ClassTR: Classifying Within-Host Heterogeneity Based on Tandem Repeats with Application to Mycobacterium tuberculosis Infections.

Genomic tools have revealed genetically diverse pathogens within some hosts. Within-host pathogen diversity, which we refer to as "complex infection", is increasingly recognized as a determinant of treatment outcome for infections like tuberculosis. Complex infection arises through two mechanisms: within-host mutation (which results in clonal heterogeneity) and reinfection (which results in mixed infections). Estimates of the frequency of within-host mutation and reinfection in populations are critical for understanding the natural history of disease. These estimates influence projections of disease trends and effects of interventions. The genotyping technique MLVA (multiple loci variable-number tandem repeats analysis) can identify complex infections, but the current method to distinguish clonal heterogeneity from mixed infections is based on a rather simple rule. Here we describe ClassTR, a method which leverages MLVA information from isolates collected in a population to distinguish mixed infections from clonal heterogeneity. We formulate the resolution of complex infections into their constituent strains as an optimization problem, and show its NP-completeness. We solve it efficiently by using mixed integer linear programming and graph decomposition. Once the complex infections are resolved into their constituent strains, ClassTR probabilistically classifies isolates as clonally heterogeneous or mixed by using a model of tandem repeat evolution. We first compare ClassTR with the standard rule-based classification on 100 simulated datasets. ClassTR outperforms the standard method, improving classification accuracy from 48% to 80%. We then apply ClassTR to a sample of 436 strains collected from tuberculosis patients in a South African community, of which 92 had complex infections. We find that ClassTR assigns an alternate classification to 18 of the 92 complex infections, suggesting important differences in practice. By explicitly modeling tandem repeat evolution, ClassTR helps to improve our understanding of the mechanisms driving within-host diversity of pathogens like Mycobacterium tuberculosis

Образ города в записках Н. Дуровой “Кавалерист-девица. Происшествие в России”

Статья посвящена анализу записок Надежды Дуровой как путевому дневнику, в котором изображены многие города из разных стран в мирное и военное время. Автор статьи доказывает, что восприятие города зависит от исторического времени, от настроения мемуаристки, от физического состояния; акцентирует внимание на том, что в записках Дуровой нашли отражение обычаи и традиции жизни не только дворянства и высших кругов, но и простого народа, солдат, офицеров. В статье сделана попытка сравнить описание городов у нескольких украинских мемуаристов (Т. Шевченко, С. Капнист-Скалон), показать различный подход в изображении действительности у мемуаристов и писателей.Стаття присвячена аналізу записок Надії Дурової як дорожньому щоденнику, в якому змальовано багато міст з різних країн в мирний і військовий час. Автор статті доводить, що сприйняття міста залежить від історичного часу, від настрою мемуаристки, від фізичного стану; акцентується увага на тому, що в записках Дурової відображені звичаї і традиції життя не лише дворянства і вищих кругів, але й простого народу, солдатів, офіцерів. У статті зроблена спроба порівняти опис міс у декількох українських мемуаристів (Т. Шевченко, С. Капніст-Скалон), показати різний підхід в зображенні дійсності у мемуаристів і письменників.This article analyzes the notes of Nadezhda Durova as travel diary, which shows many cities from different countries in peacetime and wartime. The author of the article proves that the perception of the city depends on the historical time, the mood of the memoirist, on the physical state; focuses on the fact that the notes of Durova reflect customs and traditions of life not only the nobility and the higher circles, but also ordinary people, soldiers, officers . An attempt to compare description of cities by another Ukrainian memorialists (T. of Shevchenko, P. Kapnist-Skalon) is done in the article. А different approach in the image of reality in memoirists and writers is also shown

Sink or link? The bacterial role in benthic carbon cycling in the Arabian Sea's oxygen minimum zone

The bacterial loop, the consumption of dissolved organic matter (DOM) by bacteria and subsequent transfer of bacterial carbon to higher trophic levels, plays a prominent role in pelagic food webs. However, its role in sedimentary ecosystems is not well documented. Here we present the results of isotope tracer experiments performed under in situ oxygen conditions in sediments from inside and outside the Arabian Sea's oxygen minimum zone (OMZ) to study the importance of the microbial loop in this setting. Particulate organic matter, added as phytodetritus, was processed by bacteria, protozoa and metazoans, while dissolved organic matter was processed only by bacteria and there was very little, if any, transfer to higher trophic levels within the 7 day experimental period. This lack of significant transfer of bacterial-derived carbon to metazoan consumers indicates that the bacterial loop is rather inefficient, in sediments both inside and outside the OMZ. Moreover, metazoans directly consumed labile particulate organic matter resources and thus competed with bacteria for phytodetritus

The Radio Relics and Halo of El Gordo, a Massive z=0.870z=0.870 Cluster Merger

We present 610 MHz and 2.1 GHz imaging of the massive SZE-selected z=0.870 cluster merger ACT-CL J0102-4915 (El Gordo), obtained with the GMRT and the ATCA, respectively. We detect two complexes of radio relics separated by 3.4' (1.6 Mpc) along the system's NW-to-SE collision axis that have high integrated polarizations (33%) and steep spectral indices, consistent with creation via Fermi acceleration by shocks in the ICM. From the spectral index of the relics, we compute a Mach number of 2.5^{+0.7}_{-0.3} and shock speed of 2500^{+400}_{-300} km/s. With our ATCA data, we compute the Faraday depth across the NW relic and find a mean value of 11 rad/m^2 and standard deviation of 6 rad/m^2. With the integrated line-of-sight gas density derived from new Chandra observations, our Faraday depth measurement implies B_parallel~0.01 \mu G in the cluster outskirts. The extremely narrow shock widths in the relics (<23 kpc) prevent us from placing a meaningful constraint on |B| using cooling time arguments. In addition to the relics, we detect a large (1.1 Mpc radius), powerful (log L_1.4[W/Hz]= 25.66+-0.12) radio halo with a Bullet-like morphology. The spectral-index map of the halo shows the synchrotron spectrum is flattest near the relics, along the collision axis, and in regions of high T_gas, all locations associated with recent energy injection. The spatial and spectral correlation between the halo emission and cluster X-ray properties supports primary-electron processes like turbulent reacceleration as the halo production mechanism. The halo's integrated 610 MHz to 2.1 GHz spectral index is 1.2+-0.1, consistent with the cluster's high T_gas in view of previously established global scaling relations. El Gordo is the highest-redshift cluster known to host a radio halo and/or radio relics, and provides new constraints on the non-thermal physics in clusters at z>0.6. [abridged]Comment: 22 pages, 19 figures, accepted in Ap

The Santa Fe Light Cone Simulation Project: II. The Prospects for Direct Detection of the WHIM with SZE Surveys

Detection of the Warm-Hot Intergalactic Medium (WHIM) using Sunyaev-Zeldovich effect (SZE) surveys is an intriguing possibility, and one that may allow observers to quantify the amount of "missing baryons" in the WHIM phase. We estimate the necessary sensitivity for detecting low density WHIM gas with the South Pole Telescope (SPT) and Planck Surveyor for a synthetic 100 square degree sky survey. This survey is generated from a very large, high dynamic range adaptive mesh refinement cosmological simulation performed with the Enzo code. We find that for a modest increase in the SPT survey sensitivity (a factor of 2-4), the WHIM gas makes a detectable contribution to the integrated sky signal. For a Planck-like satellite, similar detections are possible with a more significant increase in sensitivity (a factor of 8-10). We point out that for the WHIM gas, the kinematic SZE signal can sometimes dominate the thermal SZE where the thermal SZE decrement is maximal (150 GHz), and that using the combination of the two increases the chance of WHIM detection using SZE surveys. However, we find no evidence of unique features in the thermal SZE angular power spectrum that may aid in its detection. Interestingly, there are differences in the power spectrum of the kinematic SZE, which may not allow us to detect the WHIM directly, but could be an important contaminant in cosmological analyses of the kSZE-derived velocity field. Corrections derived from numerical simulations may be necessary to account for this contamination.Comment: 9 pages, submitted to Astrophysical Journa

Antiretroviral Therapy outcomes among adolescents and youth in rural Zimbabwe

Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10-30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10-15 (young adolescents) 15.1-19 years (adolescents), 19.1-24 years (young adults) and 24.1-29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17-4.35). Young adults and adolescents had a 2-3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62-4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults

Lie symmetries for equations in conformal geometries

We seek exact solutions to the Einstein field equations which arise when two spacetime geometries are conformally related. Whilst this is a simple method to generate new solutions to the field equations, very few such examples have been found in practice. We use the method of Lie analysis of differential equations to obtain new group invariant solutions to conformally related Petrov type D spacetimes. Four cases arise depending on the nature of the Lie symmetry generator. In three cases we are in a position to solve the master field equation in terms of elementary functions. In the fourth case special solutions in terms of Bessel functions are obtained. These solutions contain known models as special cases.Comment: 19 pages, To appear in J. Phys.

The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure