Meta-analysis of data from animal studies:A practical guide

AbstractMeta-analyses of data from human studies are invaluable resources in the life sciences and the methods to conduct these are well documented. Similarly there are a number of benefits in conducting meta-analyses on data from animal studies; they can be used to inform clinical trial design, or to try and explain discrepancies between preclinical and clinical trial results. However there are inherit differences between animal and human studies and so applying the same techniques for the meta-analysis of preclinical data is not straightforward. For example preclinical studies are frequently small and there is often substantial heterogeneity between studies. This may have an impact on both the method of calculating an effect size and the method of pooling data. Here we describe a practical guide for the meta-analysis of data from animal studies including methods used to explore sources of heterogeneity

A High-Resolution Neutron-Diffraction Study Of The Structure Of Amorphous Hydrogenated Carbon, a-CH

Current structural models for amorphous hydrogenated carbon (a-C:H) are called into question on the basis of neutron-diffraction experimental work carried out al the ISIS pulsed neutron source (UK) on a-C:H. The nature of the neutron source allows the collection of data over an exceptionally wide dynamic range that ensures a real-space resolution sufficient to allow direct observation, for the first time, of contributions from the principal C-C bond types. The data also reveal details of the C-H correlations, and the presence of trapped molecular hydrogen

The Structure Of Amorphous Hydrogenated Carbon By Neutron-Diffraction

Neutron diffraction data from a large, off-substrate sample of amorphous hydrogenated carbon (a-C:H) is presented and discussed. The material is prepared using a fast-atom deposition system using acetylene as the precursor gas. The experiments were performed on the ISIS pulsed neutron source (Rutherford Appleton Laboratory, UK) which is capable of yielding data over an exceptionally wide dynamic range; this ensures a real-space resolution sufficient to resolve directly, for the first time, contributions from the principle C-C bond types. Precise details on the C-H correlations are also revealed by the data, including the presence of molecular hydrogen trapped within distorted spheroidal cages. Quantitative complementary data on the vibrational states of the bonded hydrogen, derived from inelastic neutron scattering (INS) using a simple force-field model, is also presented. In particular, the INS data is used to provide a reliable estimate of the CH:CH2 ratio

The Effect Of Hydrogen Dilution On The Interatomic Bonding Of Amorphous Hydrogenated Silicon - Carbon

The effect of hydrogen dilution of the precursor gas mixture on the local bonding environment in glow-discharge deposited a-Si:C:H has been studied by neutron diffraction and inelastic neutron scattering. The neutron diffraction results show a large increase in the silicon-carbon bonding upon hydrogen dilution, at the expense of silicon-silicon bonding. The inelastic neutron scattering provides complementary information on the hydrogen bonding environment. The hydrogen is predominantly bonded in SiH and SiH2 groups, with a large increase in the SiH2 group concentration occurring upon hydrogen dilution. The data presented here show that SiH3 and CH(n) groups are present as a very small fraction of H bonding sites, if at all

A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation

Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX2 to be a major therapeutic target in stroke. Systematic review and MA of all available NOX2(-/y) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX2 as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias