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

Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surf acta nt proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar ravages, GM-CSF replacement, bone marrow grafting or lung transplantation

Dysphoria and hopelessness following battering: The role of perceived control, coping, and self-esteem

Coping, perceived control, dysphoria, hopelessness, and self-esteem in a sample of 100 battered women were assessed. Participants reported dysphoria and low self-esteem, but not hopelessness. High perceived control over current abuse and greater use of drugs, behavioral disengagement, denial, and self-blame as coping mechanisms were associated with increased dysphoria and low self-esteem. High expectations for control over future abuse were associated with decreased dysphoria and hopelessness and increased self-esteem. After controlling for the effects of abuse severity and low self-esteem, self-blame was a unique contributor to dysphoria and high expectations for control of future abuse were unique contributors to hopelessness. Results are discussed in terms of their implications for clinical intervention with battered women

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Science education for responsible social action

This dissertation explores a model of science education for responsible social action, tested in practice through field implementation during a teacher workshop and revised using data and self-reflection. Change was recognized as a basic phenomenon of the universe and schools were offered as logical means for preparing for social change. The intent of this study was to provide a broad framework for science education while at the same time broadening what it entails. Movement from a focus on content to one of preparation for social action is the major objective presented for science education. This study is both analytical and introspective in that an educational model was developed and altered after analysis and self-reflection. There appears to be an intimate and necessary relation between the action experiences of the model developer and the model itself. An attempt is made to identify and explore those dimensions which might make the model more workable

Reaching Across Borderlines: Collected Essays from the UNCW-IIUI D.O.S. Partnership

Bringing together scholars from the U.S. and Pakistan, this double-blind, peer-reviewed collection of essays-the culmination of a four-year partnership between universities in the two countries- grapples with questions of critical interpretation of literature, international and cultural relations, and pedagogy. Print copies available at: https://uncpress.org/book/9781469672847/reaching-across-borderlines

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Detection of codon 12 K- ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas

K- ras activation by point mutation in codon 12 has been reported in lung adenocarcinomas in various models of experimental lung tumours induced by chemical carcinogens. The hypothesis of the presence of cells containing K- ras mutation in non neoplastic bronchial carina, the main site of impaction of airborne contaminants, was investigated by evaluating concurrent lung tumour and non-neoplastic proximal bronchial carinae from 19 patients with lung adenocarcinomas. The restriction fragment length polymorphism enriched PCR method used can detect one mutant allele among 103normal alleles. A mutation was detected in 42% of lung adenocarcinoma samples. No mutation was detected in either tumour or bronchial carinae in nine patients (47%). K- ras mutation was detected in the lung tumour but not in bronchial carinae in four patients (21%), in both the lung tumour and bronchial carinae in four other patients (21%). In two patients (11%), K- ras mutation was detected in at least one bronchial carina, but not in the lung tumour. Mutations of codon 12, confirmed by sequencing analysis of ten samples, were G to T transversion, mostly TGT and GTT in bronchial carinae and lung tumours. Our data show that activated K- ras by point mutation can be present in non-neoplastic bronchial carina mucosa even when no mutation is detected in tumour samples. © 2000 Cancer Research Campaig

Multiparameter Telemetry as a Sensitive Screening Method to Detect Vaccine Reactogenicity in Mice

Refined vaccines and adjuvants are urgently needed to advance immunization against global infectious challenges such as HIV, hepatitis C, tuberculosis and malaria. Large-scale screening efforts are ongoing to identify adjuvants with improved efficacy profiles. Reactogenicity often represents a major hurdle to the clinical use of new substances. Yet, irrespective of its importance, this parameter has remained difficult to screen for, owing to a lack of sensitive small animal models with a capacity for high throughput testing. Here we report that continuous telemetric measurements of heart rate, heart rate variability, body core temperature and locomotor activity in laboratory mice readily unmasked systemic side-effects of vaccination, which went undetected by conventional observational assessment and clinical scoring. Even minor aberrations in homeostasis were readily detected, ranging from sympathetic activation over transient pyrogenic effects to reduced physical activity and apathy. Results in real-time combined with the potential of scalability and partial automation in the industrial context suggest multiparameter telemetry in laboratory mice as a first-line screen for vaccine reactogenicity. This may accelerate vaccine discovery in general and may further the success of vaccines in combating infectious disease and cancer

Reoccurring patterns in hierarchical protein materials and music: The power of analogies

Complex hierarchical structures composed of simple nanoscale building blocks form the basis of most biological materials. Here we demonstrate how analogies between seemingly different fields enable the understanding of general principles by which functional properties in hierarchical systems emerge, similar to an analogy learning process. Specifically, natural hierarchical materials like spider silk exhibit properties comparable to classical music in terms of their hierarchical structure and function. As a comparative tool here we apply hierarchical ontology logs (olog) that follow a rigorous mathematical formulation based on category theory to provide an insightful system representation by expressing knowledge in a conceptual map. We explain the process of analogy creation, draw connections at several levels of hierarchy and identify similar patterns that govern the structure of the hierarchical systems silk and music and discuss the impact of the derived analogy for nanotechnology.Comment: 13 pages, 3 figure