The Impact of Study Size on Meta-analyses: Examination of Underpowered Studies in Cochrane Reviews

Background: Most meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published metaanalyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results. Methods and Findings: For 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as $50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the metaanalyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P,0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P,0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range 21% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease. Conclusions: When at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews

Generating and Adding Flows on Locally Complete Metric Spaces

As a generalization of a vector field on a manifold, the notion of an arc field on a locally complete metric space was introduced in \cite{BC}. In that paper, the authors proved an analogue of the Cauchy-Lipschitz Theorem i.e they showed the existence and uniqueness of solution curves for a time independent arc field. In this paper, we extend the result to the time dependent case, namely we show the existence and uniqueness of solution curves for a time dependent arc field. We also introduce the notion of the sum of two time dependent arc fields and show existence and uniqueness of solution curves for this sum.Comment: 29 pages,6 figure

Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool.

To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT)

Finality revived: powers and intentionality

Proponents of physical intentionality argue that the classic hallmarks of intentionality highlighted by Brentano are also found in purely physical powers. Critics worry that this idea is metaphysically obscure at best, and at worst leads to panpsychism or animism. I examine the debate in detail, finding both confusion and illumination in the physical intentionalist thesis. Analysing a number of the canonical features of intentionality, I show that they all point to one overarching phenomenon of which both the mental and the physical are kinds, namely finality. This is the finality of ‘final causes’, the long-discarded idea of universal action for an end to which recent proponents of physical intentionality are in fact pointing whether or not they realise it. I explain finality in terms of the concept of specific indifference, arguing that in the case of the mental, specific indifference is realised by the process of abstraction, which has no correlate in the case of physical powers. This analysis, I conclude, reveals both the strength and weakness of rational creatures such as us, as well as demystifying (albeit only partly) the way in which powers work

Dynamic and approximate pattern matching in 2D

International audienc

Taxation and Development: a Review of Donor Support to Strengthen Tax Systems in Developing Countries

Recent years have seen a growing interest among donors on taxation in developing countries. This reflects a concern for domestic revenue mobilization to finance public goods and services, as well as recognition of the centrality of taxation for growth and redistribution. The global financial crisis has also led many donor countries to pay more attention to the extent and effectiveness of the aid they provide, and to ensuring that they support rather than discourage the developing countries’ own revenue-raising efforts. This paper reviews the state of knowledge on aid and tax reform in developing countries, with a particular focus on sub-Saharan Africa. Four main issues are addressed: (1) impacts of donor assistance to strengthen tax systems, including what has worked, or not, and why; (2) challenges in ‘scaling up’ donor efforts; (3) how to best provide assistance to reform tax systems; and (4) knowledge gaps to be filled in order to design better donor interventions. The paper argues that donors should complement the traditional ‘technical’ approach to tax reform with measures that encourage constructive engagement between governments and citizens over tax issues.Department for International DevelopmentBill and Melinda Gates Foundatio

Prevalence of hepatitis B virus marker positivity and evolution of hepatitis B virus profile, during chemotherapy, in patients with solid tumours

To prospectively evaluate the prevalence of hepatitis B virus (HBV) positivity and study the evolution of HBV profile during cancer chemotherapy, serum HBV markers and liver biochemistry were determined in 1008 of 1402 (72%) cancer patients admitted in our Unit and in all 920 (91%) who received chemotherapy. We found that 54 (5.3%) were HBsAg carriers while 443 (44%) had at least one HBV marker positive. Of the latter, 405 (91%) were HBcAb+ve, 321 (72%) HBsAb+ve and 212 (48%) HBeAb+ve. No patient was HBeAg+ve. Among 920 chemotherapy receivers, 374 (41%) were HBcAb+ve, 280 (30%) HBsAb+ve and 178 (19%) HBeAb+ve. Fifty (5.4%) were HBsAg carriers (versus 0.6% in Greek blood donors). All 50 were systematically screened for HBsAg and HBsAb status throughout chemotherapy, during follow-up or until their death, and liver biochemistry was performed before each chemotherapy course. Stable antigenaemia was observed in 43/50 (86%) while 7/50 (14%) developed clinical and/or biochemical hepatitis. Six of these seven developed serum anti-HBs antibodies with an associated decrease of serum HBsAg titres. We conclude that reactivation of HBV infection during chemotherapy is not rare (14%), while disappearance of HBs antigenaemia is neither a frequent nor usually a permanent phenomenon. © 1999 Cancer Research Campaig

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

Digit-only sauropod pes trackways from China - evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all