Life course longitudinal growth and risk of knee osteoarthritis at age 53 years: evidence from the 1946 British birth cohort study

Objective: To examine the relationship between height gain across childhood and adolescence with knee osteoarthritis in the MRC National Survey of Health and Development (NSHD). / Materials and methods: Data are from 3035 male and female participants of the NSHD. Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at ages 20 years. Associations between (1) height at each age (2) height gain during specific life periods (3) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity, and knee osteoarthritis at 53 years were tested. / Results: In sex-adjusted models, estimated associations between taller height and decreased odds of knee osteoarthritis at age 53 years were small at all ages - the largest associations were an OR of knee osteoarthritis of 0.9 per 5 cm increase in height at age 4, (95% CI 0.7–1.1) and an OR of 0.9 per 5 cm increase in height, (95% CI 0.8–1.0) at age 6. No associations were found between height gain during specific life periods or the SITAR growth curve variables and odds of knee osteoarthritis. / Conclusions: There was limited evidence to suggest that taller height in childhood is associated with decreased odds of knee osteoarthritis at age 53 years in this cohort. This work enhances our understanding of osteoarthritis predisposition and the contribution of life course height to this

A method for conducting suppression assays using small numbers of tissue-isolated regulatory T cells

The suppression assay is a commonly performed assay, measuring the ability of regulatory T cells (Treg) to suppress T cell proliferation. Most frequently, Treg are obtained from the peripheral blood or spleen. Lower yields are obtained by isolation from other tissues, rendering downstream suppression assays challenging to perform. Furthermore, the importance of suppressive subpopulations of Treg favours their isolation by fluorescent-activated cell sorting. Here we describe a method to isolate Treg from human tissues, using colorectal cancer tissue as an example. Treg suppressive capacity was further examined by expression of CCR5 to demonstrate the ability of our method to assess the suppressive capacity of regulatory T cell subsets. To optimise the standard suppression assay to achieve our research aims, the following modifications were made: • Treg, isolated from tissues, were sorted directly into a well-plate. • Responder T cells, which had been fluorescently-labelled prior to sorting, were added directly into the well-plate. • Human Treg Suppression Inspector beads (Miltenyi Biotec Ltd., UK) provided a polyclonal stimulus for proliferation and were added to each well at a bead:lymphocyte ratio of 1:2. This method quantified the suppression of responder T cell proliferation by small numbers of strictly-defined Treg populations isolated from tissues

Social Quality theory in perspective

For its theoretical development, the social quality (SQ) theory was given birth in 1997, with its original aim directed at addressing the social dimension of state-policy making in Europe, against the neo-liberal Washington consensus, and the handmaiden position of all other public policies. However, after a decade of development, this theory has been developed from various dimensions, as evidenced where SQ theories are applied to particular topics. Accordingly, the merits of this theory can be understood as a normative guideline for policy-making and practice, as a scheme of reference for understanding relevant conditional structures as the basis for this guideline, and as a socio-political goal to enable people to act in a democratic way

Injury Risk Estimation Expertise Assessing the ACL Injury Risk Estimation Quiz

Background: Available methods for screening anterior cruciate ligament (ACL) injury risk are effective but limited in application as they generally rely on expensive and time-consuming biomechanical movement analysis. A potential efficient alternative to biomechanical screening is skilled movement analysis via visual inspection (ie, having experts estimate injury risk factors based on observations of athletes’ movements). Purpose: To develop a brief, valid psychometric assessment of ACL injury risk factor estimation skill: the ACL Injury Risk Estimation Quiz (ACL-IQ). Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 660 individuals participated in various stages of the study, including athletes, physicians, physical therapists, athletic trainers, exercise science researchers/students, and members of the general public in the United States. The ACL-IQ was fully computerized and made available online (www.ACL-IQ.org). Item sampling/reduction, reliability analysis, cross-validation, and convergent/discriminant validity analysis were conducted to optimize the efficiency and validity of the assessment. Results: Psychometric optimization techniques identified a short (mean time, 2 min 24 s), robust, 5-item assessment with high reliability (test-retest: r = 0.90) and consistent discriminability (average difference of exercise science professionals vs general population: Cohen d = 1.98). Exercise science professionals and general population individuals scored 74% and 53% correct, respectively. Convergent and discriminant validity was demonstrated. Scores on the ACL-IQ were most associated with ACL knowledge and various cue utilities and were least associated with domain-general spatial/decision-making ability, personality, or other demographic variables. Overall, 23% of the total sample (40% exercise science professionals; 6% general population) performed better than or equal to the ACL nomogram. Conclusion: This study presents the results of a systematic approach to assess individual differences in ACL injury risk factor estimation skill; the assessment approach is efficient (ie, it can be completed in\3 min) and psychometrically robust. The results provide evidence that some individuals have the ability to visually estimate ACL injury risk factors more accurately than other instrument-based ACL risk estimation methods (ie, ACL nomogram). The ACL-IQ provides the foundation for assessing the efficacy of observational ACL injury risk factor assessment (ie, does simple skilled visual inspection reduce ACL injuries?). It also provides a representative task environment that can be used to increase our understanding of the perceptual-cognitive mechanisms underlying observational movement analysis and to improve injury risk assessment performance

