Search

Although the association between sleep behavior and morbidity and mortality risk has been reported before, there is still uncertainty whether the observed associations are causal or confounding. Therefore, we investigated the causal relationships between sleep-behavioral traits and terminated healthspan risk using Mendelian randomization (MR). We conducted a one-sample MR analysis to evaluate causality between six sleep-behavioral traits (sleep duration, chronotype/morningness, napping, sleeplessness/insomnia, and getting up from bed) and risk of healthspan termination among 388, 909 UK Biobank (UKB) participants. Instrumental variables for sleep behaviors (N = 590) were obtained from recent genome-wide association studies (GWAS). We defined healthspan based on eight predominant health-terminating events associated with longevity (congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, diabetes, cancer, and death). We further constructed a sleep score and a weighted genetic risk score to increase the predictive ability of the sleep-behavioral traits. Cox regression models and Inverse Probability Treatment Weighting (IPTW) were implemented, followed by MR to assess causation. We used inverse-variance-weighted MR to estimate causal effects, and weighted-median and MR-egger for sensitivity analysis to test the pleiotropic effects. In IPTW, we observed a decreased risk of terminated healthspan for healthy sleep behaviors such as 'sleep duration 7-8h/d' (Hazard ratio, HR = 0.93; 95 % confidence interval, CI: 0.92–0.96; P < 0.001); 'morningness' (HR = 0.95; 95%CI: 0.93–0.98; P < 0.01); 'napping' (HR = 0.93; 95%CI: 0.91–0.94; P < 0.001); 'easy getting up from bed' (HR = 0.91; 95%CI: 0.88–0.93; P < 0.001); and, 'never/rarely experience sleeplessness/insomnia' (HR = 0.94; 95%CI: 0.92–0.96; P < 0.001). MR results further indicated causal associations between healthy sleep duration (OR = 0.98; 95%CI: 0.97–1.00; P = 0.036) and insomnia (OR = 1.02; 95%CI: 1.01–1.03; P < 0.001) with terminated healthspan. MR-egger did not suggest any potential pleiotropy. This study supports abnormal sleep duration and insomnia as potential causal risk factors for terminated healthspan. Thus, healthy sleep behavior is valuable for the extension of healthspan, and well-designed and tailored sleep health interventions are warranted. [ABSTRACT FROM AUTHOR]

Aim: Human immunodeficiency virus (HIV) nursing has become more prominent with the increase in chronic HIV infections. This study examined articles related to HIV nursing to determine how the profession has developed and its future direction. Design: A bibliometric analysis was conducted. Methods: HIV nursing‐related articles published in the Web of Science core collection between 1999 and 2022 were searched. VOSviewer was used to identify the contributions of countries, institutions and authors in HIV‐related care. Collaborative maps, hot topics and keywords trends were analysed using VOSviewer and CiteSpace. Results: A total of 1513 publications were extracted. An increase in articles published between 1999 and 2012 was observed. After 2012, the increase in the number of publications was relatively stable. Since 2016, a downward trend in the number of publications has occurred. The USA, South Africa and the UK were the leading contributors to publications related to HIV nursing. The focus of the HIV nursing research has gradually shifted from "HIV infection", "risk factors", and "transmission routes" to "social support", "depression", and "public health". The result shows that increased collaboration among countries/regions can improve the development of HIV nursing and effectively reduce the global HIV infection rate. The mental health of patients has become a research centre in the field of HIV nursing. This study provides direction in clinical practice and future research areas in this field. [ABSTRACT FROM AUTHOR]

