Fostering a psychologically healthy workplace through leadership

viii, 147 leaves : illustrations ; 29 cmIncludes abstract and appendices.Includes bibliographical references (leaves 112-134).Although the impact of psychologically healthy workplaces on organizational and employee level outcomes has received increased attention over recent years (e.g., Day & Randell, 2014; Loughlin & Mercer, 2014), leaders and organizations often feel challenged as to how to foster a psychologically healthy workplace (Grawitch, Ledford, Ballard, & Barber, 2009). Given the success of leadership interventions in improving employee and organizational outcomes (e.g., Barling, Weber, & Kelloway, 1996) and the importance of incorporating leaders into interventions (Kelloway & Barling, 2010), this study drew on the Conservation of Resources Theory (Hobfoll, 1998; Hobfoll & Shirom, 2001) the Job Demands Resource Model (Demerouti, Bakker, Nachreiner, & Schaufeli, 2001), and the Effort-Reward Imbalance Model (Siegrist, 2001), and the role of leaders and healthy workplaces as resources in promoting employee wellbeing. I developed and validated a training program aimed at improving leaders’ behaviours that contribute to a healthy workplace and positive employee outcomes. In Study 1, I conducted interviews and focus groups with subject matter experts (N = 35) to develop a scale to assess leadership behaviours that contribute to a healthy workplace. In Study 2, I examined the psychometric properties of the scale in terms of reliability, and construct and criterion-validity (N = 601). In Study 3, I developed a leadership training program (Leading Healthy Workplaces: Fostering a Psychologically Healthy Workplace through Leadership) and evaluated it using a longitudinal waitlist control training design (N = 68). Leaders reported increases in some of their own Healthy Workplace Leadership Behaviours. Direct reports reported perceived increases in one of their leaders’ behaviours (i.e., Promotion of a Healthy Workplace)

Lessons learned from additional research analyses of unsolved clinical exome cases

BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. RESULTS: Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). CONCLUSION: An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery of 187 Novel Risk Variants

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

An examination of individual and work-related factors influencing program success of an employee health intervention

vii, 70 leaves : col. ill. ; 29 cm.Includes abstract and appendix.Includes bibliographical references (leaves 39-47).Some studies have assessed the impact of workplace interventions on increasing recovery experiences and reducing stress and strain through training (e.g., Hahn, Binnewies, Sonnentag, & Mojza, 2011; MacDonald, 2012; Stevens, 2010). However, little research has examined factors influencing the effectiveness of such interventions. The training literature states that individual and situational characteristics can influence the effectiveness of a training program and influence behaviour change (Mathieu & Martineau, 1997; Noe & Schmitt, 1986). Therefore, using two separate samples of archival data of 119 and 117 employees from 15 and 10 organizations, I examined several individual and work-related factors that may influence the effectiveness of an employee health intervention (i.e., Achieving Balance in Life and Employment; ABLE program), which aims to increase recovery experiences and reduce stress and strain. Results of this study provide preliminary evidence that individual and work-related variables can influence one’s success in an employee health intervention

Meat-Reduced Dietary Practices and Efforts in 5 Countries: Analysis of Cross-Sectional Surveys in 2018 and 2019.

BACKGROUND: Diets that reduce reliance on animal-source foods are recommended in some contexts. OBJECTIVES: This study aimed to compare proportions of respondents who reported following meat-reduced dietary practices (i.e., vegetarian, vegan, or pescatarian diets) and/or making efforts to reduce animal-source foods, and to examine sociodemographic correlates across 5 countries. METHODS: Online surveys were conducted in November and December 2018 and 2019 with 41,607 adults from Australia (n = 7926), Canada (n = 8031), Mexico (n = 8110), the United Kingdom (n = 9129), and the United States (n = 8411) as part of the International Food Policy Study. Respondents were asked whether they would describe themselves as vegetarian, vegan, or pescatarian, and whether they had made efforts to consume less red meat, less of all meats, or less dairy in the past year. Logistic regressions examined differences in the likelihood of each behavior between countries and sociodemographic subgroups. RESULTS: Approximately 1 in 10 respondents reported following a vegetarian, vegan, or pescatarian diet, ranging from 8.6% (Canada) to 11.7% (UK). In the past 12 months, the proportions of respondents who reported efforts to consume less red meat ranged from 34.5% (Australia) to 44.4% (Mexico), less of all meats ranged from 27.9% (US) to 35.2% (Mexico), and to consume less dairy ranged from 20.6% (UK) to 41.3% (Mexico). Respondents were more likely to report efforts to consume less animal-source products in 2019 compared to 2018 in most countries. Sociodemographic patterns varied by country; in general, women, those with higher education levels, and those in minority ethnic groups were more likely to report following meat-reduced dietary practices or efforts to consume fewer animal-source products. CONCLUSIONS: Nearly half of respondents reported following a meat-reduced diet or efforts to reduce animal-source products, with differences between countries and population subgroups. Population-level approaches and policies that support meat reduction may further reduce consumption of animal-source products.Funding for the International Food Policy Study was provided by a Canadian Institutes of Health Research (CIHR) Project Grant (PJT-162167), with additional support from Health Canada, the Public Health Agency of Canada (PHAC), and a CIHR-PHAC Applied Public Health Chair (DH). MW is supported with funding for a research programme in the MRC Epidemiology Unit, University of Cambridge, UK (MRC grant number: MC/UU/00006/7)