The effect of time constraint on anticipation, decision making, and option generation in complex and dynamic environments

Researchers interested in performance in complex and dynamic situations have focused on how individuals predict their opponent(s) potential courses of action (i.e., during assessment) and generate potential options about how to respond (i.e., during intervention). When generating predictive options, previous research supports the use of cognitive mechanisms that are consistent with long-term working memory (LTWM) theory (Ericsson and Kintsch in Phychol Rev 102(2):211–245, 1995; Ward et al. in J Cogn Eng Decis Mak 7:231–254, 2013). However, when generating options about how to respond, the extant research supports the use of the take-the-first (TTF) heuristic (Johnson and Raab in Organ Behav Hum Decis Process 91:215–229, 2003). While these models provide possible explanations about how options are generated in situ, often under time pressure, few researchers have tested the claims of these models experimentally by explicitly manipulating time pressure. The current research investigates the effect of time constraint on option-generation behavior during the assessment and intervention phases of decision making by employing a modified version of an established option-generation task in soccer. The results provide additional support for the use of LTWM mechanisms during assessment across both time conditions. During the intervention phase, option-generation behavior appeared consistent with TTF, but only in the non-time-constrained condition. Counter to our expectations, the implementation of time constraint resulted in a shift toward the use of LTWM-type mechanisms during the intervention phase. Modifications to the cognitive-process level descriptions of decision making during intervention are proposed, and implications for training during both phases of decision making are discussed

Corrigendum: The Gambian Bone and Muscle Ageing Study: Baseline Data From a Prospective Observational African Sub-Saharan Study.

[This corrects the article on p. 219 in vol. 8, PMID: 28912754.]

Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

© 2017 The Author(s). Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research

Stereospecific decarboylative allylation of sulfones

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja104196x.Allyl sulfonyl acetic esters undergo highly stereospecific, palladium-catalyzed decarboxylative allylation. The reaction allows the stereospecific formation of tertiary homoallylic sulfones in high yield. In contrast to related reactions that proceed at -100 °C and require highly basic preformed organometallics, the decarboxylative coupling described herein occurs under mild non-basic conditions and requires no stoichiometric additives. Allylation of the intermediate α-sulfonyl anion is more rapid than racemization, leading to a highly enantiospecific process. DFT calculations indicate that the barrier for racemization is 9.9 kcal/mol and thus the barrier of allylation must be <9.9 kcal/mol

Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development.

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.NSHD: The authors are grateful to NSHD study members who took part in the clinic data collection for their continuing support. We thank members of the NSHD scientific and data collection teams at the following centres: MRC Unit for Lifelong Health and Ageing; Wellcome Trust (WT) Clinical Research Facility (CRF) Manchester; WTCRF and Medical Physics at the Western General Hospital in Edinburgh; WTCRF and Department of Nuclear Medicine at University Hospital Birmingham; WTCRF and the Department of Nuclear Medicine at University College London Hospital; CRF and the Department of Medical Physics at the University Hospital of Wales; CRF and Twin Research Unit at St Thomas’ Hospital London. ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford Univeristy Press

Capturing and testing perceptual-cognitive expertise: A comparison of stationary and movement response methods

Numerous methods have been used to study expertise and performance. In the present article, we compare the cognitive thought processes of skilled soccer players when responding to film-based simulations of defensive situations involving two different experimental conditions. Participants either remained stationary in a seated position (n = 10) or were allowed to move (n = 10) in response to life-size film sequences of 11 versus 11 open-play soccer situations viewed from a player’s perspective. Response accuracy and retrospective verbal reports of thinking were collected across the two task conditions. In the movement-based response group, participants generated a greater number of verbal report statements, including a higher proportion of evaluation, prediction, and action planning statements, than did participants in the stationary group. Findings suggest that the processing strategies employed during performance differ depending on the nature of the response required of participants. Implications for behavioral methods and experimental design are discussed