Highly variable upper and abyssal overturning cells in the South Atlantic

The Meridional Overturning Circulation (MOC) is a primary mechanism driving oceanic heat redistribution on Earth, thereby affecting Earth’s climate and weather. However, the full-depth structure and variability of the MOC are still poorly understood, particularly in the South Atlantic. This study presents unique multiyear records of the oceanic volume transport of both the upper (~3100 meters) overturning cells based on daily moored measurements in the South Atlantic at 34.5°S. The vertical structure of the time-mean flows is consistent with the limited historical observations. Both the upper and abyssal cells exhibit a high degree of variability relative to the temporal means at time scales, ranging from a few days to a few weeks. Observed variations in the abyssal flow appear to be largely independent of the flow in the overlying upper cell. No meaningful trends are detected in either cell.Fil: Kersalé, Marion. National Ocean And Atmospheric Administration; Estados Unidos. University of Miami; Estados UnidosFil: Meinen, Christopher S.. National Ocean And Atmospheric Administration; Estados UnidosFil: Perez, Renellys C.. National Ocean And Atmospheric Administration; Estados UnidosFil: Le Hénaff, Matthieu. National Ocean And Atmospheric Administration; Estados Unidos. University of Miami; Estados UnidosFil: Valla, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; ArgentinaFil: Lamont, Tarron. University of Cape Town; SudáfricaFil: Sato, Olga T.. Universidade de Sao Paulo; BrasilFil: Dong, Shenfu. National Ocean And Atmospheric Administration; Estados UnidosFil: Terre, T.. University of Brest; Francia. Centre National de la Recherche Scientifique; FranciaFil: van Caspel, M.. Universidade de Sao Paulo; BrasilFil: Chidichimo, María Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; ArgentinaFil: van den Berg, Marcel Alexander. Department of Environmental Affairs; SudáfricaFil: Speich, Sabrina. University Of Cape Town; SudáfricaFil: Piola, Alberto Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ecole Normale Superieure. Laboratoire de Meteorologie Dynamique; Francia. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; Argentina. Universidad de Buenos Aires; ArgentinaFil: Campos, Edmo. Universidade de Sao Paulo; Brasil. American University Of Sharjah.; Emiratos Árabes UnidosFil: Ansorge, Isabelle. University of Cape Town; SudáfricaFil: Volkov, Denis L.. University of Miami; Estados Unidos. National Ocean And Atmospheric Administration; Estados UnidosFil: Lumpkin, Rick. National Ocean And Atmospheric Administration; Estados UnidosFil: Garzoli, S. L.. University of Miami; Estados Unidos. National Ocean And Atmospheric Administration; Estados Unido

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Prognostic Model to Predict Post-Autologous Stem-Cell Transplantation Outcomes in Classical Hodgkin Lymphoma

Purpose: Our aim was to capture the biology of classical Hodgkin lymphoma (cHL) at the time of relapse and discover novel and robust biomarkers that predict outcomes after autologous stem-cell transplantation (ASCT). Materials and Methods: We performed digital gene expression profiling on a cohort of 245 formalin-fixed, paraffin-embedded tumor specimens from 174 patients with cHL, including 71 with biopsies taken at both primary diagnosis and relapse, to investigate temporal gene expression differences and associations with post-ASCT outcomes. Relapse biopsies from a training cohort of 65 patients were used to build a gene expression-based prognostic model of post-ASCT outcomes (RHL30), and two independent cohorts were used for validation. Results: Gene expression profiling revealed that 24% of patients exhibited poorly correlated expression patterns between their biopsies taken at initial diagnosis and relapse, indicating biologic divergence. Comparative analysis of the prognostic power of gene expression measurements in primary versus relapse specimens demonstrated that the biology captured at the time of relapse contained superior properties for post-ASCT outcome prediction. We developed RHL30, using relapse specimens, which identified a subset of high-risk patients with inferior post-ASCT outcomes in two independent external validation cohorts. The prognostic power of RHL30 was independent of reported clinical prognostic markers (both at initial diagnosis and at relapse) and microenvironmental components as assessed by immunohistochemistry. Conclusion: We have developed and validated a novel clinically applicable prognostic assay that at the time of first relapse identifies patients with unfavorable post-ASCT outcomes. Moving forward, it will be critical to evaluate the clinical use of RHL30 in the context of positron emission tomography-guided response assessment and the evolving cHL treatment landscape

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

P2Y12-inhibitor monotherapy after coronary stenting: are all P2Y12-inhibitors equal?

Introduction: P2Y12-inhibitor monotherapy following 1–3 months of dual antiplatelet therapy (DAPT) reduces (major) bleeding without an apparent increase in ischemic events and has therefore emerged as an alternative to 6–12 months of DAPT following percutaneous coronary intervention (PCI). However, there are important differences between the available P2Y12-inhibitors (clopidogrel, prasugrel, and ticagrelor) as agents of choice for P2Y12-inhibitor monotherapy. Areas covered: This review critically appraises the evidence for P2Y12-inhibitor monotherapy after PCI using either clopidogrel, prasugrel, or ticagrelor. Furthermore, we discuss ongoing trials and future directions for research. Expert opinion: P2Y12-inhibitor monotherapy following 1–3 months of DAPT is an alternative to 6–12 months of DAPT following PCI. Ticagrelor may be considered the current preferred option due to its reliable effect on platelet reactivity and its predominant use in clinical trials. Prasugrel could serve as a useful substitute for those not tolerating ticagrelor, but more research into prasugrel monotherapy is warranted. Alternatively, clopidogrel can be used, although there are concerns of high platelet reactivity, especially when genotyping and/or platelet function testing are not used. Future research will need to address the minimal duration of DAPT before switching to P2Y12-inhibitor monotherapy and what the optimal antithrombotic therapy beyond 12 months is

P2Y12-inhibitor monotherapy after coronary stenting: are all P2Y12-inhibitors equal?

Introduction: P2Y12-inhibitor monotherapy following 1–3 months of dual antiplatelet therapy (DAPT) reduces (major) bleeding without an apparent increase in ischemic events and has therefore emerged as an alternative to 6–12 months of DAPT following percutaneous coronary intervention (PCI). However, there are important differences between the available P2Y12-inhibitors (clopidogrel, prasugrel, and ticagrelor) as agents of choice for P2Y12-inhibitor monotherapy. Areas covered: This review critically appraises the evidence for P2Y12-inhibitor monotherapy after PCI using either clopidogrel, prasugrel, or ticagrelor. Furthermore, we discuss ongoing trials and future directions for research. Expert opinion: P2Y12-inhibitor monotherapy following 1–3 months of DAPT is an alternative to 6–12 months of DAPT following PCI. Ticagrelor may be considered the current preferred option due to its reliable effect on platelet reactivity and its predominant use in clinical trials. Prasugrel could serve as a useful substitute for those not tolerating ticagrelor, but more research into prasugrel monotherapy is warranted. Alternatively, clopidogrel can be used, although there are concerns of high platelet reactivity, especially when genotyping and/or platelet function testing are not used. Future research will need to address the minimal duration of DAPT before switching to P2Y12-inhibitor monotherapy and what the optimal antithrombotic therapy beyond 12 months is