Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

Perturbations of Gauss-Bonnet Black Strings in Codimension-2 Braneworlds

We derive the Lichnerowicz equation in the presence of the Gauss-Bonnet term. Using the modified Lichnerowicz equation we study the metric perturbations of Gauss-Bonnet black strings in Codimension-2 Braneworlds.Comment: 26 pages, no figures, clarifying comments and one reference added, to be published in JHE

Apparent correlation of palaeomagnetic intensity and climatic records in deep-sea sediments

Most reports of a correlation between Pleistocene climate and geomagnetic field intensity rely strongly on the assumption that sediment natural remanent magnetic (NRM) intensity provides a record of geomagnetic field strength and is not sensitive to local changes in properties of the sediment. Critical assessment of relevant data presented here and elsewhere from deep-sea sediment cores shows that a pronounced dependence of NRM intensity on sediment composition can occur which implies that this assumption is unlikely to be generally valid. As sediment composition often reflects varying depositional conditions induced by climatic change, the significance of correlations proposed between Pleistocene palaeomagnetism and climatic indicators in deep-sea sediments may be less dramatic than sometimes supposed

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Accounting for density reduction and structural loss in standing dead trees: Implications for forest biomass and carbon stock estimates in the United States

<p>Abstract</p> <p>Background</p> <p>Standing dead trees are one component of forest ecosystem dead wood carbon (C) pools, whose national stock is estimated by the U.S. as required by the United Nations Framework Convention on Climate Change. Historically, standing dead tree C has been estimated as a function of live tree growing stock volume in the U.S.'s National Greenhouse Gas Inventory. Initiated in 1998, the USDA Forest Service's Forest Inventory and Analysis program (responsible for compiling the Nation's forest C estimates) began consistent nationwide sampling of standing dead trees, which may now supplant previous purely model-based approaches to standing dead biomass and C stock estimation. A substantial hurdle to estimating standing dead tree biomass and C attributes is that traditional estimation procedures are based on merchantability paradigms that may not reflect density reductions or structural loss due to decomposition common in standing dead trees. The goal of this study was to incorporate standing dead tree adjustments into the current estimation procedures and assess how biomass and C stocks change at multiple spatial scales.</p> <p>Results</p> <p>Accounting for decay and structural loss in standing dead trees significantly decreased tree- and plot-level C stock estimates (and subsequent C stocks) by decay class and tree component. At a regional scale, incorporating adjustment factors decreased standing dead quaking aspen biomass estimates by almost 50 percent in the Lake States and Douglas-fir estimates by more than 36 percent in the Pacific Northwest.</p> <p>Conclusions</p> <p>Substantial overestimates of standing dead tree biomass and C stocks occur when one does not account for density reductions or structural loss. Forest inventory estimation procedures that are descended from merchantability standards may need to be revised toward a more holistic approach to determining standing dead tree biomass and C attributes (i.e., attributes of tree biomass outside of sawlog portions). Incorporating density reductions and structural loss adjustments reduces uncertainty associated with standing dead tree biomass and C while improving consistency with field methods and documentation.</p

The C2HDM revisited

The complex two-Higgs doublet model is one of the simplest ways to extend the scalar sector of the Standard Model to include a new source of CP-violation. The model has been used as a benchmark model to search for CP-violation at the LHC and as a possible explanation for the matter-antimatter asymmetry of the Universe. In this work, we re-analyse in full detail the softly broken $\mathbb{Z}_2$ symmetric complex two-Higgs doublet model (C2HDM). We provide the code C2HDM_HDECAY implementing the C2HDM in the well-known HDECAY program which calculates the decay widths including the state-of-the-art higher order QCD corrections and the relevant off-shell decays. Using C2HDM_HDECAY together with the most relevant theoretical and experimental constraints, including electric dipole moments (EDMs), we review the parameter space of the model and discuss its phenomenology. In particular, we find cases where large CP-odd couplings to fermions are still allowed and provide benchmark points for these scenarios. We examine the prospects of discovering CP-violation at the LHC and show how theoretically motivated measures of CP-violation correlate with observables.The work of D.F., J.C.R. and J.P.S. is supported in part by the Portuguese Fundacao para a Ciencia e Tecnologia (FCT) under contracts CERN/FIS-NUC/0010/2015 and UID/FIS/00777/2013. MM acknowledges financial support from the DFG project "Precision Calculations in the Higgs Sector - Paving the Way to the New Physics Landscape" (ID: MU 3138/1-1).info:eu-repo/semantics/publishedVersio

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Use of Data-Biased Random Walks on Graphs for the Retrieval of Context-Specific Networks from Genomic Data

Extracting network-based functional relationships within genomic datasets is an important challenge in the computational analysis of large-scale data. Although many methods, both public and commercial, have been developed, the problem of identifying networks of interactions that are most relevant to the given input data still remains an open issue. Here, we have leveraged the method of random walks on graphs as a powerful platform for scoring network components based on simultaneous assessment of the experimental data as well as local network connectivity. Using this method, NetWalk, we can calculate distribution of Edge Flux values associated with each interaction in the network, which reflects the relevance of interactions based on the experimental data. We show that network-based analyses of genomic data are simpler and more accurate using NetWalk than with some of the currently employed methods. We also present NetWalk analysis of microarray gene expression data from MCF7 cells exposed to different doses of doxorubicin, which reveals a switch-like pattern in the p53 regulated network in cell cycle arrest and apoptosis. Our analyses demonstrate the use of NetWalk as a valuable tool in generating high-confidence hypotheses from high-content genomic data

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom