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This research aimed to describe and evaluate research on the Postgraduate Taught (PGT) sector in the UK from January 2008 to October 2019. The focus on PGT allowed a detailed analysis of an often overlooked part of the HE sector. Methodologically, the research is original in its use of an innovative machine learning approach to a systematic scoping review. The review scrutinised subject areas, topics studied and methodological approaches taken. Initial searches found 9,814 potentially relevant studies which were reduced to 693 for analysis. The machine learning approach was successful in reducing time without compromising accuracy. We conclude that this methodological approach is appropriate for similar reviews within education. Findings show a dominance of research into professional education programmes; a majority of research with PGT as the context rather than focus; a small number of comparative and large-scale studies; and substantial research categorised as 'scholarship of teaching'. While further research is required to ascertain if the findings are transferable to other national contexts, this study provides a reproducible methodology and identifies areas for future research to examine.

This study explored the experiences of professionals and parents from the United Kingdom and China of autism-relevant policies, school involvement, and applied behavior analysis-based interventions. Semistructured interviews involving 36 parents and professionals and direct behavioral observations were carried out of five parents and three professionals. Results found: (1) a lack of autism support and applied behavior analysis-related services in both countries; (2) applied behavior analysis-based intervention was not as widely endorsed by healthcare or educational systems in the United Kingdom; Chinese parents faced challenges around inclusive education and accessing high-quality services and there was a social stigma attached to autism; (3) a limited awareness and application of early intensive behavior intervention in both regions; and (4) intervention fidelity with regards to the practice of one particular applied behavior analysis-based intervention, discrete trial teaching, was similar and increased with ongoing training. Professional and parental experiences were discussed in the context of policy and educational involvement. This study illustrates the need to support children with autism and to consider regional adaptations of evidence-based practice of behavior analysis for the affected population.

Background and aims: Smokers typically have a lower body mass index (BMI) than non‐smokers, while smoking cessation is associated with weight gain. In pre‐clinical research, nicotine in tobacco smoking suppresses appetite and influences subsequent eating behaviour; however, this relationship is unclear in humans. This study measured the associations of smoking with different eating and dietary behaviours. Design: A cross‐sectional analysis of data from health assessments conducted between 2004 and 2022. Setting: An independent healthcare‐based charity within the United Kingdom. Participants: A total of 80 296 men and women (mean ± standard deviation [SD]: age, 43.0 ± 10.4 years; BMI, 25.7 ± 4.2 kg/m2; 62.5% male) stratified into two groups based on their status as a smoker (n = 6042; 7.5%) or non‐smoker (n = 74 254; 92.5%). Measurements Smoking status (self‐report) was the main exposure, while the primary outcomes were selected eating and dietary behaviours. Age, sex and socioeconomic status (index of multiple deprivation [IMD]) were included as covariates and interaction terms, while moderate‐to‐vigorous exercise and sleep quality were included as covariates only. Findings Smokers had lower odds of snacking between meals and eating food as a reward or out of boredom versus non‐smokers (all odds ratio [OR] ≤ 0.82; P < 0.001). Furthermore, smokers had higher odds of skipping meals, going more than 3 h without food, adding salt and sugar to their food, overeating and finding it hard to leave something on their plate versus non‐smokers (all OR ≥ 1.06; P ≤ 0.030). Additionally, compared with non‐smokers, smoking was associated with eating fried food more times per week (rate ratio [RR] = 1.08; P < 0.001), eating fewer meals per day, eating sweet foods between meals and eating dessert on fewer days per week (all RR ≤ 0.93; P < 0.001). Several of these relationships were modified by age, sex and IMD. Conclusions: Smoking appears to be associated with eating and dietary behaviours consistent with inhibited food intake, low diet quality and altered food preference. Several of these relationships are moderated by age, sex and socioeconomic status. [ABSTRACT FROM AUTHOR]

The high prevalence of conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) makes early prevention of AD extremely critical. Neuroticism, a heritable personality trait associated with mental health, has been considered a risk factor for conversion from aMCI to AD. However, whether the neuroticism genetic risk could predict the conversion of aMCI and its underlying neural mechanisms is unclear. Neuroticism polygenic risk score (N‐PRS) was calculated in 278 aMCI patients with qualified genomic and neuroimaging data from ADNI. After 1‐year follow‐up, N‐PRS in patients of aMCI‐converted group was significantly greater than those in aMCI‐stable group. Logistic and Cox survival regression revealed that N‐PRS could significantly predict the early‐stage conversion risk from aMCI to AD. These results were well replicated in an internal dataset and an independent external dataset of 933 aMCI patients from the UK Biobank. One sample Mendelian randomization analyses confirmed a potentially causal association from higher N‐PRS to lower inferior parietal surface area to higher conversion risk of aMCI patients. These analyses indicated that neuroticism genetic risk may increase the conversion risk from aMCI to AD by impairing the inferior parietal structure. [ABSTRACT FROM AUTHOR]

Purpose: To explore the potential causal links between obesity, type 2 diabetes (T2D), and lifestyle choices (such as smoking, alcohol and coffee consumption, and vigorous physical activity) on stress urinary incontinence (SUI), this study employs a Mendelian Randomization approach. This research aims to clarify these associations, which have been suggested but not conclusively established in prior observational studies. Methods: Genetic instruments associated with the exposures at the genome‐wide significance (p < 5 × 10−8) were selected from corresponding genome‐wide association studies. Summary‐level data for SUI, was obtained from the UK Biobank. A two‐sample MR analysis was employed to estimate causal effects, utilizing the inverse‐variance weighted (IVW) method as the primary analytical approach. Complementary sensitivity analyses including MR‐PRESSO, MR‐Egger, and weighted median methods were performed. The horizontal pleiotropy was detected by using MR‐Egger intercept and MR‐PRESSO methods, and the heterogeneity was assessed using Cochran's Q statistics. Results: Our findings demonstrate a significant causal relationship between higher body mass index (BMI) and the risk of SUI, with increased abdominal adiposity (WHRadjBMI) similarly linked to SUI. Smoking initiation is also causally associated with an elevated risk. However, our analysis did not find definitive causal connections for other factors, including T2D, alcohol consumption, coffee intake, and vigorous physical activity. Conclusions: These findings provide valuable insights for clinical strategies targeting SUI, suggesting a need for heightened awareness and potential intervention in individuals with higher BMI, WHR, and smoking habits. Further research is warranted to explore the complex interplay between genetic predisposition and lifestyle choices in the pathogenesis of SUI. [ABSTRACT FROM AUTHOR]

The concept of biological age has emerged as a measurement that reflects physiological and functional decline with ageing. Here we aimed to develop a deep neural network (DNN) model that predicts biological age from optical coherence tomography (OCT). A total of 84,753 high-quality OCT images from 53,159 individuals in the UK Biobank were included, among which 12,631 3D-OCT images from 8,541 participants without any reported medical conditions at baseline were used to develop an age prediction model. For the remaining 44,618 participants, OCT age gap, the difference between the OCT-predicted age and chronological age, was calculated for each participant. Cox regression models assessed the association between OCT age gap and mortality. The DNN model predicted age with a mean absolute error of 3.27 years and showed a strong correlation of 0.85 with chronological age. After a median follow-up of 11.0 years (IQR 10.9–11.1 years), 2,429 deaths (5.44%) were recorded. For each 5-year increase in OCT age gap, there was an 8% increased mortality risk (hazard ratio [HR] = 1.08, CI:1.02–1.13, P = 0.004). Compared with an OCT age gap within ± 4 years, OCT age gap less than minus 4 years was associated with a 16% decreased mortality risk (HR = 0.84, CI: 0.75–0.94, P = 0.002) and OCT age gap more than 4 years showed an 18% increased risk of death incidence (HR = 1.18, CI: 1.02–1.37, P = 0.026). OCT imaging could serve as an ageing biomarker to predict biological age with high accuracy and the OCT age gap, defined as the difference between the OCT-predicted age and chronological age, can be used as a marker of the risk of mortality. [ABSTRACT FROM AUTHOR]

Background and aims: Few studies have examined the relationship between daytime napping and risk of kidney diseases. We aimed to investigate the association of daytime napping with the incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). We also examined whether sleep duration modified the association of nap with CKD or ESKD. Methods: We recruited 460,571 European middle- to older-aged adults without prior CKD or ESKD between March 13, 2006, and October 1, 2010, in the UK Biobank. Sleep behavior data were obtained through questionnaires administered during recruitment. The analysis of the relationship between napping and the occurrence of CKD and ESKD utilized Cox proportional hazards regression models. The modification role of sleep duration on the effect of nap on CKD and ESKD was also examined. Results: After a mean follow-up of 11.1 (standard deviation 2.2) years, we observed 28,330 incident CKD cases and 927 ESKD cases. The daytime napping was associated with incident CKD (P for trend =.004). After fully adjusted, when compared with participants who did not take nap, those in sometimes and usually nap groups had higher risk of CKD. Nevertheless, the available evidence did not support a link between daytime napping and ESKD (P for trend =.06). Simultaneously, there was insufficient evidence suggesting that sleeping duration modified the association of daytime napping with incident CKD or ESKD. Conclusion: Daytime napping was associated with an increased risk of CKD. However, the absence of conclusive evidence did not indicate a connection between daytime napping and ESKD. [ABSTRACT FROM AUTHOR]

Objective: To identify the causal role of sodium‐glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. Methods: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. Results: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. Conclusions: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers. [ABSTRACT FROM AUTHOR]

In the process of decarbonization, the configuration of renewable energy and energy storage plays a crucial role. In current research, there is often a singular focus on the isolated optimization of either renewable energy configurations or energy storage configurations, resulting in limitations within the optimized outcomes. Therefore, we propose a collaborative configuration approach for renewable energy and energy storage under fixed investment, considering the impact of uncertainty on optimization results. By employing the W/S (wind-to-solar ratio) and E/P (energy-to-power ratio) and constructing a model with an hourly granularity, we can obtain the configurations of renewable energy and energy storage at crucial time points. Using the UK as a case study, we calculate the configurations for renewable energy and energy storage from 2020 to 2050, offering effective recommendations for the decarbonization efforts in the UK. [ABSTRACT FROM AUTHOR]

This research aimed to describe and evaluate research on the Postgraduate Taught (PGT) sector in the UK from January 2008 to October 2019. The focus on PGT allowed a detailed analysis of an often overlooked part of the HE sector. Methodologically, the research is original in its use of an innovative machine learning approach to a systematic scoping review. The review scrutinised subject areas, topics studied and methodological approaches taken. Initial searches found 9,814 potentially relevant studies which were reduced to 693 for analysis. The machine learning approach was successful in reducing time without compromising accuracy. We conclude that this methodological approach is appropriate for similar reviews within education. Findings show a dominance of research into professional education programmes; a majority of research with PGT as the context rather than focus; a small number of comparative and large-scale studies; and substantial research categorised as 'scholarship of teaching'. While further research is required to ascertain if the findings are transferable to other national contexts, this study provides a reproducible methodology and identifies areas for future research to examine. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between work‐related factors and amyotrophic lateral sclerosis (ALS) is unclear. We used a Mendelian randomization (MR) analysis to investigate the unconfounded association between work‐related factors and ALS. Methods: Univariable MR analyses were conducted to evaluate the causal effects of work‐related factors on ALS. Instrumental variables from the UK Biobank on work‐related factors (n = 263,615) were used as proxies. The outcome dataset used ALS (n case = 20,806, n control = 59,804) summary‐level data from a large‐scale genome‐wide association study based on European ancestry. MR analysis used inverse variance weighted (IVW), MR‐Egger, and weighted median (WM) to assess causal effects and other methods of MR for sensitivity analysis. Further multivariable MR analyses were performed to explore potential mediating effects. Results: In univariable MR, IVW methods support evidence that genetically determined job involves heavy manual or physical work (OR = 2.04, 95% CI: 1.26–3.31; p =.004) was associated with an increased risk of ALS, and the WM methods also confirm this result (OR = 2.36, 95% CI: 1.30–4.28; p =.005). No evidence of heterogeneity or horizontal pleiotropy was found in the results. In multivariable MR, the association was absent after adjusting for smoking and blood pressure. Conclusions: Our MR analysis results demonstrate the potential causal relationship between jobs that involve heavy manual or physical work and ALS, which might be mediated by smoking and high systolic blood pressure. [ABSTRACT FROM AUTHOR]

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment. [ABSTRACT FROM AUTHOR]

Background Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk. Methods In this cohort study, we included 429 566 UK Biobank participants (94.5% white, 54% women, age 56 ± 8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were risk of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias. Results During an average follow-up of 10.11 years, 4427 incident strokes occurred, among which 3447 were ischemic and 1163 were hemorrhagic. After adjustment for confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 mL/min/1.73 m2 decrement in eGFRcys were 1.10 (1.05–1.14) for total stroke and 1.11 (1.08–1.15) for ischemic stroke. A similar pattern was observed with eGFRcr, although the association was weaker. When either type of eGFR was below 75 mL/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. A U-shaped relationship was witnessed if eGFRcr was used instead. There was a null association between eGFR and hemorrhagic stroke. Conclusions The risks of total stroke and ischemic stroke increased exponentially when the eGFRcys fell below 75 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. Methods: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. Results: Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. Conclusions: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce mortality. The UK National Screening Committee recommended targeted lung cancer screening on Sept 29, 2022, and asked for more modelling work to be done to help refine the recommendation. This study aims to develop and validate a risk prediction model—the CanPredict (lung) model—for lung cancer screening in the UK and compare the model performance against seven other risk prediction models. For this retrospective, population-based, cohort study, we used linked electronic health records from two English primary care databases: QResearch (Jan 1, 2005–March 31, 2020) and Clinical Practice Research Datalink (CPRD) Gold (Jan 1, 2004–Jan 1, 2015). The primary study outcome was an incident diagnosis of lung cancer. We used a Cox proportional-hazards model in the derivation cohort (12·99 million individuals aged 25–84 years from the QResearch database) to develop the CanPredict (lung) model in men and women. We used discrimination measures (Harrell's C statistic, D statistic, and the explained variation in time to diagnosis of lung cancer [R2 D ]) and calibration plots to evaluate model performance by sex and ethnicity, using data from QResearch (4·14 million people for internal validation) and CPRD (2·54 million for external validation). Seven models for predicting lung cancer risk (Liverpool Lung Project [LLP] v2 , LLP v3 , Lung Cancer Risk Assessment Tool [LCRAT], Prostate, Lung, Colorectal, and Ovarian [PLCO] M2012 , PLCO M2014 , Pittsburgh, and Bach) were selected to compare their model performance with the CanPredict (lung) model using two approaches: (1) in ever-smokers aged 55–74 years (the population recommended for lung cancer screening in the UK), and (2) in the populations for each model determined by that model's eligibility criteria. There were 73 380 incident lung cancer cases in the QResearch derivation cohort, 22 838 cases in the QResearch internal validation cohort, and 16 145 cases in the CPRD external validation cohort during follow-up. The predictors in the final model included sociodemographic characteristics (age, sex, ethnicity, Townsend score), lifestyle factors (BMI, smoking and alcohol status), comorbidities, family history of lung cancer, and personal history of other cancers. Some predictors were different between the models for women and men, but model performance was similar between sexes. The CanPredict (lung) model showed excellent discrimination and calibration in both internal and external validation of the full model, by sex and ethnicity. The model explained 65% of the variation in time to diagnosis of lung cancer R2 D in both sexes in the QResearch validation cohort and 59% of the R2 D in both sexes in the CPRD validation cohort. Harrell's C statistics were 0·90 in the QResearch (validation) cohort and 0·87 in the CPRD cohort, and the D statistics were 2·8 in the QResearch (validation) cohort and 2·4 in the CPRD cohort. Compared with seven other lung cancer prediction models, the CanPredict (lung) model had the best performance in discrimination, calibration, and net benefit across three prediction horizons (5, 6, and 10 years) in the two approaches. The CanPredict (lung) model also had higher sensitivity than the current UK recommended models (LLP v2 and PLCO M2012), as it identified more lung cancer cases than those models by screening the same amount of individuals at high risk. The CanPredict (lung) model was developed, and internally and externally validated, using data from 19·67 million people from two English primary care databases. Our model has potential utility for risk stratification of the UK primary care population and selection of individuals at high risk of lung cancer for targeted screening. If our model is recommended to be implemented in primary care, each individual's risk can be calculated using information in the primary care electronic health records, and people at high risk can be identified for the lung cancer screening programme. Innovate UK (UK Research and Innovation). For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

This article is a response to Pike and Dunne's research. The focus of their analysis is on reflections of studying science post-16. Pike and Dunne draw attention to under enrollments in science, technology, engineering, and mathematics (STEM) fields, in particular, in the field of physics, chemistry and biology in the United Kingdom. We provide an analysis of how the authors conceptualize the problem of scientific career choices, the theoretical framework through which they study the problem, and the methodology they use to collect and analyze data. In addition, we examine the perspective they provide in light of new developments in the field of students' attitudes towards science and mathematics. More precisely, we draw attention to and explicate the authors' use of identity from the perspective of emerging theories that explore the relationships between the learner and culture in the context of science and mathematics.

The purpose of this study was to begin to explore the link of gesture and voice when teaching children and to examine how the children used these gestures in singing. Semi-structured interviewing techniques and observation were used extensively to collect information from the respondents. Five children were asked to participate in this preliminary work individually. The results demonstrated that there was a link between children's singing voice and their use of gesture by observing the Dalcrozian mirror and follow games. The functions of gestures could be defined as being for focus, guidance, support, good intonation and sensation. In addition, some specific teaching techniques were required for achieving a more effective gesture and a more successful sound. Gesture techniques helped the children to improve their vocal techniques and correct their vocal faults. This study opened the field for the full study of gesture in aiding children's singing. (Contains 3 figures and 2 tables.)

Nighttime Light Emission (NLE) is associated with diminished mental and physical health. The present study examines how NLE and associated urban features (e.g., air pollution, low green space) impact mental and physical wellbeing. We included 200,393 UK Biobank Cohort participants with complete data. The study was carried out in two steps. In Step1, we assessed the relationship between NLE, deprivation, pollution, green space, household poverty and mental and physical symptoms. In Step2, we examined the role of NLE on environment-symptom networks. We stratified participants into high and low NLE and used gaussian graphical model to identify nodes which bridged urban features and mental and physical health problems. We then compared the global strength of these networks in high vs low NLE. We found that higher NLE associated with higher air pollution, less green space, higher economic and neighborhood deprivation, higher household poverty and higher depressed mood, higher tiredness/lethargy and obesity (Rtraining_mean = 0.2624, Ptraining_mean <.001; Rtest_mean = 0.2619, Ptest_mean <.001). We also found that the interaction between environmental risk factors and mental, physical problems (overall network connectivity) was higher in the high NLE network than in the low NLE network (t = 0.7896, P <.001). In areas with high NLE, economic deprivation, household poverty and waist circumference acted as bridge factors between the key urban features and mental health symptoms. In conclusion, NLE, urban features, household poverty and mental and physical symptoms are all interrelated. In areas with high NLE, urban features associate with mental and physical health problems at a greater magnitude than in areas with low NLE. [ABSTRACT FROM AUTHOR]

This study is a response to calls for a more comprehensive treatment of service operations management amid concerns over the prevalence of poor service quality. Building upon the ideas of total quality management as an ethos of continual learning and quality improvement, this study aims to elucidate different managerial mindsets towards service quality and the resulting impact on the organisational learning environment. Using a qualitative case study methodology of a sample of UK-based service organisations, the findings point to a trichotomy of managerial mindsets towards service quality each connected to different types of organisational learning. These include (i) outcome mindset with a focus on short-term learning, (ii) process mindset with a focus on intermittent learning, and (iii) process-outcome mindset with a focus on continuous learning. We suggest several propositions for further empirical testing and highlight practical implications of the findings. [ABSTRACT FROM AUTHOR]

Background: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern. Methods: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25–30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events. Results: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7–13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73–6.28] for normal weight, 2.50 [95% CI: 1.34–4.66] for overweight, and 3.42 [95% CI: 1.81–6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36–3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10–1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91). Conclusions: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention. [ABSTRACT FROM AUTHOR]

Background: To determine whether serum gamma‐glutamyl transpeptidase (GGT) level is associated with pancreatic cancer risk in a large prospective cohort. Methods: The study analyzed serum GGT concentration at baseline of 421,032 participants recruited in the UK Biobank since 2006 through 2010. Information on incidence of pancreatic cancer was obtained from cancer and death registers, updated until 2015 in Scotland or 2016 in England and Wales. Adjusted Cox proportional hazards models were used to measure the association between serum GGT and pancreatic cancer risk. Results: The study identified 586 cases of pancreatic cancer over a median follow‐up period of 7.16 years. In the multivariable‐adjusted Cox model, serum GGT level was associated with 14% higher pancreatic cancer risk (hazard ratio (HR) per one standard deviation increment of log2 GGT level = 1.14, 95% confidence interval (CI) 1.02–1.28, p = 0.025). In the total population, the HR for the highest GGT group was 1.68 (95%CI: 1.22–2.30) versus the lowest GGT group. The HR for the highest GGT group in men (≥50.2 U/L) was 1.72 (95%CI: 1.14–2.61) and that in women (≥31.6 U/L) was 1.75 (95%CI: 1.06–2.88) versus the lowest GGT group. Conclusion: Our findings suggested a positive association of serum GGT in pancreatic cancer etiology, implying the potential of monitoring GGT level for identifying at‐risk individuals for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background and aims: Epidemiological evidence regarding the association of air pollution with the risk of non‐alcoholic fatty liver disease (NAFLD) is limited. This study was to examine the associations of long‐term exposure to various air pollutants and overall air pollution with risk of incident NAFLD as well as cirrhosis, a major liver‐related morbidity for NAFLD. Methods: Included were 456 687 UK residents. Air pollution data included PM2.5, PM2.5–10, PM10, NO2 and NOx. A weighted air pollution score was also generated from PM10 and NOx. Cox proportional hazard models were employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 4978 cases of NAFLD and 1575 cases of incident cirrhosis, over a median follow‐up of 11.9 years. PM2.5, PM10, NO2 and NOx exposures contributed to the excess risk of NAFLD associated with air pollution score; and the corresponding adjusted HRs (95% CI) were 1.10 (1.05, 1.14), 1.14 (1.09, 1.20), 1.19 (1.13, 1.24) and 1.11 (1.07, 1.15), respectively, for each interquartile range increase in the above specific air pollutants. Similar patterns were also indicated for cirrhosis risk. Alcohol consumption was an effect modifier for the association between air pollution score and NAFLD risk, whereas body mass index modified the association for cirrhosis risk. Conclusion: Long‐term exposure to air pollution was associated with risks of NAFLD and cirrhosis among the UK population. [ABSTRACT FROM AUTHOR]

Background: Many observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine‐based estimated glomerular filtration rate (eGFRcrea), cystatin C‐based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin‐to‐creatinine ratio (UACR)). Methods: For both directions, single‐nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state‐of‐the‐art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary‐level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente. Results: Based on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR = 0.007, 95% CI:2.6 × 10−4–0.569, p = 0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR <1, p < 0.05). For UACR, it showed a strong causal effect on kidney cancer, after adjusting for body composition (OR = 14.503, 95% CI: 2.546–96.001, p = 0.032). Due to lacking significant signals and effect power for the reverse MR, further investigations are warranted. Conclusions: Our study suggested a potential causal effect of damaged kidney function on kidney cancer. EGFRcrea and UACR might be causally associated with kidney cancer, especially when patients were comorbid with obesity or diabetes. We called for larger sample‐size studies to further unravel the underlying causal relationship and the exact mechanism. [ABSTRACT FROM AUTHOR]

Background Polypharmacy among older people represents a global challenge due to its association with adverse drug events. The reported prevalence of polypharmacy varies widely across countries, and is particularly high in Asian countries. However, there is no multinational study using standardised measurements exploring variations in prescribing trends. Objective To compare polypharmacy trends in older people in Asia, Australia and the United Kingdom. Design Multinational, retrospective, time-trend, observational study using a common study protocol. Setting Outpatient and community settings. Subjects All individuals aged ≥ 65 years between 2013 and 2016. Methods We defined polypharmacy as the concomitant use of ≥5 medications for ≥45 days per year. We estimated the annual prevalence of polypharmacy and calculated average annual percentage change (AAPC) to assess the time trends. Results A total of 1.62 million individuals were included in this study. The highest prevalence of polypharmacy was observed in Hong Kong (46.4%), followed by Taiwan (38.8%), South Korea (32.0%), the United Kingdom (23.5%) and Australia (20.1%) in 2016. For the time trend, the Asian region showed a steady increase, particularly in Hong Kong and South Korea (AAPC: Hong Kong, 2.7%; South Korea, 1.8%; Taiwan, 1.0%). However, Australia and the United Kingdom showed a decreasing trend (Australia, −4.9%; the United Kingdom, −1.1%). Conclusions Polypharmacy prevalence in older people was higher in Hong Kong, Taiwan and South Korea, with an increasing trend over time, compared with Australia and the United Kingdom. Our findings underline the necessity to monitor polypharmacy among older people in Asia by conducting government-level interventions and introducing medicine-optimisation strategies. [ABSTRACT FROM AUTHOR]

Accident severity prediction is a hot topic of research aimed at ensuring road safety as well as taking precautionary measures for anticipated future road crashes. In the past decades, both classical statistical methods and machine learning algorithms have been used to predict traffic crash severity. However, most of these models suffer from several drawbacks including low accuracy, and lack of interpretability for people. To address these issues, this paper proposed a hybrid of Balanced Bagging Classification (BBC) and Light Gradient Boosting Machine (LGBM) to improve the accuracy of crash severity prediction and eliminate the issues of bias and variance. To the best of the author's knowledge, this is one of the pioneer studies which explores the application of BBC-LGBM to predict traffic crash severity. On the accident dataset of Great Britain (UK) from 2013 to 2019, the proposed model has demonstrated better performance when compared with other models such as Gaussian Naïve Bayes (GNB), Support vector machines (SVM), and Random Forest (RF). More specifically, the proposed model managed to achieve better performance among all metrics for the testing dataset (accuracy = 77.7%, precision = 75%, recall = 73%, F1-Score = 68%). Moreover, permutation importance is used to interpret the results and analyze the importance of each factor influencing crash severity. The accuracy-enhanced model is significant to several stakeholders including drivers for early alarm and government departments, insurance companies, and even hospitals for the services concerned about human lives and property damage in road crashes. [ABSTRACT FROM AUTHOR]

Aims. Cardiovascular diseases (CVDs) are the leading cause of deaths globally. Mortality and incidence of CVDs are significantly higher in people with mood disorders. About 81.1% of CVD patients were reported with comorbidities in 2019, where the second most common comorbidity was due to major depressive disorder (MDD). This study, therefore, aimed to evaluate the genetic correlation between CVDs and mood disorders by using data from the UK Biobank towards understanding the influence of genetic factors on the comorbidity due to CVDs and mood disorders. Methods. The UK Biobank database provides genetic and health information from half a million adults, aged 40-69 years, recruited between 2006 and 2010. A total of 117,925 participants and 6,128,294 variants were included for analysis after applying exclusion criteria and quality control steps. This study focused on two CVD phenotypes, two mood disorders and 12 cardiometabolic-related traits to conduct association studies. Results. The results indicated a significant positive genetic correlation between CVDs and overall mood disorders and MDD specifically, showing substantial genetic overlap. Genetic correlation between CVDs and bipolar disorder was not significant. Furthermore, significant genetic correlation between mood disorders and cardiometabolic traits was also reported. Conclusions. The results of this study can be used to understand that CVDs and mood disorders share a great deal of genetic liability in individuals of European ancestry. [ABSTRACT FROM AUTHOR]

Background: Some observational studies had found that shift work would increase risks of metabolic disorders, cancers, and cardiovascular diseases, but there was no homogeneous evidence of such an association between shift work and incident dementia. This study aimed to investigate whether shift work would increase the risk of dementia in a general population. Methods: One hundred seventy thousand seven hundred twenty-two employed participants without cognitive impairment or dementia at baseline recruited between 2006 and 2010 were selected from the UK Biobank cohort study. Follow-up occurred through June 2021. Shift work status at baseline was self-reported by participants and they were categorized as non-shift workers or shift workers. Among shift workers, participants were further categorized as night shift workers or shift but non-night shift workers. The primary outcome was all-cause dementia in a time-to-event analysis, and the secondary outcomes were subtypes of dementia, including Alzheimer's disease, vascular dementia, and other types of dementia. Results: In total, 716 dementia cases were observed among 170,722 participants over a median follow-up period of 12.4 years. Shift workers had an increased risk of all-cause dementia as compared with non-shift workers after multivariable adjustment (hazard ratio [HR], 1.30, 95% confidence interval [CI], 1.08–1.58); however, among shift workers, night shift work was not associated with the risk of dementia (HR, 1.04, 95% CI, 0.73–1.47). We found no significant interaction between shift work and genetic predisposition to dementia on the primary outcome (P for interaction = 0.77). Conclusions: Shift work at baseline was associated with an increased risk of all-cause dementia. Among shift workers, there was no significant association between night shift work and the risk of dementia. The increased incidence of dementia in shift workers did not differ between participants in different genetic risk strata for dementia. [ABSTRACT FROM AUTHOR]

Background Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals with a family history suffer elevated NPC risk, requiring effective genetic counseling for risk stratification and individualized prevention. Methods We performed whole-exome sequencing on 502 familial NPC patients and 404 unaffected relatives and controls. We systematically evaluated the established cancer predisposition genes and investigated novel NPC susceptibility genes, making comparisons with 21 other familial cancers in the UK biobank (N = 5218). Results Rare pathogenic mutations in the established cancer predisposition genes were observed in familial NPC patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), and BRCA1 (0.80%). Additionally, 6 novel susceptibility genes were identified. RAD54L , involved in the DNA repair pathway together with ERCC2 , MUTYH , and BRCA1 , showed the highest frequency (4.18%) in familial NPC. Enrichment analysis found mutations in TP63 were enriched in familial NPC, and RAD54L and EML2 were enriched in both NPC and other Epstein-Barr virus–associated cancers. Besides rare variants, common variants reported in the studies of sporadic NPC were also associated with familial NPC risk. Individuals in the top quantile of common variant-derived genetic risk score while carrying rare variants exhibited increased NPC risk (odds ratio = 13.47, 95% confidence interval = 6.33 to 28.68, P  =   1.48 × 10–11); men in this risk group showed a cumulative lifetime risk of 24.19%, much higher than those in the bottom common variant-derived genetic risk score quantile and without rare variants (2.04%). Conclusions This study expands the catalog of NPC susceptibility genes and provides the potential for risk stratification of individuals with an NPC family history. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between sensory impairments and the risk of dementia is inconclusive. We aim to investigate the association of visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) with incident dementia. Methods: The UK Biobank study recruited more than 500,000 participants aged 40–69 years across the United Kingdom. Participants with available visual acuity (VA) measurements and speech-reception-threshold (SRT) information and free of dementia at the baseline assessment were included in the analysis. VI was defined as VA worse than 0.3 LogMAR units and HI were defined as an SRT of −5.5 dB or over. DSI was defined as the presence of both VI and HI. Incident dementia was identified through linked data to primary care or hospital admission records and death registries. Multivariable Cox proportional hazard regression models were used to examine the association of VI, HI, and DSI with incident dementia. Results: Among 113,511 participants (mean age: 56.8 ± 8.09 years, female: 54.4%), a total number of 1,135 (1.00%) cases of incident dementia were identified during a median follow up period of 11.1 years [interquartile range (IQR): 10.9–11.4 years]. The incidence of dementia showed significant differences among the non-sensory impairment (NSI) group, VI-only group, HI-only group, and DSI group (p < 0.001). After adjusting for demographic, lifestyle, health, and genetic factors, isolated VI (HR = 1.50, 95% CI : 1.06–2.12, p = 0.023), isolated HI (HR = 1.42, 95% CI :1.20–1.69, p < 0.001), and DSI (HR = 1.82, 95% CI : 1.10–3.00, p = 0.020) were independently associated with higher risks of incident dementia. Conclusions: Visual, hearing, and dual sensory impairments were associated with an increased risk of developing dementia, suggesting that visual and hearing impairments are modifiable risk factors that can be targeted to prevent dementia. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the effects of long-term/recurrent use of antibiotics in childhood on developing cognitive impairment in middle and old age from UK Biobank Database. Methods: UK Biobank recruited participants aged 37–73 years. Cognitive impairment was ascertained by fluid intelligence questionnaire. Primary outcome was the occurrence of cognitive impairment in middle and old age. Multivariate logistic regression models were used to explore the relationship between long-term/recurrent use of antibiotics and cognitive impairment. Results: Over 3.8–10.8 years' follow-up, 4,781 of the 35,921 participants developed cognitive impairment. The odds of cognitive impairment in middle and old age among long-term/recurrent use of antibiotics in childhood were increased by 18% compared with their counterparts (adjusted odd ratio 1.18, 95% confidence interval 1.08–1.29, p < 0.01). The effect of long-term/recurrent use of antibiotics in childhood on cognitive impairment was homogeneous across different categories of various subgroup variables such as sex, age, APOE4, ethnic groups, income before tax, smoking status, alcohol status, BMI, hypertension and diabetes but the effect of long-term/recurrent use of antibiotics in childhood was modified by the educational qualification (p- value for interaction <0.05). Conclusion: Long-term/recurrent use of antibiotics in childhood may increase the risk of cognitive impairment in middle and old age. [ABSTRACT FROM AUTHOR]

There are over a 100 driver gene mutations in patients with diffuse large B‐cell lymphoma (DLBCL), but their clinical significance remains unclear. Here, we first analyzed the DLBCL dataset from the UK‐based Haematological Malignancy Research Network. Patients were divided into high‐ and low‐risk groups based on whether lymphoma progressed within 24 months. Genes showing significantly different frequencies between groups were selected. Survival data for patients with the selected mutant genes were analyzed. The results were validated using two other large databases to evaluate the relationship between the selected mutant genes and prognosis. The mutation frequencies of 11 genes (MYD88[L265P], SGK1, MPEG1, TP53, SPEN, NOTCH1, ETV6, TNFRSF14, MGA, CIITA, and PIM1) significantly differed between the high‐ and low‐risk groups. The relationships between these mutant genes and patient survival were analyzed. Patients who harbored SGK1 (serum and glucocorticoid‐inducible kinase 1) mutations exhibited the best prognosis. Most patients with SGK1 mutation are germinal center B‐cell (GCB) subtype. Among patients with GCB DLBCL, those harboring SGK1 mutations exhibited better prognosis than those without SGK1 mutations. Most SGK1 mutations were single‐base substitutions, primarily scattered throughout the catalytic domain‐encoding region. Multiple SGK1 mutations were identified in a single patient. Thus, SGK1 mutations are a marker of good prognosis for DLBCL and occur predominantly in the GCB subtype of DLBCL. SGK1 mutation status can further stratify patients with GCB DLBCL into different prognostic subgroups. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer has the worst survival rate among all cancers. Almost 70% of patients in the UK were diagnosed at Stage IV.Aim: This study aimed to investigate the symptoms associated with the diagnoses of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine neoplasms (PNEN), and comparatively characterise the symptomatology between the two tumour types to inform earlier diagnosis.Design and Setting: A nested case-control study in primary care was conducted using data from the QResearch® database. Patients aged ≥25 years and diagnosed with PDAC or PNEN during 2000 to 2019 were included as cases. Up to 10 controls from the same general practice were matched with each case by age, sex, and calendar year using incidence density sampling.Method: Conditional logistic regression was used to investigate the association between the 42 shortlisted symptoms and the diagnoses of PDAC and (or) PNEN in different timeframes relative to the index date, adjusting for patients' sociodemographic characteristics, lifestyle, and relevant comorbidities.Results: A total of 23 640 patients were identified as diagnosed with PDAC and 596 with PNEN. Of the symptoms identified, 23 were significantly associated with PDAC, and nine symptoms with PNEN. The two alarm symptoms for both tumours were jaundice and gastrointestinal bleeding. The two newly identified symptoms for PDAC were thirst and dark urine. The risk of unintentional weight loss may be longer than 2 years before the diagnosis of PNEN.Conclusion: PDAC and PNEN have overlapping symptom profiles. The QCancer® (pancreas) risk prediction model could be updated by including the newly identified symptoms and comorbidities, which could help GPs identify high-risk patients for timely investigation in primary care. [ABSTRACT FROM AUTHOR]

This study examines how a firm's tax disclosures in a CSR report are influenced by its tax avoidance behavior. Using a sample of public U.K. firms, our empirical analysis reveals that firms engaging in higher levels of tax avoidance are more likely to provide tax-specific disclosures in their CSR reports. In addition, the tax disclosures tend to be longer, contain more justification words, and contain more soft claims than hard information. Further cross-sectional analyses suggest that the positive association between tax avoidance and tax disclosures is attenuated when firms exhibit better CSR performance as well as stronger corporate governance. Collectively, our findings provide evidence that firms appear to legitimize their tax avoidance behavior by providing more tax disclosures in their communications with stakeholders. JEL Classifications: H26; M14; M4. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated an inverse association between parathyroid hormone (PTH) and the risk of osteoarthritis (OA). However, it remains unknown whether such association reflects causality. We aimed to apply a Mendelian randomization (MR) approach to investigate the causal association between PTH and OA. Materials and Methods: We performed a two-sample MR analysis using summary statistics from 13 cohorts (PTH, N = 29,155) and a recent genome-wide association study meta-analysis (OA, N = 455,221) by the UK Biobank and Arthritis Research UK OA Genetics (arcOGEN). MR analyses were carried out mainly using the inverse-variance-weighted method. Sensitivity analyses were performed to test the robustness of the associations using the weighted median method, the MR–Egger method, and "leave-one-out" analysis. Analyses were performed again to test whether the associations remained statistically significant after excluding any outlier variants that were detected using the MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) test. Results: Five single-nucleotide polymorphisms (SNPs) were selected as instrumental variables at the genome-wide significance threshold (p < 5 × 10–8). The causal effect between PTH and OA was genetically predicted using the inverse-variance-weighted method (odds ratio = 0.67, 95% confidence interval: 0.50–0.90; p = 0.008). This result was borne out using the weighted median method (odds ratio = 0.73, 95% confidence interval: 0.60–0.90; p = 0.004). The causality remained robust after discarding the outlier variants as well as SNPs associated with confounding factors. Conclusion: MR analysis supported a potential causative relationship between decreased serum circulating PTH and a higher risk of hip and knee OA. [ABSTRACT FROM AUTHOR]

Clinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDL-C) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks. We included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC. Observational analyses showed L-shaped associations of HDL-C with CVD, with no further risk reduction when HDL-C levels exceeded 70 mg/dL. Multivariable MR analyses across entire distribution of HDL-C found no association of HDL-C with CVD, after control of the pleiotropic effect on other lipids and unmeasured pleiotropism. However, in stratified MR analyses, significant inverse associations of HDL-C with CVD were observed in the stratum of participants with HDL-C ≤ 50 mg/dL (odds ratio per unit increase, 0.86; 95 % confidence interval, 0.79–0.94), while null associations were observed in any stratum above 50 mg/dL. Our data suggest a potentially causal inverse association of HDL-C at low levels with CVD risks. These findings advance our knowledge about the role of HDL as a potential target in CVD prevention and therapy. • Large-scale individual-level genetic data and GWAS summary data were used. • Observational analyses showed L-shaped associations of HDL-C with CVD. • Conventional linear mendelian analyses showed no association of HDL-C with CVD. • Stratified mendelian analyses suggested causal associations when HDL-C ≤ 50 mg/dL. • No association was found in any stratum >50 mg/dL in stratified mendelian analyses. [ABSTRACT FROM AUTHOR]

