The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of ...movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim,walk/paddle). Strikingly,movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.
Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory ...approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.
ACC/AHA Task Force Members Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, MACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair¶ Sana M. Al-Khatib, MD, ...MHS, FACC, FAHA Joshua A. Beckman, MD, MS, FAHA Kim K. Birtcher, MS, PharmD, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA¶ Ralph G. Brindis, MD, MPH, MACC¶ Joaquin E. Cigarroa, MD, FACC Anita Deswal, MD, MPH, FACC, FAHA Lesley H. Curtis, PhD, FAHA¶ Lee A. Fleisher, MD, FACC, FAHA Federico Gentile, MD, FACC Samuel Gidding, MD, FAHA¶ Zachary D. Goldberger, MD, MS, FACC, FAHA Mark A. Hlatky, MD, FACC, FAHA John Ikonomidis, MD, PhD, FAHA José A. Joglar, MD, FACC, FAHA Laura Mauri, MD, MSc, FAHA Barbara Riegel, PhD, RN, FAHA Susan J. Pressler, PhD, RN, FAHA¶ Duminda N. Wijeysundera, MD, PhD¶Former Task Force member; current member during the writing effort.Table of Contents Preamblee93 Introductione95 1.1.Methodology and Evidence Reviewe95 1.2.Organization of the Writing Committeee95 1.3.Document Review and Approvale95 1.4.Scope of the Guidelinee97 1.5.Abbreviationse99 2. Evidence Gaps and Future Research Needse182 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)e214 Appendix 2 Reviewer Relationships With Industry and Other Entities (Comprehensive)e216 Preamble Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines with recommendations to improve cardiovascular health. Adherence to recommendations can be enhanced by shared decision-making between healthcare providers and patients, with patient engagement in selecting interventions based on individual values, preferences, and associated conditions and comorbidities.Methodology and Modernization The ACC/AHA Task Force on Clinical Practice Guidelines (Task Force) continuously reviews, updates, and modifies guideline methodology on the basis of published standards from organizations including the Institute of Medicine (P-1,P-2) and on the basis of internal reevaluation. Publication of new, potentially practice-changing study results that are relevant to an existing or new medication, device, or management strategy will prompt evaluation by the Task Force, in consultation with the relevant guideline writing committee, to determine whether a focused update should be commissioned.
Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and ...posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy n = 545: hazard ratio HR, 50.3; SibCy n = 279: HR, 47.7; SibCNI n = 1065: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
•PTCy increased the risk of CMV infection in seropositive Haplo and Sib HCT recipients relative to Sib HCT with conventional GVHD prophylaxis.•CMV infection was associated with higher chronic GVHD in PTCy recipients, potentially negating the protective effect of PTCy.
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We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event ...is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.
Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and ...usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.
VALUE is an open European collaboration to intercompare downscaling approaches for climate change research, focusing on different validation aspects (marginal, temporal, extremes, spatial, ...process‐based, etc.). Here we describe the participating methods and first results from the first experiment, using “perfect” reanalysis (and reanalysis‐driven regional climate model (RCM)) predictors to assess the intrinsic performance of the methods for downscaling precipitation and temperatures over a set of 86 stations representative of the main climatic regions in Europe. This study constitutes the largest and most comprehensive to date intercomparison of statistical downscaling methods, covering the three common downscaling approaches (perfect prognosis, model output statistics—including bias correction—and weather generators) with a total of over 50 downscaling methods representative of the most common techniques.
Overall, most of the downscaling methods greatly improve (reanalysis or RCM) raw model biases and no approach or technique seems to be superior in general, because there is a large method‐to‐method variability. The main factors most influencing the results are the seasonal calibration of the methods (e.g., using a moving window) and their stochastic nature. The particular predictors used also play an important role in cases where the comparison was possible, both for the validation results and for the strength of the predictor–predictand link, indicating the local variability explained. However, the present study cannot give a conclusive assessment of the skill of the methods to simulate regional future climates, and further experiments will be soon performed in the framework of the EURO‐CORDEX initiative (where VALUE activities have merged and follow on).
Finally, research transparency and reproducibility has been a major concern and substantive steps have been taken. In particular, the necessary data to run the experiments are provided at http://www.value‐cost.eu/data and data and validation results are available from the VALUE validation portal for further investigation: http://www.value‐cost.eu/validationportal.
The largest and most comprehensive to date intercomparison of statistical downscaling methods is presented, with a total of over 50 downscaling methods representative of the most common approaches and techniques. Overall, most of the downscaling methods greatly improve raw model biases and no approach is superior in general, due to the large method‐to‐method variability. The main factors influencing the results are the seasonal calibration of the methods and their stochastic nature, for biases in the mean and variance.
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