Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials?

Compared with smear microscopy, the Xpert MTB/RIF assay (Xpert), with superior accuracy and capacity to diagnose rifampicin resistance, has advanced TB diagnostic capability. However, recent trials of Xpert impact have not demonstrated reductions in patient morbidity and mortality. We conducted a narrative review of Xpert impact trials to summarize which patient-relevant outcomes Xpert has improved and explore reasons for no observed morbidity or mortality reductions. We searched PubMed, Google Scholar, Cochrane Library and Embase and identified eight trials meeting inclusion criteria: three individually randomized, three cluster-randomized, and two pre-post trials. In six trials Xpert increased diagnostic yield of bacteriologically-confirmed TB from sputa and in four trials Xpert shortened time to TB treatment. However, all-cause mortality was similar between arms in all six trials reporting this outcome, and the only trial to assess Xpert impact on morbidity reported no impact. Trial characteristics that might explain lack of observed impact on morbidity and mortality include: higher rates of empiric TB treatment in microscopy compared with Xpert arms, enrollment of study populations not comprised exclusively of populations most likely to benefit from Xpert, and health system weaknesses. So far as equipoise exists, future trials that address past limitations are needed to inform Xpert use in resource-limited settings

Early empirical TB treatment in HIV-positive patients admitted to hospital in South Africa: an observational cohort study

Background: Empirical TB treatment in HIV-positive inpatients is common and may undermine the impact of new diagnostics. We sought to describe empirical TB treatment and compare characteristics and outcomes with patients treated for TB after screening. Methods: Retrospective observational cohort study of HIV-positive inpatients treated empirically for TB prior to TB screening. Data on clinical characteristics, investigations and outcomes were collected from medical records. Comparison cohorts with microbiologically-confirmed or empirical TB treatment after TB screening with Xpert MTB/RIF and urine lipoarabinomannan assays were taken from South African STAMP trial site. In-hospital mortality was compared using a competing-risks analysis adjusted for age, sex and CD4 count. Results: Between January 2016 and September 2017, 100 patients excluded from STAMP were treated for TB empirically prior to TB screening. After enrolment in STAMP and TB screening, 240/1177 (20.4%) patients received TB treatment, of whom 123 had positive TB tests and 117 were treated empirically. Characteristics were similar among early empirically treated patients and those treated after TB screening. 50% of early empirical TB treatment was based on radiological investigations, 22% on cerebrospinal or pleural fluid testing, and 28% on clinical features alone. Only 11/100 empirically treated patients had subsequent microbiological confirmation. In-hospital mortality was lower in patients with microbiologically-confirmed TB compared to those treated empirically (adjusted sub-distribution HR 0.5, 95% CI 0.3-0.9). Conclusions: Empirical TB treatment remains common in severely ill HIV-positive inpatients. These patients may benefit from TB screening using existing rapid diagnostics, both to improve confirmation of TB disease and reduce over-treatment for TB

Ocean processes at the Antarctic continental slope

The Antarctic continental shelves and slopes occupy relatively small areas, but, nevertheless, are important for global climate, biogeochemical cycling and ecosystem functioning. Processes of water mass transformation through sea ice formation/melting and ocean-atmosphere interaction are key to the formation of deep and bottom waters as well as determining the heat flux beneath ice shelves. Climate models, however, struggle to capture these physical processes and are unable to reproduce water mass properties of the region. Dynamics at the continental slope are key for correctly modelling climate, yet their small spatial scale presents challenges both for ocean modelling and for observational studies. Cross-slope exchange processes are also vital for the flux of nutrients such as iron from the continental shelf into the mixed layer of the Southern Ocean. An © 2014 The Authors

Yield stress, heterogeneities and activated processes in soft glassy materials

The rheological behavior of soft glassy materials basically results from the interplay between shearing forces and an intrinsic slow dynamics. This competition can be described by a microscopic theory, which can be viewed as a nonequilibrium schematic mode-coupling theory. This statistical mechanics approach to rheology results in a series of detailed theoretical predictions, some of which still awaiting for their experimental verification. We present new, preliminary, results about the description of yield stress, flow heterogeneities and activated processes within this theoretical framework.Comment: Paper presented at "III Workshop on Non Equilibrium Phenomena...", Pisa 22-27 Sep. 200

Wigs, disguises and child's play : solidarity in teacher education

It is generally acknowledged that much contemporary education takes place within a dominant audit culture, in which accountability becomes a powerful driver of educational practices. In this culture both pupils and teachers risk being configured as a means to an assessment and target-driven end: pupils are schooled within a particular paradigm of education. The article discusses some ethical issues raised by such schooling, particularly the tensions arising for teachers, and by implication, teacher educators who prepare and support teachers for work in situations where vocational aims and beliefs may be in in conflict with instrumentalist aims. The article offers De Certeau’s concept of ‘la perruque’ to suggest an opening to playful engagement for human ends in education, as a way of contending with and managing the tensions generated. I use the concept to recover a concept of solidarity for teacher educators and teachers to enable ethical teaching in difficult times

Advanced InSAR atmospheric correction: MERIS/MODIS combination and stacked water vapour models

A major source of error for repeat-pass Interferometric Synthetic Aperture Radar (InSAR) is the phase delay in radio signal propagation through the atmosphere (especially the part due to tropospheric water vapour). Based on experience with the Global Positioning System (GPS)/Moderate Resolution Imaging Spectroradiometer (MODIS) integrated model and the Medium Resolution Imaging Spectrometer (MERIS) correction model, two new advanced InSAR water vapour correction models are demonstrated using both MERIS and MODIS data: (1) the MERIS/MODIS combination correction model (MMCC); and (2) the MERIS/MODIS stacked correction model (MMSC). The applications of both the MMCC and MMSC models to ENVISAT Advanced Synthetic Aperture Radar (ASAR) data over the Southern California Integrated GPS Network (SCIGN) region showed a significant reduction in water vapour effects on ASAR interferograms, with the root mean square (RMS) differences between GPS- and InSAR-derived range changes in the line-of-sight (LOS) direction decreasing from ,10mm before correction to ,5mm after correction, which is similar to the GPS/MODIS integrated and MERIS correction models. It is expected that these two advanced water vapour correction models can expand the application of MERIS and MODIS data for InSAR atmospheric correction. A simple but effective approach has been developed to destripe Terra MODIS images contaminated by radiometric calibration errors. Another two limiting factors on the MMCC and MMSC models have also been investigated in this paper: (1) the impact of the time difference between MODIS and SAR data; and (2) the frequency of cloud-free conditions at the global scale

Factors related to discontinued clinic attendance by patients with podoconiosis in southern Ethiopia: a qualitative study

Background Podoconiosis is a lymphoedema of non-infectious cause which results in long-term ill health in affected individuals. Simple, effective treatment is available in certain parts of Ethiopia, but evidence indicates that not all patients continue collecting treatment supplies from clinic sites once started. We used qualitative techniques to explore factors related to discontinued attendance at outreach clinics of a non-government organization in southern Ethiopia. Methods A cross-sectional qualitative study was conducted in four clinic sites through unstructured in-depth interviews, key informant interviews and focus group discussions with the involvement of 88 study subjects. Results Discontinuation of clinic visits is common among podoconiosis patients. The reasons were: remoteness from the clinic sites, unrealistic expectation of ‘special’ aid, worry about increasing stigma, illness and misconceptions about treatment. Conclusions Several of these factors are remediable through community and individual information and education. Appropriate routes to deliver this information must be identified. Certain factors (such as distance to clinic sites and stigma) require substantial expansion of services or liaison with village-level government health services

Interpolating the Sherrington-Kirkpatrick replica trick

The interpolation techniques have become, in the past decades, a powerful approach to lighten several properties of spin glasses within a simple mathematical framework. Intrinsically, for their construction, these schemes were naturally implemented into the cavity field technique, or its variants as the stochastic stability or the random overlap structures. However the first and most famous approach to mean field statistical mechanics with quenched disorder is the replica trick. Among the models where these methods have been used (namely, dealing with frustration and complexity), probably the best known is the Sherrington-Kirkpatrick spin glass: In this paper we are pleased to apply the interpolation scheme to the replica trick framework and test it directly to the cited paradigmatic model: interestingly this allows to obtain easily the replica-symmetric control and, synergically with the broken replica bounds, a description of the full RSB scenario, both coupled with several minor theorems. Furthermore, by treating the amount of replicas $n\in(0,1]$ as an interpolating parameter (far from its original interpretation) this can be though of as a quenching temperature close to the one introduce in off-equilibrium approaches and, within this viewpoint, the proof of the attended commutativity of the zero replica and the infinite volume limits can be obtained.Comment: This article is dedicated to David Sherrington on the occasion of his seventieth birthda

Risk factors for poor virological outcome at 12 months in a workplace-based antiretroviral therapy programme in South Africa: A cohort study

<p>Abstract</p> <p>Background</p> <p>Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined.</p> <p>Methods</p> <p>Among ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load >= 400 copies/ml.</p> <p>Results</p> <p>Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 × 10⁶/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56–8.68), viral load at baseline (OR 3.63 [95% CI 1.88–7.00] and OR 3.54 [95% CI 1.79–7.00] for 10,001–100,000 and >100,000 compared to <= 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92–6.35]), WHO stage (OR 2.08 [95% CI 1.28–3.34] and OR 2.03 [95% CI 1.14–3.62] for stage 3 and 4 compared to stage 1–2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had >= 1 log decrease in viral load.</p> <p>Conclusion</p> <p>Virological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.</p

Non-linear Response of the trap model in the aging regime : Exact results in the strong disorder limit

We study the dynamics of the one dimensional disordered trap model presenting a broad distribution of trapping times $p(\tau) \sim 1/\tau^{1+\mu}$, when an external force is applied from the very beginning at $t=0$, or only after a waiting time $t_w$, in the linear as well as in the non-linear response regime. Using a real-space renormalization procedure that becomes exact in the limit of strong disorder $\mu \to 0$, we obtain explicit results for many observables, such as the diffusion front, the mean position, the thermal width, the localization parameters and the two-particle correlation function. In particular, the scaling functions for these observables give access to the complete interpolation between the unbiased case and the directed case. Finally, we discuss in details the various regimes that exist for the averaged position in terms of the two times and the external field.Comment: 27 pages, 1 eps figur