T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedTo estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.This work was supported by European and Developing Countries Clinical Trials Partnership grant # IP.2009.33011.004; trial foods were prepared and supplied by Nutriset, Malauney, Franc

Risk-based bridge scour management:a survey

Scour is one of the major causes of bridge failure worldwide and results in significant economic losses through disruption to operation. This phenomenon naturally affects bridges with underwater foundations and is exacerbated during high river and/or turbulent flows (e.g. due to extreme events). When scour reaches the bottom or undermines shallow foundations it is likely to trigger various damage mechanisms that may in-fluence the safety of the structure and force asset managers to reduce traffic capacity. Currently, assessing risk of scour is a heuristic process, heavily reliant on qualitative approaches and expert opinion (e.g. visual inspections). These types of assessments typically suffer from insufficient knowledge of influencing factors (e.g. hydraulic parameters) and the requirement to rely on several assumptions (e.g. foundation depth). As a result, current scour assessment and bridge management practices do not provide reliable solutions for ad-dressing the potential risk of bridge failures. In this paper, cross-cutting needs and challenges related to the development of decision support tools for scour-risk management are highlighted and some preliminary re-sults of a literature survey are reported. The review has been performed with several objectives: (i) identify-ing scour-risk indicators describing hydrodynamic actions and the asset condition; (ii) defining indirect and direct consequences needed to assess the risks associated to different decision alternatives related to scour management; and (iii) identifying existing approaches to scour inspections and monitoring as support tools for informed decisions. The results of this survey will serve as a base for future research aimed to develop an informed decision support tool to manage scour risk at both the bridge and at the network level

Importance of Electronic Relaxation for Inter-Coulombic Decay in Aqueous Systems

Inspired by recent photoelectron spectroscopy experiments on hydroxide solutions, we have examined the conditions necessary for enhanced (and, in the case of solutions, detectable) inter-Coulombic decay (ICD)—Auger emission from an atomic site other than that originally excited. We present general guidelines, based on energetic and spatial overlap of molecular orbitals, for this enhancement of inter-Coulombic decay-based energy transfer in solutions. These guidelines indicate that this decay process should be exhibited by broad classes of biomolecules and suggest a design criterion for targeted radiooncology protocols. Our findings show that photoelectron spectroscopy cannot resolve the current hydroxide coordination controversy

Nuclear quantum effects in the structure and lineshapes of the N2 near-edge x-ray absorption fine structure spectrum

We study the relative ability of several models of x-ray absorption spectra to capture the Franck–Condon structure apparent from an experiment on gaseous nitrogen. In doing so, we adopt the Born–Oppenheimer approximation and a constrained density functional theory method for computing the energies of the x-ray-excited molecule. Starting from an otherwise classical model for the spectrum, we systematically introduce more realistic physics, first by substituting the quantum mechanical nuclear radial density in the bond separation R for the classical radial density, then by adding the effect of zero-point energy and other level shifts, and finally by including explicit rovibrational quantization of both the ground and excited states. The quantization is determined exactly, using a discrete variable representation (DVR). We show that the near-edge x-ray absorption fine structure (NEXAFS) spectrum can be predicted semiquantitatively within this framework. We also address the possibility of non-trivial temperature dependence in the spectrum. By using constrained density functional theory in combination with more accurate potentials, we demonstrate that it is possible to improve the predicted spectrum. Ultimately, we establish the predictive limits of our method with respect to vibrational fine structure in NEXAFS spectra

Super-Eddington Atmospheres that Don't Blow Away

We show that magnetized, radiation dominated atmospheres can support steady state patterns of density inhomogeneity that enable them to radiate at far above the Eddington limit, without suffering mass loss. The inhomogeneities consist of periodic shock fronts bounding narrow, high-density regions, interspersed with much broader regions of low density. The radiation flux avoids the regions of high density, which are therefore weighed down by gravity, while gas in the low-density regions is slammed upward into the shock fronts by radiation force. As the wave pattern moves through the atmosphere, each parcel of matter alternately experiences upward and downward forces, which balance on average. Magnetic tension shares the competing forces between regions of different densities, preventing the atmosphere from blowing apart. We calculate the density structure and phase speed of the wave pattern, and relate these to the wavelength, the density contrast, and the factor by which the net radiation flux exceeds the Eddington limit. In principle, this factor can be as large as the ratio of magnetic pressure to mean gas pressure, or the ratio of radiation pressure to gas pressure, whichever is smaller. Although the magnetic pressure must be large compared to the mean gas pressure in order to support a large density contrast, it need not be large compared to the radiation pressure. These highly inhomogeneous flows could represent the nonlinear development of the "photon bubble" instability discovered by Gammie. We briefly discuss the applicability of these solutions to astrophysical systems.Comment: 11 pages, 1 figure, accepted for publication in The Astrophysical Journa

