Showing papers by "University of Münster published in 2017"
University of Ulm1, Fred Hutchinson Cancer Research Center2, King's College London3, University of Rome Tor Vergata4, University of Münster5, Brigham and Women's Hospital6, University of Chicago7, Memorial Sloan Kettering Cancer Center8, Leipzig University9, VU University Amsterdam10, University of Valencia11, National Taiwan University12, Monash University13, Alfred Hospital14, Erasmus University Medical Center15, Ohio State University16
TL;DR: An international panel to provide updated evidence- and expert opinion-based recommendations for diagnosis and management of acute myeloid leukemia in adults includes a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
4,066 citations
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
1,573 citations
13 Jun 2017
TL;DR: This work describes the ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation, and describes the challenges in crowd-sourcing this data at scale.
Abstract: Neural networks trained on datasets such as ImageNet have led to major advances in visual object classification. One obstacle that prevents networks from reasoning more deeply about complex scenes and situations, and from integrating visual knowledge with natural language, like humans do, is their lack of common sense knowledge about the physical world. Videos, unlike still images, contain a wealth of detailed information about the physical world. However, most labelled video datasets represent high-level concepts rather than detailed physical aspects about actions and scenes. In this work, we describe our ongoing collection of the “something-something” database of video prediction tasks whose solutions require a common sense understanding of the depicted situation. The database currently contains more than 100,000 videos across 174 classes, which are defined as caption-templates. We also describe the challenges in crowd-sourcing this data at scale.
1,062 citations
Columbia University1, University of Amsterdam2, University of Mainz3, University of Coimbra4, New York University Abu Dhabi5, University of Zurich6, Stockholm University7, Rensselaer Polytechnic Institute8, Max Planck Society9, Weizmann Institute of Science10, University of Freiburg11, Purdue University12, University of Nantes13, University of Bologna14, University of California, San Diego15, University of Münster16, University of Chicago17, Rice University18, Pierre-and-Marie-Curie University19, University of California, Los Angeles20
TL;DR: The first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy, are reported and a profile likelihood analysis shows that the data are consistent with the background-only hypothesis.
Abstract: We report the first dark matter search results from XENON1T, a ∼2000-kg-target-mass dual-phase (liquid-gas) xenon time projection chamber in operation at the Laboratori Nazionali del Gran Sasso in Italy and the first ton-scale detector of this kind The blinded search used 342 live days of data acquired between November 2016 and January 2017 Inside the (1042±12)-kg fiducial mass and in the [5,40] keVnr energy range of interest for weakly interacting massive particle (WIMP) dark matter searches, the electronic recoil background was (193±025)×10-4 events/(kg×day×keVee), the lowest ever achieved in such a dark matter detector A profile likelihood analysis shows that the data are consistent with the background-only hypothesis We derive the most stringent exclusion limits on the spin-independent WIMP-nucleon interaction cross section for WIMP masses above 10 GeV/c2, with a minimum of 77×10-47 cm2 for 35-GeV/c2 WIMPs at 90% CL
1,061 citations
TL;DR: In this article, the authors place the lithium ion technology in a historical context and give insights into the battery technology diversity that evolved during the past decades and which will, in turn, influence future research and development.
Abstract: Since their market introduction in 1991, lithium ion batteries (LIBs) have developed evolutionary in terms of their specific energies (Wh/kg) and energy densities (Wh/L). Currently, they do not only dominate the small format battery market for portable electronic devices, but have also been successfully implemented as the technology of choice for electromobility as well as for stationary energy storage. Besides LIBs, a variety of different technologically promising battery concepts exists that, depending on the respective technology, might also be suitable for various application purposes. These systems of the “next generation,” the so-called post-lithium ion batteries (PLIBs), such as metal/sulfur, metal/air or metal/oxygen, or “post-lithium technologies” (systems without Li), which are based on alternative single (Na+, K+) or multivalent ions (Mg2+, Ca2+), are currently being studied intensively. From today’s point of view, it seems quite clear that there will not only be a single technology for all applications (technology monopoly), but different battery systems, which can be especially suitable or combined for a particular application (technology diversity). In this review, we place the lithium ion technology in a historical context and give insights into the battery technology diversity that evolved during the past decades and which will, in turn, influence future research and development.
730 citations
VU University Medical Center1, University of Southern California2, Max Planck Society3, McMaster University4, University of Adelaide5, University of California, Irvine6, Erasmus University Rotterdam7, Delft University of Technology8, Erasmus University Medical Center9, German Center for Neurodegenerative Diseases10, Greifswald University Hospital11, University of Münster12, University of Marburg13, University of Queensland14, QIMR Berghofer Medical Research Institute15, Queensland University of Technology16, Virginia Commonwealth University17, University of Göttingen18, University Hospital Heidelberg19, University of Sydney20, Trinity College, Dublin21, Otto-von-Guericke University Magdeburg22, University of Regensburg23, University Medical Center Groningen24, Leiden University Medical Center25, University of Melbourne26, University of Texas Health Science Center at Houston27, Charité28, University of Bonn29, University of Lübeck30, University Medical Center Freiburg31, Stanford University32, University of Calgary33, Warneford Hospital34, Royal Edinburgh Hospital35, University of Edinburgh36, University of Bern37, Cardiff University38, Leibniz Institute for Neurobiology39, University of Tübingen40, Siberian State Medical University41, Mental Health Research Institute42, Tomsk State University43
TL;DR: In this article, the authors present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD.
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
728 citations
University of Queensland1, University of the Witwatersrand2, University of Bristol3, University of East Anglia4, University of Arizona5, University of Münster6, Max Planck Society7, University of Ottawa8, Istituto Nazionale di Fisica Nucleare9, University of Glasgow10, Innsbruck Medical University11, State University of New York System12, The Institute of Optics13, Polytechnic University of Catalonia14, University of Victoria15, University of Southern California16, University of Oregon17, Purdue University18
TL;DR: In this paper, the key fields within structured light from the perspective of experts in those areas, providing insight into the current state and the challenges their respective fields face, as well as the exciting prospects for the future that are yet to be realized.
Abstract: Structured light refers to the generation and application of custom light fields. As the tools and technology to create and detect structured light have evolved, steadily the applications have begun to emerge. This roadmap touches on the key fields within structured light from the perspective of experts in those areas, providing insight into the current state and the challenges their respective fields face. Collectively the roadmap outlines the venerable nature of structured light research and the exciting prospects for the future that are yet to be realized.
639 citations
TL;DR: The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients.
Abstract: 177Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients.
Methods:
145 patients (median age 73 years, range 43-88) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (CTCAE 4.0) based on serial blood tests and the attending physician’s report. Primary endpoint for efficacy was biochemical response as defined by a PSA decline ≥ 50% from baseline to at least two weeks after start of RLT.
Results:
A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response were available in 99 patients and data for physician-reported/lab-based toxicity in 145/121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles, while 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response.
Conclusion:
The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third line systemic therapies in mCRPC patients. Future Phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.
595 citations
TL;DR: In this article, the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated acute kidney injury (AKI) in high risk patients defined by renal biomarkers was evaluated.
Abstract: Purpose
Care bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.
543 citations
TL;DR: It is shown that high-impact-factor developmental journals are heavily skewed toward publishing articles with data from WEIRD populations, and there is a habitual dependence on convenience sampling and little evidence that the discipline is making any meaningful movement toward drawing from diverse samples.
523 citations
Heidelberg University1, German Cancer Research Center2, University Hospital Heidelberg3, University of Zurich4, Medical University of Vienna5, Goethe University Frankfurt6, University of Bristol7, Otto-von-Guericke University Magdeburg8, University of Mannheim9, Saarland University10, University of Bonn11, Charité12, University of Cambridge13, University of Münster14
TL;DR: Compared with WHO grading, classification by individual and combined methylation classes more accurately identifies patients at high risk of disease progression in tumours with WHO grade I histology, and patients at lower risk of recurrence among WHO grade II tumours.
Abstract: Summary Background The WHO classification of brain tumours describes 15 subtypes of meningioma. Nine of these subtypes are allotted to WHO grade I, and three each to grade II and grade III. Grading is based solely on histology, with an absence of molecular markers. Although the existing classification and grading approach is of prognostic value, it harbours shortcomings such as ill-defined parameters for subtypes and grading criteria prone to arbitrary judgment. In this study, we aimed for a comprehensive characterisation of the entire molecular genetic landscape of meningioma to identify biologically and clinically relevant subgroups. Methods In this multicentre, retrospective analysis, we investigated genome-wide DNA methylation patterns of meningiomas from ten European academic neuro-oncology centres to identify distinct methylation classes of meningiomas. The methylation classes were further characterised by DNA copy number analysis, mutational profiling, and RNA sequencing. Methylation classes were analysed for progression-free survival outcomes by the Kaplan-Meier method. The DNA methylation-based and WHO classification schema were compared using the Brier prediction score, analysed in an independent cohort with WHO grading, progression-free survival, and disease-specific survival data available, collected at the Medical University Vienna (Vienna, Austria), assessing methylation patterns with an alternative methylation chip. Findings We retrospectively collected 497 meningiomas along with 309 samples of other extra-axial skull tumours that might histologically mimic meningioma variants. Unsupervised clustering of DNA methylation data clearly segregated all meningiomas from other skull tumours. We generated genome-wide DNA methylation profiles from all 497 meningioma samples. DNA methylation profiling distinguished six distinct clinically relevant methylation classes associated with typical mutational, cytogenetic, and gene expression patterns. Compared with WHO grading, classification by individual and combined methylation classes more accurately identifies patients at high risk of disease progression in tumours with WHO grade I histology, and patients at lower risk of recurrence among WHO grade II tumours (p=0·0096) from the Brier prediction test). We validated this finding in our independent cohort of 140 patients with meningioma. Interpretation DNA methylation-based meningioma classification captures clinically more homogenous groups and has a higher power for predicting tumour recurrence and prognosis than the WHO classification. The approach presented here is potentially very useful for stratifying meningioma patients to observation-only or adjuvant treatment groups. We consider methylation-based tumour classification highly relevant for the future diagnosis and treatment of meningioma. Funding German Cancer Aid, Else Kroner-Fresenius Foundation, and DKFZ/Heidelberg Institute of Personalized Oncology/Precision Oncology Program.
TL;DR: The design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and the methodology for drilling and deployment are described, including the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis.
Abstract: The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.
TL;DR: An implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients.
Abstract: PurposeCare bundles are recommended in patients at high risk for acute kidney injury (AKI), although they have not been proven to improve outcomes. We sought to establish the efficacy of an implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines to prevent cardiac surgery-associated AKI in high risk patients defined by renal biomarkers.MethodsIn this single-center trial, we examined the effect of a “KDIGO bundle” consisting of optimization of volume status and hemodynamics, avoidance of nephrotoxic drugs, and preventing hyperglycemia in high risk patients defined as urinary [TIMP-2]·[IGFBP7] > 0.3 undergoing cardiac surgery. The primary endpoint was the rate of AKI defined by KDIGO criteria within the first 72 h after surgery. Secondary endpoints included AKI severity, need for dialysis, length of stay, and major adverse kidney events (MAKE) at days 30, 60, and 90.ResultsAKI was significantly reduced with the intervention compared to controls [55.1 vs. 71.7%; ARR 16.6% (95 CI 5.5–27.9%); p = 0.004]. The implementation of the bundle resulted in significantly improved hemodynamic parameters at different time points (p < 0.05), less hyperglycemia (p < 0.001) and use of ACEi/ARBs (p < 0.001) compared to controls. Rates of moderate to severe AKI were also significantly reduced by the intervention compared to controls. There were no significant effects on other secondary outcomes.ConclusionAn implementation of the KDIGO guidelines compared with standard care reduced the frequency and severity of AKI after cardiac surgery in high risk patients. Adequately powered multicenter trials are warranted to examine mortality and long-term renal outcomes.
TL;DR: In this paper, the authors use the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.
TL;DR: It is demonstrated that Tregs in skin play a major role in HF biology by promoting the function of HF SCs and expression of Jag1 facilitated HFSC function and efficient HF regeneration.
IT University of Copenhagen1, Framingham State University2, Katholieke Universiteit Leuven3, Johns Hopkins University4, Middlesex University5, Université catholique de Louvain6, Umeå University7, Stockholm University8, Stetson University9, University of Derby10, Erasmus University Rotterdam11, Karolinska Institutet12, Villanova University13, University of Oxford14, University of Münster15, Kore University of Enna16, University of Sydney17, Ghent University18
TL;DR: It is claimed that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life and the healthy majority of gamers will be affected negatively.
Abstract: Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world.
TL;DR: Jupiter is the oldest planet of the Solar System, and its solid core formed well before the solar nebula gas dissipated, consistent with the core accretion model for giant planet formation.
Abstract: The age of Jupiter, the largest planet in our Solar System, is still unknown. Gas-giant planet formation likely involved the growth of large solid cores, followed by the accumulation of gas onto these cores. Thus, the gas-giant cores must have formed before dissipation of the solar nebula, which likely occurred within less than 10 My after Solar System formation. Although such rapid accretion of the gas-giant cores has successfully been modeled, until now it has not been possible to date their formation. Here, using molybdenum and tungsten isotope measurements on iron meteorites, we demonstrate that meteorites derive from two genetically distinct nebular reservoirs that coexisted and remained spatially separated between ∼1 My and ∼3-4 My after Solar System formation. The most plausible mechanism for this efficient separation is the formation of Jupiter, opening a gap in the disk and preventing the exchange of material between the two reservoirs. As such, our results indicate that Jupiter's core grew to ∼20 Earth masses within <1 My, followed by a more protracted growth to ∼50 Earth masses until at least ∼3-4 My after Solar System formation. Thus, Jupiter is the oldest planet of the Solar System, and its solid core formed well before the solar nebula gas dissipated, consistent with the core accretion model for giant planet formation.
Jamia Millia Islamia1, Hanoi University of Science2, Vietnam Academy of Science and Technology3, Saitama University4, Aarhus University5, University of California, Santa Barbara6, Commissariat à l'énergie atomique et aux énergies alternatives7, University of Münster8, University of Connecticut9, University of Manchester10, Indian Institute of Technology Guwahati11, Leiden University12, Northwestern University13, Federal University of Paraíba14, Centre national de la recherche scientifique15, Universidade Federal do ABC16, University of Southampton17, Argonne National Laboratory18, Karlsruhe Institute of Technology19, University of Mainz20, Technische Universität München21, Max Planck Society22, Heidelberg University23, University of Tübingen24, Massachusetts Institute of Technology25, Durham University26, University of California, San Diego27, C. N. Yang Institute for Theoretical Physics28, Russian Academy of Sciences29, Moscow Institute of Physics and Technology30, University of Sydney31, University of Copenhagen32, Université libre de Bruxelles33, Paris Diderot University34, Niels Bohr Institute35, Estácio S.A.36, CERN37, University of California, Santa Cruz38, Institute on Taxation and Economic Policy39, University of Bern40, Institute for Advanced Study41, RWTH Aachen University42, Chinese Academy of Sciences43, East China University of Science and Technology44, University of Chicago45, Autonomous University of Madrid46, King's College London47, INAF48, Lawrence Berkeley National Laboratory49, University of Bari50, Istituto Nazionale di Fisica Nucleare51, University of Geneva52, Petersburg Nuclear Physics Institute53, University of Genoa54, Kapteyn Astronomical Institute55, Fermilab56, Spanish National Research Council57, Oak Ridge National Laboratory58, University of California, Berkeley59, École Polytechnique Fédérale de Lausanne60, University of Paris61, University of Zurich62, Mitchell Institute63, Tohoku University64, Princeton University65, Shimane University66, University of Maryland, College Park67, Dresden University of Technology68
TL;DR: A comprehensive review of keV-scale neutrino Dark Matter can be found in this paper, where the role of active neutrinos in particle physics, astrophysics, and cosmology is reviewed.
Abstract: We present a comprehensive review of keV-scale sterile neutrino Dark Matter, collecting views and insights from all disciplines involved—cosmology, astrophysics, nuclear, and particle physics—in each case viewed from both theoretical and experimental/observational perspectives. After reviewing the role of active neutrinos in particle physics, astrophysics, and cosmology, we focus on sterile neutrinos in the context of the Dark Matter puzzle. Here, we first review the physics motivation for sterile neutrino Dark Matter, based on challenges and tensions in purely cold Dark Matter scenarios. We then round out the discussion by critically summarizing all known constraints on sterile neutrino Dark Matter arising from astrophysical observations, laboratory experiments, and theoretical considerations. In this context, we provide a balanced discourse on the possibly positive signal from X-ray observations. Another focus of the paper concerns the construction of particle physics models, aiming to explain how sterile neutrinos of keV-scale masses could arise in concrete settings beyond the Standard Model of elementary particle physics. The paper ends with an extensive review of current and future astrophysical and laboratory searches, highlighting new ideas and their experimental challenges, as well as future perspectives for the discovery of sterile neutrinos.
TL;DR: The varying offset between the virtual and the physical tracking space makes the HTC Vive at present unsuitable for scientific experiments that require accurate visual stimulation of self-motion through a virtual world, but it may be suited for other experiments that do not have this requirement.
Abstract: The advent of inexpensive consumer virtual reality equipment enables many more researchers to study perception with naturally moving observers One such system, the HTC Vive, offers a large field-of-view, high-resolution head mounted display together with a room-scale tracking system for less than a thousand US dollars If the position and orientation tracking of this system is of sufficient accuracy and precision, it could be suitable for much research that is currently done with far more expensive systems Here we present a quantitative test of the HTC Vive's position and orientation tracking as well as its end-to-end system latency We report that while the precision of the Vive's tracking measurements is high and its system latency (22 ms) is low, its position and orientation measurements are provided in a coordinate system that is tilted with respect to the physical ground plane Because large changes in offset were found whenever tracking was briefly lost, it cannot be corrected for with a one-time calibration procedure We conclude that the varying offset between the virtual and the physical tracking space makes the HTC Vive at present unsuitable for scientific experiments that require accurate visual stimulation of self-motion through a virtual world It may however be suited for other experiments that do not have this requirement
TL;DR: An international consensus statement on the classification of endometriosis is produced through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometiosis.
Abstract: Author(s): Johnson, Neil P; Hummelshoj, Lone; Adamson, G David; Keckstein, Jorg; Taylor, Hugh S; Abrao, Mauricio S; Bush, Deborah; Kiesel, Ludwig; Tamimi, Rulla; Sharpe-Timms, Kathy L; Rombauts, Luk; Giudice, Linda C; World Endometriosis Society Sao Paulo Consortium | Abstract: Study questionWhat is the global consensus on the classification of endometriosis that considers the views of women with endometriosis?Summary answerWe have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis.What is known alreadyClassification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis.Study design, size, durationA consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken.Participants/materials, setting, methodsA consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.Main results and the role of chanceA total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken.Limitations, reasons for cautionThis consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements.Wider implications of the findingsThis is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries - has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis.Study funding/competing interestsThe World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher a Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jorg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor.Trial registration numberN/A.
TL;DR: This work reports the development of a hardware synapse, implemented entirely in the optical domain via a photonic integrated-circuit approach, delivering an incredibly simple yet powerful approach that heralds systems with a continuously variable synaptic plasticity resembling the true analog nature of biological synapses.
Abstract: The search for new “neuromorphic computing” architectures that mimic the brain’s approach to simultaneous processing and storage of information is intense. Because, in real brains, neuronal synapses outnumber neurons by many orders of magnitude, the realization of hardware devices mimicking the functionality of a synapse is a first and essential step in such a search. We report the development of such a hardware synapse, implemented entirely in the optical domain via a photonic integrated-circuit approach. Using purely optical means brings the benefits of ultrafast operation speed, virtually unlimited bandwidth, and no electrical interconnect power losses. Our synapse uses phase-change materials combined with integrated silicon nitride waveguides. Crucially, we can randomly set the synaptic weight simply by varying the number of optical pulses sent down the waveguide, delivering an incredibly simple yet powerful approach that heralds systems with a continuously variable synaptic plasticity resembling the true analog nature of biological synapses.
TL;DR: It is reported that deep neural networks can learn to resolve reactivity conflicts and to prioritize the most suitable transformation rules.
Abstract: Reaction prediction and retrosynthesis are the cornerstones of organic chemistry. Rule-based expert systems have been the most widespread approach to computationally solve these two related challenges to date. However, reaction rules often fail because they ignore the molecular context, which leads to reactivity conflicts. Herein, we report that deep neural networks can learn to resolve reactivity conflicts and to prioritize the most suitable transformation rules. We show that by training our model on 3.5 million reactions taken from the collective published knowledge of the entire discipline of chemistry, our model exhibits a top10-accuracy of 95 % in retrosynthesis and 97 % for reaction prediction on a validation set of almost 1 million reactions.
National Institutes of Health1, AstraZeneca2, University of Turku3, Durham University4, Robertson Centre for Biostatistics5, University of Münster6, Daiichi Sankyo7, GlaxoSmithKline8, Boehringer Ingelheim9, Bayer HealthCare Pharmaceuticals10, Pfizer11, University of Glasgow12, Food and Drug Administration13, Campbell University14, Edwards Lifesciences Corporation15, University of Lorraine16, French Institute of Health and Medical Research17
TL;DR: This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research and highlights the importance of collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors.
Abstract: Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.
TL;DR: Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited and possible sequences include TKI-mTOR-TKI or TKI–TKI- mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.
Abstract: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC). A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing. Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-α) in patients with non-clear cell RCC (non-ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR-targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited. Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI–TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy.
Newcastle University1, Imperial College London2, University of East Anglia3, Zoological Society of London4, American Museum of Natural History5, BirdLife International6, University of Cambridge7, National Autonomous University of Mexico8, Lancaster University9, University of Connecticut10, University of Oxford11, State University of Santa Cruz12, Oregon State University13, University of Liverpool14, Ghent University15, National University of Colombia16, University of Pretoria17, University of Western Ontario18, University of Wisconsin-Madison19, Federal University of Mato Grosso do Sul20, University of Münster21, University of Kent22, Pontifical Xavierian University23, John Carroll University24, California State University, Los Angeles25
TL;DR: A global dataset on species responses to fragmentation and a statistical approach for quantifying edge impacts in heterogeneous landscapes are assembled to quantify edge-determined changes in abundance of 1,673 vertebrate species and highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.
Abstract: Forest edges influence more than half of the world's forests and contribute to worldwide declines in biodiversity and ecosystem functions. However, predicting these declines is challenging in heterogeneous fragmented landscapes. Here we assembled a global dataset on species responses to fragmentation and developed a statistical approach for quantifying edge impacts in heterogeneous landscapes to quantify edge-determined changes in abundance of 1,673 vertebrate species. We show that the abundances of 85% of species are affected, either positively or negatively, by forest edges. Species that live in the centre of the forest (forest core), that were more likely to be listed as threatened by the International Union for Conservation of Nature (IUCN), reached peak abundances only at sites farther than 200-400 m from sharp high-contrast forest edges. Smaller-bodied amphibians, larger reptiles and medium-sized non-volant mammals experienced a larger reduction in suitable habitat than other forest-core species. Our results highlight the pervasive ability of forest edges to restructure ecological communities on a global scale.
TL;DR: This tutorial review introduces different categories of chiral NHCs and provides a guide to the structural fine-tuning of ligand requirements and stereochemical models.
Abstract: Chiral ligands play a central role in enantioselective transition-metal catalysis. The success of achiral N-heterocyclic carbenes (NHCs) as stable electron-rich neutral ligands in homogeneous catalysis led to the development of a manifold of chiral NHCs as stereodirecting ancillary ligands for various enantioselective transformations. Due to the modular design of NHCs and the ease of access to their azolium salt precursors, tailor-made NHCs are readily available. Many chiral NHC scaffolds have been synthesised and tested in catalysis. Herein, we highlight only those NHC structures which have enabled high degrees of enantioselectivity in transition-metal catalysis. Following a brief introduction to the field of chiral NHCs, this tutorial review introduces different categories of chiral NHCs and provides a guide to the structural fine-tuning of ligand requirements and stereochemical models.
University of Tübingen1, Goethe University Frankfurt2, Children's Hospital of Philadelphia3, Pennsylvania State University4, University of Toronto5, University of Bern6, Columbia University7, University of Münster8, Duke University9, Istituto Giannina Gaslini10, University of Genoa11, St. Jude Children's Research Hospital12
TL;DR: Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation and future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.
Abstract: Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.
TL;DR: In this paper, the origin of high-energy neutrinos has not yet been fully answered and only a small fraction of what is known about this flux comes from a small ev...
Abstract: Since the recent detection of an astrophysical flux of high-energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small ev ...
TL;DR: The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates.
Abstract: Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 ( $\sqrt{s_{NN}}=$ 2.7--4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials ( $\mu_B > 500$ MeV), effects of chiral symmetry, and the equation of state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2024, in the context of the worldwide efforts to explore high-density QCD matter.
TL;DR: The evidence for the observed increase in the incidence of skin cancer over recent decades is reviewed, and whether this is a true increase or an artefact of greater screening and over-diagnosis is investigated.
Abstract: Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection.