A biological, latent variable model of health (EarlyBird 68).

OBJECTIVE: To determine whether factor analysis of a set of health-related biomarkers provides evidence of an underlying common dimension of variation, and to explore the relationship between this dimension of variation with positive and negative affect. METHOD: Twelve health-related metabolic, immune and body-composition biomarkers at ages 5, 7, 9, 11, 14 and 16years were obtained from the EarlyBird longitudinal cohort of 347 children and supplemented by positive affect (PA) and negative affect (NA) measured at age 16years. RESULTS: At each age, principal factor analysis revealed that nine of the 12 biomarkers consistently loaded on the first extracted factor, accounting for 25% of the variance at age 5, and 37-44% of the variance at 7-16years. High loading biomarkers included physical indicators of adiposity, insulin resistance, C-reactive protein, triglycerides, and cholesterol. Factor scores at different ages correlated between .48 and .85. Correlations between the first factor scores and mood measured at age 16 were r=-.17 (p=.02) for PA and r=.13 (p=.07) for NA. CONCLUSIONS: There is a latent variable, h, that accounts for about a third of the variance of a set of health related physical and biochemical biomarkers. h is comparatively stable during childhood and is a weak predictor of mood. These data provide a rationale for aggregating biomarkers in psychoneuroimmunological research. The concept of h provides a possible biological rationale for the role of common factors in disease onset and progression, mental illness, and functional disorders

Enhancing Trial Delivery in Parkinson\u27s Disease: Qualitative Insights from PD STAT

\ua9 2022 - The authors. Published by IOS Press. Background: Recruitment and retention of participants in clinical trials for Parkinson\u27s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials

Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9–16 years (EarlyBird 66)

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this recordthere is another ORE record for this publication: http://hdl.handle.net/10871/18754Aims/hypothesis: The aim of this work was to test whether the mid-adolescent peak in insulin resistance (IR) and trends in other metabolic markers are influenced by long-term exposure to physical activity. Methods: Physical activity (7 day ActiGraph accelerometry), HOMA-IR and other metabolic markers (glucose, fasting insulin, HbA1c, lipids and BP) were measured annually from age 9 years to 16 years in 300 children (151 boys) from the EarlyBird study in Plymouth, UK. The activity level of each child was characterised, with 95% reliability, by averaging their eight annual physical activity measures. Age-related trends in IR and metabolic health were analysed by multi-level modelling, with physical activity as the exposure measure (categorical and continuous) and body fat percentage (assessed by dual-energy X-ray absorptiometry) and pubertal status (according to age at peak height velocity and Tanner stage) as covariates. Results: The peak in IR at age 12–13 years was 17% lower (p < 0.001) in the more active adolescents independently of body fat percentage and pubertal status. However, this difference diminished progressively over the next 3 years and had disappeared completely by the age of 16 years (e.g. difference was −14% at 14 years, −8% at 15 years and +1% at 16 years; ‘physical activity × age2’ interaction, p < 0.01). Triacylglycerol levels in girls (−9.7%, p = 0.05) and diastolic blood pressure in boys (−1.20 mmHg, p = 0.03) tended to be lower throughout adolescence in the more active group. Conclusions/interpretation: Our finding that physical activity attenuates IR during mid-adolescence may be clinically important. It remains to be established whether the temporary attenuation in IR during this period has implications for the development of diabetes in adolescence and for future metabolic health generally.The EarlyBird study (BSM, JH, MM, ANJ, LDV, TJW) was supported by the Bright Future Trust, the Kirby Laing Foundation, the Peninsula Foundation and the EarlyBird Diabetes Trust. WEH was supported by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Membrane permeability of small molecules from unbiased molecular dynamics simulations

Permeation of many small molecules through lipid bilayers can be directly observed in molecular dynamics simulations on the nano- and microsecond timescale. While unbiased simulations provide an unobstructed view of the permeation process, their feasibility for computing permeability coefficients depends on various factors that differ for each permeant. The present work studies three small molecules for which unbiased simulations of permeation are feasible within less than a microsecond, one hydrophobic (oxygen), one hydrophilic (water), and one amphiphilic (ethanol). Permeabilities are computed using two approaches: counting methods and a maximum-likelihood estimation for the inhomogeneous solubility diffusion (ISD) model. Counting methods yield nearly model-free estimates of the permeability for all three permeants. While the ISD-based approach is reasonable for oxygen, it lacks precision for water due to insufficient sampling and results in misleading estimates for ethanol due to invalid model assumptions. It is also demonstrated that simulations using a Langevin thermostat with collision frequencies of 1/ps and 5/ps yield oxygen permeabilities and diffusion constants that are lower than those using Nose-Hoover by statistically significant margins. In contrast, permeabilities from trajectories generated with Nose-Hoover and the microcanonical ensemble do not show statistically significant differences. As molecular simulations become more affordable and accurate, calculation of permeability for an expanding range of molecules will be feasible using unbiased simulations. The present work summarizes theoretical underpinnings, identifies pitfalls, and develops best practices for such simulations

Enhancing Trial Delivery in Parkinson’s Disease: Qualitative Insights from PD STAT

Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials.</jats:p

Taguchi Loss Function for Varus/Valgus Alignment in Total Knee Arthroplasty

Methods of designing equipment to improve quality have been developed by Taguchi. A key feature of these methods is the development of loss function, which quantifies the financial cost (loss) resulting from deviations from target dimensions. Total knee arthroplasties can fail due to prosthetic component malalignment. A Taguchi loss function for varus/valgus alignment of the prosthesis and revision rates was developed. Six studies were identified from a comprehensive literature search. Varus and extreme valgus alignments correlated with an increased percentage of prosthetic failure. A loss function of L( y) = $326.80y2 , where y was deviation from ideal varus/valgus angle, was determined. The expected loss function was EL=$326.80y¯2+s2 , where y¯ was the mean deviance from the ideal varus/valgus angle and s2 was the variance in varus/valgus angle. This loss function was used to estimate the cost savings of using computer-assisted surgical navigation in total knee arthroplasty (TKA). The average savings of a navigated TKA versus a conventional TKA, based on the expected loss equation derived from the Taguchi loss function, was $2,304 per knee. The expected loss function derived here can serve as a tool for biomedical engineers seeking to use Taguchi quality engineering methods in designing orthopaedic devices

Mothers' perceptions of child weight status and the subsequent weight gain of their children : a population based longitudinal study

BACKGROUND: There is a plethora of cross sectional work on maternal perceptions of child weight status showing that mothers typically do not classify their overweight child as being overweight according to commonly used clinical criteria. Awareness of overweight in their child is regarded as an important prerequisite for mothers to initiate appropriate action. The gap in the literature is determining whether, if mothers do classify their overweight child's weight status correctly, this is associated with a positive outcome for the child's body mass index (BMI) at a later stage. OBJECTIVE: To explore longitudinal perceptions of child weight status from mothers of a contemporary population-based birth cohort (Gateshead Millennium Study) and relationships of these perceptions with future child weight gain. METHODS: Data collected in the same cohort at 7, 12 and 15 years of age: mothers' responses to two items concerning their child's body size; child's and mother's BMI; pubertal maturation; demographic information. RESULTS: Mothers' perceptions of whether their child was overweight did not change markedly over time. Child BMI was the only significant predictor of mothers' classification of overweight status, and it was only at the extreme end of the overweight range and in the obese range that mothers reliably described their child as overweight. Even when mothers did appropriately classify their child as overweight at an earlier stage, this was not related to relatively lower child BMI a few years later. CONCLUSIONS: Mothers tend to classify their child as overweight in only more extreme cases. It is an important finding that no beneficial impact was shown on later child BMI in overweight children whose mothers classified their child's weight status as overweight at an earlier stage.International Journal of Obesity accepted article preview online, 25 January 2017. doi:10.1038/ijo.2017.20

The Kinematic Properties of BHB and RR Lyrae stars towards the Anticentre and the North Galactic Pole: The Transition between the Inner and the Outer Halo

We identify 51 blue horizontal branch (BHB) stars, 12 possible BHB stars and 58 RR Lyrae stars in Anticentre fields. Their selection does not depend on their kinematics. Light curves and ephemerides are given for 7 previously unknown RR Lyrae stars. All but 4 of the RR Lyrae stars are of Oosterhoff type I. Our selection criteria for BHB stars give results that agree with those used by Smith et al. (2010) and Ruhland et al. (2011). We use 5 methods to determine distances for the BHB stars and 3 methods for the RR Lyrae stars to get distances on a uniform scale. Absolute proper motions (largely derived from the GSCII and SDSS (DR7) databases) are given for these stars; radial velocities are given for 31 of the BHB stars and 37 of the RR Lyrae stars. Combining these data for BHB and RR Lyrae stars with those previously found in fields at the North Galactic Pole, we find that retrograde orbits dominate for galactocentric distances greater than 12.5 kpc. The majority of metal-poor stars in the solar neighbourhood are known to be concentrated in a Lperp vs. Lz angular momentum plot. We show that the ratio of the number of outliers to the number in the main concentration increases with galactocentric distance. The location of these outliers with Lperp and Lz shows that the halo BHB and RR Lyrae stars have more retrograde orbits and a more spherical distribution with increasing galactocentric distance. Six RR Lyrae stars are identified in the H99 group of outliers; the small spread in their [Fe/H] suggests that they could have come from a single globular cluster. Another group of outliers contains two pairs of RR Lyrae stars; the stars in each pair have similar properties.Comment: 40 pages, 19 figures, to be published in MNRA