Deep Underground Science and Engineering Laboratory - Preliminary Design Report

The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations

Development of lifetime comorbidity in the world health organization world mental health surveys

CONTEXT: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. DESIGN: Nationally or regionally representative community surveys. SETTING: Fourteen countries. PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study

Associations between mental disorders and subsequent onset of hypertension

Background Previous work has suggested significant associations between various psychological symptoms (e.g. depression, anxiety, anger, alcohol abuse) and hypertension. However, the presence and extent of associations between common mental disorders and subsequent adult onset of hypertension remains unclear. Further, there is little data available on how such associations vary by gender or over life course. Methods Data from the World Mental Health Surveys (comprising 19 countries, and 52,095 adults) were used. Survival analyses estimated associations between first onset of common mental disorders and subsequent onset of hypertension, with and without psychiatric comorbidity adjustment. Variations in the strength of associations by gender and by life course stage of onset of both the mental disorder and hypertension were investigated. Results After psychiatric comorbidity adjustment, depression, panic disorder, social phobia, specific phobia, binge eating disorder, bulimia nervosa, alcohol abuse, and drug abuse were significantly associated with subsequent diagnosis of hypertension (with ORs ranging from 1.1 to 1.6). Number of lifetime mental disorders was associated with subsequent hypertension in a doseresponse fashion. For social phobia and alcohol abuse, associations with hypertension were stronger for males than females. For panic disorder, the association with hypertension was particularly apparent in earlier onset hypertension. Conclusions Depression, anxiety, impulsive eating disorders, and substance use disorders disorders were significantly associated with the subsequent diagnosis of hypertension. These data underscore the importance of early detection of mental disorders, and of physical health monitoring in people with these conditions

Non-fatal disease burden for subtypes of depressive disorder: population-based epidemiological study

Background: Major depression is the leading cause of non-fatal disease burden. Because major depression is not a homogeneous condition, this study estimated the non-fatal disease burden for mild, moderate and severe depression in both single episode and recurrent depression. All estimates were assessed from an individual and a population perspective and presented as unadjusted, raw estimates and as estimates adjusted for comorbidity. Methods: We used data from the first wave of the second Netherlands-Mental-Health-Survey-and-Incidence-Study (NEMESIS-2, n = 6646; single episode Diagnostic and Statistical Manual (DSM)-IV depression, n = 115; recurrent depression, n = 246). Disease burden from an individual perspective was assessed as 'disability weight * time spent in depression' for each person in the dataset. From a population perspective it was assessed as 'disability weight * time spent in depression *number of people affected'. The presence of mental disorders was assessed with the Composite International Diagnostic Interview (CIDI) 3.0. Results: Single depressive episodes emerged as a key driver of disease burden from an individual perspective. From a population perspective, recurrent depressions emerged as a key driver. These findings remained unaltered after adjusting for comorbidity. Conclusions: The burden of disease differs between the subtype of depression and depends much on the choice of perspective. The distinction between an individual and a population perspective may help to avoid misunderstandings between policy makers and clinicians. © 2016 Biesheuvel-Leliefeld et al

Health status of the advanced elderly in six european countries: results from a representative survey using EQ-5D and SF-12

<p>Abstract</p> <p>Background</p> <p>Due to demographic change, the advanced elderly represent the fastest growing population group in Europe. Health problems tend to be frequent and increasing with age within this cohort.</p> <p>Aims of the study</p> <p>To describe and compare health status of the elderly population in six European countries and to analyze the impact of socio-demographic variables on health.</p> <p>Methods</p> <p>In the European Study of the Epidemiology of Mental Disorders (ESEMeD), representative non-institutionalized population samples completed the EQ-5D and Short Form-12 (SF-12) questionnaires as part of personal computer-based home interviews in 2001-2003. This study is based on a subsample of 1659 respondents aged ≥ 75 years from Belgium (n = 194), France (n = 168), Germany (n = 244), Italy (n = 317), the Netherlands (n = 164) and Spain (n = 572). Descriptive statistics, bivariate- (chi-square tests) and multivariate methods (linear regressions) were used to examine differences in population health.</p> <p>Results</p> <p>68.8% of respondents reported problems in one or more EQ-5D dimensions, most frequently pain/discomfort (55.2%), followed by mobility (50.0%), usual activities (36.6%), self-care (18.1%) and anxiety/depression (11.6%). The proportion of respondents reporting any problems increased significantly with age in bivariate analyses (age 75-79: 65.4%; age 80-84: 69.2%; age ≥ 85: 81.1%) and differed between countries, ranging from 58.7% in the Netherlands to 72.3% in Italy. The mean EQ VAS score was 61.9, decreasing with age (age 75-79: 64.1; age 80-84: 59.8; age ≥ 85: 56.7) and ranging from 60.0 in Italy to 72.9 in the Netherlands. SF-12 derived Physical Component Summary (PCS) and Mental Component Summary (MCS) scores varied little by age and country. Age and low educational level were associated with lower EQ VAS and PCS scores. After controlling for socio-demographic variables and reported EQ-5D health states, mean EQ VAS scores were significantly higher in the Netherlands and Belgium, and lower in Germany than the grand mean.</p> <p>Conclusions</p> <p>More than two thirds of the advanced elderly report impairment of health status. Impairment increases rapidly with age but differs considerably between countries. In all countries, health status is significantly associated with socio-demographic variables.</p

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Reproducibility and Variability of Protein Analytes Measured Using a Multiplexed Modified Aptamer Assay.

BACKGROUND:There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. METHODS:We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4-9 weeks) and long-term (approximately 20 years) variability using paired t-tests with log-transformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). RESULTS:The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs &lt; 5.0%, Spearman correlations &gt; 0.89, and ICCs &gt; 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P &lt; 1.4 × 10-5, 681 increased, 185 decreased). PC1 had high correlations with age (-0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31). CONCLUSIONS:Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Estimating the Holdout Problem in Land Assembly

The Supreme Court's recent decision in Kelo v. New London allows the use of eminent domain to facilitate private economic development. While the court's condition for allowing takings was highly expansive, there may be a market failure that warrants state intervention when parcels of land need to be combined for redevelopment. The collective action or strategic holdout problem associated with land assembly may limit redevelopment of older communities when one or more existing owners seek to capture a disproportionate share of the potential surplus. The problem may be compounded by landowners' uncertainty as to the true value of the expected surplus to be divided (Eckart, 1985; Strange, 1995). At the same time, developers may attempt to disguise the assemblage through the use of straw purchasers. This paper employs administrative Geographic Information System and assessor data from Seattle, Washington, to identify lots that were ultimately assembled. The paper then matches them to their pre-assembly sales. Controlling for lot and existing structure characteristics and census tract-year fixed effects, I find that land bought in the process of a successful assembly commands an 18 percent premium. Consistent with theory, this premium falls with a parcel's relative size in the assemblage. I also find some evidence that parcels toward the center of the development may command a larger premium than those at the edge, suggesting that developers retain or are perceived to retain some design flexibility

Circulating levels of liver enzymes and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities cohort

Elevated levels of circulating liver enzymes have been associated with increased risk of cardiovascular disease. Their possible association with atrial fibrillation (AF) has received little attention