Clinical Predictors of Drug Resistance and Mortality Among Tuberculosis Patients in a Rural South African Hospital: A Case-Control Study

The recent discovery of a high prevalence of multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in rural South Africa, where HIV is rampant, has provoked alarms about the future of tuberculosis control in the region. Little is known about the clinical manifestations of MDR-TB in general, and XDR-TB in particular, in the high HIV prevalence settings of Sub-Saharan Africa. We performed a retrospective, case-control study of patients diagnosed with tuberculosis at a rural hospital in KwaZulu Natal, South Africa, where large numbers of MDR-TB and XDRTB cases have been identified. All MDR-TB and XDR-TB patients who began treatment for TB between June 1, 2005 and August 31, 2006 and whose charts were available were included in the study. A comparison group of patients without resistance to both isoniazid and rifampicin (non- MDR-TB), matched 1:1 with the size of the MDR-TB and XDR-TB groups, was created. Clinical and laboratory data were obtained through review of hospital records, clinic registers, and the laboratory system. We compared clinical characteristics to identify risk factors for MDRTB, XDR-TB, and mortality. Bivariate and multivariate analyses were performed. A total of 170 patients were enrolled in the study: 52 MDR-TB, 61 XDR-TB and 57 non-MDR-TB. Greater than 75% of patients from all groups were tested for HIV; HIV prevalence among those tested was 94% in the non-MDR group, 93% in the MDR group, and 100% in the XDR-TB group (P=1.000 for MDR versus non-MDR; p=0.089 for XDR versus non-MDR). Forty percent of MDR-TB patients and 57% of XDR-TB patients had no previous history of TB treatment, strongly suggesting transmitted drug resistance. Significant associations and risk factors for MDR-TB and XDR-TB in bivariate analysis included positive sputum smear (P=0.015, P=0.005), TB treatment in the past year (P\u3c0.0001, P\u3c0.001), and hospitalization in the past two years (P=0.007, P=0.004). In multivariate logistic regression, positive sputum smear remained a significant risk factor for XDR-TB (adjusted odds ratio (AOR) 2.79, 1.20-6.47), and TB treatment in the past year remained a risk factor for both MDR-TB and XDR-TB (AOR 8.33, 95% CI 1.64-42.33; AOR 7.19, 95% CI 1.35-38.17). Mortality for the non-MDR, MDR and XDR groups was 36.8%, 73.1% and 85.3%, respectively (P= 0.0001 for MDR versus non MDR; P\u3c0.0001 for XDR versus non-MDR; P=0.109 for XDR versus MDR); median survival from TB diagnosis was 199 days, 103 days, and 92 days, respectively (P\u3c0.001). In Cox Proportional Hazards model, positive sputum smear (P=0.003), MDR-TB (P=0.028), XDR-TB (P=0.002), and CD4 cell count less than 200 cells/mm3 (P=0.037) were significant risk factors for mortality. Forty of the 170 patients had sputum isolates with differing resistance patterns, and 18 moved from a lower to a higher resistance category; this increasing drug resistance appeared to be more likely the result of super-infection than amplification. A significant proportion of MDR-TB and all XDR-TB appear to be due to primary resistance, with nosocomial transmission playing a critical role. MDR-TB and XDR-TB carry extraordinarily high mortality rates in this setting; previous hospitalization, previous TB treatment, positive sputum smear and low CD4 count may be used to target drug susceptibility testing for patients at high risk of drug resistant TB and mortality

Complexity in Mathematical Models of Public Health Policies: A Guide for Consumers of Models

Sanjay Basu and colleagues explain how models are increasingly used to inform public health policy yet readers may struggle to evaluate the quality of models. All models require simplifying assumptions, and there are tradeoffs between creating models that are more “realistic” versus those that are grounded in more solid data. Indeed, complex models are not necessarily more accurate or reliable simply because they can more easily fit real-world data than simpler models can. Please see later in the article for the Editors' Summar

Deploying 87 Satellites in One Launch: Design trades completed for the 2015 SHERPA flight hardware

Launch remains an obstacle for small satellites, which are often limited to small platforms, aft bulkheads, and accommodations for a single P-Pod. While launch vehicles have expanded the space available to small satellites, the largest number of satellites deployed in a single launch stands at thirty-seven. Spaceflight has secured a single launch opportunity in 2015 for no less than 87 small satellites. The ability to support so many satellites stems from tactical design decisions. This paper focuses on the design trades for the payload adapters developed for the 2015 SHERPA launch. Three unique payload adapters were designed to interface to the Moog ESPA Grande ring, the core of the SHERPA spacecraft. Each is an aluminum plate that interfaces to the 24” bolt-hole pattern on the five ESPA Grande ports. For these adapters, a balance was struck between designing to the unique payload in the flight configuration and developing a reusable system. The paper discusses the initial design trades regarding the adapter plate capabilities and how these trades have affected the plates’ utility on later SHERPA missions

Bathymetric terrain model of the Atlantic margin for marine geological investigations.

Bathymetric terrain models of seafloor morphology are an important component of marine geological investigations. Advances in acquisition and processing technologies of bathymetric data have facilitated the creation of high-resolution bathymetric surfaces that approach the resolution of similar surfaces available for onshore investigations. These bathymetric terrain models provide a detailed representation of the Earth’s subaqueous surface and, when combined with other geophysical and geological datasets, allow for interpretation of modern and ancient geological processes. The purpose of the bathymetric terrain model presented in this report is to provide a high-quality bathymetric surface of the Atlantic margin of the United States that can be used to augment current and future marine geological investigations. The input data for this bathymetric terrain model, covering almost 305,000 square kilometers, were acquired by several sources, including the U.S. Geological Survey, the National Oceanic and Atmospheric Administration National Geophysical Data Center and the Ocean Exploration Program, the University of New Hampshire, and the Woods Hole Oceanographic Institution. These data have been edited using hydrographic data processing software to maximize the quality, usability, and cartographic presentation of the combined terrain model

Automating biomedical data science through tree-based pipeline optimization

Over the past decade, data science and machine learning has grown from a mysterious art form to a staple tool across a variety of fields in academia, business, and government. In this paper, we introduce the concept of tree-based pipeline optimization for automating one of the most tedious parts of machine learning---pipeline design. We implement a Tree-based Pipeline Optimization Tool (TPOT) and demonstrate its effectiveness on a series of simulated and real-world genetic data sets. In particular, we show that TPOT can build machine learning pipelines that achieve competitive classification accuracy and discover novel pipeline operators---such as synthetic feature constructors---that significantly improve classification accuracy on these data sets. We also highlight the current challenges to pipeline optimization, such as the tendency to produce pipelines that overfit the data, and suggest future research paths to overcome these challenges. As such, this work represents an early step toward fully automating machine learning pipeline design.Comment: 16 pages, 5 figures, to appear in EvoBIO 2016 proceeding

Study of the decay B+ → K+ π0 at LHCb and mechanical development for the design of the Upstream Tracker

The LHCb experiment at the Large Hadron Collider (LHC) is designed to measure the properties of particles containing charm (c) and bottom (b) quarks. This dissertation documents two major studies I have completed, one analyzing data collected by the LHCb detector, and another contributing to the design and development of an extensive upgrade to the detector. The pattern of CP asymmetry measurements of the B → K π family of decays deviates from expectations derived from the SM, a contradiction known as the “K π puzzle.” The present size of the experimental errors are such that more precise measurements in the B+ → K+ π0 decay channel are especially important. An analysis of the B+ → K+ π0 decay using data collected during Run 1 is performed. Despite low reconstruction and trigger efficiencies and enormous combinatorial backgrounds, a signal is found with a statistical significance of 3.7σ. This achievement has led to the creation of a dedicated B+ → K+ π0 trigger, and has inspired the creation of a number of dedicated triggers for decay modes with similar topologies. A preliminary analysis of data collected during Run 2 demonstrates that the new trigger is a major success, with excellent prospects for making the world’s best measurements in the B+ → K+ π0 decay channel using the entire Run 2 data set. Run 2 of the LHC will conclude at the end of 2018, and will be followed by Run 3, scheduled to begin in early 2021. In the interim, the LHCb detector will be upgraded to be read-out in real-time at 40 MHz, and to withstand the radiation damage associated with collecting 50 fb^(−1) of integrated luminosity by the conclusion of Run 4. A key part of this upgrade is the design and construction of a new silicon-strip tracking detector—the upstream tracker (UT). Regions at the periphery of the UT suffer from severe electrical and mechanical constraints, making a high-fidelity CAD model a critical element of the design process. The result is a mechanical integration solution that is entirely non-trivial, and which has had significant influences on the UT design. This solution and the constraints that influence it are shown in detail

Diagnosis of Influenza from Lower Respiratory Tract Sampling after Negative Upper Respiratory Tract Sampling

In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis

Geomorphic characterization of the U.S. Atlantic continental margin

This paper is not subject to U.S. copyright. The definitive version was published in Marine Geology 338 (2013): 46–63, doi:10.1016/j.margeo.2012.12.008.The increasing volume of multibeam bathymetry data collected along continental margins is providing new opportunities to study the feedbacks between sedimentary and oceanographic processes and seafloor morphology. Attempts to develop simple guidelines that describe the relationships between form and process often overlook the importance of inherited physiography in slope depositional systems. Here, we use multibeam bathymetry data and seismic reflection profiles spanning the U.S. Atlantic outer continental shelf, slope and rise from Cape Hatteras to New England to quantify the broad-scale, across-margin morphological variation. Morphometric analyses suggest the margin can be divided into four basic categories that roughly align with Quaternary sedimentary provinces. Within each category, Quaternary sedimentary processes exerted heavy modification of submarine canyons, landslide complexes and the broad-scale morphology of the continental rise, but they appear to have preserved much of the pre-Quaternary, across-margin shape of the continental slope. Without detailed constraints on the substrate structure, first-order morphological categorization the U.S. Atlantic margin does not provide a reliable framework for predicting relationships between form and process.This work was funded by the USGS Mendenhall Postdoctoral Fellowship Program and the U.S. Nuclear Regulatory Commission