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Purpose: Previous studies have demonstrated that physical exercise can modulate the endogenous melatonin level in children with autism spectrum disorder (ASD) and improve their sleep quality. However, it remains unclear whether physical exercise or melatonin supplement, or a combination of both, is more effective in improving sleep quality in this population. The purpose of this study is to answer this research question by comparing the effectiveness of three types of interventions (physical exercise vs. melatonin supplement or a combination of both) in improving sleep quality in children with ASD. Methods: Sixty-two (62) children diagnosed with ASD were randomly assigned to one of four groups--cycling (n = 18), melatonin supplement (n = 14), a combination of both (n = 12), and placebo control group (n = 18). Four (4) sleep parameters (sleep efficiency, sleep onset latency, sleep duration, and wake after sleep onset) were assessed. Results: The results revealed a significant improvement in sleep efficiency, sleep onset latency, and sleep duration in all of the interventions, but not in the placebo control group. However, no significant group differences were found among the interventions (ps > 0.05). Conclusion: Our findings suggest similar effectiveness of physical exercise and melatonin supplementation in improving sleep quality in children with ASD.

Abstract Background Existing patient-reported outcome (PRO) measures may not be relevant to the full range of functional and vision-related quality of life (VR-QOL) concerns of individuals with vision impairment due to severe peripheral field loss (PFL). Measurement of VR-QOL in severe PFL is important in order to determine the effectiveness of vision rehabilitation interventions for this population. The purpose of this study was to characterize the impact of severe PFL due to retinitis pigmentosa (RP) and glaucoma on VR-QOL as the initial phase in the development of a novel PRO measure. Methods Individuals with severe PFL due to RP or glaucoma were recruited from the Kellogg Eye Center and the Association for the Blind and Visually Impaired. Participants completed semi-structured qualitative interviews, the Impact of Vision Impairment (IVI) questionnaire and the RAND 36-Item Health Survey. Interviews were analyzed by two coders using thematic analysis. A matrix analysis was conducted to compare VR-QOL by cause of severe PFL. Sample size was determined by thematic saturation. Results The study included 37 participants (19 RP, 18 glaucoma). Median best-corrected visual acuity for those with RP and glaucoma was 20/40 and 20/27.5, while Pelli-Robson contrast sensitivity was 1.2 log contrast sensitivity (logCS) and 1.1 logCS, respectively. Median domain scores on the IVI (reading, mobility, well-being) ranged from a low of − 0.2 to a high of 0.7 logits in those with RP and from 0.5 to 1.2 logits in those with glaucoma. Qualitative interviews identified six VR-QOL themes relevant across participants with both RP and glaucoma, including activity limitations, driving, emotional well-being, reading, mobility, and social function. VR-QOL concerns were largely consistent among those with severe PFL due to RP and glaucoma. These overarching themes contained content relevant to specific challenges related to severe PFL. Conclusions There are commonly occurring VR-QOL concerns among individuals with severe PFL due to RP and glaucoma. The outlined themes will serve as the basis for development of the Low Vision Severely Constricted Peripheral Eyesight (LV-SCOPE) Questionnaire.

Abstract Background About half of people with glaucoma do not adhere to their recommended medications. Interventions for other chronic conditions have successfully utilized reminder systems and motivational interviewing (MI)-based counseling. This study was designed to pilot a personalized intervention that leverages these strategies to assess their impact on medication adherence in glaucoma patients. Methods Glaucoma patients taking ≥ 1 medication will be pre-screened by telephone survey for adherence to their medication(s). Those who self-report poor adherence will be enrolled in a 3-month monitoring period to measure medication adherence using electronic medication monitors. Participants who are non-adherent (take

Abstract Background To determine alignment of proposed international standard outcomes sets for ophthalmic conditions to metrics currently reported by eye hospitals. Methods Mixed methods comparative benchmark study, including eight eye hospitals in Australia, India, Singapore, Sweden, U.K., and U.S. All are major international tertiary care and training centers in ophthalmology. Main outcome measure is consistency of ophthalmic outcomes measures reported. Results International agreed standard outcomes (ICHOM) sets are available for cataract surgery (10 metrics) and macular degeneration (7 metrics). The eight hospitals reported 22 different metrics for cataract surgery and 2 for macular degeneration, which showed only limited overlap with the proposed ICHOM metrics. None of the hospitals reported patient reported visual functioning or vision-related quality of life outcomes measures (PROMs). Three hospitals (38%) reported rates for uncomplicated cataract surgeries only. There was marked variation in how and at what point postoperatively visual outcomes following cataract, cornea, glaucoma, strabismus and oculoplastics procedures were reported. Seven (87.5%) measured post-operative infections and four (50%) measured 30 day unplanned reoperation rates. Conclusions Outcomes reporting for ophthalmic conditions currently widely varies across hospitals internationally and does not include patient-reported outcomes. Reaching consensus on measures and consistency in data collection will allow meaningful comparisons and provide an evidence base enabling improved sharing of “best practices” to improve eye care globally. Implementation of international standards is still a major challenge and practice-based knowledge on measures should be one of the inputs of the international standardization process.

Physical exercise is widely reported beneficial to executive functions in children with autism spectrum disorder. However, its impact on self-regulation in the population remains unknown. This study is to test whether two types of physical exercise (cognitively engaging vs non-cognitively engaging) benefited self-regulation and whether the social, emotional, and physical needs of an individual mediated the exercise--executive function and exercise--self-regulation relationships. Sixty-four children diagnosed with autism spectrum disorder were randomly assigned into 1 of 3 groups: learning to ride a bicycle (n = 23), stationary cycling (n = 19), or an active control with walking (n = 22). Two executive functions (flexibility and inhibition), self-regulation and the mediating roles of perceived social support, enjoyment, stress, physical self-efficacy, and perceived physical fitness were assessed. Participants in the learning to ride a bicycle group significantly improved their executive functions (p values < 0.01). The learning to ride a bicycle group and the stationary cycling group also significantly enhanced their self-regulation (p values < 0.001). Mediation analyses showed that physical self-efficacy and perceived physical fitness partially mediated the exercise--executive function relationship. Meanwhile, perceived social support significantly mediated the exercise--self-regulation relationship (p < 0.05). Our findings highlight the value of cognitively engaging exercise on enhancing executive functions in children with autism spectrum disorder in part by improving their physical self-efficacy and perceptions of fitness.

Abstract Objective To develop and institute a standardized ophthalmology-specific operating room checklist, and to test adherence to the surgical checklist components after implementation. Design An ophthalmology-specific operative room checklist was developed using recommendations from surgical preoperative checklists from other subspecialties and checklists specific to cataract surgery. This standardized checklist was then implemented into the operating rooms. Operative room staff was trained on its use. Adherence to the checklist was measured prospectively. Setting Surgical centers at Kellogg Eye Center in Ann Arbor and Livonia, Michigan. Participants Patients undergoing ophthalmic surgery at the Livonia and Ann Arbor surgical centers. Main Outcome(s) and Measure(s) The primary outcome measures were surgical team adherence to each category of the operative checklist (preop, prebrief, preanesthesia verification, time-out, intraocular lens measurement/confirmation for cataract cases, debrief). Adherence to the subsections of the operative checklist was measured during three periods over the course of 1 year: baseline, postintervention (after introduction of the checklist in all operating rooms), and postadjustment (after additional training was provided to operating room staff and incentives to collect data were provided to personnel responsible for collecting it). Results A total of 2,532 surgical cases were included in the analysis. Baseline adherence ranged from 87 to 90% across preop, prebrief, preanesthesia, and time-out verification sections of the operative checklist. After the institution of the intervention and adjustments, adherence to the surgical checklist improved significantly across all areas of the checklist to 97–98% (p

Abstract Background Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness. Methods Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale’s structure. Concurrent validity, internal consistency, and test-retest reliability were also examined. Results A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p

Abstract Background Little evidence is available to verify the mediating effect of dispositional mindfulness on the association between gaming disorder and various impulsivity traits. The present study aimed to investigate the mediating effect of dispositional mindfulness on the association between the five UPPS-P impulsivity traits and the risk of gaming disorder among young adults. Methods It was an inter-regional cross-sectional study using online survey in Australia, Japan, The Philippines and China. Impulsivity measured by the UPPS-P Impulsive Behavior Scale–Short version; dispositional mindfulness measured by the Mindfulness Attention Awareness Scale; and the risk of gaming disorder measured by the Internet Gaming Disorder Scale were collected in the focal regions. Structural equation modeling was performed by SPSS AMOS version 26 to verify the study hypotheses. Bootstrapped 95% confidence interval was reported. Statistical significance was indicated by the p-value below 0.05. Results Among the 1,134 returned questionnaires, about 40% of them aged 18–20 years and 21–23 years, respectively. 53.8% were male. 40.7% had been playing digital and video games for over 10 years. The prevalence of gaming disorder was 4.32%. The model fitness indices reflected that the constructed model had an acceptable model fit (χ2(118) = 558.994, p

Summary: Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeutic targets for human disease by nominating causal genes in genome-wide association study (GWAS) loci. We conducted cis-IV analyses for 20,125 genes and 1,746 plasma proteins with CAD using molecular trait quantitative trait loci variant (QTLs) data from three different studies. 19 proteins and 119 genes were significantly associated with CAD risk by IV analyses and demonstrated evidence of genetic colocalization. Notably, our analyses validated well-established targets such as PCSK9 and ANGPTL4 while also identifying HTRA1 and endotrophin (a cleavage product of COL6A3) as proteins whose levels are causally associated with CAD risk. Further experimental studies are needed to confirm the causal role of the genes and proteins identified through our multiomic cis-IV analyses on human disease.

Objectives. To describe glaucoma patients' trust in the physician and to test the hypothesis that increased interpersonal trust is associated with increased medication adherence. Methods. One hundred ninety-five subjects with open-angle glaucoma seen by multiple glaucoma subspecialists participated in a cross-sectional patient survey and concomitant chart review which included a test of health literacy and the Trust in Physician Scale (TPS), a scale from 1–100, with 100 indicating greatest trust. Charts were reviewed for visual acuity and visual field results. Subjects' pharmacies were contacted to ascertain medication refill rates over the preceding six months. Results. TPS scores ranged from 57.5 to 100, 78.7±8.4 (mean±SD,) median 75.0. When age, race, gender, baseline visual acuity and visual field status, education level, and literacy status were considered, only race was associated with TPS. Caucasians expressed slightly higher levels of trust (n=108; TPS 80.1±8.2) than non-Caucasians, (n=87 (82 Africans Americans); TPS 77.1±8.4; P=.012). TPS score was not associated with refill rates (P=.190). Conclusions. Trust in physician is generally high in this group of glaucoma patients but varies slightly by race. Trust in physician was not associated with glaucoma medication adherence in this tertiary care population.

Background After the rapid implementation of digital health services during the COVID-19 pandemic, a paucity of research exists about the suitability of remote consulting in people with intellectual disabilities and their carers, particularly for neuropsychiatric reviews. Aim This study examines when remote neuropsychiatric routine consulting is suitable for this population. Method A survey was conducted of people with intellectual disabilities and their carers, examining their preference between face-to-face and video consultations for ongoing neuropsychiatric reviews within a rural countywide intellectual disability service in Cornwall, England (population: 538 000). The survey was sent to all adults with intellectual disabilities open to the service on 30 July 2022, closing on 30 September 2022. Participants were asked to provide responses on 11 items predesigned and co-produced between clinicians and experts by experience. The entire service caseload of people had White ethnicity, reflecting the ethnic demographics of Cornwall. Responses received without consent were excluded from the study dataset. Results Of 271 eligible participants, 119 responses were received, 104 of whom consented to having their anonymised data used for research analysis. There were no significant differences between preferences and age and gender variables. There was no statistically significant difference regarding preference for the reintroduction of face-to-face appointments (52.0%) compared with video consultations (48.0%). Travel distance (>10 miles) to the clinical setting was important but did not outweigh benefits for those preferring a face-to-face appointment. Conclusions This study offers insights into the factors that influence preferences about what type of neuropsychiatric appointment is most suitable for people with intellectual disabilities.

Introduction Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain.Methods and analysis A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews.Ethics approval and dissemination Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country.Trial registration number ISRCTN18010240.

Primary adenoid cystic carcinoma (ACC) accounts for less than 0.2 % of all primary lung malignancies. Here we present two cases of lung ACC (ACCL), first is a 65-year-old female who was diagnosed with ACCL and surgically treated at another institution. She presented with recurrent tumor which was resected at our hospital. No adjuvant treatment was given, and she is without any signs of residual tumor or recurrence after 6 months. The second case is a 68-year-old female with a right upper lobe nodule noticed in 2017 but declined biopsy due to fear of possible complications. In 2022 she underwent biopsy at our institution which showed ACCL and was treated surgically without adjuvant therapy. Till date she is with no evidence of residual tumor or recurrence. Multiple disciplines need to work together to provide the best patient care from accurate diagnosis to surgical resection and additional therapy. More research is needed to generate guidelines for treatment of this rare malignancy, especially the indications for chemotherapy.

Abstract Background To the best of our knowledge, although ageing-induced fatigue could cause adverse outcomes such as frailty, there is currently no intervention for it. This study evaluated the effects of an individualised exercise programme with/without BCE strategies on reducing fatigue in older adults. Methods A three-armed cluster-randomised controlled trial (RCT) was conducted with 184 participants (mean age: 79.1 ± 6.4; mean frailty score: 2.8 + 0.8) from 21 community centres (ClinicalTrials.gov: NCT03394495). They were randomised into either: the COMB group (n = 64), receiving 16 weeks of exercise training plus the BCE programme; the EXER group (n = 65), receiving exercise training and health talks; or the control group (n = 55), receiving only health talks. Fatigue was assessed using the Multi-dimensional Fatigue Inventory (range: 20 to 100, with higher scores indicating higher fatigue levels) at baseline, and immediately, 6 months, and 12 months post-intervention. Results The GEE analyses showed significant interaction (time x group) between the COMB and control groups immediately (p

Abstract Machine learning (ML) models trained for triggering clinical decision support (CDS) are typically either accurate or interpretable but not both. Scaling CDS to the panoply of clinical use cases while mitigating risks to patients will require many ML models be intuitively interpretable for clinicians. To this end, we adapted a symbolic regression method, coined the feature engineering automation tool (FEAT), to train concise and accurate models from high-dimensional electronic health record (EHR) data. We first present an in-depth application of FEAT to classify hypertension, hypertension with unexplained hypokalemia, and apparent treatment-resistant hypertension (aTRH) using EHR data for 1200 subjects receiving longitudinal care in a large healthcare system. FEAT models trained to predict phenotypes adjudicated by chart review had equivalent or higher discriminative performance (p

Abstract Background Cognitive frailty is a risk for many adverse health outcomes that are commonly observed in older people. Physical activity is known to be effective to reserve cognitive frailty but the prevalence of physical inactivity is still high in older people. E-health enhances behavioural change effects through an innovative way to deliver behavioural change methods that can enhance the behavioural change effects. However, its effects on older people with cognitive frailty, its effects compared with conventional behavioural change methods, and the sustainability of the effects are unclear. Methods This study employs a single-blinded, two-parallel-group, non-inferiority, randomized controlled trial design with a 1:1 group allocation ratio. Eligible participants are aged 60 years or above, have cognitive frailty and physical inactivity, and possess a smartphone for more than six months. The study will be conducted in community settings. In the intervention group, participants will receive a 2-week brisk-walking training followed by a 12-week e-health intervention. In the control group, participants will receive a 2-week brisk-walking training followed by a 12-week conventional behavioural change intervention. The primary outcome is minutes of moderate-to-vigorous physical activity (MVPA). This study aims to recruit a total of 184 participants. Generalized estimating equations (GEE) will be used to examine the effects of the intervention. Ethics and dissemination The trial has been registered at ClinicalTrials.gov (Identifier: NCT05758740) on 7th March 2023, https://clinicaltrials.gov/ct2/show/NCT05758740 , and all items come from the World Health Organization Trial Registration Data Set. It has been approved by the Research Ethics Committee of Tung Wah College, Hong Kong (reference number: REC2022136). The findings will be disseminated in peer-reviewed journals and presented at international conferences relevant to the subject fields. Trial registration The trial has been registered at ClinicalTrials.gov (Identifier: NCT05758740) and all items come from the World Health Organization Trial Registration Data Set. The latest version of the protocol was published online on 7th March 2023.

Abstract This study evaluated the long-term myopia control effect and safety in children wearing Defocus Incorporated Multiple Segments (DIMS) spectacle lenses. Participants who completed the 2-year RCT were followed for a total of 6 years; their cycloplegic refractions and axial length were measured. Group 1 (n = 36) wore DIMS spectacles for 6 years; Group 2 (n = 14) wore DIMS lens for the first 3.5 years and SV spectacles afterwards; Group 3 (n = 22) wore SV spectacles in the first 2 years and switched to DIMS; Group 4 (n = 18) wore SV spectacles in the first 2 years, switched to DIMS for 1.5 years and then SV spectacles again. Group 1 showed no significant differences in myopia progression (− 0.52 ± 0.66 vs. − 0.40 ± 0.72D) and axial elongation (0.32 ± 0.26 vs. 0.28 ± 0.28 mm, both p > 0.05) between the first and the later 3 years. In the last 2.5 years, DIMS lens groups (Groups 1 and 3) had less myopia progression and axial elongation than the single vision groups (Groups 2 and 4). There was no evidence of rebound after stopping the treatment. Post-wear visual functions in all groups were within norms. The results supported that DIMS lenses provided sustained myopia control without adverse effects over the 6-year study period. Trial registration: clinicaltrials.gov; NCT02206217.

BackgroundN95 respirators are used to limit the transmission of respiratory viruses in clinical settings. There are two to three major types of N95 available for all healthcare workers in Hong Kong. However, after the coronavirus outbreak and the consequent shortage of many commonly used respirators, several new N95 respirators were adopted temporarily in clinical settings without evaluation. Prior literature indicates that traditional N95 respirators used in hospitals in Hong Kong are not fit for Chinese people and have fit rates ranging from 50 to 60%. This study aims to investigate and compare the fit rate, real-time leakage, and mask usability of traditional and new N95 respirators among Chinese healthcare workers.MethodsThis study will employ two sequential phases. Phase 1 has a cross-sectional exploratory design used to investigate the fit rate and mask usability of three types of respirators. Phase 2 will examine the effectiveness of respiratory protection by comparing traditional and new N95 respirators by a randomized crossover trial. Eligible participants will be randomly allocated through a controlled crossover experiment to either a traditional or new respirator group (n = 100 in each arm) for performing standard clinical procedures. The primary outcome (real-time leakage) will be recorded at 30 s intervals during nasopharyngeal suctioning and cardiopulmonary resuscitation. The secondary outcomes are the fit rate and mask usability. After a 2 min suctioning (15 s twice) and 4 min one-person CPR, the fit rate (assessed by standard N95 fit testing) and mask usability (measured by self-reported mask usability scale) will be recorded as data of post-procedure. After 10 min rest, measurement of real-time leakage (i.e., crossover), fit test, and usability will be repeated.DiscussionThe result of real-time leakage will be a vital indicator of the respiratory protection of Chinese healthcare workers while performing prevalent clinical procedures, such as resuscitation. The fit rate and usability result will serve as an essential reference for consumable purchase policy in clinical settings.Trial registration: ISRCTN registry: ISRCTN40115047. Retrospectively registered on May 9, 2023. https://www.isrctn.com/ISRCTN40115047.

SVEP1 is linked to numerous human diseases, though its disease-promoting mechanism has remained unclear. Here, the authors identify SVEP1 as a ligand for the orphan receptor PEAR1 and provide insight into the role of this interaction in cardiovascular disease.

Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding transactive response DNA-binding protein 43 kDa (TDP-43), account for less than 1% of all ALS cases, TDP-43–positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS–causing (fALS-causing) mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer’s disease, and Parkinson’s disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a function of nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and life span deficits in 2 distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared through the autophagy/lysosome pathway, targeted reduction of Nlk represents a potential approach to therapy development for multiple neurodegenerative disorders.

Background There has been little focus on autism and attention-deficit hyperactivity disorder (ADHD) in occupational groups, particularly in high-demand roles such as the police. Aims To describe the characteristics and experiences of UK-based police force employees who are autistic and/or have ADHD, including the benefits and challenges their conditions bring to their occupation, their need for reasonable adjustments, and their co-occurring mental illnesses. Method An online survey was developed, containing both quantitative and qualitative elements. Survey invitations were disseminated through the National Police Autism Association. The survey was open from 23 April to 23 July 2022. Results A total of 117 participants participated in the survey, including 66 who were autistic and 51 with ADHD. Participants who were autistic and/or had ADHD widely reported both benefits and challenges related to their condition(s) in policing work. Both the autistic and ADHD groups widely reported having requested workplace adjustments related to their condition(s), although these were frequently not made. Anxiety (n = 57; 49%) and depression (n = 40; 36%) were both highly prevalent among the participants. The qualitative findings identified four themes: (a) motivations for taking on this career, (b) rewards of the role, (c) challenges of the job and (d) challenges regarding career progression. Conclusions Police force employees who are autistic and/or have ADHD reported that their conditions provided both benefits and challenges with respect to policing work, and that they had requested related workplace adjustments, although such adjustments frequently do not take place. Healthcare professionals need to recognise the importance of workplace considerations and advocacy for people who are autistic and/or have ADHD.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real‐world” setting. Untreated low‐density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow‐up, despite multiple lipid‐lowering treatment, low‐density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid‐lowering treatments were prescribed for 18%; 40% were on no lipid‐lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid‐lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Methods: Samples were collected from 9361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables. Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had threefold greater odds of SARS-CoV-2 infection over the next 6–9 months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK ‘Shielded Patient List’ had consistently greater odds (two- to fourfold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing – National Core Study (LHW-NCS) HMT/UKRI/MRC ([MC_PC_20030] and [MC_PC_20059]). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant [COV-LT-0009]). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. The UK Medical Research Council and Wellcome (Grant ref: [217065/Z/19/Z]) and the University of Bristol provide core support for ALSPAC.

PurposeTo explore the effect of bilberry and fish oil combination supplement on a small clinical sample patient-base with severe dry eyes.MethodsTwenty-four subjects were recruited with twelve randomly assigned to the intervention and control groups, respectively. Inclusion criteria included severe dry eye symptoms determined by scores >33 from the Ocular Surface Disease Index (OSDI) questionnaire. The intervention group was instructed to take an oral supplement with key ingredients of 600 mg bilberry extract and 240 mg docosahexaenoic acid-refined fish oil once daily for 3 months. The control group did not take any supplements. Mean changes in OSDI score, non-invasive tear break-up time (NITBUT), phenol red thread test (PRT), and percentage of meibomian gland openings were used as outcome measures. Testing was done at baseline, 1-month, and 3-month follow-up. Comparison between the treatment and control groups, and the younger adult and middle-age groups were performed.ResultsThe mean baseline values for the treatment and control groups were not clinically different. The OSDI score, NITBUT, PRT, and percentage of meibomian gland openings improved after taking the supplements for 3 months. The OSDI score, NITBUT, and PRT showed clinical improvements between the intervention and control groups. These improvements were consistent between the two age groups.ConclusionThis study suggested preliminary improvements in signs and symptoms of severe dry eyes that were independent of age after taking dietary supplementation of bilberry extract and fish oil for 3 months. Further studies using more device-based measures and a placebo supplement are warranted.

Summary: Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation.

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

Background: In research using accelerometers to measure physical activity, the number of accelerometers that can be utilized in a study and the study duration are both constrained. It means that increasing the number of accelerometer wearing days for all subjects leads to a decrease in the total number of participants the study can recruit. We used simulations to find the optimal combination of the number of wearing days and number of participant given a fixed number of accelerometer days. Methods: Two scenarios were studied here, including estimation of population physical activity level and the association between physical activity level and a health outcome. Another similar simulation was conducted by bootstrapping the National Health and Nutrition Examination Survey (NHANES) 2003–2006 accelerometer data (n = 4,069). Results: The simulation results of the first scenario showed that the error was minimized when the number of wearing days was 1 to 2. Simulation results of the second scenario showed that the optimal number of wearing days increased with the total number of accelerometer days and decreased with intra-class correlation (ICC). Conclusion: We developed a tool for researchers to determine the optimal combination of the number of the accelerometer wearing days and the total number of participants and showed that 1 to 2 accelerometer wearing days is optimal for estimation of population physical activity level.

Background Self-harm and suicidal behaviour are recognised as public health concerns. Prolonged social withdrawal behaviour, or hikikomori, is reported as a risk factor for suicidal behaviour. Aims To examine the occurrence and additional risk of prolonged social withdrawal behaviour on self-harm and suicidal behaviour among Chinese university students. Method A cross-sectional online survey was conducted with three universities in southern China. A two-stage random sampling was adopted for recruitment, with students in different years of study, in different departments of each participating university. Hierarchical logistic regression analyses were conducted to investigate the sociodemographic and psychological correlates of self-harm and suicidal behaviours among male and female participants with hikikomori status. Results Of the students who completed the online survey, 1735 (72.23%) were included in the analysis; 11.5% (n = 200) reported self-harm behaviour and 11.8% (n = 204) reported suicidal behaviours in the past 12 months. Men showed a higher prevalence rate of self-harm than women (14.7% v. 10.8%, P = 0.048), but a similar rate of suicidal behaviours (11.9% v. 11.3%, P = 0.78). The overall prevalence rate of social withdrawal behaviour was 3.2% (7.0% for men and 2.3% for women, P < 0.001). Prolonged social withdrawal behaviour status was significantly associated with self-harm (odds ratio 2.00, 95% CI 1.22–3.29) and suicidal behaviour (odds ratio 2.35, 95% CI 1.45–3.81). However, the associations became statistically insignificant after adjustment for psychological factors in the final models in the logistic regression analyses. Conclusions Prolonged social withdrawal behaviour appears to be associated with self-harm and suicidal behaviour, but psychological factors have stronger links with suicidality.

Summary: Background: Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods: A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings: We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation: Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding: Bill & Melinda Gates Foundation.

The neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1) affects the cerebellum and inferior olive, though previous research has focused primarily on the cerebellum. As a result, it is unknown what molecular alterations are present in the inferior olive, and whether these changes are found in other affected tissues. This study addresses these questions for the first time using two different SCA1 mouse models. We found that differentially regulated genes in the inferior olive segregated into several biological pathways. Comparison of the inferior olive and cerebellum demonstrates that vulnerable tissues in SCA1 are not uniform in their gene expression changes, and express largely discrete but some commonly enriched biological pathways. Importantly, we also found that brain-region-specific differences occur early in disease initiation and progression, and they are shared across the two mouse models of SCA1. This suggests different mechanisms of degeneration at work in the inferior olive and cerebellum.

Introduction: Metabolic syndrome (MetS) is a multiplex cardiometabolic manifestation associated with type 2 diabetes mellitus and cardiovascular diseases. Yoga training has been shown to alleviate MetS. Recently, circulatory ghrelin profile was demonstrated to be associated with MetS. This study examined the effects of 1 year of yoga training on β-cell function and insulin resistance, and the involvement of metabolic peptides, including unacylated ghrelin (UnAG), acylated ghrelin (AG), obestatin, growth hormone (GH), and insulin, in the beneficial effects of yoga training in centrally obese adults with MetS.Methods: This was a follow up study, in which data of risk factors of MetS, physical performance tests [resting heart rate (HR), chair stand test (CS), chair sit and reach test (CSR), back scratch test (BS), and single leg stand tests (SLS)] and serum samples of 79 centrally obese MetS subjects aged 58 ± 8 years (39 subjects received 1-year yoga training and 40 subjects received no training) were retrieved for analyses. β-cell function and insulin resistance were examined by Homeostasis Model Assessment (HOMA). Circulating levels of UnAG, AG, obestatin, GH, and insulin were determined by enzyme-linked immunosorbent assay using fasting serum samples. Generalized estimating equation analysis and Mann–Whitney U-test were used to detect statistically significant differences between groups.Results: Waist circumference (WC) was significantly decreased after yoga intervention (control: +2%; yoga: -4%). Significant improvements in HR (control: +2%; yoga: -5%), CS (control: -1%; yoga: +24%), CSR left (control: worsen by 0.90 cm; yoga: improved by 4.21 cm), CSR right (control: worsen by 0.75 cm; yoga: improved by 4.28 cm), right side of BS (control: improved by 0.19 cm; yoga: improved by 4.31 cm), SLS left (control: -10%; yoga: +86%), and SLS right (control: -6%; yoga: +47%) were observed after 1-year yoga training. No significant difference was found between the two groups in insulin, HOMA indices, and disposition index. Yoga training significantly increased circulating GH (control: -3%; yoga: +22%), total circulating ghrelin (control: -26%; yoga: +13%), and UnAG (control: -27%; yoga: +14%), whereas decreased AG (control: -7%; yoga: -33%) and obestatin (control: +24%; yoga: -29%).Conclusion: One-year of yoga training modulated total ghrelin, UnAG, AG, obestatin, and GH while exerting beneficial effects on physical functions and central obesity in adults with MetS. The beneficial effects of yoga may be associated with the alteration of ghrelin gene product and GH.

Central obesity and hypertension are common risk factors for the metabolic syndrome, cardiovascular and renal diseases. Studies have shown that it is more difficult to control blood pressure and prevent end-organ damage in obese individuals with hypertension compared to their non-obese counterparts, especially among women. Obese females have a 6 times higher risk of developing hypertension than non-obese females while obese males are at a 1.5 times higher risk of developing hypertension, compared to their non-obese counterparts. Indeed, the inter-relationship between obesity and hypertension is unclear. Adipokines have been proposed to play a mediating role in the relationship between obesity and hypertension and are involved in the pathogenesis of metabolic diseases. Therefore, this study sought to determine the role of adipokines (adiponectin, plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-α) in hypertensive Hong Kong Chinese women with central obesity. A total of 387 women aged 58 ± 11 years who were examined with a 2 × 2 factorial design for central obesity (waist circumference ≥ 80 cm) and hypertension (blood pressure ≥ 140/90 mmHg), were recruited from a pool of 1,492 Hong Kong Chinese adults who were previously screened for metabolic syndrome. Subjects with hyperglycemia, hypertriglyceridemia, and dyslipidemia were excluded to eliminate confounding effects. Our findings revealed that hypertensive women with central obesity had a lower anti-inflammatory status (adiponectin) and a higher pro-inflammatory status (TNF-α) than obese alone or hypertensive alone women. Also, women with central obesity had higher circulatory PAI-1 and leptin concentrations than their non-obese counterparts. We conclude that obesity may shift toward a more pro-inflammatory state and may become more severe in the presence of hypertension or vice versa.

As the Malacca and Singapore Straits are part of the shortest route between Europe and Asia any impedance to shipping has serious commercial and strategic repercussions. What would be the consequences to tankers and container shipping if access was restricted or prevented? This issue is addressed by examining the costs of using alternative tanker routes to the Straits and the flow-on consequences of removing a mega-hub port from the container-shipping network. The analysis highlights differences between tanker shipping, where the ship itself is the prime unit of interest, and container shipping, where the door-to-door network is of paramount importance.

Port competition attracted much scholarly attention in Northwest Europe during the 1980s. Following the rise of powerful economies in East Asia, particularly during the 1980s and 1990s, port competition has become an important phenomenon with the top five container ports in the world being located in the region. This paper aims to overview major port competition issues and outlines and analyzes the main alternative methodologies that researchers have employed to address them, referring to 70 items, mostly papers but including a few books and reports