Employees\u27 Views and Ethical, Legal, and Social Implications Assessment of Voluntary Workplace Genomic Testing

Employers have begun to offer voluntary workplace genomic testing (wGT) as part of employee wellness benefit programs, but few empirical studies have examined the ethical, legal, and social implications (ELSI) of wGT. To better understand employee perspectives on wGT, employees were surveyed at a large biomedical research institution. Survey respondents were presented with three hypothetical scenarios for accessing health-related genomic testing: via (1) their doctor; (2) their workplace; and 3) a commercial direct-to-consumer (DTC) genetic testing company. Overall, 594 employees (28%) responded to the survey. Respondents indicated a preference for genomic testing in the workplace setting (70%; 95% CI 66-74%), followed by doctor\u27s office (54%; 95% CI 50-58%), and DTC testing (20%; 95% CI 17-24%). Prior to participating in wGT, respondents wanted to know about confidentiality of test results (79%), existence of relevant laws and policies (70%), and privacy protection (64%). Across scenarios, 92% of respondents preferred to view the test results with a genetic counselor. These preliminary results suggest that many employees are interested and even prefer genetic testing in the workplace and would prefer testing with support from genetic health professionals. Confirmation in more diverse employer settings will be needed to generalize such findings

Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design

Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Protein Phosphatase 2A Controls Ethylene Biosynthesis by Differentially Regulating the Turnover of ACC Synthase Isoforms

The gaseous hormone ethylene is one of the master regulators of development and physiology throughout the plant life cycle. Ethylene biosynthesis is stringently regulated to permit maintenance of low levels during most phases of vegetative growth but to allow for rapid peaks of high production at developmental transitions and under stress conditions. In most tissues ethylene is a negative regulator of cell expansion, thus low basal levels of ethylene biosynthesis in dark-grown seedlings are critical for optimal cell expansion during early seedling development. The committed steps in ethylene biosynthesis are performed by the enzymes 1-aminocyclopropane 1-carboxylate synthase (ACS) and 1-aminocyclopropane 1-carboxylate oxidase (ACO). The abundance of different ACS enzymes is tightly regulated both by transcriptional control and by post-translational modifications and proteasome-mediated degradation. Here we show that specific ACS isozymes are targets for regulation by protein phosphatase 2A (PP2A) during Arabidopsis thaliana seedling growth and that reduced PP2A function causes increased ACS activity in the roots curl in 1-N-naphthylphthalamic acid 1 (rcn1) mutant. Genetic analysis reveals that ethylene overproduction in PP2A-deficient plants requires ACS2 and ACS6, genes that encode ACS proteins known to be stabilized by phosphorylation, and proteolytic turnover of the ACS6 protein is retarded when PP2A activity is reduced. We find that PP2A and ACS6 proteins associate in seedlings and that RCN1-containing PP2A complexes specifically dephosphorylate a C-terminal ACS6 phosphopeptide. These results suggest that PP2A-dependent destabilization requires RCN1-dependent dephosphorylation of the ACS6 C-terminus. Surprisingly, rcn1 plants exhibit decreased accumulation of the ACS5 protein, suggesting that a regulatory phosphorylation event leads to ACS5 destabilization. Our data provide new insight into the circuitry that ensures dynamic control of ethylene synthesis during plant development, showing that PP2A mediates a finely tuned regulation of overall ethylene production by differentially affecting the stability of specific classes of ACS enzymes

