Cardiometabolic responses of body-weight exercises with and without vibration

This investigation examined the interactive effect of body-weight (BW) exercises and vibration on cardiometabolic responses. Fourteen subjects performed a BW exercise protocol with (BW+V) and without (BW‒V) vibration in a randomized order. The BW exercise protocol consisted of three circuits of eight calisthenics-based exercises including prisoner squat, push-up, isometric squat, reverse dip, lunge, flutter kicks, isometric lunge, and T push-up. Vibratory frequency and amplitude were set at 40 Hz and 4 mm, respectively. Oxygen uptake (VO2), heart rate (HR), expired ventilation (VE), and blood lactate [La] were determined during the protocol and 30-minute recovery. The mean VO2 reached 48% and 50% of VO2max and the mean HR reached 80% and 83% of HRmax in BW‒V and BW+V, respectively. During the protocol, while the mean VE was greater (p=.031) in BW+V than BW‒V, no differences were seen for VO2 and HR between the two conditions. During recovery, while mean VO2 was greater (p=.002) in BW+V than BW-V, no differences were seen for VE and HR between the two conditions. [La] values were significantly elevated but remained similar between the two conditions. Exercise-specific VO2 was higher during the prisoner squat (p=.003) and isometric squat (p=.042) in BW+V than BW‒V, while no differences in VO2 were observed for all other exercises. Performing three circuits of eight BW exercises in a rapid-and-intense manner produced a sufficient increase in cardiometabolic responses. Metabolic potentiation associated with combining vibration with BW exercises seemed to be influenced by how the exercises were carried out on a vibration plate

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

‘Everyone thought I was a very very bad person… no one want to know you like the nurses and doctors’:using focus groups to elicit the views of adults with learning disability who use challenging behaviour services

and Tables S1–S3. (PDF 3090 kb

An epigenetic clock for gestational age at birth based on blood methylation data

Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances.Peer reviewe

Response scale selection in adult pain measures: results from a literature review

Abstract Background The purpose of this literature review was to examine the existing patient-reported outcome measurement literature to understand the empirical evidence supporting response scale selection in pain measurement for the adult population. Methods The search strategy involved a comprehensive, structured, literature review with multiple search objectives and search terms. Results The searched yielded 6918 abstracts which were reviewed against study criteria for eligibility across the adult pain objective. The review included 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles providing insights into optimal response scale selection for pain assessment in the adult population. Based on the extensive and varied literature on pain assessments, the adult pain studies typically use simple response scales with single-item measures of pain—a numeric rating scale, visual analog scale, or verbal rating scale. Across 42 review articles, consensus guidelines, expert opinion pieces, and primary research articles, the NRS response scale was most often recommended in these guidance documents. When reviewing the empirical basis for these recommendations, we found that the NRS had slightly superior measurement properties (e.g., reliability, validity, responsiveness) across a wide variety of contexts of use as compared to other response scales. Conclusions Both empirical studies and review articles provide evidence that the 11-point NRS is likely the optimal response scale to evaluate pain among adult patients without cognitive impairment

Cohort profile: the ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS)

PurposeExposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations.ParticipantsThe ECHO-PATHWAYS consortium harmonises extant data from 2684 mother-child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5-15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083).Findings to dateEarly analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution.Future plansThe first wave of data from the unified protocol (child age 8-9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms

Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns

Importance: Preeclampsia, gestational hypertension, and gestational diabetes, the most common pregnancy complications, are associated with substantial morbidity and mortality in mothers and children. Little is known about the biological processes that link the occurrence of these pregnancy complications with adverse child outcomes; altered biological aging of the growing fetus up to birth is one molecular pathway of increasing interest. Objective: To evaluate whether exposure to each of these 3 pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia) is associated with accelerated or decelerated gestational biological age in children at birth.Design, Setting, and Participants: Children included in these analyses were born between 1998 and 2018 and spanned multiple geographic areas of the US. Pregnancy complication information was obtained from maternal self-report and/or medical record data. DNA methylation measures were obtained from blood biospecimens collected from offspring at birth. The study used data from the national Environmental Influences on Child Health Outcomes (ECHO) multisite cohort study collected and recorded as of the August 31, 2021, data lock date. Data analysis was performed from September 2021 to December 2022. Exposures: Three pregnancy conditions were examined: gestational hypertension, preeclampsia, and gestational diabetes.Main Outcomes and Measures: Accelerated or decelerated biological gestational age at birth, estimated using existing epigenetic gestational age clock algorithms.Results: A total of 1801 child participants (880 male [48.9%]; median [range] chronological gestational age at birth, 39 [30-43] weeks) from 12 ECHO cohorts met the analytic inclusion criteria. Reported races included Asian (49 participants [2.7%]), Black (390 participants [21.7%]), White (1026 participants [57.0%]), and other races (92 participants [5.1%]) (ie, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, multiple races, and other race not specified). In total, 524 participants (29.0%) reported Hispanic ethnicity. Maternal ages ranged from 16 to 45 years of age with a median of 29 in the analytic sample. A range of maternal education levels, from less than high school (260 participants [14.4%]) to Bachelor's degree and above (629 participants [34.9%]), were reported. In adjusted regression models, prenatal exposure to maternal gestational diabetes (β, -0.423; 95% CI, -0.709 to -0.138) and preeclampsia (β, -0.513; 95% CI, -0.857 to -0.170), but not gestational hypertension (β, 0.003; 95% CI, -0.338 to 0.344), were associated with decelerated epigenetic aging among exposed neonates vs those who were unexposed. Modification of these associations, by sex, was observed with exposure to preeclampsia (β, -0.700; 95% CI, -1.189 to -0.210) and gestational diabetes (β, -0.636; 95% CI, -1.070 to -0.200), with associations observed among female but not male participants.Conclusions and Relevance: This US cohort study of neonate biological changes related to exposure to maternal pregnancy conditions found evidence that preeclampsia and gestational diabetes delay biological maturity, especially in female offspring.</p

Cardiometabolic Pregnancy Complications in Association with Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD), but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental influences on Child Health Outcomes (ECHO) program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale (SRS). Four metabolic pregnancy complications were examined individually, and combined, in association with SRS scores, using crude and adjusted linear regression as well as quantile regression. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß=4.64, 95% CI 3.27, 6.01) and gestational diabetes (ß=5.21, 95% CI 2.41, 8.02) specifically, but not with hypertension or preeclampsia. Results in children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits not only above a diagnostic threshold relevant to ASD, but also across the population