, but the probability of the diagnosis can also be estimated based on symptoms, signs of malnutrition in blood tests, fecal elastase 1 levels and signs of morphologically severe chronic pancreatitis on imaging. Treatment for pancreatic exocrine insufficiency includes support to stop smoking and alcohol consumption, dietary consultation, enzyme replacement therapy and a structured follow-up of nutritional status and the effect of treatment. Pancreatic enzyme replacement therapy is administered in the form of enteric-coated minimicrospheres during meals. The dose should be in proportion to the fat content of the meal, usually 40-50000 lipase units per main meal, and half the dose is required for a snack. In cases that do not respond to initial treatment, the doses can be doubled, and proton inhibitors can be added to the treatment. This review focuses on current concepts of the diagnosis and treatment of pancreatic exocrine insufficiency. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.


Devries K.M.,London School of Hygiene and Tropical Medicine | Mak J.Y.,London School of Hygiene and Tropical Medicine | Bacchus L.J.,London School of Hygiene and Tropical Medicine | Child J.C.,London School of Hygiene and Tropical Medicine | And 4 more authors.
PLoS Medicine | Year: 2013

Background:Depression and suicide are responsible for a substantial burden of disease globally. Evidence suggests that intimate partner violence (IPV) experience is associated with increased risk of depression, but also that people with mental disorders are at increased risk of violence. We aimed to investigate the extent to which IPV experience is associated with incident depression and suicide attempts, and vice versa, in both women and men.Methods and Findings:We conducted a systematic review and meta-analysis of longitudinal studies published before February 1, 2013. More than 22,000 records from 20 databases were searched for studies examining physical and/or sexual intimate partner or dating violence and symptoms of depression, diagnosed major depressive disorder, dysthymia, mild depression, or suicide attempts. Random effects meta-analyses were used to generate pooled odds ratios (ORs). Sixteen studies with 36,163 participants met our inclusion criteria. All studies included female participants; four studies also included male participants. Few controlled for key potential confounders other than demographics. All but one depression study measured only depressive symptoms. For women, there was clear evidence of an association between IPV and incident depressive symptoms, with 12 of 13 studies showing a positive direction of association and 11 reaching statistical significance; pooled OR from six studies = 1.97 (95% CI 1.56-2.48, I2 = 50.4%, pheterogeneity = 0.073). There was also evidence of an association in the reverse direction between depressive symptoms and incident IPV (pooled OR from four studies = 1.93, 95% CI 1.51-2.48, I2 = 0%, p = 0.481). IPV was also associated with incident suicide attempts. For men, evidence suggested that IPV was associated with incident depressive symptoms, but there was no clear evidence of an association between IPV and suicide attempts or depression and incident IPV.Conclusions:In women, IPV was associated with incident depressive symptoms, and depressive symptoms with incident IPV. IPV was associated with incident suicide attempts. In men, few studies were conducted, but evidence suggested IPV was associated with incident depressive symptoms. There was no clear evidence of association with suicide attempts.Please see later in the article for the Editors' Summary. © 2013 Devries et al.


Jagers S.C.,Lulea University of Technology | Berlin D.,Gothenburg University | Jentoft S.,University of Tromsø
Marine Policy | Year: 2012

Why do fishers break rules? And why do they follow them? The answers to these pertinent questions could contribute to reducing overfishing, stock decimation, environmental degradation, economic losses and community failures. This explorative paper presents findings from a nationwide survey among Swedish fishers, who were asked what, in their opinion, would justify non-compliance, why fisheries management regulations are not being respected, and what might help improve the situation. The survey was conducted to test four inducements often suggested in the literature: Fishers' compliance/non-compliance is based on (a) their own benefit, (b) whether they feel morally compelled to do one way or another, (c) whether compliance is believed to create a negative impression among peers and (d) whether they accept the justification given for introducing the rules. Among other things, the study finds that the moral motives of law-abidingness and peer group solidarity rank the highest among the reasons for compliance, that large-scale fishers are more concerned about deterrence than small- and medium-scale fishers and also that co-management experience makes fishers less inclined to accept non-compliance by fishers who seek to boost their income. © 2012 Elsevier Ltd.


Bernhardsson S.,Gothenburg University | Klintberg I.H.,Sahlgrenska University Hospital | Wendt G.K.,Sahlgrenska University Hospital
Clinical Rehabilitation | Year: 2011

Objective: To evaluate the effect on pain intensity and function of an exercise concept focusing on specific eccentric strength training of the rotator cuff in patients with subacromial impingement syndrome. Design: Single-subject research design with baseline and treatment phases (AB design). Setting: Home-based training programme supervised and supported by visits to physiotherapy clinic. Subjects: Ten patients, mean (SD) age 54 (8.6) years, symptom duration 12 (9.1) months. Intervention: Daily eccentric strengthening exercises of the rotator cuff during 12 weeks. Main measures: Primary outcome measures: Pain intensity, assessed with a visual analogue scale, and function, using the Patient-Specific Functional Scale. Secondary outcome measures: Shoulder function evaluated with the Constant score, and shoulder-related quality of life evaluated with the Western Ontario Rotator Cuff Index. Results: Pain intensity decreased significantly in eight of the ten subjects. Function improved significantly in all ten subjects. Constant score increased in nine subjects and Western Ontario Rotator Cuff Index increased in seven subjects. Mean Constant score for the whole group increased significantly from 44 to 69 points (P = 0.008). Mean Western Ontario Rotator Cuff Index increased from 51 to 71% (P = 0.021). Conclusion: A 12-week eccentric strengthening programme targeting the rotator cuff and incorporating scapular control and correct movement pattern can be effective in decreasing pain and increasing function in patients with subacromial impingement syndrome. A randomized controlled trial is necessary to provide stronger evidence of the method. © 2011 The Author(s).


Zhang H.,China Agricultural University | Liu K.,Gothenburg University
Human Reproduction Update | Year: 2015

BACKGROUND: The first small follicles to appear in the mammalian ovaries are primordial follicles. The initial pool of primordial follicles serves as the source of developing follicles and oocytes for the entire reproductive lifespan of the animal. Although the selective activation of primordial follicles is critical for female fertility, its underlying mechanisms have remained poorly understood. METHODS: A search of PubMed was conducted to identify peer-reviewed literature pertinent to the study of mammalian primordial follicle activation, especially recent reports of the role of primordial follicle granulosa cells (pfGCs) in regulating this process. RESULTS: In recent years, molecular mechanisms that regulate the activation of primordial follicles have been elucidated, mostly through the use of genetically modified mouse models. Several molecules and pathways operating in both the somatic pfGCs and oocytes, such as the phosphatidylinositol 3 kinase (PI3K) and the mechanistic target of rapamycin complex 1 (mTORC1) pathways, have been shown to be important for primordial follicle activation. More importantly, recent studies have provided an updated view of how exactly signaling pathways in pfGCs and in oocytes, such as the KIT ligand (KL) and KIT, coordinate in adult ovaries so that the activation of primordial follicles is achieved. CONCLUSIONS: In this review, we have provided an updated picture of how mammalian primordial follicles are activated. The functional roles of pfGCs in governing the activation of primordial follicles in adulthood are highlighted. The in-depth understanding of the cellular and molecular mechanisms of primordial follicle activation will hopefully lead to more treatments of female infertility, and the current progress indicates that the use of existing primordial follicles as a source for obtaining fertilizable oocytes as a new treatment for female infertility is just around the corner. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Wu J.,Dana-Farber Cancer Institute | Bostrom P.,Dana-Farber Cancer Institute | Sparks L.M.,Maastricht University | Ye L.,Dana-Farber Cancer Institute | And 13 more authors.
Cell | Year: 2012

Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential. © 2012 Elsevier Inc.


Bath M.,Gothenburg University | Bath M.,Sahlgrenska University Hospital
Radiation Protection Dosimetry | Year: 2010

There are many ways in which imaging systems can be evaluated. The aim of the present paper is to provide an overview of a number of selected approaches to evaluating imaging systems, often encountered by the medical physicist, and discuss their validity and reliability. Specifically, it will cover (i) characterisation of an imaging system in terms of its detective quantum efficiency using linear-systems analysis; (ii) attempts to calculate relevant measures directly in images using the Rose model and the pixel signal-to-noise ratio; (iii) task-based methods incorporating human observers such as receiver-operating characteristics and (iv) visual grading-based methods using experienced radiologists as observers. © The Author 2010. Published by Oxford University Press.


Dalsgaard T.,University of Aarhus | De Brabandere L.,University of Southern Denmark | Hall P.O.J.,Gothenburg University
Geochimica et Cosmochimica Acta | Year: 2013

Removal of fixed nitrogen in the water column of the eastern Gotland Basin, central Baltic Sea, was studied during two cruises in September 2008 and August 2010. The water column was stratified with anoxic sulfidic bottom water meeting oxic nitrate containing water at the oxic-anoxic interface. Anammox was never detected whereas denitrification was found in all incubations from anoxic depths and occurred immediately below the oxic-anoxic interface. Sulfide (H2S+HS-+S2-) was in most cases the only electron donor for denitrification but, in contrast to previous findings, denitrification was in some situations driven by organic matter alone. Nitrous oxide (N2O) became an increasingly important product of denitrification with increasing sulfide concentration and was >80% of the total N gas formation at 10μM sulfide. The potential rates of denitrification measured in incubations at elevated NO3- or sulfide concentrations were converted to in situ rates using the measured water column concentrations of NO3- and sulfide and the actual measured relations between NO3- and sulfide concentrations and denitrification rates. In situ denitrification ranged from 0.24 to 15.9nMN2h-1. Assuming that these rates were valid throughout the anoxic NO3- containing zone, depth integrated in situ denitrification rates of 0.06-2.11mmol Nm-2d-1 were estimated. The thickness of this zone was generally 3-6m, which is probably what can be maintained through regular turbulent mixing induced by internal waves at the oxic-anoxic interface. However, layers of up to 55m thickness with low O2 water (<10μM) were observed which was probably the result of larger scale mixing. In such a layer nitrification may produce NO3- and once the O2 has been depleted denitrification will follow resulting in enormous rates per unit area. Even with an active denitrification layer of 3-6m thickness the pelagic denitrification per unit area clearly exceeded sediment denitrification rates elsewhere in the Baltic Sea. When extrapolated to the entire Baltic Proper (BP) denitrification in the water column was in the range of 132-547ktonNyr-1 and was thus at least as important as sediment denitrification which has recently been estimated to 191ktonNyr-1. With a total external N-input of 773ktonNyr-1 it is clear that denitrification plays a significant role in the N-budget of the BP. © 2013 Elsevier Ltd.


Galfalk M.,Linköping University | Bastviken D.,Linköping University | Fredriksson S.,Gothenburg University | Arneborg L.,Gothenburg University
Journal of Geophysical Research: Biogeosciences | Year: 2013

The transport of gasses dissolved in surface waters across the water-atmosphere interface is controlled by the piston velocity (k). This coefficient has large implications for, e.g., greenhouse gas fluxes but is challenging to quantify in situ. At present, empirical k-wind speed relationships from a small number of studies and systems are often extrapolated without knowledge of model performance. This study compares empirical k estimates from flux chamber and surface water gas concentration measurements (chamber method), eddy cell modeling and dissipation rates of turbulent kinetic energy (dissipation method), and a surface divergence method based on IR imaging, at a fetch limited coastal observation station. We highlight strengths and weaknesses of the methods, and relate measured k values to parameters such as wave height, and surface skin velocities. The chamber and dissipation methods yielded k values in the same order of magnitude over a 24 h period with varying wind conditions (up to 10 m s-1, closest weather station) and wave heights (0.01-0.30 m). The surface divergence method most likely did not resolve the small turbulent eddies that cause the main divergence. Flux chamber estimates showed the largest temporal variability, with lower k values than the dissipation method during calm conditions, where the dissipation method failed as waves and instrument noise dominated over the turbulence signal. There was a strong correspondence between k from chambers, the RMS of surface velocities from IR imaging, and wave height. We propose a method to estimate area integrated values of k from wave measurements. Key Points Different methods for measuring the piston velocity k were comparedThe chamber and dissipation k-methods agree, except at calm conditionsNew k method proposed, based on strong correlation between k and wave height ©2013. American Geophysical Union. All Rights Reserved.


Norrman E.,Gothenburg University | Bergh C.,Sahlgrenska University Hospital | Wennerholm U.-B.,Gothenburg University
Human Reproduction | Year: 2015

STUDY QUESTION What is the child morbidity after IVF in women who have received a kidney transplant? SUMMARY ANSWER Overall, obstetric outcome and morbidity in children of women who had undergone renal transplantation and IVF treatment were favourable. WHAT IS KNOWN ALREADY There are several studies of the obstetric outcome in women with spontaneous conception after solid organ transplantation as well as studies of obstetric outcome after IVF in general. There are only a few case reports of women with kidney or pancreas-kidney transplantation and deliveries after IVF treatment. STUDY DESIGN, SIZE, DURATION A population-based retrospective register study was carried out in Sweden including all women with solid organ transplantation and deliveries after IVF; however, only women with kidney transplants were recruited. It also included information on all singleton deliveries after kidney transplantation and spontaneous conception between 1973 and 2012. PARTICIPANTS/MATERIALS, SETTING AND METHODS We cross-linked the IVF registers with the Medical Birth Register, the Patient Register and the Cause of Death Register. Study group 1 consisted of women with kidney transplantation and deliveries after IVF treatment. Study group 2 consisted of women with kidney transplantation and singleton deliveries after spontaneous conception. Group 3 (control group to singletons in study group 1) consisted of women without organ transplantation and with singleton deliveries after IVF, matched for maternal age, parity and date of birth. Group 4 (control group to study group 2) consisted of women without organ transplantation and with singleton deliveries after spontaneous conception, matched for maternal age, parity and year of birth. MAIN RESULTS AND THE ROLE OF CHANCE Seven singletons and one set of twins were born after organ transplantation and IVF. All women in this group had renal transplants. Among singletons, two (28.6%) were preterm births (PTB), one (14.3%) had very low birthweight (VLBW) (672 g) and one (14.3%) was small for gestational age (SGA). Two infants had minor birth defects. One woman developed pre-eclampsia (14.3%). Mean age at follow-up of the children was 9.7 years (SD 4.2). Two children were diagnosed with hyperactivity disorders. There were 199 singletons born after renal transplantation and spontaneous conception. The rates of pre-eclampsia (23.6%), PTB (48.5%), LBW (43.7%) and SGA (21.2%) were significantly higher in pregnancies of women with renal transplants who had conceived spontaneously than in pregnancies where there was no transplantation and conception was spontaneous. Neonatal morbidity, early neonatal and infant mortality were all significantly higher. No increase in birth defects was seen. Mean age at follow-up of the children was 14.7 years (SD 9.4). Acute bronchitis, systemic lupus erythematosus and hyperactivity disorders were more common in children delivered to women with renal transplantation than in children delivered to women with no transplanted organs. Otherwise, long-term child morbidity was comparable. LIMITATIONS, REASONS FOR CAUTION The women who had received renal transplants and who had given birth after IVF were a small group and may represent a selected group of comparatively healthy women. WIDER IMPLICATIONS OF THE FINDINGS The results are important to transplant recipients with infertility problems. Neonatal outcomes after maternal renal transplantation and spontaneous conception were in agreement with the literature. Long-term follow-up of this group of children has long been asked for and findings are included in this report. STUDY FUNDING/COMPETING INTERESTS No conflict of interest was reported. The study was supported by grants from Swedish Association of Local Authorities and Regions and by grants from the University of Gothenburg/Sahlgrenska University hospital (LUA/ALF 70940). © 2014 © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Background: Intensive treatment of patients with type 1 diabetes delays the onset of long-term complications. Objectives: On the basis of the information from two nation-wide quality registers, we investigated to which extent HbA1c values 3-15months after diagnosis in childhood are related to metabolic control, albuminuria, and retinopathy in early adulthood. Methods: In Sweden, physicians register all children and adolescents with type 1 diabetes mellitus in the Swedish Pediatric Quality Registry. After 18yr of age, people with diabetes are followed by the Swedish National Diabetes Register. We identified 1543 children and adolescents with a mean age of 13.9yr at diagnosis and a mean duration of type 1 diabetes mellitus of 7.1yr. Results: Children and adolescents with poor metabolic control (mean HbA1c ≥ 70mmol/mol (8.6 %)) adjacent to diagnosis had a significantly higher mean HbA1c value years later as adults than did patients with a good metabolic control [<50mmol/mol (6.7%) (p<0.001)]. The patients in the high group were also less physically active and smoked more as adults. The proportion of females was higher in the poor metabolic group. Patients with a high mean HbA1c 3-15months after diagnosis had significantly more often macroalbuminuria and retinopathy in early adulthood. Conclusions: Metabolic control adjacent to the diagnosis of type 1 diabetes in childhood or adolescence can predict metabolic control in early adulthood. It is therefore very important that pediatric diabetes teams identify key factors for successful early metabolic control. Actively using quality registries may be one such factor. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Horvath G.,Gothenburg University | Andersson H.,Sahlgrenska University Hospital | Nemes S.,Sahlgrenska University Hospital
BMC Cancer | Year: 2013

Background: In recent decades it has been noted that trained dogs can detect specific odor molecules emitted by cancer cells. We have shown that the same odor can also be detected in the patient's blood with high sensitivity and specificity by trained dogs. In the present study, we examined how the ability of dogs to detect this smell was affected by treatment to reduce tumor burden, including surgery and five courses of chemotherapy.Methods: In Series I, one drop of plasma from each of 42 ovarian cancer patients (taken between the fifth and sixth courses of chemotherapy) and 210 samples from healthy controls were examined by two trained dogs. All 42 patients in Series I had clinical complete responses, all except two had normal CA-125 values and all were declared healthy after primary treatment. In Series II, the dogs examined blood taken from a new subset of 10 patients at 3 and 6 months after the last (sixth) course of chemotherapy.Results: In Series I, the dogs showed high sensitivity (97%) and specificity (99%), for detecting viable cancer cells or molecular cancer markers in the patients' plasma. Indeed, 29 of 42 patients died within 5 years. In Series II, the dogs indicated positive samples from three of the 10 patients at both the 3- and 6-month follow-up. All three patients had recurrences, and two died 3-4 years after the end of treatment. This was one of the most important findings of this study. Seven patients were still alive in January 2013.Conclusions: Although our study was based on a limited number of selected patients, it clearly suggests that canine detection gave us a very good assessment of the prognosis of the study patients. Being able to detect a marker based on the specific cancer odor in the blood would enhance primary diagnosis and enable earlier relapse diagnosis, consequently increasing survival. © 2013 Horvath et al.; licensee BioMed Central Ltd.


Tremaroli V.,Sahlgrenska University Hospital | Tremaroli V.,Gothenburg University | Backhed F.,Sahlgrenska University Hospital | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS
Nature | Year: 2012

The link between the microbes in the human gut and the development of obesity, cardiovascular disease and metabolic syndromes, such as type 2 diabetes, is becoming clearer. However, because of the complexity of the microbial community, the functional connections are less well understood. Studies in both mice and humans are helping to show what effect the gut microbiota has on host metabolism by improving energy yield from food and modulating dietary or the host-derived compounds that alter host metabolic pathways. Through increased knowledge of the mechanisms involved in the interactions between the microbiota and its host, we will be in a better position to develop treatments for metabolic disease. © 2012 Macmillan Publishers Limited. All rights reserved.


Rebesco M.,National Institute of Oceanography and Applied Geophysics - OGS | Hernandez-Molina F.J.,Royal Holloway, University of London | Van Rooij D.,Ghent University | Wahlin A.,Gothenburg University
Marine Geology | Year: 2014

The contourite paradigm was conceived a few decades ago, yet there remains a need to establish a sound connection between contourite deposits, basin evolution and oceanographic processes. Significant recent advances have been enabled by various factors, including the establishment of two IGCP projects and the realisation of several IODP expeditions. Contourites were first described in the Northern and Southern Atlantic Ocean, and since then, have been discovered in every major ocean basin and even in lakes. The 120 major contourite areas presently known are associated to myriad oceanographic processes in surface, intermediate and deep-water masses. The increasing recognition of these deposits is influencing palaeoclimatology & palaeoceanography, slope-stability/geological hazard assessment, and hydrocarbon exploration. Nevertheless, there is a pressing need for a better understanding of the sedimentological and oceanographic processes governing contourites, which involve dense bottom currents, tides, eddies, deep-sea storms, internal waves and tsunamis. Furthermore, in light of the latest knowledge on oceanographic processes and other governing factors (e.g. sediment supply and sea-level), existing facies models must now be revised. Persistent oceanographic processes significantly affect the seafloor, resulting in large-scale depositional and erosional features. Various classifications have been proposed to subdivide a continuous spectrum of partly overlapping features. Although much progress has been made in the large-scale, geophysically based recognition of these deposits, there remains a lack of unambiguous and commonly accepted diagnostic criteria for deciphering the small-scaled contourite facies and for distinguishing them from turbidite ones. Similarly, the study of sandy deposits generated or affected by bottom currents, which is still in its infancy, offers great research potential: these deposits might prove invaluable as future reservoir targets. Expectations for the forthcoming analysis of data from the IODP Expedition 339 are high, as this work promises to tackle much of the aforementioned lack of knowledge. In the near future, geologists, oceanographers and benthic biologists will have to work in concert to achieve synergy in contourite research to demonstrate the importance of bottom currents in continental margin sedimentation and evolution. © 2014 The Authors.


Tait K.,Plymouth Marine Laboratory | Havenhand J.,Gothenburg University
Molecular Ecology | Year: 2013

Increased settlement on bacterial biofilms has been demonstrated for a number of marine invertebrate larvae, but the nature of the cue(s) responsible is not well understood. We tested the hypothesis that the bay barnacle Balanus improvisus utilizes the bacterial signal molecules N-acylhomoserine lactones (AHLs) as a cue for the selection of sites for permanent attachment. Single species biofilms of the AHL-producing bacteria Vibrio anguillarum, Aeromonas hydrophila and Sulfitobacter sp. BR1 were attractive to settling cypris larvae of B. improvisus. However, when AHL production was inactivated, either by mutation of the AHL synthetic genes or by expression of an AHL-degrading gene (aiiA), the ability of the bacteria to attract cyprids was abolished. In addition, cyprids actively explored biofilms of E. coli expressing the recombinant AHL synthase genes luxI from Vibrio fischeri (3-oxo-C6-HSL), rhlI from Pseudomonas aeruginosa (C4-HSL/C6-HSL), vanI from V. anguillarum (3-oxo-C10-HSL) and sulI from Sulfitobacter sp. BR1 (C4-HSL, 3-hydroxy-C6-HSL, C8-HSL and 3-hydroxy-C10-HSL), but not E. coli that did not produce AHLs. Finally, synthetic AHLs (C8-HSL, 3-oxo-C10-HSL and C12-HSL) at concentrations similar to those found within natural biofilms (5 μm) resulted in increased cyprid settlement. Thus, B. improvisus cypris exploration of and settlement on biofilms appears to be mediated by AHL-signalling bacteria in the laboratory. This adds to our understanding of how quorum sensing inhibition may be used as for biofouling control. Nonetheless, the significance of our results for larvae settling naturally in the field, and the mechanisms that underlay the observed responses to AHLs, is as yet unknown. © 2013 Blackwell Publishing Ltd.


Sunnerhagen K.S.,Gothenburg University | Olver J.,Monash University | Francisco G.E.,University of Texas Health Science Center at Houston
Neurology | Year: 2013

Poststroke spasticity (PSS) is associated with significant consequences for a patient's functional status and quality of life. Nonetheless, no uniform definition of spasticity exists that can be utilized across clinical research settings, and difficulties in validating proper assessment tools-both clinical and nonclinical-complicate the ability to evaluate and appropriately treat spasticity. Consequently, the current state of defining, assessing, and treating spasticity requires improved consistency and ongoing validation as clinical research efforts advance. When selecting clinical measures for PSS assessment (e.g., the Modified Ashworth, Tone Assessment, Tardieu, Modified Rankin, and Disability Assessment scales, and the Barthel Index), it is critical to understand the levels of impairment or functional limitation each tool assesses as well as their benefits and limitations. The use of quantitative methods-such as electrophysiologic, biomechanical, and imaging techniques-adjunctive to traditional clinical measures also allows for sensitivity in quantifying the abnormal muscle activity associated with spasticity. In addition to accurate evaluation and assessment of PSS, realistic treatment goal setting for patients as well as family members and caregivers is critical, because it promotes motivation and cooperation as well as proper management of expectations and can favorably affect recovery. Goal attainment scaling has been shown to help organize, focus, and clarify the aims of treatment, thereby enhancing the PSS rehabilitative process. Furthermore, integration of therapeutic modalities and treatment strategies, including both nonpharmacologic intervention and pharmacotherapy, is also important for improved outcomes. © 2013 American Academy of Neurology.


Wenneras C.,Sahlgrenska University Hospital | Wenneras C.,Gothenburg University
Clinical Microbiology and Infection | Year: 2015

Candidatus Neoehrlichia mikurensis, which has rodents as its natural hosts, is an emerging tick-borne pathogen in Europe and Asia. This intracellular bacterium causes the infectious disease neoehrlichiosis. Immunocompromised patients may contract a severe form of neoehrlichiosis with high fever and vascular/thromboembolic events. As it is not detected with routine culture-based methods, neoehrlichiosis is underdiagnosed. © 2015 European Society of Clinical Microbiology and Infectious Diseases.


Stanton G.R.,University of Pennsylvania | Norrby P.-O.,Gothenburg University | Carroll P.J.,University of Pennsylvania | Walsh P.J.,University of Pennsylvania
Journal of the American Chemical Society | Year: 2012

Nucleophilic additions to α-chiral α-halo carbonyl derivatives are well-known to generate Cornforth-Evans products via a nonchelation pathway. What was unprecedented before this report is C-X bonds reversing the diastereoselectivity through coordination to metals during C-C bond-forming reactions (chelation control). Herein we describe chelation control involving C-X bonds in highly diastereoselective additions of organozinc reagents to a variety of α-chloro aldimines. The unique ability of alkylzinc halide Lewis acids to coordinate to the Cl, N, and O of α-chloro sulfonyl imine substrates is supported by computational studies. © 2012 American Chemical Society.


Lennartsson A.-K.,The Institute of Stress Medicine | Lennartsson A.-K.,Gothenburg University | Jonsdottir I.H.,The Institute of Stress Medicine | Jonsdottir I.H.,Gothenburg University
Psychoneuroendocrinology | Year: 2011

Background: Serum levels of the anterior pituitary hormone prolactin have been reported to increase in response to different types of psychological stressors in humans. However, experimental laboratory stress studies investigating the acute response of prolactin to psychological stress show inconsistent results as increased, as well as decreased or unchanged levels of prolactin have been reported. Objective: The aim of this study was to investigate the effect of acute psychosocial stress on serum concentrations of prolactin in healthy men and women and possible sex differences. Method: Thirty men and 15 women (age 30-50 years) underwent Trier Social Stress Test (TSST), a tool for investigating psychobiological stress responses in a laboratory setting. Blood samples were collected before and directly after the stress test and after 30. min of recovery. Results: We observed significantly elevated prolactin levels - along with significantly increased plasma adrenocorticotropic hormone (ACTH), serum cortisol, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) - in response to the stressor. The prolactin response pattern did not differ between men and women, but there was some indication that women might have higher magnitude of response. Large individual differences regarding the magnitude of response were seen in general. The magnitude of the prolactin response was significantly related to the magnitude of the response of the hypothalamic-pituitary-adrenal (HPA) axis and, to some extent, the cardiovascular responses, indicating that individual differences in prolactin response in healthy men and women are dependent on the general physiological stress activation. In women, the magnitude of response was also related to estradiol level. Conclusion: Prolactin does increase in response to psychosocial stress, however, with large individual variation in magnitude of response. The pattern of prolactin response does not differ between men and women. However, there was some indication that women might have higher magnitude of increase than men, and that the magnitude of response in women was dependent on estradiol levels, and this needs to be further studied. © 2011 Elsevier Ltd.


Nilsson M.,Gothenburg University | Fagman H.,Sahlgrenska University Hospital
Current Topics in Developmental Biology | Year: 2013

Thyroid dysgenesis is the most common cause of congenital hypothyroidism that affects 1 in 3000 newborns. Although a number of pathogenetic mutations in thyroid developmental genes have been identified, the molecular mechanism of disease is unknown in most cases. This chapter summarizes the current knowledge of normal thyroid development and puts the different developmental stages in perspective, from the time of foregut endoderm patterning to the final shaping of pharyngeal anatomy, for understanding how specific malformations may arise. At the cellular level, we will also discuss fate determination of follicular and C-cell progenitors and their subsequent embryonic growth, migration, and differentiation as the different thyroid primordia evolve and merge to establish the final size and shape of the gland. © 2013 Elsevier Inc.


Okin P.M.,New York Medical College | Kjeldsen S.E.,University of Michigan | Dahlof B.,Gothenburg University | Devereux R.B.,New York Medical College
Circulation: Cardiovascular Quality and Outcomes | Year: 2011

Background-Blacks have A higher prevalence of heart failure (HF) than nonblacks, possibly reflecting A greater burden of HF risk factors, including hypertension. Although HF incidence is significantly higher in blacks during long-term follow-up of young adults, the relationship of incident HF to race in hypertensive patients undergoing treatment is unclear. Methods and Results-Incident HF was evaluated in 497 black and 8199 nonblack hypertensive patients with no history of HF randomly assigned to losartan- or atenolol-based treatment. During 4.7±.1.1 years mean follow-up, HF hospitalization occurred in 265 patients (3.0%); 5-year HF incidence was significantly greater in black than nonblack patients (7.0 versus 3.1%, P< 0.001). In Cox multivariate analyses adjusting for randomized treatment, age, sex, the presence of the strain pattern on the baseline ECG, and other HF risk factors treated as standard covariates, and for incident myocardial infarction, in-treatment QRS duration, diastolic and systolic pressure, Cornell product, and Sokolow-Lyon voltage criteria for left ventricular hypertrophy (LVH) treated as time-varying covariates, black race remained associated with A 130% increased risk of developing new HF (hazard ratio 2.30, 95% confidence interval 1.24 to 4.28). Conclusions-Incident HF is substantially more common among black than nonblack hypertensive patients. The increased risk of developing new HF in blacks persists after adjusting for the higher prevalence of HF risk factors in blacks, for treatment effects and in-treatment blood pressure, and for the known predictive value of the ECG strain pattern and in-treatment ECG LVH and QRS duration for incident HF in this population. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260. (Circ Cardiovasc Qual Outcomes. 2011;4:157-164.). © 2011 American Heart Association, Inc.


Dorey N.,Gothenburg University | Lancon P.,Gothenburg University | Thorndyke M.,Royal Swedish Academy Of Sciences | Dupont S.,Gothenburg University
Global Change Biology | Year: 2013

Our ability to project the impact of global change on marine ecosystem is limited by our poor understanding on how to predict species sensitivity. For example, the impact of ocean acidification is highly species-specific, even in closely related taxa. The aim of this study was to test the hypothesis that the tolerance range of a given species to decreased pH corresponds to their natural range of exposure. Larvae of the green sea urchin Strongylocentrotus droebachiensis were cultured from fertilization to metamorphic competence (29 days) under a wide range of pH (from pHT = 8.0/pCO2 ≈ 480 μatm to pHT = 6.5/pCO2 ≈ 20 000 μatm) covering present (from pHT 8.7 to 7.6), projected near-future variability (from pHT 8.3 to 7.2) and beyond. Decreasing pH impacted all tested parameters (mortality, symmetry, growth, morphometry and respiration). Development of normal, although showing morphological plasticity, swimming larvae was possible as low as pHT ≥ 7.0. Within that range, decreasing pH increased mortality and asymmetry and decreased body length (BL) growth rate. Larvae raised at lowered pH and with similar BL had shorter arms and a wider body. Relative to a given BL, respiration rates and stomach volume both increased with decreasing pH suggesting changes in energy budget. At the lowest pHs (pHT ≤ 6.5), all the tested parameters were strongly negatively affected and no larva survived past 13 days post fertilization. In conclusion, sea urchin larvae appeared to be highly plastic when exposed to decreased pH until a physiological tipping point at pHT = 7.0. However, this plasticity was associated with direct (increased mortality) and indirect (decreased growth) consequences for fitness. © 2013 John Wiley & Sons Ltd.


Niego B.,Monash University | Freeman R.,Monash University | Puschmann T.B.,University of Melbourne | Puschmann T.B.,Gothenburg University | And 2 more authors.
Blood | Year: 2012

Tissue-type plasminogen activator (t-PA) can modulate permeability of the neurovascular unit and exacerbate injury in ischemic stroke. We examined the effects of t-PA using in vitro models of the blood-brain barrier. t-PA caused a concentration-dependent increase in permeability. This effect was dependent on plasmin formation and potentiated in the presence of plasminogen. An inactive t-PA variant inhibited the t-PA-mediated increase in permeability, whereas blockade of lowdensity lipoprotein receptors or exposed lysine residues resulted in similar inhibition, implying a role for both a t-PA receptor, most likely a low-density lipoprotein receptor, and a plasminogen receptor. This effect was selective to t-PA and its close derivative tenecteplase. The truncated t-PA variant reteplase had a minor effect on permeability, whereas urokinase and desmoteplase were ineffective. t-PA also induced marked shape changes in both brain endothelial cells and astrocytes. Changes in astrocyte morphology coincided with increased F-actin staining intensity, larger focal adhesion size, and elevated levels of phosphorylated myosin. Inhibition of Rho kinase blocked these changes and reduced t-PA/plasminogen-mediated increase in permeability. Hence plasmin, generated on the cell surface selectively by t-PA, modulates the astro-cytic cytoskeleton, leading to an increase in blood-brain barrier permeability. Blockade of the Rho/Rho kinase pathway may have beneficial consequences during thrombolytic therapy. © 2012 by The American Society of Hematology.


Holmgren K.E.M.,Gothenburg University | Mardby A.-C.M.,Sahlgrenska University Hospital
Epidemiology Biostatistics and Public Health | Year: 2014

Background: The aim of this study was to investigate if low self-efficacy was associated with increased risk of sick-leave, in a general population of employed women and men. The aim was also to analyse differences in self-efficacy concerning age, education, income, and socio-economic position. Methods: This cross-sectional study was based on data collected in western Sweden, 2008. The study population consisted of 2,900 employed sick-listed individuals (E-SL) and 2,649 random working population individuals (R-WP). Both mailed questionnaire, including the General Self- Efficacy Scale (GSE) and register data on age, education, income and socio-economic position were used. A continuous mean score of the total GSE was calculated for each individual. A low GSE-score indicated low general self-efficacy. Results: Lower general self-efficacy had an increased odds ratio (OR) of belonging to a sick-listed general working population among both men (OR=1.60; 95% CI 1.32-1.94) and women (OR=1.26; 95% CI 1.08-1.47). The OR remained significant after adjustments for socio-demographic variables. Yet, men in the R-WP and women in both the R-WP and E-SL with lower education, income or socioeconomic position had lower general self-efficacy compared with those in each cohort with higher education, income or socio-economic position. Conclusions: Low self-efficacy was associated with increased probability of belonging to a sicklisted general working population. Although more research is needed, it seems highly relevant to take both self-efficacy and socio-economic factors into account in preventive and rehabilitation work targeting people on sick-leave.


Sarno G.,Uppsala University | Lagerqvist B.,Uppsala University | Frobert O.,Örebro University | Nilsson J.,Umeå University | And 5 more authors.
European Heart Journal | Year: 2012

Aims To compare the long-term outcome after percutaneous coronary intervention with 'new-generation' drug-eluting stents (n-DES) to 'older generation' DES (o-DES), and bare-metal stents (BMS) in a real-world population. Methods and results We evaluated 94 384 consecutive stent implantations (BMS, n 64 631; o-DES, n 19 202; n-DES, n 10 551) in Sweden from November 2006 to October 2010. All cases of definite stent thrombosis (ST) and restenosis were documented in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Older generation DES were classified as: Cypher and Cypher Select (Cordis Corporation, Miami, FL, USA), Taxus Express and Taxus Libert (Boston Scientific Corporation), and Endeavor (Medtronic Inc.) and n-DES as: Endeavor Resolute (Medtronic Inc.), XienceV, Xience Prime (Abbott Laboratories) and Promus, Promus Element (Boston Scientific Corporation). The Cox regression analyses unadjusted and adjusted for clinical and angiographic covariates showed a statistically significant lower risk of restenosis in n-DES compared with BMS [adjusted hazard ratio (HR) 0.29; 95 confidence interval (CI): 0.250.33] and o-DES (HR 0.62; 95 CI: 0.530.72). A lower risk of definite ST was found in n-DES compared with BMS (HR 0.38; 95 CI: 0.280.52) and o-DES (HR, 0.57; 95 CI: 0.410.79). The risk of death was significantly lower in n-DES compared with o-DES (adjusted HR: 0.77; 95 CI: 0.630.95) and BMS (adjusted HR: 0.55; 95 CI: 0.460.67). Conclusion Percutaneous coronary intervention with n-DES is associated with a 38 lower risk of clinically meaningful restenosis, a 43 lower risk of definite ST, and a 23 lower risk of death compared with o-DES in this observational study from a large real-world population. © 2011 The Author.


Bjornsson E.,Reykjavik University | Jacobsen E.I.,Reykjavik University | Kalaitzakis E.,Gothenburg University
Journal of Hepatology | Year: 2012

Background & Aims: Limited data exist on drug-induced liver injury (DILI) associated with statins. Methods: Reports on adverse reactions suspected to be due to statins received by the Swedish Adverse Drug Reactions Advisory Committe 1988-2010 were analyzed. Only cases with >5 × upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2 × ULN were included. Results: The most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had at least possible relationship, median age 64 years (57-73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations of liver tests and 26 due to unlikely relationship and/or lack of data. A statin-related DILI episode was reported in 1.2/100,000 users. Atorvastatin was implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and others. Two patients died of acute liver failure, one underwent liver transplantation and 25 (34%) had jaundice. Three patients were rechallenged with the same statin producing similar patterns of liver injury. The median duration of therapy was 90 days (30-120), 120 (39-248) for atorvastatin, and 75 (30-150) for simvastatin (NS). Cholestatic/mixed injury was more common with atorvastatin, 17/30 (56%) than with simvastatin, 7/28 (24%) (p = 0.018). Conclusions: Idiosyncratic liver injury associated with statins is rare but can be severe. After recovery, a similar pattern of liver injury can be reproduced on re-exposure. Most patients experience liver injury 3-4 months after start of therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas hepatocellular injury is more common with simvastatin. © 2011 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.


Ramser K.,Lulea University of Technology | Hanstorp D.,Gothenburg University
Journal of Biophotonics | Year: 2010

In the last decade optical manipulation has evolved from a field of interest for physicists to a versatile tool widely used within life sciences. This has been made possible in particular due to the development of a large variety of imaging techniques that allow detailed information to be gained from investigations of single cells. The use of multiple optical traps has high potential within single-cell analysis since parallel measurements provide good statistics. Multifunctional optical tweezers are, for instance, used to study cell heterogeneity in an ensemble, and force measurements are used to investigate the mechanical properties of individual cells. Investigations of molecular motors and forces on the single-molecule level have led to discoveries that would have been difficult to make with other techniques. Optical manipulation has prospects within the field of cell signalling and tissue engineering. When combined with microfluidic systems the chemical environment of cells can be precisely controlled. Hence the influence of pH, salt concentration, drugs and temperature can be investigated in real time. Fast advancing technical developments of automated and user-friendly optical manipulation tools and cross-disciplinary collaboration will contribute to the routinely use of optical manipulation techniques within the life sciences. Applications of optical manipulation are multiple trapping and arrangements of cells (left upper part), force measurements of molecular forces and motors (right upper part), laser scalpel for diffusion experiments (left part below), or sorting (right part below), to name a few. This review aims to highlight the use of optical manipulation tools on biological cells. © 2010 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Dahlgren E.,Gothenburg University | Kjolhede P.,Linköping University
Acta Obstetricia et Gynecologica Scandinavica | Year: 2011

Objective. To determine the long-term objective and subjective outcomes of use of a porcine skin graft (Pelvicolâ¢) compared with conventional colporrhaphy in recurrent pelvic organ prolapse surgery and to analyze risk factors and safety. Design. Open randomized controlled multicenter study. Setting. Eight Swedish hospitals. Population. 135 consecutive women with recurrent cystocele and/or rectocele admitted for vaginal prolapse surgery; 132 completed the study, 64 were randomly allocated to receive conventional colporrhaphy and 68 to Pelvicol. Methods. Conventional anterior and posterior colporrhaphy and colporrhaphy with use of Pelvicol™ mesh reinforcement. Clinical evaluation by means of pelvic organ prolapse quantification (POP-Q) and symptom questionnaire preoperatively, three months and three years postoperatively. Main outcome measures. Anatomical and subjective outcome. Recurrence was defined as POP-Q≥stage 2. Results. At three-month follow-up, early recurrence/surgical failures occurred significantly more often in the Pelvicol™ group, but at the three-year follow-up the recurrence rates were similar. The recurrence rates in the anterior compartment were 57-62% and 44-23% in the posterior compartment for the colporrhaphy and Pelvicol™ groups, respectively. Symptoms were substantially and equally reduced in the two groups after surgery. Sexual activity and function did not seem to be affected adversely in any group. The complication rate was low. Risk factors for anatomical recurrence were age, body mass index and preoperative stage of the prolapse. Conclusions. With the surgical technique used in this study, Pelvicol™ did not provide advantages over conventional colporrhaphy in recurrent pelvic organ prolapse concerning anatomical and subjective outcomes. © 2011 Nordic Federation of Societies of Obstetrics and Gynecology.


Dupont S.,Gothenburg University | Thorndyke M.,Royal Swedish Academy Of Sciences
Journal of Experimental Marine Biology and Ecology | Year: 2012

Anthropogenic CO 2 emissions are acidifying the world's oceans. A growing body of evidence demonstrates that ocean acidification can impact survival, growth, development and physiology of marine invertebrates. However, little is known on the impact of elevated pCO 2 on immune-response. Here we investigate the impact of short-term (5-7days) exposure to elevated pCO 2 (1275μatm compared to 350μatm in the control) on extracellular pH (pHe) and cellular immune response in two polar echinoderm species, the green sea urchin Strongylocentrotus droebachiensis and the seastar Leptasterias polaris. Both species experienced extracellular acidosis following short term exposure to elevated pCO 2. While this acidosis remained uncompensated within 7days for L. polaris, pHe was fully compensated after 5days for S. droebachiensis. For both species, coelomic fluid acidosis was associated with an increase in total coelomocyte number and a reduction in vibratile cells in S. droebachiensis. A relationship between pHe and phagocyte numbers was observed in S. droebachiensis suggesting a direct link between pHe and cellular immune-response. Further studies would require the coordinated effort of ecologists and immunologists to understand the role of elevated pCO 2 on the host-pathogen interactions that are involved in the stability of ecosystems. © 2012 Elsevier B.V.


Stenman G.,Gothenburg University | Persson F.,Gothenburg University | Persson F.,Sahlgrenska University Hospital | Andersson M.K.,Gothenburg University
Oral Oncology | Year: 2014

Salivary gland carcinomas (SGCs) are uncommon tumors, constituting approximately 5% of all cancers of the head and neck. They are a heterogeneous group of diseases that pose significant diagnostic and therapeutic challenges. The treatment of patients with SGCs is mainly restricted to surgery and/or radiation therapy and there is only limited data available on the role of conventional systemic and targeted therapies in the management of patients with advanced disease. There is thus a great need to develop new molecular biomarkers to improve the diagnosis, prognostication, and therapeutic options for these patients. In this review, we will discuss the most recent developments in this field, with focus on pathognomonic gene fusions and other driver mutations of clinical significance. Comprehensive cytogenetic and molecular genetic analyses of SGCs have revealed a translocation-generated network of fusion oncogenes. The molecular targets of these fusions are transcription factors, transcriptional coactivators, and tyrosine kinase receptors. Prominent examples of clinically significant fusions are the MYB-NFIB fusion in adenoid cystic carcinoma and the CRTC1-MAML2 fusion in mucoepidermoid carcinoma. The fusions are key events in the molecular pathogenesis of these tumor types and contribute as new diagnostic, prognostic, and therapeutic biomarkers. Moreover, next-generation sequencing analysis of SGCs have revealed new druggable driver mutations, pinpointing alternative therapeutic options for subsets of patients. Continued molecular characterization of these fusions and their down-stream targets will ultimately lead to the identification of novel driver genes in SGCs and will form the basis for development of new therapeutic strategies for these patients. © 2014 Elsevier Ltd. All rights reserved.


Dupont S.,Gothenburg University | Lundve B.,Gothenburg University | Thorndyke M.,Royal Swedish Academy Of Sciences
Journal of Experimental Zoology Part B: Molecular and Developmental Evolution | Year: 2010

Ocean acidification (OA) is believed to be a major threat for near-future marine ecosystems, and that the most sensitive organisms will be calcifying organisms and the free-living larval stages produced by most benthic marine species. In this respect, echinoderms are one of the taxa most at risk. Earlier research on the impact of near-future OA on echinoderm larval stages showed negative effects, such as a decreased growth rate, increased mortality, and developmental abnormalities. However, all the long-term studies were performed on planktotrophic larvae while alternative life-history strategies, such as nonfeeding lecithotrophy, were largely ignored. Here, we show that lecithotrophic echinoderm larvae and juveniles are positively impacted by ocean acidification. When cultured at low pH, larvae and juveniles of the sea star Crossaster papposus grow faster with no visible affects on survival or skeletogenesis. This suggests that in future oceans, lecithotrophic species may be better adapted to deal with the threat of OA compared with planktotrophic ones with potentially important consequences at the ecosystem level. For example, an increase in populations of the top predator C. papposus will likely have huge consequences for community structure. Our results also highlight the importance of taking varying life-history strategies into account when assessing the impacts of climate change, an approach that also provides insight into understanding the evolution of life-history strategies. © 2010 Wiley-Liss, Inc.


Nordanstig J.,Sahlgrenska University Hospital | Taft C.,Gothenburg University | Hensater M.,Sahlgrenska University Hospital | Perlander A.,Sahlgrenska University Hospital | And 2 more authors.
Circulation | Year: 2014

Background-The quality of evidence for invasive revascularization in intermittent claudication is low or very low. This prospective, randomized, controlled study tested the hypothesis that an invasive treatment strategy versus continued noninvasive treatment improves health-related quality of life after 1 year in unselected patients with intermittent claudication. Methods and Results-After clinical and duplex ultrasound assessment, unselected patients with intermittent claudication requesting treatment for claudication were randomly assigned to invasive (n=79) or noninvasive (n=79) treatment groups. Primary end point was health-related quality of life after 1 year, assessed with Medical Outcomes Study Short Form 36 version 1 and Vascular Quality of Life Questionnaire, and secondary end points included walking distances on a graded treadmill. The Medical Outcomes Study Short Form 36 version 1 physical component summary (P<0.001) and 2 Medical Outcomes Study Short Form 36 version 1 physical subscales improved significantly more in the invasive versus the noninvasive treatment group. Overall, Vascular Quality of Life Questionnaire score (P<0.01) and 3 of 5 domain scores improved significantly more in the invasive versus the noninvasive treatment group. Intermittent claudication distance improved significantly in the invasive (+124 m) versus the noninvasive (+50 m) group (P=0.003), whereas the change in maximum walking distance was not significantly different between groups. Conclusions-An invasive treatment strategy improves health-related quality of life and intermittent claudication distance after 1 year in patients with stable lifestyle-limiting claudication receiving current medical management. Long-term follow-up data and health-economic assessments are warranted to further establish the role for revascularization in intermittent claudication. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01219842. © 2014 American Heart Association, Inc.


Benrick A.,Gothenburg University | Wallenius V.,Sahlgrenska University Hospital | Asterholm I.W.,Gothenburg University
Experimental Physiology | Year: 2012

Interleukin-6 (IL-6) is released from working skeletal muscle during exercise. We investigated the acute and the long-term beneficial effects of IL-6 on exercise-induced glucose uptake in skeletal muscle and insulin sensitivity. The acute effect on exercise-induced glucose uptake was measured in IL-6-deficient (IL-6-/-) mice and wild-type control animals using a tracer technique. There was no difference in serum disappearance of 3[H]2-deoxyglucose after a single bout of exercise between IL-6-/- and wild-type mice (13565 ± 426 versus 14343 ± 1309 d.p.m. min ml-1, P= 0.5). The glucose uptake rate in the extensor digitorum longus muscle was, however, lower in IL-6-/- compared with wild-type mice (398 ± 44 versus 657 ± 41 nmol g-1 min-1, P < 0.01). In a long-term study, we monitored insulin sensitivity, serum retinol-binding protein-4 (RBP-4) levels, running activity, food intake, body weight and body composition in IL-6-/- and wild-type mice on a high-fat diet (HFD), with or without access to running wheels. In sedentary IL-6-/- and wild-type mice, the HFD decreased insulin sensitivity (glucose area under the concentration-time curve increased about 20% during an insulin tolerance test, P < 0.05 for both genotypes versus baseline) and led to a 30% increase in serum RBP-4 levels (P < 0.01 for both genotypes versus baseline). Wild-type mice with access to running wheels were protected against these effects of the HFD and maintained their baseline insulin sensitivity and serum RBP-4 levels. In contrast, IL-6-/- mice did not benefit from running to the same extent as wild-type animals. The IL-6-/- mice with access to running wheels had a similar decrease in insulin sensitivity to their sedentary littermates (glucose area under the concentration-time curve during an insulin tolerance test in runners versus sedentary IL-6-/- HFD mice, 312 ± 14 versus 340 ± 22 mmol min l-1, P= 0.4) and displayed a 14% increase in serum RBP-4 compared with baseline levels (P < 0.01). Our results indicate that endogenous IL-6 contributes to the exercise-induced increase in insulin sensitivity, but plays only a minor role for glucose uptake into skeletal muscle during exercise. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.


Tatlisumak T.,Gothenburg University | Tatlisumak T.,Sahlgrenska University Hospital
Stroke | Year: 2015

Timely recanalization leads to improved patient outcomes in acute ischemic stroke. Recent trial results demonstrated a strong benefit for endovascular therapies over standard medical care in patients with acute ischemic stroke and a major intracranial artery occlusion ≤6 hours or even beyond from symptom onset and independent of patients' age. Previous studies have shown the benefit of intravenous thrombolysis that had gradually, albeit slowly, reshaped acute stroke care worldwide. Now, given the superior benefits of endovascular intervention, the whole structure of acute stroke care needs to be reorganized to meet patient needs and to deliver evidence-based treatments effectively. However, a blueprint for success with novel stroke treatments should be composed of numerous elements and requires efforts from various parties. Regarding the endovascular therapies, the strengths of Europe include highly organized democratic society structures, high rate of urbanization, well-developed revenue-based healthcare systems, and high income levels, whereas the obstacles include the east-west disparity in wealth, the ongoing economic crisis hindering spread of fairly costly new treatments, and the quickly aging population putting more demands on health care in general. Regional and national plans for covering whole population with 24/7 adequate acute stroke care are necessary in close cooperation of professionals and decision-makers. Europe-wide new training programs for expert physicians in stroke care should be initiated shortly. European Stroke Organisation has a unique role in providing expertise, consultation, guidelines, and versatile training in meeting new demands in stroke care. This article discusses the current situation, prospects, and challenges in Europe offering personal views on potential solutions. © 2015 American Heart Association, Inc.


Bach L.,University of Aarhus | Dahllof I.,Gothenburg University
Aquatic Toxicology | Year: 2012

The objective of this study was to investigate whether populations inhabiting a contaminated environment are affected in terms of decreased genetic diversity due to selection of tolerant genotypes and if such effect carries a cost. Marine arctic amphipod populations (Orchomenella pinguis) were collected from sites within a contaminated fjord, as well as from sites outside the fjord on the west-coast of Greenland over three years (2006-2008). Impacts on genetic diversity, effects on resilience such as development of tolerance and cost were determined. AFLP-analysis was used to explore within and between population genetic diversity, and exposure studies were performed where the populations were subjected to known and unknown stressors to assess resilience. Populations collected at three contaminated sites all had reduced genetic diversity in 2007 compared to populations outside the fjord. This pattern was different in 2008 as all contaminated site populations increased in diversity, whereas a decrease in diversity occurred at the outer sites. However, tolerance, but even more so, cost, was related to contamination exposure in 2008, in spite of the shift in genetic diversity. We suggest that contamination rapidly induces effects that can be captured as tolerance and associated cost, whereas effects on genetic diversity can be difficult to separate from recent migration events that dilute eventual decreases in diversity due to contamination pressure. As long as impacted populations can be influenced by migration events that increase the genetic diversity and add health to an affected population, populations in contaminated areas may have enhanced probability of survival. © 2012 Elsevier B.V.


Abtahi J.,Linköping University | Tengvall P.,Gothenburg University | Aspenberg P.,Linköping University
Bone | Year: 2012

Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6. months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohen's d = 1.3). The average difference in increase in ISQ, and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2. months (p = 0.012) and at 6. months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants. © 2012 Elsevier Inc.


Zetterberg H.,Gothenburg University | Smith D.H.,University of Pennsylvania | Blennow K.,Gothenburg University
Nature Reviews Neurology | Year: 2013

Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head. © 2013 Macmillan Publishers Limited. All rights reserved.


Stener-Victorin E.,Gothenburg University | Stener-Victorin E.,Heilongjiang University of Chinese Medicine
Molecular and Cellular Endocrinology | Year: 2013

Clinical and experimental evidence indicates that acupuncture may be a safe alternative or complement in the treatment of endocrine and reproductive function in women with polycystic ovary syndrome (PCOS). This review describes potential etiological factors of PCOS with the aim to support potential mechanism of action of acupuncture to relieve PCOS related symptoms. The theory that increased sympathetic activity contributes to the development and maintenance of PCOS is presented, and that the effects of acupuncture are, at least in part, mediated by modulation of sympathetic outflow. While there are no relevant randomized controlled studies on the use of acupuncture to treat metabolic abnormalities in women with PCOS, a number of experimental studies indicate that acupuncture may improve metabolic dysfunction. For each aspect of PCOS, it is important to pursue new treatment strategies that have fewer negative side effects than drug treatments, as women with PCOS often require prolonged treatment. © 2013 Elsevier Ireland Ltd.


Vaidya A.,Kathmandu Medical College | Vaidya A.,Nordic School of Public Health | Krettek A.,Gothenburg University | Krettek A.,Nordic School of Public Health
International Journal of Behavioral Nutrition and Physical Activity | Year: 2014

Background: Physical inactivity is a leading risk factor for cardiovascular and other noncommunicable diseases in high-, low- and middle-income countries. Nepal, a low-income country in South Asia, is undergoing an epidemiological transition. Although the reported national prevalence of physical inactivity is relatively low, studies in urban and peri-urban localities have always shown higher prevalence. Therefore, this study aimed to measure physical activity in three domains-work, travel and leisure-in a peri-urban community and assess its variations across different sociodemographic correlates.Methods: Adult participants (n = 640) from six randomly selected wards of the Jhaukhel-Duwakot Health Demographic Surveillance Site (JD-HDSS) near Kathmandu responded to the Global Physical Activity Questionnaire. To determine total physical activity, we calculated the metabolic equivalent of task in minutes/week for each domain and combined the results. Respondents were categorized into high, moderate or low physical activity. We also calculated the odds ratio for low physical activity in various sociodemographic variables and self-reported cardiometabolic states.Results: The urbanizing JD-HDSS community showed a high prevalence of low physical activity (43.3%; 95% CI 39.4-47.1). Work-related activity contributed most to total physical activity. Furthermore, women and housewives and older, more educated and self-or government-employed respondents showed a greater prevalence of physical inactivity. Respondents with hypertension, diabetes or overweight/obesity reported less physical activity than individuals without those conditions. Only 5% of respondents identified physical inactivity as a cardiovascular risk factor.Conclusions: Our findings reveal a high burden of physical inactivity in a peri-urban community of Nepal. Improving the level of physical activity involves sensitizing people to its importance through appropriate multi-sector strategies that provide encouragement across all sociodemographic groups. © 2014 Vaidya and Krettek; licensee BioMed Central Ltd.


Schoots I.G.,Erasmus Medical Center | Petrides N.,University College London | Giganti F.,University College London | Giganti F.,San Raffaele Scientific Institute | And 6 more authors.
European Urology | Year: 2015

Context There is great interest in using magnetic resonance imaging (MRI) for men on active surveillance for prostate cancer. Objective To systematically review evidence regarding the use of MRI in men with low- or intermediate-risk prostate cancer suitable for active surveillance. Evidence acquisition Ovid Medline and Embase databases were searched for active surveillance, prostate cancer, and MRI from inception until April 25, 2014 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Evidence synthesis A lesion on MRI suspicious for prostate cancer (positive MRI) is seen in two-thirds of men otherwise suitable for active surveillance. A positive MRI makes the identification of clinically significant disease at repeat biopsy more likely, especially when biopsies are targeted to suspicious MRI lesions. Radical prostatectomy data show that positive MRI is more likely to be associated with upgrading (Gleason score >3 + 3) than a negative MRI (43% vs 27%). A positive MRI is not significantly more likely to be associated with upstaging at radical prostatectomy (>T2) than a negative MRI (10% vs 8%). Although MRI is of interest in the monitoring of men on active surveillance, robust data on the use of repeat MRI in active surveillance are lacking. Prospective studies with clear definitions of radiological significance and progression are needed before this approach can be adopted. Conclusions MRI is useful for detection of clinically significant disease at initial assessment of men considering active surveillance. To use MRI as a monitoring tool in surveillance, it will be necessary to define both radiological significance and radiological progression. Patient summary This review assesses evidence for the use of magnetic resonance imaging (MRI) in men on active surveillance for prostate cancer. MRI at the start of surveillance can detect clinically significant disease in one-third to half of men. There are few data to assess the use of MRI as a monitoring tool during surveillance, so there is a need to define significant disease on MRI and significant changes over time. © 2014 European Association of Urology. All rights reserved.


