Academic chartered data safety committees versus industry sponsored data safety committees: The need for different recommendations

Dear Editor, We read with great interest the recently published paper by Calis et al.1 We applaud the authors and the working group for developing this important set of recommendations for data monitoring committees (DMC). Recommendations for organizing a DMC are long overdue. Our academic institution has had a formal DMC for many years which administratively reports to an academic official who directs the research efforts. It has a formal charter and broad membership that includes clinicians, clinical trial specialists, and a biostatistician. It accepts for review studies that require a DMC (usually phase II or III trials) and are not sponsored by industry, which usually set up their own DMC. Most studies are supported by the institution, US Government research funding sources (e.g. National Institutes of Health (NIH), Centers for Disease Control and Prevention), or research foundations

Classifying medical histories in US medicare beneficiaries using fixed vs all‐available look‐back approaches

Purpose: Evaluate use of fixed and all‐available look‐backs to identify eligibility criteria and confounders among Medicare beneficiaries. Methods: We identified outpatient visits (2007‐2012) with recently documented (≤180 days) cardiovascular risk and classified patients according to whether the exposure (statin) was initiated within 14 days. We selected each beneficiary's first eligible visit (in each treatment group) that met criteria during the respective look‐backs: continuous enrollment (1 or 3 years for fixed look‐back; 180 days for all‐available), no cancer history, and no statin claims. We estimated crude and standardized mortality ratio weighted hazard ratios (HRs) for the effect of statin initiation on incident 6‐month cancer (a known null effect) and 2‐year mortality, separately, adjusting for covariates assessed by using each look‐back. Results: Analyzing short‐term cancer, the estimated HR from the all‐available approach (HR = 0.90, 95% CI: 0.83, 0.98) was less biased than the 1‐year look‐back (HR = 0.79, 95% CI: 0.73, 0.84), which included beneficiaries with prevalent cancer. The 3‐year look‐back (HR = 1.05, 95% CI: 0.90, 1.21) was somewhat less biased than the all‐available estimate but less precise due the exclusion of a large proportion of observations without sufficient continuous enrollment (62.0% and 59.9% of initiators and non‐initiators, respectively). All approaches produced similar estimates of the effect on all‐cause mortality. Alternative look‐backs did not differ in their ability to control confounding. Conclusions: The all‐available look‐back performed nearly as well as the 3‐year fixed, which produced the least biased point estimate. If 3‐year look‐backs are infeasible (eg, due to power/sample), all‐available look‐backs may be preferable to short (1‐year) fixed look‐backs

Combination therapy improves survival after acute myocardial infarction in the elderly with chronic kidney disease

Background: Individuals with chronic kidney disease have a high mortality rate after acute myocardial infarction. It is not known how frequently these individuals are prescribed combination cardioprotective therapy and if survival is affected by such therapy after acute myocardial infarction. Methods: A retrospective cohort study of 1,342 Medicare recipients with acute myocardial infarction. Data were collected by medical chart abstraction as part of the Cooperative Cardiovascular Project in 60 hospitals in North Carolina during 5/30/1996-12/28/1997. We categorized cardioprotective medication use as aspirin alone, aspirin with beta-blockers, and aspirin with beta-blockers and ace-inhibitors. Chronic kidney disease was defined as a derived glomerular filtration rate (GFR) ranging from 15-89 mL/min/1.73 m2. Cox proportional hazards regression analyses were performed to determine the effect of cardioprotective medication use on survival while controlling for potential explanatory variables. Results: The prevalence of cardioprotective medication use differed among levels of chronic kidney disease. Those with severe kidney disease (GFR 15-29 mL/min/1.73 m2) were less frequently prescribed aspirin with beta-blockers, 27.1%, and only 8.6% were prescribed aspirin with beta-blockers and ace-inhibitors. Survival was improved with prescribed cardioprotective medication use. In severe kidney disease (GFR 15-29 mL/min/1.73 m2), the hazards risk for death was 0.21 (0.08, 0.53) for aspirin alone, 0.17 (0.06, 0.51) for aspirin with beta-blockers, and 0.35 (0.09, 1.42) for aspirin with beta-blockers and ace-inhibitors. Conclusions: Individuals with chronic kidney disease benefit from combination cardioprotective therapy, but are less likely to be prescribed them after acute myocardial infarction. Further investigation is warranted to identify possible reasons for these observed treatment disparities

Is the Sun Embedded in a Typical Interstellar Cloud?

