The effect of accounting for biarticularity in hip flexor and hip extensor joint torque representations

Subject-specific torque-driven models have ignored biarticular effects at the hip. The aim of this study was to establish the contribution of monoarticular hip flexors and hip extensors to total hip flexor and total hip extensor joint torques for an individual and to investigate whether torque-driven simulation models should consider incorporating biarticular effects at the hip joint. Maximum voluntary isometric and isovelocity hip flexion and hip extension joint torques were measured for a single participant together with surface electromyography. Single-joint and two-joint representations were fitted to the collected torque data and used to determine the maximum voluntary joint torque capacity. When comparing two-joint and single-joint representations, the single-joint representation had the capacity to produce larger maximum voluntary hip flexion torque (larger by around 9% of maximum torque) and smaller maximum voluntary hip extension torque (smaller by around 33% of maximum torque) with the knee extended. Considering the range of kinematics found for jumping movements, the single-joint hip flexors had the capacity to produce around 10% additional torque, while the single joint hip extensors had about 70% of the capacity of the two-joint representation. Two-joint representations may overcome an over-simplification of single-joint representations by accounting for biarticular effects, while building on the strength of determining subject-specific parameters from measurements on the participant

Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Stomatal responses of Eucalyptus species to elevated CO2 concentration and drought stress

Five species of Eucalyptus (E. grandis, E. urophylla, E. camaldulensis, E. torelliana, and E. phaeotrica), among the ten species most commonly used in large scale plantations, were selected for studies on the effects of elevated CO2 concentration [CO2] and drought stress on stomatal responses of 2.5-month old seedlings. The first three species belong to the subgenus Smphyomyrtus, whereas the fourth species belongs to the subgenus Corymbia and E. phaeotrica is from the subgenus Monocalyptus. Seedlings were grown in four pairs of open-top chambers, arranged to have 2 plants of each species in each chamber, with four replications in each of two CO2 concentrations: 350 ± 30 mumol mol-1 and 700 ± 30 mumol mol-1. After 100 days in the chambers, a series of gas exchange measurements were made. Half the plants in each chamber, one plant per species per chamber, were drought-stressed by withholding irrigation, while the remaining plants continued to be watered daily. Drought stress decreased stomatal conductance, photosynthesis and transpiration rates in all the species. The effect of drought stress on stomatal closure was similar in both [CO2]. The positive effects of elevated [CO2] on photosynthesis and water use efficiency were maintained longer during the stress period than under well-watered conditions. The photosynthetic rate of E. phaeotrica was higher even in the fourth day of the drought stress. Drought stress increased photoinhibition of photosynthesis, as measured by chlorophyll fluorescence, which varied among the species, as well as in relation to [CO2]. The results are in agreement with observed differences in stomatal responses between some eucalyptus species of the subgenera Symphyomyrtus and Monocalyptus

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

Justify your alpha

In response to recommendations to redefine statistical significance to p ≤ .005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council