Shift work and cardiovascular events: systematic review and meta-analysis

The prevalence of shift work is increasing in the general population. There is conflicting epidemiologic evidence on the association between shift work and cardiovascular disease. We performed a systematic review and meta-analysis of observational studies that measured shift work-cardiovascular disease associations. We screened 12,350 articles and identified 35 eligible studies. The pooled risk ratios (RR) for myocardial infarction, all coronary events and ischemic stroke were 1.23 (95% confidence interval [CI] 1.15 to 1.31, I2 = 0), 1.24 (95% CI 1.10 to 1.39, I2 = 85%) and 1.05 (95% CI 1.01 to 1.09, I2 = 0), respectively. The population-attributable risks from shift work for myocardial infarction, all coronary events and ischemic stroke in Canada would be 7%, 7.3% and 1.6%, respectively. We found no evidence of publication bias. We report significant yet relatively modest associations for shift work and cardiovascular events. These results have implications for public policy and occupational medicine

Shift work and vascular events: Systematic review and meta-analysis.

OBJECTIVE: To synthesise the association of shift work with major vascular events as reported in the literature. DATA SOURCES: Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines. STUDY SELECTION: Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ( day ) workers or the general population. DATA EXTRACTION: Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, ischaemic stroke, and any coronary event. Heterogeneity was measured with the I(2) statistic and computed random effects models. RESULTS: 34 studies in 2,011,935 people were identified. Shift work was associated with myocardial infarction (risk ratio 1.23, 95% confidence interval 1.15 to 1.31; I(2)=0) and ischaemic stroke (1.05, 1.01 to 1.09; I(2)=0). Coronary events were also increased (risk ratio 1.24, 1.10 to 1.39), albeit with significant heterogeneity across studies (I(2)=85%). Pooled risk ratios were significant for both unadjusted analyses and analyses adjusted for risk factors. All shift work schedules with the exception of evening shifts were associated with a statistically higher risk of coronary events. Shift work was not associated with increased rates of mortality (whether vascular cause specific or overall). Presence or absence of adjustment for smoking and socioeconomic status was not a source of heterogeneity in the primary studies. 6598 myocardial infarctions, 17,359 coronary events, and 1854 ischaemic strokes occurred. On the basis of the Canadian prevalence of shift work of 32.8%, the population attributable risks related to shift work were 7.0% for myocardial infarction, 7.3% for all coronary events, and 1.6% for ischaemic stroke. CONCLUSIONS: Shift work is associated with vascular events, which may have implications for public policy and occupational medicine

Genome-wide association studies of the self-rating of effects of ethanol (SRE).

The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders

Divergent in situ expression of IL-31 and IL-31RA between bullous pemphigoid and pemphigus vulgaris

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients

Genomic, Proteomic and Phenotypic Biomarkers of COVID-19 Severity::Protocol for a Retrospective Observational Study

Background:Background - Health organisations and countries around the world have found it difficult to control the spread of the coronavirus disease 2019. To minimise the impact on the NHS and improve patient care, there is a drive for rapid tests capable of detecting individuals who are at high risk of contracting severe COVID-19. Early work focused on single omic approaches, highlighting a limited amount of information.Objective:Objective - The Covid Response Study (COVRES, NCT05548829) aims to carry out an integrated multi-omic analysis of factors contributing to host susceptibility to SARS-CoV-2 among a patient cohort of 1000 people from the geographically isolated island of Ireland.Methods:Methods - The protocol below describes the study to be carried out in Northern Ireland (NI-COVRES) by Ulster University, the Republic of Ireland component will be described separately. All participants (n=519) were recruited from the Western Health and Social Care Trust, Northern Ireland, forty patients are also being followed up at 1, 3, 6 and 12 months to assess the longitudinal impact of infection on symptoms, general health, and immune response, this is ongoing. Data will be sourced from whole blood, saliva samples, and clinical data from the Northern Ireland Electronic Care Record, general health questionnaire, and the GHQ12 mental health survey. Saliva and blood samples were processed for DNA and RNA prior to whole genomic sequencing, RNA sequencing, DNA methylation, microbiome, 16S, and proteomic analysis. Multi-omics data will be combined with clinical data to produce sensitive and specific prognostic models of severity risk.Results:Results - An initial profile of the cohort has been completed: n=249 hospitalised and n=270 non-hospitalised patients were recruited, 64% were female, the mean age was 45 years. High levels of comorbidity were evident in the hospitalised cohort, with cardiovascular disease and metabolic and respiratory disorders (P<0.001) being the most significant.Conclusions:Conclusion – This study will provide a comprehensive opportunity to study multi-omic mechanisms of COVID-19 severity in re-contactable participants. Clinical Trial: Trial Registration - The trial has been registered as an observational study on clinicaltrials.gov as NCT05548829. An outline of the trial protocol is included; SPIRIT checklist (Supplementary Figure 1)

Tool path pattern and feed direction selection in robotic milling for increased chatter-free material removal rate

Robotic milling becomes increasingly relevant to large-scale part manufacturing industries thanks to its cost-effective and portable manufacturing concept compared to large-scale CNC machine tools. Integration of milling processes with industrial robots is proposed to be well aligned with the aims and objective of the recent fourth industrial revolution. However, the industrial robots introduce position-dependent and asymmetrical dynamic flexibility, which may reflect to the tool tip dynamics under several conditions. Under such circumstances, the stability limits become dependent on the machining location and the feed direction. In this respect, selection of machining tool path patterns is crucial for increased chatter-free material removal rates (MRR). This paper proposes an approach to evaluate and select tool path patterns, offered by the existing CAM packages, for increased chatter-free MRR. The machining area is divided into number of machining locations. The optimal feed direction is decided based on the absolute stability at each region considering the asymmetrical and position-dependent tool tip dynamics. Then, the alternative tool path patterns are evaluated and the corresponding optimum feed direction is decided for increased chatter-free material removal. The application of the proposed approach is demonstrated through simulations and representative experiments

Performance Analysis of Space-Time Block Codes in Flat Fading MIMO Channels with Offsets

We consider the effect of imperfect carrier offset compensation on the performance of space-time block codes. The symbol error rate (SER) for orthogonal space-time block code (OSTBC) is derived here by taking into account the carrier offset and the resulting imperfect channel state information (CSI) in Rayleigh flat fading MIMO wireless channels with offsets.https://doi.org/10.1155/2007/3054

Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.</p> <p>Methods/Design</p> <p>The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.</p> <p>Discussion</p> <p>It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=ISRCTN02839188">ISRCTN02839188</a></p

Genome wide association studies of the Self-Rating of Effects of Ethanol (SRE)

The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders