CD4 count and tuberculosis risk in HIV-positive adults not on ART: a systematic review and meta-analysis

Background: CD4 cell count in adults with human immunodeficiency virus (HIV) infection (PLHIV) not receiving antiretroviral therapy (ART) influences tuberculosis (TB) risk. Despite widespread use in models informing resource allocation, this relationship has not been systematically reviewed. Methods: We systematically searched MEDLINE, Aidsinfo, Cochrane review database and Google Scholar for reports in English describing TB incidence stratified by updated CD4 cell count in cohorts of HIV-positive adults (age ≥15 years) not on ART (PROSPERO protocol no: CRD42016048888). Among inclusion criteria were: reporting precision for TB incidence, repeated CD4 measurements, and TB incidence reported for those not on ART or monotherapy. Study quality was assessed via the Newcastle-Ottawa tool for cohort studies. A Bayesian hierarchical model was fitted to estimate the pooled factor increase in TB incidence with respect to CD4 cell count decrement. Results: A total of 1,555 distinct records were identified from which 164 full text articles were obtained. Common reasons for exclusion of full texts were: no valid TB incidence, no repeat CD4 measurements, and not reporting TB incidence by ART status. The seven studies included reported on 1,206 TB cases among 41,271 individuals, with a typical median follow-up of four years. Studies were generally rated as moderate or high quality. Our meta-analysis estimated a 1.43 (95% credible interval: 1.16-1.88)-fold increase in TB incidence per 100 cells per mm3 decrease in CD4 cell count. Discussion: Our analysis confirms previous estimates of exponential increase in TB incidence with declining CD4 cell count in adults, emphasizing the importance of early ART initiation to reduce TB risk in PLHIV

Membranes for Topological M-Theory

We formulate a theory of topological membranes on manifolds with G_2 holonomy. The BRST charges of the theories are the superspace Killing vectors (the generators of global supersymmetry) on the background with reduced holonomy G_2. In the absence of spinning formulations of supermembranes, the starting point is an N=2 target space supersymmetric membrane in seven euclidean dimensions. The reduction of the holonomy group implies a twisting of the rotations in the tangent bundle of the branes with ``R-symmetry'' rotations in the normal bundle, in contrast to the ordinary spinning formulation of topological strings, where twisting is performed with internal U(1) currents of the N=(2,2) superconformal algebra. The double dimensional reduction on a circle of the topological membrane gives the strings of the topological A-model (a by-product of this reduction is a Green-Schwarz formulation of topological strings). We conclude that the action is BRST-exact modulo topological terms and fermionic equations of motion. We discuss the role of topological membranes in topological M-theory and the relation of our work to recent work by Hitchin and by Dijkgraaf et al.Comment: 22 pp, plain tex. v2: refs. adde

Pre-Treatment of Human Mesenchymal Stem Cells with Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium

Background: Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Hypothesis: Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Study Design: Controlled laboratory study. Methods: We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Results: Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Conclusion: Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. Clinical Relevance: To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA

A nonlinear hydrodynamical approach to granular materials

We propose a nonlinear hydrodynamical model of granular materials. We show how this model describes the formation of a sand pile from a homogeneous distribution of material under gravity, and then discuss a simulation of a rotating sandpile which shows, in qualitative agreement with experiment, a static and dynamic angle of repose.Comment: 17 pages, 14 figures, RevTeX4; minor changes to wording and some additional discussion. Accepted by Phys. Rev.

Entanglement Interpretation of Black Hole Entropy in String Theory

We show that the entropy resulting from the counting of microstates of non extremal black holes using field theory duals of string theories can be interpreted as arising from entanglement. The conditions for making such an interpretation consistent are discussed. First, we interpret the entropy (and thermodynamics) of spacetimes with non degenerate, bifurcating Killing horizons as arising from entanglement. We use a path integral method to define the Hartle-Hawking vacuum state in such spacetimes and discuss explicitly its entangled nature and its relation to the geometry. If string theory on such spacetimes has a field theory dual, then, in the low-energy, weak coupling limit, the field theory state that is dual to the Hartle-Hawking state is a thermofield double state. This allows the comparison of the entanglement entropy with the entropy of the field theory dual, and thus, with the Bekenstein-Hawking entropy of the black hole. As an example, we discuss in detail the case of the five dimensional anti-de Sitter, black hole spacetime

Effect of arthritic synovial fluids on the expression of immunomodulatory factors by mesenchymal stem cells: An explorative in vitro study

Background:In diseased joints, the catabolic environment results in progressive joint damage. Mesenchymal stem cells (MSCs) can have immunomodulatory effects by secreting anti-inflammatory factors. To exert these effects, MSCs need to be triggered by proinflammatory cytokines. To explore the potential of MSCs as a treatment for diseased joints, we studied the effect of synovial fluid (SF) from donors with different joint diseases and donors without joint pathology on the immunomodulatory capacities of human MSCs in vitro. We hypothesized that SF of diseased joints influences the immunomodulatory effects of MSCs. Materials and Methods: MSCs were cultured in medium with SF of six osteoarthritis (OA) or six rheumatoid arthritis (RA) donors and three donors without joint pathology were used as control. Gene expressions of IL-6, HGF, TNFa, TGFb1, and indoleamine 2,3-dioxygenase (IDO) were analyzed. L-kynurenine concentration in conditioned medium (CM) by MSCs with SF was determined as a measure of IDO activity by MSCs. Furthermore, the effect of CM with SF on proliferation of activated lymphocytes was analyzed. Results: Addition of SF significantly up-regulated the mRNA expression of IL-6 and IDO in MSCs. SF(OA) induced significantly higher expression of IDO than SF(control), although no difference in IDO activity of the MSCs could be shown with a L-kynurenine assay. Medium conditioned by MSCs with SF(OA or RA) suppressed activated lymphocyte proliferation in vitro more than medium conditioned by MSCs without SF or with SF(control). Discussion: SF can influence the expression of genes involved in immunomodulation by MSCs and the effect on lymphocyte proliferation. We found indications for disease-specific differences between SFs but the variation between donors, even within one disease group was high. These data warrant further research to examine the potential application of MSC therapy in arthritic joints

Generation of continuous variable squeezing and entanglement of trapped ions in time-varying potentials

We investigate the generation of squeezing and entanglement for the motional degrees of freedom of ions in linear traps, confined by time-varying and oscillating potentials, comprised of an DC and an AC component. We show that high degrees of squeezing and entanglement can be obtained by controlling either the DC or the AC trapping component (or both), and by exploiting transient dynamics in regions where the ions' motion is unstable, without any added optical control. Furthermore, we investigate the time-scales over which the potentials should be switched in order for the manipulations to be most effective.Comment: 10 pages, submitted to Quantum Information Processing (special issue on Quantum Decoherence and Entanglement

Quantum Interference: From Kaons to Neutrinos (with Quantum Beats in between)

Using the vehicle of resolving an apparent paradox, a discussion of quantum interference is presented. The understanding of a number of different physical phenomena can be unified, in this context. These range from the neutral kaon system to massive neutrinos, not to mention quantum beats, Rydberg wave packets, and neutron gravity.Comment: 12 pages, LaTeX, 3 figure

A Massive Renormalizable Abelian Gauge Theory in 2+1 Dimensions

The standard formulation of a massive Abelian vector field in $2+1$ dimensions involves a Maxwell kinetic term plus a Chern-Simons mass term; in its place we consider a Chern-Simons kinetic term plus a Stuekelberg mass term. In this latter model, we still have a massive vector field, but now the interaction with a charged spinor field is renormalizable (as opposed to super renormalizable). By choosing an appropriate gauge fixing term, the Stuekelberg auxiliary scalar field decouples from the vector field. The one-loop spinor self energy is computed using operator regularization, a technique which respects the three dimensional character of the antisymmetric tensor $\epsilon_{\alpha\beta\gamma}$. This method is used to evaluate the vector self energy to two-loop order; it is found to vanish showing that the beta function is zero to two-loop order. The canonical structure of the model is examined using the Dirac constraint formalism.Comment: LaTeX, 17 pages, expanded reference list and discussion of relationship to previous wor

Properties of pattern formation and selection processes in nonequilibrium systems with external fluctuations

We extend the phase field crystal method for nonequilibrium patterning to stochastic systems with external source where transient dynamics is essential. It was shown that at short time scales the system manifests pattern selection processes. These processes are studied by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed by means of numerical simulations.Comment: 15 poages, 8 figure