Serotonin–Norepinephrine Reuptake Inhibitor and Selective Serotonin Reuptake Inhibitor Use and Risk of Fractures: A New-User Cohort Study Among US Adults Aged 50 Years and Older

Antidepressants may increase the risk of fractures by disrupting sensory-motor function, thereby increasing the risk of falls, and by decreasing bone mineral density and consequently increasing the fall- or impact-related risk of fracture. Selective serotonin reuptake inhibitor (SSRI) antidepressants appear to increase fracture risk relative to no treatment, while less is known about the effect of serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants, despite SNRIs being prescribed with increasing frequency. No prior study has directly examined how fracture risk differs among patients initiating SNRIs versus those initiating SSRIs

Children’s moderate-to-vigorous physical activity on weekdays versus weekend days:A multi-country analysis

PURPOSE: The Structured Days Hypothesis (SDH) posits that children's behaviors associated with obesity - such as physical activity - are more favorable on days that contain more 'structure' (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children's moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset. METHODS: Data were received from the International Children's Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status. RESULTS/FINDINGS: Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively. CONCLUSIONS: Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active

Children’s moderate-to-vigorous physical activity on weekdays versus weekend days: a multi-country analysis

Abstract: Purpose: The Structured Days Hypothesis (SDH) posits that children’s behaviors associated with obesity – such as physical activity – are more favorable on days that contain more ‘structure’ (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children’s moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset. Methods: Data were received from the International Children’s Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status. Results/findings: Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively. Conclusions: Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Socially relevant ethnic groups, ethnic structure, and AMAR

Protracted conflicts over the status and demands of ethnic and religious groups have caused more instability and loss of human life than any other type of local, regional, and international conflict since the end of World War II. Yet we still have accumulated little in the way of accepted knowledge about the ethnic landscape of the world. In part this is due to empirical reliance on the limited data in the Minorities at Risk (MAR) project, whose selection biases are well known. In this article we tackle the construction of a list of ‘socially relevant’ ethnic groups meeting newly justified criteria in a dataset we call AMAR (A for All). We find that one of the principal difficulties in constructing the list is determining the appropriate level of aggregation for groups. To address this issue, we enumerate subgroups of the commonly recognized groups meeting our criteria so that scholars can use the subgroup list as one reference in the construction of the list of ethnic groups most appropriate for their study. Our conclusion outlines future work on the data using this expanded dataset on ethnic groups