Ground Contact Time Imbalances Strongly Related to Impaired Running Economy

Running economy (RE) is defined as the oxygen consumption (VO2) or caloric unit cost required to move at a specific velocity and is an important performance marker. Ground contact time (GCT) has been associated with RE; however, it has not been established how GCT imbalances between feet impact RE. Purpose: Determine the relationship between cadence, GCT, and GCT imbalances and RE. Methods: 11 NCAA Division I distance runners (7 male) completed a graded exercise test on a treadmill to determine lactate threshold (LT) and VO2max. Body composition was also assessed via DEXA. Subjects ran with a heart rate monitor capable of measuring cadence, GCT, and GCT balance between feet. VO2 and respiratory exchange ratio were recorded over the last minute of the 5-minute stages. RE expressed as caloric unit cost (kcal·kg-1· km-1) was calculated for the stage determined to be just below the LT (prior to \u3e 4mmol/L) and was correlated with cadence, GCT, and GCT imbalance by Pearson correlations. Results: Pearson correlations between RE and the running dynamics measures were as follows: cadence (r = -.444, p = .171), GCT (r = .492, p = .125), GCT Imbalance (r = .808, p \u3c .005). An independent t-test revealed greater (p = .023) leg lean mass imbalances in runners with larger GCT imbalances compared to runners with smaller GCT imbalances. Conclusion: GCT imbalances are strongly related to impaired RE. Future research should determine how to improve GCT imbalances and if doing so improves RE

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Tropical Atlantic bamboo corals bomb radiocarbon and nitrogen isotopes

Deep-sea bamboo corals (family Isididae) have been used as archives for reconstructing changes in the past ocean. However, uncertainties remain regarding the interpretation of geochemical signals from their organic nodes, specifically the water depth of the signals recorded by the coral. Here we explore this question by measuring 14C and 15N compositions of six bamboo corals collected from the central and eastern tropical Atlantic between 700 m and 2000 m water depth. By comparing coral 14C to measured seawater data, regional shallow-water coral records and climate-model outputs, we find contrasting results. Our bamboo coral 14C results from the eastern tropical Atlantic support previous studies that suggest organic node carbon is sourced primarily from the upper mixed layer of the ocean. By contrast, bamboo corals from the oligotrophic central Atlantic suggests that organic node radiocarbon records the Δ14C of the deep chlorophyll maximum layer rather than the surface mixed layer. Combined with δ15N data, this observation suggests that sinking and/or ambient zooplankton supported by phytoplankton from the deep chlorophyll maximum layer can contribute a significant proportion of the diet of bamboo corals. These results suggest that the age models of bamboo corals residing beneath oligotrophic regions should not be determined from mixed layer Δ14C. Radiocarbon analyses were conducted at the Bristol Radiocarbon Accelerator Mass Spectrometry (BRAMS) Facility at the University of Bristol following the procedure of Knowles et al. (2019, doi:10.1017/RDC.2019.28). δ15N were gently ground to homogenise, weighed out into 0.5 - 1 mg aliquots into 3.5 × 5 mm tin capsules (part #041060) from Costech Analytical Technologies, Inc and sent out for the δ15N analyses to the Center for Stable Isotope Biogeochemistry (CSIB), University of California Berkeley

A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

© 2018 The Author(s). We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library in just a few hours, evaluating each along multiple performance axes. To demonstrate the power of this approach, we created a genetically encoded fluorescent voltage indicator, simultaneously optimizing its brightness and membrane localization using our microscopy-guided cell-picking strategy. We produced the high-performance opsin-based fluorescent voltage reporter Archon1 and demonstrated its utility by imaging spiking and millivolt-scale subthreshold and synaptic activity in acute mouse brain slices and in larval zebrafish in vivo. We also measured postsynaptic responses downstream of optogenetically controlled neurons in C. elegans

Climate refugia: joint inference from fossil records, species distribution models, and phylogeography

Climate refugia, locations where taxa survive periods of regionally adverse climate, are thoughtto be critical for maintaining biodiversity through the glacial–interglacial climate changes of theQuaternary. A critical research need is to better integrate and reconcile the three major lines ofevidence used to infer the existence of past refugia – fossil records, species distribution modelsand phylogeographic surveys – in order to characterize the complex spatiotemporal trajectoriesof species and populations in and out of refugia. Here we review the complementary strengths,limitations and new advances for these three approaches. We provide case studies to illustratetheir combined application, and point the way towards new opportunities for synthesizing thesedisparate lines of evidence. Case studies with European beech, Qinghai spruce and Douglas-firillustrate how the combination of these three approaches successfully resolves complex specieshistories not attainable from any one approach. Promising new statistical techniques cancapitalize on the strengths of each method and provide a robust quantitative reconstruction ofspecies history. Studying past refugia can help identify contemporary refugia and clarify theirconservation significance, in particular by elucidating the fine-scale processes and the particulargeographic locations that buffer species against rapidly changing climate