Immersive Installation: “A Virtual St Kilda”

This paper discusses a Virtual Histories project, which developed a digital reconstruction of St Kilda. St Kilda is the most remote and western part of the United Kingdom. It was evacuated in the 1930s and lay empty for several decades. It is a world heritage site for both built and natural environment . The Virtual St Kilda acted as a focus for the collection and presentation of tangible and intangible cultural heritage. It was on show as an exhibition in the Taigh Chearsabah museum (Figure 5) located in North Uist Scotland. The exhibition is built around the OpenSimulator Open VirtualWorld server using commodity hardware. The simulation covers some 4 square km of virtual space, and models both tangible and intangible culture. It is integrated into an exhibition and articulates an interpretation of the St Kilda legacy through the prism of contemporary North Uist life.Postprin

Is Socioeconomic Status of the Rearing Environment Causally Related to Obesity in the Offspring?

We attempt to elucidate whether there might be a causal connection between the socioeconomic status (SES) of the rearing environment and obesity in the offspring using data from two large-scale adoption studies: (1) The Copenhagen Adoption Study of Obesity (CASO), and (2) The Survey of Holt Adoptees and Their Families (HOLT). In CASO, the SES of both biological and adoptive parents was known, but all children were adopted. In HOLT, only the SES of the rearing parents was known, but the children could be either biological or adopted. After controlling for relevant covariates (e.g., adoptee age at measurement, adoptee age at transfer, adoptee sex) the raw (unstandardized) regression coefficients for adoptive and biological paternal SES on adoptee body mass index (BMI: kg/m2) in CASO were -.22 and -.23, respectively, both statistically significant (p = 0.01). Controlling for parental BMI (both adoptive and biological) reduced the coefficient for biological paternal SES by 44% (p = .034) and the coefficient for adoptive paternal SES by 1%. For HOLT, the regression coefficients for rearing parent SES were -.42 and -.25 for biological and adoptive children, respectively. Controlling for the average BMI of the rearing father and mother (i.e., mid-parental BMI) reduced the SES coefficient by 47% in their biological offspring (p≤.0001), and by 12% in their adoptive offspring (p = .09). Thus, despite the differing structures of the two adoption studies, both suggest that shared genetic diathesis and direct environmental transmission contribute about equally to the association between rearing SES and offspring BMI

Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts

In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Reported suicide attempts and completed suicides per drug.832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern

Genetic variation in TLR genes in Ugandan and South African populations and comparison with HapMap data

Genetic epidemiological studies of complex diseases often rely on data from the International HapMap Consortium for identification of single nucleotide polymorphisms (SNPs), particularly those that tag haplotypes. However, little is known about the relevance of the African populations used to collect HapMap data for study populations conducted elsewhere in Africa. Toll-like receptor (TLR) genes play a key role in susceptibility to various infectious diseases, including tuberculosis. We conducted full-exon sequencing in samples obtained from Uganda (n = 48) and South Africa (n = 48), in four genes in the TLR pathway: TLR2, TLR4, TLR6, and TIRAP. We identified one novel TIRAP SNP (with minor allele frequency [MAF] 3.2%) and a novel TLR6 SNP (MAF 8%) in the Ugandan population, and a TLR6 SNP that is unique to the South African population (MAF 14%). These SNPs were also not present in the 1000 Genomes data. Genotype and haplotype frequencies and linkage disequilibrium patterns in Uganda and South Africa were similar to African populations in the HapMap datasets. Multidimensional scaling analysis of polymorphisms in all four genes suggested broad overlap of all of the examined African populations. Based on these data, we propose that there is enough similarity among African populations represented in the HapMap database to justify initial SNP selection for genetic epidemiological studies in Uganda and South Africa. We also discovered three novel polymorphisms that appear to be population-specific and would only be detected by sequencing efforts

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Interhospital Transfers Among Medicare Beneficiaries Admitted for Acute Myocardial Infarction at Nonrevascularization Hospitals

Background—Patients with acute myocardial infarction (AMI) who are admitted to hospitals without coronary revascularization are frequently transferred to hospitals with this capability, yet we know little about the basis for how such revascularization hospitals are selected. Methods and Results—We examined interhospital transfer patterns in 71 336 AMI patients admitted to hospitals without revascularization capabilities in the 2006 Medicare claims using network analysis and regression models. A total of 31 607 (44.3%) AMI patients were transferred from 1684 nonrevascularization hospitals to 1104 revascularization hospitals. Median time to transfer was 2 days. Median transfer distance was 26.7 miles, with 96.1% within 100 miles. In 45.8% of cases, patients bypassed a closer hospital to go to a farther hospital that had a better 30-day risk standardized mortality rates. However, in 36.8% of cases, another revascularization hospital with lower 30-day risk-standardized mortality was actually closer to the original admitting nonrevascularization hospital than the observed transfer destination. Adjusted regression models demonstrated that shorter transfer distances were more common than transfers to the hospitals with lowest 30-day mortality rates. Simulations suggest that an optimized system that prioritized the transfer of AMI patients to a nearby hospital with the lowest 30-day mortality rate might produce clinically meaningful reductions in mortality. Conclusions—More than 40% of AMI patients admitted to nonrevascularization hospitals are transferred to revascular- ization hospitals. Many patients are not directed to nearby hospitals with the lowest 30-day risk-standardized mortality, and this may represent an opportunity for improvement. (Circ Cardiovasc Qual Outcomes. 2010;3:468-475.)This work was supported by 1K08HL091249-01 from the NIH/ NHLBI and used the Measurement Core of the Michigan Diabetes Research and Training Center (NIH/NIDDK, P60DK-20572). This project was also funded in part under a grant from the Pennsylvania Department of Health, which specifically disclaims responsibility for any analyses, interpretations, or conclusions. The funders were not involved in study design, interpretation, or the decision to publish.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78005/1/10.I.Circ.Outcomes.pd

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV Core DII protein

Host cell lipid droplets (LD) are essential in the hepatitis C virus (HCV) life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein’s lipid binding domain II (DII-core) induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV