Simple rules for evidence translation in complex systems: a qualitative study

Background Ensuring patients benefit from the latest medical and technical advances remains a major challenge, with rational-linear and reductionist approaches to translating evidence into practice proving inefficient and ineffective. Complexity thinking, which emphasises interconnectedness and unpredictability, offers insights to inform evidence translation theories and strategies. Drawing on detailed insights into complex micro-systems, this research aimed to advance empirical and theoretical understanding of the reality of making and sustaining improvements in complex healthcare systems. Methods Using analytical auto-ethnography, including documentary analysis and literature review, we assimilated learning from 5 years of observation of 22 evidence translation projects (UK). We used a grounded theory approach to develop substantive theory and a conceptual framework. Results were interpreted using complexity theory and ‘simple rules’ were identified reflecting the practical strategies that enhanced project progress. Results The framework for Successful Healthcare Improvement From Translating Evidence in complex systems (SHIFT-Evidence) positions the challenge of evidence translation within the dynamic context of the health system. SHIFT-Evidence is summarised by three strategic principles, namely (1) ‘act scientifically and pragmatically’ – knowledge of existing evidence needs to be combined with knowledge of the unique initial conditions of a system, and interventions need to adapt as the complex system responds and learning emerges about unpredictable effects; (2) ‘embrace complexity’ – evidence-based interventions only work if related practices and processes of care within the complex system are functional, and evidence-translation efforts need to identify and address any problems with usual care, recognising that this typically includes a range of interdependent parts of the system; and (3) ‘engage and empower’ – evidence translation and system navigation requires commitment and insights from staff and patients with experience of the local system, and changes need to align with their motivations and concerns. Twelve associated ‘simple rules’ are presented to provide actionable guidance to support evidence translation and improvement in complex systems. Conclusion By recognising how agency, interconnectedness and unpredictability influences evidence translation in complex systems, SHIFT-Evidence provides a tool to guide practice and research. The ‘simple rules’ have potential to provide a common platform for academics, practitioners, patients and policymakers to collaborate when intervening to achieve improvements in healthcare

A survey of 557 GHz water vapor emission in the NGC 1333 molecular cloud

Using NASA\u27s Submillimeter Wave Astronomy Satellite (SWAS), we have examined the production of water in quiescent and shocked molecular gas through a survey of the 556.936 GHz 110-101 transition of ortho-H2O in the NGC 1333 molecular core. These observations reveal broad emission lines associated with the IRAS 2, IRAS 4, IRAS 7, and HH 7-11 outflows. Toward three positions we detect narrow (Δv ~ 2-3 km s-1) emission lines clearly associated with the ambient gas. The SWAS observations, with a resolution of ~4\u27, are supplemented with observations from the Infrared Space Observatory (ISO) and by an unbiased survey of a ~17\u27 × 15\u27 area, with ~50\u27\u27 resolution, in the low-J transitions of CO, 13CO, C18O, N2H+, CH3OH, and SiO. Using these combined data sets, with consistent assumptions, we find beam-averaged ortho-H2O abundances of greater than 10-6 relative to H2 for all four outflows. A comparison of SWAS and ISO water data is consistent with nondissociative shock models, provided the majority of the ortho-H2O (110-101) emission arises from cool postshock material with enhanced abundances. In the ambient gas the ortho-H2O abundance is found to lie between 0.1 × 10-7 and 1 × 10-7 relative to H2 and is enhanced when compared to cold prestellar molecular cores. A comparison of the water emission with tracers of dense condensations and shock chemistry finds no clear correlation. However, the water emission appears to be associated with the presence of luminous external heating sources that power the reflection nebula and the photodissociation region (PDR). Simple PDR models are capable of reproducing the water and high-J 13CO emission, suggesting that a PDR may account for the excitation of water in low-density undepleted gas, as suggested by Spaans & van Dishoeck

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence

OBJECTIVE: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness and the acute BP response to exercise in a large birth cohort of adolescents. METHODS: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8±0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO2 max ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. RESULTS: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking and socioeconomic status (standardized β: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). CONCLUSION: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realised with more-favourable body composition

A survey of UK medical schools' arrangements for early patient contact

Background: Many U.K. medical schools have patient contact in the first two years of the undergraduate course. Aim: To compare the purposes and organization of early patient contact in UK medical schools and to relate these arrangements to the schools' curricular objectives. Methods: A telephone survey of lead educators in UK medicals schools. Categories of contact were plotted against phases of the course to discern patterns of organisation. Results: The quantity of contact varies considerably (four to 65 days). There is a pattern, with learning objectives around the social context of health and illness preceding skills based work and integrated clinical knowledge for practice coming later. Schools fall into three categories: close adherence to the preclinical/clinical split, with limited early contact acting as an introduction to social aspects of health; provision of substantial patient contact to maximize the integration of knowledge and skills; and transitional, with limited clinical goals. General practice provides between one third and one half of early patient contact. Conclusions: Arrangements meet the objectives set by each school and reflect differing educational philosophies. Change is toward more early contact. There appears to be no national guidance which supports a minimum quantity of patient contact or specific educational purpose in the early years of U.K. basic medical training

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

Lentiviral vectors can be used for full-length dystrophin gene therapy

Duchenne Muscular Dystrophy (DMD) is caused by a lack of dystrophin expression in patient muscle fibres. Current DMD gene therapy strategies rely on the expression of internally deleted forms of dystrophin, missing important functional domains. Viral gene transfer of full-length dystrophin could restore wild-type functionality, although this approach is restricted by the limited capacity of recombinant viral vectors. Lentiviral vectors can package larger transgenes than adeno-associated viruses, yet lentiviral vectors remain largely unexplored for full-length dystrophin delivery. In our work, we have demonstrated that lentiviral vectors can package and deliver inserts of a similar size to dystrophin. We report a novel approach for delivering large transgenes in lentiviruses, in which we demonstrate proof-of-concept for a 'template-switching' lentiviral vector that harnesses recombination events during reverse-transcription. During this work, we discovered that a standard, unmodified lentiviral vector was efficient in delivering full-length dystrophin to target cells, within a total genomic load of more than 15,000 base pairs. We have demonstrated gene therapy with this vector by restoring dystrophin expression in DMD myoblasts, where dystrophin was expressed at the sarcolemma of myotubes after myogenic differentiation. Ultimately, our work demonstrates proof-of-concept that lentiviruses can be used for permanent full-length dystrophin gene therapy, which presents a significant advancement in developing an effective treatment for DMD

A combined transmission spectrum of the Earth-sized exoplanets TRAPPIST-1 b and c

Three Earth-sized exoplanets were recently discovered close to the habitable zone of the nearby ultracool dwarf star TRAPPIST-1. The nature of these planets has yet to be determined, since their masses remain unmeasured and no observational constraint is available for the planetary population surrounding ultracool dwarfs, of which the TRAPPIST-1 planets are the first transiting example. Theoretical predictions span the entire atmospheric range from depleted to extended hydrogen-dominated atmospheres. Here, we report a space-based measurement of the combined transmission spectrum of the two inner planets made possible by a favorable alignment resulting in their simultaneous transits on 04 May 2016. The lack of features in the combined spectrum rules out cloud-free hydrogen-dominated atmospheres for each planet at 10-$\sigma$ levels; TRAPPIST-1 b and c are hence unlikely to harbor an extended gas envelope as they lie in a region of parameter space where high-altitude cloud/haze formation is not expected to be significant for hydrogen-dominated atmospheres. Many denser atmospheres remain consistent with the featureless transmission spectrum---from a cloud-free water vapour atmosphere to a Venus-like atmosphere.Comment: Early release to inform further the upcoming review of HST's Cycle 24 proposal

Explicit BCJ Numerators from Pure Spinors

We derive local kinematic numerators for gauge theory tree amplitudes which manifestly satisfy Jacobi identities analogous to color factors. They naturally emerge from the low energy limit of superstring amplitudes computed with the pure spinor formalism. The manifestation of the color--kinematics duality is a consequence of the superstring computation involving no more than (n-2)! kinematic factors for the full color dressed n-point amplitude. The bosonic part of these results describe gluon scattering independent on the number of supersymmetries and captures any N^kMHV helicity configuration after dimensional reduction to D=4 dimensions.Comment: 32 pages, harvma

Association between overweight, obesity and self-perceived job insecurity in German employees

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown an association between job insecurity and morbidity as well as mortality, however until now, knowledge about a potential association between job insecurity and overweight or obesity has been lacking.</p> <p>Methods</p> <p>In order to identify a possible association between job insecurity and overweight or obesity, we analysed data from the German Socioeconomic Panel (GSOEP) 2004/2005, a longitudinal study of private households in Germany. In this representative cohort of the German adult population, living and working conditions were observed. Data on Body Mass Index (BMI) and self-perceived probability of job loss within the next 2 years were available for 10,747 adults either employed or attending training programs.</p> <p>Results</p> <p>We identified 5,216 (49%) individuals as being overweight (BMI > 25 kg/m²) and 1,358(13%) individuals as being obese (BMI > 30 kg/m²). A total of 5,941 (55%) participants reported having concerns regarding job insecurity. In the multivariate analysis - after adjustment for relevant confounders - a statistically significant association between obesity and job insecurity (100% probability for losing the job in the following two years) could be observed with an adjusted odds ratio of 2.55 (95% confidence interval: 1.09-5.96).</p> <p>Conclusions</p> <p>Because of these results, we were able to conclude that overweight and obese persons perceive job insecurity more often than their normal weight counterparts in Germany and that the concurrence of obesity and job insecurity might lead employees into a vicious cycle. Further research with an emphasis on the occupational setting might be necessary in order to establish useful preventive programmes at the workplace.</p