2,442 research outputs found
Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study
Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within
RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of
criteria that will facilitate the grading of evidence for moderators, in systematic reviews.
Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique,
and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising
authors who have published methodological papers in this area, and researchers who have been active in the
study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles
appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus
and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’
Handbook, and the process was repeated.
Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups
analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori
statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for
inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study:
Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of
adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions
must be presented.
Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess
moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts
resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support
hypotheses about moderators and exploratory findings to inform future research. These recommendations are
discussed in reference to previous recommendations for evaluating and reporting moderator studies
Recommended from our members
The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola
Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state
Hail Suppression: Impacts and Issues: Final Report Technology Assessment of the Suppression of Hail
published or submitted for publicationis peer reviewedOpe
Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3
The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use
BMQ
BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals
On the rate of quantum ergodicity in Euclidean billiards
For a large class of quantized ergodic flows the quantum ergodicity theorem
due to Shnirelman, Zelditch, Colin de Verdi\`ere and others states that almost
all eigenfunctions become equidistributed in the semiclassical limit. In this
work we first give a short introduction to the formulation of the quantum
ergodicity theorem for general observables in terms of pseudodifferential
operators and show that it is equivalent to the semiclassical eigenfunction
hypothesis for the Wigner function in the case of ergodic systems. Of great
importance is the rate by which the quantum mechanical expectation values of an
observable tend to their mean value. This is studied numerically for three
Euclidean billiards (stadium, cosine and cardioid billiard) using up to 6000
eigenfunctions. We find that in configuration space the rate of quantum
ergodicity is strongly influenced by localized eigenfunctions like bouncing
ball modes or scarred eigenfunctions. We give a detailed discussion and
explanation of these effects using a simple but powerful model. For the rate of
quantum ergodicity in momentum space we observe a slower decay. We also study
the suitably normalized fluctuations of the expectation values around their
mean, and find good agreement with a Gaussian distribution.Comment: 40 pages, LaTeX2e. This version does not contain any figures. A
version with all figures can be obtained from
http://www.physik.uni-ulm.de/theo/qc/ (File:
http://www.physik.uni-ulm.de/theo/qc/ulm-tp/tp97-8.ps.gz) In case of any
problems contact Arnd B\"acker (e-mail: [email protected]) or Roman
Schubert (e-mail: [email protected]
Investigation of the Role of Infusate Properties Related to Midline Catheter Failure in an Ovine Model
Fitting the integrated Spectral Energy Distributions of Galaxies
Fitting the spectral energy distributions (SEDs) of galaxies is an almost
universally used technique that has matured significantly in the last decade.
Model predictions and fitting procedures have improved significantly over this
time, attempting to keep up with the vastly increased volume and quality of
available data. We review here the field of SED fitting, describing the
modelling of ultraviolet to infrared galaxy SEDs, the creation of
multiwavelength data sets, and the methods used to fit model SEDs to observed
galaxy data sets. We touch upon the achievements and challenges in the major
ingredients of SED fitting, with a special emphasis on describing the interplay
between the quality of the available data, the quality of the available models,
and the best fitting technique to use in order to obtain a realistic
measurement as well as realistic uncertainties. We conclude that SED fitting
can be used effectively to derive a range of physical properties of galaxies,
such as redshift, stellar masses, star formation rates, dust masses, and
metallicities, with care taken not to over-interpret the available data. Yet
there still exist many issues such as estimating the age of the oldest stars in
a galaxy, finer details ofdust properties and dust-star geometry, and the
influences of poorly understood, luminous stellar types and phases. The
challenge for the coming years will be to improve both the models and the
observational data sets to resolve these uncertainties. The present review will
be made available on an interactive, moderated web page (sedfitting.org), where
the community can access and change the text. The intention is to expand the
text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics &
Space Scienc
Ion traps with enhanced optical and physical access
Small, controllable, highly accessible quantum systems can serve as probes at
the single quantum level to study multiple physical effects, for example in
quantum optics or for electric and magnetic field sensing. The applicability of
trapped atomic ions as probes is highly dependent on the measurement situation
at hand and thus calls for specialized traps. Previous approaches for ion traps
with enhanced optical access included traps consisting of a single ring
electrode or two opposing endcap electrodes. Other possibilities are planar
trap geometries, which have been investigated for Penning traps and rf-trap
arrays. By not having the electrodes lie in a common plane the optical access
in the latter cases can be substantially increased. Here, we discuss the
fabrication and experimental characterization of a novel radio-frequency (rf)
ion trap geometry. It has a relatively simple structure and provides largely
unrestricted optical and physical access to the ion, of up to 96% of the total
4pi solid angle in one of the three traps tested. We also discuss potential
applications in quantum optics and field sensing. As a force sensor, we
estimate sensitivity to forces smaller than 1 yN Hz^(-1/2).Comment: 6 pages, 3 figures. Corrections of some typos, application section
expanded to account for reviewer comment
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