Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

MANOVA modelling of a chiropractic longitudinal study using multiple imputation

The purpose of this report is to present the detailed statistical analysis of a randomised, placebo-controlled trial comparing two different treatment modalities to an intervention of no known benefit for people with acute or subacute thoracic spine pain. The therapy arms consist of Spinal Manipulative Therapy (SMT) and Graston Technique (GT) and the placebo is a non-functional ultrasound. A placebo group was utilised because at present there are no proven treatments for non-specific thoracic pain. This trial is registered with the Australia and New Zealand Clinical Trials Registry. Ethics approval has been granted by Murdoch University Human Research and Ethics Committee, number 2007/274. The aim of this three arm trial was to test the efficacy of SMT and GT as independent modalities compared to detuned ultrasound for the outcomes of pain and disability. The latter were measured using the Visual Analogue Scale (VAS) and a modified Oswestry Back Pain Disability Index. The study was conducted at the Murdoch University Chiropractic student clinic in Perth, Australia, and the protocol published in Crothers et al (2008). In this report, Section 2 provides an initial exploratory analysis of the data, Section 3 outlines the statistical models used in the final analysis, Section 4 defines these models in mathematical terms, Section 5 discusses the management of missing values via multiple imputation and Section 6 presents the results of the statistical modelling and hypothesis tests. The clinical study will be published in full elsewhere

The effects of different strains of zooxanthellae on the secondary-metabolite chemistry and development of the soft-coral host Lobophytum compactum

We have assessed the secondary-metabolite chemistry of freshly metamorphosed coral polyps, with and without zooxanthellae, using extremely sensitive electro-spray and Fourier-transform mass spectrometry. Coral larvae of the soft coral Lobophytum compactum of the same genetic background were reared, then inoculated with zooxanthellar strains of different taxonomic and geographic origin, and their terpenoid chemistry analysed. The identification of isolobophytolide in individuals of all treatment groups, including aposymbiotic control polyps, demonstrates that control of terpene production lies with the host coral and not their symbiotic algae

Transformation of soft coral (Coelenterata: Octocorallia) terpenes by Ovula ovum (Mollusca: Prosobranchia)

The faecal pellets from specimens of the prosobranch mollusc Ovula ovum found feeding on the soft coral Sarcophyton sp. at Eclipse Island, Palm Island Group (18°46'S; 146°33'E) in November 1980 were analysed. The only terpene present in the faeces, 7,8-deoxysarcophytoxide, differed from the major constituent of the soft coral, sarcophytoxide, suggesting that the latter had been transformed into the former within the cowrie. This transformation is not trivial, and could not be produced simply by acid catalysis. Subsequent analysis of tissues dissected from different regions of O. ovum indicates that the transformation is probably effected by enzymes in the digestive diverticula stomach region of the prosobranch. The transformed compound is significantly less toxic to the mosquito fish Gambusia affinis Baird and Girard than the ingested compound

Outcomes of Usual Chiropractic. The OUCH randomized controlled trial of adverse events

Study Design: Blinded parallel group randomised controlled Objective: Establish the frequency and severity of adverse effects from short term usual chiropractic treatment of the spine when compared to a sham treatment group. Summary of Background Data: Previous studies have demonstrated that adverse events occur during chiropractic treatment. However, as a result of design limitations in previous studies, particularly the lack of sham-controlled randomised trials, understanding of these adverse events and their relation with chiropractic treatment, is suboptimal. Methods: We conducted a trial to examine the occurrence of adverse events resulting from chiropractic treatment. It was conducted across 12 chiropractic clinics in Perth, Western Australia. The participants comprised 183 adults, aged 20-85, with spinal pain. Ninety two participants received individualized care consistent with the chiropractors' usual treatment approach; 91 participants received a sham intervention. Each participant received two treatments. Results: Completed adverse questionnaires were returned by 94.5% of the participants after appointment one and 91.3% after appointment two. Thirty three per cent of the sham group and 42% of the usual care group reported at least one adverse event. Common adverse events were increased pain (sham 29%; usual care 36%), muscle stiffness (sham 29%; usual care 37%), headache (sham 17%; usual care 9%). The relative risk was not significant for either adverse event occurrence (RR = 1.24 95% CI 0.85 to 1.81); occurrence of severe adverse events (RR = 1.9; 95% CI 0.98 to 3.99); adverse event onset (RR = 0.16; 95% CI 0.02 to 1.34); or adverse event duration (RR = 1.13; 95% CI 0.59 to 2.18). No serious adverse events were reported. Conclusions: A substantial proportion of adverse events following chiropractic treatment may result from natural history variation and non-specific effects