Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses.

BackgroundClinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment.MethodsWe prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection.ResultsOver a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L).ConclusionJudged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses

Tracking Rural Health Facility Financial Data in Resource-Limited Settings: A Case Study from Rwanda

Chunling Lu and colleagues describe a project for tracking health center financial data in two rural districts of Rwanda, which could be adapted for other low- or middle-income countries. Please see later in the article for the Editors' Summar

The role of the emergency department in the management of acute heart failure: an international perspective on education and research

Emergency departments are a major entry point for the initial management of acute heart failure (AHF) patients throughout the world. The initial diagnosis, management and disposition - the decision to admit or discharge - of AHF patients in the emergency department has significant downstream implications. Misdiagnosis, under or overtreatment, or inappropriate admission may place patients at increased risk for adverse events, and add costs to the healthcare system. Despite the critical importance of initial management, data are sparse regarding the impact of early AHF treatment delivered in the emergency department compared to inpatient or chronic heart failure management. Unfortunately, outcomes remain poor, with nearly a third of patients dying or re-hospitalised within 3 months post-discharge. In the absence of robust research evidence, consensus is an important source of guidance for AHF care. Thus, we convened an international group of practising emergency physicians, cardiologists and advanced practice nurses with the following goals to improve outcomes for AHF patients who present to the emergency department or other acute care setting through: (a) a better understanding of the pathophysiology, presentation and management of the initial phase of AHF care; (b) improving initial management by addressing knowledge gaps between best practices and current practice through education and research; and (c) to establish a framework for future emergency department-based international education and research

Editor's Choice-The role of the emergency department in the management of acute heart failure : An international perspective on education and research

Emergency departments are a major entry point for the initial management of acute heart failure (AHF) patients throughout the world. The initial diagnosis, management and disposition - the decision to admit or discharge - of AHF patients in the emergency department has significant downstream implications. Misdiagnosis, under or overtreatment, or inappropriate admission may place patients at increased risk for adverse events, and add costs to the healthcare system. Despite the critical importance of initial management, data are sparse regarding the impact of early AHF treatment delivered in the emergency department compared to inpatient or chronic heart failure management. Unfortunately, outcomes remain poor, with nearly a third of patients dying or re-hospitalised within 3 months post-discharge. In the absence of robust research evidence, consensus is an important source of guidance for AHF care. Thus, we convened an international group of practising emergency physicians, cardiologists and advanced practice nurses with the following goals to improve outcomes for AHF patients who present to the emergency department or other acute care setting through: (a) a better understanding of the pathophysiology, presentation and management of the initial phase of AHF care; (b) improving initial management by addressing knowledge gaps between best practices and current practice through education and research; and (c) to establish a framework for future emergency department-based international education and research.Peer reviewe

Rapidly detecting disorder in rhythmic biological signals: A spectral entropy measure to identify cardiac arrhythmias

We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This spectral entropy measure is motivated by characteristic differences in the spectra of beat timings during the three rhythms. We plot patient data derived from ten-beat windows on a "disorder map" and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classification of periods of atrial fibrillation from the time series of patients' beats. When the algorithm is set to identify abnormal rhythms within 6 s it agrees with 85.7% of the annotations of professional rhythm assessors; for a response time of 30 s this becomes 89.5%, and with 60 s it is 90.3%. The algorithm provides a rapid way to detect atrial fibrillation, demonstrating usable response times as low as 6 s. Measures of disorder in the frequency domain have practical significance in a range of biological signals: the techniques described in this paper have potential application for the rapid identification of disorder in other rhythmic signals.Comment: 11 page

Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation Pattern

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In “selective” sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the “selective” fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both ‘poly-scGal’ and ‘null-scGal’ lines survived poorly relative to PpapJ-sympatric L. major FV1 and other ‘mono-scGal’ lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing ‘null-scGal’-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a ‘PpapJ-optimal’ scGal-LPG PAMP. Unexpectedly, these “L. major FV1-cloaked” L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific ‘mono-scGal’ pattern. However, failure of ‘mono-scGal’ L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is “selective” or “permissive”, with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania

Minimum Technical Data Elements for Liquid Biopsy Data Submitted to Public Databases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154656/1/cpt1747.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154656/2/cpt1747-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154656/3/cpt1747_am.pd

Rapid Effects of Hearing Song on Catecholaminergic Activity in the Songbird Auditory Pathway

Catecholaminergic (CA) neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH), a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good