Co-trimoxazole prophylaxis in HIV : the evidence

BibliographyHuman immunodeficiency virus (HIV) damages the body’s immune system, making secondary (or opportunistic) infections more common. Treatment and prevention of such infections is integral to the management of patients with HIV infection. Co-trimoxazole is a prophylactic treatment that has a wide range of action against common bacteria, parasites, fungi and yeasts. As part of a minimum care package, UNAIDS/ WHO recommends co-trimoxazole prophylaxis for HIVinfected adults with symptomatic disease (WHO stage II, III or IV), or asymptomatic individuals with CD4 counts ≤500 cells/μl, and for all HIV-positive pregnant women after the first trimester.1 Co-trimoxazole is also recommended for use in children with proven HIV infection and infants exposed to HIV (from 4 - 6 weeks of age until infection with HIV is ruled out).2 The object of this report is to summarise the effects of co-trimoxazole prophylaxis on morbidity and mortality among HIV-infected individuals

In-depth analysis of the Naming Game dynamics: the homogeneous mixing case

Language emergence and evolution has recently gained growing attention through multi-agent models and mathematical frameworks to study their behavior. Here we investigate further the Naming Game, a model able to account for the emergence of a shared vocabulary of form-meaning associations through social/cultural learning. Due to the simplicity of both the structure of the agents and their interaction rules, the dynamics of this model can be analyzed in great detail using numerical simulations and analytical arguments. This paper first reviews some existing results and then presents a new overall understanding.Comment: 30 pages, 19 figures (few in reduced definition). In press in IJMP

Hofstadter butterflies of carbon nanotubes: Pseudofractality of the magnetoelectronic spectrum

The electronic spectrum of a two-dimensional square lattice in a perpendicular magnetic field has become known as the Hofstadter butterfly [Hofstadter, Phys. Rev. B 14, 2239 (1976).]. We have calculated quasi-one-dimensional analogs of the Hofstadter butterfly for carbon nanotubes (CNTs). For the case of single-wall CNTs, it is straightforward to implement magnetic fields parallel to the tube axis by means of zone folding in the graphene reciprocal lattice. We have also studied perpendicular magnetic fields which, in contrast to the parallel case, lead to a much richer, pseudofractal spectrum. Moreover, we have investigated magnetic fields piercing double-wall CNTs and found strong signatures of interwall interaction in the resulting Hofstadter butterfly spectrum, which can be understood with the help of a minimal model. Ubiquitous to all perpendicular magnetic field spectra is the presence of cusp catastrophes at specific values of energy and magnetic field. Resolving the density of states along the tube circumference allows recognition of the snake states already predicted for nonuniform magnetic fields in the two-dimensional electron gas. An analytic model of the magnetic spectrum of electrons on a cylindrical surface is used to explain some of the results.Comment: 14 pages, 12 figures update to published versio

Sharp transition towards shared vocabularies in multi-agent systems

What processes can explain how very large populations are able to converge on the use of a particular word or grammatical construction without global coordination? Answering this question helps to understand why new language constructs usually propagate along an S-shaped curve with a rather sudden transition towards global agreement. It also helps to analyze and design new technologies that support or orchestrate self-organizing communication systems, such as recent social tagging systems for the web. The article introduces and studies a microscopic model of communicating autonomous agents performing language games without any central control. We show that the system undergoes a disorder/order transition, going trough a sharp symmetry breaking process to reach a shared set of conventions. Before the transition, the system builds up non-trivial scale-invariant correlations, for instance in the distribution of competing synonyms, which display a Zipf-like law. These correlations make the system ready for the transition towards shared conventions, which, observed on the time-scale of collective behaviors, becomes sharper and sharper with system size. This surprising result not only explains why human language can scale up to very large populations but also suggests ways to optimize artificial semiotic dynamics.Comment: 12 pages, 4 figure

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Calibration of optimal execution of financial transactions in the presence of transient market impact

Trading large volumes of a financial asset in order driven markets requires the use of algorithmic execution dividing the volume in many transactions in order to minimize costs due to market impact. A proper design of an optimal execution strategy strongly depends on a careful modeling of market impact, i.e. how the price reacts to trades. In this paper we consider a recently introduced market impact model (Bouchaud et al., 2004), which has the property of describing both the volume and the temporal dependence of price change due to trading. We show how this model can be used to describe price impact also in aggregated trade time or in real time. We then solve analytically and calibrate with real data the optimal execution problem both for risk neutral and for risk averse investors and we derive an efficient frontier of optimal execution. When we include spread costs the problem must be solved numerically and we show that the introduction of such costs regularizes the solution.Comment: 31 pages, 8 figure

Information transmission in oscillatory neural activity

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al, 1999; Brenner et al, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.Comment: 18 pages, 8 figures, to appear in Biological Cybernetic

Was the Old English Aristocracy Destroyed by the Wars of the Roses?

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A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems

In this paper we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware-experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects