The impact of image and performance enhancing drugs on atrial structure and function in resistance trained individuals.

BACKGROUND: Image and performance enhancing drugs (IPEDs) are commonly used in resistance trained (RT) individuals and negatively impact left ventricular (LV) structure and function. Few studies have investigated the impact of IPEDs on atrial structure and function with no previous studies investigating bi-atrial strain. Additionally, the impact of current use vs. past use of IPEDs is unclear. METHODS: Utilising a cross-sectional design, male (n = 81) and female (n = 15) RT individuals were grouped based on IPED user status: current (n = 57), past (n = 19) and non-users (n = 20). Participants completed IPED questionnaires, anthropometrical measurements, electrocardiography, and transthoracic echocardiography with strain imaging. Structural cardiac data was allometrically scaled to body surface area (BSA) according to laws of geometric similarity. RESULTS: Body mass and BSA were greater in current users than past and non-users of IPEDs (p < 0.01). Absolute left atrial (LA) volume (60 ± 17 vs 46 ± 12, p = 0.001) and right atrial (RA) area (19 ± 4 vs 15 ± 3, p < 0.001) were greater in current users than non-users but this difference was lost following scaling (p > 0.05). Left atrial reservoir (p = 0.008, p < 0.001) and conduit (p < 0.001, p < 0.001) strain were lower in current users than past and non-users (conduit: current = 22 ± 6, past = 29 ± 9 and non-users = 31 ± 7 and reservoir: current = 33 ± 8, past = 39 ± 8, non-users = 42 ± 8). Right atrial reservoir (p = 0.015) and conduit (p = 0.007) strain were lower in current than non-users (conduit: current = 25 ± 8, non-users = 33 ± 10 and reservoir: current = 36 ± 10, non-users = 44 ± 13). Current users showed reduced LV diastolic function (A wave: p = 0.022, p = 0.049 and E/A ratio: p = 0.039, p < 0.001) and higher LA stiffness (p = 0.001, p < 0.001) than past and non-users (A wave: current = 0.54 ± 0.1, past = 0.46 ± 0.1, non-users = 0.47 ± 0.09 and E/A ratio: current = 1.5 ± 0.5, past = 1.8 ± 0.4, non-users = 1.9 ± 0.4, LA stiffness: current = 0.21 ± 0.7, past = 0.15 ± 0.04, non-users = 0.15 ± 0.07). CONCLUSION: Resistance trained individuals using IPEDs have bi-atrial enlargement that normalises with allometric scaling, suggesting that increased size is, in part, associated with increased body size. The lower LA and RA reservoir and conduit strain and greater absolute bi-atrial structural parameters in current than non-users of IPEDs suggests pathological adaptation with IPED use, although the similarity in these parameters between past and non-users suggests reversibility of pathological changes with withdrawal.

Agreement of Two Physical Behaviour Monitors for Characterising Posture and Stepping in Children Aged 6-12 Years.

All new physical behaviour measurement devices should be assessed for compatibility with previous devices. Agreement was assessed between the activPAL4TM and activPAL3TM physical behavior monitors within a laboratory and a multi-day free-living context. Healthy children aged 6-12 years performed standardised (sitting, standing, stepping) (12 min) and non-standardised (6 min) activities in a laboratory and a multi-day (median 3 days) free-living assessment whilst wearing both monitors. Agreement was assessed using Bland-Altman plots, sensitivity, and the positive predictive value (PPV). There were 15 children (7M/8F, 8.4 ± 1.8 years old) recruited. For the laboratory-based standardised activities, sitting time, stepping time, and fast walking/jogging step count were all within ±5% agreement. However, the activPAL4TM standing time was lower (-6.4%) and normal speed walking step count higher (+7.8%) than those of the activPAL3TM. For non-standardised activities, a higher step count was recorded by the activPAL4TM (+4.9%). The standardised activity sensitivity and PPV were all >90%, but the non-standardised activity values were lower. For free-living agreement, the standing time was lower (-7.6%) and step count higher (all steps + 2.2%, steps with cadence >100 step/min + 6.6%) for the activPAL4TM than the activPAL3TM. This study highlights differences in outcomes as determined by the activPAL4TM and activPAL3TM, which should be considered when comparing outcomes between studies.

Full-Day Physical Activity and Sedentary Behaviour Levels of Typically Developing Children and Adolescents in the Middle East: A Systematic Review.

Physical activity (PA) and sedentary behaviour (SB) are important components of physical behaviour associated with long-term health outcomes. Environmental and cultural factors may influence physical behaviour. To explore full day PA and SB in children and adolescents (2-18 years old) in the Middle East, a systematic literature review was performed including 183 journal articles. A wide range of PA and SB outcomes were reported, in some cases making synthesis of results difficult. As a consequence, results were generally reported narratively (MVPA time, total PA, SB time). Meta-regression of daily step count revealed females took 4600 fewer steps than males, with 3000 fewer steps on weekdays than weekends, and overweight individuals taking 2800 fewer steps/day. Steps decreased with age. Meta-regression for TV viewing time demonstrated an increase by 0.04 h per year of age. Even though environmental and cultural conditions may be different, PA and SB of children and adolescents in the Middle East were largely comparable to those of Europeans and North Americans. The wide range of data collection instruments used (both self-report questionnaire and body-worn devices) and heterogeneity of data made synthesis of reported data across studies very difficult, suggesting a need for greater standardisation of data collection methods.

Validity and Reliability of the activPAL4TM for Measurement of Body Postures and Stepping Activity in 6-12-Year-Old Children.

A link between inappropriate physical behaviour patterns (low physical activity and high sedentary behaviour) and poor health outcomes has been observed. To provide evidence to quantify this link, it is important to have valid and reliable assessment tools. This study aimed to assess the validity and reliability of the activPAL4TM monitor for distinguishing postures and measuring stepping activity of 6-12-year-old children. Thirteen children (8.5 ± 1.8 years) engaged in pre-determined standardised (12 min) and non-standardised (6 min) activities. Agreement, specificity and positive predictive value were assessed between the activPAL4TM and direct observation (DO) (nearest 0.1 s). Between-activPAL4TM (inter-device) and between-observer (inter-rater) reliability were determined. Detection of sitting and stepping time and forward purposeful step count were all within 5% of DO. Standing time was slightly overestimated (+10%) and fast walking/jogging steps underestimated (-20%). For non-standardised activities, activPAL4TM step count matched most closely to combined backward and forward purposeful steps; however, agreement varied widely. The activPAL4TM demonstrated high levels of reliability (ICC(1, 1) > 0.976), which were higher in some instances than could be achieved through direct observation (ICC(2, 1) > 0.851 for non-standardised activities). Overall, the activPAL4TM recorded standardised activities well. However, further work is required to establish the exact nature of steps counted by the activPAL4TM.

Development of Human Pituitary Neuroendocrine Tumor Organoids to Facilitate Effective Targeted Treatments of Cushing's Disease.

(1) Background: Cushing's disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient's tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients.

Generation of an iPSC line from a Pontocerebellar Hypoplasia 1B patient harboring a homozygous c.395 A > C mutation in EXOSC3 along with a family matched control.

Pontocerebellar Hypoplasia 1B (PCH1B) is a severe autosomal recessive neurological disorder that is associated with mutations in the exosome complex component RRP40 (EXOSC3) gene. We generated and characterized an iPSC line from an individual with PCH1B that harbors a recessive homozygous c.395 A > C mutation in EXOSC3 and a family matched control from the probands unaffected mother. Each iPSC line presents with normal morphology and karyotype and express high levels of pluripotent markers. UAZTi009-A and UAZTi011-A are capable of directed differentiation and can be used as a vital experimental tool to study the development of PCH1B.

Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.

The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure. Specifically, transcriptome changes were identified in the tumor necrosis factor (TNF), interferon α/ß, and mitogen-activated protein kinase (MAPK) (hPSC-CMs) as well as nuclear factor kappa-B (NF-κB) (hECs) signaling pathways. However, pre-treatment of hPSC-CMs or hECs with two widely prescribed antihypertensive medications, losartan and lisinopril, did not affect the susceptibility of either cell type to SARS-CoV-2 infection. These findings demonstrate the toxic effects of SARS-CoV-2 in hPSC-CMs/hECs and, taken together with newly emerging multicenter trials, suggest that antihypertensive drug treatment alone does not alter SARS-CoV-2 infection.

Quantifying upper limb tremor in people with multiple sclerosis using Fast Fourier Transform based analysis of wrist accelerometer signals.

INTRODUCTION: Tremor is a disabling symptom of Multiple Sclerosis (MS). The development of objective methods of tremor characterisation to assess intervention efficacy and disease progression is therefore important. The possibility of using a Fast Fourier Transform (FFT) method for tremor detection was explored. METHODS: Acceleration from a wrist-worn device was analysed using FFTs to identify and characterise tremor magnitude and frequency. Processing parameters were explored to provide insight into the optimal algorithm. Participants wore a wrist tri-axial accelerometer during 9 tasks. The FAHN clinical assessment of tremor was used as the reference standard. RESULTS: Five people with MS and tremor (57.6 ± 15.3 years, 3 F/2M) and ten disease-free controls (42.4 ± 10.9 years, 5 M/5F) took part. Using specific algorithm settings tremor identification was possible (peak frequency 3-15Hz; magnitude greater than 0.06 g; 2 s windows with 50% overlap; using 2 of 3 axes of acceleration), giving sensitivity 0.974 and specificity 0.971 (38 tremor occurrences out of 108 tasks, 1 false positive, 2 false negatives). Tremor had frequency 3.5-13.0 Hz and amplitude 0.07-2.60g. CONCLUSIONS: Upper limb tremor in people with MS can be detected using a FFT approach based on acceleration recorded at the wrist, demonstrating the possibility of using this minimally encumbering technique within clinical practice.

Dynamic Profiling of Protein Mole Synthesis Rates during C2C12 Myoblast Differentiation.

Mole (MSR) and fractional (FSR) synthesis rates of proteins during C2C12 myoblast differentiation are investigated. Myoblast cultures supplemented with D2 O during 0-24 h or 72-96 h of differentiation are analyzed by LC-MS/MS to calculate protein FSR and MSR after samples are spiked with yeast alcohol dehydrogenase (ADH1). Profiling of 153 proteins detected 70 significant (p ≤ 0.05, FDR ≤ 1%) differences in abundance between cell states. Early differentiation is enriched by clusters of ribosomal and heat shock proteins, whereas later differentiation is associated with actin filament binding. The median (first-third quartile) FSR (%/h) during early differentiation 4.1 (2.7-5.3) is approximately twofold greater than later differentiation 1.7 (1.0-2.2), equating to MSR of 0.64 (0.38-1.2) and 0.28 (0.1-0.5) fmol h-1  µg-1 total protein, respectively. MSR corresponds more closely with abundance data and highlights proteins associated with glycolytic processes and intermediate filament protein binding that are not evident among FSR data. Similarly, MSR during early differentiation accounts for 78% of the variation in protein abundance during later differentiation, whereas FSR accounts for 4%. Conclusively, the interpretation of protein synthesis data differs when reported in mole or fractional terms, which has consequences when studying the allocation of cellular resources.

Single-cell protein expression of hiPSC-derived cardiomyocytes using Single-Cell Westerns.

The ability to reprogram human somatic cells into human induced pluripotent stem cells (hiPSCs) has enabled researchers to generate cell types in vitro that have the potential to faithfully recapitulate patient-specific disease processes and phenotypes. hiPSC-derived cardiomyocytes (hiPSC-CMs) offer the promise of in vitro patient- and disease-specific models for drug testing and the discovery of novel therapeutic approaches for treating cardiovascular diseases. While methods to differentiate hiPSCs into cardiomyocytes have been demonstrated, the heterogeneity and immaturity of these differentiated populations have restricted their potential in reproducing human disease and the associated target cell phenotypes. These barriers may be overcome through comprehensive single-cell characterization to dissect the rich heterogeneity of hiPSC-CMs and to study the source of varying cell fates. In this study, we optimized and validated a new Single-Cell Western method to assess protein expression in hiPSC-CMs. To better understand distinct subpopulations generated from cardiomyocyte differentiations and to track populations at single-cell resolution over time, we measured and quantified the expression of cardiomyocyte subtype-specific proteins (MLC2V and MLC2A) using Single-Cell Westerns. By understanding their heterogeneity through single-cell protein expression and quantification, we may improve upon current cardiomyocyte differentiation protocols, generate hiPSC-CMs that are more representative of in vivo derived cardiomyocytes for disease modeling, and utilize hiPSC-CMs for regenerative medicine purposes. Single-Cell Westerns provide a robust platform for protein expression analysis at single-cell resolution.

Collaboration during a crisis - the Lighthouse Lab volunteers.

As a group of early-career researchers, we recount our experiences of volunteering at one of the national Lighthouse Labs based at the UK Biocentre in Milton Keynes. We worked together as part of a multidisciplinary team to support the large-scale processing of coronavirus disease 2019 (COVID-19) swabs from across the whole of the UK.

The application of proteomics in muscle exercise physiology.

INTRODUCTION: Exercise offers protection from non-communicable diseases and extends healthspan by offsetting natural physiological declines that occur in older age. Striated muscle is the largest bodily organ; it underpins the capacity for physical work, and the responses of muscle to exercise convey the health benefits of a physically active lifestyle. Proteomic surveys of muscle provide a means to study the protective effects of exercise and this review summaries some key findings from literature listed in PubMed during the last 10 years that have led to new insight in muscle exercise physiology. AREAS COVERED: 'Bottom-up' analyses involving liquid-chromatography tandem mass spectrometry (LC-MS/MS) of peptide digests have become the mainstay of proteomic studies and have been applied to muscle mitochondrial fractions. Enrichment techniques for post-translational modifications, including phosphorylation, acetylation and ubiquitination, have evolved and the analysis of site-specific modifications has become a major area of interest in exercise proteomics. Finally, we consider emergent techniques for dynamic analysis of muscle proteomes that offer new insight to protein turnover and the contributions of synthesis and degradation to changes in protein abundance in response to exercise training. EXPERT OPINION: Burgeoning methods for dynamic proteome profiling offer new opportunities to study the mechanisms of muscle adaptation.

A mixed linear modelling characterisation of gender and speed related changes in spatiotemporal and kinematic characteristics of gait across a wide speed range in healthy adults.

In exploring the relationship between the kinematics of gait and speed of progression individual variation in patterns and gender differences have not always been adequately taken into account. In the current study mixed linear modelling was used to isolate changes with speed from those associated with individual variation and gender. Three-dimensional motion analysis of 20 participants (10M/10F, 25.7 ±â€¯5.1 years) walking at a wide range of speeds (normalised speeds 0.10-0.55 ∼0.41-2.26 m/s) was recorded (775 walks). Spatiotemporal (speed, cadence, step length, percentage of single and double support) and kinematic characteristics (pelvis through ankle) were determined. Significant between participant differences were highlighted in both intercept and slope of relationships. In addition females exhibiting different peak pelvic tilt and obliquity, hip flexion and internal rotation and ankle dorsiflexion compared to males. Spatiotemporal parameters exhibited non-linear relationships with normalised speed (R2 > 0.5). Kinematic features exhibited significant relationships with normalised speed, varying from linear to cubic, from very weak to strong in fit (0.010 > R2 > 0.672). Mixed linear modelling highlighted gender dependent, speed related changes in addition to inter-individual variation. Gender and speed are both important determinants of gait patterns, however, individual variations remain.

Spatiotemporal and kinematic characteristics of gait initiation across a wide speed range.

BACKGROUND: Gait initiation can be performed at a range of speeds. Those with disability tend to use a slower speed compared to those without disability. In assessing the spatiotemporal and kinematic characteristics of gait initiation it is therefore important to consider the effects of speed on outcomes. RESEARCH QUESTION: What is the effect of speed of performance on spatiotemporal and kinematic characteristics of gait initiation? METHODS: Spatiotemporal and kinematic characteristics were measured across a wide range of speeds from very slow to very fast (normalised initiating leg (swing or SW limb) step speed 0.1-0.5) for 20 health adults (10 men/10 women, 22-44 years) using three-dimensional motion analysis of the first two steps of gait. RESULTS: Mixed linear modelling of 295 walking trials indicated differences between individuals, sexes and strong non-linear relationships between normalised initiating leg step speed and cadence and step lengths (R2 > 0.5). Particular characteristics of joint kinematics (maxima and minima for both initiating (SW) and contralateral limb (stance or ST limb)) demonstrated significant non-linear (squared, cubic and power law) changes with speed. Moderate to strong relationships were identified for sagittal plane pelvis, hip and knee kinematics as well as hip adduction (0.3 < R2 < 0.7). SIGNIFICANCE: Gait initiation spatiotemporal and kinematic characteristics were quantified across the maximum range of speeds achievable, providing comprehensive characterisation of changes with speed. Significant, non-linear changes with speed were identified, suggesting different strategies are employed to modify speed at low and high speeds. The highlighted changes with speed illustrate the importance of taking speed into account when comparing outcomes between healthy adults and those with pathology.

Distal upper limb kinematics during functional everyday tasks.

Quantitative characterisation of upper limb motion allows the evaluation of the effect of pathology on functional task performance, potentially directing rehabilitation strategies. Movement patterns of the distal upper limb in healthy adults during functional tasks have not been extensively characterised. During five loaded functional tasks (drinking from a glass, pouring from a kettle, turning a handle, lifting a bag to a shelf, turning a key) the movement patterns were characterised using three-dimensional motion analysis with a minimal marker set in 16 healthy adults (10 M,6F, 27 (IQR:25-43)years). Joint angles reported include flexion/extension at the elbow and wrist, forearm supination/pronation and digits 2-5 metacarpophalangeal (MCP) joint flexion/extension. Additionally for the thumb the angle between the metacarpal of the thumb and the 2nd digit (Thumb base), the thumb MCP (Thumb MCP) and interphalangeal (Thumb IP) joint angles are presented. Durations of activities performed at self-selected comfortable speeds (3.36 (IQR:3.07,3.66)s turning a key to 6.20 (IQR:5.44,6.38)s drinking from a glass) are reported. The maximum joint angles used (median of participants' maxima) were 141° of elbow flexion, 116° forearm supination, 36° wrist extension, 56° Thumb base, 14° Thumb MCP flexion, 18° Thumb IP flexion, 85° MCP2-5 flexion. The tasks of drinking from a glass, lifting a bag to a shelf and turning a key appeared to have the least variation in performance, suggesting that these activities are better suited to be selected as standardized tasks for assessing the impact of pathology on movement than pouring from a kettle and turning a handle.

Total Hip Arthroplasty Improves Pain and Function but Not Physical Activity.

BACKGROUND: People with hip osteoarthritis are likely to limit physical activity (PA) engagement due to pain and lack of function. Total hip arthroplasty (THA) reduces pain and improves function, potentially allowing increased PA. PA of THA patients was quantified to 12 months postoperation. The hypothesis was that postoperatively levels of PA would increase. METHODS: PA of 30 THA patients (67 ± 7 years) was objectively measured preoperatively and 3 and 12 months postoperation. Harris Hip Score (HHS), Oxford Hip Score (OHS), and 6-minute walk test (6MWT) were recorded. Mixed linear modelling was used to examine relationships of outcomes with time, baseline body mass index (BMI), age, gender, and baseline HHS. RESULTS: Time was not a significant factor in predicting volume measures of PA, including sit-to-stand transitions, upright time, and steps. Notably, baseline BMI was a significant predictor of upright time, steps, largest number of steps in an upright bout, HHS, and 6MWT. Baseline HHS helped predict longest upright bout, cadence of walking bouts longer than 60 seconds, and OHS. The significant effect of participant as a random intercept in the model for PA outcomes suggested habituation from presurgery to postsurgery. CONCLUSION: Volume measures of PA did not change from presurgery to 12 months postsurgery despite improvement in HHS, OHS, and 6MWT. Baseline BMI was a more important predictor of upright activity and stepping than time. Preoperative and postoperative PA promotion could be used to modify apparently habitual low levels of PA to enable full health benefits of THA to be gained.

Can arterial wave augmentation in young adults help account for variability of cardiovascular risk in different British ethnic groups?

OBJECTIVE: Traditional cardiovascular risk factors do not fully account for ethnic differences in cardiovascular disease. We tested if arterial function indices, particularly augmentation index (AIx), and their determinants from childhood could underlie such ethnic variability among young British adults in the 'DASH' longitudinal study. METHODS: DASH, at http://dash.sphsu.mrc.ac.uk/, includes representative samples of six main British ethnic groups. Pulse wave velocity (PWV) and AIx were recorded using the Arteriograph device at ages 21-23 years in a subsample (n = 666); psychosocial, anthropometric, and blood pressure (BP) measures were collected then and in two previous surveys at ages 11-13 years and 14-16 years. For n = 334, physical activity was measured over 5 days (ActivPal). RESULTS: Unadjusted values and regression models for PWVs were similar or lower in ethnic minority than in White UK young adults, whereas AIx was higher - Caribbean (14.9, 95% confidence interval 12.3-17.0%), West African (15.3, 12.9-17.7%), Indian (15.1, 13.0-17.2%), and Pakistani/Bangladeshi (15.7, 13.7-17.7%), compared with White UK (11.9, 10.2-13.6%). In multivariate models, adjusted for sex, central SBP, height, and heart rate, Indian and Pakistani/Bangladeshi young adults had higher AIx (ß = 3.35, 4.20, respectively, P < 0.01) than White UK with a similar trend for West Africans and Caribbeans but not statistically significant. Unlike PWV, physical activity, psychosocial or deprivation measures were not associated with AIx, with borderline associations from brachial BP but no other childhood variables. CONCLUSION: Early adult AIx, but not arterial stiffness, may be a useful tool for testing components of excess cardiovascular risk in some ethnic minority groups.

Agreement of the activPAL3 and activPAL for characterising posture and stepping in adults and children.

Characterisation of physical activity and sedentary behaviour under free-living conditions is becoming increasingly important in light of growing evidence for the health implications of these behaviours. The integrity of long-term follow-up and the ability to compare outcomes between studies is critically dependent on the agreement of outcomes from successive generations of monitors. This study evaluated the agreement of the activPAL and second generation activPAL3 devices. Agreement was assessed in both adults (median 27.6y IQR 22.6) (n=20) and young people (median 12.0y IQR 4.1) (n=8) during standardised and daily living (ADL) test activities. During standardised activities; sedentary duration, upright duration, stepping duration and overall number of steps were all detected within small limits of agreement (≤5%). However, the activPAL characterised more steps during jogging than the activPAL3 (adults +8.36%, young people +6.80%). Also during ADL differences arose due to different posture characterisation in young people and lower step detection in the activPAL than the activPAL3 (adults -20.58%, young people -11.43%). Second-by-second posture analysis demonstrated high levels (>90%) of agreement for all activities between monitors. However, sensitivity (68.7%) and positive predictive value (78.8%) for adult stepping demonstrated disagreement between monitor interpretation of movement patterns during ADL. Agreement between monitor outcomes for standardised activities provides confidence that these outcomes can be considered almost equivalent. However, for characterisation of jogging and smaller movements during ADL, it is likely that significant differences between monitor outcomes will arise.

Ethnic Differences in and Childhood Influences on Early Adult Pulse Wave Velocity: The Determinants of Adolescent, Now Young Adult, Social Wellbeing, and Health Longitudinal Study.

Early determinants of aortic stiffness as pulse wave velocity are poorly understood. We tested how factors measured twice previously in childhood in a multiethnic cohort study, particularly body mass, blood pressure, and objectively assessed physical activity affected aortic stiffness in young adults. Of 6643 London children, aged 11 to 13 years, from 51 schools in samples stratified by 6 ethnic groups with different cardiovascular risk, 4785 (72%) were seen again at aged 14 to 16 years. In 2013, 666 (97% of invited) took part in a young adult (21-23 years) pilot follow-up. With psychosocial and anthropometric measures, aortic stiffness and blood pressure were recorded via an upper arm calibrated Arteriograph device. In a subsample (n=334), physical activity was measured >5 days via the ActivPal. Unadjusted pulse wave velocities in black Caribbean and white UK young men were similar (mean±SD 7.9±0.3 versus 7.6±0.4 m/s) and lower in other groups at similar systolic pressures (120 mm Hg) and body mass (24.6 kg/m(2)). In fully adjusted regression models, independent of pressure effects, black Caribbean (higher body mass/waists), black African, and Indian young women had lower stiffness (by 0.5-0.8; 95% confidence interval, 0.1-1.1 m/s) than did white British women (6.9±0.2 m/s). Values were separately increased by age, pressure, powerful impacts from waist/height, time spent sedentary, and a reported racism effect (+0.3 m/s). Time walking at >100 steps/min was associated with reduced stiffness (P<0.01). Effects of childhood waist/hip were detected. By young adulthood, increased waist/height ratios, lower physical activity, blood pressure, and psychosocial variables (eg, perceived racism) independently increase arterial stiffness, effects likely to increase with age.