Showing papers by "University of Bern published in 2010"
TL;DR: This update of the CONSORT statement improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias.
Abstract: Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials.
5,957 citations
TL;DR: Cai et al. as discussed by the authors used a surface-assisted coupling of the precursors into linear polyphenylenes and their subsequent cyclodehydrogenation to produce GNRs of different topologies and widths.
Abstract: Graphene nanoribbons, narrow straight-edged strips of the single-atom-thick sheet form of carbon, are predicted to exhibit remarkable properties, making them suitable for future electronic applications. Before this potential can be realized, more chemically precise methods of production will be required. Cai et al. report a step towards that goal with the development of a bottom-up fabrication method that produces atomically precise graphene nanoribbons of different topologies and widths. The process involves the deposition of precursor monomers with structures that 'encode' the topology and width of the desired ribbon end-product onto a metal surface. Surface-assisted coupling of the precursors into linear polyphenylenes is then followed by cyclodehydrogenation. Given the method's versatility and precision, it could even provide a route to more unusual graphene nanoribbon structures with tuned chemical and electronic properties. Graphene nanoribbons (GNRs) have structure-dependent electronic properties that make them attractive for the fabrication of nanoscale electronic devices, but exploiting this potential has been hindered by the lack of precise production methods. Here the authors demonstrate how to reliably produce different GNRs, using precursor monomers that encode the structure of the targeted nanoribbon and are converted into GNRs by means of surface-assisted coupling. Graphene nanoribbons—narrow and straight-edged stripes of graphene, or single-layer graphite—are predicted to exhibit electronic properties that make them attractive for the fabrication of nanoscale electronic devices1,2,3. In particular, although the two-dimensional parent material graphene4,5 exhibits semimetallic behaviour, quantum confinement and edge effects2,6 should render all graphene nanoribbons with widths smaller than 10 nm semiconducting. But exploring the potential of graphene nanoribbons is hampered by their limited availability: although they have been made using chemical7,8,9, sonochemical10 and lithographic11,12 methods as well as through the unzipping of carbon nanotubes13,14,15,16, the reliable production of graphene nanoribbons smaller than 10 nm with chemical precision remains a significant challenge. Here we report a simple method for the production of atomically precise graphene nanoribbons of different topologies and widths, which uses surface-assisted coupling17,18 of molecular precursors into linear polyphenylenes and their subsequent cyclodehydrogenation19,20. The topology, width and edge periphery of the graphene nanoribbon products are defined by the structure of the precursor monomers, which can be designed to give access to a wide range of different graphene nanoribbons. We expect that our bottom-up approach to the atomically precise fabrication of graphene nanoribbons will finally enable detailed experimental investigations of the properties of this exciting class of materials. It should even provide a route to graphene nanoribbon structures with engineered chemical and electronic properties, including the theoretically predicted intraribbon quantum dots21, superlattice structures22 and magnetic devices based on specific graphene nanoribbon edge states3.
2,905 citations
University of Kiel1, Cedars-Sinai Medical Center2, Wellcome Trust Sanger Institute3, University of Pennsylvania4, QIMR Berghofer Medical Research Institute5, Peninsula College of Medicine and Dentistry6, University of Edinburgh7, University of Cambridge8, University of Otago9, University of Washington10, University of Groningen11, University of Liège12, Harvard University13, Casa Sollievo della Sofferenza14, King's College London15, University of Chicago16, Yale University17, Johns Hopkins University18, Ludwig Maximilian University of Munich19, Charité20, McGill University21, Lille University of Science and Technology22, Cincinnati Children's Hospital Medical Center23, Ghent University24, Torbay Hospital25, Mater Health Services26, Université libre de Bruxelles27, RWTH Aachen University28, University of Utah29, Örebro University30, Leiden University31, University of Paris32, Technion – Israel Institute of Technology33, University of Western Australia34, Tel Aviv University35, University of Dundee36, University of Manchester37, University of Pittsburgh38, Royal Hospital for Sick Children39, Katholieke Universiteit Leuven40, Guy's and St Thomas' NHS Foundation Trust41, University of Bern42, University of Toronto43, University of Amsterdam44, Karolinska Institutet45, University of Zurich46, Université de Montréal47, Emory University48, Newcastle University49
TL;DR: A meta-analysis of six Crohn's disease genome-wide association studies and a series of in silico analyses highlighted particular genes within these loci implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP.
Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
2,482 citations
TL;DR: A toolbox with definitions of key theoretical elements and a synthesis of the current understanding of the molecular and genetic mechanisms underlying plasticity relevant to climate change is provided to provide clear directives for future research and stimulate cross-disciplinary dialogue on the relevance of phenotypic plasticity under climate change.
1,569 citations
TL;DR: It is concluded that invasive alien species had higher values for those traits related to performance than non-invasive species, suggesting that it might become possible to predict future plant invasions from species traits.
Abstract: A major aim in ecology is identifying determinants of invasiveness. We performed a meta-analysis of 117 field or experimental-garden studies that measured pair-wise trait differences of a total of 125 invasive and 196 non-invasive plant species in the invasive range of the invasive species. We tested whether invasiveness is associated with performance-related traits (physiology, leaf-area allocation, shoot allocation, growth rate, size and fitness), and whether such associations depend on type of study and on biogeographical or biological factors. Overall, invasive species had significantly higher values than non-invasive species for all six trait categories. More trait differences were significant for invasive vs. native comparisons than for invasive vs. non-invasive alien comparisons. Moreover, for comparisons between invasive species and native species that themselves are invasive elsewhere, no trait differences were significant. Differences in physiology and growth rate were larger in tropical regions than in temperate regions. Trait differences did not depend on whether the invasive alien species originates from Europe, nor did they depend on the test environment. We conclude that invasive alien species had higher values for those traits related to performance than non-invasive species. This suggests that it might become possible to predict future plant invasions from species traits.
1,497 citations
TL;DR: The unique adaptations of the intestinal immune system that maintain homeostatic interactions with a diverse resident microbiota are discussed.
Abstract: Humans harbour nearly 100 trillion intestinal bacteria that are essential for health. Millions of years of co-evolution have moulded this human-microorganism interaction into a symbiotic relationship in which gut bacteria make essential contributions to human nutrient metabolism and in return occupy a nutrient-rich environment. Although intestinal microorganisms carry out essential functions for their hosts, they pose a constant threat of invasion owing to their sheer numbers and the large intestinal surface area. In this Review, we discuss the unique adaptations of the intestinal immune system that maintain homeostatic interactions with a diverse resident microbiota.
1,227 citations
TL;DR: The association of the IL28B locus with natural and treatment-associated control of HCV indicates the importance of innate immunity and interferon lambda in the pathogenesis ofHCV infection.
1,154 citations
TL;DR: It is shown with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium, and shows that full VEGFR3 signalling is coupled to receptor internalization.
Abstract: In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.
1,046 citations
TL;DR: It is shown that stratospheric water vapor is an important driver of decadal global surface climate change, by acting to slow the rate of warming by about 25% compared to that which would have occurred due only to carbon dioxide and other greenhouse gases.
Abstract: Stratospheric water vapor concentrations decreased by about 10% after the year 2000. Here we show that this acted to slow the rate of increase in global surface temperature over 2000–2009 by about 25% compared to that which would have occurred due only to carbon dioxide and other greenhouse gases. More limited data suggest that stratospheric water vapor probably increased between 1980 and 2000, which would have enhanced the decadal rate of surface warming during the 1990s by about 30% as compared to estimates neglecting this change. These findings show that stratospheric water vapor is an important driver of decadal global surface climate change.
1,014 citations
Spanish National Research Council1, Autonomous University of Barcelona2, Academy of Sciences of the Czech Republic3, Environmental Protection Agency4, University of Bern5, Klaipėda University6, Institut national de la recherche agronomique7, Natural Environment Research Council8, Canterbury of New Zealand9
TL;DR: In this paper, the authors present a review of the financial costs of alien species in Europe, as the first step toward calculating an estimate of the economic consequences of extraterrestrial species.
Abstract: Recent comprehensive data provided through the DAISIE project (www.europe-aliens.org) have facilitated the development of the first pan-European assessment of the impacts of alien plants, vertebrates, and invertebrates – in terrestrial, freshwater, and marine environments – on ecosystem services. There are 1094 species with documented ecological impacts and 1347 with economic impacts. The two taxonomic groups with the most species causing impacts are terrestrial invertebrates and terrestrial plants. The North Sea is the maritime region that suffers the most impacts. Across taxa and regions, ecological and economic impacts are highly correlated. Terrestrial invertebrates create greater economic impacts than ecological impacts, while the reverse is true for terrestrial plants. Alien species from all taxonomic groups affect “supporting”, “provisioning”, “regulating”, and “cultural” services and interfere with human well-being. Terrestrial vertebrates are responsible for the greatest range of impacts, and these are widely distributed across Europe. Here, we present a review of the financial costs, as the first step toward calculating an estimate of the economic consequences of alien species in Europe.
985 citations
TL;DR: This update of the CONSORT statement improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias.
Abstract: Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www. consort-statement. org) should be helpful resources to improve reporting of randomised trials.
TL;DR: In this article, the authors review the literature on the role of users during innovation, critique it and develop some of the research questions that could be explored to contribute to this literature and to the theoretical perspectives that underpin the literature.
University of Göttingen1, University of Minnesota2, University of Jena3, University of Zurich4, University of Potsdam5, University of Bern6, Max Planck Society7, Helmholtz Centre for Environmental Research - UFZ8, Leipzig University9, Humboldt State University10, University of Cologne11, ETH Zurich12, Lüneburg University13, Tallinn University of Technology14, Imperial College London15, University of British Columbia16, American Museum of Natural History17
TL;DR: It is shown that plant diversity effects dampen with increasing trophic level and degree of omnivory, and the results suggest that plant Diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophIC levels.
Abstract: Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels However, only a few studies have so far incorporated an explicit food-web perspective In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory This was true both for abundance and species richness of organisms Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores Density and richness of carnivorous taxa was independent of vegetation structure Below-ground responses to plant diversity were consistently weaker than above-ground responses Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades
University of British Columbia1, University of Idaho2, Harvard University3, University of California, Santa Barbara4, University of California, Berkeley5, University of Georgia6, Humboldt State University7, University of Minnesota8, Dartmouth College9, Clarkson University10, Yale University11, Imperial College London12, University of Missouri–St. Louis13, University of Bern14, Swiss Federal Institute of Aquatic Science and Technology15, National Evolutionary Synthesis Center16, Oregon State University17, Pontificia Universidad Católica del Ecuador18, Simon Fraser University19
TL;DR: It is suggested that the classical model of adaptive radiation, where morphological evolution is initially rapid and slows through time, may be rare in comparative data.
Abstract: George Gaylord Simpson famously postulated that much of life's diversity originated as adaptive radiations-more or less simultaneous divergences of numerous lines from a single ancestral adaptive type. However, identifying adaptive radiations has proven difficult due to a lack of broad-scale comparative datasets. Here, we use phylogenetic comparative data on body size and shape in a diversity of animal clades to test a key model of adaptive radiation, in which initially rapid morphological evolution is followed by relative stasis. We compared the fit of this model to both single selective peak and random walk models. We found little support for the early-burst model of adaptive radiation, whereas both other models, particularly that of selective peaks, were commonly supported. In addition, we found that the net rate of morphological evolution varied inversely with clade age. The youngest clades appear to evolve most rapidly because long-term change typically does not attain the amount of divergence predicted from rates measured over short time scales. Across our entire analysis, the dominant pattern was one of constraints shaping evolution continually through time rather than rapid evolution followed by stasis. We suggest that the classical model of adaptive radiation, where morphological evolution is initially rapid and slows through time, may be rare in comparative data.
Katholieke Universiteit Leuven1, Ottawa Hospital Research Institute2, University of Turin3, University of Bern4, Cliniques Universitaires Saint-Luc5, Bristol-Myers Squibb6, University of Melbourne7, Peter MacCallum Cancer Centre8, University of Sydney9, Flinders University10, Catholic University of Leuven11
TL;DR: In this paper, the authors studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with metastatic colorectal cancer treated with cetuximab between 2001 and 2008.
Abstract: Context Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. Objective To test the hypothesis that KRAS codon 13 mutations are associated with a better outcome after treatment with cetuximab than observed with other KRAS mutations. Design, Setting, and Patients We studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. Patients were included in the CO. 17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off-study treatment. Univariate and multivariate analyses, adjusting for possible prognostic factors and data set, were performed. The effect of the different mutations was studied in vitro by constructing isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles and treating them with cetuximab. Main Outcome Measures The main efficacy end point was overall survival. Secondary efficacy end points were response rate and progression-free survival. Results In comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n=32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P=.005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P=.004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14-0.67; P=.003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. Conclusions In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted. JAMA. 2010; 304(16): 1812-1820
TL;DR: A reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation is reported, and specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.
Abstract: The lower intestine of adult mammals is densely colonized with nonpathogenic (commensal) microbes. Gut bacteria induce protective immune responses, which ensure host-microbial mutualism. The continuous presence of commensal intestinal bacteria has made it difficult to study mucosal immune dynamics. Here, we report a reversible germ-free colonization system in mice that is independent of diet or antibiotic manipulation. A slow (more than 14 days) onset of a long-lived (half-life over 16 weeks), highly specific anticommensal immunoglobulin A (IgA) response in germ-free mice was observed. Ongoing commensal exposure in colonized mice rapidly abrogated this response. Sequential doses lacked a classical prime-boost effect seen in systemic vaccination, but specific IgA induction occurred as a stepwise response to current bacterial exposure, such that the antibody repertoire matched the existing commensal content.
TL;DR: The data suggest that the N-back task is not a useful measure of individual differences in WM, partly because of its insufficient reliability, but the task seems to be useful for experimental research in WM and also well predicts inter-individual differences in other higher cognitive functions, such as fluid intelligence, especially when used at higher levels of load.
Abstract: The N-back task is used extensively in literature as a working memory (WM) paradigm and it is increasingly used as a measure of individual differences. However, not much is known about the psychometric properties of this task and the current study aims to shed more light on this issue. We first review the current literature on the psychometric properties of the N-back task. With three experiments using task variants with different stimuli and load levels, we then investigate the nature of the N-back task by investigating its relationship to WM, and its role as an inter-individual difference measure. Consistent with previous literature, our data suggest that the N-back task is not a useful measure of individual differences in WM, partly because of its insufficient reliability. Nevertheless, the task seems to be useful for experimental research in WM and also well predicts inter-individual differences in other higher cognitive functions, such as fluid intelligence, especially when used at higher levels of load.
TL;DR: Ranibizumab is effective in improving BCVA and is well tolerated in DME, and future clinical trials are required to confirm its long-term efficacy and safety.
Abstract: OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age >18 years, type 1 or 2 diabetes, central retinal thickness [CRT] ≥300 μm, and best corrected visual acuity [BCVA] of 73–39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n = 51 each) or sham ( n = 49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set ( n = 151, patients receiving ≥1 injection). RESULTS At month 12, mean ± SD BCVA improved from baseline by 10.3 ± 9.1 letters with ranibizumab and declined by 1.4 ± 14.2 letters with sham ( P P P CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
TL;DR: The Biodiversity Exploratories (www.biodiversityexploratories.de ) as mentioned in this paper is a large-scale and long-term project for functional biodiversity, which includes a hierarchical set of standardized field plots in three different regions of Germany covering manifold management types and intensities in grasslands and forests.
TL;DR: Metaregression analyses showed that the risk of IRIS is associated with CD4 cell count at the start of ART, with a high risk in patients with fewer than 50 cells per microL, and might be reduced by initiation of ART before immunodeficiency becomes advanced.
Abstract: In patients with HIV-1 infection who are starting combination antiretroviral therapy (ART), the incidence of immune reconstitution inflammatory syndrome (IRIS) is not well defined. We did a meta-analysis to establish the incidence and lethality of the syndrome in patients with a range of previously diagnosed opportunistic infections, and examined the relation between occurrence and the degree of immunodeficiency. Systematic review identified 54 cohort studies of 13 103 patients starting ART, of whom 1699 developed IRIS. We calculated pooled cumulative incidences with 95% credibility intervals (CrI) by Bayesian methods and did a random-effects metaregression to analyse the relation between CD4 cell count and incidence of IRIS. In patients with previously diagnosed AIDS-defining illnesses, IRIS developed in 37.7% (95% CrI 26.6-49.4) of those with cytomegalovirus retinitis, 19.5% (6.7-44.8) of those with cryptococcal meningitis, 15.7% (9.7-24.5) of those with tuberculosis, 16.7% (2.3-50.7) of those with progressive multifocal leukoencephalopathy, and 6.4% (1.2-24.7) of those with Kaposi's sarcoma, and 12.2% (6.8-19.6) of those with herpes zoster. 16.1% (11.1-22.9) of unselected patients starting ART developed any type of IRIS. 4.5% (2.1-8.6) of patients with any type of IRIS died, 3.2% (0.7-9.2) of those with tuberculosis-associated IRIS died, and 20.8% (5.0-52.7) of those with cryptococcal meningitis died. Metaregression analyses showed that the risk of IRIS is associated with CD4 cell count at the start of ART, with a high risk in patients with fewer than 50 cells per microL. Occurrence of IRIS might therefore be reduced by initiation of ART before immunodeficiency becomes advanced.
Erasmus University Rotterdam1, Praxis2, Medical University of Silesia3, University of Copenhagen4, Leipzig University5, Ludwig Maximilian University of Munich6, Imperial College London7, Tel Aviv University8, München Klinik Bogenhausen9, Boston Scientific Corporation10, Medtronic plc11, University of Bern12
TL;DR: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus -elutingStent in a population of patients who had minimal exclusion criteria.
Abstract: BACKGROUND: New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration. METHODS: In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months. RESULTS: At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P = 0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (±SD) of in-stent stenosis (21.65±14.42% for zotarolimus vs. 19.76±14.64% for everolimus, P = 0.04 for noninferiority). In-stent late lumen loss was 0.27±0.43 mm in the zotarolimus-stent group versus 0.19±0.40 mm in the everolimusstent group (P = 0.08). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria.
TL;DR: In this article, the authors used the ATLAS detector to detect dijet asymmetry in the collisions of lead ions at the Large Hadron Collider and found that the transverse energies of dijets in opposite hemispheres become systematically more unbalanced with increasing event centrality, leading to a large number of events which contain highly asymmetric di jets.
Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.
University of Glasgow1, University of Oxford2, University of Texas Health Science Center at San Antonio3, Novartis4, Moscow State University5, University of North Carolina at Chapel Hill6, University College Cork7, Federal University of São Paulo8, National Taiwan University9, Centre Hospitalier Universitaire de Nantes10, The Chinese University of Hong Kong11, University of Leicester12, University of California, Berkeley13, University of Bern14, Tulane University15, Royal North Shore Hospital16, Medical University of Warsaw17, Harvard University18, Istanbul University19, University of Tromsø20, University of Washington21, Alfred Hospital22, University of Toronto23, University of Cape Town24, Cordoba University25, University of Illinois at Chicago26, Lahey Hospital & Medical Center27, University Medical Center Utrecht28, Umeå University29, Dresden University of Technology30, University of Liège31, Aarhus University32, Cardiovascular Institute of the South33, University of Copenhagen34, Semmelweis University35, University of Helsinki36, Duke University37
TL;DR: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events.
Abstract: BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)
TL;DR: This editorial aims to provide practical guidance for the incorporation of absolute minimum standards encompassing the key assay parameters for accurate design, documentation and reporting of qPCR experiments (MIQE précis) and guidance on the publication of pure 'reference gene' articles.
Abstract: The conclusions of thousands of peer-reviewed publications rely on data obtained using fluorescence-based quantitative real-time PCR technology. However, the inadequate reporting of experimental detail, combined with the frequent use of flawed protocols is leading to the publication of papers that may not be technically appropriate. We take the view that this problem requires the delineation of a more transparent and comprehensive reporting policy from scientific journals. This editorial aims to provide practical guidance for the incorporation of absolute minimum standards encompassing the key assay parameters for accurate design, documentation and reporting of qPCR experiments (MIQE precis) and guidance on the publication of pure 'reference gene' articles.
TL;DR: The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tracts, and emphasizes the importance for quantitative analyses and the use of particle doses derived from real world exposures.
Abstract: Particle biokinetics is important in hazard identification and characterization of inhaled particles. Such studies intend to convert external to internal exposure or biologically effective dose, and may help to set limits in that way. Here we focus on the biokinetics of inhaled nanometer sized particles in comparison to micrometer sized ones.The presented approach ranges from inhaled particle deposition probability and retention in the respiratory tract to biokinetics and clearance of particles out of the respiratory tract. Particle transport into the blood circulation (translocation), towards secondary target organs and tissues (accumulation), and out of the body (clearance) is considered. The macroscopically assessed amount of particles in the respiratory tract and secondary target organs provides dose estimates for toxicological studies on the level of the whole organism. Complementary, microscopic analyses at the individual particle level provide detailed information about which cells and subcellular components are the target of inhaled particles. These studies contribute to shed light on mechanisms and modes of action eventually leading to adverse health effects by inhaled nanoparticles.We review current methods for macroscopic and microscopic analyses of particle deposition, retention and clearance. Existing macroscopic knowledge on particle biokinetics and microscopic views on particle organ interactions are discussed comparing nanometer and micrometer sized particles. We emphasize the importance for quantitative analyses and the use of particle doses derived from real world exposures.
TL;DR: No prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection are found, and better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.
Abstract: Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.
TL;DR: A new model is required in which memory systems are distinguished based on the processing operations involved rather than by consciousness, because consciousness seems to be a poor criterion for differentiating between declarative and nondeclarative types of memory.
Abstract: Prominent models of human long-term memory distinguish between memory systems on the basis of whether learning and retrieval occur consciously or unconsciously. Episodic memory formation requires the rapid encoding of associations between different aspects of an event which, according to these models, depends on the hippocampus and on consciousness. However, recent evidence indicates that the hippocampus mediates rapid associative learning with and without consciousness in humans and animals, for long-term and short-term retention. Consciousness seems to be a poor criterion for differentiating between declarative (or explicit) and non declarative (or implicit) types of memory. A new model is therefore required in which memory systems are distinguished based on the processing operations involved rather than by consciousness.
TL;DR: In this paper, changes in marine net primary productivity (PP) and export of particulate organic carbon (EP) are projected over the 21st century with four global coupled carbon cycle-climate models.
Abstract: Changes in marine net primary productivity (PP) and export of particulate organic carbon (EP) are projected over the 21st century with four global coupled carbon cycle-climate models. These include representations of marine ecosystems and the carbon cycle of different structure and complexity. All four models show a decrease in global mean PP and EP between 2 and 20% by 2100 relative to preindustrial conditions, for the SRES A2 emission scenario. Two different regimes for productivity changes are consistently identified in all models. The first chain of mechanisms is dominant in the low- and mid-latitude ocean and in the North Atlantic: reduced input of macro-nutrients into the euphotic zone related to enhanced stratification, reduced mixed layer depth, and slowed circulation causes a decrease in macro-nutrient concentrations and in PP and EP. The second regime is projected for parts of the Southern Ocean: an alleviation of light and/or temperature limitation leads to an increase in PP and EP as productivity is fueled by a sustained nutrient input. A region of disagreement among the models is the Arctic, where three models project an increase in PP while one model projects a decrease. Projected changes in seasonal and interannual variability are modest in most regions. Regional model skill metrics are proposed to generate multi-model mean fields that show an improved skill in representing observation-based estimates compared to a simple multi-model average. Model results are compared to recent productivity projections with three different algorithms, usually applied to infer net primary production from satellite observations.
TL;DR: It is demonstrated that in the absence of two ABCC-type transporters, At ABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides and engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs is possible.
Abstract: Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC–metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]–PC2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)–PC2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs.
TL;DR: Because the perception of social support seems important for CHD prognosis, monitoring of functional social support is indicated in patients with CHD, and interventions to increase the Perception of positive social resources are warranted.
Abstract: To conduct a systematic review and meta-analysis on the relevance of low social support for the development and course of coronary heart disease (CHD).