Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Vestibular schwannoma: role of conservative management

Objective: To assess the outcome of conservative management of vestibular schwannoma.Study design: Observational study. Setting: Tertiary referral centre.Patients: Four hundred and thirty-six patients with vestibular schwannoma (490 tumours), including 327 sporadic tumours and 163 tumours in 109 patients with neurofibromatosis type two.Main outcome measures: The relationship of tumour growth to tumour size at presentation, and to certain demographic features.Results: The initial tumour size was significantly larger in the neurofibromatosis type two group (11 mm) than in the sporadic vestibular schwannoma group (5.1 mm). In both groups, 68 per cent of tumours did not grow during follow up (mean 3.6 years; range one to 14 years). The mean growth rate was 1.1 mm/year (range 0-15 mm/year) for sporadic tumours and 1.7 mm/year (range 0-18 mm/year) for neurofibromatosis type two tumours. The tumour growth rate correlated positively with tumour size in the sporadic tumour group, and correlated negatively with age in the neurofibromatosis type two group.Conclusion: Two-thirds of vestibular schwannomas did not grow. Radiological surveillance is an acceptable approach in carefully selected patients. Once a sporadic vestibular schwannoma reaches 2 cm in intracranial diameter, it is likely to continue growing. We do not recommend conservative management for sporadic tumours with an intracranial diameter of 1.5 cm or more. Vestibular schwannoma management is more complex in patients with neurofibromatosis type two

Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro

Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge. Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FA

How dynamic are ice-stream beds?

Projections of sea-level rise contributions from West Antarctica's dynamically thinning ice streams contain high uncertainty because some of the key processes involved are extremely challenging to observe. An especially poorly observed parameter is sub-decadal stability of ice-stream beds, which may be important for subglacial traction, till continuity and landform development. Only two previous studies have made repeated geophysical measurements of ice-stream beds at the same locations in different years, but both studies were limited in spatial extent. Here, we present the results from repeat radar measurements of the bed of Pine Island Glacier, West Antarctica, conducted 3–6 years apart, along a cumulative ∼ 60 km of profiles. Analysis of the correlation of bed picks between repeat surveys shows that 90 % of the bed displays no significant change despite the glacier increasing in speed by up to 40 % over the last decade. We attribute the negligible detection of morphological change at the bed of Pine Island Glacier to the ubiquitous presence of a deforming till layer, wherein sediment transport is in steady state, such that sediment is transported along the basal interface without inducing morphological change to the radar-sounded basal interface. Given the precision of our measurements, the upper limit of subglacial erosion observed here is 500 mm a‾¹, far exceeding erosion rates reported for glacial settings from proglacial sediment yields, but substantially below subglacial erosion rates of 1.0 m a‾¹ previously reported from repeat geophysical surveys in West Antarctica

P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

DeepBrain: Functional Representation of Neural In-Situ Hybridization Images for Gene Ontology Classification Using Deep Convolutional Autoencoders

This paper presents a novel deep learning-based method for learning a functional representation of mammalian neural images. The method uses a deep convolutional denoising autoencoder (CDAE) for generating an invariant, compact representation of in situ hybridization (ISH) images. While most existing methods for bio-imaging analysis were not developed to handle images with highly complex anatomical structures, the results presented in this paper show that functional representation extracted by CDAE can help learn features of functional gene ontology categories for their classification in a highly accurate manner. Using this CDAE representation, our method outperforms the previous state-of-the-art classification rate, by improving the average AUC from 0.92 to 0.98, i.e., achieving 75% reduction in error. The method operates on input images that were downsampled significantly with respect to the original ones to make it computationally feasible

Using discrete choice experiments to investigate subject preferences for preventive asthma medication

Background and objective: Long-term adherence to inhaled corticosteroids is poor despite the crucial role of preventer medications in achieving good asthma outcomes. This study was undertaken to explore patient preferences in relation to their current inhaled corticosteroid medication, a hypothetical preventer or no medication. Methods: A discrete choice experiment was conducted in 57 adults with mild-moderate asthma and airway hyper-responsiveness, who were using inhaled corticosteroid ≤500 μg/day (beclomethasone equivalent). In the discrete choice experiment, subjects evaluated 16 hypothetical scenarios made up of 10 attributes that described the process and outcomes of taking asthma medication, with two to four levels for each attribute. For each scenario, subjects chose between the hypothetical medication, the medication they were currently taking and no asthma medication. A random parameter multinomial logit model was estimated to quantify subject preferences for the aspects of taking asthma medication and the influence of attributes on medication decisions. Results: Subjects consistently made choices in favour of being able to do strenuous and sporting activities with or without reliever, experiencing no side-effects and never having to monitor their peak flow. Frequency of collecting prescriptions, frequency of taking the medication, its route of administration and the strength of the doctor recommendation about the medication were not significant determinants of choice. Conclusions: The results of this study suggest that patients prefer a preventer that confers capacity to maximize physical activity, has no side-effects and does not require daily peak flow monitoring. © 2007 The Authors