Genomic signatures of pre-resistance in Mycobacterium tuberculosis

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period. After reconstructing ancestral genomes on time-calibrated phylogenetic trees, we developed and applied a genome-wide survival analysis to determine the hazard of resistance acquisition. We demonstrate that M. tuberculosis lineage 2 has a higher risk of acquiring resistance than lineage 4, and estimate a higher hazard of rifampicin resistance evolution following isoniazid mono-resistance. Furthermore, we describe loci and genomic polymorphisms associated with a higher risk of resistance acquisition. Identifying markers of future antibiotic resistance could enable targeted therapy to prevent resistance emergence in M. tuberculosis and other pathogens

Effectiveness of proactive telephone counselling for smoking cessation in parents: Study protocol of a randomized controlled trial

Contains fulltext : 99284.pdf (publisher's version ) (Open Access)Background Smoking is the world's fourth most common risk factor for disease, the leading preventable cause of death, and it is associated with tremendous social costs. In the Netherlands, the smoking prevalence rate is high. A total of 27.7% of the population over age 15 years smokes. In addition to the direct advantages of smoking cessation for the smoker, parents who quit smoking may also decrease their children's risk of smoking initiation. Methods/Design A randomized controlled trial will be conducted to evaluate the effectiveness of proactive telephone counselling to increase smoking cessation rates among smoking parents. A total of 512 smoking parents will be proactively recruited through their children's primary schools and randomly assigned to either proactive telephone counselling or a control condition. Proactive telephone counselling will consist of up to seven counsellor-initiated telephone calls (based on cognitive-behavioural skill building and Motivational Interviewing), distributed over a period of three months. Three supplementary brochures will also be provided. In the control condition, parents will receive a standard brochure to aid smoking cessation. Assessments will take place at baseline, three months after start of the intervention (post-measurement), and twelve months after start of the intervention (follow-up measurement). Primary outcome measures will include sustained abstinence between post-measurement and follow-up measurement and 7-day point prevalence abstinence and 24-hours point prevalence abstinence at both post- and follow-up measurement. Several secondary outcome measures will also be included (e.g., smoking intensity, smoking policies at home). In addition, we will evaluate smoking-related cognitions (e.g., attitudes towards smoking, social norms, self-efficacy, intention to smoke) in 9-12 year old children of smoking parents. Discussion This study protocol describes the design of a randomized controlled trial to evaluate the effectiveness of proactive telephone counselling in smoking cessation. It is expected that, in the telephone counseling condition, parental smoking cessation rates will be higher and children's cognitions will be less favorable about smoking compared to the control condition. Trial registration The protocol for this study is registered with the Netherlands Trial Register NTR2707.6 p

Photo-production of Nucleon Resonances and Nucleon Spin Structure Function in the Resonance Region

The photo-production of nucleon resonances is calculated based on a chiral constituent quark model including both relativistic corrections H{rel} and two-body exchange currents, and it is shown that these effects play an important role. We also calculate the first moment of the nucleon spin structure function g1 (x,Q^2) in the resonance region, and obtain a sign-changing point around Q^2 ~ 0.27 {GeV}^2 for the proton.Comment: 23 pages, 5 figure

Femtometer Toroidal Structures in Nuclei

The two-nucleon density distributions in states with isospin $T=0$, spin $S$=1 and projection $M_S$=0 and $\pm$1 are studied in $^2$H, $^{3,4}$He, $^{6,7}$Li and $^{16}$O. The equidensity surfaces for $M_S$=0 distributions are found to be toroidal in shape, while those of $M_S$=$\pm$1 have dumbbell shapes at large density. The dumbbell shapes are generated by rotating tori. The toroidal shapes indicate that the tensor correlations have near maximal strength at $r<2$ fm in all these nuclei. They provide new insights and simple explanations of the structure and electromagnetic form factors of the deuteron, the quasi-deuteron model, and the $dp$, $dd$ and $\alpha d$ $L$=2 ($D$-wave) components in $^3$He, $^4$He and $^6$Li. The toroidal distribution has a maximum-density diameter of $\sim$1 fm and a half-maximum density thickness of $\sim$0.9 fm. Many realistic models of nuclear forces predict these values, which are supported by the observed electromagnetic form factors of the deuteron, and also predicted by classical Skyrme effective Lagrangians, related to QCD in the limit of infinite colors. Due to the rather small size of this structure, it could have a revealing relation to certain aspects of QCD.Comment: 35 pages in REVTeX, 25 PostScript figure

Weak Decays Beyond Leading Logarithms

We review the present status of QCD corrections to weak decays beyond the leading logarithmic approximation including particle-antiparticle mixing and rare and CP violating decays. After presenting the basic formalism for these calculations we discuss in detail the effective hamiltonians for all decays for which the next-to-leading corrections are known. Subsequently, we present the phenomenological implications of these calculations. In particular we update the values of various parameters and we incorporate new information on m_t in view of the recent top quark discovery. One of the central issues in our review are the theoretical uncertainties related to renormalization scale ambiguities which are substantially reduced by including next-to-leading order corrections. The impact of this theoretical improvement on the determination of the Cabibbo-Kobayashi-Maskawa matrix is then illustrated in various cases.Comment: 229 pages, 32 PostScript figures (included); uses RevTeX, epsf.sty, rotate.sty, rmpbib.sty (included), times.sty (included; requires LaTeX 2e); complete PostScript version available at ftp://feynman.t30.physik.tu-muenchen.de/pub/preprints/tum-100-95.ps.gz or ftp://feynman.t30.physik.tu-muenchen.de/pub/preprints/tum-100-95.ps2.gz (scaled down and rotated version to print two pages on one sheet of paper

Elastic electron deuteron scattering with consistent meson exchange and relativistic contributions of leading order

The influence of relativistic contributions to elastic electron deuteron scattering is studied systematically at low and intermediate momentum transfers ($Q^2\leq 30$ fm$^{-2}$). In a $(p/M)$-expansion, all leading order relativistic $\pi$-exchange contributions consistent with the Bonn OBEPQ models are included. In addition, static heavy meson exchange currents including boost terms and lowest order $\rho\pi\gamma$-currents are considered. Sizeable effects from the various relativistic two-body contributions, mainly from $\pi$-exchange, have been found in form factors, structure functions and the tensor polarization $T_{20}$. Furthermore, static properties, viz. magnetic dipole and charge quadrupole moments and the mean square charge radius are evaluated.Comment: 15 pages Latex including 5 figures, final version accepted for publication in Phys.Rev.C Details of changes: (i) The notation of the curves in Figs. 1 and 2 have been clarified with respect to left and right panels. (ii) In Figs. 3 and 4 an experimental point for T_20 has been added and a corresponding reference [48] (iii) At the end of the text we have added a paragraph concerning the quality of the Bonn OBEPQ potential

A1C as a Diagnostic Criteria for Diabetes in Low- and Middle-Income Settings: Evidence from Peru

OBJECTIVES: To determine the prevalence of type 2 diabetes mellitus, in three groups of Peruvian adults, using fasting glucose and glycosylated hemoglobin (A1C). METHODOLOGY/PRINCIPAL FINDINGS: This study included adults from the PERU MIGRANT Study who had fasted ≥ 8 h. Fasting glucose ≥ 126 mg/dL and A1C ≥ 6.5% were used, separately, to define diabetes. Subjects with a current diagnosis of diabetes were excluded. 964 of 988 subjects were included in this analysis. Overall, 0.9% (95%CI 0.3-1.5) and 3.5% (95%CI 2.4-4.7) had diabetes using fasting glucose and A1C criteria, respectively. Compared to those classified as having diabetes using fasting glucose, newly classified subjects with diabetes using A1C (n = 25), were older, poorer, thinner and more likely to come from rural areas. Of these, 40% (10/25) had impaired fasting glucose (IFG). CONCLUSIONS: This study shows that the use of A1C as diagnostic criteria for type 2 diabetes mellitus identifies people of different characteristics than fasting glucose. In the PERU MIGRANT population using A1C to define diabetes tripled the prevalence; the increase was more marked among poorer and rural populations. More than half the newly diagnosed people with diabetes using A1C had normal fasting glucose

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

Lymphocyte subsets and the role of Th1/Th2 balance in stressed chronic pain patients

Background: The complex regional pain syndrome (CRPS) and fibromyalgia (FM) are chronic pain syndromes occurring in highly stressed individuals. Despite the known connection between the nervous system and immune cells, information on distribution of lymphocyte subsets under stress and pain conditions is limited. Methods: We performed a comparative study in 15 patients with CRPS type I, 22 patients with FM and 37 age- and sex-matched healthy controls and investigated the influence of pain and stress on lymphocyte number, subpopulations and the Th1/Th2 cytokine ratio in T lymphocytes. Results: Lymphocyte numbers did not differ between groups. Quantitative analyses of lymphocyte subpopulations showed a significant reduction of cytotoxic CD8+ lymphocytes in both CRPS (p < 0.01) and FM (p < 0.05) patients as compared with healthy controls. Additionally, CRPS patients were characterized by a lower percentage of IL-2-producing T cell subpopulations reflecting a diminished Th1 response in contrast to no changes in the Th2 cytokine profile. Conclusions: Future studies are warranted to answer whether such immunological changes play a pathogenetic role in CRPS and FM or merely reflect the consequences of a pain-induced neurohumoral stress response, and whether they contribute to immunosuppression in stressed chronic pain patients. Copyright (c) 2008 S. Karger AG, Basel