The whole is greater than the sum of the parts: Recognising missed opportunities for an optimal response to the rapidly maturing TB-HIV co-epidemic in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite widely acknowledged WHO guidelines for the integration of TB and HIV services, heavily burdened countries have been slow to implement these and thus significant missed opportunities have arisen.</p> <p>Discussion</p> <p>The individual-centred, rights-based paradigm of the SA National AIDS Policy, remains dissonant with the compelling public-health approach of TB control. The existence of independent and disconnected TB and HIV services results in a wastage of scarce health resources, an increased burden on patients' time and finances, and ignores evidence of patients' preference for an integrated service. The current situation translates into a web of unacceptable, ongoing missed opportunities such as failure to maximize collaborative disease surveillance, VCT, adherence support, infection control, and positive prevention. TB services present a readily identifiable cohort for HIV provider-initiated testing. Integrating HAART and DOTS will promote efficient usage of health workers' time and a more navigable experience for patients, ultimately ensuring increased TB treatment completion rates and MDR-TB prevention. As direct observation evolves into a more supportive, empowering experience for patients, adherence to both TB drugs and HAART will be bolstered. Little attention has been paid to the transmission of TB within HIV services. Low cost infection control interventions include: triaging patients, scheduling new and follow-up patients separately; well-ventilated, sheltered waiting rooms; and the use of personal respirators by patients and staff. A more patient-centred approach to TB care may be able to recruit the active participation of TB patients in positive prevention efforts, including maximizing personal infection control, limiting exposure of social contacts to TB during the intensive phase of treatment, advocating isoniazid prophylaxis within the home and patient-centred education efforts to reduce overall transmission. Several model programmes demonstrated synergy, in which the impact of the "whole" or integrated response was greater than the sum of the non-integrated parts.</p> <p>Summary</p> <p>The full potential of an integrated TB-HIV service has not been fully harvested. Missed opportunities discount existing efforts in both programmes, will perpetuate the burden of disease, and prevent major gains in future interventions. This paper outlines simple, readily-implementable strategies to narrow the gap and reclaim existing missed opportunities.</p

Assessment of examiner leniency and stringency ('hawk-dove effect') in the MRCP(UK) clinical examination (PACES) using multi-facet Rasch modelling

BACKGROUND: A potential problem of clinical examinations is known as the hawk-dove problem, some examiners being more stringent and requiring a higher performance than other examiners who are more lenient. Although the problem has been known qualitatively for at least a century, we know of no previous statistical estimation of the size of the effect in a large-scale, high-stakes examination. Here we use FACETS to carry out a multi-facet Rasch modelling of the paired judgements made by examiners in the clinical examination (PACES) of MRCP(UK), where identical candidates were assessed in identical situations, allowing calculation of examiner stringency. METHODS: Data were analysed from the first nine diets of PACES, which were taken between June 2001 and March 2004 by 10,145 candidates. Each candidate was assessed by two examiners on each of seven separate tasks. with the candidates assessed by a total of 1,259 examiners, resulting in a total of 142,030 marks. Examiner demographics were described in terms of age, sex, ethnicity, and total number of candidates examined. RESULTS: FACETS suggested that about 87% of main effect variance was due to candidate differences, 1% due to station differences, and 12% due to differences between examiners in leniency-stringency. Multiple regression suggested that greater examiner stringency was associated with greater examiner experience and being from an ethnic minority. Male and female examiners showed no overall difference in stringency. Examination scores were adjusted for examiner stringency and it was shown that for the present pass mark, the outcome for 95.9% of candidates would be unchanged using adjusted marks, whereas 2.6% of candidates would have passed, even though they had failed on the basis of raw marks, and 1.5% of candidates would have failed, despite passing on the basis of raw marks. CONCLUSION: Examiners do differ in their leniency or stringency, and the effect can be estimated using Rasch modelling. The reasons for differences are not clear, but there are some demographic correlates, and the effects appear to be reliable across time. Account can be taken of differences, either by adjusting marks or, perhaps more effectively and more justifiably, by pairing high and low stringency examiners, so that raw marks can be used in the determination of pass and fail

Linear, Deterministic, and Order-Invariant Initialization Methods for the K-Means Clustering Algorithm

Over the past five decades, k-means has become the clustering algorithm of choice in many application domains primarily due to its simplicity, time/space efficiency, and invariance to the ordering of the data points. Unfortunately, the algorithm's sensitivity to the initial selection of the cluster centers remains to be its most serious drawback. Numerous initialization methods have been proposed to address this drawback. Many of these methods, however, have time complexity superlinear in the number of data points, which makes them impractical for large data sets. On the other hand, linear methods are often random and/or sensitive to the ordering of the data points. These methods are generally unreliable in that the quality of their results is unpredictable. Therefore, it is common practice to perform multiple runs of such methods and take the output of the run that produces the best results. Such a practice, however, greatly increases the computational requirements of the otherwise highly efficient k-means algorithm. In this chapter, we investigate the empirical performance of six linear, deterministic (non-random), and order-invariant k-means initialization methods on a large and diverse collection of data sets from the UCI Machine Learning Repository. The results demonstrate that two relatively unknown hierarchical initialization methods due to Su and Dy outperform the remaining four methods with respect to two objective effectiveness criteria. In addition, a recent method due to Erisoglu et al. performs surprisingly poorly.Comment: 21 pages, 2 figures, 5 tables, Partitional Clustering Algorithms (Springer, 2014). arXiv admin note: substantial text overlap with arXiv:1304.7465, arXiv:1209.196

Separate and combined analysis of successive dependent outcomes after breast-conservation surgery: recurrence, metastases, second cancer and death

<p>Abstract</p> <p>Background</p> <p>In the setting of recurrent events, research studies commonly count only the first occurrence of an outcome in a subject. However this approach does not correctly reflect the natural history of the disease. The objective is to jointly identify prognostic factors associated with locoregional recurrences (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer than breast and breast cancer death and to evaluate the correlation between these events.</p> <p>Methods</p> <p>Patients (n = 919) with a primary invasive breast cancer and treated in a cancer center in South-Western France with breast-conserving surgery from 1990 to 1994 and followed up to January 2006 were included. Several types of non-independent events could be observed for the same patient: a LRR, a contralateral breast cancer, DM, other primary cancer than breast and breast cancer death. Data were analyzed separately and together using a random-effects survival model.</p> <p>Results</p> <p>LRR represent the most frequent type of first failure (14.6%). The risk of any event is higher for young women (less than 40 years old) and in the first 10 years of follow-up after the surgery. In the combined analysis histological tumor size, grade, number of positive nodes, progesterone receptor status and treatment combination are prognostic factors of any event. The results show a significant dependence between these events with a successively increasing risk of a new event after the first and second event. The risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51-7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI: 2.23-6.96) as compared to patients who did not develop a first event.</p> <p>Conclusion</p> <p>We illustrated that the random effects survival model is a more satisfactory method to evaluate the natural history of a disease with multiple type of events.</p

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Predicting smear negative pulmonary tuberculosis with classification trees and logistic regression: a cross-sectional study

BACKGROUND: Smear negative pulmonary tuberculosis (SNPT) accounts for 30% of pulmonary tuberculosis cases reported yearly in Brazil. This study aimed to develop a prediction model for SNPT for outpatients in areas with scarce resources. METHODS: The study enrolled 551 patients with clinical-radiological suspicion of SNPT, in Rio de Janeiro, Brazil. The original data was divided into two equivalent samples for generation and validation of the prediction models. Symptoms, physical signs and chest X-rays were used for constructing logistic regression and classification and regression tree models. From the logistic regression, we generated a clinical and radiological prediction score. The area under the receiver operator characteristic curve, sensitivity, and specificity were used to evaluate the model's performance in both generation and validation samples. RESULTS: It was possible to generate predictive models for SNPT with sensitivity ranging from 64% to 71% and specificity ranging from 58% to 76%. CONCLUSION: The results suggest that those models might be useful as screening tools for estimating the risk of SNPT, optimizing the utilization of more expensive tests, and avoiding costs of unnecessary anti-tuberculosis treatment. Those models might be cost-effective tools in a health care network with hierarchical distribution of scarce resources

Patient-centred measurement in ophthalmology – a paradigm shift

Ophthalmologists and researchers in ophthalmology understand what a rapidly evolving field ophthalmology is, and that to conduct good research it is essential to use the latest and best methods. In outcomes research, one modern initiative has been to conduct holistic measurement of outcomes inclusive of the patient's point of view; patient-centred outcome. This, of course, means including a questionnaire. However, the irony of trying to improve outcomes research by being inclusive of many measures is that the researcher may not be expert in all measures used. Certainly, few people conducting outcomes research in ophthalmology would claim to be questionnaire experts. Most tend to be experts in their ophthalmic subspecialty and probably simply choose a popular questionnaire that appears to fit their needs and think little more about it. Perhaps, unlike our own field, we assume that the field of questionnaire research is relatively stable. This is far from the case. The measurement of patient-centred outcomes with questionnaires is a rapidly evolving field. Indeed, over the last few years a paradigm shift has occurred in patient-centred measurement

Transcript analysis of the extended hyp-operon in the cyanobacteria Nostoc sp. strain PCC 7120 and Nostoc punctiforme ATCC 29133

<p>Abstract</p> <p>Background</p> <p>Cyanobacteria harbor two [NiFe]-type hydrogenases consisting of a large and a small subunit, the Hup- and Hox-hydrogenase, respectively. Insertion of ligands and correct folding of nickel-iron hydrogenases require assistance of accessory maturation proteins (encoded by the <it>hyp</it>-genes). The intergenic region between the structural genes encoding the uptake hydrogenase (<it>hupSL</it>) and the accessory maturation proteins (<it>hyp </it>genes) in the cyanobacteria <it>Nostoc </it>PCC 7120 and <it>N. punctiforme </it>were analysed using molecular methods.</p> <p>Findings</p> <p>The five ORFs, located in between the uptake hydrogenase structural genes and the <it>hyp</it>-genes, can form a transcript with the <it>hyp</it>-genes. An identical genomic localization of these ORFs are found in other filamentous, N₂-fixing cyanobacterial strains. In <it>N. punctiforme </it>and <it>Nostoc </it>PCC 7120 the ORFs upstream of the <it>hyp</it>-genes showed similar transcript level profiles as <it>hupS </it>(hydrogenase structural gene), <it>nifD </it>(nitrogenase structural gene), <it>hypC </it>and <it>hypF </it>(accessory hydrogenase maturation genes) after nitrogen depletion. <it>In silico </it>analyzes showed that these ORFs in <it>N. punctiform</it>e harbor the same conserved regions as their homologues in <it>Nostoc </it>PCC 7120 and that they, like their homologues in <it>Nostoc </it>PCC 7120, can be transcribed together with the <it>hyp</it>-genes forming a larger extended <it>hyp-</it>operon. DNA binding studies showed interactions of the transcriptional regulators CalA and CalB to the promoter regions of the extended <it>hyp</it>-operon in <it>N. punctiforme </it>and <it>Nostoc </it>PCC 7120.</p> <p>Conclusions</p> <p>The five ORFs upstream of the <it>hyp</it>-genes in several filamentous N₂-fixing cyanobacteria have an identical genomic localization, in between the genes encoding the uptake hydrogenase and the maturation protein genes. In <it>N. punctiforme </it>and <it>Nostoc </it>PCC 7120 they are transcribed as one operon and may form transcripts together with the <it>hyp</it>-genes. The expression pattern of the five ORFs within the extended <it>hyp</it>-operon in both <it>Nostoc punctiforme </it>and <it>Nostoc </it>PCC 7120 is similar to the expression patterns of <it>hupS</it>, <it>nifD</it>, <it>hypF </it>and <it>hypC</it>. CalA, a known transcription factor, interacts with the promoter region between <it>hupSL </it>and the five ORFs in the extended <it>hyp</it>-operon in both <it>Nostoc </it>strains.</p