The physical properties and kinematics of the partially ionized interstellar material near the Sun are typical of warm diffuse clouds in the solar vicinity. The interstellar magnetic field at the heliosphere and the kinematics of nearby clouds are naturally explained in terms of the S1 superbubble shell. The interstellar radiation field at the Sun appears to be harder than the field ionizing ambient diffuse gas, which may be a consequence of the low opacity of the tiny cloud surrounding the heliosphere. The spatial context of the Local Bubble is consistent with our location in the Orion spur.Comment: "From the Outer Heliosphere to the Local Bubble", held at International Space Sciences Institute, October 200

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

History of clinical transplantation

How transplantation came to be a clinical discipline can be pieced together by perusing two volumes of reminiscences collected by Paul I. Terasaki in 1991-1992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLAs) that are widely used today for tissue matching.1 The other focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration in the mid-1940s by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 © 2008 Springer New York

A MODEST review

We present an account of the state of the art in the fields explored by the research community invested in 'Modeling and Observing DEnse STellar systems'. For this purpose, we take as a basis the activities of the MODEST-17 conference, which was held at Charles University, Prague, in September 2017. Reviewed topics include recent advances in fundamental stellar dynamics, numerical methods for the solution of the gravitational N-body problem, formation and evolution of young and old star clusters and galactic nuclei, their elusive stellar populations, planetary systems, and exotic compact objects, with timely attention to black holes of different classes of mass and their role as sources of gravitational waves. Such a breadth of topics reflects the growing role played by collisional stellar dynamics in numerous areas of modern astrophysics. Indeed, in the next decade, many revolutionary instruments will enable the derivation of positions and velocities of individual stars in the Milky Way and its satellites and will detect signals from a range of astrophysical sources in different portions of the electromagnetic and gravitational spectrum, with an unprecedented sensitivity. On the one hand, this wealth of data will allow us to address a number of long-standing open questions in star cluster studies; on the other hand, many unexpected properties of these systems will come to light, stimulating further progress of our understanding of their formation and evolution.Comment: 42 pages; accepted for publication in 'Computational Astrophysics and Cosmology'. We are much grateful to the organisers of the MODEST-17 conference (Charles University, Prague, September 2017). We acknowledge the input provided by all MODEST-17 participants, and, more generally, by the members of the MODEST communit

Electron and photon energy calibration with the ATLAS detector using LHC Run 2 data

This paper presents the electron and photon energy calibration obtained with the ATLAS detector using 140 fb-1 of LHC proton-proton collision data recorded at √(s) = 13 TeV between 2015 and 2018. Methods for the measurement of electron and photon energies are outlined, along with the current knowledge of the passive material in front of the ATLAS electromagnetic calorimeter. The energy calibration steps are discussed in detail, with emphasis on the improvements introduced in this paper. The absolute energy scale is set using a large sample of Z-boson decays into electron-positron pairs, and its residual dependence on the electron energy is used for the first time to further constrain systematic uncertainties. The achieved calibration uncertainties are typically 0.05% for electrons from resonant Z-boson decays, 0.4% at ET ∼ 10 GeV, and 0.3% at ET ∼ 1 TeV; for photons at ET ∼ 60 GeV, they are 0.2% on average. This is more than twice as precise as the previous calibration. The new energy calibration is validated using J/ψ → ee and radiative Z-boson decays