Citations

The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55–58% sequence diversity threshold range for genera and at the 23–36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel “filovirus.” Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences.

AbstractIntroductionThe objective of this study was to evaluate the relationship between self‐reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers.MethodsIn 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self‐reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression.ResultsNo differences in brain amyloid load, CSF Aβ42, or CSF tau were observed between low and high exercise groups. Nevertheless, when examining only those already accumulating AD pathology (i.e., amyloid positive), low exercisers had higher mean levels of brain amyloid than high exercisers. Furthermore, the interaction between exercise and estimated years from expected symptom onset was a significant predictor of brain amyloid levels.DiscussionOur findings indicate a relationship exists between self‐reported exercise levels and brain amyloid in autosomal dominant AD mutation carriers.

Job burnout is highly prevalent in graduate medical trainees. Numerous demands and stressors drive the development of burnout in this population, leading to significant and potentially tragic consequences, not only for trainees but also for the patients and communities they serve. The literature on interventions to reduce resident burnout is limited but suggests that both individual- and system-level approaches are effective. Work hours limitations and mindfulness training are each likely to have modest benefit. Despite concerns that physician trainee wellness programs might be costly, attention to physician wellness may lead to important benefits such as greater patient satisfaction, long-term physician satisfaction, and increased physician productivity. A collaborative of medical educators, academic leaders, and researchers recently formed with the goal of improving trainee well-being and mitigating burnout. Its first task is outlining this framework of initial recommendations in a call to action. These recommendations are made at the national, hospital, program, and nonwork levels and are meant to inform stakeholders who have taken up the charge to address trainee well-being. Regulatory bodies and health care systems need to be accountable for the well-being of trainees under their supervision and drive an enforceable mandate to programs under their charge. Programs and individuals should develop and engage in a “menu” of wellness options to reach a variety of learners and standardize the effort to ameliorate burnout. The impact of these multilevel changes will promote a culture where trainees can learn in settings that will sustain them over the course of their careers.

Background and objectivesExtracorporeal membrane oxygenation (ECMO) is a method of life support for either isolated cardiac failure or respiratory failure, with or without cardiac failure. When used for hemodynamic support, the ECMO circuit presents a non‐endothelialized, artificial surface to blood inciting an inflammatory response which activates haemostatic pathways. Anticoagulation may complicate a pre‐existing coagulopathy and/or inadequate surgical hemostasis of varying severity. There is no standardized method to achieve and monitor anticoagulation or guide transfusion therapy during ECMO. We tested the hypothesis that institutions across the world conduct similar management of anticoagulation and transfusion during adult ECMO support.MethodsThis is a descriptive, self‐reporting cross‐sectional survey of anticoagulation and transfusion practice for patients age 18 or older on ECMO. This 38 multiple‐choice question survey was sent to 166 institutions, internationally, utilizing adult ECMO. About 32·4% (54) of institutions responded. Responses were anonymously collected. Descriptive analyses were calculated.ResultsOur findings indicate there appears to be a significant practice variation among institutions regarding anticoagulation and transfusion during adult ECMO support.DiscussionThe lack of standard practices among institutions may reflect a paucity of data regarding optimal anticoagulation and transfusion for patients requiring ECMO. Standardized protocols for anticoagulation and transfusion may help increase quality of care for and reduce morbidity, mortality and cost to patients and healthcare centres. Further study is required for standardized, high quality care.

Skeletal muscle lymphoma is rare, comprising only a very small subset of lymphoma cases. There are characteristic imaging features which, if recognized, can prevent delay in diagnosis and treatment, particularly when not suspected clinically. Herein, we report two cases of skeletal muscle lymphoma with nearly identical imaging features; the first is an example of primary muscle lymphoma in a 17-year-old boy with back and thigh pain, and the second represents lymphoma recurrence in a 55-year-old man with HIV. Characteristic features seen on MRI were key in raising suspicion for the disease and helped prevent a delay in pathologic diagnosis.

Single-cell diversity in the brain The cells that make up an organism may all start from one genome, but somatic mutations mean that somewhere along the line of development, an organism's individual cellular genomes diverge. McConnell et al. review the implications and causes of single-cell genomic diversity for brain function. Somatic mutations caused by mobile genetic elements or errors in DNA repair may underlie certain neuropsychiatric disorders. Science , this issue p. eaal1641

Nanoliposomal irinotecan (nal‐IRI) is a liposomal formulation of irinotecan with a longer half‐life (t1/2), higher plasma total irinotecan (tIRI), and lower SN‐38 maximum concentration (Cmax) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal‐IRI was performed for tIRI and total SN‐38 (tSN38) using patient samples from six studies. PK‐safety association was evaluated for neutropenia and diarrhea in 353 patients. PK‐efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN‐38 (uSN38) above a threshold and higher Cavgof tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38Cmaxand diarrhea with tIRICmax. Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal‐IRI dose of 70 mg/m2(free‐base; equivalent to 80 mg/m2salt base) Q2W over 100 mg/m2Q3W.