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05–3.39), 1.62 (1.23–2.12), 2.06 (1.73–2.45), 1.20 (1.16–1.25), and 1.07 (1.05–1.08) per 10 μg/m3 increase in PM 2.5 , PM 2.5–10 , PM 10 , NO 2 , and NO x , respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33–1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health. [Display omitted] • Air pollution is a risk factor for respiratory mortality. • Long-term exposure to air pollution increased respiratory mortality risk. • The AP score showed a dose-response association with respiratory mortality risk. [ABSTRACT FROM AUTHOR]

This qualitative study aimed to explore the psychological effects of female genital cutting in the United Kingdom within a systemic psychological framework. Semi-structured interviews were carried out with 13 women who had experienced female genital cutting. Four key themes emerged from thematic analysis of the data: (1) wholeness contested, (2) sexuality milestones and female genital cutting awareness, (3) salvaging family relationships and (4) for our own good. Findings highlight the importance of recognising the relational nature of how women perceive the psychological effects of female genital cutting and how these reactions are negotiated in their social sphere. [ABSTRACT FROM AUTHOR]

In this study, we have investigated a hybrid thin film PV vacuum glazing called: ‘PV VG-4L’. The glazing involves an integration between a thin film PV glazing with a double vacuum glazing (both manufactured independently), and an additional layer of self-cleaning coated glass which totalling four layers of glass. The mathematical model of the PV VG-4L designs were developed and numerically solved in MATLAB. To evaluate the performance of the PV VG-4L, the prototype was manufactured and investigated at lab-scale and also under real conditions. Lab-scale experiments were conducted at steady state conditions using a TEC driven calibrated hot box at the Sustainable Energy Research Lab, University of Nottingham, UK. Meanwhile, outdoors, the prototype was tested at a research house at the University of Nottingham, UK. Under the influence of solar irradiance, the electrical performance of the PV-VG and the temperature difference between the surfaces of the glazing were analysed. However, the measurement of U-value under real conditions is not reliable due to the influence of solar irradiance on the heat flux sensor and also due to the absorbed solar irradiance by the thin film PV layer. Nevertheless, during low to zero solar irradiance, the U-value of the prototype can be estimated. The developed model was then validated against the experimental results by direct comparison to the trend of the experimental and theoretical curves obtained, and also by conducting error analysis using root mean squared percentage deviation (RMSPD) method. Testing using the calibrated hot box, adhering closely to ISO 12567 standards, resulted in an average measured total U-value of 0.6 W/m²K which is when compared to a single thin film PV glazing with a typical U-value of 5 W/m²K; the U-value is higher by almost 90%. From the analysis, the computed RMSPD value for the glazing surface temperature and the U-value are 4.02% and 0.92% respectively. Meanwhile, field testing under real conditions with a 0.4 m × 0.4 m PV VG-4L prototype found that 14 W/m² power can be generated by the PV VG-4L at average solar irradiance of ~600 W/m². RMSPD computed glazing surface temperatures, electrical power generated under real conditions and U-value are 2.90%, 8.70% and 2.89% respectively. The theoretical and experimental results are concluded to be in good agreement. This study has significant contributions to the knowledge of building integrated photovoltaic PV technology. The mathematical model that has been developed can be used for PV VG-4L design optimisation and also to simulate the performance of PV VG-4L under various conditions. At building efficiency level, the PV VG-4L not only can produce power, but it also has high insulating properties. The promising U-value implies its range of potential applications which can be improved depending on the energy needs and applications, such as for BIPV solar façade (PV curtain walling) in commercial buildings, greenhouses, skylight and conservatory [ABSTRACT FROM AUTHOR]

Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large prospective cohort study was to explore these links. A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis. During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM 2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01–1.06, P = 0.009), PM 10 (HR: 1.07, 95% CI: 1.04–1.10, P < 0.001), NO 2 (HR: 1.10, 95% CI: 1.07–1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01–1.07, P = 0.005) in the main model. The air pollution score showed a dose response association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04–1.19, P = 0.002) and 1.17 (95% CI: 1.09–1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001). Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine. [Display omitted] • Air pollution is a risk factor for new-onset migraine. • Long-term exposure to air pollutants increased the risk of new-onset migraine. • The AP score showed a dose-response relation with the risk of new-onset migraine. [ABSTRACT FROM AUTHOR]

Background: In the CELESTIAL trial for patients with advanced hepatocellular carcinoma (HCC), cabozantinib showed improved survival compared with placebo but comes at a price. We aimed to investigate the cost‐effectiveness of cabozantinib for sorafenib‐resistant HCC from the payer's perspective of the USA, UK and China. Methods: We developed Markov models to simulate the patients pre‐treated with first‐line sorafenib following the CELESTIAL trial. Quality‐adjusted life‐years (QALYs) and incremental cost‐effectiveness ratio (ICER) were calculated for the treatment with cabozantinib or best supportive care. The list price for drugs was acquired from the Red Book, the British National Formulary, West China hospital and reported literature. Adverse events, utilities weights, and transition likelihood between states were sourced from the published randomized phase III trial. A willing‐to‐pay threshold was set $150 000/QALY in the USA, $70 671/QALY (£50 000/QALY) in the UK and $26 481/QALY (3x GDP per capita) in China. Deterministic and probabilistic sensitivity analyses were developed to test the models' uncertainty. Results: In the base case, treatment with cabozantinib increased effectiveness by 0.13 QALYs, resulting in an ICER vs best supportive care of $833 497/QALY in the USA, $304 177/QALY in the UK and $156 437/QALY in China. The models were most sensitive to assumptions about transitions to progression with both cabozantinib and best supportive care, the utility associated with being progression free. These results were robust across a range of scenarios and sensitivity analyses, including deterministic and probabilistic analyses. Conclusions: Cabozantinib at its current cost would not be a cost‐effective treatment option for patients with sorafenib‐resistant HCC from the payer's perspective in the USA, UK or China. Substantial discounts are necessary to meet conventional cost‐effectiveness thresholds. [ABSTRACT FROM AUTHOR]

• A net-zero DN model composed of solely non-dispatchable DGs and BESSs has been considered to tackle severe windstorms. • The proposed framework is particularly effective in DNs with high shares of converter-based DGs. • The proposed three-stage resilience assessment can provide up to 25 percent load shedding reduction. • A detailed spatiotemporal representation of the DN was implemented to accurately estimate the status of the grid. Increasing incidences of extreme weather events pose significant challenges to the electrical grids in terms of the ability to withstand those high-impact eventualities. This paper proposes a resilience assessment framework for net-zero active distribution networks (ADNs) to tackle the impacts of extreme windstorms where only renewable energy resources (RESs) and battery energy storage systems (BESSs) are considered. To accurately capture the influence of windstorms on the grid, a detailed spatiotemporal representation of grid system assets and their exposure to the wind has been implemented. The suggested day-ahead resilience assessment is based on a three-stage approach. The first stage computes the probabilities of failure of each line and determines the most vulnerable ones. The second stage obtains the optimal grid configuration based on the outcomes of the first stage given the available non-dispatchable RESs and commits the available resources in each island to minimize the loss of load during the windstorm. If such a value is still larger than zero after the second stage, a novel voltage regulation scheme is applied in the third stage, taking advantage of the RESs and BESSs in each island. The proposed resilience assessment has been evaluated using the IEEE 33-bus test system with the meteorological data retrieved from an actual windstorm event occurred in the UK on the 20th of February. The outcomes of this paper underscore that a significant reduction in load shedding during such extreme events can be achieved, thus having a notable enhancement to the overall resilience of the system. Finally, the performance of this approach is compared with other resilience-oriented methods for windstorms, where the benefits of using the scheme reported in this paper are highlighted and quantified. [ABSTRACT FROM AUTHOR]