Background: The appropriateness of hypertension thresholds for triggering action to prevent cardiovascular and renal complications among non-White populations in the UK is subject to question. Our objective was to establish ethnicity-specific systolic blood pressure (SBP) cutoffs for ethnic minority populations and assess the efficacy of these ethnicity-specific cutoffs in predicting adverse outcomes. Methods: We analyzed data from UK Biobank, which included 444,418 participants from White, South Asian, Black Caribbean, and Black African populations with no history of cardiorenal complications. We fitted Poisson regression models with continuous SBP and ethnic groups, using Whites as the referent category, for the composite outcome of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. We determined ethnicity-specific thresholds equivalent to the risks observed in Whites at SBP levels of 120, 130, and 140 mm Hg. We adjusted models for clinical characteristics, sociodemographic factors, and behavioral factors. The performance of ethnicity-specific thresholds for predicting adverse outcomes and associated population-attributable fraction (PAF) was assessed in ethnic minority groups. Results: After a median follow-up of 12.5 years (interquartile range, 11.7–13.2), 32,662 (7.4%) participants had incident composite outcomes. At any given SBP, the predicted incidence rate of the composite outcome was the highest for South Asians, followed by White, Black Caribbean, and Black African. For an equivalent risk of outcomes observed in the White population at an SBP level of 140 mm Hg, the SBP threshold was lower for South Asians (123 mm Hg) and higher for Black Caribbean (156 mm Hg) and Black African (165 mm Hg). Furthermore, hypertension defined by ethnicity-specific thresholds was a stronger predictor and resulted in a larger PAF for composite outcomes in South Asians (21.5% [95% CI, 2.4,36.9] vs. 11.3% [95% CI, 2.6,19.1]) and Black Africans (7.1% [95% CI, 0.2,14.0] vs. 5.7 [95% CI, -16.2,23.5]) compared to hypertension defined by guideline-recommended thresholds. Conclusions: Guideline-recommended blood pressure thresholds may overestimate risks for the Black population and underestimate risks for South Asians. Using ethnicity-specific SBP thresholds may improve risk estimation and optimize hypertension management toward the goal of eliminating ethnic disparities in cardiorenal complications. [ABSTRACT FROM AUTHOR]

Objective: The causal association between osteoarthritis (OA) and bladder cancer remains unclear. This Mendelian randomization (MR) study was carried out to assess the potential causal effects of any OA, knee OA and hip OA, and bladder cancer. Method: Genome-wide association study (GWAS) summary data for OA and bladder cancer were obtained in GWAS CATALOG, UK Biobank, and FinnGen Consortium. Inverse-variance weighted (IVW) approach was primarily conducted to evaluate the causal relationships between OA and bladder cancer, and MR-Egger intercept and Cochran's Q test were mainly used to estimate heterogeneity and pleiotropy. MR-PRESSO was used to test the presence of horizontal outliers. Leave-one-out analysis was utilized to ensure the reliability of the results. Results: A higher genetic predisposition to any OA has a causal association with bladder cancer risk, while neither knee OA nor hip OA is causally linked to bladder cancer. MR-Egger intercept analysis exhibited that any OA and knee OA had no pleiotropic effect on the risk of bladder cancer, and Cochran's Q test showed that any OA, knee OA and hip OA had no heterogeneity on bladder cancer risk. Neither MR PRESSO analysis nor leave-one-out analysis revealed any outlier SNPs. Conclusions: This MR study exhibited a positive cause-and-effect relationship between any type of OA and bladder cancer risk, but not between site-specific OA, knee OA and hip OA, and bladder cancer. Attention should be paid to the screening and prevention of bladder cancer in OA patients at any site. [ABSTRACT FROM AUTHOR]

The concept of reverse teaching, considered by some as the education model of the future due to increasing technological availability in the classroom, has received great attention in education research lately. However, the focus of these studies has mainly been on the understanding of reverse teaching in terms of its application rather than exploring the students' perceptions of reverse teaching itself. This study explores the students' perceptions of reverse teaching. Based on 28 in-depth interviews, this study submits a conceptualization of reverse teaching from the students' point-of-view. The concept of reverse teaching constitutes three dimensions, expanding our knowledge of the construct. The study posits a crucial link between "preparation, interaction, outcomes", and the understanding of reverse teaching. Guidelines are proposed for reverse teaching, extending existing literatures, with insights and implications for educators.

Self-reported tiredness or low energy, often referred to as fatigue, has been linked to lifestyle factors, although data from randomized–controlled trials are lacking. We investigate whether modifiable lifestyle factors including smoking and alcohol intake related exposures (SAIEs) are causal factors for fatigue using Mendelian randomization (MR). A two-sample MR study was performed by using genome-wide association summary results from UK Biobank (UKBB), and each of the sample size is more than 100,000. We used the inverse variance weighted method, and sensitivity analyses (MR Egger, weighted median, penalized median estimators, and multivariable MR) to account for pleiotropy. The two-sample MR analyses showed inverse causal effect of never-smoking status and positive effect of current smoking status on the risk of fatigue. Similarly, genetically predicted alcoholic intake was positively associated with fatigue. The results were consistent across the different MR methods. Our Mendelian randomization analyses do support that the cessation of smoking and alcohol can decrease the risk of fatigue, and limit alcohol intake frequency can also reduce the risk. [ABSTRACT FROM AUTHOR]

The evidence that dyslipidemia is associated with hyperglycemia calls for an investigation of whether dyslipidemia, as well as lipid-modifying agents, could affect the subsequent development of diabetic retinopathy (DR). Therefore, we aimed to address these unanswered questions by utilizing Mendelian randomization (MR) analysis. Genetic variants were selected from the UK Biobank as instruments to serve as proxies for lipid traits [high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (APOA-I) and apolipoprotein B (APOB)]. Univariable and multivariable MR analyses were performed to examine the associations of these lipid traits with DR and different levels of severity of DR. Based on the evidence for the effects of lipids on outcomes, we estimated the causal relevance of cholesteryl ester transfer protein (CETP) inhibitors in severe nonproliferative and proliferative DR using protein quantitative trait loci (pQTLs) and expression quantitative trait loci (eQTLs) as instruments. Genetically determined HDL-C levels were inversely associated with the risk of severe nonproliferative DR (OR = 0.70, 95% CI = 0.52–0.94) and proliferative DR (OR = 0.90, 95% CI = 0.83–0.97) in the main analyses utilizing the inverse variance-weighted (IVW) MR method and a couple of sensitivity analyses. No association was noted between genetically proxied CETP inhibitors and DR. This MR study suggests the casual protective roles of HDL-C in severe nonproliferative DR and proliferative DR, which calls for further studies to confirm these findings. Current lipid-modifying agents acting on HDL-C may not reduce the risk of DR and new treatments are required in the future. [Display omitted] • Mendelian randomization was used to assess the effects of lipids and drugs on diabetic retinopathy (DR). • HDL-C was inversely related to severe nonproliferative DR and proliferative DR. • No association between CETP inhibitor and DR was found. [ABSTRACT FROM AUTHOR]

Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non‐liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006–2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (<20%), intermediate (20%–49%), and high (≥50%). We also examined the associations by age of cancer diagnosis (earlier onset [<60] vs. ≥60). A total of 273 incident liver cancer and 4789 non‐liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41‐fold risk of liver cancer (RR = 2.41, 95% CI: 1.73–3.35) and 23% increased risk of non‐liver GI cancers (RR = 1.23, 95% CI: 1.14–1.32) (all ptrend < 0.001). Stronger associations were observed for men and individuals who were obese (all pinteraction < 0.05). NAFLD‐associated elevated risk was stronger for earlier‐onset cancers. For each 25% increase in NAFLD risk, the RRs for earlier‐onset cancers were 1.32 (95% CI: 1.05–1.66) for esophageal cancer, 1.35 (95% CI: 1.06–1.72) for gastric cancer, 1.34 (95% CI: 1.09–1.65) for pancreatic cancer, and 1.10 (95% CI: 1.01–1.20) for colorectal cancer. Conclusion: NAFLD risk was associated with an increased risk of liver and most GI cancers, especially those of earlier onset. [ABSTRACT FROM AUTHOR]

The emergence of genetic data coupled to longitudinal electronic medical records (EMRs) offers the possibility of phenome-wide association studies (PheWAS). In PheWAS, the whole phenome can be divided into numerous phenotypic categories according to the genetic architecture across phenotypes. Currently, statistical analyses for PheWAS are mainly univariate analyses, which test the association between one genetic variant and one phenotype at a time. In this article, we derived a novel and powerful multivariate method for PheWAS. The proposed method involves three steps. In the first step, we apply the bottom-up hierarchical clustering method to partition a large number of phenotypes into disjoint clusters within each phenotypic category. In the second step, the clustering linear combination method is used to combine test statistics within each category based on the phenotypic clusters and obtain p-values from each phenotypic category. In the third step, we propose a new false discovery rate (FDR) control approach. We perform extensive simulation studies to compare the performance of our method with that of other existing methods. The results show that our proposed method controls FDR very well and outperforms other methods we compared with. We also apply the proposed approach to a set of EMR-based phenotypes across more than 300,000 samples from the UK Biobank. We find that the proposed approach not only can well-control FDR at a nominal level but also successfully identify 1,244 significant SNPs that are reported to be associated with some phenotypes in the GWAS catalog. Our open-access tools and instructions on how to implement HCLC-FC are available at https://github.com/XiaoyuLiang/HCLCFC. [ABSTRACT FROM AUTHOR]

Background The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. Objectives We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. Methods This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. Results The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). Conclusions Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested associations between testosterone, genetic factors, and a series of complex diseases, but the associations with the lifespan phenotype, such as health span, remain unclear. Methods: In this prospective cohort study, we analyzed 145,481 men and 147,733 women aged 38–73 years old from UK Biobank (UKB) to investigate the sex-specific associations of total testosterone (TT), free testosterone (FT), or polygenic risk score (PRS) with health span termination (HST) risk. At baseline, serum testosterone levels were measured. HST was defined by eight events strongly associated with longevity. PRS, an efficient tool combining the effect of common genetic variants to discriminate genetic risk of complex phenotypes, was constructed by 12 single-nucleotide polymorphisms related to health span from UKB (P ≤ 5.0 × 10−8). We used multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up time of 7.70 years, 26,748 (18.39%) men and 18,963 (12.84%) women had HST. TT was negatively associated with HST in men [HR per standard deviation (SD) increment of log-TT: 0.92, 95% CI: 0.88–0.97]. Inversely, both TT (HR per SD increment of log-TT: 1.05, 95% CI: 1.02–1.08) and FT (HR per SD increment of log-FT: 1.08, 95% CI: 1.05–1.11) presented an increased risk of HST in women. PRS was positively associated with HST risk (quintile 5 versus quintile 1, men, HR: 1.19, 95% CI: 1.15–1.24; women, HR: 1.21, 95% CI: 1.16–1.27). Moreover, men with high TT and low genetic risk showed the lowest HST risk (HR: 0.80, 95% CI: 0.73–0.88), whereas HST risk for women with both high TT and genetic risk increased obviously (HR: 1.32, 95% CI: 1.19–1.46). Similar joint effects were observed for FT in both genders. Conclusions: We observed sex-specific associations that testosterone was negatively associated with HST risk in men and positively associated with HST risk in women. Genetic factors increased the HST risk, suggesting that participants with both high genetic risk and abnormal testosterone levels (high level in women or low level in men) should be the target for early intervention. Although our findings highlight the associations between testosterone and health span, further mechanistic studies and prospective trials are warranted to explore the causation behind. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations between sleep quality and health span using a prospective cohort design based on the UK Biobank (UKB). Materials and Methods: This longitudinal cohort study enrolled 328,850 participants aged between 37 and 73 years from UKB to examine the associations between sleep quality and risk of terminated health span. End of health span was defined by eight events strongly associated with longevity (cancer, death, congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, and diabetes), and a sleep score was generated according to five sleep behavioral factors (sleep duration, chronotype, sleeplessness, daytime sleepiness, and snoring) to characterize sleep quality. The hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by multivariate-adjusted Cox proportional hazards model. Moreover, we calculated population attributable risk percentage (PAR%) to reflect the public health significance of healthy sleep quality. Results: Compared with poor sleep quality, participants with healthy sleep quality had a 15% (HR: 0.85, 95% CI: 0.81–0.88) reduced risk of terminated health span, and those of less-healthy sleep quality had a 12% (HR: 0.88, 95% CI: 0.85–0.92) reduced risk. Linear trend results indicated that the risk of terminated health span decreased by 4% for every additional sleep score. Nearly 15% health span termination events in this cohort would have been prevented if a healthy sleep behavior pattern was adhered to (PAR%: 15.30, 95% CI: 12.58–17.93). Conclusion: Healthy sleep quality was associated with a reduced risk of premature end of health span, suggesting healthy sleep behavior may extend health span. However, further studies are suggested for confirmation of causality and potential mechanism. [ABSTRACT FROM AUTHOR]

• Risks in global critical metals (CMs) supply have risen significantly. However, knowledge about CM flows remain low, causing issues like low CM recycling rates. • Quantified CM flows contained in the purchase, in-use stock, and waste of UK household electrical and electronic equipment (EEE) annually between 2011 and 2020. • Total amounts of CMs contained in UK household EEE in-use stock, purchase, and waste increased from 86, 13, and 8 kt in 2011 to 140, 30, and 16 (worth £1.8 billion) kt in 2020, respectively. • Provided higher granularity on both CM (19) and EEE (43) flows in UK households. • Help to achieve a comprehensive understanding of the flows of CMs and associated economic values and environmental impacts, informing a sustainable circular economy. Demand for critical metals (CMs) has risen significantly, causing substantial supply risks globally. One key factor is the lack of holistic understanding of stocks and flows of different CMs contained in electrical and electronic equipment (EEE) over time, resulting in low recycling rate for CMs from waste EEE (WEEE). This study aims to quantify stocks and flows of CMs in UK household EEE purchase, in-use stock and WEEE during 2011–2020, using a novel methodology to estimate annual purchase of a wide range of EEE products. We find that the total amounts of 19 different CMs contained in UK household EEE in-use stock, purchase, and WEEE had increased from 86, 13, and 8 thousand tonnes in 2011 to 140, 30, and 16 (worth £1.8 billion) in 2020, respectively. The findings provide new evidence that can assist decision makers develop strategies to make CMs more circular and sustainable. [ABSTRACT FROM AUTHOR]

Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09–6.32] in EIMDS, and 4.31 [1.39–13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05–1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes. • Diabetic patients with RIA had a higher risk of CKD compared to normal aldosterone or renin-dependent aldosteronism. • Two-sample Mendelian randomization analysis indicated that RIA was causally associated with CKD in diabetic patients. • Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetic patients. [ABSTRACT FROM AUTHOR]

Evaluations of food, energy and water (FEW) linkages are rapidly emerging in contemporary nexus studies. This paper demonstrates, from a food consumption perspective, the potential of life cycle thinking in understanding the complex and often “hidden” linkages between FEW systems. Our study evaluates the upstream virtual water and embodied energy in food consumption in the Tamar catchment, South West England, distinguishing between domestic production and imports origin. The study also evaluates key inputs, including virtual nutrients and animal feed, when tracking supply chain of food products. Based on current dietary patterns and food products selection, the catchment consumes annually 834 TJ, 17 hm 3 and 244 hm 3 of energy, blue water and green water, respectively. Tamar is not self-sufficient in terms of food and requires imports of food products, as well as imports of virtual nutrients and animal feed for local production. Consequently, 51% of the embodied energy and 88% blue and 45% green virtual water in food consumed within the catchment are imported. Most of the embodied energy (58%) and green virtual water (90%) are because of animal feed production, where nearly half of embodied energy (48%) and green virtual water (42%) come from imports. 92% of blue virtual water is used for irrigation and primarily happens elsewhere due to imports. Irrigation is the process that demands the largest amount of energy for the crop-based products, with 38% of their total energy demand, followed by fertilisers production (24%). Our study illustrates water and energy hotspots in the food life cycle and highlights potential FEW risks and trade-offs through trade. This is useful considering potential unexpected changes in trade under recent global socio-political trends. Currently available databases and software make LCA a key tool for integrated FEW nexus assessments. [ABSTRACT FROM AUTHOR]

