Citations

AbstractIn the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID‐19), including among patients with innate or acquired immunosuppression. However, the association between COVID‐19‐associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched‐control registry study of 143 COVID‐19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID‐19 patients with immunosuppression. We review clinical features and treatment protocols of COVID‐19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID‐19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune‐deficient and immune‐suppressed patients with COVID‐19 warrants further investigation.

World-class athletes are substantively faster, wearing marathon racing shoes with technological advancements than other shoes when competing in the marathon. Our findings suggest that technological advances in footwear contributed to the recent improvements in marathon finishing times among elite runners and in record-setting marathon performances. This investigation highlights the importance of sports analytics and may have broad implications for the regulation of running footwear during competition.

Abstract Background Across complex traits, common variants explain only a modest amount of variance, with SNP-heritability consistently below heritability estimates from close relatives. Here, we examined the contribution of rare variant to tobacco use risk in up to 26,000 individuals of European ancestry in the Trans-Omics for Precision Medicine (TOPMed) program with whole genome sequence (WGS;~30X coverage).Method We grouped about 35 million genetic variants by their minor allele frequencies (MAF) and linkage disequilibrium (LD) and estimated SNP-heritability for age of smoking initiation (N = 14,747), cigarettes smoked per day (N = 15,425), smoking cessation (N = 17,871) and initiation (N = 26,340) using linear mixed model. Rare variant population structure is detected and adjusted for by permutation procedure. We estimated an upper bound for narrow-sense heritability for tobacco use using available pedigrees consisting of close relatives in TOPMed.Results Rare variants with MAF 0.1–0.01%, mostly from non-protein altering region, accounted for 26% of variation in age of initiation and 15% for cessation. Follow-up analysis indicated that about one-third of these rare variants contribtion is potentially confounded with rare variants structure even after adjusting for principal components. After further conservative adjustment of population structure, we estimated SNP-based heritability to be 0.21 (SE = 0.08) for age of initiation, 0.15 (0.06) for cigarettes per day, 0.21 (0.09) for cessation, and 0.24 (0.07) for initiation, 1.8–4.5 times higher than previous SNP-based estimates. Our pedigree-based upper-bound for SNP-based heritability ranged from 0.18–0.35.Conclusion The substantial contribution of rare variants for several smoking phenotypes sheds light on the missing heritability and genetic etiology of tobacco use. It also informs fine-mapping strategies since the majority of the rare variant contribution was located in non-coding regulatory regions.

Environmental stressors, such as heat or altitude, elicit dissimilar physiological adaptations to endurance training programs. Whether these differences (i.e., increased hemoglobin mass vs plasma volume) differentially influence performance is debated. We review data in support of our novel hypothesis, which proposes altitude as the preferred environmental training stimulus for elite endurance athletes preparing to compete in temperate, sea-level climates (5°C–18°C).

ABSTRACT Introduction An adequate increase in minute ventilation to defend arterial oxyhemoglobin saturation (SpO 2 ) during hypoxic exercise is commonly viewed as an important factor contributing to large inter-individual variations in the degree of exercise performance impairment in hypoxia. Although the hypoxic ventilatory response (HVR) could provide insight into the underpinnings of such impairments, it is typically measured at rest under isocapnic conditions. Thus, we aimed to determine whether 1) HVR at rest and during exercise are similar and 2) exercise HVR is related to the degree of impairment in cycling time trial (TT) performance from normoxia to acute hypoxia (∆TT). Methods Sixteen endurance-trained men (V˙O 2peak , 62.5 ± 5.8 mL·kg −1 ·min −1 ) performed two poikilocapnic HVR tests: one during seated rest (HVR REST ) and another during submaximal cycling (HVR EX ). On two separate visits, subjects ( n = 12) performed a 10-km cycling TT while breathing either room air (F i O 2 = 0.21) or hypoxic gas mixture (F i O 2 = 0.16) in a randomized order. Results HVR EX was significantly ( P < 0.001) greater than HVR REST (1.52 ± 0.47 and 0.22 ± 0.13 L·min −1 ·%SpO 2 −1 , respectively), and these measures were not correlated ( r = −0.16, P = 0.57). ∆TT was not correlated with HVR REST ( P = 0.70) or HVR EX ( P = 0.54), but differences in ventilation and end-tidal CO 2 between hypoxic and normoxic TT and the ventilatory equivalent for CO 2 during normoxic TT explained ~85% of the variance in performance impairment in acute hypoxia ( P < 0.01). Conclusion We conclude that 1) HVR is not an appropriate measure to predict the exercise ventilatory response or performance impairments in acute hypoxia and 2) an adequate and metabolically matched increase in exercise ventilation, but not the gain in the ventilatory response to hypoxia, is essential for mitigating hypoxia-induced impairments in endurance cycling performance.