Moving from a serious knee injury back into a heathy exercise regime: mapping the rehabilitation experiences of older persons in the UK

Knee injuries are by some margin the most commonly-sustained in all athletic pursuits. While there is a strong body of contemporary research exploring the physiological and psychological rehabilitation/recovery of individuals who have sustained serious knee injuries, it would be uncontroversial to propose that the great majority of such studies have been concerned with the elite athletic domain. Considerably less research has addressed the comparable experiences of amateur athletes and exercisers, despite the much greater numbers thereof, and less still has explored how physically active older persons negotiate the journey from initial injury back to regular exercising. With ever-larger numbers of individuals in the UK (and elsewhere) now remaining active into later life than ever before, this is a matter that will likely need much more dedicated investigation in the future, in order to assure the best quality of care for a category of persons with a diverse set of needs, but diversity of needs rather different to that of young professional sportspersons. The study reported here, using Interpretative Phenomenological Analysis (IPA), therefore, takes some steps to qualitatively identify key features of the rehabilitative journeys of N=5 individuals aged between 50 and 70 years, all of whom identified as very physically active. Each of these individuals had sustained a knee injury which (a) required suspension of all rigorous physical activity while (b) undergoing structured professional rehabilitation. With full institutional ethical approval, these participants were recruited to sit for extended semi-structured interviews to assess their experiences of being injured, their rehabilitation programme and their reflections on their personal pathway to recovery. All collected data were stored in line with GDPR, transcribed in full and analysed using the established techniques of IPA. Provisional superordinate themes to emerge from this analysis are: (1) the multifaceted experience of pain; (2) anxiety around reinjury, and its impacts on future choices of activity/surface; (3) unhealthy social influences that contribute to poor management of older people during exercise; (4) the social and psychological support provided by nominally physiological rehabilitators. The findings, at this stage, both confirm some existing research themes, while also offering some novel insights on the particular participant group. It is contended that they can contribute positively to a small but growing body of research in the area, with potentially constructive practical applications

Structural operational semantics for stochastic and weighted transition systems

We introduce weighted GSOS, a general syntactic framework to specify well-behaved transition systems where transitions are equipped with weights coming from a commutative monoid. We prove that weighted bisimilarity is a congruence on systems defined by weighted GSOS specifications. We illustrate the flexibility of the framework by instantiating it to handle some special cases, most notably that of stochastic transition systems. Through examples we provide weighted-GSOS definitions for common stochastic operators in the literature

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome

“Am I able? Is it worth it?” Adolescent girls’ motivational predispositions to school physical education: Associations with health-enhancing physical activity

The study purpose was to investigate predictive associations between adolescent girls&rsquo; motivational predispositions to physical education (PE) and habitual physical activity. Two hundred girls (age 13.1 &plusmn; 0.6 years) completed the Physical Education Predisposition Scale and the Physical Activity Questionnaire for Older Children. ANCOVAs revealed that girls with the highest Perceived PE Worth and Perceived PE Ability scores were the most habitually active groups (p &lt; .0001). Significant predictors of physical activity identified by hierarchical regression were Perceived PE Ability and body mass index, which accounted for 17% and 3% of variance, respectively. As Perceived PE Ability was strongly associated with physical activity, the correlates of this construct should be further established to inform future school and PE-based interventions. <br /

Planar Cell Polarity Effector Proteins Inturned and Fuzzy Form a Rab23 GEF Complex

A subset of Rab GTPases have been implicated in cilium formation in cultured mammalian cells [1-6]. Rab11 and Rab8, together with their GDP-GTP exchange factors (GEFs), TRAPP-II and Rabin8, promote recruitment of the ciliary vesicle to the mother centriole and its subsequent maturation, docking, and fusion with the cell surface [2-5]. Rab23 has been linked to cilium formation and membrane trafficking at mature cilia [1, 7, 8]; however, the identity of the GEF pathway activating Rab23, a member of the Rab7 subfamily of Rabs, remains unclear. Longin-domain-containing complexes have been shown to act as GEFs for Rab7 subfamily GTPases [9-12]. Here, we show that Inturned and Fuzzy, proteins previously implicated as planar cell polarity (PCP) effectors and in developmentally regulated cilium formation [13, 14], contain multiple longin domains characteristic of the Mon1-Ccz1 family of Rab7 GEFs and form a specific Rab23 GEF complex. In flies, loss of Rab23 function gave rise to defects in planar-polarized trichome formation consistent with this biochemical relationship. In cultured human and mouse cells, Inturned and Fuzzy localized to the basal body and proximal region of cilia, and cilium formation was compromised by depletion of either Inturned or Fuzzy. Cilium formation arrested after docking of the ciliary vesicle to the mother centriole but prior to axoneme elongation and fusion of the ciliary vesicle and plasma membrane. These findings extend the family of longin domain GEFs and define a molecular activity linking Rab23-regulated membrane traffic to cilia and planar cell polarity

Review: The Journal of Dramaturgy, volume 27, issue 1

Contents include: Editors\u27 Note; The Making of a Conference: Practices in Transnational Planning, Programming, and Translation; Tripped Up by the Small Things: Dramaturging Institutional Processes in DEI Work; The New Colossus Project: A Model for Rapid Response Theatre Around Immigration; Pregnant and Performing: Embodied Dramaturgical Methodologies.https://soundideas.pugetsound.edu/lmdareview/1054/thumbnail.jp

A Simplified Score to Quantify Comorbidity in COPD

Importance Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes. Materials and Methods Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS. Results Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV1 (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624–0·7676), MMRC (0·7590–0·7644), 6MWD (0·7531–0·7560) and exacerbation risk (0·6831–0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341). Conclusions Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease:the ALL-HEART RCT and economic evaluation

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1: 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a ‘within trial’ cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval −0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout.</p

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease : the ALL-HEART RCT and economic evaluation

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.Peer reviewe