Search

In the UK, speech and language therapists (SLTs) and educational psychologists (EPs) are professionals who support children with speech, language and communication needs (SLCN). Legislative and socio-economic changes within the UK and continuing concern about poor outcomes for children with SLCN provided the impetus for a focus on interprofessional collaboration between these two groups. An online survey was distributed to qualified EPs and SLTs in the UK enquiring about facilitators and barriers to collaboration. Responses from 125 EPs and 182 SLTs were content analysed. Responses indicated that communication and working environments were key factors impacting interprofessional collaboration. Relationships and commitment to joint working were also cited as facilitators. Challenges related to reduced resourcing, staffing and changes to working environments as a result of austerity. A framework illustrating possible inter-relationships between factors is presented, indicating hypothesised pathways that could underpin planning for development and change. In summary, despite positive moves towards shared policy and guidance for children with SLCN, findings suggest that a continued focus on maximising effective interprofessional collaboration is crucial to ensure that assessment and early intervention are available to support children with speech, language and communication needs.

In the field of Educational Psychology, consultation is both a core competency to be achieved by the end of pre-service training and a practice that infuses all aspects of service delivery post-qualification. The present study aimed to explore the perspectives of university educators on preparing trainee educational psychologists to consult, especially following significant systemic change at social-political and professional standard levels. A qualitative exploratory design was chosen to inform semi-structured interviews with 14 participants from 16 universities in the United Kingdom providing post-graduate training. These interviews were analyzed thematically, with 10 over-arching themes identified. Themes are discussed across three aspects: (i) systemic factors, (ii) facilitators and barriers in consultation training in the current UK context and (iii) curriculum content and pedagogic methods used in consultation training at pre-service level. Strengths, limitations, and implications for applied practice and future research are discussed.

Since the outbreak of the coronavirus pandemic, socio-economic inequalities have become exacerbated and COVID-19 related hate crimes have increased. This paper explores how citizenship education might be reimagined in response to this context, with the vision of rebuilding a more equitable and compassionate society. By using a collective autobiographical writing approach, this study documented six different autobiographical reflexivities of citizenship education scholars who were from different parts of the world: China, South Korea, the Philippines, the United States, Nepal and the United Kingdom. It also observed the way the pandemic played out in the location where they were situated during the research as well as how it played out in their countries of origin, and further, how it affected the civic development in each context. The scholars' range of autobiographical expressions resulted in insights for developing a type of citizenship education, namely, education for active and compassionate citizenship.

Background: Accelerated biological aging has been verified to be a critical risk factor for a number of age-related diseases, but its role in dementia remained unclear. Whether it modified the effects of genetic factors was also unknown. This study evaluated the associations between accelerated biological aging and dementia and the moderating role of accelerated biological aging in the genetic susceptibility to the disease. Methods: We included 200,731 participants in the UK biobank. Nine clinical blood biomarkers and chronological age were used to calculate Phenotypic age acceleration (PhenoAgeAccel), which is a novel indicator for accelerated biological aging. The associations of PhenoAgeAccel with dementia, both young-onset and late-onset dementia, were assessed by Cox proportional hazard models. Apolipoprotein E (APOE) alleles and polygenic risk scores (PRS) were used to evaluate the genetic risk of dementia. The interactions between genetic susceptibility and biological aging were tested on both multiplicative and additive scales. Results: These findings showed individuals who were in the highest quartile of PhenoAgeAccel had a higher risk with incidence of dementia compared to individuals in the lowest quartile of PhenoAgeAccel (HR: 1.145 (95% CI: 1.050, 1.249)). Individuals with biologically older had a higher risk of dementia than individuals with biologically younger (HR: 1.069 (95% CI: 1.004, 1.138)). Furthermore, compared to individuals with biologically younger and low APOE ε4-related genetic risk, individuals with biologically younger and high APOE ε4-related genetic risk (HR:3.048 (95% CI: 2.811, 3.305)) had a higher risk of dementia than individuals with biologically older and high APOE ε4-related genetic risk (HR: 2.765 (95% CI: 2.523, 3.029)). Meanwhile, referring to low dementia PRS and biologically younger, the risk of dementia increased by 72.7% (HR: 1.727 (95% CI: 1.538, 1.939) in the biologically younger and high PRS group and 58.7% (HR: 1.587 (95% CI: 1.404, 1.793) in the biologically older and high PRS group, respectively. The negative interactions between PhenoAgeAccel with APOE ε4 and PRS were also tested on the additive scale. Conclusions: Accelerated biological aging could bring the extra risk of dementia but attenuate the effects of genetic risk on dementia. These findings provide insights for precise prevention and intervention of dementia. [ABSTRACT FROM AUTHOR]

This paper explores trainee educational psychology doctoral students' experiences of Objective Structured Professional Assessments (OSPAs), implemented at three UK universities and involving participation in a series of timed, simulated scenarios. Focus groups were audio-recorded, transcribed, and subjected to thematic analysis. Themes linked with cognitions included identification of learning processes (reflection, discovery, reception) or practical constraints (authenticity and timing of scenarios). Statements of emotion included positive responses (containment, reassurance, and relief) as well as more adverse reactions to the experience (anxiety and anger). Overall, the findings suggest that many students valued OSPAs as worthwhile and useful in developing professional competencies.

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Composite time trade-off (cTTO) utilities have been found to be higher when adults value health states for children than for themselves. It is not clear if these differences reflect adults assigning truly higher utilities to the same health state in different perspectives, or if they are caused by other factors, which are not accounted for in the valuation procedure. We test if the difference between children's and adults' cTTO valuations changes if a longer duration than the standard 10 years is used. Personal interviews with a representative sample of 151 adults in the UK were conducted. We employed the cTTO method to estimate utilities of four different health states, where adults considered states both from their own and a 10-year-old child's perspective, for durations of 10 and 20 years. We corrected the cTTO valuations for perspective-specific time preferences in a separate task, again for both perspectives. We replicate the finding that cTTO utilities are higher for the child perspective than for the adult perspective, although the difference is only significant when controlling for other variables in a mixed effects regression. Time preferences are close to 0 on average, and smaller for children than adults. After correcting TTO utilities for time preferences, the effect of perspective is no longer significant. No differences were found for cTTO tasks completed with a 10- or 20-year duration. Our results suggest that the child–adult gap is partially related to differences in time preferences and, hence, that correcting cTTO utilities for these preferences could be useful. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease among children and poses a significant threat to their health. This study aims to assess the relationship between various plasma proteins and childhood asthma, thereby identifying potential therapeutic targets. Methods: Based on publicly available genome‐wide association study summary statistics, we employed a two‐sample Mendelian randomization (MR) approach to elucidate the causal relationship between plasma proteins and asthma. Mediation analysis was then conducted to evaluate the indirect influence of plasma proteins on childhood asthma mediated through risk factors. Comprehensive analysis was also conducted to explore the association between plasma proteins and various phenotypes using the UK Biobank dataset. Results: MR analysis uncovered a causal relationship between 10 plasma proteins and childhood asthma. Elevated levels of seven proteins (TLR4, UBP25, CBR1, Rac GTPase‐activating protein 1 [RGAP1], IL‐21, MICB, and PDE4D) and decreased levels of three proteins (GSTO1, LIRB4 and PIGF) were associated with an increased risk of childhood asthma. Our findings further validated the connections between reported risk factors (body mass index, mood swings, hay fever or allergic rhinitis, and eczema or dermatitis) and childhood asthma. Mediation analysis revealed the influence of proteins on childhood asthma outcomes through risk factors. Furthermore, the MR analysis identified 73 plasma proteins that exhibited causal associations with at least one risk factor for childhood asthma. Among them, RGAP1 mediates a significant proportion (25.10%) of the risk of childhood asthma through eczema or dermatitis. Finally, a phenotype‐wide association study based on these 10 proteins and 1403 diseases provided novel associations between these biomarkers and multiple phenotypes. Conclusion: Our study comprehensively investigated the causal relationship between plasma proteins and childhood asthma, providing novel insights into potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Early-onset prostate cancer (EOPC, ≤ 55 years) has a unique clinical entity harboring high genetic risk, but the majority of EOPC patients still substantial opportunity to be early-detected thus suffering an unfavorable prognosis. A refined understanding of age-based polygenic risk score (PRS) for prostate cancer (PCa) would be essential for personalized risk stratification. Methods: We included 167,517 male participants [4882 cases including 205 EOPC and 4677 late-onset PCa (LOPC)] from UK Biobank. A General-, an EOPC- and an LOPC-PRS were derived from age-specific genome-wide association studies. Weighted Cox proportional hazard models were applied to estimate the risk of PCa associated with PRSs. The discriminatory capability of PRSs were validated using time-dependent receiver operating characteristic (ROC) curves with additional 4238 males from PLCO and TCGA. Phenome-wide association studies underlying Mendelian Randomization were conducted to discover EOPC linking phenotypes. Results: The 269-PRS calculated via well-established risk variants was more strongly associated with risk of EOPC [hazard ratio (HR) = 2.35, 95% confidence interval (CI) 1.99–2.78] than LOPC (HR = 1.95, 95% CI 1.89–2.01; I2 = 79%). EOPC-PRS was dramatically related to EOPC risk (HR = 4.70, 95% CI 3.98–5.54) but not to LOPC (HR = 0.98, 95% CI 0.96–1.01), while LOPC-PRS had similar risk estimates for EOPC and LOPC (I2 = 0%). Particularly, EOPC-PRS performed optimal discriminatory capability for EOPC (area under the ROC = 0.613). Among the phenomic factors to PCa deposited in the platform of ProAP (Prostate cancerAge-basedPheWAS; https://mulongdu.shinyapps.io/proap), EOPC was preferentially associated with PCa family history while LOPC was prone to environmental and lifestyles exposures. Conclusions: This study comprehensively profiled the distinct genetic and phenotypic architecture of EOPC. The EOPC-PRS may optimize risk estimate of PCa in young males, particularly those without family history, thus providing guidance for precision population stratification. [ABSTRACT FROM AUTHOR]

Objective Structured Professional Assessments (OSPAs) were developed and evaluated at three universities in the United Kingdom, to supplement supervisor assessments of trainee educational psychologists' placement practice. Participating second year students on three educational psychology doctoral programmes (n = 31) and tutors (n = 12) were surveyed. Scenarios, developed with experienced practitioners, were considered authentic and relevant. Tutor feedback indicated that the marking scheme was a good basis for judgements, but required further calibration and standardisation. Strengths and limitations relating to authenticity of scenarios and practical arrangements were identified. Students considered OSPAs to be a valid assessment of communication and perspective-taking skills, although some found them to be anxiety provoking. Levels of authenticity and complexity were deemed appropriate, although there were concerns over time allowed and how the assessment criteria were interpreted. The discussion highlights how OSPAs address issues relating to assessment reliability by improving objectivity, reducing bias and providing uniformity to student assessment experiences.

There is a need for outreach programs to attract a diverse range of students to the computing discipline. The lack of qualified computing graduates to fill the growing number of computing vacancies is of concern to government and industry and there are few female students entering the computing pipeline at high school level. This paper presents three outreach programs that have the underlying assumption that students need to be reminded about the creativity and potential of computing so that it remains on the radar of their future career options. Each program instigated social and cultural change through a paradigm shift where girls moved from being ICT consumers to ICT creators. By exposing students to a wide variety of ICT activities and careers during secondary schooling, they were more likely to consider studying information systems, computer science or any other computing course at the university level. Results are presented showing student attitudinal changes as well as observed increases in enrolments at secondary school and university courses.

The Children and Families Act (2014) extends statutory protections for young people with special educational needs and disabilities until age 25. Consequently the core curriculum for trainee educational psychologists (TEPs) needs to be developed beyond the current focus of work with early years and school-age children. In order to define requisite professional competencies for working with young people aged 16-25 with learning difficulties and disabilities, and mental health needs, the Delphi Technique was employed to obtain consensus amongst an expert reference group. Two rounds of an online questionnaire and a face-to-face meeting with educational psychologists (EPs) reporting expertise in working with post-16 learners enabled the identification of areas to be added to, or extended within, existing training curricula. A competency framework for EPs working with young people aged 16-25 is proposed and implications for both TEPs and practitioner EPs explored.

Introduction: Limited evidence indicates an association between sleep factors and the risk of Parkinson's disease (PD). However, large prospective cohort studies including both sexes are needed to verify the association between daytime sleepiness, sleep duration, and PD risk. Furthermore, other sleep factors like chronotype and snoring and their impact on increased PD risk should be explored by simultaneously considering daytime sleepiness and snoring. Methods: This study included 409,923 participants from the UK Biobank. Data on five sleep factors (chronotype, sleep duration, sleeplessness/insomnia, snoring, and daytime sleepiness) were collected using a standard self-administered questionnaire. PD occurrence was identified using linkages with primary care, hospital admission, death register, or self-report. Cox proportional hazard models were used to investigate the association between sleep factors and PD risk. Subgroup (age and sex) and sensitivity analyses were performed. Results: During a median follow-up of 11.89 years, 2,158 incident PD cases were documented. The main association analysis showed that prolonged sleep duration (hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.05, 1.37) and occasional daytime sleepiness (HR: 1.15, 95% CI: 1.04, 1.26) increased the PD risk. Compared to those who self-reported never or rarely having sleeplessness/insomnia, participants who reported usually having sleeplessness/insomnia had a decreased risk of PD (HR: 0.85, 95% CI: 0.75, 0.96). Subgroup analysis revealed that women who self-reported no snoring had a decreased PD risk (HR: 0.85; 95% CI: 0.73, 0.99). Sensitivity analyses indicated that the robustness of the results was affected by potential reverse causation and data completeness. Conclusion: Long sleep duration increased the PD risk, especially among men and participants ≥60 years, while snoring increased the risk of PD in women. Additional studies are needed to (i) further consider other sleep traits (e.g., rapid eye movement sleep behavior disorder and sleep apnea) that might be related to PD, (ii) objectively measure sleep-related exposure, and (iii) confirm the effects of snoring on PD risk by considering the impact of obstructive sleep apnea and investigating its underlying mechanisms. [ABSTRACT FROM AUTHOR]

This article reports on the results of a project which used a social network site to support students on a year abroad and foster informal learning, particularly in the area of intercultural communication. The project employed a peer-mentoring structure to solve the problem of role conflict, in which users of these sites may feel some tension as the academic and social dimensions--two contexts usually kept fairly separate--of their lives collide. This article describes how students used the site, reports on the benefits of the project to both students and mentors, and sets out some recommendations for increasing the sustainability of social network sites as pedagogical tools in other educational contexts.

Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we apply a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size from 166,891 to 408,511. We detect 158 rare variants and 105 genes significantly associated with one or more of five kidney function traits, including genes not previously linked to kidney disease in humans. The imputation-powered findings derive support from clinical record-based kidney disease information, such as for a previously unreported splice allele in PKD2, and from functional studies of a previously unreported frameshift allele in CLDN10. This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource (https://ckdgen-ukbb.gm.eurac.edu/) to direct experimental and clinical studies of kidney disease. An exome wide association study of UK Biobank data revealed 158 variants and 105 genes significantly associated with kidney function traits and disease. The findings are supported by functional evidence for a previously unreported mutation in CLDN10. [ABSTRACT FROM AUTHOR]

Perspectives of 107 pupils, parents and school staff involved in inclusion initiatives in two Local Education Authorities in the UK were obtained though interviews and focus groups. The format of the interview was semistructured, with a predetermined set of questions and prompts being delivered according to a standardized protocol. Transcripts were analysed using a qualitative procedure and commonalities and differences of view identified. All groups reported academic and social advantages as positive benefits of returning pupils with special educational needs from special to mainstream settings. Teachers identified changing attitudes and values and sharing staff expertise as important. Teachers' main concerns were organizational (planning, timetabling, curriculum). All groups highlighted some academic and social concerns, though for pupils relatively higher incidences of social concerns were recorded. All groups considered pupil progress to be a primary indicator of successful inclusion: parents placed greater emphasis on academic progress and pupils on social progress. Teachers and parents identified good planning and preparation and supportive communication as prerequisites for successful inclusion. The importance of establishing effective systems of communication is discussed in relation to the further development of inclusive practices. (Contains 7 tables.)

Introduction: Alcohol beverages in many countries are required to display health information and warnings on all product packaging, given the individual and societal harm caused by alcohol. It is unclear whether consumers purchasing alcohol online are able to easily view such information. This study examines the presence, type and location of mandatory and voluntary health information and warnings consumers are exposed to when entering online alcohol retail shopping environments in the United Kingdom (UK) and New Zealand (NZ). Methods: Using an observational study design, 1407 randomly sampled alcoholic beverages from 14 online alcohol retailers (7 per country) were reviewed to ascertain the visual presence or absence of mandatory and voluntary health information and warnings. Results: UK online alcohol retailers were more compliant than NZ retailers in showing mandatory health information (e.g., alcohol by volume percentage was visible on 92% of alcoholic beverages sold online in the UK, compared to 31% in NZ, p < 0.001). A similar pattern was noted for voluntary health warnings. Online retailers in both countries had a low proportion of alcohol products with the viewable mandatory information, and voluntary health warnings were rarely present and/or viewable. Discussion and Conclusions: Mandatory health information and warnings for alcoholic beverages are not fully adhered to within the UK and NZ online retail environments, impacting the ability of consumers to make informed purchase decisions. In both countries, alcohol policy needs to stipulate that mandatory health information and warnings should be clearly viewable on the product page and product imagery of online alcohol retailers. [ABSTRACT FROM AUTHOR]

Background and Objectives Existing research reveals that single men living alone are at a heightened risk of isolation and precarity. This study traced the impact of the pandemic on the daily lives of a group of single men over three waves of the COVID-19 pandemic in the United Kingdom. Research Design and Methods A qualitative longitudinal study with older people aged 50 and older (n = 102), interviewed by telephone in 2020–2021. This analysis focuses on a subsample comprising single men (n = 16) who lived alone and were interviewed three times (n = 48). The men were White British, Black, and Asian, aged 58–88 years, and were identified as facing difficulties in their lives arising from long-term health problems and or/social isolation. Participants were asked about the impact of, and response to, three lockdowns. Data were analyzed using themes identified in the secondary literature using thematic and longitudinal analysis. Results For single men living alone, precarity intensified during the pandemic due to worsening physical and/or mental health combined with restricted access to relationships and activities. Key moments in the life course influenced how these men experienced and viewed the impact of COVID-19. Discussion and Implications This analysis sheds light on the deepening precarity of older men living alone during the pandemic, highlighting the emergence of new vulnerabilities for some. The findings emphasize the need, given the likelihood of future waves of the pandemic, to target support at those living alone, particularly in relation to the provision of community health services, social infrastructure, and combating digital exclusion. [ABSTRACT FROM AUTHOR]

Context: Care homes in the UK were hit badly by the COVID-19 pandemic, with numerous outbreaks and deaths of residents and staff. Objectives: To capture the impact of the pandemic on care home staff well-being and share insights and learning about how to optimise support for the workforce. Methods: Fifteen senior care staff from care homes looking after older people in England were interviewed between December 2020 and March 2021, when the sector was still under strict restriction measures. The topic guide was developed in consultation with care home staff. Interviews were transcribed and analysed using a reflexive thematic analysis approach to identify themes and sub-themes of the impact on staff well-being. Findings: The impact of the pandemic was overwhelmingly negative, with those interviewed reporting both mental and physical health implications. We identified three themes: emotional exhaustion (upset and trauma, increased responsibility and workload, feelings of guilt); frustration (feeling misunderstood, undervalued, unrecognised, abandoned); and relationships (the importance of supportive working relationships within the care home and with external agencies). Limitations: Staff interviewed were managers or in other senior roles; it would be beneficial to synthesise this research with studies involving other care home staff and residents and their relatives. Given the disparate nature of the care home sector, a larger sample may have identified additional insights. Implications: This study provides insight into the resilience of care home staff during the pandemic and challenges to this; this could help to inform future efforts as to support of the workforce and sector. [ABSTRACT FROM AUTHOR]

Background: Research has highlighted a need for more theoretical work in arts interventions, including the role of the dyad. This study aimed to test theories from a literature review on the impact of including carers in museum programmes for people with dementia, and develop a model which can be used in other programmes to consider the impact of including carers more broadly. Methods: Using a realist evaluation approach, theory was developed through interviews and participant-observation at six museums in the UK. Findings: The impacts of including carers fell into seven broad areas – caring responsibility, session function, controlling access, preventing engagement, comparisons and losses, long-term impact of in-the-moment activities, and reducing social isolation and opening up the museum. Conclusions: Including carers may have both unanticipated benefits and negative consequences, and greater attention is needed on how both carers and people with dementia can be supported in shared sessions. Carers should be viewed as participants of programmes, and can even be the main beneficiaries, even where the programme is ostensibly 'for' the person with dementia – it's not simply that carers are the enablers of, or barriers to, the impacts on the person with dementia. [ABSTRACT FROM AUTHOR]

Background: Home exercise regimes are a well-utilised rehabilitation intervention for many conditions; however, adherence to prescribed programmes remains low. Digital interventions are recommended as an adjunct to face-to-face interventions by the National Health Service in the UK and may offer increased exercise adherence, however the evidence for this is conflicting. Method: A systematic review was undertaken using MEDLINE and CINAHL databases using the PRISMA guidelines. Randomised controlled trials in any clinical population evaluating the adherence to prescribed home exercise interventions with and without additional digital interventions were included. Publication quality was assessed using the Cochrane Risk of Bias tool. Results: The search strategy returned a total of 1336 articles, of which 10 randomised controlled trials containing data for 1117 participants were eligible for inclusion. 565 participants were randomised to receive the interventions, and 552 to the control. Seven of the ten trials reported a significant difference in adherence between the control and intervention groups favouring an additional digital intervention. Three trials reported equivalent findings. These three reported longer-term outcomes, suggesting an interaction between adherence and duration of intervention. There was substantial heterogeneity in outcome assessment metrics used across the trials prohibiting formal meta-analysis. This included studies were of low to moderate quality in terms of risk of bias. Conclusion: The addition of a digital interventions to prescribed home exercise programmes can likely increase exercise adherence in the short term, with longer term effects less certain. [ABSTRACT FROM AUTHOR]

Background and purpose: We used two‐sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid‐modifying drugs on intracranial aneurysm (IA). Methods: Genetic variants for the effects of high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A1, low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein B, and triglycerides and targets for lipid‐modifying drugs were selected from the genome‐wide discovery analyses of the UK Biobank. Summary‐level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Results: Univariate MR analyses showed that the HDL‐C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715–0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663–0.906, p = 0.001). The multivariate MR–inverse variance weighted analysis showed that the HDL‐C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434–0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347–0.913, p = 0.02), and the LDL‐C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191–0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160–0.883, p = 0.025). Using genetic proxies of known lipid‐modifying drugs, we found that the increased HDL‐C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747–0.973, p = 0.018), and the decreased LDL‐C with 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080–2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022–3.371, p = 0.042). Conclusions: Genetically determined HDL‐C and LDL‐C reduce the risk of IA and rIA. The effects of different lipid‐modifying drugs on IA need to be further investigated. [ABSTRACT FROM AUTHOR]

Objectives: The growing rate of retraction of scientific publications has attracted much attention within the academic community, but there is little knowledge about the nature of such retractions in schizophrenia-related research. This study aimed to analyze the characteristics of retractions of schizophrenia-related publications. Materials and methods: The Web of Science was searched for eligible studies. A bibliometric analysis was conducted to describe the characteristics of the retractions using R software and Excel 2019. Content analysis was conducted to examine the essential components of retraction notices. Results: A total of 36 retracted publications with 415 citations were identified from 1997 to 2021, of which, 83.3% occurred in the last decade. The overall retraction rate was 0.19%, with most of them (29; 80.56%) from the United Kingdom. The retractions were published in 33 journals, and the 2020 IFs ranged between 0.17 and 49.96 (Median = 3.93). The retractions involved 21 research areas, particularly in Psychiatry (19; 52.78%), Neurosciences and Neurology (10; 27.78%), and Psychology (7; 19.44%). Data issues (17; 42.22%), administrative errors of the publishers (5; 13.89%), and study design (4; 11.11%) were the top three reasons for retractions. Conclusion: This study provides an insight into retractions of schizophreniarelated publications. Institutional governance should be further strengthened to improve the scrutiny of publications, prevent continuing citations, and erroneous propagation after retraction. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study is to understand why some individuals avoid developing Parkinson disease (PD) despite being at relatively high genetic risk, using the largest datasets of individual‐level genetic data available. Methods: We calculated polygenic risk score to identify controls and matched PD cases with the highest burden of genetic risk for PD in the discovery cohort (International Parkinson's Disease Genomics Consortium, 7,204 PD cases and 9,412 controls) and validation cohorts (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease, 8,968 cases and 7,598 controls; UK Biobank, 2,639 PD cases and 14,301 controls; Accelerating Medicines Partnership–Parkinson's Disease Initiative, 2,248 cases and 2,817 controls). A genome‐wide association study meta‐analysis was performed on these individuals to understand genetic variation associated with resistance to disease. We further constructed a polygenic resilience score, and performed multimarker analysis of genomic annotation (MAGMA) gene‐based analyses and functional enrichment analyses. Results: A higher polygenic resilience score was associated with a lower risk for PD (β = −0.054, standard error [SE] = 0.022, p = 0.013). Although no single locus reached genome‐wide significance, MAGMA gene‐based analyses nominated TBCA as a putative gene. Furthermore, we estimated the narrow‐sense heritability associated with resilience to PD (h2 = 0.081, SE = 0.035, p = 0.0003). Subsequent functional enrichment analysis highlighted histone methylation as a potential pathway harboring resilience alleles that could mitigate the effects of PD risk loci. Interpretation: The present study represents a novel and comprehensive assessment of heritable genetic variation contributing to PD resistance. We show that a genetic resilience score can modify the penetrance of PD genetic risk factors and therefore protect individuals carrying a high‐risk genetic burden from developing PD. ANN NEUROL 2022;92:270–278 [ABSTRACT FROM AUTHOR]

GP registrars are required to demonstrate capabilities in 'community orientation', reflecting skills in developing and working with services that respond to community needs. These skills have sometimes been seen as vague and difficult to obtain. In the Yorkshire and the Humber Deanery of Health Education England we developed a novel programme of community placements to overcome this. Registrars spent two half-days with a community organisation of their choosing, working in their practice area. To evaluate if and how community placements enabled registrars to develop capabilities in community orientation. All registrars completing placements were invited to participate in the evaluation; 13 (7%) accepted. Semi-structured, face-to-face and telephone interviews explored registrars' perceptions and experiences of the programme. Interviews were audio-recorded, transcribed verbatim and analysed thematically. The majority of participants reported that placements enabled them to attain a range of capabilities in community orientation. Registrars described an improved understanding of their practice community and the social determinants of health. Placements impacted their clinical practice by stimulating a holistic approach to the assessment and management of health needs. Our analysis described five key mechanisms for this learning: building confidence, building communities and networks of practice, gaining novel perspectives, generating a hunger for general practice and experiential learning. Community placements enabled GP registrars to attain capabilities in community orientation. Further research is required to determine the transferability of our findings and further evaluate mechanisms of learning through placements outside of training and their role in the development of professional practice. [ABSTRACT FROM AUTHOR]

In recent years, many studies have indicated that vitamin C might be negatively associated with the risk of cancer, but the actual relationship between vitamin C and cancer remains ambivalent. Therefore, we utilized a two-sample Mendelian randomization (MR) study to explore the causal associations of genetically predicted vitamin C with the risk of a variety of cancers. Single-nucleotide polymorphisms (SNPs) associated with vitamin C at a significance level of p < 5 × 10–8 and with a low level of linkage disequilibrium (LD) (r2 < 0.01) were selected from a genome-wide association study (GWAS) meta-analysis of plasmid concentration of vitamin C consisting of 52,018 individuals. The data of the GWAS outcomes were obtained from United Kingdom Biobank, FinnGen Biobank and the datasets of corresponding consortia. In the inverse-variance weight (IVW) method, our results did not support the causal association of genetically predicted vitamin C with the risk of overall cancer and 14 specific types of cancer. Similar results were observed in sensitivity analyses where the weighted median and MR-Egger methods were adopted, and heterogeneity and pleiotropy were not observed in statistical models. Therefore, our study suggested that vitamin C was not causally associated with the risk of cancer. Further studies are warranted to discover the potential protective and therapeutic effects of vitamin C on cancer, and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers.Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.Trial Registration: Current controlled trials ISRCTN10497306 . Registered on 16 August 2018. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging with magnetic resonance cholangiopancreatography (MRI‐MRCP) in primary sclerosing cholangitis (PSC) is currently based on qualitative assessment and has high interobserver variability. We investigated the utility and performance of quantitative metrics derived from a three‐dimensional biliary analysis tool in adult patients with PSC. MRI‐MRCP, blood‐based biomarkers, and FibroScan were prospectively performed in 80 participants with large‐duct PSC and 20 healthy participants. Quantitative analysis was performed using MRCP+ (Perspectum Ltd., United Kingdom), and qualitative reads were performed by radiologists. Inter‐reader agreements were compared. Patients were classified into high risk or low risk for disease progression, using Mayo risk score (MRS), Amsterdam‐Oxford model (AOM), upper limit of normal (ULN) alkaline phosphatase (ALP), disease distribution, and presence of dominant stricture. Performance of noninvasive tools was assessed using binomial logistic regressions and receiver operating characteristic curve analyses. Quantitative biliary metrics performed well to distinguish abnormal from normal bile ducts (P < 0.0001). Interobserver agreements for MRCP+ dilatation metrics (intraclass correlation coefficient, 0.90‐0.96) were superior to modified Amsterdam intrahepatic stricture severity score (κ = 0.74) and Anali score (κ = 0.38). MRCP+ intrahepatic dilatation severity showed excellent performance to classify patients into high‐risk and low‐risk groups, using predictors of disease severity as the reference (MRS, P < 0.0001; AOM, P = 0.0017; 2.2 × ULN ALP, P = 0.0007; 1.5 × ULN ALP, P = 0.0225; extrahepatic disease, P = 0.0331; dominant stricture, P = 0.0019). MRCP+ intrahepatic dilatation severity was an independent predictor of MRS >0 (odds ratio, 31.3; P = 0.035) in the multivariate analysis. Conclusion: Intrahepatic biliary dilatation severity calculated using MRCP+ is elevated in patients with high‐risk PSC and may be used as an adjunct for risk stratification in PSC. This exploratory study has provided the groundwork for examining the utility of novel quantitative biliary metrics in multicenter studies. [ABSTRACT FROM AUTHOR]

The year 2018 marked 40 years since the birth of Louise Brown, the first baby born as a result of pioneering in vitro fertilization (IVF) treatment. Since then, advances have seen a wide range of reproductive technologies emerge into clinical practice, including adjuvant treatments often referred to as IVF "add-ons." However, these "optional extras" have faced growing criticism, especially when they have often come at additional financial cost to the patient and have little evidence supporting their efficacy to improve pregnancy or birth rates. Despite this, according to the latest national patient survey by the Human Fertilisation and Embryology Authority, three quarters of patients who had fertility treatment in the United Kingdom in the past two years had at least one type of treatment add-on highlighting the growing demand for these interventions. This article uses a psychosocial perspective to consider the motivations behind patient and clinician behavior along with the wider societal and economic factors that may be impacting upon the increase in the use of adjuvant treatments in fertility clinics more widely. It suggests the reasons fertility patients use unproven "optional extras" are complex, with interpersonal, psychological, and social factors intertwining to generate an increase in the use of IVF add-ons. [ABSTRACT FROM AUTHOR]

Motivation Transcriptome-wide association studies (TWAS) have successfully facilitated the discovery of novel genetic risk loci for many complex traits, including late-onset Alzheimer's disease (AD). However, most existing TWAS methods rely only on gene expression and ignore epigenetic modification (i.e. DNA methylation) and functional regulatory information (i.e. enhancer-promoter interactions), both of which contribute significantly to the genetic basis of AD. Results We develop a novel gene-level association testing method that integrates genetically regulated DNA methylation and enhancer–target gene pairs with genome-wide association study (GWAS) summary results. Through simulations, we show that our approach, referred to as the CMO (cross methylome omnibus) test, yielded well controlled type I error rates and achieved much higher statistical power than competing methods under a wide range of scenarios. Furthermore, compared with TWAS, CMO identified an average of 124% more associations when analyzing several brain imaging-related GWAS results. By analyzing to date the largest AD GWAS of 71 880 cases and 383 378 controls, CMO identified six novel loci for AD, which have been ignored by competing methods. Availabilityand implementation The data used in this work were obtained from the following publicly available datasets: IGAP1, GWAX, UK Biobank, a 2019 meta-analyzed AD GWAS results and a imaging-derived phenotype GWAS results. The data resources are summarized in Supplementary Table S7. We used the publicly available software and tools for competing methods. All codes used to generate results that are reported in this manuscript and software for our newly proposed method CMO are available at https://github.com/ChongWuLab/CMO. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

With a recent surge of research on narcissism, narcissism questionnaires are increasingly being translated and applied in various countries. The measurement invariance of an instrument across countries is a precondition for being able to compare scores across countries. We investigated the cross-cultural measurement invariance of three narcissism questionnaires (Brief Pathological Narcissism Inventory [B-PNI], Narcissistic Personality Inventory [NPI], and Narcissistic Admiration and Rivalry Questionnaire [NARQ]) and mean-level differences across samples from the United States (N = 2,464), the United Kingdom (N = 307), and Germany (N = 925). Overall, the B-PNI and NARQ functioned equivalently for the U.S. and U.K. participants. More violations of measurement invariance were found between Germany and the combined U.S. and U.K. samples, and for the NPI. In the B-PNI and NARQ, Americans scored higher than individuals from the United Kingdom regarding agentic aspects (self-sacrificing self-enhancement, admiration), while Germans scored lower than both Americans and U.K. individuals regarding antagonistic (entitlement rage, rivalry) and neurotic (hiding the self, contingent self-esteem) aspects. More inconsistent results were found for NPI facets. When noninvariance was present, observed means yielded biased results. Thus, the degree of measurement invariance across translated instrument versions should be considered in cross-cultural comparisons, even with culturally similar countries. [ABSTRACT FROM AUTHOR]

This book examines the decline in practitioners of the Roman Catholic faith in the United States and Britain. Professor Bullivant uses the Vatican II Council as a pivotal point in this decline but is careful to identify the cultural shifts pre-Council that fertilized the grounds from which increasing dissension grew. Bullivant provides abundant discussion with richly detailed examples of the need for both parish life and CREDs in maintaining a vibrant atmosphere of faith. [Extracted from the article]

The use of non‐medical referral, community referral or social prescribing interventions has been proposed as a cost‐effective alternative to help those with long‐term conditions manage their illness and improve health and well‐being. However, the evidence base for social prescribing currently lags considerably behind practice. In this paper, we explore what is known about whether different methods of social prescribing referral and supported uptake do (or do not) work. Supported by an Expert Advisory Group, we conducted a realist review in two phases. The first identified evidence specifically relating to social prescribing in order to develop programme theories in the form of 'if‐then' statements, articulating how social prescribing models are expected to work. In the second phase, we aimed to clarify these processes and include broader evidence to better explain the proposed mechanisms. The first phase resulted in 109 studies contributing to the synthesis, and the second phase 34. We generated 40 statements relating to organising principles of how the referral takes place (Enrolment), is accepted (Engagement), and completing an activity (Adherence). Six of these statements were prioritised using web‐based nominal group technique by our Expert Group. Studies indicate that patients are more likely to enrol if they believe the social prescription will be of benefit, the referral is presented in an acceptable way that matches their needs and expectations, and concerns elicited and addressed appropriately by the referrer. Patients are more likely to engage if the activity is both accessible and transit to the first session supported. Adherence to activity programmes can be impacted through having an activity leader who is skilled and knowledgeable or through changes in the patient's conditions or symptoms. However, the evidence base is not sufficiently developed methodologically for us to make any general inferences about effectiveness of particular models or approaches. [ABSTRACT FROM AUTHOR]

There are more than 40,000 agricultural cooperatives in Europe with 9 million farmer members and over 600,000 workers. Due to the democratic nature of the cooperative form, it is assumed agricultural cooperatives empower their members and allow small farmers to have a stronger voice in the supply chain. However, much of the academic literature on agricultural cooperatives focuses on the economic analysis of their performance, while hardly any research has been done on analysing the impact that policy, long supply chains and the internationalisation of the food system have on members and labour dimensions. This article contributes to covering this gap by analysing how agricultural cooperatives are being shaped and misshaped by European farming policy and the architecture of global food systems. Following Schneiberg's thesis on social movements being a condition for processes of diffusion and mutualism, this article reflects on critical issues in organisational studies related to agricultural cooperatives, the cooperative movement and sustainable food systems. Case studies from Spain and United Kingdom are used to illustrate the Northern and Southern European perspective. The concept of deviant mainstreaming is applied to discuss how agricultural cooperatives are being co-opted and losing their transformative potential as a result of pressures to remain competitive, with effects on members, social justice and the environment. The findings suggest policy changes at the European level, and the increasing internationalisation of the food system is fuelling the amalgamation of agricultural cooperatives, which is threatening their local embeddedness and creating organisational tensions between the local, co-operative space and the global, capitalist space. [ABSTRACT FROM AUTHOR]

Community supported agriculture schemes are a prominent example of localized alternatives to the global food system. They are presented as alternative nodes of food production, where the consumer experiences a much closer relationship to the produce they are consuming and to the labour involved in producing it. They lift the commodity veil by inviting the consumer into the world of production – of labour. However, there has been little analysis of labour undertaken in the setting of community supported agriculture, particularly the labour of community supported agriculture consumers, or members. Marxian analysis of the food system at the macro level has underpinned powerful critiques of its shortcomings and highlighted inequalities of land and labour, but has rarely been employed to understand the possibilities of alternative food networks at a more micro level. In this article, I draw on Marx's concept of alienation to explore the experience and organization of labour within a community supported agriculture scheme in the United Kingdom. In doing so, I present a case study of how labour in a community supported agriculture scheme counteracts experiences of alienation created by capitalism and consider how this might inform (re)organization of labour in the food system, more generally. [ABSTRACT FROM AUTHOR]

The centrally coordinated response that controlled the polio epidemics of the 1950s through immunisation led to the development of a national immunisation strategy in the UK and the formation of the Joint Committee on Vaccination and Immunisation (JCVI) in 1963, which oversees the immunisation programme and advises the UK Department of Health on new vaccine introductions. As a result of technological advances in vaccine development and scientific advances in immunology and microbiology over the 56 years since then, and the formation of a comprehensive public health surveillance system for vaccine-preventable disease, the National Health Service immunisation programme now covers 18 serious diseases of childhood, with an astonishing impact on child health. Here we consider the formation of the JCVI and the development of the national immunisation programme and review the introduction of vaccines over the past half century to defend public health. [ABSTRACT FROM AUTHOR]

This study reviewed perceived changes to planning and management of transitions to adulthood for young people with special educational needs and disabilities in three local authorities in England, following implementation of the Children and Families Act (2014). Wenger's 'community of practice' theoretical framework was used to examine how groups of professionals and managers working in education, health and social care in three areas, set about implementing selected radical changes required by the legislation. Telephone interviews with sixteen participants were transcribed and subjected to thematic analysis. Themes identified related to professional activity, planning and organisation, implications for young people and families and outcomes. There were indications of shifts in professional conceptualisations and reported practices as a result of the Act. Participants described enhanced cross‐service communication and co‐ordinated working practices, achieved though service restructuring, co‐location and changed lines of accountability. An increased emphasis on long‐term planning and involving young people in planning and decision‐making was evident with regard to defining outcomes, and living and working as an adult. The results are considered in relation to the extent that mandated change can influence attitudes and cultures within communities of practice, contributing to the contemporary theoretical debate to incorporate issues relating to power. [ABSTRACT FROM AUTHOR]

Background: People with head and neck cancer have higher comorbidity levels but it remains unclear if pretreatment comorbidity is an independent prognosticator in head and neck cancer. Methods: Survival analyses were performed using data from participants in a UK multicentre cohort study with cancers of the oral cavity (n = 668), oropharynx (n = 1074), and larynx (n = 530). Survival analyses were incrementally adjusted for age, sex, marital status, income, education, stage, alcohol, and smoking. Results: After adjusting for demographic, clinical, and behavioral confounders, higher baseline comorbidity was associated with reduced overall survival (mild comorbidity HR = 1.4, 95% CI = 1.1, 1.7; moderate comorbidity HR = 1.7, 95% CI = 1.3, 2.2; severe comorbidity HR = 2.8, 95% CI = 1.9, 4.; P‐trend<.001). Conclusions: Our findings suggest that comorbidity is an independent prognosticator for overall survival in head and neck cancer. Comorbid illnesses should be considered in the assessment and treatment planning of people with head and neck cancer. [ABSTRACT FROM AUTHOR]

The article looks at the accounting measurement practices in France, Germany, and Great Britain and the differences in the effects of their financial statements. The differences in financial ratios and stock market valuation of accounting data are not explained by macroeconomic factors, they are predictable, and they are present in net income. The directives of enacted legislation by the European Union do not affect the cross-country differences despite efforts to create an integrated set of financial reporting standards.

The article discusses geographic income shifting in a sample of 191 U.S. multinational corporations due to worldwide tax rate changes during the period of 1984-90. Great Britain had corporate tax rates reduced from 45% to 35% between 1984 and 1986. France lowered rates from 50% to 45% in 1986 which led to the U.S. lowering corporate tax rates from 46% to 34% between 1986 and 1988. However, Canada increased their rates between 1984 and 1986 before lowering them in 1989. Differential tax rate changes are incentives for multinational corporations to conduct geographic income shifting.

The objective of the present paper is to draw lessons from policy development on sustainable diets. It considers the emergence of sustainable diets as a policy issue and reviews the environmental challenge to nutrition science as to what a 'good' diet is for contemporary policy. It explores the variations in how sustainable diets have been approached by policy-makers. The paper considers how international United Nations and European Union (EU) policy engagement now centres on the 2015 Sustainable Development Goals and Paris Climate Change Accord, which require changes across food systems. The paper outlines national sustainable diet policy in various countries: Australia, Brazil, France, the Netherlands, Qatar, Sweden, UK and USA. While no overarching common framework for sustainable diets has appeared, a policy typology of lessons for sustainable diets is proposed, differentiating (a) orientation and focus, (b) engagement styles and (c) modes of leadership. The paper considers the particularly tortuous rise and fall of UK governmental interest in sustainable diet advice. Initial engagement in the 2000s turned to disengagement in the 2010s, yet some advice has emerged. The 2016 referendum to leave the EU has created a new period of policy uncertainty for the UK food system. This might marginalise attempts to generate sustainable diet advice, but could also be an opportunity for sustainable diets to be a goal for a sustainable UK food system. The role of nutritionists and other food science professions will be significant in this period of policy flux. [ABSTRACT FROM AUTHOR]

Background: There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-methyl-D-aspartate receptor (NMDAR) and the voltage-gated potassium channel (VGKC)-complex reported in a few patients with first-episode psychosis (FEP). Methods: Participants were recruited from psychiatric services in South London, UK, from 2009 to 2011 as part of the Genetics and Psychosis study. We conducted a case–control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex. Leucine-rich glioma inactiviated-1 (LGI1) and contactin-associated protein (CASPR) antibodies were also measured. Notably, patients with suspicion of organic disease were excluded. Results: VGKC-complex antibodies were found in both cases (n = 3) and controls (n = 2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls. Conclusions: This case–control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Care Excellence (NICE) invited Servier, the company manufacturing trifluridine and tipiracil (T/T; trade name: Lonsurf®), to submit evidence for the clinical and cost effectiveness of T/T compared with best supportive care (BSC) for metastatic colorectal cancer (third-line or later). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the Evidence Review Group (ERG). This paper presents a summary of the company's submission (CS), the ERG report and the development of the NICE guidance for the use of this drug in England and Wales by the appraisal committee (AC). The ERG produced a critical review of the clinical and cost effectiveness of T/T based upon the CS. In the CS, pooled evidence of two trials (a phase II trial and RECOURSE) showed that T/T resulted in a significant increase in overall survival [OS; hazard ratio (HR) 0.67, 95% CI 0.58-0.78] and progression-free survival (PFS; HR 0.46, 95% CI 0.40-0.53). The AC considered the survival benefit of T/T clinically meaningful although relatively small. The ERG highlighted that none of the participants in the phase II trial and approximately half of the RECOURSE participants (394 of 800) were from Europe, which might limit the applicability of the study findings to the NHS. Moreover, the ERG's critical assessment of the company's economic evaluation highlighted a number of concerns that resulted in 11 adjustments to the company's base-case analysis. The ERG adjustments that had the largest impact were using the RECOURSE trial data only (instead of the pooled evidence), fixing errors and violations and using the utilities from the CORRECT trial (identified in the literature review) only. The ERG preferred to use the RECOURSE trial data only given the suboptimal methodology used by the company to pool the evidence. However, since there were no fundamental arguments to prevent the two trials from being pooled, the ERG also presented its base-case analysis based on the pooled effectiveness estimates. The company base-case resulted in an incremental cost effectiveness ratio (ICER) of £44,032 per QALY gained while the ERG base-case resulted in ICERs of £52,695 and £49,392 per QALY gained based on the RECOURSE trial only and pooled evidence, respectively. Since the AC concluded that the most plausible ICER was £49,392 per QALY gained, and that T/T meets end-of-life criteria, T/T was recommended as a cost effective use of NHS resources. [ABSTRACT FROM AUTHOR]

This study uses boundary crossing in activity theory as one normative framework for opening a deliberative inquiry in new discursive spaces to elicitgender awarenessin teachers’ practices. We illustrate this framework by drawing from data in one European teacher education project. Seven case studies were conducted and data were analysed from a convenience sample of teacher educators who alongside the authors acted as national coordinators for the project. Data sources included questionnaires of initial ratings, case study reports, transcripts of team meetings and interviews. A cluster analysis of ratings was guided in a step-wise manner and yielded two distinct cluster groups where one group of case studies had high ratings of gender-specific settings. This finding was then used in a qualitative interpretation of data sources for deeper contextual understandings of teacher educators’ perspectives. Gender-specific settings had a reported context of aspects in an activity system which three case studies grasped as school-based planning, pedagogical innovation and mentoring supports. The framework for analysis of higher order gender aspects showed success in distinguishing case studies with isolated views of gender. Findings also showed limitations in the partially restricted framing of gender as an activity system at the outset of the project and indicated in some instances, reluctant teacher educators. The study underscores the explanatory power of the framework adopted and opens up hypotheses for further research and consideration. [ABSTRACT FROM PUBLISHER]

There is increasing demand for a systems approach within national healthcare guidelines to provide a systematic and sustainable framework for improvements in patient safety. Supported by this is the growing body of evidence within Human Factors/Ergonomics (HFE) healthcare literature for the inclusion of this approach in health service design, provision and evaluation. This paper considers the current interpretation of this within UK healthcare systems and the dichotomy which exists in the challenge to implement a systems approach. Three case studies, from primary and secondary care, present a systems approach, offering a novel perspective of primary care and blood sampling. These provide practical illustrations of how HFE methods have been used in collaboration with healthcare staff to understand the system for the purpose of professional education, design and safety of clinical activities. The paper concludes with the challenge for implementation and proposes five roles for systems HFE to support patient safety. Practitioner Summary:healthcare is classified as a complex and dynamic system within this paper and as such HFE system methods are presented as desirable to understand the system, to develop HFE tools, to deliver education and integrate HFE within healthcare systems. [ABSTRACT FROM PUBLISHER]

This paper investigates the relationship between tax and expenditure limits (TELs) and local government deficit financing decisions following the recent recession. Cities under the resource constraints are hypothesised to practise conservatism in financial management decisions and thus less likely to deficit finance during difficult times. Using data from 2005 to 2012 Comprehensive Annual Financial Reports of the 50 largest US cities, this paper finds that cities subject to a binding TEL are more likely to control expenditure growth from pre-crisis years to years following the recession; these cities are also less likely to increase deficit financing following the recession, as indicated by a relative increase in their net assets. Although continuous deficit erodes fiscal sustainability and is an undesirable management practice, deficit financing during recessions may be needed for smoothing expenditure and sustaining service provision. The management conservatism associated with the fiscal rules may contribute to the cyclicality of local spending. [ABSTRACT FROM PUBLISHER]