Nutrition, Diabetes and Tuberculosis in the Epidemiological Transition

BACKGROUND: Diabetes prevalence and body mass index reflect the nutritional profile of populations but have opposing effects on tuberculosis risk. Interactions between diabetes and BMI could help or hinder TB control in growing, aging, urbanizing populations. METHODS AND FINDINGS: We compiled data describing temporal changes in BMI, diabetes prevalence and population age structure in rural and urban areas for men and women in countries with high (India) and low (Rep. Korea) TB burdens. Using published data on the risks of TB associated with these factors, we calculated expected changes in TB incidence between 1998 and 2008. In India, TB incidence cases would have increased (28% from 1.7 m to 2.1 m) faster than population size (22%) because of adverse effects of aging, urbanization, changing BMI and rising diabetes prevalence, generating an increase in TB incidence per capita of 5.5% in 10 years. In India, general nutritional improvements were offset by a fall in BMI among the majority of men who live in rural areas. The growing prevalence of diabetes in India increased the annual number of TB cases in people with diabetes by 46% between 1998 and 2008. In Korea, by contrast, the number of TB cases increased more slowly (6.1% from 40,200 to 42,800) than population size (14%) because of positive effects of urbanization, increasing BMI and falling diabetes prevalence. Consequently, TB incidence per capita fell by 7.8% in 10 years. Rapid population aging was the most significant adverse effect in Korea. CONCLUSIONS: Nutritional and demographic changes had stronger adverse effects on TB in high-incidence India than in lower-incidence Korea. The unfavourable effects in both countries can be overcome by early drug treatment but, if left unchecked, could lead to an accelerating rise in TB incidence. The prevention and management of risk factors for TB would reinforce TB control by chemotherapy

The pulsating hot subdwarf Balloon 090100001: results of the 2005 multisite campaign

We present the results of a multisite photometric campaign on the pulsating sdB star Balloon 090100001. The star is one of the two known hybrid hot subdwarfs with both long- and short-period oscillations. The campaign involved eight telescopes with three obtaining UBVR data, four B-band data, and one Stromgren uvby photometry. The campaign covered 48 nights, providing a temporal resolution of 0.36microHz with a detection threshold of about 0.2mmag in B-filter data. Balloon 090100001 has the richest pulsation spectrum of any known pulsating subdwarf B star and our analysis detected 114 frequencies including 97 independent and 17 combination ones. The strongest mode (f_1) in the 2.8mHz region is most likely radial while the remaining ones in this region form two nearly symmetric multiplets: a triplet and quintuplet, attributed to rotationally split \ell=1 and 2 modes, respectively. We find clear increases of splitting in both multiplets between the 2004 and 2005 observing campaigns, amounting to 15% on average. The observed splittings imply that the rotational rate in Bal09 depends on stellar latitude and is the fastest on the equator. We use a small grid of models to constrain the main mode (f_1), which most likely represents the radial fundamental pulsation. The groups of p-mode frequencies appear to lie in the vicinity of consecutive radial overtones, up to the third one. Despite the large number of g-mode frequencies observed, we failed to identify them, most likely because of the disruption of asymptotic behaviour by mode trapping. The observed frequencies were not, however, fully exploited in terms of seismic analysis which should be done in the future with a larger grid of reliable evolutionary models of hot subdwarfs.Comment: accepted for publication in MNRA

UWISH2 -- The UKIRT Widefield Infrared Survey for H2

We present the goals and preliminary results of an unbiased, near-infrared, narrow-band imaging survey of the First Galactic Quadrant (10deg<l<65deg ; -1.3deg<b<+1.3deg). This area includes most of the Giant Molecular Clouds and massive star forming regions in the northern hemisphere. The survey is centred on the 1-0S(1) ro-vibrational line of H2, a proven tracer of hot, dense molecular gas in star-forming regions, around evolved stars, and in supernova remnants. The observations complement existing and upcoming photometric surveys (Spitzer-GLIMPSE, UKIDSS-GPS, JCMT-JPS, AKARI, Herschel Hi-GAL, etc.), though we probe a dynamically active component of star formation not covered by these broad-band surveys. Our narrow-band survey is currently more than 60% complete. The median seeing in our images is 0.73arcsec. The images have a 5sigma detection limit of point sources of K=18mag and the surface brightness limit is 10^-19Wm^-2arcsec^-2 when averaged over our typical seeing. Jets and outflows from both low and high mass Young Stellar Objects are revealed, as are new Planetary Nebulae and - via a comparison with earlier K-band observations acquired as part of the UKIDSS GPS - numerous variable stars. With their superior spatial resolution, the UWISH2 data also have the potential to reveal the true nature of many of the Extended Green Objects found in the GLIMPSE survey.Comment: 14pages, 8figures, 2tables, accepted for publication by MNRAS, a version with higher resolution figures can be found at http://astro.kent.ac.uk/~df

Worms take to the slo lane: a perspective on the mode of action of emodepside

The cyclo-octapdepsipeptide anthelmintic emodepside exerts a profound paralysis on parasitic and free-living nematodes. The neuromuscular junction is a significant determinant of this effect. Pharmacological and electrophysiological analyses in the parasitic nematode Ascaris suum have resolved that emodepside elicits a hyperpolarisation of body wall muscle, which is dependent on extracellular calcium and the efflux of potassium ions. The molecular basis for emodepside’s action has been investigated in forward genetic screens in the free-living nematode Caenorhabditis elegans. Two screens for emodepside resistance, totalling 20,000 genomes, identified several mutants of slo-1, which encodes a calcium-activated potassium channel homologous to mammalian BK channels. Slo-1 null mutants are more than 1000-fold less sensitive to emodepside than wild-type C. elegans and tissue-specific expression studies show emodepside acts on SLO-1 in neurons regulating feeding and motility as well as acting on SLO-1 in body wall muscle. These genetic data, combined with physiological measurements in C. elegans and the earlier physiological analyses on A. suum, define a pivotal role for SLO-1 in the mode of action of emodepside. Additional signalling pathways have emerged as determinants of emodepside’s mode of action through biochemical and hypothesis-driven approaches. Mutant analyses of these pathways suggest a modulatory role for each of them in emodepside’s mode of action; however, they impart much more modest changes in the sensitivity to emodepside than mutations in slo-1. Taken together these studies identify SLO-1 as the major determinant of emodepside’s anthelmintic activity. Structural information on the BK channels has advanced significantly in the last 2 years. Therefore, we rationalise this possibility by suggesting a model that speculates on the nature of the emodepside pharmacophore within the calcium-activated potassium channels

Antiretroviral Therapy Outcomes in HIV-Infected Children after Adjusting Protease Inhibitor Dosing during Tuberculosis Treatment

Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6-24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB. Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons. Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation

Josephson Coupling and Fiske Dynamics in Ferromagnetic Tunnel Junctions

We report on the fabrication of Nb/AlO_x/Pd_{0.82}Ni_{0.18}/Nb superconductor/insulator/ferromagnetic metal/superconductor (SIFS) Josephson junctions with high critical current densities, large normal resistance times area products, high quality factors, and very good spatial uniformity. For these junctions a transition from 0- to \pi-coupling is observed for a thickness d_F ~ 6 nm of the ferromagnetic Pd_{0.82}Ni_{0.18} interlayer. The magnetic field dependence of the \pi-coupled junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd_{0.82}Ni_{0.18} has an out-of-plane anisotropy and large saturation magnetization, indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes provides information on the junction quality factor and the relevant damping mechanisms up to about 400 GHz. Whereas losses due to quasiparticle tunneling dominate at low frequencies, the damping is dominated by the finite surface resistance of the junction electrodes at high frequencies. High quality factors of up to 30 around 200 GHz have been achieved. Our analysis shows that the fabricated junctions are promising for applications in superconducting quantum circuits or quantum tunneling experiments.Comment: 15 pages, 9 figure

High-Resolution Melting Analysis for the Rapid Detection of Fluoroquinolone and Streptomycin Resistance in Mycobacterium tuberculosis

published_or_final_versio

Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: A molecular epidemiological study

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the molecular characteristics of isoniazid resistant <it>Mycobacterium tuberculosis </it>(MTB), as well as its contribution to the dissemination of multi-drug resistant TB (MDR-TB) in rural areas of eastern China.</p> <p>Methods</p> <p>A population-based epidemiological study was conducted in two rural counties of eastern China from 2004 to 2005. In total, 131 isoniazid resistant MTB isolates were molecularly characterized by DNA sequencing and genotyped by IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotyping.</p> <p>Results</p> <p>The <it>katG</it>315Thr mutation was observed in 74 of 131 isoniazid resistant isolates and more likely to be MDR-TB (48.6%) and have mutations in <it>rpoB </it>gene (47.3%). Spoligotyping identified 80.2% of isoniazid resistant MTB isolates as belonging to the Beijing family. Cluster analysis by genotyping based on IS<it>6110 </it>RFLP, showed that 48.1% isoniazid resistant isolates were grouped into 26 clusters and <it>katG</it>315Thr mutants had a significantly higher clustering proportion compared to those with <it>katG </it>wild type (73%.vs.18%; OR, 12.70; 95%CI, 6.357-14.80). Thirty-one of the 53 MDR-TB isolates were observed in 19 clusters. Of these clusters, isoniazid resistance in MDR-TB isolates was all due to the <it>katG</it>315Thr mutation; 18 clusters also contained mono-isoniazid resistant and other isoniazid resistant isolates.</p> <p>Conclusions</p> <p>These results highlighted that isoniazid resistant MTB especially with <it>katG</it>315Thr is likely to be clustered in a community, develop extra resistance to rifampicin and become MDR-TB in Chinese rural settings.</p

Extragalactic millimeter-wave sources in South Pole Telescope survey data: source counts, catalog, and statistics for an 87 square-degree field

We report the results of an 87 square-degree point-source survey centered at R.A. 5h30m, decl. -55 deg. taken with the South Pole Telescope (SPT) at 1.4 and 2.0 mm wavelengths with arc-minute resolution and milli-Jansky depth. Based on the ratio of flux in the two bands, we separate the detected sources into two populations, one consistent with synchrotron emission from active galactic nuclei (AGN) and one consistent with thermal emission from dust. We present source counts for each population from 11 to 640 mJy at 1.4 mm and from 4.4 to 800 mJy at 2.0 mm. The 2.0 mm counts are dominated by synchrotron-dominated sources across our reported flux range; the 1.4 mm counts are dominated by synchroton-dominated sources above ~15 mJy and by dust-dominated sources below that flux level. We detect 141 synchrotron-dominated sources and 47 dust-dominated sources at S/N > 4.5 in at least one band. All of the most significantly detected members of the synchrotron-dominated population are associated with sources in previously published radio catalogs. Some of the dust-dominated sources are associated with nearby (z << 1) galaxies whose dust emission is also detected by the Infrared Astronomy Satellite (IRAS). However, most of the bright, dust-dominated sources have no counterparts in any existing catalogs. We argue that these sources represent the rarest and brightest members of the population commonly referred to as sub-millimeter galaxies (SMGs). Because these sources are selected at longer wavelengths than in typical SMG surveys, they are expected to have a higher mean redshift distribution and may provide a new window on galaxy formation in the early universe.Comment: 35 emulateapj pages, 12 figures, 5 table