CAROTID PLAQUE AND INTIMA MEDIA THICKNESS IN THE ASSESSMENT OF CARDIOVASCULAR RISK

Dramatic advances have been demonstrated over the past decade in the prevention and treatment of cardiovascular disease (CVD). Despite these major strides, CVD continues to be our nation's most significant cause of morbidity and mortality. The risk status of persons without known CVD varies greatly and thus requires a range of intense screening and interventions. This dissertation focuses on subclinical CVD measures as well as a new methodology that will improve the evaluation of CVD in clinical trials and eventually improve primary prevention of CVD. There are three related projects in this dissertation, each of which uses noninvasive subclinical methodologies to assess cardiovascular risk. The first project focuses on a high-risk population, the elderly, and evaluates the association calcified carotid plaques with cardiovascular outcomes. Carotid plaque characterization is a new focus of research across the nation and what makes one plaque more dangerous than another is unclear. We do know that as plaques age, the plaques often become more complicated and often calcify. However, the significance of calcification in the carotid arteries is poorly understood. In this project, I assess if carotid calcification is predictive of cardiovascular outcomes.The second project focuses on another high cardiovascular risk population, women systemic lupus erythematosus (SLE). Women with SLE have a significantly high risk of myocardial infarction compared to women without SLE. The role that lupus-related risk factors have in cardiovascular disease progression above the traditional risk factors is unclear. Using carotid ultrasound, associations are evaluated between intima-media thickness and plaque with both cardiovascular and SLE-specific risk factors. The third and final project is the development of a protocol that will allow new computerized assessment of carotid artery plaques. Over the past decade both ultrasound technology and computerized assessment tools have improved. This creates opportunity for improved plaque assessment in vivo. This methodology characterized plaque components, possibly identifying plaques that may be dangerous. Plaque characterization software is now available for use with ultrasound and I have developed the protocols to execute this technique in the Ultrasound Research Laboratory. The final project outlines the software and testing process development, staff training, worksheet design, quality control processes, and a pilot study to evaluate the reproducibility of the measure. This research will contribute to public health through new cardiovascular risk assessment techniques and may lead to improved primary prevention and research methods

Community-Based Population Health Research: A Report from the Field

This Forum, “Community-Based Population Health Research: A Report from the Field” highlights the work of 1889 Jefferson Center for Population Health and Mainline Center for Population Health Research. Leaders from both research centers provide an overview of the history and purpose of the centers and describe accomplishments and current initiatives. Objectives: Describe two innovative models for population health research centers List three benefits of partnering with a University when establishing a population health center Characterize challenges associated with the development of community-engaged and health system embedded, population health research centers Presentation: 49:1

Conceptual understanding of screen media parenting: report of a working group

Screen media (television, computers, and videogames) use has been linked to multiple child outcomes, including obesity. Parents can be an important influence on children\u27s screen use. There has been an increase in the number of instruments available to assess parenting in feeding and physical activity contexts, however few measures are available to assess parenting practices regarding children\u27s screen media use. A working group of screen media and parenting researchers convened at the preconference workshop to the 2012 International Society for Behavioral Nutrition and Physical Activity (ISBNPA) annual meeting, “Parenting Measurement: Current Status and Consensus Reports,” to identify and prioritize issues in assessing screen media parenting practices. The group identified that screen media use can pose different risks for children, depending on their age and developmental stage, across physiologic, psychosocial, and development outcomes. With that in mind, a conceptual framework of how parents may influence their child\u27s screen-viewing behaviors was proposed to include the screen media content, context of viewing, and amount viewed. A research agenda was proposed to prioritize a validation of the framework and enhance the ability of researchers to best assess parenting influences across the three domains of content, context and amount of children\u27s screen media use

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

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

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

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake