Enhancing clinical and public health interpretation of accelerometer-assessed physical activity with age-referenced values based on UK Biobank data

Purpose: Higher accelerometer-assessed volume and intensity of physical activity (PA) have been associated with a longer life expectancy but can be difficult to translate into recommended doses of PA. We aimed to: (a) improve interpretability by producing UK Biobank age-referenced centiles for PA volume and intensity; (b) inform public-health messaging by examining how adding recommended quantities of moderate and vigorous PA affect PA volume and intensity. Methods: 92,480 UK-Biobank participants aged 43-80 with wrist-worn accelerometer data were included. Average acceleration and intensity gradient were derived as proxies for PA volume and intensity. We generated sex-specific centile curves using Generalized Additive Models for Location Scale and Shape (GAMLSS) and modelled the effect of adding moderate (walking) or vigorous (running) activity on the combined change in the volume and intensity centiles (change in PA profile). Results: In men, volume was lower as age increased while intensity was lower after age 55; in women, both volume and intensity were lower as age increased. Adding 150-minutes moderate PA weekly - 5 x 30-minutes walking - increased the PA profile by 4 percentage points. Defining moderate PA as brisk walking ~doubled the increase (9 percentage points) while 75-minutes vigorous PA weekly (5 x 15-minutes running) trebled the increase (13 percentage points). Conclusion: These UK Biobank reference centiles provide a benchmark for interpretation of accelerometer data. Application of our translational methods demonstrate that meeting PA guidelines through shorter duration vigorous activity is more beneficial to the PA profile (volume and intensity) than longer duration moderate activity

Copying and Evolution of Neuronal Topology

We propose a mechanism for copying of neuronal networks that is of considerable interest for neuroscience for it suggests a neuronal basis for causal inference, function copying, and natural selection within the human brain. To date, no model of neuronal topology copying exists. We present three increasingly sophisticated mechanisms to demonstrate how topographic map formation coupled with Spike-Time Dependent Plasticity (STDP) can copy neuronal topology motifs. Fidelity is improved by error correction and activity-reverberation limitation. The high-fidelity topology-copying operator is used to evolve neuronal topologies. Possible roles for neuronal natural selection are discussed

Association of timing and balance of physical activity and rest/sleep with risk of COVID-19: a UK Biobank study

Behavioral lifestyle factors are associated with cardiometabolic disease and obesity, which are risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate whether physical activity, and the timing and balance of physical activity and sleep/rest, were associated with SARS-CoV-2 positivity and COVID-19 severity. Data from 91,248 UK Biobank participants with accelerometer data and complete covariate and linked COVID-19 data to July 19, 2020, were included. The risk of SARS-CoV-2 positivity and COVID-19 severity-in relation to overall physical activity, moderate-to-vigorous physical activity (MVPA), balance between activity and sleep/rest, and variability in timing of sleep/rest-was assessed with adjusted logistic regression. Of 207 individuals with a positive test result, 124 were classified as having a severe infection. Overall physical activity and MVPA were not associated with severe COVID-19, whereas a poor balance between activity and sleep/rest was (odds ratio [OR] per standard deviation: 0.71; 95% confidence interval [CI], 0.62 to 0.81]). This finding was related to higher daytime activity being associated with lower risk (OR, 0.75; 95% CI, 0.61 to 0.93) but higher movement during sleep/rest being associated with higher risk (OR, 1.26; 95% CI, 1.12 to 1.42) of severe infection. Greater variability in timing of sleep/rest was also associated with increased risk (OR, 1.21; 95% CI, 1.08 to 1.35). Results for testing positive were broadly consistent. In conclusion, these results highlight the importance of not just physical activity, but also quality sleep/rest and regular sleep/rest patterns, on risk of COVID-19. Our findings indicate the risk of COVID-19 was consistently approximately 1.2-fold greater per approximately 40-minute increase in variability in timing of proxy measures of sleep, indicative of irregular sleeping patterns

Comparing 24 h physical activity profiles: Office workers, women with a history of gestational diabetes and people with chronic disease condition(s)

This study demonstrates a novel data-driven method of summarising accelerometer data to profile physical activity in three diverse groups, compared with cut-point determined moderate-to-vigorous physical activity (MVPA). GGIR was used to generate average daily acceleration, intensity gradient, time in MVPA and MX metrics (acceleration above which the most active X-minutes accumulate) from wrist-worn accelerometer data from three datasets: office-workers (OW, N = 697), women with a history of post-gestational diabetes (PGD, N = 267) and adults with ≥1 chronic disease (CD, N = 1,325). Average acceleration and MVPA were lower in CD, but not PGD, relative to OW (−5.2 mg and −30.7 minutes, respectively, P < 0.001). Both PGD and CD had poorer intensity distributions than OW (P < 0.001). Application of a cut-point to the M30 showed 7%, 17% and 28%, of OW, PGD and CD, respectively, accumulated 30 minutes of brisk walking per day. Radar plots showed OW had higher overall activity than CD. The relatively poor intensity distribution of PGD, despite similar overall activity to OW, was due to accumulation of more light and less higher intensity activity. These data-driven methods identify aspects of activity that differ between groups, which may be missed by cut-point methods alone

Estimating the fitness effect of an insertion sequence

Since its discovery, mobile DNA has fascinated researchers. In particular, many researchers have debated why insertion sequences persist in prokaryote genomes and populations. While some authors think that insertion sequences persist only because of occasional beneficial effects they have on their hosts, others argue that horizontal gene transfer is strong enough to overcome their generally detrimental effects. In this study, we model the long-term fate of a prokaryote cell population, of which a small proportion of cells has been infected with one insertion sequence per cell. Based on our model and the distribution of IS5, an insertion sequence for which sufficient data is available in 525 fully sequenced proteobacterial genomes, we show that the fitness cost of insertion sequences is so small that they are effectively neutral or only slightly detrimental. We also show that an insertion sequence infection can persist and reach the empirically observed distribution if the rate of horizontal gene transfer is at least as large as the fitness cost, and that this rate is well within the rates of horizontal gene transfer observed in nature. In addition, we show that the time needed to reach the observed prevalence of IS5 is unrealistically long for the fitness cost and horizontal gene transfer rate that we computed. Occasional beneficial effects may thus have played an important role in the fast spreading of insertion sequences like IS5

Alpha-1 Antitrypsin Deficiency: New Developments in Augmentation and Other Therapies

Alpha 1 antitrypsin deficiency (AATD) is a rare cause of chronic obstructive pulmonary disease. The lung disease is thought to be caused primarily by a lack of effective protection against the harmful effects of neutrophil elastase due to the low AAT levels in the lung. Patients may also develop liver disease due to polymerisation of AAT within hepatocytes. Consequently there has been much research over the years into AAT augmentation therapy in patients with lung disease, initially intravenously, and more recently in inhaled forms. This review article will discuss the role of augmentation therapy in AATD and the current status of recombinant AAT. The potential for other therapeutic strategies, such as blocking polymer formation, enhancing autophagy, gene therapy and stem cell-based treatment, will also be discussed more briefly.</p