2,191 research outputs found
Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review
Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual
participant data. For continuous outcomes, especially those with naturally skewed distributions, summary
information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal,
we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis.
Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with
missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane
Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited
reference searching and emailed topic experts to identify recent methodological developments. Details recorded
included the description of the method, the information required to implement the method, any underlying
assumptions and whether the method could be readily applied in standard statistical software. We provided a
summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios.
Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in
addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis
level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical
approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following
screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and
three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when
replacing a missing SD the approximation using the range minimised loss of precision and generally performed better
than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile
performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials
gave superior results.
Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median)
reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or
variability summary statistics within meta-analyses
A ferroelectric memristor
Memristors are continuously tunable resistors that emulate synapses.
Conceptualized in the 1970s, they traditionally operate by voltage-induced
displacements of matter, but the mechanism remains controversial. Purely
electronic memristors have recently emerged based on well-established physical
phenomena with albeit modest resistance changes. Here we demonstrate that
voltage-controlled domain configurations in ferroelectric tunnel barriers yield
memristive behaviour with resistance variations exceeding two orders of
magnitude and a 10 ns operation speed. Using models of ferroelectric-domain
nucleation and growth we explain the quasi-continuous resistance variations and
derive a simple analytical expression for the memristive effect. Our results
suggest new opportunities for ferroelectrics as the hardware basis of future
neuromorphic computational architectures
In-medium hadronic spectral functions through the soft-wall holographic model of QCD
We study the scalar glueball and vector meson spectral functions in a hot and
dense medium by means of the soft-wall holographic model of QCD. Finite
temperature and density effects are implemented through the AdS/RN metric. We
analyse the behaviour of the hadron masses and widths in the plane,
and compare our results with the experimental ones and with other theoretical
determinations.Comment: 16 pages, 6 figures. matching the published versio
Modeling of Compressive Strength Development of High-Early-Strength-Concrete at Different Curing Temperatures
Uniform electron gases
We show that the traditional concept of the uniform electron gas (UEG) --- a
homogeneous system of finite density, consisting of an infinite number of
electrons in an infinite volume --- is inadequate to model the UEGs that arise
in finite systems. We argue that, in general, a UEG is characterized by at
least two parameters, \textit{viz.} the usual one-electron density parameter
and a new two-electron parameter . We outline a systematic
strategy to determine a new density functional across the
spectrum of possible and values.Comment: 8 pages, 2 figures, 5 table
Suv4-20h Histone Methyltransferases Promote Neuroectodermal Differentiation by Silencing the Pluripotency-Associated Oct-25 Gene
Post-translational modifications (PTMs) of histones exert fundamental roles in regulating gene expression. During development, groups of PTMs are constrained by unknown mechanisms into combinatorial patterns, which facilitate transitions from uncommitted embryonic cells into differentiated somatic cell lineages. Repressive histone modifications such as H3K9me3 or H3K27me3 have been investigated in detail, but the role of H4K20me3 in development is currently unknown. Here we show that Xenopus laevis Suv4-20h1 and h2 histone methyltransferases (HMTases) are essential for induction and differentiation of the neuroectoderm. Morpholino-mediated knockdown of the two HMTases leads to a selective and specific downregulation of genes controlling neural induction, thereby effectively blocking differentiation of the neuroectoderm. Global transcriptome analysis supports the notion that these effects arise from the transcriptional deregulation of specific genes rather than widespread, pleiotropic effects. Interestingly, morphant embryos fail to repress the Oct4-related Xenopus gene Oct-25. We validate Oct-25 as a direct target of xSu4-20h enzyme mediated gene repression, showing by chromatin immunoprecipitaton that it is decorated with the H4K20me3 mark downstream of the promoter in normal, but not in double-morphant, embryos. Since knockdown of Oct-25 protein significantly rescues the neural differentiation defect in xSuv4-20h double-morphant embryos, we conclude that the epistatic relationship between Suv4-20h enzymes and Oct-25 controls the transit from pluripotent to differentiation-competent neural cells. Consistent with these results in Xenopus, murine Suv4-20h1/h2 double-knockout embryonic stem (DKO ES) cells exhibit increased Oct4 protein levels before and during EB formation, and reveal a compromised and biased capacity for in vitro differentiation, when compared to normal ES cells. Together, these results suggest a regulatory mechanism, conserved between amphibians and mammals, in which H4K20me3-dependent restriction of specific POU-V genes directs cell fate decisions, when embryonic cells exit the pluripotent state
STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage
STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al
Immune response in adverse reactions to metal debris following metal-on-metal total hip arthroplasty
Use of Oral Cholera Vaccines in an Outbreak in Vietnam: A Case Control Study
Simple measures such as adequate sanitation and clean water stops the spread of cholera; however, in areas where these are not available, cholera spreads quickly and may lead to death in a few hours if treatment is not initiated immediately. The use of life-saving rehydration therapy is the mainstay in cholera control, however, the rapidity of the disease and the limited access to appropriate healthcare units in far-flung areas together result in an unacceptable number of deaths. The WHO has recommended the use of oral cholera vaccines as a preventive measure against cholera outbreaks since 2001, but this was recently updated so that vaccine use may also be considered once a cholera outbreak has begun. The findings from this study suggest that reactive use of killed oral cholera vaccines provides protection against the disease and may be a potential tool in times of outbreaks. Further studies must be conducted to confirm these findings
Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs
Non-conding RNAs play a key role in the post-transcriptional regulation of
mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact
with their target RNAs through protein-mediated, sequence-specific binding,
giving rise to extended and highly heterogeneous miRNA-RNA interaction
networks. Within such networks, competition to bind miRNAs can generate an
effective positive coupling between their targets. Competing endogenous RNAs
(ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk.
Albeit potentially weak, ceRNA interactions can occur both dynamically,
affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA
networks as a whole can be implicated in the composition of the cell's
proteome. Many features of ceRNA interactions, including the conditions under
which they become significant, can be unraveled by mathematical and in silico
models. We review the understanding of the ceRNA effect obtained within such
frameworks, focusing on the methods employed to quantify it, its role in the
processing of gene expression noise, and how network topology can determine its
reach.Comment: review article, 29 pages, 7 figure
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