Requirements for a global data infrastructure in support of CMIP6

The World Climate Research Programme (WCRP)’s Working Group on Climate Modelling (WGCM) Infrastructure Panel (WIP) was formed in 2014 in response to the explosive growth in size and complexity of Coupled Model Intercomparison Projects (CMIPs) between CMIP3 (2005–2006) and CMIP5 (2011–2012). This article presents the WIP recommendations for the global data infrastruc- ture needed to support CMIP design, future growth, and evolution. Developed in close coordination with those who build and run the existing infrastructure (the Earth System Grid Federation; ESGF), the recommendations are based on several principles beginning with the need to separate requirements, implementation, and operations. Other im- portant principles include the consideration of the diversity of community needs around data – a data ecosystem – the importance of provenance, the need for automation, and the obligation to measure costs and benefits. This paper concentrates on requirements, recognizing the diversity of communities involved (modelers, analysts, soft- ware developers, and downstream users). Such requirements include the need for scientific reproducibility and account- ability alongside the need to record and track data usage. One key element is to generate a dataset-centric rather than system-centric focus, with an aim to making the infrastruc- ture less prone to systemic failure. With these overarching principles and requirements, the WIP has produced a set of position papers, which are summa- rized in the latter pages of this document. They provide spec- ifications for managing and delivering model output, includ- ing strategies for replication and versioning, licensing, data quality assurance, citation, long-term archiving, and dataset tracking. They also describe a new and more formal approach for specifying what data, and associated metadata, should be saved, which enables future data volumes to be estimated, particularly for well-defined projects such as CMIP6. The paper concludes with a future facing consideration of the global data infrastructure evolution that follows from the blurring of boundaries between climate and weather, and the changing nature of published scientific results in the digital age

Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases

Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology

Extracorporeal adsorption therapy: A Method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies.

Purpose: Radiolabeled anti-CD20 antibodies have demonstrated impressive efficacy in the treatment of relapsed non-Hodgkin's lymphoma. However, the amount of radiation that can be delivered to eradicate the malignancy is limited by toxicity to normal organs. We examined an “extracorporeal adsorption therapy” (ECAT) method to remove circulating unbound radioimmunoconjugate and improve the ratios of radiation delivered to B-cells in a macaque model. Experimental Design: ECAT was applied with an avidin-agarose column 24 hours after an injection of 111In- or 177Lu-DOTA-biotin-rituximab (anti-CD20 antibody) to normal macaques. Two (2) animals were studied in initial blood clearance studies, and 6 additional animals were evaluated in subsequent detailed biodistribution experiments. After the injection of 111In- or 177Lu-antibody, 3 animals underwent ECAT circulating one volume/hour while 3 served as controls. Serial blood, marrow, and lymph node samples, gamma-camera images, and necropsy tissues were obtained to..

Integrative Clinical Genomics of Advanced Prostate Cancer

SummaryToward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the international collaboration of Endocarditis-Prospective Cohort Study

Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis–Prospective Cohort Study. Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non–S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39–1.15]; P = .15). Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE

Grand Challenges in Understanding the Interplay of Climate and Land Changes

Half of Earth's land surface has been altered by human activities, creating various consequences on the climate and weather systems at local to global scales, which in turn affect a myriad of land surface processes and the adaptation behaviors. This study reviews the status and major knowledge gaps in the interactions of land and atmospheric changes and present 11 grand challenge areas for the scientific research and adaptation community in the coming decade. These land-cover and land-use change (LCLUC)-related areas include 1) impacts on weather and climate, 2) carbon and other biogeochemical cycles, 3) biospheric emissions, 4) the water cycle, 5) agriculture, 6) urbanization, 7) acclimation of biogeochemical processes to climate change, 8) plant migration, 9) land-use projections, 10) model and data uncertainties, and, finally, 11) adaptation strategies. Numerous studies have demonstrated the effects of LCLUC on local to global climate and weather systems, but these putative effects vary greatly in magnitude and even sign across space, time, and scale and thus remain highly uncertain. At the same time, many challenges exist toward improved understanding of the consequences of atmospheric and climate change on land process dynamics and services. Future effort must improve the understanding of the scale-dependent, multifaceted perturbations and feedbacks between land and climate changes in both reality and models. To this end, one critical cross-disciplinary need is to systematically quantify and better understand measurement and model uncertainties. Finally, LCLUC mitigation and adaptation assessments must be strengthened to identify implementation barriers, evaluate and prioritize opportunities, and examine how decisionmaking processes work in specific contexts