Dupont S.,Gothenburg University | Dorey N.,Gothenburg University | Thorndyke M.,Royal Swedish Academy Of Sciences
Estuarine, Coastal and Shelf Science | Year: 2010

Ocean acidification has been proposed as a major threat for marine biodiversity. Hendriks et al. [Hendriks, I.E., Duarte, C.M., Alvarez, M., 2010. Vulnerability of marine biodiversity to ocean acidification: a meta-analysis. Estuarine, Coastal and Shelf Science, doi:10.1016/j.ecss.2009.11.022.] proposed an alternative view and suggested, based on a meta-analysis, that marine biota may be far more resistant to ocean acidification than hitherto believed. However, such a meta-analytical approach can mask more subtle features, for example differing sensitivities during the life-cycle of an organism. Using a similar metric on an echinoderm database, we show that key bottlenecks present in the life-cycle (e.g. larvae being more vulnerable than adults) and responsible for driving the whole species response may be hidden in a global meta-analysis. Our data illustrate that any ecological meta-analysis should be hypothesis driven, taking into account the complexity of biological systems, including all life-cycle stages and key biological processes. Available data allow us to conclude that near-future ocean acidification can/will have dramatic negative impact on some marine species, including echinoderms, with likely consequences at the ecosystem level. © 2010 Elsevier Ltd.


Sparud-Lundin C.,Gothenburg University | Wennergren M.,Sahlgrenska University Hospital | Elfvin A.,Sahlgrenska University Hospital | Berg M.,Gothenburg University
Diabetes Care | Year: 2011

OBJECTIVE - To identify predictive factors for initiation and maintenance of breastfeeding with a focus on mothers with type 1 diabetes. RESEARCH DESIGN AND METHODS - This is a prospective observation survey, using a case-control design, comparing the outcomes of 108 mothers with type 1 diabetes with 104 mothers without diabetes that were matched for parity and gestational age. Mother and infant outcomes were collected from medical records and through telephone interviews 2 and 6 months after delivery. Predictive factors were calculated by logistic regression analyses. RESULTS - Mothers with diabetes were less likely to partly or exclusively breastfeed their children at 2 months (OR 0.42 [95% CI 0.18-0.96], P = 0.041) and 6 months (0.50 [0.27-0.90], P = 0.022) than mothers without diabetes. On multivariable analysis, type 1 diabetes did not remain an independent predictive factor. Instead, higher education level and breastfeeding at discharge from hospital were predictive factors for breastfeeding at 2 months postpartum. These variables as well as delivery >37 weeks and early breastfeeding predicted breastfeeding 6 months postpartum. CONCLUSIONS - Factors associated with maternal diabetes, such as problems with establishing breastfeeding in the early postpartum period, affects the likelihood of long-term breastfeeding. © 2011 by the American Diabetes Association.


Rolandsson B.,University of Bors | Bergquist M.,Gothenburg University | Ljungberg J.,Gothenburg University
Research Policy | Year: 2011

Opening up firms to open source has changed professional programmers' work in software development. In their work practice they must cope with two modes of software production: one based on proprietary, closed work situations, the other built around open source community ways of cooperation and knowledge sharing. In this article we present a study of how programmers cope with the co-existence of an industrial/commercial and a community/commons based mode of production. We analyze how they develop strategies to handle tensions that arise from contradictions between these two modes, and how it changes programmers' approach towards open source software development in the company. The study covers proprietary companies that have gradually incorporated open source software (hybrid companies) and SMEs entirely built around open source business concepts (pure-play companies). Four strategies are elaborated and discussed in-depth: Engineering in the lab, Market driven tailoring, Developing the community consortium and Peer-production. At a more general level, the study contributes to our understanding of how the transformation of proprietary production processes into a more open mode of knowledge work is not only associated with company strategies, but also with tensions and new demands on how work is strategically handled by knowledge workers. © 2010 Elsevier B.V. All rights reserved.


News Article | February 22, 2017
Site: www.eurekalert.org

To withstand external mechanical stress and handle trafficking of various substances, a cell needs to adjust its surrounding membrane. This is done through small indentations on the cell surface called caveolae. In order to stabilize its membrane, cells use the protein EHD2, which can be turned on and off to alternate between an inactive closed form and an active open form. The discovery, made by Umeå University researchers and colleagues, was recently published in the journal PNAS. Caveolae play a key role when cells adjust to their surrounding environment. An absence of these small indentations is associated with severe diseases where muscles and fat cells disintegrate or where cells of the blood vessels are malfunctioning. In a collaboration involving a broad spectrum of biophysical, biochemical and cell biological analysis, researchers have identified the mechanistic cycle of the protein EHD2 and how it regulates the dynamics of caveolae on the cell membrane. "The fact that the EHD2 protein helps the cells to adjust to their environment could be critically important for how caveolae affect the ability of muscle cells to repair or the absorption and storing abilities of fat cells," says Richard Lundmark, who is researcher at the Department of Integrative Medical Biology at Umeå University and corresponding author of the article. The discovery was made by the research group of Richard Lundmark at the Department of Integrative Medical Biology and the Laboratory of Molecular Infection Medicine Sweden (MIMS), along with colleagues at Gothenburg University in Sweden and Albert-Ludwigs-Universität Freiburg and Martin Luther University Halle-Wittenberg in Germany. The researchers demonstrate how the molecule ATP serves as a fuel allowing EHD2 to bind to the cell membrane and assume an open state where parts of the protein are inserted into the cell membrane. This position allows for the formation of so-called oligomers from the protein, which stabilizes the membrane in a fixed state. When the ATP-molecules have been spent, the protein is released from the membrane and assumes an inactive and closed state. The EHD2 protein's internal domains keeps it in this inhibited form when it is not in contact with a cell membrane. "This research shows how the mechanistic cycle of EHD2 that we describe plays a key role for the caveolae's ability to stabilize cell membranes," says Richard Lundmark. In the article, the researchers also describe how they used a new method based on the absorption and reflection of infrared light. Together with advanced analytics, this new method can be used to study structures of the membrane-bound states of proteins, which is difficult to achieve using other techniques. Using this method, the researchers were able to show the drastic conformational change in EHD2 when it binds to a membrane. PNAS, article: EHD2 restrains dynamics of caveolae by an ATP dependent, membrane-bound, open conformation. Authors: Hoernke M, Mohan J, Larsson E, Blomberg J, Kahra D, Westenhoff S, Schwieger C, and Lundmark R. DOI: 10.1073/pnas.1614066114.


Bendz H.,Lund University | Schon S.,Ryhov County Hospital | Attman P.-O.,Gothenburg University | Aurell M.,Gothenburg University
Kidney International | Year: 2010

We sought to establish the prevalence of lithium-induced end-stage renal disease in two regions of Sweden with 2.7 million inhabitants corresponding to about 30% of the Swedish population. Eighteen patients with lithium-induced end-stage renal disease were identified among the 3369 patients in the general lithium-treated population, representing a sixfold increase in prevalence compared with the general population for renal replacement therapy. All lithium-treated patients were older than 46 years at end-stage renal disease with a mean lithium treatment time of 23 years with ten patients having discontinued lithium treatment an average of 10 years before the start of renal replacement therapy. The prevalence of chronic kidney disease (defined as plasma creatinine over 150 mol/l) in the general lithium-treated population was about 1.2% (excluding patients on renal replacement therapy). Compared with lithium-treated patients without renal failure, those with chronic kidney disease were older and most were men but, as groups, their mean serum lithium levels and psychiatric diagnoses did not differ. We found that end-stage renal disease is an uncommon but not rare consequence of long-term lithium treatment and is more prevalent than previously thought. Time on lithium was the only identified risk factor in this study, suggesting that regular monitoring of renal function in these patients is mandatory. © 2010 International Society of Nephrology.


Ben-Menachem E.,Gothenburg University | Revesz D.,Gothenburg University | Simon B.J.,ElectroCore | Silberstein S.,Thomas Jefferson University
European Journal of Neurology | Year: 2015

Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses. © 2015 The Authors.


Simren M.,Gothenburg University | Barbara G.,University of Bologna | Flint H.J.,University of Aberdeen | Spiegel B.M.R.,University of California at Los Angeles | And 5 more authors.
Gut | Year: 2013

It is increasingly perceived that gut hostemicrobial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.


Larsson S.,Boston Consulting Groups Stockholm | Lawyer P.,Boston Consulting Groups Minneapolis office | Garellick G.,Gothenburg University | Lindahl B.,Uppsala University | Lundstrom M.,Lund University
Health Affairs | Year: 2012

As health care systems worldwide struggle with rising costs, a consensus is emerging to refocus reform efforts on value, as determined by the evaluation of patient outcomes relative to costs. One method of using outcome data to improve health care value is the disease registry. An international study of thirteen registries in five countries (Australia, Denmark, Sweden, the United Kingdom, and the United States) suggests that by making outcome data transparent to both practitioners and the public, well-managed registries enable medical professionals to engage in continuous learning and to identify and share best clinical practices. The apparent result: improved health outcomes, often at lower cost. For example, we calculate that if the United States had a registry for hip replacement surgery comparable to one in Sweden that enabled reductions in the rates at which these surgeries are performed a second time to replace or repair hip prostheses, the United States would avoid $2 billion of an expected $24 billion in total costs for these surgeries in 2015.


Bacona C.D.,Smithsonian Tropical Research Institute | Bacona C.D.,Gothenburg University | Silvestro D.,Gothenburg University | Silvestro D.,Swiss Institute of Bioinformatics | And 5 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The linking of North and South America by the Isthmus of Panama had major impacts on global climate, oceanic and atmospheric currents, and biodiversity, yet the timing of this critical event remains contentious. The Isthmus is traditionally understood to have fully closed by ca. 3.5 million years ago (Ma), and this date has been used as a benchmark for oceanographic, climatic, and evolutionary research, but recent evidence suggests a more complex geological formation. Here, we analyze both molecular and fossil data to evaluate the tempo of biotic exchange across the Americas in light of geological evidence. We demonstrate significant waves of dispersal of terrestrial organisms at approximately ca. 20 and 6 Ma and corresponding events separating marine organisms in the Atlantic and Pacific oceans at ca. 23 and 7 Ma. The direction of dispersal and their rates were symmetrical until the last ca. 6 Ma, when northern migration of South American lineages increased significantly. Variability among taxa in their timing of dispersal or vicariance across the Isthmus is not explained by the ecological factors tested in these analyses, including biome type, dispersal ability, and elevation preference. Migration was therefore not generally regulated by intrinsic traits but more likely reflects the presence of emergent terrain several millions of years earlier than commonly assumed. These results indicate that the dramatic biotic turnover associated with the Great American Biotic Interchange was a long and complex process that began as early as the Oligocene-Miocene transition.


Sjoholm K.,Gothenburg University | Sjostrom E.,Gothenburg University | Carlsson L.M.S.,Gothenburg University | Peltonen M.,Finnish National Institute for Health and Welfare
Diabetes Care | Year: 2016

OBJECTIVE It has been suggested that weight change-independent effects on fasting insulin and glucose levels are present after gastric bypass (GBP) but not after banding and vertical banded gastroplasty (VBG).Wetherefore evaluatedweight change-adjusted effects of GBP, compared with restrictive surgical procedures, on long-term changes in fasting levels of glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the Swedish Obese Subjects (SOS) study. RESEARCH DESIGN AND METHODS Participants who completed the 2-year (n = 1,762) and/or the 10-year (n = 1,216) follow-up were divided into threeweight change classes (weight loss >30%, 20-30%, or ≤20%), and by surgical method (banding, VBG, or GBP). Glucose, insulin, and HOMA-IR changes were analyzed in relation to weight change over 2 and 10 years. Analyses were performed in the full cohort and also in subgroups based on baseline glucose status. RESULTS Within weight change classes, reductions in glucose, insulin, and HOMA-IR were similar in the three surgery groups both at 2 and at 10 years. Reductions in glucose, insulin, and HOMA-IR increased with increasing weight loss, and changes were typically related to weight change within each surgery group. Moreover, the association between weight change and change in glucose, insulin, or HOMA-IR did not differ between the surgery groups at 2 and 10 years. When patients were subdivided also by baseline glucose status, similar relationships between weight changes and changes in glucose, insulin, and HOMA-IR were observed. CONCLUSIONS Even though weight loss-independent effects are important for short-term diabetes remission, our results suggest that degree of weight loss is more important for long-term reductions in fasting insulin and glucose than choice of bariatric surgery procedure. © 2016 by the American Diabetes Association.


Hawkins N.M.,Liverpool Heart and Chest Hospital | Petrie M.C.,Golden Jubilee National Hospital | MacDonald M.R.,Golden Jubilee National Hospital | Jhund P.S.,University of Glasgow | And 3 more authors.
Journal of the American College of Cardiology | Year: 2011

The combination of heart failure and chronic obstructive pulmonary disease presents many therapeutic challenges. The cornerstones of therapy are beta-blockers and beta-agonists, respectively. Their pharmacological effects are diametrically opposed, and each is purported to adversely affect the alternative condition. The tolerability of beta-blockade in patients with mild and fixed airflow obstruction likely extends to those with more severe disease. However, the evidence is rudimentary. The long-term influence of beta-blockade on pulmonary function, symptoms, and quality of life is unclear. Low-dose initiation and gradual up-titration of cardioselective beta-blockers is currently recommended. Robust clinical trials are needed to provide the answers that may finally allay physicians' mistrust of beta-blockers in patients with chronic obstructive pulmonary disease. Beta-agonists are associated with incident heart failure in patients with pulmonary disease and with increased mortality and hospitalization in those with existing heart failure. These purported adverse effects require further investigation. In the meantime, clinicians should consider carefully the etiology of dyspnea and obtain objective evidence of airflow obstruction before prescribing beta-agonists to patients with heart failure. © 2011 American College of Cardiology Foundation.


Wernstedt Asterholm I.,Touchstone Diabetes Center | Wernstedt Asterholm I.,Gothenburg University | Tao C.,Touchstone Diabetes Center | Morley T.S.,Touchstone Diabetes Center | And 5 more authors.
Cell Metabolism | Year: 2014

Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin. © 2014 Elsevier Inc.


Clemens J.,ICCDR | Clemens J.,University of California at Los Angeles | Holmgren J.,Gothenburg University
Current Topics in Microbiology and Immunology | Year: 2014

Cholera continues to be a major global health problem, at times causing major and prolonged outbreaks in both endemic and nonendemic settings in developing countries. While improved water quality, sanitation, and hygiene (WASH) will provide the ultimate solution to prevention of this disease burden, this is a far-off goal for most developing countries. Oral cholera vaccines cholera vaccines (OCVs) have been demonstrated to be effective in the control of cholera outbreaks, and constitute useful tools to be used in conjunction with efforts to improve WASH. Two killed OCVs are prequalified by WHO for purchase by UN agencies for international use. Recently, WHO has launched a global stockpile stockpile of killed OCVs for use to control outbreaks. Rational deployment of OCV from this stockpile will require consideration of costs, feasibility, disease epidemiology epidemiology, and the protective characteristics of the vaccine deployed, as well as effective and rapid coordination of processes and logistics logistics used to make decisions on deployment and delivery of the vaccine to the population in need. Despite not having data on all the questions of relevance as to how to use OCVs to control cholera outbreaks in different settings, there is clearly more than enough evidence to initiate their use, as answers to remaining questions and refinement of policies will mainly come with experience. © 2014 Springer-Verlag Berlin Heidelberg.


Dekosky S.T.,University of Virginia | Blennow K.,Gothenburg University | Ikonomovic M.D.,University of Pittsburgh | Gandy S.,Mount Sinai School of Medicine
Nature Reviews Neurology | Year: 2013

Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE) - which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression - has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE. © 2013 Macmillan Publishers Limited. All rights reserved.


Bohn L.,Gothenburg University | Storsrud S.,Gothenburg University | Liljebo T.,Karolinska University Hospital | Collin L.,Sabbatsbergs Hospital | And 4 more authors.
Gastroenterology | Year: 2015

Background and Aims A diet with reduced content of fermentable short-chain carbohydrates (fermentable oligo-, di-, monosaccharides, and polyols [FODMAPs]) has been reported to be effective in the treatment of patients with irritable bowel syndrome (IBS). However, there is no evidence of its superiority to traditional dietary advice for these patients. We compared the effects of a diet low in FODMAPs with traditional dietary advice in a randomized controlled trial of patients with IBS. Methods We performed a multi-center, parallel, single-blind study of 75 patients who met Rome III criteria for IBS and were enrolled at gastroenterology outpatient clinics in Sweden. Subjects were randomly assigned to groups that ate specific diets for 4 weeks - a diet low in FODMAPs (n = 38) or a diet frequently recommended for patients with IBS (ie, a regular meal pattern; avoidance of large meals; and reduced intake of fat, insoluble fibers, caffeine, and gas-producing foods, such as beans, cabbage, and onions), with greater emphasis on how and when to eat rather than on what foods to ingest (n = 37). Symptom severity was assessed using the IBS Symptom Severity Scale, and patients completed a 4-day food diary before and at the end of the intervention. Results A total of 67 patients completed the dietary intervention (33 completed the diet low in FODMAPs, 34 completed the traditional IBS diet). The severity of IBS symptoms was reduced in both groups during the intervention (P <.0001 in both groups before vs at the end of the 4-week diet), without a significant difference between the groups (P =.62). At the end of the 4-week diet period, 19 patients (50%) in the low-FODMAP group had reductions in IBS severity scores ≥50 compared with baseline vs 17 patients (46%) in the traditional IBS diet group (P =.72). Food diaries demonstrated good adherence to the dietary advice. Conclusions A diet low in FODMAPs reduces IBS symptoms as well as traditional IBS dietary advice. Combining elements from these 2 strategies might further reduce symptoms of IBS. ClinicalTrials.gov ID NCT02107625. © 2015 AGA Institute.


Silvestro D.,Gothenburg University | Silvestro D.,University of Lausanne | Silvestro D.,Swiss Institute of Bioinformatics | Antonelli A.,Gothenburg University | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The history of biodiversity is characterized by a continual replacement of branches in the tree of life. The rise and demise of these branches (clades) are ultimately determined by changes in speciation and extinction rates, often interpreted as a response to varying abiotic and biotic factors. However, understanding the relative importance of these factors remains a major challenge in evolutionary biology. Here we analyze the rich North American fossil record of the dog family Canidae and of other carnivores to tease apart the roles of competition, body size evolution, and climate change on the sequential replacement of three canid subfamilies (two of which have gone extinct). We develop a novel Bayesian analytic framework to show that competition from multiple carnivore clades successively drove the demise and replacement of the two extinct canid subfamilies by increasing their extinction rates and suppressing their speciation. Competitive effects have likely come from ecologically similar species from both canid and felid clades. These results imply that competition among entire clades, generally considered a rare process, can play a more substantial role than climate change and body size evolution in determining the sequential rise and decline of clades. © 2015, National Academy of Sciences. All rights reserved.


Konttinen H.,University of Helsinki | Peltonen M.,Finnish National Institute for Health and Welfare | Sjostrom L.,Gothenburg University | Carlsson L.,Gothenburg University | Karlsson J.,Örebro University
American Journal of Clinical Nutrition | Year: 2015

Background: There is a need for a better understanding of the factors that influence long-term weight outcomes after bariatric surgery. Objective: We examined whether pretreatment and posttreatment levels of cognitive restraint, disinhibition, and hunger and 1-y changes in these eating behaviors predict short- and long-term weight changes after surgical and conventional treatments of severe obesity. Design: Participants were from an ongoing, matched (nonrandomized) prospective intervention trial of the Swedish Obese Subjects (SOS) study. The current analyses included 2010 obese subjects who underwent bariatric surgery and 1916 contemporaneously matched obese controls who received conventional treatment. Physical measurements (e.g., weight and height) and questionnaires (e.g., Three-Factor Eating Questionnaire) were completed before the intervention and 0.5, 1, 2, 3, 4, 6, 8, and 10 y after the start of the treatment. Structural equation modeling was used as the main analytic strategy. Results: The surgery group lost more weight and reported greater decreases in disinhibition and hunger at 1- and 10-y follow-ups (all P < 0.001 in both sexes) than the control group did. Pretreatment eating behaviors were unrelated to subsequent weight changes in surgically treated patients. However, patients who had lower levels of 6-mo and 1-y disinhibition and hunger (β = 0.13-0.29, P < 0.01 in men; β = 0.11-0.28, P < 0.001 in women) and experienced larger 1-y decreases in these behaviors (β = 0.31-0.48, P < 0.001 in men; β = 0.24-0.51, P < 0.001 in women) lost more weight 2, 6, and 10 y after surgery. In control patients, larger 1-y increases in cognitive restraint predicted a greater 2-y weight loss in both sexes. Conclusion: A higher tendency to eat in response to various internal and external cues shortly after surgery predicted less-successful shortand long-term weight outcomes, making postoperative susceptibility for uncontrolled eating an important indicator of targeted interventions. This trial was registered at clinicaltrials.gov as NCT01479452. © 2015 American Society for Nutrition


Bohm M.,Universitatsklinikum des Saarlandes | Swedberg K.,Gothenburg University | Komajda M.,University Pierre and Marie Curie | Borer J.S.,New York University | And 4 more authors.
The Lancet | Year: 2010

Background Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population. Methods We analysed cardiovascular outcomes in the placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided by quintiles of baseline heart rate in the placebo group. The primary composite endpoint was cardiovascular death or hospital admission for worsening heart failure. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes. Analysis adjusted to change in heart rate was used to study heart-rate reduction as mechanism for risk reduction by ivabradine directly. Findings In the placebo group, patients with the highest heart rates (≥87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2·34, 95 CI 1·84-2·98, p<0·0001). Risk of primary composite endpoint events increased by 3 with every beat increase from baseline heart rate and 16 for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17·4, 95 CI 15·3-19·6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0·95, 0·85-1·06, p=0·352). Interpretation Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure. Funding Servier, France. © 2010 Elsevier Ltd.


Dudas K.,Gothenburg University | Lappas G.,Gothenburg University | Stewart S.,Baker IDI Heart and Diabetes Institute | Rosengren A.,Gothenburg University
Circulation | Year: 2011

Background-: Case fatality associated with a first coronary event is often underestimated when only those who survive to reach a hospital are considered. Few studies have examined long-term trends in case fatality associated with a major coronary event that occurs out of the hospital. Methods and results-: Record linkage documented all case subjects 35 to 84 years of age in Sweden during 1991 to 2006 with a first major coronary event (out-of-hospital coronary death or hospitalization for acute myocardial infarction). Of the 384 597 cases identified, 111 319 (28.9%) died out of the hospital, and another 36 552 (9.5%) died in the hospital or within 28 days of hospitalization. From 1991 to 2006, out-of hospital deaths as a proportion of all major coronary events declined from 30.5% to 25.6% (adjusted mean annual decrease 2.2%, 95% confidence interval 2.1% to 2.4%), however, with a larger decline in 28-day case fatality in hospitalized cases (adjusted mean annual decrease 5.8%, 95% confidence interval 5.5% to 6.0%). As a result of the faster decline in in-hospital deaths, the relative contribution of out-of-hospital deaths to overall case fatality increased, particularly among younger individuals (eg, among those 35 to 54 years of age, no more than 10.8% of all deaths occurred in hospitalized cases during 2003-2006). Although female sex (odds ratio 0.85, 95% confidence interval 0.83 to 0.87) and older age (odds ratio 0.972, 95% confidence interval 0.971 to 0.974 per year) were associated with lower risk for initial out-of-hospital death, each successive calendar year was associated with increased risk (odds ratio 1.041, 95% confidence interval 1.038 to 1.044). Conclusions-: The great majority of all fatal coronary events occur outside the hospital, and this proportion is increasing, particularly among younger individuals. Copyright © 2011 American Heart Association. All rights reserved.


Bejger M.,Copernicus Astronomical Center | Piran T.,Hebrew University of Jerusalem | Abramowicz M.,Copernicus Astronomical Center | Abramowicz M.,Gothenburg University | Hakanson F.,Chalmers University of Technology
Physical Review Letters | Year: 2012

Collisions of particles in black hole ergospheres may result in an arbitrarily large center-of-mass energy. This led recently to the suggestion that black holes can act as ultimate particle accelerators. If the energy of an outgoing particle is larger than the total energy of the infalling particles, the energy excess must come from the rotational energy of the black hole and hence, a Penrose process is involved. However, while the center-of-mass energy diverges, the position of the collision makes it impossible for energetic particles to escape to infinity. Following an earlier work on collisional Penrose processes, we show that even under the most favorable idealized conditions the maximal energy of an escaping particle is only a modest factor above the total initial energy of the colliding particles. This implies that one should not expect collisions around a black hole to act as spectacular cosmic accelerators. © 2012 American Physical Society.


Bajor A.,Sahlgrenska Academy | Tornblom H.,Sahlgrenska Academy | Tornblom H.,Gothenburg University | Rudling M.,Metabolism Unit | And 4 more authors.
Gut | Year: 2014

Objective: Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS.Design: We measured75Se-labelled homocholic acidtaurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms.Results: Compared with controls, patients with IBS had lower75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220 ±109 vs 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8).Conclusions: Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted.


Croy I.,Gothenburg University | Maboshe W.,University of Dresden Medical School | Hummel T.,University of Dresden Medical School
International Journal of Psychophysiology | Year: 2013

Objective: The hedonic value of odors is reflected in chemosensory evoked potentials with more salient unpleasant odors being processed differently from pleasant odors. However, it is not known if this effect is stable over time. It was examined if chemosensory evoked potentials towards pleasant and unpleasant odors change with repeated presentation. Methods: 42 participants received two pleasant (Peach and PEA) and one unpleasant (H2S) intensity matched odors in a block design. Intensity and pleasantness were rated after each presentation. Subjective ratings, as well as N1 and P2 of the first stimulus of each block were compared with the two following stimuli of each block. Results: Early and late components of the chemosensory evoked potentials had shorter latencies in response to the unpleasant H2S compared to PEA and Peach. Pleasantness ratings for H2S increased with repeated presentation but were far below neutral even for the third stimulus in a row. In line with this, for H2S only, the P2 amplitude diminished with repeated presentation. Conclusion: We assume that unpleasant stimuli catch more attention first hand. However, repeated presentation leads to reduced emotional salience of unpleasant stimuli only, which is mirrored in a decrease of neuronal activation. © 2013 Elsevier B.V..


Andersson A.K.,Gothenburg University | Chapman L.,University of Birmingham
Accident Analysis and Prevention | Year: 2011

Winter weather can be a significant cause of road traffic accidents. This paper uses UKCIP climate change scenarios and a temporal analogue to investigate the relationship between temperature and severe road accidents in the West Midlands, UK. This approach also allows quantification of the changes in the severity of the winter season over the next century in the region. It is demonstrated that the predicted reduction in the number of frost days should in turn reduce the number of road accidents caused due to slipperiness by approximately 50%. However, the paper concludes by warning against complacency in winter maintenance regimes. A warmer climate may result in budget cuts for highway maintenance which in turn may well reverse declining accident trends. © 2010 Elsevier Ltd.


Jaraj D.,Institute of Neuroscience and Physiology | Rabiei K.,Institute of Neuroscience and Physiology | Marlow T.,Institute of Neuroscience and Physiology | Jensen C.,Gothenburg University | And 2 more authors.
Neurology | Year: 2014

Objectives: The aim of this study was to determine the prevalence of idiopathic normal-pressure hydrocephalus (iNPH) in elderly persons in a large population-based sample using radiologic and clinical examinations. Methods: We examined representative elderly populations aged 70 years and older that had undergone neuropsychiatric evaluations and CT of the brain between 1986 and 2000 (n = 1,238). Gait was evaluated by clinical examination and history of walking difficulty. Cognitive function was evaluated with the Mini-Mental State Examination and urinary incontinence by self-report. iNPH was diagnosed in concordance with the American-European iNPH guidelines. Exclusion criteria were history of meningitis, severe head trauma, and subarachnoid hemorrhage. Results: The prevalence of probable iNPH was 0.2% in those aged 70-79 years (n = 2) and 5.9% (n = 24) in those aged 80 years and older, with no difference between men and women. Only 2 of these persons had been treated for iNPH. Hydrocephalic ventricular enlargement, i.e., a CT image consistent with NPH, was found in 56 persons (4.5%). An Evans Index >0.3 was found in 256 (20.7%) and occluded sulci at the high convexity in 67 persons (5.4%). All of these findings were more common in the older age groups. Conclusions: Many elderly possess clinical and imaging features of iNPH, especially those older than 80 years. The number of persons with iNPH is probably much higher than the number of persons currently treated. © 2014 American Academy of Neurology.


Lanata N.,Rutgers University | Strand H.U.R.,Gothenburg University
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We extend the time-dependent Gutzwiller variational approach, recently introduced by Schirò and Fabrizio, to impurity problems. Furthermore, we derive a consistent theory for the steady state, and show its equivalence with the previously introduced nonequilibrium steady-state extension of the Gutzwiller approach. The method is shown to be able to capture dissipation in the leads, so that a steady state is reached after a sufficiently long relaxation time. The time-dependent method is applied to the single-orbital Anderson impurity model at half filling, modeling a quantum dot coupled to two leads. In these exploratory calculations, the Gutzwiller projector is limited to act only on the impurity. The strengths and the limitations of this approximation are assessed via comparison with state-of-the-art continuous-time quantum Monte Carlo results. Finally, we discuss how the method can be systematically improved by extending the region of action of the Gutzwiller projector. © 2012 American Physical Society.


Croy I.,Gothenburg University | Croy I.,University of Dresden Medical School | Nordin S.,Umeå University | Hummel T.,University of Dresden Medical School
Chemical Senses | Year: 2014

Olfactory disorders are common and affect about one-fifth of the general population. The main causes of olfactory loss are post viral upper respiratory infection, nasal/sinus disease, and head trauma and are therefore very frequent among patients in ear, nose, and throat clinics. We have systematically reviewed the impact of quantitative, qualitative, and congenital olfactory disorders on daily life domains as well as on general quality of life and depression. From the extensive body of literature, it can be concluded that loss of the sense of smell leads to disturbances in important areas, mainly in food enjoyment, detecting harmful food and smoke, and to some extent in social situations and working life. Most patients seem to deal well and manage those restrictions. However, a smaller proportion has considerable problems and expresses a noticeable reduction in general quality of life and enhanced depression. The impact of coping strategies is discussed. © The Author 2014.


Irwin D.E.,University of North Carolina at Chapel Hill | Kopp Z.S.,Pfizer | Agatep B.,Pfizer | Milsom I.,Gothenburg University | Abrams P.,Southmead Hospital
BJU International | Year: 2011

Objective • To estimate and predict worldwide and regional prevalence of lower urinary tract symptoms (LUTS), overactive bladder (OAB), urinary incontinence (UI) and LUTS suggestive of bladder outlet obstruction (LUTS/BOO) in 2008, 2013 and 2018 based on current International Continence Society symptom definitions in adults aged ≥20 years. Patients and Methods • Numbers and prevalence of individuals affected by each condition were calculated with an estimation model using gender- and age-stratified prevalence data from the EPIC study along with gender- and age-stratified worldwide and regional population estimates from the US Census Bureau International Data Base. Results • An estimated 45.2%, 10.7%, 8.2% and 21.5% of the 2008 worldwide population (4.3 billion) was affected by at least one LUTS, OAB, UI and LUTS/BOO, respectively. By 2018, an estimated 2.3 billion individuals will be affected by at least one LUTS (18.4% increase), 546 million by OAB (20.1%), 423 million by UI (21.6%) and 1.1 billion by LUTS/BOO (18.5%). • The regional burden of these conditions is estimated to be greatest in Asia, with numbers of affected individuals expected to increase most in the developing regions of Africa (30.1-31.1% increase across conditions, 2008-2018), South America (20.5-24.7%) and Asia (19.7-24.4%). Conclusions • This model suggests that LUTS, OAB, UI and LUTS/BOO are highly prevalent conditions worldwide. Numbers of affected individuals are projected to increase with time, with the greatest increase in burden anticipated in developing regions. • There are important worldwide public-health and clinical management implications to be considered over the next decade to effectively prevent and manage these conditions. © 2010 The Authors. BJU International.


Bayat A.,University College London | Johannesson H.,Gothenburg University | Bose S.,University College London | Sodano P.,Federal University of Rio Grande do Norte | Sodano P.,National Institute of Nuclear Physics, Italy
Nature Communications | Year: 2014

A quantum phase transition may occur in the ground state of a system at zero temperature when a controlling field or interaction is varied. The resulting quantum fluctuations which trigger the transition produce scaling behaviour of various observables, governed by universal critical exponents. A particularly interesting class of such transitions appear in systems with quantum impurities where a non-extensive term in the free energy becomes singular at the critical point. Curiously, the notion of a conventional order parameter that exhibits scaling at the critical point is generically missing in these systems. Here we explore the possibility to use the Schmidt gap, which is an observable obtained from the entanglement spectrum, as an order parameter. A case study of the two-impurity Kondo model confirms that the Schmidt gap faithfully captures the scaling behaviour by correctly predicting the critical exponent of the dynamically generated length scale at the critical point. © 2014 Macmillan Publishers Limited. All rights reserved.


Naredla R.R.,Northern Illinois University | Zheng C.,Northern Illinois University | Nilsson Lill S.O.,Gothenburg University | Klumpp D.A.,Northern Illinois University
Journal of the American Chemical Society | Year: 2011

This Article presents the results from studies related to the chemistry of tricationic superelectrophiles. A series of triaryl methanols were ionized in Brønsted superacids, and the corresponding tricationic intermediates were formed. The trications are found to participate in two types of reactions; both are characteristic of highly charged organic cations. One set of reactions occurs through charge migration. A second set of reactions occurs through deprotonation of an unusually acidic site on the tricationic species. One of the tricationic intermediates has been directly observed by low temperature NMR spectroscopy. These highly charged ions and their reactions have also been studied using density functional theory calculations. As a result of charge migration, electron density at a carbocation site is found to increase with progression from monocationic to pentacationic structures. © 2011 American Chemical Society.


Edvinsson L.,Lund University | Linde M.,Norwegian University of Science and Technology | Linde M.,Gothenburg University | Linde M.,St Olavs Hospital
The Lancet | Year: 2010

Although the triptan drugs provide effective relief from migraine for many patients, a substantial number of affected individuals are unresponsive to these compounds, and such therapy can also lead to a range of adverse effects. Telcagepant represents a new class of antimigraine drug - the calcitonin gene-related peptide receptor blockers. This compound exerts its effects by blocking receptors for the calcitonin-gene-related peptide at several sites in the trigeminal and central nervous systems, resulting in pain relief. Telcagepant does not cause vasoconstriction, a major limitation in the use of triptans. Comparisons with triptans in clinical trials for acute treatment of migraine attacks revealed clinical effects similar to those of triptans but better than those of placebo. Telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs. In patients who need prophylaxis because of frequent attacks of migraine, topiramate is a first-line drug for migraine prevention in many countries; it is generally safe and reasonably well tolerated. Data suggest that topiramate could aid reversion of chronic migraine to episodic migraine. © 2010 Elsevier Ltd.


Antonelli A.,Gothenburg Botanical Garden | Antonelli A.,Gothenburg University | Sanmartin I.,Real Jardyn Botanico
Systematic Biology | Year: 2011

Chloranthaceae is a small family of flowering plants (65 species) with an extensive fossil record extending back to the Early Cretaceous. Within Chloranthaceae, Hedyosmum is remarkable because of its disjunct distribution-1 species in the Paleotropics and 44 confined to the Neotropics-and a long "temporal gap" between its stem age (Early Cretaceous) and the beginning of the extant radiation (late Cenozoic). Is this gap real, reflecting low diversification and a recent radiation, or the signature of extinction? Here we use paleontological data, relaxed-clock molecular dating, diversification analyses, and parametric ancestral area reconstruction to investigate the timing, tempo, and mode of diversification in Hedyosmum. Our results, based on analyses of plastid and nuclear sequences for 40 species, suggest that the ancestor of Chloranthaceae and the Hedyosmum stem lineages were widespread in the Holarctic in the Late Cretaceous. High extinction rates, possibly associated with Cenozoic climatic fluctuations, may have been responsible for the low extant diversity of the family. Crown group Hedyosmum originated c. 36-43 Ma and colonized South America from the north during the Early-Middle Miocene (c. 20 Ma). This coincided with an increase in diversification rates, probably triggered by the uplift of the Northern Andes from the Mid-Miocene onward. This study illustrates the advantages of combining paleontological, phylogenetic, and biogeographic data to reconstruct the spatiotemporal evolution of an ancient lineage, for which the extant diversity is only a remnant of past radiations. It also shows the difficulties of inferring patterns of lineage diversification when incomplete taxon sampling is combined with high extinction rates. © 2011 The Author(s).


Hellstrom A.,Gothenburg University | Smith L.E.H.,Boston Childrens Hospital | Smith L.E.H.,Harvard University | Dammann O.,Tufts University | And 2 more authors.
The Lancet | Year: 2013

The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal-fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identifi cation and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifi able risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulinlike growth factor 1 and ?-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and infl ammation to promote normal growth and limit suppression of neurovascular development.


Background: To explore to what extent measurement error can explain the variation of mean patient HbA1c between clinics. Methods: For each year 2005-2010 data from 5380-6985 children, age < 18 years, in 35-43 Swedish pediatric clinics was analyzed. Each year 13,000-19,000 HbA1c analyses were evaluated. Year mean HbA1c for each patient was calculated for HbA1c values when insulin dose was ≥ 0.5 U/kg. In Sweden HbA1c values were during the study period standardized to the Mono S level, HbA1c(Mono S)%, but are given also in the international unit HbA1c(IFCC), mmol/mol. Performance of locally measured HbA 1c is monitored by Equalis through monthly external quality assessment (EQA) schemes. Results: The yearly mean bias term for each clinic varied from -0.54 to 0.41 HbA1c(Mono S)%. The bias between clinic HbA1c and target value improved during the 6 years and the mean bias was for 79%-88% of clinics within the recommended level ± 0.14 HbA 1c% the last 2 years. Inter-clinic mean HbA1c had a wide interquartile range, 0.30-0.43 HbA1c(Mono S)% [3.2-4.5 HbA 1c(IFCC) mmol/mol]. Conclusions: Regular participation in EQA schemes is necessary when comparing HbA1c values. The measurement error decreased during the 6-year period and explained from 28% to < 10% of the inter-clinic variation in year mean clinic HbA1c.


Lundby C.,University of Zürich | Lundby C.,Gothenburg University | Robach P.,Ecole Nationale des Sports de Montagne
Physiology | Year: 2015

Our objective is to highlight some key physiological determinants of endurance exercise performance and to discuss how these can be further improved. V˙O2max remains remarkably stable throughout an athletic career. By contrast, exercise economy, lactate threshold, and critical power may be improved in world-class athletes by specific exercise training regimes and/or with more years of training. © 2015 Int. Union Physiol. Sci./Am. Physiol. Soc.


Gillberg C.,Gothenburg University | Fernell E.,Gothenburg University | Fernell E.,Skaraborgs Hospital
Journal of Autism and Developmental Disorders | Year: 2014

The reported prevalence of autism is going up and up. We propose that some—even much—of the increase in the rate of autism spectrum disorder (ASD) is driven by “Autism Plus”. Autism Plus refers to autism with comorbidities (including intellectual developmental disorder, language disorder, and attention-deficit/hyperactivity disorder), and this is what is now being diagnosed by clinicians as ASD. In clinical practice, a diagnosis of ASD much more often entails that the child will receive support at school and in the community, which is not the case for other diagnoses. In the past the comorbidities were given diagnostic priority and the “autistic features” might, or might not be mentioned as the “plus bit” in the diagnostic summary. It is high time that the comorbidities, sometimes even more important than the autism, came back on the diagnostic agenda. Autism is but one of the Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examination (ESSENCE), not the one and only. © 2014, Springer Science+Business Media New York.


Abramowicz M.A.,Gothenburg University | Abramowicz M.A.,pernicus Astronomical Center | Fragile P.C.,College of Charleston
Living Reviews in Relativity | Year: 2013

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).


Constantinescu R.,Gothenburg University | Mondello S.,University of Florida
Frontiers in Neurology | Year: 2013

The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives. © 2013 Constantinescu and Mondello.


Rydenhag B.,Gothenburg University | Flink R.,Uppsala University Hospital | Malmgren K.,Gothenburg University
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

Purpose: Seizure outcome after epilepsy surgery is to an important extent related to underlying aetiology. In this study of patients who underwent epilepsy surgery with a lesional aetiology in Sweden 1990-2004, the aim was to investigate seizure outcome and prognostic factors. Methods: All patients operated on during the time period with a histopathological diagnosis of an epileptogenic tumour (ganglioglioma (GGL), dysembryoblastic neuroepithelial tumour (DNET) and low grade astrocytoma (AST)) or a cavernous haemangioma (CAH) were identified in the population based Swedish National Epilepsy Surgery Register. Univariate and multivariate analyses were performed to determine the independent contribution of the following variables to seizure outcome: age at surgery; epilepsy duration; preoperative seizure frequency; localisation of the resection; and histopathology. Results: Of the 156 identified patients who had a 2 year follow-up (103 adults and 53 children), 71% had temporal, 16% frontal and 13% parietal and occipital lobe resections. Mean presurgical epilepsy duration was 13 years in adults and 5 years in children. Main histopathological diagnosis was GGL or DNET in 67, CAH in 42 and AST in 47 patients. 77% of patients had sustained seizure freedom (with or without aura) 2 years after surgery. In the multivariate analysis, only diagnosis other than AST was independently associated with becoming seizure free. Conclusion: In this population based series, 120/156 patients (77%) with epileptogenic tumours and cavernomas were seizure free 2 years after surgery. Many had a very long epilepsy history. Seizure outcome can be improved if epilepsy surgery is considered earlier in patients with epileptogenic lesions.


Raja E.K.,Northern Illinois University | Nilsson Lill S.O.,Gothenburg University | Klumpp D.A.,Northern Illinois University
Chemical Communications | Year: 2012

Despite the relatively low reactivities of urea and thiourea functional groups towards nucleophilic attack, we have found conditions in which they are useful substrates in Friedel-Crafts reactions. The Bronsted superacid, triflic acid, promotes these reactions and a mechanism is proposed involving dicationic, superelectrophilic intermediates. © 2012 The Royal Society of Chemistry.


Edwards A.M.,University of Bath | Potts J.R.,University of York | Josefsson E.,Gothenburg University | Massey R.C.,University of Bath
PLoS Pathogens | Year: 2010

Entry of Staphylococcus aureus into the bloodstream can lead to metastatic abscess formation and infective endocarditis. Crucial to the development of both these conditions is the interaction of S. aureus with endothelial cells. In vivo and in vitro studies have shown that the staphylococcal invasin FnBPA triggers bacterial invasion of endothelial cells via a process that involves fibronectin (Fn) bridging to a 5b 1 integrins. The Fn-binding region of FnBPA usually contains 11 non-identical repeats (FnBRs) with differing affinities for Fn, which facilitate the binding of multiple Fn molecules and may promote integrin clustering. We thus hypothesized that multiple repeats are necessary to trigger the invasion of endothelial cells by S. aureus. To test this we constructed variants of fnbA containing various combinations of FnBRs. In vitro assays revealed that endothelial cell invasion can be facilitated by a single high-affinity, but not low-affinity FnBR. Studies using a nisin-inducible system that controlled surface expression of FnBPA revealed that variants encoding fewer FnBRs required higher levels of surface expression to mediate invasion. High expression levels of FnBPA bearing a single low affinity FnBR bound Fn but did not invade, suggesting that FnBPA affinity for Fn is crucial for triggering internalization. In addition, multiple FnBRs increased the speed of internalization, as did higher expression levels of FnBPA, without altering the uptake mechanism. The relevance of these findings to pathogenesis was demonstrated using a murine sepsis model, which showed that multiple FnBRs were required for virulence. In conclusion, multiple FnBRs within FnBPA facilitate efficient Fn adhesion, trigger rapid bacterial uptake and are required for pathogenesis. © 2010 Edwards et al.


Fillinger L.,Alfred Wegener Institute for Polar and Marine Research | Janussen D.,Forschungsinstitut und Naturmuseum Senckenberg | Lundalv T.,Gothenburg University | Richter C.,Alfred Wegener Institute for Polar and Marine Research
Current Biology | Year: 2013

Over 30% of the Antarctic continental shelf is permanently covered by floating ice shelves [1], providing aphotic conditions [2, 3] for a depauperate fauna sustained by laterally advected food [4, 5]. In much of the remaining Antarctic shallows (<300 m depth), seasonal sea-ice melting allows a patchy primary production supporting rich megabenthic communities [6, 7] dominated by glass sponges (Porifera, Hexactinellida) [8-10]. The catastrophic collapse of ice shelves due to rapid regional warming along the Antarctic Peninsula in recent decades [11] has exposed over 23,000 km2 of seafloor to local primary production [12]. The response of the benthos to this unprecedented flux of food [13] is, however, still unknown. In 2007, 12 years after disintegration of the Larsen A ice shelf, a first biological survey interpreted the presence of hexactinellids as remnants of a former under-ice fauna with deep-sea characteristics [14]. Four years later, we revisited the original transect, finding 2- and 3-fold increases in glass sponge biomass and abundance, respectively, after only two favorable growth periods. Our findings, along with other long-term studies [15], suggest that Antarctic hexactinellids, locked in arrested growth for decades [8, 16], may undergo boom-and-bust cycles, allowing them to quickly colonize new habitats. The cues triggering growth and reproduction in Antarctic glass sponges remain enigmatic. © 2013 Elsevier Ltd.


News Article | February 22, 2017
Site: phys.org

To withstand external mechanical stress and handle trafficking of various substances, a cell needs to adjust its surrounding membrane. This is done through small indentations on the cell surface called caveolae. In order to stabilize its membrane, cells use the protein EHD2, which can be turned on and off to alternate between an inactive closed form and an active open form. The discovery, made by Umeå University researchers and colleagues, was recently published in the journal PNAS. Caveolae play a key role when cells adjust to their surrounding environment. An absence of these small indentations is associated with severe diseases where muscles and fat cells disintegrate or where cells of the blood vessels are malfunctioning. In a collaboration involving a broad spectrum of biophysical, biochemical and cell biological analysis, researchers have identified the mechanistic cycle of the protein EHD2 and how it regulates the dynamics of caveolae on the cell membrane. "The fact that the EHD2 protein helps the cells to adjust to their environment could be critically important for how caveolae affect the ability of muscle cells to repair or the absorption and storing abilities of fat cells," says Richard Lundmark, who is researcher at the Department of Integrative Medical Biology at Umeå University and corresponding author of the article. The discovery was made by the research group of Richard Lundmark at the Department of Integrative Medical Biology and the Laboratory of Molecular Infection Medicine Sweden (MIMS), along with colleagues at Gothenburg University in Sweden and Albert-Ludwigs-Universität Freiburg and Martin Luther University Halle-Wittenberg in Germany. The researchers demonstrate how the molecule ATP serves as a fuel allowing EHD2 to bind to the cell membrane and assume an open state where parts of the protein are inserted into the cell membrane. This position allows for the formation of so-called oligomers from the protein, which stabilizes the membrane in a fixed state. When the ATP-molecules have been spent, the protein is released from the membrane and assumes an inactive and closed state. The EHD2 protein's internal domains keeps it in this inhibited form when it is not in contact with a cell membrane. "This research shows how the mechanistic cycle of EHD2 that we describe plays a key role for the caveolae's ability to stabilize cell membranes," says Richard Lundmark. In the article, the researchers also describe how they used a new method based on the absorption and reflection of infrared light. Together with advanced analytics, this new method can be used to study structures of the membrane-bound states of proteins, which is difficult to achieve using other techniques. Using this method, the researchers were able to show the drastic conformational change in EHD2 when it binds to a membrane. Explore further: The first analysis of Ewing's sarcoma methyloma opens doors to new treatments More information: Maria Hoernke et al, EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1614066114


Pleijel H.,Gothenburg University | Hogy P.,University of Hohenheim
Environmental Pollution | Year: 2015

Data from three Swedish open-top chamber and four German FACE experiments were combined to derive response functions for elevated CO2 (eCO2) effects on Cd, Zn, Mn, protein, grain yield, grain mass and grain number of wheat. Grain yield and grain number were increased by ∼6% and ∼7%, respectively, per 100 ppm CO2; the former effect was linked to plant nitrogen status. Grain mass was not influenced by eCO2, whereas Cd concentration was reduced. Unlike Zn, Mn and protein, effects on Cd yield were not related to effects on grain yield. Yields of Mn, Zn and (weakly) protein were positively affected by eCO2. For protein, grain yield, grain mass and grain number, the results were consistent among the FACE and OTC experiments. A key conclusion was that yields of essential nutrients were enhanced (Mn > Zn > protein), although less than grain yield, which would not be expected from a simple dilution model. © 2014 Elsevier Ltd All rights reserved.


Neff K.J.,University College Dublin | Olbers T.,Carlanderska Hospital | Olbers T.,Gothenburg University | le Roux C.W.,University College Dublin | le Roux C.W.,Gothenburg University
BMC Medicine | Year: 2013

Obesity is recognized as a global health crisis. Bariatric surgery offers a treatment that can reduce weight, induce remission of obesity-related diseases, and improve the quality of life. In this article, we outline the different options in bariatric surgery and summarize the recommendations for selecting and assessing potential candidates before proceeding to surgery. We present current data on post-surgical outcomes and evaluate the psychosocial and economic effects of bariatric surgery. Finally, we evaluate the complication rates and present recommendations for post-operative care. © 2013 Neff et al; licensee BioMed Central Ltd.


Karlstrom A.,Mid Sweden University | Lindgren H.,Gothenburg University | Hildingsson I.,Mid Sweden University | Hildingsson I.,Karolinska Institutet
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2013

Objective To compare maternal complications and infant outcomes for women undergoing elective caesarean sections based on a maternal request and without recorded medical indication with those of women who underwent spontaneous onset of labour with the intention to have a vaginal birth. Design Retrospective register study. Setting Sweden; Medical Birth Register used for data collection. Methods A case-control study of 5877 birth records of women undergoing caesarean sections without medical indication and a control group of 13 774 women undergoing births through spontaneous onset of labour. The control group was further divided into women who actually had a vaginal birth and women who ended up with an emergency caesarean section. Results Maternal complications occurred more frequently among women undergoing caesarean section with odds ratios (OR) for bleeding complications of 2.5 (95% CI 2.1-3.0) in the elective caesarean group and 2.0 (95% CI 1.5-2.6) in the emergency caesarean group. The OR for infections was 2.6 in both groups. Breastfeeding complications were most common in women having an elective caesarean section: 6.8 (95% CI 3.2-14.5). Infant outcomes showed a higher incidence of respiratory distress with an OR of 2.7 (95% CI 1.8-3.9) in the elective caesarean section group compared with infants born by emergency caesarean section. The risk of hypoglycaemia was at least twice as high for infants in the caesarean group. Conclusions Caesarean sections without medical indication as well as emergency caesarean sections were associated with higher risks for maternal and infant morbidity. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.


Charkoudian N.,U.S. Army | Wallin B.G.,Gothenburg University
Comprehensive Physiology | Year: 2014

The sympathetic nervous system is a ubiquitous, integrating controller of myriad physiological functions. In the present article, we review the physiology of sympathetic neural control of cardiovascular function with a focus on integrative mechanisms in humans. Direct measurement of sympathetic neural activity (SNA) in humans can be accomplished using microneurography, most commonly performed in the peroneal (fibular) nerve. In humans, muscle SNA (MSNA) is composed of vasoconstrictor fibers; its best-recognized characteristic is its participation in transient, moment-to-moment control of arterial blood pressure via the arterial baroreflex. This property of MSNA contributes to its typical "bursting" pattern which is strongly linked to the cardiac cycle. Recent evidence suggests that sympathetic neural mechanisms and the baroreflex have important roles in the long term control of blood pressure as well. One of the striking characteristics of MSNA is its large interindividual variability. However, in young, normotensive humans, higher MSNA is not linked to higher blood pressure due to balancing influences of other cardiovascular variables. In men, an inverse relationship between MSNA and cardiac output is a major factor in this balance, whereas in women, beta-adrenergic vasodilation offsets the vasoconstrictor/pressor effects of higher MSNA. As people get older (and in people with hypertension) higher MSNA is more likely to be linked to higher blood pressure. Skin SNA (SSNA) can also be measured in humans, although interpretation of SSNA signals is complicated by multiple types of neurons involved (vasoconstrictor, vasodilator, sudomotor and pilomotor). In addition to blood pressure regulation, the sympathetic nervous system contributes to cardiovascular regulation during numerous other reflexes, including those involved in exercise, thermoregulation, chemoreflex regulation, and responses to mental stress. © 2000-2014 by John Wiley & Sons.


Busch S.,Gothenburg University | Acar A.,University of Manchester | Magnusson Y.,Gothenburg University | Gregersson P.,Gothenburg University | And 2 more authors.
Oncogene | Year: 2015

Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine with the capability to act as tumour suppressor or tumour promoter depending on the cellular context. TGF-beta receptor type-2 (TGFBR2) is the ligand-binding receptor for all members of the TGF-β family. Data from mouse model experiments demonstrated that loss of Tgfbr2 expression in mammary fibroblasts was linked to tumour initiation and metastasis. Using a randomised tamoxifen trial cohort including in total 564 invasive breast carcinomas, we examined TGFBR2 expression (n=252) and phosphorylation level of downstream target SMAD2 (pSMAD2) (n=319) in cancer-associated fibroblasts (CAFs) and assessed links to clinicopathological markers, prognostic and treatment-predictive values. The study revealed that CAF-specific TGFBR2 expression correlated with improved recurrence-free survival. Multivariate analysis confirmed CAF-TGFBR2 to be an independent prognostic marker (multivariate Cox regression, hazard ratio: 0.534, 95% (CI): 0.360-0.793, P=0.002). CAF-specific pSMAD2 levels, however, did not associate with survival outcome. Experimentally, TGF-β signalling in fibroblasts was modulated using a TGF-β ligand and inhibitor or through lentiviral short hairpin RNA-mediated TGFBR2-specific knockdown. To determine the role of fibroblastic TGF-β pathway on breast cancer cells, we used cell contact-dependent cell growth and clonogenicity assays, which showed that knockdown of TGFBR2 in CAFs resulted in increased cell growth, proliferation and clonogenic survival. Further, in a mouse model transfected CAFs were co-injected with MCF7 and tumour weight and proportion was monitored. We found that mouse xenograft tumours comprising TGFBR2 knockdown fibroblasts were slightly bigger and displayed increased tumour cell capacity. Overall, our data demonstrate that fibroblast-related biomarkers possess clinically relevant information and that fibroblasts confer effects on breast cancer cell growth and survival. Regulation of tumour-stromal cross-talk through fibroblastic TGF-β pathway may depend on fibroblast phenotype, emphasising the importance to characterise tumour microenvironment subtypes.


Buchhave P.,Lund University | Buchhave P.,Skåne University Hospital | Minthon L.,Lund University | Minthon L.,Skåne University Hospital | And 6 more authors.
Archives of General Psychiatry | Year: 2012

Context: Early detection of prodromal Alzheimer disease (AD) is important because new disease-modifying therapies are most likely to be effective when initiated during the early stages of disease. Objectives: To assess the ability of the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42) to predict future development ofADdementia within 9.2 years in patients with mild cognitive impairment (MCI) and to compare CSF biomarkers between early and late converters to AD. Design: A clinical study with a median follow-up of 9.2 years (range, 4.1-11.8 years). Setting: Memory disorder clinic. Patients: A total of 137 patients with MCI who underwent lumbar puncture at baseline. Main Outcome Measure: Conversion to AD dementia. Results: During follow-up, 72 patients (53.7%) developed AD and 21 (15.7%) progressed to other forms of dementia. At baseline, CSF Aβ42 levels were reduced and T-tau and P-tau levels were elevated in patients who converted to AD during follow-up compared with nonconverters (P<.001). Baseline CSF Aβ42 levels were equally reduced in patients with MCI who converted toADwithin 0 to 5 years (early converters) compared with those who converted between 5 and 10 years (late converters). However, CSF T-tau and P-tau levels were significantly higher in early converters vs late converters. A baseline Aβ42:P-tau ratio predicted the development ofADwithin 9.2 years with a sensitivity of 88%, specificity of 90%, positive predictive value of 91%, and negative predictive value of 86%. Conclusions: Approximately 90% of patients with MCI and pathologic CSF biomarker levels at baseline develop AD within 9 to 10 years. Levels of Aβ42 are already fully decreased at least 5 to 10 years before conversion to AD dementia, whereas T-tau and P-tau seem to be later markers. These results provide direct support in humans for the hypothesis that altered Aβ metabolism precedes tau-related pathology and neuronal degeneration. ©2012 American Medical Association. All rights reserved.


Joyner M.J.,Mayo Medical School | Wallin B.G.,Gothenburg University | Charkoudian N.,U.S. Army
Experimental Physiology | Year: 2016

Arterial pressure is a key regulated variable in the cardiovascular system with important health implications. Over the last 12 years, we have used physiological measurements, including muscle sympathetic nerve activity (MSNA), to explore the balance among mean arterial blood pressure, cardiac output and total peripheral resistance (TPR) in normotensive humans. We have shown that these determinants of blood pressure can vary widely in different subjects and how they vary depends on sex and age. In young men, there is a direct relationship between MSNA and TPR but no relationship with blood pressure. This is because cardiac output is proportionally lower in those with high MSNA and TPR. In contrast, in young women there is no relationship between MSNA and TPR (or cardiac output); this is because β-adrenergic vasodilator mechanisms offset α-adrenergic vasoconstriction. Thus, blood pressure is unrelated to MSNA in young women. In older women, β-adrenergic vasodilator mechanisms are diminished, and a direct relationship between MSNA and TPR is seen. In older men, the relationships among these variables are less clear cut, perhaps owing to age-related alterations in endothelial function. With ageing, the relationship between MSNA and blood pressure becomes positive, more so in women than in men. The finding that the physiological control of blood pressure is so different in men and women and that it varies with age suggests that future studies of mechanisms of hypertension will reveal corresponding differences among groups. © 2016 The Physiological Society.


Landstedt E.,Mid Sweden University | Persson S.,Gothenburg University
Scandinavian Journal of Public Health | Year: 2014

Objective: To investigate the factors associated with exposure to in-real-life (IRL) bullying, cyberbullying, and both IRL and cyberbullying and to explore the relationship between these types of bullying and mental health among 13-16-year-old Swedish boys and girls. Methods: Data was derived from a cross-sectional web-based study of 13-16-year-old students in northern Sweden (n=1214, response rate 81.9%). Results: The combination of IRL- and cyberbullying was the most common type of bullying. A non-supportive school environment and poor body image were related to exposure to bullying for both genders but the relationship was more distinct in girls. All types of bullying were associated with depressive symptoms in both boys and girls and all forms of bullying increased the likelihood of psychosomatic problems in girls. Conclusions: Cyberbullying can be seen as an extension of IRL bullying. A combination of IRL- and cyberbullying seems to be particularly negative for mental health. Interventions should focus on improved school environment and body image as well as anti-violence programmes. Gender aspects of bullying need to be acknowledged. © 2014 the Nordic Societies of Public Health.


Hol E.M.,University Utrecht | Hol E.M.,An Institute of the Royal Netherlands Academy of Arts and science | Hol E.M.,University of Amsterdam | Pekny M.,Gothenburg University | And 2 more authors.
Current Opinion in Cell Biology | Year: 2015

Glial fibrillary acidic protein (GFAP) is the hallmark intermediate filament (IF; also known as nanofilament) protein in astrocytes, a main type of glial cells in the central nervous system (CNS). Astrocytes have a range of control and homeostatic functions in health and disease. Astrocytes assume a reactive phenotype in acute CNS trauma, ischemia, and in neurodegenerative diseases. This coincides with an upregulation and rearrangement of the IFs, which form a highly complex system composed of GFAP (10 isoforms), vimentin, synemin, and nestin. We begin to unravel the function of the IF system of astrocytes and in this review we discuss its role as an important crisis-command center coordinating cell responses in situations connected to cellular stress, which is a central component of many neurological diseases. © 2015 Elsevier Ltd.


Rothwell P.M.,University of Oxford | Howard S.C.,University of Oxford | Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin | And 4 more authors.
The Lancet Neurology | Year: 2010

Background: Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that β blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. Methods: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65-74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). Results: In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0·0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0·0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0·78, 95% CI 0·67-0·90) was partly attenuated by adjusting for mean SBP during follow-up (0·84, 0·72-0·98), but was abolished by also adjusting for within-individual SD of clinic SBP (0·99, 0·85-1·16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0·0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0·0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. Interpretation: The opposite effects of calcium-channel blockers and β blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both. Funding: None. © 2010 Elsevier Ltd. All rights reserved.


Katcher M.H.,Princeton University | Norrby P.-O.,Gothenburg University | Norrby P.-O.,Astrazeneca | Doyle A.G.,Princeton University
Organometallics | Year: 2014

A computational and experimental approach was employed to study the mechanism of the palladium(0)-catalyzed fluorination of allylic chlorides with AgF as fluoride source. Our findings indicate that an allylpalladium fluoride is a key intermediate necessary for the generation of both the nucleophile and electrophile. Evidence was also obtained to support a homobimetallic mechanism in which C-F bond formation occurs by nucleophilic attack of a neutral allylpalladium fluoride on a cationic allylpalladium electrophile (with fluoride as counterion). The high branched selectivity and unusual ligand effects observed in the regioselective fluorination are assessed in light of this mechanism and calculated transition states. These results may have important implications for the mechanism of other transition-metal-catalyzed fluorinations. © 2014 American Chemical Society.


McMahon J.,University of Tasmania | Barker-Ruchti N.,Gothenburg University
Sport, Education and Society | Year: 2015

This paper explores three female swimmers’ relationships with their male coaches and the body practices they were exposed to within Australian swimming. Particular attention is given to how the relationships and practices might relate to gender. Additionally, the article examines how (if at all) the conduct contributed to the social construction of an accepted female swimmer body. Through narrative accounts, the three adolescent female athletes articulate hierarchical male coach–female athlete relationships and specific body encounters they were exposed to and/or engaged with. Their experiences reveal how a sexually maturing body (growing breasts, female body shape and menstruating) was deemed unsuitable for performance and the swimmers were thus encouraged to transform their bodies and behaviours towards that of the boys. Using a feminist Foucauldian perspective, these accounts points to how the three swimmers came to regulate their diet, training and appearance in order to fulfil expectations. This self-regulation is problematic in two ways: first, no scientific evidence shows that a boy like physique is essential for best performance. Second, the stress from being pressured to achieve a particular body, as well as the shame that resulted from being unable to achieve the idealised physique, eventually caused the swimmers to develop an unhealthy relationship with their developing bodies. We highlight how those immersed in sporting contexts should recognise the serious implications of gender practices and power relations underpinning the male coach–female athlete dynamic in competitive sport. © 2015 Taylor & Francis


Rothwell P.M.,University of Oxford | Howard S.C.,University of Oxford | Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin | And 4 more authors.
The Lancet | Year: 2010

Background: The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. Methods: We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied. Findings: In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6·22, 95% CI 4·16-9·29, p<0·0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12·08, 7·40-19·72, p<0·0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15·01, 6·56-34·38, p<0·0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3·25, 2·32-4·54, p<0·0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (


Archer T.,Gothenburg University | Kostrzewa R.M.,East Tennessee State University
Neurotoxicity Research | Year: 2015

Schizophrenia spectrum disorders are characterized by symptom profiles consisting of positive and negative symptoms, cognitive impairment, and a plethora of genetic, epigenetic, and phenotypic biomarkers. Assorted animal models of these disorders and clinical neurodevelopmental indicators have implicated neurodegeneration as an element in the underlying pathophysiology. Physical exercise or activity regimes—whether aerobic, resistance, or endurance—ameliorate regional brain and functional deficits not only in affected individuals but also in animal models of the disorder. Cognitive deficits, often linked to regional deficits, were alleviated by exercise, as were quality-of-life, independent of disorder staging and risk level. Apoptotic processes intricate to the etiopathogenesis of schizophrenia were likewise attenuated by physical exercise. There is also evidence of manifest benefits endowed by physical exercise in preserving telomere length and integrity. Not least, exercise improves overall health and quality-of-life. The notion of scaffolding as the outcome of physical exercise implies the “buttressing” of regional network circuits, neurocognitive domains, anti-inflammatory defenses, maintenance of telomeric integrity, and neuro-reparative and regenerative processes. © 2015, Springer Science+Business Media New York.


Linke S.,Gothenburg University | Jentoft S.,University of Tromsø
Marine Policy | Year: 2013

Current and prospective changes in European fisheries governance suggest not only a "communicative turn" but a complete turnaround in the relationships between government, science, and the fishing industry. At the heart of these changes are the so-called Regional Advisory Councils (RACs) and the idea of partially replacing the burden of proof on the resource users (fishing industry). This change entails new forms of interaction between fishers' representatives, other stakeholders (e.g. NGOs), policy-makers and scientists. By drawing on experiences from the Baltic Sea RAC, the analysis focuses on two aspects of fisheries governance: institutional design and the process of negotiation and decision-making. It is concluded that to allow for a partial shift in the burden of proof, stakeholder organisations such as RACs need to adapt both institutionally as well as process-wise to enable a more constructive and responsible fisheries governance system. © 2012 Elsevier Ltd.


Yu M.,University of Massachusetts Amherst | Nagurney A.,University of Massachusetts Amherst | Nagurney A.,Gothenburg University
European Journal of Operational Research | Year: 2013

In this paper, we develop a network-based food supply chain model under oligopolistic competition and perishability, with a focus on fresh produce. The model incorporates food deterioration through the introduction of arc multipliers, with the inclusion of the discarding costs associated with the disposal of the spoiled food products. We allow for product differentiation due to product freshness and food safety concerns, as well as the evaluation of alternative technologies associated with various supply chain activities. We then propose an algorithm with elegant features for computation. A case study focused on the cantaloupe market is investigated within this modeling and computational framework, in which we analyze different scenarios prior/during/after a foodborne disease outbreak. © 2012 Elsevier B.V. All rights reserved.


Gustafsson C.M.,Gothenburg University | Falkenberg M.,Gothenburg University | Larsson N.-G.,Max Planck Institute for Biology of Ageing | Larsson N.-G.,Karolinska Institutet
Annual Review of Biochemistry | Year: 2016

Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for the function of the oxidative phosphorylation system, which is composed of four respiratory-chain complexes and adenosine triphosphate (ATP) synthase. Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial import of hundreds of nuclear-encoded proteins that control genome maintenance, replication, transcription, RNA maturation, and mitochondrial translation. The importance of this complex regulatory system is underscored by the identification of numerous mutations of nuclear genes that impair mtDNA maintenance and expression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifestations. The basic scientific understanding of the mechanisms controlling mtDNA function has progressed considerably during the past few years, thanks to advances in biochemistry, genetics, and structural biology. The challenges for the future will be to understand how mtDNA maintenance and expression are regulated and to what extent direct intramitochondrial cross talk between different processes, such as transcription and translation, is important. © Copyright 2016 by Annual Reviews. All rights reserved.


Dillin A.,Howard Hughes Medical Institute | Gottschling D.E.,Fred Hutchinson Cancer Research Center | Nystrom T.,Gothenburg University
Current Opinion in Cell Biology | Year: 2014

Over 40 years ago, Francois Jacob proposed that levels of 'integrons' explain how biological systems are constructed. Today, these networks of interactions between tissues, cells, organelles, metabolic pathways, genes, and individual molecules provide key insights into biology. We suggest that the wiring and interdependency between subsystems within a network are useful to understand the aging process. The breakdown of one subsystem (e.g. an organelle) can have ramifications for other interconnected subsystems, leading to the sequential collapse of subsystem functions. But yet, the interconnected nature of homeostatic wiring can provide organisms with the means of compensating for the decline of one subsystem. This occurs at multiple levels in an organism. - for example, between organelles or between tissues. We review recent data that highlight the importance of such interconnectivity/communication in the aging process, in both progressive decline and longevity assurance. © 2013.


Barrett S.,Columbia University | Barrett S.,Princeton University | Dannenberg A.,Columbia University | Dannenberg A.,Gothenburg University
Nature Climate Change | Year: 2014

Despite more than two decades of diplomatic effort, concentrations of greenhouse gases continue to trend upwards, creating the risk that we may someday cross a threshold for 'dangerous' climate change. Although climate thresholds are very uncertain, new research is trying to devise 'early warning signals' of an approaching tipping point. This research offers a tantalizing promise: whereas collective action fails when threshold uncertainty is large, reductions in this uncertainty may bring about the behavioural change needed to avert a climate 'catastrophe'. Here we present the results of an experiment, rooted in a game-theoretic model, showing that behaviour differs markedly either side of a dividing line for threshold uncertainty. On one side of the dividing line, where threshold uncertainty is relatively large, free riding proves irresistible and trust illusive, making it virtually inevitable that the tipping point will be crossed. On the other side, where threshold uncertainty is small, the incentive to coordinate is strong and trust more robust, often leading the players to avoid crossing the tipping point. Our results show that uncertainty must be reduced to this 'good' side of the dividing line to stimulate the behavioural shift needed to avoid 'dangerous' climate change. © 2014 Macmillan Publishers Limited. All rights reserved.


Linke S.,Gothenburg University | Jentoft S.,University of Troms
Marine Policy | Year: 2014

Fisheries management is said to be in a perpetual state of crisis, both globally and in Europe. The causes and possible remedies of these problems often create political controversy. Is the solution more and better science or more and better politics? Does one need to improve the former, the latter or both? Or is something else missing? This paper investigates these questions by drawing on social theory and theories of knowledge. The issue of science versus politics and the role of different knowledge perspectives from stakeholders in decision-making are discussed with reference to the Regional Advisory Councils within EU fisheries, in particular, the council for the Baltic Sea. It is argued that a lost 'value-rationality' and the aspects of phronetic knowledge and research need to be included in the highly instrumental and science-based EU fisheries policy system to establish environmental and social sustainability in the sector. © 2013 Elsevier Ltd.


Zuberbier T.,Charité - Medical University of Berlin | Lotvall J.,Gothenburg University | Simoens S.,Catholic University of Leuven | Subramanian S.V.,Harvard University | Church M.K.,Charité - Medical University of Berlin
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background: In the European Union (EU), between 44 and 76 million individuals of the 217 million EU employees suffer from allergic disease of the airways or the skin. Up to 90% of these persons are untreated or insufficiently treated. This has major socio-economic consequences such as absence from work (absenteeism), particularly reduced productivity at work (presenteeism).Methods: We used published literature and online statistical information from Eurostat and Eurofound to assess the costs of allergic disease to society.Results: Allergies have an impact on direct, indirect, intangible and opportunity costs. Most importantly, for the EU, avoidable indirect costs per patient insufficiently treated for allergy range between €55 and €151 billion per annum due to absenteeism and presenteeism, that is, €2405 per untreated patient per year. On the other hand, appropriate therapy for allergic diseases is available at comparatively low costs at an average of €125 per patient annually, equalling only 5% of the costs of untreated disease, allowing potential savings of up to €142 billion.Conclusions: A better care for allergies based on guideline-based treatment would allow Europe's economy substantial savings. In addition, allergies have an impact on learning and performance at school and university, leading to opportunity costs for society. This cannot be calculated moneywise but will have an impact in a modern knowledge-based society. Still allergies are trivialized in society, noting that the costs of therapy are paid by patients and healthcare services, whereas economic savings are made by employers and society. A change of this mindset is urgently needed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Larsson H.,Karolinska Institutet | Anckarsater H.,Gothenburg University | Rastam M.,Lund University | Chang Z.,Karolinska Institutet | Lichtenstein P.,Karolinska Institutet
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2012

Background: Although the clinical utility of categorically defined attention-deficit hyperactivity disorder (ADHD) is well established, there is also strong evidence supporting the notion of ADHD as an extreme of a continuous trait. Nevertheless, the question of whether the etiology is the same for different levels of DSM-IV ADHD symptoms remains to be investigated. The aim of this study was to assess genetic links between the extreme and the subthreshold range of ADHD symptoms. Method: Parents of all Swedish 9- and 12-year-old twins born between 1992 and 2000 were interviewed for DSM-IV ADHD symptoms and associated conditions. Two validated cutoff values were used for screening and assigning research diagnoses. Response rate was 80%. Twin methods were applied to investigate the extent to which ADHD is etiologically distinct from subthreshold variations in ADHD symptoms. Results: Extremes analyses indicated a strong genetic link between the extreme and the subthreshold variation, with almost identical group heritability estimates around.60 for the diagnostic (prevalence 1.78%) and screening (prevalence 9.75%) criteria of ADHD. Conclusion: A strong genetic link between the extreme and the subthreshold variation of DSM-IV based assessments of ADHD symptoms was found. The data suggest that ADHD is best viewed as the quantitative extreme of genetic and environmental factors operating dimensionally throughout the distribution of ADHD symptoms, indicating that the same etiologic factors are involved in the full range of symptoms of inattention, hyperactivity and impulsivity. © 2011 Association for Child and Adolescent Mental Health.


Ahlin A.,Karolinska Institutet | Fasth A.,Gothenburg University
Current Opinion in Hematology | Year: 2015

Purpose of review We update and summarize the recent findings in conventional treatment and hematopoietic stem cell transplantation in chronic granulomatous disease (CGD). We also summarize the contemporary view on when hematopoietic stem cell transplantation should be the preferred treatment of choice in CGD. Recent findings Azole antifungal treatment in CGD has improved survival. With prolonged survival, inflammatory complications are an emerging problem in CGD. Several studies now present excellent results with stem cell transplantation in severe CGD, also with reduced intensity conditioning. Summary Several lines of evidence now suggest that stem cell transplantation should be the preferred treatment of choice in severe CGD, if there is an available donor. This should be performed as soon as possible to avoid severe sequelae from infection and inflammation. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Fernell E.,Gothenburg University | Eriksson M.A.,Gothenburg University | Eriksson M.A.,Karolinska Institutet | Gillberg C.,Gothenburg University
Clinical Epidemiology | Year: 2013

Autism spectrum disorders involve a set of clinical phenotypes that mirror an early onset of neurodevelopmental deviations, with core symptoms that can probably be related to a deficiency in the social instinct. Underlying the cognitive impairments there are physiological brain problems, caused by a large number of medical factors. This narrative review of systematic reviews and meta-analyses from the last 5 years (2008-2012) presents aspects from many areas in autism spectrum disorder research, with a particular focus on early intervention and the subsequent impact on prognosis. Other major areas discussed are epidemiology, early symptoms and screening, early diagnosis, neuropsychology, medical factors, and the existence of comorbidities. There is limited evidence that any of the broadband "early intervention" programs are effective in changing the natural long-term outcome for many individuals with an early diagnosis of autism. However, there is some evidence that Early Intensive Behavioral Intervention (EIBI) is an effective treatment for some children with ASD. Nevertheless, there is emerging consensus that early diagnosis and information are needed in order that an autism-friendly environment be "created" around affected individuals. © 2013 Fernell et al, publisher and licensee Dove Medical Press Ltd.


Enge S.,Gothenburg University | Nylund G.M.,Gothenburg University | Harder T.,University of New South Wales | Pavia H.,Gothenburg University
Ecology | Year: 2012

Invasion success of introduced species is often attributed to a lack of natural enemies as stated by the enemy release hypothesis (ERH). The ERH intuitively makes sense for specialized enemies, but it is less evident why invaders in their new area escape attacks by generalist enemies. A recent hypothesis explains low herbivore damage on invasive plants with plant defense chemicals that are evolutionarily novel to native herbivores. Support for this novel weapon hypothesis (NWH) is so far based on circumstantial evidence. To corroborate the NWH, there is a need for direct evidence through explicit characterizations of the novel chemicals and their effects on native consumers. This study evaluated the NWH using the highly invasive red alga Bonnemaisonia hamifera. In pairwise feeding experiments, preferences between B. hamifera and native competitors were assessed for four common generalist herbivores in the invaded area. Through a bioassay-guided fractionation, we identified the deterrent compound and verified its effect in an experiment with the synthesized compound at natural concentrations. The results showed that native herbivores strongly preferred native algae to B. hamifera. The resistance against herbivores could be tracked down to the algal metabolite 1,1,3,3-tetrabromo-2- heptanone, a compound not known from native algae in the invaded area. The importance of the chemical defense was further underlined by the feeding preference of herbivores for individuals with a depleted content of 1,1,3,3-tetrabromo-2- heptanone. This study thus provides the first conclusive example of a highly successful invader where low consumption in the new range can be directly attributed to a specific chemical defense against evolutionarily naïve native generalists. In conclusion, our results support the notion that novel chemical weapons against naïve herbivores can provide a mechanistic explanation for plant invasion success. © 2012 by the Ecological Society of America.


Jensen P.H.,Research Frontiers | Jensen P.H.,University of Southern Denmark | Karlsson N.G.,Gothenburg University | Kolarich D.,Research Frontiers | And 2 more authors.
Nature Protocols | Year: 2012

This protocol shows how to obtain a detailed glycan compositional and structural profile from purified glycoproteins or protein mixtures, and it can be used to distinguish different isobaric glycan isomers. Glycoproteins are immobilized on PVDF membranes before the N-glycans are enzymatically released by PNGase F, isolated and reduced. Subsequently, O-glycans are chemically released from the same protein spot by reductive β-elimination. After desalting with cation exchange microcolumns, the glycans are separated and analyzed by porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Optionally, the glycans can be treated with sialidases or other specific exoglycosidases to yield more detailed structural information. The sample preparation takes approximately 4 d, with a heavier workload on days 2 and 3, and a lighter load on days 1 and 4. The time for data interpretation depends on the complexity of the samples analyzed. This method can be used in conjunction with the analysis of enriched glycopeptides by capillary/nanoLC-ESI-MS/MS, which together provide detailed information regarding the site heterogeneity of glycosylation. © 2012 Nature America, Inc. All rights reserved.


Pettersson E.,Karolinska Institutet | Anckarsater H.,Gothenburg University | Gillberg C.,Gothenburg University | Lichtenstein P.,Karolinska Institutet
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2013

Background Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed overlap among neurodevelopmental problems, and explore whether this potential factor was primarily genetic or environmental in origin. The second aim was to explore whether there was systematic covariation, either genetic or environmental, over and above that contributed by the potential general factor, unique to each syndrome. Method Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2002 were targeted for interview regarding problems typical of autism spectrum disorders, ADHD and other neurodevelopmental conditions (response rate: 80 percent). Structural equation modeling was conducted on 6,595 pairs to examine the genetic and environmental structure of 53 neurodevelopmental problems. Results One general genetic factor accounted for a large proportion of the phenotypic covariation among the 53 symptoms. Three specific genetic subfactors identified 'impulsivity,' 'learning problems,' and 'tics and autism,' respectively. Three unique environment factors identified 'autism,' 'hyperactivity and impulsivity,' and 'inattention and learning problems,' respectively. Conclusion One general genetic factor was responsible for the wide-spread phenotypic overlap among all neurodevelopmental symptoms, highlighting the importance of addressing broad patient needs rather than specific diagnoses. The unique genetic factors may help guide diagnostic nomenclature, whereas the unique environmental factors may highlight that neurodevelopmental symptoms are responsive to change at the individual level and may provide clues into different mechanisms and treatments. Future research would benefit from assessing the general factor separately from specific factors to better understand observed overlap among neurodevelopmental problems. © 2013 The Authors. Journal of Child Psychology and Psychiatry.


Svensson L.,Karolinska Institutet | Bohm K.,Karolinska Institutet | Castren M.,Karolinska Institutet | Pettersson H.,Karolinska Institutet | And 3 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Emergency medical dispatchers give instructions on how to perform cardiopulmonary resuscitation (CPR) over the telephone to callers requesting help for a patient with suspected cardiac arrest, before the arrival of emergency medical services (EMS) personnel. A previous study indicated that instructions to perform CPR consisting of only chest compression result in a treatment efficacy that is similar or even superior to that associated with instructions given to perform standard CPR, which consists of both compression and ventilation. That study, however, was not powered to assess a possible difference in survival. The aim of this prospective, randomized study was to evaluate the possible superiority of compression-only CPR over standard CPR with respect to survival. METHODS: Patients with suspected, witnessed, out-of-hospital cardiac arrest were randomly assigned to undergo either compression-only CPR or standard CPR. The primary end point was 30-day survival. RESULTS: Data for the primary analysis were collected from February 2005 through January 2009 for a total of 1276 patients. Of these, 620 patients had been assigned to receive compression-only CPR and 656 patients had been assigned to receive standard CPR. The rate of 30-day survival was similar in the two groups: 8.7% (54 of 620 patients) in the group receiving compression-only CPR and 7.0% (46 of 656 patients) in the group receiving standard CPR (absolute difference for compression-only vs. standard CPR, 1.7 percentage points; 95% confidence interval, -1.2 to 4.6; P = 0.29). CONCLUSIONS: This prospective, randomized study showed no significant difference with respect to survival at 30 days between instructions given by an emergency medical dispatcher, before the arrival of EMS personnel, for compression-only CPR and instructions for standard CPR in patients with suspected, witnessed, out-of-hospital cardiac arrest. (Funded by the Swedish Heart-Lung Foundation and others; Karolinska Clinical Trial Registration number, CT20080012.) Copyright © 2010 Massachusetts Medical Society. All rights reserved.


Coyne K.S.,United Biosource Corporation | Kvasz M.,Pfizer | Ireland A.M.,United Biosource Corporation | Milsom I.,Gothenburg University | And 2 more authors.
European Urology | Year: 2012

Background: Differences in health burden associated with urinary incontinence (UI) subtypes have been previously described, but the majority of studies are in women. Additional research is needed to examine the prevalence and burden of UI subtype including postmicturition incontinence, nocturnal enuresis, coital incontinence, and incontinence for unspecified reasons. Objective: Examine the burden of UI in men and women in Sweden, the United Kingdom, and the United States. Design, setting, and participants: Secondary analyses of the Epidemiology of Lower Urinary Tract Symptoms (EpiLUTS), a cross-sectional Internet survey, were performed. Participants who reported UI were categorized as (1) urgency urinary incontinence (UUI) only, (2) stress urinary incontinence (SUI) only, (3) mixed urinary incontinence (MUI), (4) UUI plus other incontinence (OI), (5) SUI plus OI, or (6) OI. Differences in health outcomes across UI groups were explored by gender using descriptive statistics and general linear models. Measurements: Outcomes included treatment seeking for urinary symptoms, perception of bladder condition, depression, anxiety, and health-related quality of life (HRQL). Results and limitations: Of 14 140 men and 15 860 women, 6479 men (45.8%) and 10 717 women (67.6%) reported UI. The most prevalent UI subgroups were OI in men and SUI in women. MUI and SUI plus OI had the greatest treatment seeking among men, whereas MUI and UUI plus OI had the greatest treatment seeking among women. Men with MUI had the highest rates of anxiety, followed by those with UUI plus OI and SUI plus OI, and OI with a similar trend observed for depression. Anxiety and depression were highest in SUI plus OI and MUI women. MUI and UUI plus OI men and women had significantly lower HRQL compared with other UI groups. Conclusions: UI is common in men and women aged >40. Individuals with UUI combined with SUI or OI bear a greater mental health burden and report poorer HRQL. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Ronald A.,Birkbeck, University of London | Larsson H.,Karolinska Institutet | Anckarsater H.,Gothenburg University | Lichtenstein P.,Karolinska Institutet
Journal of Abnormal Psychology | Year: 2014

Autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) show high comorbidity. The following questions were addressed regarding their specific symptoms: What is the factor structure of ASD and ADHD symptoms, to what degree do different symptom domains cluster together, to what extent are these domains caused by the same genetic and environmental influences, and what is the best model of their co-occurrence? A population-based twin cohort of over 17,000 9- and 12-year-olds were assessed using the Autism-Tics, AD/HD, and other Comorbidities parental interview inventory. Principal component analyses were conducted, and symptom domain clustering was assessed. Four multivariate twin models were compared. Factors split into three ASD (social impairments, communication impairments, and restricted repetitive behaviors and interests), and three ADHD (inattention, hyperactivity, and impulsivity) symptom domains. Some ASD-ADHD symptom domain combinations clustered together often, although others not at all. A two-factor common pathway model fit the data, suggesting that ASD and ADHD symptom domains tap into separate "ASD" and "ADHD" latent factors that showed high genetic overlap. All subdomains also showed significant specific genetic and environmental influences, reflecting the etiological heterogeneity both within and between ASD and ADHD. These findings support the conceptual distinction of ASD and ADHD, and demonstrate the considerable natural co-occurrence of particular ASD/ADHD symptom domains. The results imply that more children with 1 condition show features of the other condition than show complete comorbidity. Emphasis on symptom co-occurrence, rather than complete comorbidity between disorders, may help focus clinical approaches and advance molecular genetic research. © 2014 American Psychological Association.


Rider J.R.,Brigham and Women's Hospital | Sandin F.,Regional Cancer Center | Andren O.,Örebro University | Wiklund P.,Karolinska Institutet | And 3 more authors.
European Urology | Year: 2013

Background: Limited data exist on long-term outcomes among men with prostate cancer (PCa) from population-based cohorts incorporating information on clinical risk category. Objective: To assess 15-yr mortality for men with PCa treated with noncurative intent according to clinical stage, Gleason score (GS), serum levels of prostate specific antigen (PSA), comorbidity, and age. Design, setting, and participants: Register-based cohort study of 76 437 cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009 and treated with noncurative intent. Each case was placed in one of five risk categories: (1) low risk: T1-T2 tumor, PSA level <10 ng/ml, and GS ≤6; (2) intermediate risk: T1-T2 tumor and PSA level 10-<20 ng/ml or GS 7; (3) high risk: T3 tumor or PSA level 20-<50 ng/ml or GS ≥8; (4) regional metastases: N1 or T4 tumor or PSA level 50-100 ng/ml; and (5) distant metastases: M1 tumor or PSA ≥100 ng/ml. Outcome measurements and statistical analysis: Ten- and 15-yr cumulative risk of death after diagnosis from PCa, cardiovascular disease, and other causes. Results and limitations: Among men with a Charlson Comorbidity Index (CCI) score of 0, no differences were found in observed versus expected all-cause mortality in the low-risk group. Observed mortality was only slightly greater in the intermediate-risk group, but men with high-risk localized PCa or more advanced disease had substantially higher mortality than expected. CCI was strongly associated with cumulative 10-yr mortality from causes other than PCa, especially for men <65 yr. Limitations include potential misclassification in risk category due to GS assignment. Conclusions: PCa mortality rates vary 10-fold according to risk category. The risk of death from causes other than PCa is most strongly related to comorbidity status in younger men. © 2012 European Association of Urology.


Weiss R.J.,Karolinska University Hospital | Stark A.,Karolinska Institutet | Karrholm J.,Gothenburg University
Acta Orthopaedica | Year: 2011

Background and purpose: Modular cementless revision prostheses are being used with increasing frequency. In this paper, we review risk factors for the outcome of the Link MP stem and report implant survival compared to conventional cemented long-stem hip revision arthroplasties. Patients and methods: We used data recorded in the Swedish Hip Arthroplasty Register. 812 consecutive revisions with the MP stem (mean follow-up time 3.4 years) and a control group with 1,073 cemented long stems (mean follow-up time 4.2 years) were included. Kaplan-Meier analysis was used to determine implant survival. The Cox regression model was used to study risk factors for reoperation and revision. Results: The mean age at revision surgery for the MP stem was 72 (SD 11) years. Decreasing age (HR = 1.1, 95% CI: 1-1.1), multiple previous revisions (HR = 2.6, 95% CI: 1.1-6.2), short stem length (HR = 2.4, 95% CI: 1.1-5.2), standard neck offset (HR = 5, 95% CI: 1.5-17) and short head-neck length (HR = 5.3, 95% CI 1.4-21) were risk factors for reoperation. There was an overall increased risk of reoperation (HR = 1.7, 95% CI: 1.3-2.4) and revision (HR = 1.9, 95% CI: 1.2-3.1) for the MP prostheses compared to the controls. Interpretation: The cumulative survival with both reoperation and revision as the endpoint was better for the cemented stems with up to 3 years of follow-up. Thereafter, the survival curves converged, mainly because of increasing incidence of revision due to loosening in the cemented group. We recommend the use of cemented long stems in patients with limited bone loss and in older patients. © Nordic Orthopaedic Federation.


Pekny M.,Gothenburg University | Pekna M.,Florey Institute of Neuroscience and Mental Health
Physiological Reviews | Year: 2014

Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions including the generation of new nerve cells and structural as well as functional synapse remodeling. Reactive gliosis or reactive astrogliosis is a term coined for the mor-phological and functional changes seen in astroglial cells/astrocytes responding to CNS injury and other neurological diseases. Whereas this defensive reaction of astrocytes is conceivably aimed at handling the acute stress, limiting tissue damage, and restoring homeostasis, it may also inhibit adaptive neural plasticity mechanisms underlying recovery of function. Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment. © 2014 the American Physiological Society.


Hartlova A.,Umeå University | Erttmann S.F.,Umeå University | Raffi F.A.M.,Umeå University | Schmalz A.M.,Umeå University | And 9 more authors.
Immunity | Year: 2015

Dysfunction in Ataxia-telangiectasia mutated (ATM), a central component of the DNA repair machinery, results in Ataxia Telangiectasia (AT), a cancer-prone disease with a variety of inflammatory manifestations. By analyzing AT patient samples and Atm-/- mice, we found that unrepaired DNA lesions induce type I interferons (IFNs), resulting in enhanced anti-viral and anti-bacterial responses in Atm-/- mice. Priming of the type I interferon system by DNA damage involved release of DNA into the cytoplasm where it activated the cytosolic DNA sensing STING-mediated pathway, which in turn enhanced responses to innate stimuli by activating the expression of Toll-like receptors, RIG-I-like receptors, cytoplasmic DNA sensors, and their downstream signaling partners. This study provides a potential explanation for the inflammatory phenotype of AT patients and establishes damaged DNA as a cell intrinsic danger signal that primes the innate immune system for a rapid and amplified response to microbial and environmental threats. © 2015 Elsevier Inc.


Lundstrom S.,Lund University | Chang Z.,Karolinska Institutet | Rastam M.,Lund University | Gillberg C.,Gothenburg University | And 4 more authors.
Archives of General Psychiatry | Year: 2012

Context: Autism spectrum disorders (ASDs) have been suggested to represent the extreme end of a normal distribution of autisticlike traits (ALTs). However, the evidence of this notion is inconclusive. Objective: To study whether there are similar genetic and/or environmental etiologies behind ASDs and ALTs. Design: A nationwide twin study. Participants: Consenting parents of all Swedish twins aged 9 and 12 years, born between July 1, 1992, and December 31, 2001 (n=19 208), were interviewed by telephone to screen for child psychiatric conditions, including ASDs. Main Outcome Measures: Two validated cutoffs for ASDs, 2 cutoffs encompassing the normal variation, and 1 continuous measure of ALTs were used with DeFries- Fulker extreme-end analyses and standard twin study methods. Results: We discerned a strong correlation between the 4 cutoffs and the full variation of ALTs. The correlation was primarily affected by genes. We also found that the heritability for the 4 cutoffs was similar. Conclusion: We demonstrate an etiological similarity between ASDs and ALTs in the normal variation and, with results from previous studies, our data suggest that ASDs and ALTs are etiologically linked. ©2012 American Medical Association. All rights reserved.


Wikkelso C.,Gothenburg University | Hellstrom P.,Gothenburg University | Klinge P.M.,Brown University | Tans J.T.J.,Medical Center Haaglanden
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

Objective: The objective was to determine the sensitivity, specificity, and positive and negative predictive values of the CSF Tap Test (CSF TT) and resistance to CSF outflow (Rout) for the outcome of shunting in a sample of patients with idiopathic normal pressure hydrocephalus (iNPH). Methods:115 patients were included in this European multicentre study. Diagnosis was based on clinical symptoms and signs, and MRI changes. All patients were treated with programmable ventriculoperitoneal shunts and re-examined 12 months after surgery. Outcomes were measures with a newly developed iNPH Scale and the modified Rankin Scale (mRS). Before surgery, a CSF TT and measurement of Rout was performed, with the results blinded to all caregivers. The 12 month outcome was correlated with Rout and the result of the CSF TT. Results: Rout and the results of the CSF TT showed no correlation with outcome measured by either domain, or with total iNPH score or mRS score. Only an increase in the gait task (10 m of walking at free speed) of the CSF TT correlated significantly (r=0.22, p=0.02) with improvement in iNPH score. The positive predictive value of both tests was >90% and the negative predictive value <20%. Rout >12 had an overall accuracy of 65% and the CSF TT 53%. Combining both tests did not improve their predictive power. No correlation was found between Rout and the results of the CSF TT. Conclusions: Rout and the results of the CSF TT did not correlate with outcome after 12 months. Rout and CSF TT can be used for selecting patients for shunt surgery but not for excluding patients from treatment. Trial registration: The study has been registered at clinicaltrials.gov, identifier NCT00874198.


Persson I.,Gothenburg University | Savulescu J.,Oxford Uehiro Center for Practical Ethics
Journal of Medicine and Philosophy | Year: 2010

In its basic sense, the term "human" is a term of biological classification: an individual is human just in case it is a member of the species Homo sapiens. Its opposite is "nonhuman": nonhuman animals being animals that belong to other species than H. sapiens. In another sense of human, its opposite is "inhuman," that is cruel and heartless (cf. "humane" and "inhumane"); being human in this sense is having morally good qualities. This paper argues that biomedical research and therapy should make humans in the biological sense more human in the moral sense, even if they cease to be human in the biological sense. This serves valuable biomedical ends like the promotion of health and well-being, for if humans do not become more moral, civilization is threatened. It is unimportant that humans remain biologically human, since they do not have moral value in virtue of belonging to H. sapiens. © The Author 2010.


Ronald A.,Birkbeck, University of London | Larsson H.,Karolinska Institutet | Anckarsater H.,Gothenburg University | Lichtenstein P.,Karolinska Institutet
Molecular Psychiatry | Year: 2011

This study aimed to identify empirically the number of factors underlying autism symptomssocial impairments, communication impairments, and restricted repetitive behaviors and interestswhen assessed in a general population sample. It also investigated to what extent these autism symptoms are caused by the same or different genetic and environmental influences. Autistic symptoms were assessed in a population-based twin cohort of 12 000 (9-and 12-year-old) children by parental interviews. Confirmatory factor analyses, principal component analyses and multivariate structural equation model fitting were carried out. A multiple factor solution was suggested, with nearly all analyses pointing to a three-factor model for both boys and girls and at both ages. A common pathway twin model fit the data best, which showed that there were some underlying common genetic and environmental influences across the different autism dimensions, but also significant specific genetic effects on each symptom type. These results suggest that the autism triad consists of three partly independent dimensions when assessed in the general population, and that these different autism symptoms, to a considerable extent, have partly separate genetic influences. These findings may explain the large number of children who do not meet current criteria for autism but who show some autism symptoms. Molecular genetic research may benefit from taking a symptom-specific approach to finding genes associated with autism. © 2011 Macmillan Publishers Limited All rights reserved.


Backhaus T.,Gothenburg University | Faust M.,Faust and Backhaus
Environmental Science and Technology | Year: 2012

Environmental risks of chemicals are still often assessed substance-by-substance, neglecting mixture effects. This may result in risk underestimations, as the typical exposure is toward multicomponent chemical "cocktails". We use the two well established mixture toxicity concepts (Concentration Addition (CA) and Independent Action (IA)) for providing a tiered outline for environmental hazard and risk assessments of mixtures, focusing on general industrial chemicals and assuming that the "base set" of data (EC50s for algae, crustaceans, fish) is available. As mixture toxicities higher than predicted by CA are rare findings, we suggest applying CA as a precautious first tier, irrespective of the modes/mechanisms of action of the mixture components. In particular, we prove that summing up PEC/PNEC ratios might serve as a justifiable CA-approximation, in order to estimate in a first tier assessment whether there is a potential risk for an exposed ecosystem if only base-set data are available. This makes optimum use of existing single substance assessments as more demanding mixture investigations are requested only if there are first indications of an environmental risk. Finally we suggest to call for mode-of-action driven analyses only if error estimations indicate the possibility for substantial differences between CA- and IA-based assessments. © 2012 American Chemical Society.


Dahl A.K.,Karolinska Institutet | Dahl A.K.,University Institute of Health Sciences | Hassing L.B.,Gothenburg University
Epidemiologic Reviews | Year: 2013

Obesity is a health problem that has reached epidemic proportions. Given the high prevalence of obesity, even a small adverse impact of obesity on cognitive aging might have a serious effect on public health. The purpose of this systematic review was to examine the relation between obesity and cognitive function in late life among persons not diagnosed with dementia and to evaluate the evidence for a causal association. Medline was used to search for the following terms: obesity, overweight, cognition, cognitive, age, and aged. To be included, studies must have had a population-based, dementia-free sample and a 5-year minimum interval between measurement of the predictor and the outcome. Only 11 studies met the criteria. Of these, 7 studies assessed obesity in midlife and cognitive function in later life, and 4 studies assessed obesity and cognitive function in late life. The reviewed studies showed clear evidence that midlife obesity was associated with cognitive aging, whereas this association was weaker in late life; thus, no firm conclusions could be drawn. The findings of this review suggest that, although there is evidence for an association between midlife obesity and low cognitive abilities in late life, the direction of the association and the causality remain to be clarified. © 2013 The Author. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.


Elias C.N.,Military Institute of Engineering of Rio de Janeiro | Meirelles L.,Gothenburg University
Expert Review of Medical Devices | Year: 2010

In the beginning of implantology, the procedures adopted for treating patients were performed in two surgical phases with an interval of 3-6 months. Nowadays, it is possible to insert and load a dental implant in the same surgical procedure. This change is due to several factors, such as improvement of surgical technique, modifications of the implant design, increased quality of implant manufacturing, development of the surgical instruments quality, careful patient screening and adequate treatment of the implant surface. The clinical results show that adequate treatment of surfaces is crucial for reducing healing time and treating at-risk patients. The surface properties of dental implants can be significantly improved at the manufacturing stage, affecting cells activity during the healing phase that will ultimately determine the host tissue response, a fundamental requirement for clinical success. This review focuses on different types of dental implant surfaces and the influence of surface characteristics on osseointegration. © 2010 Expert Reviews Ltd.


Sanchez J.,Autonomous University of Mexico State | Holmgren J.,Gothenburg University
Indian Journal of Medical Research | Year: 2011

After De ́s pivotal demonstration in 1959 of a diarrhoeogenic exo-enterotoxin in cell-free culture filtrates from Vibrio cholerae (of classical biotype), much insight has been gained about cholera toxin (CT), which is arguably now the best known of all microbial toxins. The subunit structure and function of CT, its receptor (the GM1 ganglioside), and its effects on the cyclic AMP system and on intestinal secretion were defined in the 1970s, and the essential aspects of the genetic organization in the 1980s. Recent findings have generated additional perspectives. The 3D-crystal structure of CT has been established, the CT- encoding operon has been shown to be carried by a non-lytic bacteriophage, and in depth knowledge has been gained on how the bacterium controls CT gene expression in response to cell density and various environmental signals. The mode of entry into target cells and the intracellular transport of CT are becoming clearer. CT has become the prototype enterotoxin and a widely used tool for elucidating important aspects of cell biology and physiology, e.g., cell membrane receptors, the cyclic AMP system, G proteins, as well as normal and pathological ion transport mechanisms. In immunology, CT has emerged as a potent, widely used experimental adjuvant, and the strong oral-mucosal immunogenicity of the non-toxic B-subunit (CTB) has led to the use of CTB as a protective antigen together with killed vibrios in a widely licensed oral cholera vaccine. CTB has also been shown to promote immunological tolerance against certain types of mucosally co-administered antigens, preferably tissue antigens linked to the CTB molecule; this has stimulated research and development to use CTB in this context for treatment of autoimmune and allergic diseases. In summary, in the 50 years after De's discovery of CT, this molecule has emerged from being the cholera patient's "foe" to also becoming a highly useful scientist's "friend".


Adriaenssens B.,University of New South Wales | Johnsson J.I.,Gothenburg University
Ecology Letters | Year: 2013

Individuals often show consistent behavioural differences where behaviours can form integrated units across functionally different contexts. However, the factors causing and maintaining behavioural syndromes in natural populations remain poorly understood. In this study, we provide evidence for the emergence of a behavioural syndrome during the first months of life in wild brown trout (Salmo trutta). Behavioural traits of trout were scored before and after a 2-month interval covering a major survival bottleneck, whereupon the consistency and covariance of behaviours were analysed. We found that selection favoured individuals with high activity levels in an open-field context, a personality trait consistent throughout the duration of the experiment. In addition, a behavioural syndrome emerged over the 2 months in the wild, linking activity to aggressiveness and exploration tendency. These novel results suggest that behavioural syndromes can emerge rapidly in nature from interaction between natural selection and behavioural plasticity affecting single behaviours. © 2012 Blackwell Publishing Ltd/CNRS.


Mazuela J.,Rovira i Virgili University | Norrby P.-O.,Gothenburg University | Andersson P.G.,Uppsala University | Andersson P.G.,University of KwaZulu - Natal | And 2 more authors.
Journal of the American Chemical Society | Year: 2011

A modular set of phosphite-oxazoline (P,N) ligands has been applied to the title reaction. Excellent ligands have been identified for a range of substrates, including previously challenging terminally disubstituted olefins, where we now have reached enantioselectivities of 99% for a range of substrates. The selectivity is best for minimally functionalized substrates with at least a moderate size difference between geminal groups. A DFT study has allowed identification of the preferred pathway. Computational prediction of enantioselectivities gave very good accuracy. © 2011 American Chemical Society.


Telford M.J.,Gothenburg University | Telford M.J.,Paris-Sorbonne University
Proceedings. Biological sciences / The Royal Society | Year: 2014

While some aspects of the phylogeny of the five living echinoderm classes are clear, the position of the ophiuroids (brittlestars) relative to asteroids (starfish), echinoids (sea urchins) and holothurians (sea cucumbers) is controversial. Ophiuroids have a pluteus-type larva in common with echinoids giving some support to an ophiuroid/echinoid/holothurian clade named Cryptosyringida. Most molecular phylogenetic studies, however, support an ophiuroid/asteroid clade (Asterozoa) implying either convergent evolution of the pluteus or reversals to an auricularia-type larva in asteroids and holothurians. A recent study of 10 genes from four of the five echinoderm classes used 'phylogenetic signal dissection' to separate alignment positions into subsets of (i) suboptimal, heterogeneously evolving sites (invariant plus rapidly changing) and (ii) the remaining optimal, homogeneously evolving sites. Along with most previous molecular phylogenetic studies, their set of heterogeneous sites, expected to be more prone to systematic error, support Asterozoa. The homogeneous sites, in contrast, support an ophiuroid/echinoid grouping, consistent with the cryptosyringid clade, leading them to posit homology of the ophiopluteus and echinopluteus. Our new dataset comprises 219 genes from all echinoderm classes; analyses using probabilistic Bayesian phylogenetic methods strongly support Asterozoa. The most reliable, slowly evolving quartile of genes also gives highest support for Asterozoa; this support diminishes in second and third quartiles and the fastest changing quartile places the ophiuroids close to the root. Using phylogenetic signal dissection, we find heterogenous sites support an unlikely grouping of Ophiuroidea + Holothuria while homogeneous sites again strongly support Asterozoa. Our large and taxonomically complete dataset finds no support for the cryptosyringid hypothesis; in showing strong support for the Asterozoa, our preferred topology leaves the question of homology of pluteus larvae open. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Liu K.,Renmin University of China | Gao S.,Gothenburg University
Journal of Physical Chemistry C | Year: 2012

The adsorption of water molecules on sodium-covered Cu(111) surfaces have been studied using first-principles calculations. Water molecules interact predominantly with the quantum well states of the Na overlayers, leading to charge transfer and reduction of the dissociation barrier. This interaction is state specific. At one monolayer Na coverage, the water molecule shows a maximum ratio between the adsorption energy and dissociation barrier, favoring the catalytic water splitting reaction. This conclusion is in accord with experimental observation and suggests the possibility for state-selective control of water-surface interactions. © 2012 American Chemical Society.


Bjornsson B.T.,Gothenburg University | Stefansson S.O.,University of Bergen | McCormick S.D.,U.S. Geological Survey
General and Comparative Endocrinology | Year: 2011

Smolting is a hormone-driven developmental process that is adaptive for downstream migration and ocean survival and growth in anadromous salmonids. Smolting includes increased salinity tolerance, increased metabolism, downstream migratory and schooling behavior, silvering and darkened fin margins, and olfactory imprinting. These changes are promoted by growth hormone, insulin-like growth factor I, cortisol, thyroid hormones, whereas prolactin is inhibitory. Photoperiod and temperature are critical environmental cues for smolt development, and their relative importance will be critical in determining responses to future climate change. Most of our knowledge of the environmental control and endocrine mediation of smolting is based on laboratory and hatchery studies, yet there is emerging information on fish in the wild that indicates substantial differences. Such differences may arise from differences in environmental stimuli in artificial rearing environments, and may be critical to ocean survival and population sustainability. Endocrine disruptors, acidification and other contaminants can perturb smolt development, resulting in poor survival after seawater entry. © 2010.


Larsson H.,Karolinska Institutet | Ryden E.,Karolinska Institutet | Boman M.,Karolinska Institutet | Langstrom N.,National Institute of Development Administration | And 2 more authors.
British Journal of Psychiatry | Year: 2013

Background: Attention-deficit hyperactivity disorder (ADHD) is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder and ADHD is aetiologically distinct from the pure disorders. Aims: To clarify whether ADHD shares genetic and environmental factors with bipolar disorder and schizophrenia. Method: By linking longitudinal Swedish national registers, we identified 61 187 persons with ADHD (the proband group) and their first- and second-degree relatives, and matched them with a control group of people without ADHD and their corresponding relatives. Conditional logistic regression was used to determine the risks of bipolar disorder and schizophrenia in the relatives of the two groups. Results: First-degree relatives of the ADHD proband group were at increased risk of both bipolar disorder (odds ratio (OR) = 1.84-2.54 for parents, offspring and full siblings) and schizophrenia (OR = 1.71-2.22 for parents, offspring and full siblings). The risks of bipolar disorder and schizophrenia among second-degree relatives were substantially lower than among full siblings. Conclusions: These findings suggest that the co-occurrence of ADHD and bipolar disorder as well as ADHD and schizophrenia is due to shared genetic factors, rather than representing completely aetiologically distinct subsyndromes.


Selander L.,Gothenburg University | Jarvenpaa S.L.,University of Texas at Austin
MIS Quarterly: Management Information Systems | Year: 2016

An emerging research agenda focuses on social media's influence on political activism. Specific attention has recently been paid to digital social movement organizing and action repertoire development. The literature acknowledges the changing face of activism at the movement level, but little is known about the relationship between social movement organizations (SMOs) and digital action repertoires. Understanding this relationship is critical because strong adherence to values is at the heart of establishing action repertoires with legitimacy and persistence. In this paper, we rely on a two-year longitudinal study of the Swedish affiliate of Amnesty International. We examine the transformation in engagement and interaction that followed the organization's introduction of new action repertoires. Drawing on resource mobilization theory and the collective action space model, we elaborate how new action repertoires both stabilized and challenged the values of the SMO, as well as gradually broadened the interactions of supporters and deepened their modes of engagement. We offer a value-based model on the antecedents and effects of new action repertoires from the SMO perspective. The empirical findings and the model build new theory on social media and digital activism at the organizational level, complementing the predominant movement level research in the extant literature.


Wermeling F.,Karolinska Institutet | Lind S.M.,Karolinska Institutet | Jordo E.D.,Karolinska Institutet | Cardell S.L.,Gothenburg University | Karlsson M.C.I.,Karolinska Institutet
Journal of Experimental Medicine | Year: 2010

Faulty activation of autoreactive B cells is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting activation of autoreactive B cells is efficient removal of apoptotic material. Mounting evidence also connects a primary defect in invariant natural killer T (iNKT) cells to autoimmune disease development. However, exactly how this unconventional T cell subset is involved remains to be defined. Here, we identify a suppressive role for iNKT cells in a model where autoantibody production is triggered by an increased load of circulating apoptotic cells, resembling the situation in SLE patients. Absence or reduction of iNKT cells as well as absence of CD1d-expression on B cells, needed for direct iNKT-B cell interaction, leads to increased autoreactive B cell activation and symptoms of disease. The suppression mediated by the iNKT cells is observed before B cell entry into germinal centers and can be rescued by transferring iNKT cells to deficient mice. This links iNKT cells to handling of dying cells and identifies a novel peripheral tolerance checkpoint relevant for autoimmune disease. Thus, these observations connect two clinical observations in SLE patients previously considered to be unrelated and define a new target for immunotherapy. © 2010 Wermeling et al.


Marschall H.-U.,Gothenburg University | Wikstrom Shemer E.,Karolinska Institutet | Ludvigsson J.F.,Karolinska University Hospital | Ludvigsson J.F.,Örebro University | Stephansson O.,Karolinska University Hospital
Hepatology | Year: 2013

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. We aimed to estimate the risk of developing hepatobiliary disease in women with ICP and the odds of developing ICP in women with prevalent hepatobiliary disease. We analyzed data of women with births between 1973 and 2009 and registered in the Swedish Medical Birth Register. By linkage with the Swedish Patient Register, we identified 11,388 women with ICP who were matched to 113,893 women without this diagnosis. Diagnoses of preexisting or later hepatobiliary disease were obtained from the Patient Register. Main outcome measures were hazard ratios (HRs) for later hepatobiliary disease in women with ICP and odds ratios (ORs) for developing ICP in preexisting hepatobiliary disease. Risk estimates were calculated through Cox and logistic regression analyses. Women with ICP were more often diagnosed with later hepatobiliary disease (HR 2.62; 95% confidence interval [CI] 2.47-2.77; increment at 1% per year), hepatitis C or chronic hepatitis (HR 4.16; 3.14-5.51 and 5.96; 3.43-10.33, respectively), fibrosis/cirrhosis (HR 5.11; 3.29-7.96), gallstone disease or cholangitis (HR 2.72; 2.55-2.91, and 4.22; 3.13-5.69, respectively) as compared to women without ICP (P<0.001 for all HRs). Later ICP was more common in women with prepregnancy hepatitis C (OR 5.76; 1.30-25.44; P=0.021), chronic hepatitis (OR 8.66; 1.05-71.48; P=0.045), and gallstone disease (OR 3.29; 2.02-5.36; P<0.0001). Conclusion: Women with ICP have substantially increased risk for later hepatobiliary disease. Beyond gallstone-related morbidity we found a strong positive association between ICP and hepatitis C both before and after ICP diagnosis. Thus, we advocate testing for hepatitis C in women with ICP, in particular, since this potentially life-threatening infection can be treated successfully in the majority of patients. © 2013 by the American Association for the Study of Liver Diseases.


The pair interaction between two charged colloidal particles, in the presence of a polyelectrolyte as well as simple salt, is analyzed theoretically. Of particular interest is the way in which such a combination of salts can be used to induce a strong, long-range attraction, with at most a minor free energy barrier. We show that the nature of the simple salt is highly relevant, i.e., 2:1, 1:1, and 1:2 salts generate quite different particle interaction free energies at the same overall ionic strength. We adopt several different theoretical levels of description. Defining simulations at the primitive model level with explicit simple salt as our reference, we invoke stepwise coarse-graining with careful evaluations of each approximation. Representing monovalent simple ions by the ionic screening they generate is one such simplification. In order to proceed further, with additional computational savings, we also develop a correlation-corrected classical density functional theory. We analyze the performance of this theory with explicit spherical particles as well as in a flat surface geometry, utilizing Derjaguin's approximation. The calculations are particularly fast in the latter case, facilitating computational savings of many (typically 5-7) orders of magnitude, compared to corresponding simulations with explicit salt. Yet, the predictions are remarkably accurate, and considering the crudeness of the model itself, the density functional theory is a very attractive alternative to simulations. © 2012 American Chemical Society.


Henoch I.,Gothenburg University | Lovgren M.,Dalarna University
European Journal of Oncology Nursing | Year: 2014

Purpose: To explore the influence of symptom clusters and the most distressing concerns on global rating of quality of life (QoL) among patients with inoperable lung cancer (LC) over a three-month period following diagnosis. Methods: Data were derived from a longitudinal study dealing with the symptom experiences of 400 patients with LC at three time points: close to diagnosis and one and three months later. The symptom clusters were derived from a QoL questionnaire using factor analysis, which resulted in three clusters: the Respiratory cluster, the Pain cluster and the Mood cluster. The most distressing concerns were derived from responses to a free listing question ('What is most distressing at present') and were categorised under three dimensions: Bodily distress, Life situation with LC and Iatrogenic distress. Cross-sectional, multivariate regression analyses with QoL as a dependent variable were used to determine predictors (symptom clusters and most distressing concerns) at the three time points. Results: All three symptom clusters predicted QoL at each time point. Close to diagnosis, none of the dimensions of most distressing concerns predicted QoL, while the dimension Bodily distress was a significant predictor of QoL after one month. The Life situation with LC dimension was a significant predictor of QoL three months after diagnosis. Conclusions: Symptom clusters are important to LC patients' QoL and need to be acknowledged by healthcare professionals. The present study shows the importance of patients' descriptions of key concerns, which vary from diagnosis onwards, and urges healthcare professionals to be vigilant to such changes. © 2013 Elsevier Ltd.


Diaz R.J.,Virginia Institute of Marine Science | Rosenberg R.,Gothenburg University
International Journal of Water Resources Development | Year: 2011

Low dissolved oxygen environments (known as hypoxic or dead zones) occur in a wide range of aquatic systems and vary in frequency, seasonality and persistence. While there have always been naturally occurring hypoxic habitats, anthropogenic activities related primarily to organic and nutrient enrichment related to sewage/industrial discharges and land runoff have led to increases in hypoxia and anoxia in both freshwater and marine systems. As a result, over the last 50 years there has been a rapid rise in the areas affected by hypoxia. The future status of hypoxia and its consequences for the environment, society and economies will depend on a combination of climatechange (primarily from warming, and altered patterns for wind, currents and precipitation) and land-use change (primarily from expanded human population, agriculture and nutrient loadings). The overall forecast is for hypoxia to worsen, with increased occurrence, frequency, intensity and duration. The consequences of eutrophication-induced hypoxia can be reversed if long-term, broadscale and persistent efforts to reduce nutrient loads are developed and implemented. © 2011 Taylor & Francis.


Yang X.,Gothenburg University | Sun G.Y.,University of Missouri | Eckert G.P.,Goethe University Frankfurt | Lee J.C.-M.,University of Missouri
Molecular Neurobiology | Year: 2014

The senile plaque is a pathologic hallmark of Alzheimer's disease (AD). Amyloid-β peptide (Aβ), the main constituent of senile plaques, is neurotoxic especially in its oligomeric form. Aβ is derived from the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases in the amyloidogenic pathway. Alternatively, APP can be cleaved by α-secretases within the Aβ domain to produce neurotrophic and neuroprotective α-secretase-cleaved soluble APP (sAPPα) in the nonamyloidogenic pathway. Since APP and α-, β-, and γ-secretases are membrane proteins, APP processing should be highly dependent on the membrane composition and the biophysical properties of cellular membrane. In this review, we discuss the role of the biophysical properties of cellular membrane in APP processing, especially the effects of phospholipases A2(PLA2s), fatty acids, cholesterol, and Aβ on membrane fluidity in relation to their effects on APP processing. © 2014, Springer Science+Business Media New York.


Granhag P.A.,Gothenburg University | Stromwall L.A.,Gothenburg University | Willen R.M.,Gothenburg University | Hartwig M.,John Jay College of Criminal Justice
Legal and Criminological Psychology | Year: 2013

Purpose. Research on real-life suspect interviews shows that disclosure of evidence is a very common tactic and that it occurs in all phases of the interview. It is therefore remarkable that there is hardly any research on the effectiveness of different disclosure tactics. The aim of this study was to examine the effects of three different disclosure tactics: presenting the evidence early and two versions of the Strategic Use of Evidence (SUE) technique. Methods. For the SUE-Basic technique (SUE-B), the evidence was disclosed late in the interview. For the SUE-Incremental technique (SUE-I), we used a stepwise disclosure tactic derived from the so-called Evidence Framing Matrix. The tactic consists of revealing evidence of increasing strength and precision. A mock-theft scenario was employed with 195 participants who were randomly allocated to one of six conditions: guilty or innocent suspects were interviewed with one of the three techniques. Two measures of inconsistency were used as dependent variables: statement-evidence inconsistency and the newly developed within-statement inconsistency. Results. By interviewing with SUE-I, strong cues to deception were elicited, especially for the statement-evidence inconsistency variable. For the SUE-B, significant but smaller differences between guilty and innocent suspects were obtained. Conclusions. We found that both when and how the evidence was disclosed moderated the effectiveness of disclosure. With respect to when, it was more effective to disclose the evidence late (vs. early), and with respect to how, it was more effective to disclose the evidence in a stepwise (vs. direct) manner. The tactical aspects of evidence disclosure are discussed. © 2012 The British Psychological Society.


Barendregt W.,Gothenburg University | Bekker T.M.,TU Eindhoven
Computers and Education | Year: 2011

Employing a mixed-method explorative approach, this study examined the in situ use of and opinions about an educational computer game for learning English introduced in three schools offering different levels of freedom to choose school activities. The results indicated that the general behaviour of the children with the game was very different for each of the schools while there were no significant differences in subjective opinions or previous computer game experience as measured with a questionnaire. The gaming records and interviews informed that children do enjoy playing the game in comparison with other formal learning activities, but appreciate it less as a leisure-time activity. Furthermore it appears that children used to teacher-initiated activities tend to depend on their teacher's directions for how and when to play. The study highlights the level of choice as one of the important aspects to consider when introducing a game in the classroom. The study also points out some suggestions for the design of educational games, such as providing communication possibilities between players and integrating fast-paced motor-skill based games with learning content in a meaningful way. © 2010 Elsevier Ltd. All rights reserved.


Bjork Bramberg E.,Gothenburg University | Dahlberg K.,Linnaeus University
Qualitative Health Research | Year: 2013

Our focus in this article is research interviews that involve two languages. We present an epistemological and methodological analysis of the meaning of qualitative interviewing with an interpreter. The results of the analysis show that such interviewing is not simply exchanging words between two languages, but means understanding, grasping the essential meanings of the spoken words, which requires an interpreter to bridge the different horizons of understanding. Consequently, a research interview including an interpreter means a three-way coconstruction of data. We suggest that interpreters be thoroughly introduced into the research process and research interview technique, that they take part in the preparations for the interview event, and evaluate the translation process with the researcher and informant after the interview. © The Author(s) 2013.


Sommer F.,Gothenburg University | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS
Mucosal Immunology | Year: 2015

The epithelium is a first line of defense against microorganisms in the gut. Reactive oxygen species (ROS) have an important role in controlling the normal gut microbiota and pathogenic bacteria. Dual oxidase 2 (DUOX2) is an important source of hydrogen peroxide in the small and large intestine, and the gut microbiota induces Duox2 expression. Here, we investigated the microbial regulation of Duox2 expression. We found that Duox2 was expressed by intestinal epithelial cells mainly in the tip of the epithelium. Duox2 expression was strongly induced by the presence of a normal microbiota in mice, but not when germ-free mice were colonized with various commensal bacteria. Duox2 expression was more rapidly induced by the gut microbiota in the colon than in the ileum. Furthermore, we showed that regulation of Duox2 expression in the ileum involved TIR-domain-containing adaptor protein including interferon-β (TRIF) and canonical nuclear factor-κB p50/p65 signaling, whereas regulation of Duox2 expression in the colon involved MyD88 and the p38 pathway. Collectively, these data indicate that the gut microbiota uses two distinct signaling pathways to induce Duox2 expression in the ileum and colon epithelium.


Caesar R.,Gothenburg University | Tremaroli V.,Gothenburg University | Kovatcheva-Datchary P.,Gothenburg University | Cani P.D.,Catholic University of Louvain | And 2 more authors.
Cell Metabolism | Year: 2015

Dietary lipids may influence the abundance of circulating inflammatory microbial factors. Hence, inflammation in white adipose tissue (WAT) induced by dietary lipids may be partly dependent on their interaction with the gut microbiota. Here, we show that mice fed lard for 11 weeks have increased Toll-like receptor (TLR) activation and WAT inflammation and reduced insulin sensitivity compared with mice fed fish oil and that phenotypic differences between the dietary groups can be partly attributed to differences in microbiota composition. Trif-/- and Myd88-/- mice are protected against lard-induced WAT inflammation and impaired insulin sensitivity. Experiments in germ-free mice show that an interaction between gut microbiota and saturated lipids promotes WAT inflammation independent of adiposity. Finally, we demonstrate that the chemokine CCL2 contributes to microbiota-induced WAT inflammation in lard-fed mice. These results indicate that gut microbiota exacerbates metabolic inflammation through TLR signaling upon challenge with a diet rich in saturated lipids. © 2015 The Authors.


Khan M.,Gothenburg University | Nieuwdorp M.,Gothenburg University | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS
Cell Metabolism | Year: 2014

The gut microbiota has emerged as an integral factor that impacts host metabolism and has been suggested to play a vital role in metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In humans, cross-sectional studies have identified microbiota profiles associated with metabolic diseases, whereas causation mainly has been demonstrated in animal models. Recent studies involving microbiota-based interventions in humans, or transfer of disease-associated microbiota into germ-free mice, underscore that an altered microbiota may directly modulate host metabolism in humans. However, it will be essential to determine whether an altered gut microbiota precedes development of insulin resistance and diabetes and to identify the underlying molecular mechanisms. Increased mechanistic insights of how the microbiota modulates metabolic disease in humans may pave the way for identification of innovative microbiota-based diagnostics and/or therapeutics. © 2014 Elsevier Inc. All rights reserved.


Bolzoni F.,Gothenburg University | Bolzoni F.,University of Milan | Pettersson L.-G.,Gothenburg University | Jankowska E.,Gothenburg University
Journal of Physiology | Year: 2013

The main aim of the study was to examine the effects of transcranial polarization on neurons in two descending motor systems, rubro- and reticulospinal. Anodal DC current was applied through an electrode in contact with the skull over the contralateral sensori-motor cortex, against an electrode placed between the skull and the ipsilateral temporal muscles in deeply anaesthetized cats. Its effects were estimated from changes in descending volleys evoked by electrical stimuli applied in the red nucleus (RN), medial longitudinal fascicle (MLF; to reticulospinal fibres) and the pyramidal tract (PT; to corticospinal or corticoreticular fibres). The descending volleys were recorded from the surface of the spinal cord at a cervical level. Rubrospinal neurones were activated either directly or indirectly, via interpositorubral fibres. Reticulospinal neurons were likewise activated directly and indirectly, via other reticulospinal or corticospinal fibres. Transcranial polarization facilitated transsynaptic activation of both rubrospinal and reticulospinal neurons, shortening the latency of the indirect descending volleys and/or increasing them, Direct activation of descending axons was much less affected. The facilitation of all subcortical neurons examined was potentiated by repeated applications of transcranial direct current stimulation (tDCS) and outlasted the polarization by at least 1-2 h, replicating tDCS effects on indirect activation of cortical neurons. The results indicate that the beneficial effects of tDCS on motor performance in humans may be due to more efficient activation of not only cortical but also subcortical neuronal systems. Combined actions of tDCS on cortical and subcortical neurones might thus further improve recovery of motor functions during rehabilitation after central injuries. 249/250 © 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society.


Sayin S.I.,Gothenburg University | Wahlstrom A.,Gothenburg University | Felin J.,Gothenburg University | Jantti S.,VTT Technical Research Center of Finland | And 7 more authors.
Cell Metabolism | Year: 2013

Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum. © 2013 Elsevier Inc.


Pansch C.,Leibniz Institute of Marine Science | Pansch C.,Gothenburg University | Schaub I.,Leibniz Institute of Marine Science | Schaub I.,University of Rostock | And 2 more authors.
Global Change Biology | Year: 2014

Energy availability and local adaptation are major components in mediating the effects of ocean acidification (OA) on marine species. In a long-term study, we investigated the effects of food availability and elevated pCO2 (ca. 400, 1000 and 3000 μatm) on growth of newly settled Amphibalanus (Balanus) improvisus to reproduction, and on their offspring. We also compared two different populations, which were presumed to differ in their sensitivity to pCO2 due to differing habitat conditions: Kiel Fjord, Germany (Western Baltic Sea) with naturally strong pCO2 fluctuations, and the Tjärnö Archipelago, Sweden (Skagerrak) with far lower fluctuations. Over 20 weeks, survival, growth, reproduction and shell strength of Kiel barnacles were all unaffected by elevated pCO2, regardless of food availability. Moulting frequency and shell corrosion increased with increasing pCO2 in adults. Larval development and juvenile growth of the F1 generation were tolerant to increased pCO2, irrespective of parental treatment. In contrast, elevated pCO2 had a strong negative impact on survival of Tjärnö barnacles. Specimens from this population were able to withstand moderate levels of elevated pCO2 over 5 weeks when food was plentiful but showed reduced growth under food limitation. Severe levels of elevated pCO2 negatively impacted growth of Tjärnö barnacles in both food treatments. We demonstrate a conspicuously higher tolerance to elevated pCO2 in Kiel barnacles than in Tjärnö barnacles. This tolerance was carried over from adults to their offspring. Our findings indicate that populations from fluctuating pCO2 environments are more tolerant to elevated pCO2 than populations from more stable pCO2 habitats. We furthermore provide evidence that energy availability can mediate the ability of barnacles to withstand moderate CO2 stress. Considering the high tolerance of Kiel specimens and the possibility to adapt over many generations, near future OA alone does not seem to present a major threat for A. improvisus. © 2013 John Wiley & Sons Ltd.


Hartstra A.V.,University of Amsterdam | Bouter K.E.C.,University of Amsterdam | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS | And 2 more authors.
Diabetes Care | Year: 2015

The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota compositionmight function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future. © 2015 by the American Diabetes Association.


Landgren M.,Skaraborg Hospital | Svensson L.,Skaraborg Hospital | Stromland K.,Gothenburg University | Gronlund M.A.,Gothenburg University
Pediatrics | Year: 2010

OBJECTIVES: The purposes of this investigation were to determine the frequencies of and associations between different neurodevelopmental disorders and to study the potential lasting effects of alcohol on children adopted from eastern Europe. METHODS: In a population-based, prospective, observational, multidisciplinary, cross-sectional, cohort study of 71 children adopted from eastern Europe, children were assessed 5 years after adoption, from pediatric, neuropsychological, and ophthalmologic perspectives. RESULTS: Fetal alcohol spectrum disorders, that is, fetal alcohol syndrome (FAS), partial FAS, and alcohol-related neurodevelopmental disorders, were identified for 52% of children; FAS was found for 30%, partial FAS for 14%, and alcohol-related neurodevelopmental disorders for 9%. Alcohol-related birth defects were found for 11% of children, all of whom also were diagnosed as having FAS. Mental retardation or significant cognitive impairment was found for 23% of children, autism for 9%, attention-deficit/hyperactivity disorder for 51%, and developmental coordination disorder for 34%. CONCLUSIONS: Fetal alcohol spectrum disorders and neurodevelopmental disorders were common in this long-term follow-up study of children adopted from orphanages in eastern Europe. Maternal alcohol consumption during pregnancy has long-lasting adverse effects, causing structural, behavioral, and cognitive damage despite a radically improved environment. Copyright © 2010 by the American Academy of Pediatrics.


Schroeder B.O.,Gothenburg University | Backhed F.,Novo Nordisk AS
Nature Medicine | Year: 2016

The ecosystem of the human gut consists of trillions of bacteria forming a bioreactor that is fueled by dietary macronutrients to produce bioactive compounds. These microbiota-derived metabolites signal to distant organs in the body, which enables the gut bacteria to connect to the immune and hormone system, to the brain (the gut-brain axis) and to host metabolism, as well as other functions of the host. This microbe-host communication is essential to maintain vital functions of the healthy host. Recently, however, the gut microbiota has been associated with a number of diseases, ranging from obesity and inflammatory diseases to behavioral and physiological abnormalities associated with neurodevelopmental disorders. In this Review, we will discuss microbiota-host cross-talk and intestinal microbiome signaling to extraintestinal organs. We will review mechanisms of how this communication might contribute to host physiology and discuss how misconfigured signaling might contribute to different diseases. © 2016 Nature America, Inc. All rights reserved.


Wahlstrom A.,Gothenburg University | Sayin S.I.,Gothenburg University | Marschall H.-U.,Gothenburg University | Backhed F.,Gothenburg University | Backhed F.,Novo Nordisk AS
Cell Metabolism | Year: 2016

The gut microbiota is considered a metabolic “organ” that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition. © 2016 Elsevier Inc.


Archer T.,Gothenburg University | Josefsson T.,Halmstad University | Lindwall M.,Gothenburg University
CNS and Neurological Disorders - Drug Targets | Year: 2014

Regular physical exercise/activity has been shown repeatedly to promote positive benefits in cognitive, emotional and motor domains concomitant with reductions in distress and negative affect. It exerts a preventative role in anxiety and depressive states and facilitates psychological well-being in both adolescents and adults. Not least, several meta-analyses attest to improvements brought about by exercise. In the present treatise, the beneficial effects of exercise upon cognitive, executive function and working memory, emotional, self-esteem and depressed mood, motivational, anhedonia and psychomotor retardation, and somatic/physical, sleep disturbances and chronic aches and pains, categories of depression are discussed. Concurrently, the amelioration of several biomarkers associated with depressive states: hypothalamic-pituitary-adrenal (HPA) axis homeostasis, anti-neurodegenerative effects, monoamine metabolism regulation and neuroimmune functioning. The notion that physical exercise may function as “scaffolding” that buttresses available network circuits, anti-inflammatory defences and neuroreparative processes, e.g. brain-derived neurotrophic factor (BDNF), holds a certain appeal. © 2014 Bentham Science Publishers.


Carlsson S.V.,Sloan Kettering Cancer Center | Carlsson S.V.,Gothenburg University | Kattan M.W.,Cleveland Clinic
Nature Reviews Clinical Oncology | Year: 2016

Prostate-specific antigen (PSA)-based screening approaches are associated with reduced prostate-cancer mortality, but can lead to overdiagnosis, unnecessary biopsies and overtreatment. Two solutions for this problem exist: to abandon PSA-based screening completely, or to improve the accuracy of PSA-based screening methods to solve the benefit-to-harm equation. Herein we explore these solutions by examining three recent publications. © 2016 Macmillan Publishers Limited. All rights reserved.


Stahlberg A.,Gothenburg University | Thomsen C.,Gothenburg University | Ruff D.,Life Technologies | Aman P.,Gothenburg University
Clinical Chemistry | Year: 2012

BACKGROUND: The single cell represents the basic unit of all organisms. Most investigations have been performed on large cell populations, but understanding cell dynamics and heterogeneity requires single-cell analysis. Current methods for single-cell analysis generally can detect only one class of analytes. METHODS: Reverse transcription and the proximity ligation assay were coupled with quantitative PCR and used to quantify any combination of DNA, mRNAs, microRNAs (miRNAs), noncoding RNAs (ncRNAs), and proteins from the same single cell. The method was used on transiently transfected human cells to determine the intracellular concentrations of plasmids, their transcribed mRNAs, translated proteins, and downstream RNA targets. RESULTS: We developed a whole-cell lysis buffer to release unfractionated DNA, RNA, and proteins that would not degrade any detectable analyte or inhibit the assay. The dynamic range, analytical sensitivity, and specificity for quantifying DNA, mRNAs, miRNAs, ncRNAs, and proteins were shown to be accurate down to the single-cell level. Correlation studies revealed that the intracellular concentrations of plasmids and their transcribed mRNAs were correlated only moderately with translated protein concentrations (Spearman correlation coefficient, 0.37 and 0.31, respectively; P <0.01). In addition, an ectopically expressed gene affected the correlations between analytes and this gene, which is related to gene regulation. CONCLUSIONS: This method is compatible with most cell-sampling approaches, and generates output for the same parameter for all measured analytes, a feature facilitating comparative data analysis. This approach should open up new avenues in molecular diagnostics for detailed correlation studies of multiple and different classes of analytes at the single-cell level. © 2012 American Association for Clinical Chemistry.


Arneborg L.,Gothenburg University | Wahlin A.K.,Gothenburg University | Bjork G.,Gothenburg University | Liljebladh B.,Gothenburg University | Orsi A.H.,Texas A&M University
Nature Geoscience | Year: 2012

The West Antarctic Ice Sheet contains enough ice to raise global sea level by several metres and, because it is grounded mainly below sea level, it is sensitive to ocean warming. Accelerated thinning of glaciers that discharge into the Amundsen Sea over the past decades has been proposed to be related to the presence of warmer waters beneath the ice shelves. Three deep troughs crosscut the continental shelf of the Amundsen Sea, forming passages through which warm ocean waters can access the ice shelves, but oceanographic data has been limited. Here we present direct measurements from an ocean mooring and ship transect of the temperatures, salinities and velocities from one of these troughs in the central Amundsen Sea during the year 2010. The data show persistent inflow towards the ice shelf of relatively warm and salty water at the bottom of the trough throughout the year, and outflow of colder water above. Superposed on this background flow are barotropic current fluctuations that do not contribute significantly to the overall transport. In contrast to numerical models, which show seasonal inflow changes in response to regional winds, we find that warm water is supplied to the Central Amundsen Shelf without strong seasonal variability. © 2012 Macmillan Publishers Limited. All rights reserved.


Josefsson T.,Halmstad University | Josefsson T.,Gothenburg University | Lindwall M.,Gothenburg University | Archer T.,Gothenburg University | Archer T.,Linnaeus University
Scandinavian Journal of Medicine and Science in Sports | Year: 2014

Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


McMurray J.J.V.,University of Glasgow | Packer M.,University of Texas Southwestern Medical Center | Desai A.S.,Brigham and Women's Hospital | Gong J.,Novartis | And 8 more authors.
New England Journal of Medicine | Year: 2014

Background We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in such patients.Methods: In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.Results: The trial was stopped early, according to prespecified rules, after a median followup of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval [CI], 0.73 to 0.87; P< 0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P< 0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P< 0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P< 0.001) and decreased the symptoms and physical limitations of heart failure (P = 0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.Conclusions: LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. Copyright © 2014 Massachusetts Medical Society.


Czerkinsky C.,Korean International Vaccine Institute | Holmgren J.,Gothenburg University
Current Topics in Microbiology and Immunology | Year: 2012

The mucosal immune system exhibits a high degree of anatomic compartmentalization related to the migratory patterns of lymphocytes activated at different mucosal sites. The selective localization of mucosal lymphocytes to specific tissues is governed by cellular "homing" and chemokine receptors in conjunction with tissue-specific addressins and epithelial cell-derived chemokines that are differentially expressed in "effector" tissues. The compartmentalization of mucosal immune responses imposes constraints on the selection of vaccine administration route. Traditional routes of mucosal immunization include oral and nasal routes. Other routes for inducing mucosal immunity include the rectal, vaginal, sublingual, and transcutaneous routes. Sublingual administration is a new approach that results in induction of mucosal and systemic T cell and antibody responses with an exceptionally broad dissemination to different mucosae, including the gastrointestinal and respiratory tracts, and the genital mucosa. Here, we discuss how sublingual and different routes of immunization can be used to generate immune responses in the desired mucosal tissue(s). © 2010 Springer-Verlag Berlin Heidelberg.


Barker D.,Gothenburg University | Quennerstedt M.,Örebro University | Annerstedt C.,Gothenburg University
Sport, Education and Society | Year: 2015

In line with contemporary constructivist pedagogies, students are frequently expected to learn through interaction in physical education (PE). There is a relatively sophisticated body of literature focusing on learning in groups, peer teaching, and cooperative learning. Current research has not, however, focused on how the body is implicated in interactional learning. This is surprising given that much learning in PE is expected to take place in the physical domain. The aim of this paper is to contribute to current theorizing by examining social interactions in PE practice. By drawing on symbolic interactionist theory, we put forward a framework for considering how inter-student interactions occur in a multimodal sense. Key ideas relate to (1) the sequential organization of interactions; (2) the ways in which semiotic resources in different fields are used to elaborate each other; (3) the importance of interpretation as a driver of interaction; (4) the creation of local environments in which participants attend to and work together within a shared world of perception; and (5) the influence of material environments on social interaction. The specific concepts employed are epistemic ecology, epistemic position, and learning trajectory. The paper includes observational data from an investigation of learning in Swedish PE to demonstrate the explanatory power and limitations of the theoretical tenets presented. The paper is concluded with practical implications of understanding group work in a multimodal manner. © 2015 The Author(s). Published by Taylor & Francis.


Cossu R.,University of Toronto | Wells M.G.,University of Toronto | Whlin A.K.,Gothenburg University
Journal of Geophysical Research: Oceans | Year: 2010

Large-scale turbidity currents in submarine channels often show a significant asymmetry in the heights of their levee banks. In the Northern Hemisphere, there are many observations of the right-hand channel levee being noticeably higher than the left-hand levee, a phenomenon that is usually attributed to the effect of Coriolis forces upon turbidity currents. This article presents results from an analog model that documents the influence of Coriolis forces on the dynamics of gravity currents flowing in straight submarine channels. The observations of the transverse velocity structure, downstream velocity, and interface slope show good agreement with a theory that incorporates Ekman boundary layer dynamics. Coriolis forces will be important for most large-scale turbidity currents and need to be explicitly modeled when the Rossby number of these flows (defined as Ro = U/Wf, where U is the mean downstream velocity, W is the channel width, and f is the Coriolis parameter defined as f = 2Ω sin(θ), with Ω being the Earth's rotation rate and θ being the latitude) is less than order 1. When Ro ≪ 1, the flow is substantially slower than a nonrotating flow with the same density contrast. The secondary flow field consists of frictionally induced Ekman transports across the channel in the benthic and interfacial boundary layers and a return flow in the interior. The cross-channel velocities are of the order of 10% of the along-channel velocities. The sediment transport associated with such transverse flow patterns should influence the evolution of submarine channel levee systems. © 2010 by the American Geophysical Union.


Perello M.,CONICET | Dickson S.L.,Gothenburg University
Journal of Neuroendocrinology | Year: 2015

'Hunger is the best spice' is an old and wise saying that acknowledges the fact that almost any food tastes better when we are hungry. The neurobiological underpinnings of this lore include activation of the brain's reward system and the stimulation of this system by the hunger-promoting hormone ghrelin. Ghrelin is produced largely from the stomach and levels are higher preprandially. The ghrelin receptor is expressed in many brain areas important for feeding control, including not only the hypothalamic nuclei involved in energy balance regulation, but also reward-linked areas such as the ventral tegmental area. By targeting the mesoaccumbal dopamine neurones of the ventral tegmental area, ghrelin recruits pathways important for food reward-related behaviours that show overlap with but are also distinct from those important for food intake. We review a variety of studies that support the notion that ghrelin signalling at the level of the mesolimbic system is one of the key molecular substrates that provides a physiological signal connecting gut and reward pathways. © 2014 The Authors.


Blanco-Pastor J.L.,Real Jardin Botanico RJB CSIC | Vargas P.,Real Jardin Botanico RJB CSIC | Pfeil B.E.,Gothenburg University
PLoS ONE | Year: 2012

We examined the phylogenetic history of Linaria with special emphasis on the Mediterranean sect. Supinae (44 species). We revealed extensive highly supported incongruence among two nuclear (ITS, AGT1) and two plastid regions (rpl32-trnLUAG, trnS-trnG). Coalescent simulations, a hybrid detection test and species tree inference in *BEAST revealed that incomplete lineage sorting and hybridization may both be responsible for the incongruent pattern observed. Additionally, we present a multilabelled *BEAST species tree as an alternative approach that allows the possibility of observing multiple placements in the species tree for the same taxa. That permitted the incorporation of processes such as hybridization within the tree while not violating the assumptions of the *BEAST model. This methodology is presented as a functional tool to disclose the evolutionary history of species complexes that have experienced both hybridization and incomplete lineage sorting. The drastic climatic events that have occurred in the Mediterranean since the late Miocene, including the Quaternary-type climatic oscillations, may have made both processes highly recurrent in the Mediterranean flora. © 2012 Blanco-Pastor et al.


Gangappa S.N.,Gothenburg University | Botto J.F.,CONICET | Botto J.F.,National Institute of Technology Durgapur
Trends in Plant Science | Year: 2014

The B-box (BBX) proteins are a class of zinc-finger transcription factors containing a B-box domain with one or two B-box motifs, and sometimes also feature a CCT (CONSTANS, CO-like, and TOC1) domain. BBX proteins are key factors in regulatory networks controlling growth and developmental processes that include seedling photomorphogenesis, photoperiodic regulation of flowering, shade avoidance, and responses to biotic and abiotic stresses. In this review we discuss the functions of BBX proteins and the role of B-box motif in mediating transcriptional regulation and protein-protein interaction in plant signaling. In addition, we provide novel insights into the molecular mechanisms of their action and the evolutionary significance of their functional divergence. © 2014 Elsevier Ltd.


Lofgren A.,Gothenburg University | Muller A.,University of Zürich
Environmental and Resource Economics | Year: 2010

This study undertakes a decomposition analysis to identify the drivers of carbon dioxide emissions change in the Swedish business and industry sectors 1993-2006. On aggregate, energy intensity decreased, but this does not seem to have been very important for reducing emissions. Rather, fuel substitution seems to have been more important, which is in line with findings from the decomposition literature on Sweden. However, at the sectoral level, we find no clear pattern of the effect of fuel substitution and energy intensity on emissions. We also draw some methodological conclusions: Decomposition analysis should be undertaken at the most disaggregate level possible; assessing decomposition results by summing results over several time periods leads to biased results; and decomposition analysis should not be based only on some initial and final years of a long time period. Furthermore, we address the problem of double counting energy flows in decomposition analysis of aggregate effects when the energy sector is included, and point out potential problems related to output measured in monetary terms. © 2010 Springer Science+Business Media B.V.


Sunday J.M.,Simon Fraser University | Sunday J.M.,University of British Columbia | Calosi P.,University of Plymouth | Dupont S.,Gothenburg University | And 4 more authors.
Trends in Ecology and Evolution | Year: 2014

Ocean acidification poses a global threat to biodiversity, yet species might have the capacity to adapt through evolutionary change. Here we summarize tools available to determine species' capacity for evolutionary adaptation to future ocean change and review the progress made to date with respect to ocean acidification. We focus on two key approaches: measuring standing genetic variation within populations and experimental evolution. We highlight benefits and challenges of each approach and recommend future research directions for understanding the modulating role of evolution in a changing ocean. © 2013 Elsevier Ltd.


Clark T.D.,Australian Institute of Marine Science | Sandblom E.,Gothenburg University | Jutfelt F.,Gothenburg University | Jutfelt F.,Sven Loven Center for Marine science
Journal of Experimental Biology | Year: 2013

Measurements of aerobic scope [the difference between minimum and maximum oxygen consumption rate (MO2,min and MO2,max, respectively)] are increasing in prevalence as a tool to address questions relating to fish ecology and the effects of climate change. However, there are underlying issues regarding the array of methods used to measure aerobic scope across studies and species. In an attempt to enhance quality control before the diversity of issues becomes too great to remedy, this paper outlines common techniques and pitfalls associated with measurements of MO2,min, MO2,max and aerobic scope across species and under different experimental conditions. Additionally, we provide a brief critique of the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis, a concept that is intricately dependent on aerobic scope measurements and is spreading wildly throughout the literature despite little evidence for its general applicability. It is the intention of this paper to encourage transparency and accuracy in future studies that measure the aerobic metabolism of fishes, and to highlight the fundamental issues with assuming broad relevance of the OCLTT hypothesis. © 2013. Published by The Company of Biologists Ltd.


Peters E.,Ohio State University | Bjalkebring P.,Ohio State University | Bjalkebring P.,Gothenburg University
Journal of Personality and Social Psychology | Year: 2015

A growing body of evidence demonstrates the practical and theoretical importance of numeracy in evaluations and choices involving numeric information, an importance that goes beyond simple accuracy in performing mathematical computations. Numeric competency, however, may be multiply determined, but little research has examined potentially separable influences in evaluations and choice. In the present article, we describe 3 numeric competencies and begin to disentangle their effects. Participants (N = 111) completed a series of tasks in 4 1-hr sessions. We first examined relations between objective numeracy, subjective numeracy, and symbolic-number mapping abilities (thought to tap into internal representations of numeric magnitude and the mapping of symbolic numbers onto those representations) using a structural equation model. We then explored their dissociations in numeric and nonnumeric tasks. Higher vs. lower scores in objective numeracy were associated with explicit number operations, including number comparisons and calculations. Those with more vs. less exact mapping had better numeric memory (but not nonnumeric) and produced valuations that were closer to (but did not equal) a risky gamble's expected value, indicating a link with superior number intuitions. Finally, individuals lower vs. higher in subjective numeracy had more negative emotional reactions to numbers and were lessmotivated and/or confident in numeric tasks. It was less clear whether subjective numeracy might also relate to more general motivations and metacognitions involving nonnumeric information. We conclude that numeric competencies should be used in a more targeted fashion to understand their multiple mechanisms in people's evaluations, choices, and life outcomes. © 2014 American Psychological Association.


Wysocki R.,Wrocław University | Tamas M.J.,Gothenburg University
FEMS Microbiology Reviews | Year: 2010

Toxic metals and metalloids are widespread in nature and can locally reach fairly high concentrations. To ensure cellular protection and survival in such environments, all organisms possess systems to evade toxicity and acquire tolerance. This review provides an overview of the molecular mechanisms that contribute to metal toxicity, detoxification and tolerance acquisition in budding yeast Saccharomyces cerevisiae. We mainly focus on the metals/metalloids arsenic, cadmium, antimony, mercury, chromium and selenium, and emphasize recent findings on sensing and signalling mechanisms and on the regulation of tolerance and detoxification systems that safeguard cellular and genetic integrity. © 2010 Federation of European Microbiological Societies. All rights reserved.


Czerkinsky C.,Korean International Vaccine Institute | Holmgren J.,Gothenburg University
Mucosal Immunology | Year: 2010

Research has yielded an abundance of vaccine candidates against mucosal infections, but only few mucosal vaccines have been registered for human use. Extensive research is being carried out to identify new and safe adjuvants for mucosal immunization, novel delivery systems, including live vectors and reporter molecules for tissue- and cell-specific targeting of vaccine antigens. If these candidates are to reach those in need, several lessons from clinical and field research carried out under resource-poor settings must be considered. These lessons include the need to develop new vaccines that can be administered topically onto the skin or to the mucosa, without needles or expensive delivery devices. Such topical vaccines must be able to protect all age groups at risk, be safe and effective in immunocompromised people, and be able to contain epidemics following complex emergencies. The anatomical compartmentalization of immune responses imposes constraints on the selection of topical route(s) of vaccine administration and on strategies for measuring these responses, especially in young infants. Thus, the selection of any particular route of immunization is critical when designing and formulating vaccines against organ-specific infections. © 2010 Society for Mucosal Immunology.


Luschnig S.,University of Zürich | Uv A.,Gothenburg University
Experimental Cell Research | Year: 2014

Tubular epithelia come in various shapes and sizes to accommodate the specific needs for transport, excretion and absorption in multicellular organisms. The intestinal tract, glandular organs and conduits for liquids and gases are all lined by a continuous layer of epithelial cells, which form the boundary of the luminal space. Defects in epithelial architecture and lumen dimensions will impair transport and can lead to serious organ malfunctions. Not surprisingly, multiple cellular and molecular mechanisms contribute to the shape of tubular epithelial structures. One intriguing aspect of epithelial organ formation is the highly coordinate behavior of individual cells as they mold the mature lumen. Here, we focus on recent findings, primarily from Drosophila, demonstrating that informative cues can emanate from the developing organ lumen in the form of solid luminal material. The luminal material is produced by the surrounding epithelium and helps to coordinate changes in shape and arrangement of the very same cells, resulting in correct lumen dimensions. © 2013 Elsevier Inc.


Kristoffersen L.,Norwegian University of Science and Technology | Skogvoll E.,Norwegian University of Science and Technology | Hafstrom M.,Gothenburg University
Pediatrics | Year: 2011

BACKGROUND: Gavage feeding is required in preterm infants who cannot feed by themselves. Insertion of the feeding tube is painful, and reducing the discomfort in these patients is desirable. OBJECTIVE: The aim of this study was to assess pain and discomfort during nasal insertion of a feeding tube, and to evaluate different measures for pain relief. METHODS: We included 24 preterm infants with postmenstrual age 28 to 32 weeks' who were in stable condition. Each infant acted as his or her own control over a 3-week period during which the tube was changed 6 times. On these occasions, 6 different treatment combinations were given in randomized order: pacifier or no pacifier, combined with no fluid, sterile water, or 30% sucrose. Pain and discomfort were assessed by at least 2 independent and experienced observers using a pain assessment tool, the Premature Infant Pain Profile; score range: 0 to 21. In general, scores of 4 to 6 are interpreted as normal or no discomfort; ≥12 usually signals significant pain and distress. RESULTS: The median Premature Infant Pain Profile score during the procedure was 9 and decreased gradually toward 4 after 5 minutes. The lowest pain score was achieved by combining a pacifier with oral sucrose. Sterile water without a pacifier gave the highest score. CONCLUSIONS: Insertion of a feeding tube in preterm infants leads to a measurable degree of pain and discomfort, according to the Premature Infant Pain Profile assessment tool. Pain relief was best achieved by combining a pacifier with 30% sucrose. Copyright © 2011 by the American Academy of Pediatrics.


Saletti G.,Korean International Vaccine Institute | Cuburu N.,Korean International Vaccine Institute | Yang J.S.,Korean International Vaccine Institute | Dey A.,Korean International Vaccine Institute | And 2 more authors.
Nature Protocols | Year: 2013

The enzyme-linked immunospot (ELISPOT) assay was originally developed to enumerate antigen-specific antibody-secreting cells (ASCs), and has subsequently been adapted for various applications, including the detection cytokine-secreting cells. Owing to its exceptionally high sensitivity, the ELISPOT has proven to be especially useful for detecting discrete populations of active cells (e.g., antigen-specific cells). Because of its versatility, the ELISPOT assay is used for a wide range of applications, including clonal analyses of immune responses after vaccination or after immunotherapy. Here we describe standard protocols for the detection of human ASCs specific to virtually any vaccine antigen after enrichment of circulating plasmablasts. In addition, a protocol is described for the measurement of mucosal ASC responses after prior immunomagnetic enrichment of mucosally derived blood lymphocytes. The protocols described allow rapid (∼6-8 h) detection of specific ASCs in small (1-2 ml) samples of blood and can be performed in resource-poor settings. © 2013 Nature America, Inc. All rights reserved.


Lindahl N.,Gothenburg University | Midtvedt D.,Chalmers University of Technology | Svensson J.,Lund University | Nerushev O.A.,University of Edinburgh | And 4 more authors.
Nano Letters | Year: 2012

Classical continuum mechanics is used extensively to predict the properties of nanoscale materials such as graphene. The bending rigidity, κ, is an important parameter that is used, for example, to predict the performance of graphene nanoelectromechanical devices and also ripple formation. Despite its importance, there is a large spread in the theoretical predictions of κ for few-layer graphene. We have used the snap-through behavior of convex buckled graphene membranes under the application of electrostatic pressure to determine experimentally values of κ for double-layer graphene membranes. We demonstrate how to prepare convex-buckled suspended graphene ribbons and fully clamped suspended membranes and show how the determination of the curvature of the membranes and the critical snap-through voltage, using AFM, allows us to extract κ. The bending rigidity of bilayer graphene membranes under ambient conditions was determined to be 35.5-15.0+20.0 eV. Monolayers are shown to have significantly lower κ than bilayers. © 2012 American Chemical Society.


Crocco C.D.,CONICET | Holm M.,Gothenburg University | Yanovsky M.J.,CONICET | Botto J.F.,CONICET
Plant Journal | Year: 2010

Plants grown at high densities perceive the reduction in the ratio of red (R) to far-red (FR) light as a warning of competition. This light signal triggers morphological responses such as hypocotyl and stem elongation, and acceleration of flowering, which are known collectively as the shade-avoidance syndrome (SAS). Mutations in the photomorphogenic repressor COP1 suppress the SAS, but how COP1 modulates these responses is uncertain. We identified a new mutant with altered responses to natural shade, named lhus (long hypocotyl under shade). lhus seedlings have longer hypocotyls than wild-type under a low R:FR ratio, but not under sunlight or darkness. The lhus phenotype is due to a mutation affecting a B-box zinc finger transcription factor encoded by At1g75540, a gene previously reported as AtBBX21 that interacts with COP1 to control de-etiolation. Mutations in genes encoding other members of this protein family also result in impaired SAS regulation. Under short-term canopy shade, LHUS/BBX21 acts as positive regulator of SAS genes such as PAR1, HFR1, PIL1 and ATHB2. In contrast, global expression analysis of wild-type and lhus/bbx21 seedlings revealed that a large number of genes involved in hormonal signalling pathways are negatively regulated by LHUS/BBX21 in response to long-term canopy shade, and this observation fits well with the phenotype of lhus/bbx21 seedlings grown under a low R:FR ratio. Moreover, the bbx21 bbx22 double mutation restored the SAS in the cop1 background. We propose that LHUS/BBX21 and other B-box-containing proteins, such as BBX22, act downstream of COP1, and play a central role in early and long-term adjustment of the SAS in natural environments. © 2010 Blackwell Publishing Ltd.


Wu M.,Gothenburg University | Strid A.,Örebro University | Eriksson L.A.,Gothenburg University
Journal of Physical Chemistry B | Year: 2014

The Arabidopsis thaliana UV RESISTANCE LOCUS8 (UVR8) protein has been identified to specifically mediate photomorphogenic UV-B responses by acting as a UV-B photoreceptor. The dimeric structure of the UVR8 protein dissociates into signaling-active monomers upon UV-B exposure, and the monomers rapidly interact with downstream signaling components to regulate gene expression. UVR8 monomers revert to dimers in the absence of UV-B radiation, thereby reversing transcription activation. UVR8 amino acid residues W233 and W285 have been identified to play critical roles in the UVR8 dimer for the response to UV-B irradiation. In the present work, the photoreaction mechanism for UVR8 monomerization is explored with quantum chemical cluster calculations and evaluated by molecular dynamics simulations using the wild-type UVR8 dimer and novel force field parameters developed for intermediate radicals formed in the photochemical process. Three different models are investigated, which show that the preferred mechanism for UVR8 monomerization involves electron transfer from residue W233 to W285 and onward to R338 initiated by UV-B irradiation, coupled to simultaneous proton transfer from W233 to D129 leading to the formation of protonated D129, a deprotonated W233 radical, and a neutral R338 radical. Due to the formation of the neutral R338 radical, salt bridges involving this residue are disrupted together with the concomitant interruption of several other key salt bridges R286-D96, R286-D107, R338-D44, R354-E43, and R354-E53. The resulting large decrease in protein-protein interaction energy arising from this sequence of events leads to the monomerization of the UVR8 dimer. The mechanism presented is in accord with all experimental data available to date. © 2014 American Chemical Society.


Boedeker W.,Federal Association of Company Health Insurance Funds BKK Bundesverband | Backhaus T.,Gothenburg University
European Journal of Epidemiology | Year: 2010

The analysis of combined effects of substances or risk factors has been a subject to science for more than a century. With different goals, combined effect analysis was addressed in almost all experimental biosciences. The major theoretical foundation can be traced back to two distinct origins. First, to the work by the pharmacologist Loewe on the concept of concentration additivity and second to the biometrician Bliss and the concept of independent action. In the search for a general solution and a unified terminology the interrelations of the concepts have extensively been studied and experimental findings reviewed. Meanwhile there seems to be consensus in experimental sciences that each concept has its role in predicting combined effect of agents and both are used for hazard und risk management. In contrast, epidemiologists describe combined effects mainly in terms of interactions in regression models. Although this approach started from a probabilistic model equivalent to the concept of independent action this origin is rarely acknowledged and effect summation is usually the preferred concept nowadays. Obscure biological meaning, the scale dependency of interaction terms as well as unavoidable residual confounding are taken as reasons why no new insights in combined effect analysis are likely to occur from epidemiology. In this paper we sketch the history of ideas and the state of the arts in combined effect analysis. We point to differences and common grounds in experimental biosciences and epidemiology. © 2010 Springer Science+Business Media B.V.


Gustafson D.R.,Gothenburg University | Gustafson D.R.,Institute for Neuroscience and Physiology
Journal of the Neurological Sciences | Year: 2010

Adipose tissue is an endocrine and paracrine organ that contributes to both metabolic and vascular homeostasis. Overweight and obesity due to excess adipose tissue, are cornerstones of vascular risk and increase risk for late-onset dementia. Vascular risk does not exist in isolation, and is accompanied by alterations in hormonal metabolism and metabolic syndromes. Thus, while vascular risk is highlighted as a primary mechanism for elevated dementia occurrence due to obesity, hormonal risk states may also precede or result from underlying dementia-related neuropathologies and direct neuronal toxicity. This is exemplified during the prodromal phase of dementia, as vascular and metabolic parameters decline in relation to dementia development, and potentially in a way that is different from 'normal' aging. In this review will be presented a review of the epidemiology of adiposity and dementia; adipose tissue biology; and two major hormones produced by adipose tissue, leptin and adiponectin, that interact directly with the brain. In addition, a synthesis related to other lines of supporting evidence for the role of adipose hormones in dementia will be provided. Understanding the role of adipose tissue in health of the brain is pivotal to a deeper understanding of dementia processes. © 2010 Elsevier B.V. All rights reserved.


Redfors Y.D.,Gothenburg University | Moller C.,Örebro University
Annals of Otology, Rhinology and Laryngology | Year: 2011

Objectives: The aims of this study were to evaluate the hearing outcomes 28 to 30 years after stapedectomy in patients with surgically confirmed otosclerosis, and to evaluate inner ear involvement. Methods: A retrospective clinical study was performed. Sixty-five consecutive patients who underwent stapedectomy at a tertiary referral center between 1977 and 1979 were included in the study. Medical records, including preoperative and postoperative audiograms, were reviewed, and a long-term follow-up clinical examination and pure tone audiometry were performed. The hearing outcome was compared with that of a reference population (ISO 7029) in terms of age and gender. Results: Thirty years after stapedectomy, 66% of the patients' ears studied showed a moderate to profound hearing loss. The deterioration was mainly caused by a sensory hearing loss. The hearing loss was significantly greater than that in the reference population for both air and bone conduction thresholds at the early and late stages of the disease. A large majority of the patients (88%) had bilateral otosclerosis. Conclusions: Patients with otosclerosis have a sensorineural hearing loss that cannot be explained by age. Otosclerosis should be regarded as a middle and inner ear disease. Almost all patients with otosclerosis are in need of ongoing audiological rehabilitation and hearing aids. © 2011 Annals Publishing Company. All rights reserved.


Toren K.,Gothenburg University | Toren K.,University of Perugia | Jarvholm B.,Umeå University
Chest | Year: 2014

Objective: The aim of the present study was to elucidate whether occupational exposure to vapors, gases, dusts, and fumes increases the mortality risk of COPD, especially among never smokers. Methods: The study population was a cohort of 354,718 male construction workers; of these, 196,329 were exposed to vapors, gases, dusts, and fumes, and 117,964 were unexposed. Exposure to inorganic dust, wood dust, vapors, fumes, gases, and irritants was based on a job-exposure matrix with a focus on exposure in the mid-1970s. The cohort was followed from 1971 to 2011 . Relative risks (RRs) were obtained using Poisson regression models adjusting for age, BMI, and smoking habits. Results: There were 1,085 deaths from COPD among the exposed workers, including 49 never smokers. Workers with any occupational exposure to vapors, gases, fumes, and dust showed an increased mortality due to COPD (RR, 1.32; 95% CI, 1.18-1.47). When comparing different exposure groups, there was a signifi cantly increased mortality due to COPD among those exposed to fumes (RR, 1.20; 95% CI, 1.07-1.36) and inorganic dust (RR, 1.19; 95% CI ,1.07-1.33). Among never smokers, there was high mortality due to COPD among workers with any occupational airborne exposure (RR, 2.11; 95% CI, 1.17-3.83). The fraction of COPD attributable to occupational exposure was 0.24 among all workers and 0.53 among never-smoking workers. Conclusions: Occupational exposure to airborne pollution increases the mortality risk for COPD, especially among never smokers. © 2014 American College of Chest Physicians.


Tian B.-X.,National University of Ireland | Eriksson L.A.,Gothenburg University
Journal of Physical Chemistry B | Year: 2012

Oxidosqualene-lanosterol cyclase (OSC) is a key enzyme in the biosynthesis of cholesterol. The catalytic mechanism and the product specificity of OSC have herein been studied using QM/MM calculations. According to our calculations, the protonation of the epoxide ring of oxidosqualene is rate-limiting. Wild-type OSC (which generates lanosterol), and the mutants H232S (which generates parkeol) and H232T (which generates protosta-12,24-dien-3-β-ol) were modeled, in order to explain the product specificity thereof. We show that the product specificity of OSC at the hydride/methyl-shifting stage is unlikely to be achieved by the stabilization of the cationic intermediates, as the precursor of lanosterol is in fact not the most stable cationic intermediate for wild-type OSC. The energy barriers for the product-determining conversions are instead found to be related to the product specificity of different OSC mutants, and we thus suggest that the product specificity of OSC is likely to be controlled by kinetics, rather than thermodynamics. © 2012 American Chemical Society.


Alstermark B.,Umeå University | Pettersson L.-G.,Gothenburg University
Frontiers in Neurology | Year: 2014

The corticospinal system is a major motor pathway in the control of skilled voluntary movements such as reaching and grasping. It has developed considerably phylogenetically to reach a peak in humans. Because rodents possess advanced forelimb movements that can be used for reaching and grasping food, it is commonly considered that the corticospinal tract (CST) is of major importance for this control also in rodents. A close homology to primate reaching and grasping has been described but with obvious limitations as to independent digit movements, which are lacking in rodents. Nevertheless, it was believed that there are, as in the primate, direct cortico-motoneuronal connections. Later, it was shown that there are no such connections. The fastest excitatory pathway is disynaptic, mediated via cortico-reticulospinal neurons and in the spinal cord the excitation is mainly polysynaptically mediated via segmental interneurons. Earlier behavioral studies have aimed at investigating the role of the CST by using pyramidotomy in the brainstem. However, in addition to interrupting the CST, a pyramidal transection abolishes the input to reticulospinal neurons. It is therefore not possible to conclude if the deficits after pyramidotomy result from interruption of the CST or the input to reticulospinal neurons or both. We have re-investigated the role of the CST by examining the effect of a CST lesion in the C1-C2 spinal segments on the success rate of reaching and grasping. This lesion spares the cortico-reticulospinal pathway. In contrast to investigations using pyramidal transections, the present study did not demonstrate marked deficits in reaching and grasping. We propose that the difference in results can be explained by the intact cortical input to reticulospinal neurons in our study and thus implicate an important role of this pathway in the control of reaching and grasping in the rat. © 2014 Alstermark and Pettersson.


Massoudi P.,FoU Kronoberg Unit for Research and Development | Hwang C.P.,Gothenburg University | Wickberg B.,Gothenburg University
Journal of Affective Disorders | Year: 2013

Background: Fathers are increasingly involved in infant care, and depression in postnatal fathers as well as mothers may have negative effects on child development and behaviour. The EPDS has been validated to identify depression in new mothers, but few validation studies have involved fathers and there is doubt as to whether the EPDS measures the same constructs in men as in women. Subjects and methods: A population-based sample of 1014 couples were sent the EPDS and the HAD-A subscale 3 months postnatally. All high-scoring fathers and a random sample of fathers scoring low were invited for a diagnostic interview to assess the presence of any depression or anxiety disorder. A factor analysis of the EPDS data was conducted for mothers and fathers. Findings: A factor analysis of the EPDS data revealed a different factor structure for fathers, implying that the scale picks up more worry, anxiety and unhappiness than depression. The EPDS yields high sensitivity and specificity, but low positive predictive value when screening for probable major depression at the optimal cut-off score of 12 or more. The accuracy of the EPDS, however, is modest for minor depression, and low for anxiety disorders. Neither the EPDS-3A score nor the HAD-A subscale reached acceptable validity in this study. Conclusions: The EPDS seems to pick up more distress than pure depression in new fathers. It is a valid instrument for screening for probable major depression, but it is questionable if it should be used to screen for minor depression. Neither the EPDS nor the HAD-A subscale can be recommended for screening for anxiety in postnatal fathers. Limitations: Confidence intervals around the estimates are wide and the interviewed fathers were selected preferentially. © 2013 Elsevier B.V.


Svanstedt N.,Gothenburg University | Woukeng J.L.,University of Dschang
Nonlinear Analysis: Real World Applications | Year: 2013

Homogenization of Wilson-Cowan type of nonlocal neural field models is investigated. Motivated by the presence of a convolution term in this type of models, we first prove some general convergence results related to convolution sequences. We then apply these results to the homogenization problem of the Wilson-Cowan-type model in a general deterministic setting. Key ingredients in this study are the notion of algebras with mean value and the related concept of sigma-convergence. © 2012 Elsevier Ltd. All rights reserved.


Herschel Conaway H.,University of Arkansas for Medical Sciences | Henning P.,Gothenburg University | Lerner U.H.,Gothenburg University | Lerner U.H.,Umeå University
Endocrine Reviews | Year: 2013

Vitamin A (retinol) is ingested as either retinyl esters or carotenoids and metabolized to active compounds such as 11-cis-retinal, which is important for vision, and all-trans-retinoic acid, which is the primary mediator of biological actions of vitamin A. All-trans-retinoic acid binds to retinoic acid receptors (RARs), which heterodimerize with retinoid X receptors. RAR-retinoid X receptor heterodimers function as transcription factors, binding RAR-responsive elements in promoters of different genes. Numerous cellular functions, including bone cell functions, are mediated by vitamin A; however, it has long been recognized that increased levels of vitamin A can have deleterious effects on bone, resulting in increased skeletal fragility. Bone mass is dependent on the balance between bone resorption and bone formation. A decrease in bone mass may be caused by either an excess of resorption or decreased bone formation. Early studies indicated that the primary skeletal effect of vitamin A was to increase bone resorption, but later studies have shown that vitamin A can not only stimulate the formation of bone-resorbing osteoclasts but also inhibit their formation. Effects of vitamin A on bone formation have not been studied in as great a detail and are not as well characterized as effects on bone resorption. Several epidemiological studies have shown an association between vitamin A, decreased bone mass, and osteoporotic fractures, but the data are not conclusive because other studies have found no associations, and some studies have suggested that vitamin A primarily promotes skeletal health. In this presentation, we have summarized how vitamin A is absorbed and metabolized and how it functions intracellularly. Vitamin A deficiency and excess are introduced, and detailed descriptions of clinical and preclinical studies of the effects of vitamin A on the skeleton are presented.© 2013.


Norlin S.,Umeå University | Parekh V.S.,Umeå University | Naredi P.,Gothenburg University | Edlund H.,Umeå University
Diabetes | Year: 2016

Type 2 diabetes (T2D) is characterized by insulin resistance and β-cell failure. Insulin resistance per se, however, does not provoke overt diabetes as long as compensatory β-cell function is maintained. The increased demand for insulin stresses the β-cell endoplasmic reticulum (ER) and secretory pathway, and ER stress is associated with β-cell failure in T2D. The tail recognition complex (TRC) pathway, including Asna1/ TRC40, is implicated in the maintenance of endomembrane trafficking and ER homeostasis. To gain insight into the role of Asna1/TRC40 in maintaining endomembrane homeostasis and β-cell function, we inactivated Asna1 in β-cells of mice. We show that Asna1β-/- mice develop hypoinsulinemia, impaired insulin secretion, and glucose intolerance that rapidly progresses to overt diabetes. Loss of Asna1 function leads to perturbed plasma membrane-to-trans Golgi network and Golgito- ER retrograde transport as well as to ER stress in β-cells. Of note, pharmacological inhibition of retrograde transport in isolated islets and insulinoma cells mimicked the phenotype of Asna1β-/- β-cells and resulted in reduced insulin content and ER stress. These data support a model where Asna1 ensures retrograde transport and, hence, ER and insulin homeostasis in β-cells. © 2016 by the American Diabetes Association.


Haugen K.,Umeå University | Vilhelmson B.,Gothenburg University
Transportation Research Part A: Policy and Practice | Year: 2013

This research explores and adds to the literature concerning the relationship between spatial structure and travel behaviour; specifically, the relationship between local and regional accessibility to service amenities and the distance of service-related trips. The analysis is based on a unique combination of national travel survey data for Sweden and official register data with detailed, geo-referenced information about the Swedish population and the location of service amenities in 1995 and 2005/2006. The results show that spatial access to service amenities increased in general over the study period, both locally (i.e., within ranges of 1. km and 5. km, respectively, of residential areas) and regionally (within 50. km). Despite increased spatial accessibility, the observed average travel distance also increased. We find strong and differing associations between spatial access to service amenities and travel distance, depending on level of scale. While the association was negative on the local scale (i.e., a numerically large supply of amenities was related to shorter travel distance), it was the opposite and positive, on the regional scale. In terms of implications for policy, the results imply that land use planning measures to promote local access, and thereby reduce traffic volumes, may per se be insufficient for attaining more sustainable levels of mobility. © 2013 Elsevier Ltd.


Zetterberg H.,Gothenburg University | Zetterberg H.,University College London
Current Opinion in Psychiatry | Year: 2015

Purpose of review. To give perspectives on current limitations and recent developments in the field of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD). Recent findings. Three CSF biomarkers for the neuropathological hallmarks of Alzheimer's disease, namely total tau (T-tau), phospho-tau (P-tau) and the 42 amino acid form of amyloid β (Aβ42), reflecting neurodegeneration, neurofibrillary tangles and amyloid/senile plaques, respectively, have been developed, validated and incorporated into new diagnostic criteria for the disease. Thanks to global collaborative research efforts, these have been to a large extent a success story but there are a number of limitations that warrant further research and discussion. First, bias and random variation in biomarker measurements both within and between laboratories remain an issue. Second, current markers only reflect part of the pathology underlying Alzheimer's disease; new markers of synaptic dysfunction, microglial activation and protein aggregates that are frequently seen alongside plaque and tangle pathology are needed. Third, fluid markers do not represent the anatomic location of any pathological change; CSF markers may be complemented with high resolution molecular imaging techniques. Summary. There has been considerable progress in the validation and standardization of assays for CSF T-tau, P-tau and Aβ42. Novel biomarkers for synaptic function, microglial activation and protein accumulations other than tau and Aβ are in development. Future fluid biomarker research should be conducted in close collaboration with molecular imaging specialists. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.