Elderly-onset atopic dermatitis (AD) is a remarkable subtype and has been put on the agenda owing to its difficulty to control. Understanding the influence of genetic and environmental exposures is crucial to preventing elderly-onset AD. To explore the association between genes and air pollution on incident elderly-onset AD. This study was based on UK Biobank that recruited over 500,000 participants. The genetic risks were categorized into low, intermediate, and high groups according to tertiles of polygenic risk scores. Mixed exposure to various air pollutants was assessed using the weighted quantile sum (WQS) and also categorized based on tertiles. Within each genetic risk group, whether air pollutant mixture was associated with incident elderly-onset AD was estimated. 337,910 participants were included in the final analysis, and the mean age was 57.1. The median years for follow-up were 12.0, and the incident cases of AD were 2545. The medium and high air pollution mixture was significantly associated with incident AD compared with the low pollution group, with HRs of 1.182 (P = 0.003) and 1.359 (P < 0.001), respectively. In contrast, HR for medium and high genetic susceptibility was only 1.065 (P = 0.249) and 1.153 (P = 0.008). The population-attributable fraction of air pollution and genetic risk was 15.5 % (P < 0.001) and 6.4 % (P = 0.004). Additionally, compared with low genetic risk and low air pollution, high genetic risk and high air pollution was significantly associated with the incidence of elderly-onset AD with a HR of up to 1.523 (P < 0.001). There were no interactive effects between each group of genetic risks and air pollution. When grouped by sex, females could observe a stronger effect by genetic and air pollutant mixture exposure. Air pollution and genetics both independently enhance the risk of newly developed AD, and the effect of air pollutants is stronger than the investigated genes. • The effect of air pollutant mixtures on incident AD was examined. • Exposure to air pollutants has a larger contribution than genetic variants. • Air pollution is associated with AD independent of genetic susceptibility. [ABSTRACT FROM AUTHOR]

The marine and coastal environment is an important economic asset in the UK, and there is a need for greater information about marine economic activities for the purposes of marine management and policy. However, due to the difficulties of quantifying some marine sectors and separating them from terrestrial activities, the current size and structure of the marine economy is unknown. This paper defines a systematic approach to quantifying the UK marine economy, aiming to capture all activities in the market economy that occur within and depend upon UK marine and coastal environments, and estimates its contribution to the UK economy as a whole. The approach draws on previous research in this area and links sectors used in marine planning with the methodologies used in national accounts. The results suggest that the marine economy contributes double the amount of previous estimates to the UK economy. Changes in the structure of the marine economy, partly due to the expansion of offshore wind energy, may affect its economic contribution. The results also show that marine and coastal leisure and recreation sectors, which were previously thought to have a small economic contribution, are the second largest sector in the UK marine economy and account for the largest number of jobs. By disaggregating the economic sectors, the approach used here can underpin a marine natural capital approach, enabling economic activities to be linked with aspects of marine natural capital. • Marine activities contribute more to the UK economy than previously thought. • Leisure and recreation is the second largest sector in the UK marine economy. • Changing energy systems are affecting the structure of the UK marine economy. • Defining a marine economy can help policy makers evaluate the effects of changes. [ABSTRACT FROM AUTHOR]

As a by-product of the coal washing process, the methods involving the resource utilization of coal slime are very few because of its strong agglomeration and large water content. In this work, we propose a new way to dispose of coal slime, which involves preparing semi-coke water slurry (SCWS) with coal slime. When using sodium humate as dispersant at a dosage of 0.8 wt%, the solid concentration of ordinary SCWS reached a maximum (63.8 wt%) , and the concentration improved to 65.3 wt% after adding 15 wt% coal slime, and the calorific value of the slurry (18.07 MJ/kg) that can meet the Chinese standard (GB/T 18855–2002). The role of coal slime in improving the ability of SCWS is to optimize the particle size distribution as a small size material; additionally, it can improve the hydrophilicity of particulates through oxygen-containing groups and minerals, which increased the performance of SCWS. Image 1 • An environment-friendly slurry fuel was prepared by semi-coke and coal slime. • The semi-coke water slurry (SCWS) has good slurry ability and high calorific value. • The solid concentration of SCWS containing 15 wt% coal slime reached the maximum. • The action mechanism of coal slime in SCWS on the slurry ability was proposed. [ABSTRACT FROM AUTHOR]

• 'Healthspan' is the number of years of living without any of seven severe aging-related morbidities. • There is no consensus on how lifestyle factors interact with genetic risk in their effects on longevity and health. • Healthy living can cut the risk of termination of the 'healthspan' by 40 %, even in the presence of high genetic risk. • Individuals at high genetic risk benefit more from healthy living. To investigate whether a polygenic risk score (PRS) and its interactions with lifestyle factors are associated with termination of the 'healthspan' (the number of years living without serious diseases or degeneration). Death or the incidence of any of seven independent morbidities (cancer, congestive heart failure, myocardial infarction, chronic obstructive pulmonary disease, stroke, dementia, and diabetes) strongly associated with aging were considered to define the termination of the healthspan. A total of 288,359 healthy participants from the UK Biobank were included in this prospective cohort study to evaluate the associations between PRS, lifestyle, and healthspan. The PRS was generated by weighting 12 healthspan-related genetic loci, which and scores were then categorized into three groups in Cox regression models. A lifestyle index was developed that incorporated body mass index (BMI), alcohol consumption, diet, smoking, and physical activity, and these scores were also categorized into three groups. The risk of termination of the healthspan was calculated across the different PRS and lifestyle index groups using Cox regression models. Interactions were estimated with the marginal effect of lifestyle on the risk of termination of healthspan across values of the moderator PRS using kernel estimation. During an average follow-up of 9.83 years, 68,903 healthspan-termination events occurred. It was calculated that people with high polygenic risk could reduce their risk of healthspan termination by 40 % if they maintain a favorable lifestyle. The marginal effect of lifestyle on the risk of healthspan termination increased with growing genetic risk. Smoking and diet showed monotonic changes in opposite directions, while BMI, physical activity, and alcohol had a U-shaped interaction with genetic risk. Favorable lifestyle can attenuate the risk of termination of the healthspan, especially for people with high genetic risk. The improvement afforded by ideal lifestyle behaviors varies for each individual. [ABSTRACT FROM AUTHOR]

Understanding how germline mutations affect Clonal Hematopoiesis (CH) will provide insights into germline predisposition to MN. We leveraged blood whole-exome sequencing data from 200,643 individuals in the UK Biobank (UKBB). The association between CH and germline mutations in 211 cancer susceptibility genes were tested among participants without hematologic malignancies at baseline using logistic regression adjusted for known confounders. Genes suggestive of association with CH were validated in 17,037 solid tumor patients with blood sequenced using Memorial Sloan Kettering (MSK) IMPACT panel. Germline pathogenic/likely pathogenic mutations were detected in 8,967 UKBB participants (4.5%). Germline mutations in TP53, ATR, ATM, and MPL were associated with increased risk of CH with odds ratios (ORs) and confidence intervals (CIs) of 4.33(1.31-14.32), 2.53(1.11-5.76), 2.21(1.23-3.97) and 1.44(1.00-2.08), correspondingly. Among 37 subjects with Li Fraumeni in the MSK-IMPACT cohort, TP53 was also associated with CH (OR: 3.75, 95% CI: 1.40-8.94) and this association was independent of cancer therapy (ORuntreated: 13.52, 95% CI: 2.94-57.48). The significant positive associations between germline TP53 mutations and CH were driven by somatic mutations in TP53 (OR:18.5, 95% CI: 2.8-72.8) and DNMT3A (OR: 5.1, 95% CI: 1.8-12.4). The rate of MN in TP53 mutation carriers was significantly increased (incidence rate ratio: 23.3; 95% CI: 6.0-65.4). The transition to MN was demarcated by a second TP53 loss of function mutation or deletion and by complex karyotype. Germline mutations in cancer susceptibility genes, particularly those in the DNA damage response pathway are independent risk factors for CH and MN development. [ABSTRACT FROM AUTHOR]