This article investigates the identity of independent art schools, and art schools in multidisciplinary universities, in the UK and China, using the concept of collective identity from organizational management theory and drawing on semi-structured interviews with Chinese and British academics. It addresses the positive and negative aspects of art schools’ ‘image’. They are taken to be both the setting for creativity and innovation, and as being less effective than the other subject disciplines at contributing to economic growth. The article explores this not through an economic argument, but a cultural one. It shows that both independent art colleges and art schools in universities preserve ‘bohemianism’ in their organizational identity. It is not novel to note that in the West, this is based in Romanticism, however, it is possible to identify an equivalent, and more ancient, strand in Chinese culture that underlies the identity of ‘real art schools’ there. [ABSTRACT FROM AUTHOR]

Summary: Environmental epidemiologists are often interested in estimating the effect of functions of time varying exposure histories, such as the 12‐month moving average, in relation to chronic disease incidence or mortality. The individual exposure measurements that comprise such an exposure history are usually mismeasured, at least moderately, and, often, more substantially. To obtain unbiased estimates of Cox model hazard ratios for these complex mismeasured exposure functions, an extended risk set regression calibration method for Cox models is developed and applied to a study of long‐term exposure to the fine particulate matter, PM2.5, component of air pollution in relation to all‐cause mortality in the nurses’ health study. Simulation studies under several realistic assumptions about the measurement error model and about the correlation structure of the repeated exposure measurements were conducted to assess the finite sample properties of this new method and found that the method has good performance in terms of finite sample bias reduction and nominal confidence interval coverage. [ABSTRACT FROM AUTHOR]

To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Objectives. The aims were to compare the performance of cardiovascular risk calculators, Framingham Risk Score (FRS) and QRISK2, in RA and matched non-RA patients and to evaluate whether their performance could be enhanced by the addition of CRP. Methods. We conducted a retrospective analysis, using a clinical practice data set linked to Hospital Episode Statistics (HES) data from the UK. Patients presenting with at least one RA diagnosis code and no prior cardiovascular events were matched to non-RA patients using disease risk scores. The overall performance of the FRS and QRISK2 was compared between cohorts, and assessed with and without CRP in the RA cohort using C-Index, Akaike Information Criterion (AIC) and the net reclassification index (NRI). Results. Four thousand seven hundred and eighty RA patients met the inclusion criteria and were followed for a mean of 3.8 years. The C-Index for the FRS in the non-RA and RA cohort was 0.783 and 0.754 (P < 0.001) and that of the QRISK2 was 0.770 and 0.744 (P < 0.001), respectively. Log[CRP] was positively associated with cardiovascular events, but improvements in the FRS and QRISK2 C-Indices as a result of inclusion of CRP were small, from 0.764 to 0.767 (P = 0.026) for FRS and from 0.764 to 0.765 (P = 0.250) for QRISK2. The NRI was 3.2% (95% CI: -2.8, 5.7%) for FRS and -2.0% (95% CI: -5.8, 4.5%) for QRISK2. Conclusion. The C-Index for the FRS and QRISK2 was significantly better in the non-RA compared with RA patients. The addition of CRP in both equations was not associated with a significant improvement in reclassification based on NRI. [ABSTRACT FROM AUTHOR]

Objective. RA is associated with a 50-60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. [ABSTRACT FROM AUTHOR]

Objective: Screening criteria for neonatal encephalopathy remain a complex combination of subjective and objective criteria. We examine the utility of universal cord blood gas testing and mandatory encephalopathy evaluation for infants with pH ≤7.10 on umbilical cord arterial blood gas (cABG) as a single screening measure for timely identification of moderate/severe encephalopathy.Design, Setting, Patients: Infants born at a single centre between 2008 and 2015, who were ≥36 weeks, had no congenital anomalies and had a cABG pH ≤7.10 were identified for a retrospective cohort study. Maternal/perinatal and patient factors were collected.Results: 27 028 infants were born during the study period; 412 met all inclusion criteria. Of those, 35/85 infants with pH <7.00 and 34/327 infants with pH between 7.00 and 7.10 had moderate/severe encephalopathy. Encephalopathy was identified on the basis of pH and examination alone (no other perinatal criteria present) in 5/35 and 13/34 infants in the two pH groups, respectively.A cABG pH threshold of ≤7.10 was associated with a sensitivity of 74.2% and a specificity of 98.7% for detection of moderate/severe encephalopathy. Based on these data, 25 infants with cABG pH between 7.00 and 7.10 will need to be screened to identify one neonate with moderate/severe encephalopathy, who might have otherwise been missed using conventional screening, a 15% increase in appropriate selection and treatment over current methods.Conclusion: Universal cord blood gas screening with a pH threshold ≤7.10 and mandatory encephalopathy examination results in greater detection of infants with moderate/severe encephalopathy and timely initiation of therapeutic hypothermia. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the introduction of non‐invasive pre‐natal testing for Down's syndrome (DS) has the potential to undermine informed choice. Participants: Three hundred and ninety‐three health professionals; 523 pregnant women. Methods: A cross‐sectional questionnaire study across nine maternity units and three conferences in the UK designed to assess opinions regarding test delivery and how information should be communicated to women when offered Down's syndrome screening (DSS) or diagnosis using invasive (IDT) or non‐invasive testing (NIPT). Results: Both pregnant women and health professionals in the NIPT and DSS groups were less likely than the IDT group to consider that testing should take place at a return visit or that obtaining written consent was necessary, and more likely to think testing should be carried out routinely. Compared to health professionals, pregnant women expressed a stronger preference for testing to occur on the same day as pre‐test counselling (P = 0.000) and for invasive testing to be offered routinely (P = 0.000). They were also more likely to indicate written consent as necessary for DSS (P = 0.000) and NIPT (P < 0.05). Conclusions: Health professionals and pregnant women view the consenting process differently across antenatal test types. These differences suggest that informed choice may be undermined with the introduction of NIPT for DS into clinical practice. To maintain high standards of care, effective professional training programmes and practice guidelines are needed which prioritize informed consent and take into account the views and needs of service users. [ABSTRACT FROM AUTHOR]