Electronic structure of warm dense copper studied by ultrafast x-ray absorption spectroscopy

We use time-resolved x-ray absorption spectroscopy to investigate the unoccupied electronic density of states of warm dense copper that is produced isochorically through the absorption of an ultrafast optical pulse. The temperature of the superheated electron-hole plasma, which ranges from 4000 to 10 000 K, was determined by comparing the measured x-ray absorption spectrum with a simulation. The electronic structure of warm dense copper is adequately described with the high temperature electronic density of state calculated by the density functional theory. The dynamics of the electron temperature is consistent with a two-temperature model, while a temperature-dependent electron-phonon coupling parameter is necessary

A Sub-Type of Familial Pancreatic Cancer: Evidence and Implications of Loss-of-Function Polymorphisms in Indoleamine-2,3-Dioxygenase-2.

BACKGROUND: Variation in an individual\u27s genetic status can impact the development of pancreatic ductal adenocarcinoma; however, the majority of familial pancreatic cancers (FPC) cannot yet be attributed to a specific inherited mutation. We present data suggesting a correlation between loss-of-function single nucleotide polymorphisms (SNPs) in an immune regulator gene, indoleamine-2,3-dioxygenase-2 (IDO2), and an increased risk of FPC. STUDY DESIGN: Germline DNA from patients who underwent resection for pancreatic ductal adenocarcinoma (n = 79) was sequenced for the IDO2 SNPs R248W and Y359Stop. Genotypes resulting in inactivation of IDO2 (Y325X homozygous, R248W homozygous) were labeled as homozygous, and the other genotypes were grouped as wild-type or heterozygous. Genotype distributions of each SNP were analyzed for Hardy-Weinberg deviation. A genotype frequency set from the 1000 Genomes Project (n = 99) was used as a genetic control for genotype distribution comparisons. RESULTS: A significant 2-fold increase in the overall prevalence of the Y359Stop homozygous genotype compared with the expected Hardy-Weinberg equilibrium was noted (p \u3c 0.05). Familial pancreatic cancer was noted in 15 cases (19%) and comparison of the FPC cohort set to the genetic control set showed a 3-fold increase in Y359Stop homozygous rates (p = 0.054). Overall in our cohort, the homozygous genotype group was associated with increased risk of FPC (odds ratio 5.4; 95% CI 1.6 to 17.6; p \u3c 0.01). Sex, age at diagnosis, and history of tobacco use were not found to be significantly associated with FPC. CONCLUSIONS: Our preliminary data suggest a strong association between the IDO2 inactivating Y359Stop SNP and an increased risk of FPC when compared with the control group. Future studies will evaluate the value of IDO2 genotyping as a prognostic, early detection marker for pancreatic ductal adenocarcinoma and a predictive marker for novel immune checkpoint therapies

Computational simulation methodologies for mechanobiological modelling: a cell-centred approach to neointima development in stents

The design of medical devices could be very much improved if robust tools were available for computational simulation of tissue response to the presence of the implant. Such tools require algorithms to simulate the response of tissues to mechanical and chemical stimuli. Available methodologies include those based on the principle of mechanical homeostasis, those which use continuum models to simulate biological constituents, and the cell-centred approach, which models cells as autonomous agents. In the latter approach, cell behaviour is governed by rules based on the state of the local environment around the cell; and informed by experiment. Tissue growth and differentiation requires simulating many of these cells together. In this paper, the methodology and applications of cell-centred techniques—with particular application to mechanobiology—are reviewed, and a cell-centred model of tissue formation in the lumen of an artery in response to the deployment of a stent is presented. The method is capable of capturing some of the most important aspects of restenosis, including nonlinear lesion growth with time. The approach taken in this paper provides a framework for simulating restenosis; the next step will be to couple it with more patient-specific geometries and quantitative parameter data