542 research outputs found
Vacuum Stability of the wrong sign Scalar Field Theory
We apply the effective potential method to study the vacuum stability of the
bounded from above (unstable) quantum field potential. The
stability ( and the mass renormalization
( conditions force the effective
potential of this theory to be bounded from below (stable). Since bounded from
below potentials are always associated with localized wave functions, the
algorithm we use replaces the boundary condition applied to the wave functions
in the complex contour method by two stability conditions on the effective
potential obtained. To test the validity of our calculations, we show that our
variational predictions can reproduce exactly the results in the literature for
the -symmetric theory. We then extend the applications
of the algorithm to the unstudied stability problem of the bounded from above
scalar field theory where classical analysis prohibits the
existence of a stable spectrum. Concerning this, we calculated the effective
potential up to first order in the couplings in space-time dimensions. We
find that a Hermitian effective theory is instable while a non-Hermitian but
-symmetric effective theory characterized by a pure imaginary
vacuum condensate is stable (bounded from below) which is against the classical
predictions of the instability of the theory. We assert that the work presented
here represents the first calculations that advocates the stability of the
scalar potential.Comment: 21pages, 12 figures. In this version, we updated the text and added
some figure
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
Compared to conventional, ecological intensive management promotes beneficial proteolytic soil microbial communities for agro-ecosystem functioning under climate change-induced rain regimes
Projected climate change and rainfall variability will affect soil microbial communities, biogeochemical cycling and agriculture. Nitrogen (N) is the most limiting nutrient in agroecosystems and its cycling and availability is highly dependent on microbial driven processes. In agroecosystems, hydrolysis of organic nitrogen (N) is an important step in controlling soil N availability. We analyzed the effect of management (ecological intensive vs. conventional intensive) on N-cycling processes and involved microbial communities under climate change-induced rain regimes. Terrestrial model ecosystems originating from agroecosystems across Europe were subjected to four different rain regimes for 263 days. Using structural equation modelling we identified direct impacts of rain regimes on N-cycling processes, whereas N-related microbial communities were more resistant. In addition to rain regimes, management indirectly affected N-cycling processes via modifications of N-related microbial community composition. Ecological intensive management promoted a beneficial N-related microbial community composition involved in N-cycling processes under climate change-induced rain regimes. Exploratory analyses identified phosphorus-associated litter properties as possible drivers for the observed management effects on N-related microbial community composition. This work provides novel insights into mechanisms controlling agro-ecosystem functioning under climate change
Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces
Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces
Statistical power considerations in genotype-based recall randomized controlled trials
Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design
Microbial Functional Capacity Is Preserved Within Engineered Soil Formulations Used In Mine Site Restoration
Mining of mineral resources produces substantial volumes of crushed rock based wastes that are characterised by poor physical structure and hydrology, unstable geochemistry and potentially toxic chemical conditions. Recycling of these substrates is desirable and can be achieved by blending waste with native soil to form a 'novel substrate' which may be used in future landscape restoration. However, these post-mining substrate based 'soils' are likely to contain significant abiotic constraints for both plant and microbial growth. Effective use of these novel substrates for ecosystem restoration will depend on the efficacy of stored topsoil as a potential microbial inoculum as well as the subsequent generation of key microbial soil functions originally apparent in local pristine sites. Here, using both marker gene and shotgun metagenome sequencing, we show that topsoil storage and the blending of soil and waste substrates to form planting substrates gives rise to variable bacterial and archaeal phylogenetic composition but a high degree of metabolic conservation at the community metagenome level. Our data indicates that whilst low phylogenetic conservation is apparent across substrate blends we observe high functional redundancy in relation to key soil microbial pathways, allowing the potential for functional recovery of key belowground pathways under targeted management
Cellular Radiosensitivity: How much better do we understand it?
Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies.
Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation
Network Neighbors of Drug Targets Contribute to Drug Side-Effect Similarity
In pharmacology, it is essential to identify the molecular mechanisms of drug action in order to understand adverse side effects. These adverse side effects have been used to infer whether two drugs share a target protein. However, side-effect similarity of drugs could also be caused by their target proteins being close in a molecular network, which as such could cause similar downstream effects. In this study, we investigated the proportion of side-effect similarities that is due to targets that are close in the network compared to shared drug targets. We found that only a minor fraction of side-effect similarities (5.8 %) are caused by drugs targeting proteins close in the network, compared to side-effect similarities caused by overlapping drug targets (64%). Moreover, these targets that cause similar side effects are more often in a linear part of the network, having two or less interactions, than drug targets in general. Based on the examples, we gained novel insight into the molecular mechanisms of side effects associated with several drug targets. Looking forward, such analyses will be extremely useful in the process of drug development to better understand adverse side effects
Physics, Astrophysics and Cosmology with Gravitational Waves
Gravitational wave detectors are already operating at interesting sensitivity
levels, and they have an upgrade path that should result in secure detections
by 2014. We review the physics of gravitational waves, how they interact with
detectors (bars and interferometers), and how these detectors operate. We study
the most likely sources of gravitational waves and review the data analysis
methods that are used to extract their signals from detector noise. Then we
consider the consequences of gravitational wave detections and observations for
physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version
<http://www.livingreviews.org/lrr-2009-2
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