The completeness of intervention descriptions in published National Institute of Health Research HTA-funded trials: a cross-sectional study

ObjectivesThe objective of this study was to assess whether National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded randomised controlled trials (RCTs) published in the HTA journal were described in sufficient detail to replicate in practice.SettingRCTs published in the HTA journal.Participants98 RCTs published in the HTA journal up to March 2011. Completeness of the intervention description was assessed independently by two researchers using a checklist, which included assessments of participants, intensity, schedule, materials and settings. Disagreements in scoring were discussed in the team; differences were then explored and resolved.Primary and secondary outcome measuresProportion of trials rated as having a complete description of the intervention (primary outcome measure). The proportion of drug trials versus psychological and non-drug trials rated as having a complete description of the intervention (secondary outcome measures).ResultsComponents of the intervention description were missing in 68/98 (69.4%) reports. Baseline characteristics and descriptions of settings had the highest levels of completeness with over 90% of reports complete. Reports were less complete on patient information with 58.2% of the journals having an adequate description. When looking at individual intervention types, drug intervention descriptions were more complete than non-drug interventions with 33.3% and 30.6% levels of completeness, respectively, although this was not significant statistically. Only 27.3% of RCTs with psychological interventions were deemed to be complete, although again these differences were not significant statistically.ConclusionsEnsuring the replicability of study interventions is an essential part of adding value in research. All those publishing clinical trial data need to ensure transparency and completeness in the reporting of interventions to ensure that study interventions can be replicated

Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice.

We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5-14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level

Manganese Abundances in the Globular Cluster Omega Centauri

We present manganese abundances in 10 red-giant members of the globular cluster Omega Centauri; 8 stars are from the most metal-poor population (RGB MP and RGB MInt1) while two targets are members of the more metal rich groups (RGB MInt2 and MInt3). This is the first time Mn abundances have been studied in this peculiar stellar system. The LTE values of [Mn/Fe] in Omega Cen overlap those of Milky Way stars in the metal poor Omega Cen populations ([Fe/H] ~ -1.5 to -1.8), however unlike what is observed in Milky Way halo and disk stars, [Mn/Fe] declines in the two more metal-rich RGB MInt2 and MInt3 targets. Non-LTE calculations were carried out in order to derive corrections to the LTE Mn abundances. The non-LTE results for Omega Cen in comparison with the non-LTE [Mn/Fe] versus [Fe/H] trend obtained for the Milky Way confirm and strengthen the conclusion that the manganese behavior in Omega Cen is distinct. These results suggest that low-metallicity supernovae (with metallicities < -2) of either Type II or Type Ia dominated the enrichment of the more metal-rich stars in Omega Cen. The dominance of low-metallicity stars in the chemical evolution of Omega Cen has been noted previously in the s-process elements where enrichment from metal-poor AGB stars is indicated. In addition, copper, which also has metallicity dependent yields, exhibits lower values of [Cu/Fe] in the RGB MInt2 and MInt3 Omega Cen populations.Comment: Accepted for publication in the Ap