A system for improving vitamin D nutrition in residential care

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Objective: To assess the feasibility of administering an inexpensive preparation of vitamin D3 100 000 IU orally 3 monthly to aged-care residents. Design: Prospective, controlled open-label implementation trial. Setting: Residential aged care, November 2003 to May 2004 (primary study). Participants: 137 ambulant residents: 107 treated (mean age, 85 years; 79 were women), 30 untreated controls (mean age, 87 years; 22 were women). Interventions: Lactose microencapsulated vitamin D3 100 000 IU orally at baseline, then 3 monthly (three or more doses); untreated subjects were observed contemporaneously. Main outcome measures: Serum levels of 25-hydroxyvitamin D [25(OH)D] at 6 months compared with baseline; acceptability of the program to residents and staff. Results: At baseline, 95% of residents assessed (n = 137) had serum 25(OH)D levels below the desirable range of 60–160 nmol/L. At 6 months, all treated residents (n = 98) achieved desired levels, with the mean (± SD) 25(OH)D level increasing from 36.4 ± 12.6 nmol/L (range, 12–75 nmol/L) at baseline to 124.0 ± 27.9 nmol/L (range, 68–244 nmol/L). In no resident did 25(OH)D approach toxic levels. The mean serum 25(OH)D level remained low in the control group (n = 27): 42.8 ± 18.3 nmol/L (range, 18–98 nmol/L). The difference between the mean 25(OH)D levels of treatment and control groups at 6 months was 81.2 nmol/L (95% CI, 69.7–92.0 nmol/L). The cost of the supplement was $4 per resident per annum. Substudies showed mean trough serum 25(OH)D levels in the desired range at 3 months (n = 31), but below the desired range at 6 months (n = 50). Subjects given 3-monthly doses for up to 2 years maintained serum 25(OH)D levels within the desired range, with no trend toward undesirable accumulation (n = 11). Conclusions: Vitamin D3 100 000 IU given orally 3 monthly is a practical, safe, effective and inexpensive way to meet the vitamin D3 requirements of aged-care residents.Alison E R Wigg, Caroline Prest, Peter Slobodian, Allan G Need and Leslie G Clelan

A genetic contribution from the Far East into Ashkenazi Jews via the ancient Silk Road

Contemporary Jews retain a genetic imprint from their Near Eastern ancestry, but obtained substantial genetic components from their neighboring populations during their history. Whether they received any genetic contribution from the Far East remains unknown, but frequent communication with the Chinese has been observed since the Silk Road period. To address this issue, mitochondrial DNA (mtDNA) variation from 55,595 Eurasians are analyzed. The existence of some eastern Eurasian haplotypes in eastern Ashkenazi Jews supports an East Asian genetic contribution, likely from Chinese. Further evidence indicates that this connection can be attributed to a gene flow event that occurred less than 1.4 kilo-years ago (kya), which falls within the time frame of the Silk Road scenario and fits well with historical records and archaeological discoveries. This observed genetic contribution from Chinese to Ashkenazi Jews demonstrates that the historical exchange between Ashkenazim and the Far East was not confined to the cultural sphere but also extended to an exchange of genes

Experimental Investigation of the Ne 19 (p,γ)20Na Reaction Rate and Implications for Breakout from the Hot CNO Cycle

The Ne19(p,γ)Na20 reaction is the second step of a reaction chain which breaks out from the hot CNO cycle, following the O15(α,γ)Ne19 reaction at the onset of x-ray burst events. We investigate the spectrum of the lowest proton-unbound states in Na20 in an effort to resolve contradictions in spin-parity assignments and extract reliable information about the thermal reaction rate. The proton-transfer reaction Ne19(d,n)Na20 is measured with a beam of the radioactive isotope Ne19 at an energy around the Coulomb barrier and in inverse kinematics. We observe three proton resonances with the Ne19 ground state, at 0.44, 0.66, and 0.82 MeV c.m. energies, which are assigned 3+, 1+, and (0+), respectively. In addition, we identify two resonances with the first excited state in Ne19, one at 0.20 MeV and one, tentatively, at 0.54 MeV. These observations allow us for the first time to experimentally quantify the astrophysical reaction rate on an excited nuclear state. Our experiment shows an efficient path for thermal proton capture in Ne19(p,γ)Na20, which proceeds through ground state and excited-state capture in almost equal parts and eliminates the possibility for this reaction to create a bottleneck in the breakout from the hot CNO cycle

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1–2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10−10, (rs8034191) and 5.74×10−10 (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer

Engaging children in meaningful charity: opening-up the spaces within which children learn to give

This paper presents qualitative evidence from an in-depth, participative action research project with 150 children aged 4-8 years old, exploring their experiences, perceptions and preferences regarding charitable giving. Most children positively engage in charitable giving through home, school and their community, however less than 20% are aware of the cause area they are being asked to support, and most have little decision-making in their giving. Children’s willingness to engage increases when they critically examine the cause area and are facilitated to lead on giving decisions, often resulting in increased and sustained efforts to support cause areas that matter to them

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

A Genome-Wide Investigation of SNPs and CNVs in Schizophrenia

We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 patients and 12,995 controls, all of European origin. We found no genome-wide significant associations, nor could we provide support for any previously reported candidate gene or genome-wide associations. We went on to examine CNVs using a subset of 1,013 cases and 1,084 controls of European ancestry, and a further set of 60 cases and 64 controls of African ancestry. We found that eight cases and zero controls carried deletions greater than 2 Mb, of which two, at 8p22 and 16p13.11-p12.4, are newly reported here. A further evaluation of 1,378 controls identified no deletions greater than 2 Mb, suggesting a high prior probability of disease involvement when such deletions are observed in cases. We also provide further evidence for some smaller, previously reported, schizophrenia-associated CNVs, such as those in NRXN1 and APBA2. We could not provide strong support for the hypothesis that schizophrenia patients have a significantly greater “load” of large (>100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia. Finally, we did not provide support for the suggestion that schizophrenia-associated CNVs may preferentially disrupt genes in neurodevelopmental pathways. Collectively, these analyses provide the first integrated study of SNPs and CNVs in schizophrenia and support the emerging view that rare deleterious variants may be more important in schizophrenia predisposition than common polymorphisms. While our analyses do not suggest that implicated CNVs impinge on particular key pathways, we do support the contribution of specific genomic regions in schizophrenia, presumably due to recurrent mutation. On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens

Author Correction: Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans

An amendment to this paper has been published and can be accessed via a link at the top of the paper