Showing papers by "University of Bern published in 2015"
TL;DR: In the Global Burden of Disease Study 2013 (GBD 2013) as mentioned in this paper, the authors estimated the quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.
4,510 citations
University of California, Los Angeles1, University of Calgary2, University of Duisburg-Essen3, University at Buffalo4, University of Toronto5, Stanford University6, University of Missouri–Kansas City7, Heidelberg University8, University of Kiel9, University of Pittsburgh10, University of Bern11, Emory University12, University of Tennessee13, Rush University Medical Center14, Goethe University Frankfurt15
TL;DR: In patients receiving intravenous t-PA for acute ischemic stroke, thrombectomy with the use of a stent retriever within 6 hours after onset improved functional outcomes at 90 days.
Abstract: BACKGROUND Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. METHODS We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). RESULTS The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P = 0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P = 0.12). CONCLUSIONS In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.)
4,101 citations
Technische Universität München1, ETH Zurich2, University of Bern3, Harvard University4, National Institutes of Health5, University of Debrecen6, University Hospital Heidelberg7, McGill University8, University of Pennsylvania9, French Institute for Research in Computer Science and Automation10, University at Buffalo11, Microsoft12, University of Cambridge13, Stanford University14, University of Virginia15, Imperial College London16, Massachusetts Institute of Technology17, Columbia University18, Sabancı University19, Old Dominion University20, RMIT University21, Purdue University22, General Electric23
TL;DR: The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) as mentioned in this paper was organized in conjunction with the MICCAI 2012 and 2013 conferences, and twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low and high grade glioma patients.
Abstract: In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients—manually annotated by up to four raters—and to 65 comparable scans generated using tumor image simulation software Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%–85%), illustrating the difficulty of this task We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource
3,699 citations
TL;DR: It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.
Abstract: As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.
2,096 citations
University of Massachusetts Amherst1, National Oceanic and Atmospheric Administration2, Université du Québec à Montréal3, Newcastle University4, University of Bern5, Chinese Academy of Sciences6, Rutgers University7, École Polytechnique Fédérale de Lausanne8, University of Graz9, University of Reading10, Shanxi University11, University of Alberta12, Environment Canada13
TL;DR: In this paper, the authors review important mechanisms that contribute towards elevation-dependent warming, such as snow albedo and surface-based feedbacks, water vapour changes and latent heat release, surface water vapours and radiative flux changes, surface heat loss and temperature change; and aerosols.
Abstract: There is growing evidence that the rate of warming is amplified with elevation, such that high-mountain environments experience more rapid changes in temperature than environments at lower elevations. Elevation-dependent warming (EDW) can accelerate the rate of change in mountain ecosystems, cryospheric systems, hydrological regimes and biodiversity. Here we review important mechanisms that contribute towards EDW: snow albedo and surface-based feedbacks; water vapour changes and latent heat release; surface water vapour and radiative flux changes; surface heat loss and temperature change; and aerosols. All lead to enhanced warming with elevation (or at a critical elevation), and it is believed that combinations of these mechanisms may account for contrasting regional patterns of EDW. We discuss future needs to increase knowledge of mountain temperature trends and their controlling mechanisms through improved observations, satellite-based remote sensing and model simulations.
1,628 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
University of Edinburgh1, University of Greifswald2, University of London3, Queen Mary University of London4, University of Trieste5, Vita-Salute San Raffaele University6, University of Tartu7, National Institutes of Health8, University of Oxford9, Johns Hopkins University10, Erasmus University Rotterdam11, University of Verona12, University of Iceland13, University of Otago14, Uppsala University15, University of Lübeck16, University of Split17, Harvard University18, University Hospital of Lausanne19, Ludwig Maximilian University of Munich20, University of Auckland21, VU University Amsterdam22, University of Regensburg23, Max Planck Society24, Greifswald University Hospital25, University of Helsinki26, Charles III University of Madrid27, Wellcome Trust Sanger Institute28, University College London29, Leiden University30, Catholic University of the Sacred Heart31, University of Bern32, University of Freiburg33
TL;DR: Interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, and regression-type analyses in a non BMI-stratified overall sample suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum.
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
1,293 citations
TL;DR: Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day.
Abstract: Background: Quantifying sexually transmitted infection (STI) prevalence and incidence is important for planning interventions and advocating for resources. The World Health Organization (WHO) periodically estimates global and regional prevalence and incidence of four curable STIs: chlamydia, gonorrhoea, trichomoniasis and syphilis.Methods and Findings: WHO's 2012 estimates were based upon literature reviews of prevalence data from 2005 through 2012 among general populations for genitourinary infection with chlamydia, gonorrhoea, and trichomoniasis, and nationally reported data on syphilis seroprevalence among antenatal care attendees. Data were standardized for laboratory test type, geography, age, and high risk subpopulations, and combined using a Bayesian meta-analytic approach. Regional incidence estimates were generated from prevalence estimates by adjusting for average duration of infection. In 2012, among women aged 15-49 years, the estimated global prevalence of chlamydia was 4.2%(95% uncertainty interval (UI): 3.7-4.7%), gonorrhoea 0.8%(0.6-1.0%), trichomoniasis 5.0%(4.0-6.4%), and syphilis 0.5%(0.4-0.6%); among men, estimated chlamydia prevalence was 2.7% (2.0-3.6%), gonorrhoea 0.6%(0.40.9%), trichomoniasis 0.6%(0.4-0.8%), and syphilis 0.48% (0.3-0.7%). These figures correspond to an estimated 131 million new cases of chlamydia (100-166 million), 78 million of gonorrhoea (53-110 million), 143 million of trichomoniasis (98-202 million), and 6 million of syphilis (4-8 million). Prevalence and incidence estimates varied by region and sex.Conclusions: Estimates of the global prevalence and incidence of chlamydia, gonorrhoea, trichomoniasis, and syphilis in adult women and men remain high, with nearly one million new infections with curable STI each day. The estimates highlight the urgent need for the public health community to ensure that well-recognized effective interventions for STI prevention, screening, diagnosis, and treatment are made more widely available. Improved estimation methods are needed to allow use of more varied data and generation of estimates at the national level.
1,235 citations
University of Warwick1, Heart of England NHS Foundation Trust2, University of Helsinki3, Oslo University Hospital4, University of Antwerp5, Ghent University6, Innsbruck Medical University7, Mario Negri Institute for Pharmacological Research8, Southmead Hospital9, The Catholic University of America10, Imperial College Healthcare11, Royal United Hospital12, Imperial College London13, University of Bern14
TL;DR: This chapter contains guidance on the techniques used during the initial resuscitation of an adult cardiac arrest victim and the use of an automated external defibrillator (AED).
1,104 citations
TL;DR: In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality.
1,018 citations
French Institute of Health and Medical Research1, Institut Gustave Roussy2, University of Pennsylvania3, University of Massachusetts Medical School4, University of Rome Tor Vergata5, University of California, San Francisco6, Virginia Commonwealth University7, Merck & Co.8, Harvard University9, University of South Australia10, University of Texas Southwestern Medical Center11, Trinity College, Dublin12, Austrian Academy of Sciences13, University of Cambridge14, University of Bern15, University of Oslo16, University of Colorado Denver17, Complutense University of Madrid18
TL;DR: The differential impact of autophagy on distinct phases of tumorigenesis is discussed and the implications of this concept for the use of Autophagy modulators in cancer therapy are discussed.
Abstract: Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.
University of Minnesota1, Leipzig University2, University College Dublin3, Centre national de la recherche scientifique4, University of Zurich5, University of Bayreuth6, Iowa State University7, Martin Luther University of Halle-Wittenberg8, University of Jena9, Swansea University10, United States Department of Agriculture11, Utrecht University12, University of Oxford13, University of Greifswald14, Sewanee: The University of the South15, University of Bern16, Technische Universität München17, Yokohama National University18, Columbia University19, University of Western Sydney20, Colorado State University21, University of California, Santa Barbara22, Virginia Tech23, Wageningen University and Research Centre24
TL;DR: Biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity toClimate events.
Abstract: It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide1. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities2. However, subsequent experimental tests produced mixed results3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16–32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability14, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events.
German Cancer Research Center1, Boston Children's Hospital2, University of Texas MD Anderson Cancer Center3, St. Jude Children's Research Hospital4, University of Toronto5, Max Planck Society6, Heidelberg University7, University of Utah8, Tel Aviv University9, University of Colorado Denver10, University of Bern11, Masaryk University12, University of Texas Health Science Center at San Antonio13, University of California, San Francisco14, New York University15, University of Cambridge16, University of Hamburg17, University of Bonn18
TL;DR: The molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.
Paris Descartes University1, Institut Gustave Roussy2, Mount Sinai Hospital3, University of Texas Southwestern Medical Center4, University of Kiel5, Thomas Jefferson University6, Seconda Università degli Studi di Napoli7, University of Toronto8, University of Massachusetts Medical School9, Louisiana State University10, Flanders Institute for Biotechnology11, Ghent University12, Cancer Research UK13, Queen Mary University of London14, Roswell Park Cancer Institute15, Karolinska Institutet16, University of Freiburg17, Buck Institute for Research on Aging18, University of California, San Francisco19, Université Paris-Saclay20, French Institute of Health and Medical Research21, University College London22, University of Rome Tor Vergata23, Northwestern University24, Memorial Sloan Kettering Cancer Center25, National Institutes of Health26, Technion – Israel Institute of Technology27, Johns Hopkins University28, University of Chieti-Pescara29, University of Ulm30, Genentech31, New York University32, Pennsylvania State University33, University of Salento34, Yale University35, Goethe University Frankfurt36, University of Burgundy37, Pasteur Institute38, University of Strasbourg39, University of Zurich40, University of Tokyo41, Technische Universität München42, University of Bern43, University of Michigan44, Medical Research Council45, University of Adelaide46, University of South Australia47, Medical University of South Carolina48, Howard Hughes Medical Institute49, University of Texas at Dallas50, St. John's University51, University of Oviedo52, University of Graz53, Istituto Superiore di Sanità54, Katholieke Universiteit Leuven55, Trinity College, Dublin56, University of Geneva57, University of Amsterdam58, Stony Brook University59, University of Washington60, University of Ferrara61, Royal College of Surgeons in Ireland62, La Trobe University63, University of Buenos Aires64, University of Virginia65, University of Padua66, University of Lisbon67, University of Cambridge68, University of Würzburg69, Soochow University (Suzhou)70, Columbia University71, University of Glasgow72, Foundation for Research & Technology – Hellas73, University of Crete74, Innsbruck Medical University75, Carlos III Health Institute76, Rutgers University77, University of Minnesota78, Harvard University79, City University of New York80, Moscow State University81
TL;DR: The Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
TL;DR: Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep‐seated, inflamed lesions in the apocrine gland‐bearing areas of the body.
Abstract: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.
TL;DR: This executive summary provides the essential treatment algorithms for the resuscitation of children and adults and highlights the main guideline changes since 2010.
TL;DR: Profex is a platform-independent open-source graphical user interface for the Rietveld refinement program BGMN.
Abstract: Profex is a graphical user interface for the Rietveld refinement program BGMN. Its interface focuses on preserving BGMN's powerful and flexible scripting features by giving direct access to BGMN input files. Very efficient workflows for single or batch refinements are achieved by managing refinement control files and structure files, by providing dialogues and shortcuts for many operations, by performing operations in the background, and by providing import filters for CIF and XML crystal structure files. Refinement results can be easily exported for further processing. State-of-the-art graphical export of diffraction patterns to pixel and vector graphics formats allows the creation of publication-quality graphs with minimum effort. Profex reads and converts a variety of proprietary raw data formats and is thus largely instrument independent. Profex and BGMN are available under an open-source license for Windows, Linux and OS X operating systems.
World Health Organization1, University of Florida2, University of Cape Town3, University of Bern4, University of London5, Bernhard Nocht Institute for Tropical Medicine6, Public Health England7, Médecins Sans Frontières8, University of Maryland, Baltimore9, Norwegian Institute of Public Health10, University of Oslo11, Harvard University12
TL;DR: The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus Disease outbreak via a ring vaccination strategy.
Wageningen University and Research Centre1, Rutgers University2, Spanish National Research Council3, Naturalis4, University of Leeds5, Institut national de la recherche agronomique6, Michigan State University7, University of Freiburg8, University of California, Berkeley9, University of New England (United States)10, University of Vermont11, University of California, Davis12, National University of Singapore13, Hungarian Academy of Sciences14, University of Göttingen15, Cornell University16, Swedish University of Agricultural Sciences17, Stellenbosch University18, Centre national de la recherche scientifique19, Simon Fraser University20, University of Reading21, University of Würzburg22, Plant & Food Research23, University of Giessen24, University of Texas at Austin25, University of Bern26, Hebrew University of Jerusalem27, Lund University28, Federal University of Bahia29
TL;DR: It is shown that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management Strategies to promote threatened bees.
Abstract: There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.
TL;DR: The diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (PCa) is concluded that mpMRI is able to detect significant PCa and may used to target prostate biopsies.
University of East Anglia1, University of Oslo2, Commonwealth Scientific and Industrial Research Organisation3, University of Exeter4, Oak Ridge National Laboratory5, Woods Hole Research Center6, University of Bristol7, Scripps Institution of Oceanography8, National Oceanic and Atmospheric Administration9, Karlsruhe Institute of Technology10, University of Miami11, Centre national de la recherche scientifique12, University of Maryland, College Park13, Aix-Marseille University14, Flanders Marine Institute15, Alfred Wegener Institute for Polar and Marine Research16, Max Planck Society17, University of Illinois at Urbana–Champaign18, Plymouth Marine Laboratory19, Netherlands Environmental Assessment Agency20, Lawrence Berkeley National Laboratory21, ETH Zurich22, Bjerknes Centre for Climate Research23, University of Paris24, Woods Hole Oceanographic Institution25, Institute of Arctic and Alpine Research26, Japan Agency for Marine-Earth Science and Technology27, National Institute for Environmental Studies28, University of Washington29, University of Bergen30, Spanish National Research Council31, Montana State University32, Leibniz Institute for Baltic Sea Research33, Japan Meteorological Agency34, Leibniz Institute of Marine Sciences35, University of Bern36, Imperial College London37, Joint Institute for the Study of the Atmosphere and Ocean38, Lamont–Doherty Earth Observatory39, Hobart Corporation40, Wageningen University and Research Centre41, VU University Amsterdam42, University of New Hampshire43, Met Office44
TL;DR: In this article, the authors presented a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community.
Abstract: Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe data sets and a methodology to quantify all major components of the global carbon budget, including their uncertainties, based on the combination of a range of data, algorithms, statistics, and model estimates and their interpretation by a broad scientific community. We discuss changes compared to previous estimates as well as consistency within and among components, alongside methodology and data limitations. CO2 emissions from fossil fuels and industry (EFF) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on combined evidence from land-cover-change data, fire activity associated with deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the annual changes in concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. The variability in SOCEAN is evaluated with data products based on surveys of ocean CO2 measurements. The global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms of the global carbon budget and compared to results of independent dynamic global vegetation models forced by observed climate, CO2, and land-cover change (some including nitrogen–carbon interactions). We compare the mean land and ocean fluxes and their variability to estimates from three atmospheric inverse methods for three broad latitude bands. All uncertainties are reported as ±1σ, reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. For the last decade available (2005–2014), EFF was 9.0 ± 0.5 GtC yr−1, ELUC was 0.9 ± 0.5 GtC yr−1, GATM was 4.4 ± 0.1 GtC yr−1, SOCEAN was 2.6 ± 0.5 GtC yr−1, and SLAND was 3.0 ± 0.8 GtC yr−1. For the year 2014 alone, EFF grew to 9.8 ± 0.5 GtC yr−1, 0.6 % above 2013, continuing the growth trend in these emissions, albeit at a slower rate compared to the average growth of 2.2 % yr−1 that took place during 2005–2014. Also, for 2014, ELUC was 1.1 ± 0.5 GtC yr−1, GATM was 3.9 ± 0.2 GtC yr−1, SOCEAN was 2.9 ± 0.5 GtC yr−1, and SLAND was 4.1 ± 0.9 GtC yr−1. GATM was lower in 2014 compared to the past decade (2005–2014), reflecting a larger SLAND for that year. The global atmospheric CO2 concentration reached 397.15 ± 0.10 ppm averaged over 2014. For 2015, preliminary data indicate that the growth in EFF will be near or slightly below zero, with a projection of −0.6 [range of −1.6 to +0.5] %, based on national emissions projections for China and the USA, and projections of gross domestic product corrected for recent changes in the carbon intensity of the global economy for the rest of the world. From this projection of EFF and assumed constant ELUC for 2015, cumulative emissions of CO2 will reach about 555 ± 55 GtC (2035 ± 205 GtCO2) for 1870–2015, about 75 % from EFF and 25 % from ELUC. This living data update documents changes in the methods and data sets used in this new carbon budget compared with previous publications of this data set (Le Quere et al., 2015, 2014, 2013). All observations presented here can be downloaded from the Carbon Dioxide Information Analysis Center (doi:10.3334/CDIAC/GCP_2015).
University of Newcastle1, University of Melbourne2, Harvard University3, University of Chicago4, University of Bordeaux5, European Organisation for Research and Treatment of Cancer6, University of Pittsburgh7, Virginia Commonwealth University8, Alberta Health Services9, University of Regensburg10, Mayo Clinic11, University of Bern12, European Institute of Oncology13, University of Milan14, University of Sydney15
TL;DR: Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population, but for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes.
Abstract: We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen–ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen–ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.)
TL;DR: Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions, and feldspathic/silica-based ceramics should be limited to applications in the anterior region.
TL;DR: Current understanding of neutrophils in host-pathogen interactions and disease involvement is summarized, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage.
Abstract: Neutrophils, the most abundant human immune cells, are rapidly recruited to sites of infection, where they fulfill their life-saving antimicrobial functions. While traditionally regarded as short-lived phagocytes, recent findings on long-term survival, neutrophil extracellular trap (NET) formation, heterogeneity and plasticity, suppressive functions, and tissue injury have expanded our understanding of their diverse role in infection and inflammation. This review summarises our current understanding of neutrophils in host-pathogen interactions and disease involvement, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage.
TL;DR: The results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis.
University of Bern1, University of Tübingen2, University of Freiburg3, Technische Universität Darmstadt4, University of Ulm5, University of Münster6, Xavier University7, Smithsonian Institution8, Free University of Berlin9, Max Planck Society10, University of Würzburg11, Smithsonian Tropical Research Institute12, Technische Universität München13, University of Jena14, University of Göttingen15, Karlsruhe Institute of Technology16, University of Potsdam17
TL;DR: Biodiversity loss explained indirect effects in a region of intermediate productivity and was most damaging when land‐use objectives favoured supporting and cultural services, and functional composition shifts, towards fast‐growing plant species, strongly increased provisioning services in more inherently unproductive grasslands.
Abstract: Global change, especially land-use intensification, affects human well-being by impacting the delivery of multiple ecosystem services (multifunctionality). However, whether biodiversity loss is a major component of global change effects on multifunctionality in real-world ecosystems, as in experimental ones, remains unclear. Therefore, we assessed biodiversity, functional composition and 14 ecosystem services on 150 agricultural grasslands differing in land-use intensity. We also introduce five multifunctionality measures in which ecosystem services were weighted according to realistic land-use objectives. We found that indirect land-use effects, i.e. those mediated by biodiversity loss and by changes to functional composition, were as strong as direct effects on average. Their strength varied with land-use objectives and regional context. Biodiversity loss explained indirect effects in a region of intermediate productivity and was most damaging when land-use objectives favoured supporting and cultural services. In contrast, functional composition shifts, towards fast-growing plant species, strongly increased provisioning services in more inherently unproductive grasslands.
Royal Free Hospital1, Institut Gustave Roussy2, University of Perugia3, University of Turin4, Imperial College London5, University of Milan6, University of Bern7, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico8, Memorial Sloan Kettering Cancer Center9, University of Marburg10, Autonomous University of Barcelona11, Erasmus University Rotterdam12, Uppsala University13, University of Genoa14, Churchill Hospital15, Kyushu University16, National Institutes of Health17, National and Kapodistrian University of Athens18, University of Reims Champagne-Ardenne19, University of Copenhagen20, Medical University of Silesia21, Curie Institute22, Aberdeen Royal Infirmary23, University College Dublin24, Charité25, Charles University in Prague26, University College London27, University of Freiburg28, Peking Union Medical College29
TL;DR: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up, and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC.
TL;DR: The authors summarize the molecular concepts of progression, discuss the potential reasons for clinical trial failure and propose new concepts of drug development, which might lead to clinical implementation of emerging targeted agents.
Abstract: Mortality owing to liver cancer has increased in the past 20 years, and the latest estimates indicate that the global health burden of this disease will continue to grow. Most patients with hepatocellular carcinoma (HCC) are still diagnosed at intermediate or advanced disease stages, where curative approaches are often not feasible. Among the treatment options available, the molecular targeted agent sorafenib is able to significantly increase overall survival in these patients. Thereafter, up to seven large, randomized phase III clinical trials investigating other molecular therapies in the first-line and second-line settings have failed to improve on the results observed with this agent. Potential reasons for this include intertumour heterogeneity, issues with trial design and a lack of predictive biomarkers of response. During the past 5 years, substantial advances in our knowledge of the human genome have provided a comprehensive picture of commonly mutated genes in patients with HCC. This knowledge has not yet influenced clinical decision-making or current clinical practice guidelines. In this Review the authors summarize the molecular concepts of progression, discuss the potential reasons for clinical trial failure and propose new concepts of drug development, which might lead to clinical implementation of emerging targeted agents.
TL;DR: It is shown that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrated that melanoma cell-intrinsic PD- 1 promotes tumorigenesis, even in mice lacking adaptive immunity, and suggested that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD -1 therapy.
TL;DR: This work shows that loss of REV7 in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition.
Abstract: Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.