Prevalence of obesity and abdominal obesity in the Lausanne population

Obesity can be defined using body mass index (BMI) or waist (abdominal obesity). Little information exists regarding its prevalence and determinants in Switzerland. Hence, we assessed the levels of obesity as defined by BMI or waist circumference in a Swiss population-based sample. Cross-sectional, population-based non-stratified random sample of 3,249 women and 2,937 men aged 35-75 years living in Lausanne, Switzerland. Overall participation rate was 41%. In men, the prevalences of overweight (BMI > or =25 kg/m2) and obesity (BMI > or =30 kg/m2) were 45.5% and 16.9%, respectively, higher than in women (28.3% and 14.3%, respectively). The prevalence of abdominal obesity (waist > or =102 in men and > or =88 cm in women) was higher in women than in men (30.6% vs. 23.9%). Obesity and abdominal obesity increased with age and decreased with higher educational level in both genders. In women, the prevalence of obesity was lower among former and current smokers, whereas in men the prevalence of obesity was higher in former smokers but did not differ between current and never smokers. Multivariate analysis showed age to be positively related, and education and physical activity to be negatively related with obesity and abdominal obesity in both genders, whereas differential effects of smoking were found between genders. The prevalence of abdominal obesity is higher than BMI-derived obesity in the Swiss population. Women presented with more abdominal obesity than men. The association between smoking and obesity levels appears to differ between genders

Algorithms for enhancing public health utility of national causes-of-death data

<p>Abstract</p> <p>Background</p> <p>Coverage and quality of cause-of-death (CoD) data varies across countries and time. Valid, reliable, and comparable assessments of trends in causes of death from even the best systems are limited by three problems: a) changes in the <it>International Statistical Classification of Diseases and Related Health Problems </it>(ICD) over time; b) the use of tabulation lists where substantial detail on causes of death is lost; and c) many deaths assigned to causes that cannot or should not be considered underlying causes of death, often called garbage codes (GCs). The Global Burden of Disease Study and the World Health Organization have developed various methods to enhance comparability of CoD data. In this study, we attempt to build on these approaches to enhance the utility of national cause-of-death data for public health analysis.</p> <p>Methods</p> <p>Based on careful consideration of 4,434 country-years of CoD data from 145 countries from 1901 to 2008, encompassing 743 million deaths in ICD versions 1 to 10 as well as country-specific cause lists, we have developed a public health-oriented cause-of-death list. These 56 causes are organized hierarchically and encompass all deaths. Each cause has been mapped from ICD-6 to ICD-10 and, where possible, they have also been mapped to the <it>International List of Causes of Death </it>1-5. We developed a typology of different classes of GCs. In each ICD revision, GCs have been identified. Target causes to which these GCs should be redistributed have been identified based on certification practice and/or pathophysiology. Proportionate redistribution, statistical models, and expert algorithms have been developed to redistribute GCs to target codes for each age-sex group.</p> <p>Results</p> <p>The fraction of all deaths assigned to GCs varies tremendously across countries and revisions of the ICD. In general, across all country-years of data available, GCs have declined from more than 43% in ICD-7 to 24% in ICD-10. In some regions, such as Australasia, GCs in 2005 are as low as 11%, while in some developing countries, such as Thailand, they are greater than 50%. Across different age groups, the composition of GCs varies tremendously - three classes of GCs steadily increase with age, but ambiguous codes within a particular disease chapter are also common for injuries at younger ages. The impact of redistribution is to change the number of deaths assigned to particular causes for a given age-sex group. These changes alter ranks across countries for any given year by a number of different causes, change time trends, and alter the rank order of causes within a country.</p> <p>Conclusions</p> <p>By mapping CoD through different ICD versions and redistributing GCs, we believe the public health utility of CoD data can be substantially enhanced, leading to an increased demand for higher quality CoD data from health sector decision-makers.</p

Membrane Docking Geometry of GRP1 PH Domain Bound to a Target Lipid Bilayer: An EPR Site-Directed Spin-Labeling and Relaxation Study

The second messenger lipid PIP3 (phosphatidylinositol-3,4,5-trisphosphate) is generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP3-specific pleckstrin homology (PH) domains to the membrane surface. Despite the broad importance of PIP3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i) PIP3 target lipid that provides specificity and affinity, and (ii) PS facilitator lipid that enhances the PIP3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral diffusion observed for PIP3-bound GRP1 PH domain on supported lipid bilayers