Development of a species-specific coproantigen ELISA for human taenia solium taeniasis

Taenia solium causes human neurocysticercosis and is endemic in underdeveloped countries where backyard pig keeping is common. Microscopic fecal diagnostic methods for human T. solium taeniasis are not very sensitive, and Taenia saginata and Taenia solium eggs are indistinguishable under the light microscope. Coproantigen (CoAg) ELISA methods are very sensitive, but currently only genus (Taenia) specific. This paper describes the development of a highly species-specific coproantigen ELISA test to detect T. solium intestinal taeniasis. Sensitivity was maintained using a capture antibody of rabbit IgG against T. solium adult whole worm somatic extract, whereas species specificity was achieved by utilization of an enzyme-conjugated rabbit IgG against T. solium adult excretory-secretory (ES) antigen. A known panel of positive and negative human fecal samples was tested with this hybrid sandwich ELISA. The ELISA test gave 100% specificity and 96.4% sensitivity for T. solium tapeworm carriers (N = 28), with a J index of 0.96. This simple ELISA incorporating anti-adult somatic and anti-adult ES antibodies provides the first potentially species-specific coproantigen test for human T. solium taeniasis

Prevalence of elevated alanine transaminase in Australia and its relationship to metabolic risk factors: A cross-sectional study of 9,447 people

BACKGROUND AND AIM: Elevated alanine transaminase (ALT) is a strong predictor of metabolic syndrome, but there are few data from the Australian population. We aimed to determine the prevalence of elevated ALT and association with metabolic risk factors. METHODS: In this cross-sectional study including adult participants (N = 9,447) from a nationwide, population-based survey, we assessed the prevalence of elevated ALT [defined as ≥ 40 IU/L (men) and ≥ 30 IU/L (women) as baseline, and ALT as ≥ 30 IU/L (men) and ≥ 19 IU/L (women) as lower threshold], distribution of metabolic risk factors, and independent predictors of elevated ALT in logistic regression models. Analyses were weighted to the population with population weights. RESULTS: Elevated ALT levels were found in 11.2% of the Australian population. People with elevated ALT were younger (43 vs 46 yrs) with more truncal adiposity (100 vs 91 cm), higher pro-atherogenic lipids and glucose and exercised less (120 vs 160 min per week, P < 0.05 for all analyses). Regression analyses indicated that younger age, male sex, diabetes, triglycerides, apolipoprotein B, and waist circumference were independent predictors of elevated ALT. The population attributable fraction of elevated ALT due to truncal obesity was estimated at 47%. CONCLUSION: These data demonstrate a high prevalence of elevated ALT in the general population that is closely associated with metabolic risk factors. Individuals with elevated ALT should be evaluated for co-existent metabolic disorders

Eliciting patient preferences, priorities and trade-offs for outcomes following kidney transplantation: A pilot best-worst scaling survey

Objectives: Eliciting preferences and trade-offs that patients may make to achieve important outcomes, can assist in developing patient-centred research and care. The pilot study aimed to test the feasibility of a case 2 best-worst scaling survey (BWS) to elicit recipient with kidney transplantation preferences after transplantation. Design: Preferences for graft survival and dying, cancer, cardiovascular disease, diabetes, infection and side effects (gastrointestinal, weight-gain and appearance) were assessed in recipients with transplantation using a BWS (20 scenarios of nine outcomes). Participants chose 'best' and 'worst' outcomes. Responses were analysed using a multinomial logit model. Selected participants were interviewed. Outcomes: Attribute coefficients and survey completion error rates. Results: 81 recipients with transplantation were approached, and 39 (48%), mean age 50.5 years, completed the BWS. 4 (10%) surveys were invalid with major errors and of 35 remaining, 7 of 1400 (0.5%) choices were missing. -23 (59%) took >20 min to complete the survey. 1 was unable to finish, and 1 did not understand the survey. 2 (5%) found it very hard and 14 (35%) moderately hard. Most attribute coefficients were significant (p<0.05) and showed face validity. Graft survival was most important with normalised coefficients from 1 (95% CI 0.89 to 1.11) to 0.06 (95% CI -0.03 to 0.16) for 30 and 1 year duration, respectively. Attribute level coefficients decreased with increasing risk of adverse outcomes. Error rates of 20% and 2% were estimated for dominant attributes '100% risk of dying' and '30 years graft survival', respectively. 7 participants were interviewed regarding counterintuitive selection of '100% risk of dying' as a 'best' outcome. Misunderstanding, not linking dying to graft survival and aversion to dialysis were reasons given. Conclusions: Recipients with transplant recipients successfully completed a complex case 2 BWS with attribute coefficients having face validity with respect to duration of graft survival and risk of adverse outcomes. Areas for refinement to reduce complexity in design have been identified

Hippocampal gabaergic inhibitory interneurons

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record In the hippocampus GABAergic local circuit inhibitory interneurons represent only ~10–15% of the total neuronal population; however, their remarkable anatomical and physiological diversity allows them to regulate virtually all aspects of cellular and circuit function. Here we provide an overview of the current state of the field of interneuron research, focusing largely on the hippocampus. We discuss recent advances related to the various cell types, including their development and maturation, expression of subtype-specific voltage-and ligand-gated channels, and their roles in network oscillations. We also discuss recent technological advances and approaches that have permitted high-resolution, subtype-specific examination of their roles in numerous neural circuit disorders and the emerging therapeutic strategies to ameliorate such pathophysiological conditions. The ultimate goal of this review is not only to provide a touchstone for the current state of the field, but to help pave the way for future research by highlighting where gaps in our knowledge exist and how a complete appreciation of their roles will aid in future therapeutic strategies.National Institute of Child Health and Human Developmen

Accuracy of the "traffic light" clinical decision rule for serious bacterial infections in young children with fever: A retrospective cohort study

Objectives To determine the accuracy of a clinical decision rule (the traffic light system developed by the National Institute for Health and Clinical Excellence (NICE)) for detecting three common serious bacterial infections (urinary tract infection, pneumonia, and bacteraemia) in young febrile children. Design Retrospective analysis of data from a two year prospective cohort study Setting A paediatric emergency department. Participants 15 781 cases of children under 5 years of age presenting with a febrile illness. Main outcome measures Clinical features were used to categorise each febrile episodes as low, intermediate, or high probability of serious bacterial infection (green, amber, and red zones of the traffic light system); these results were checked (using standard radiological and microbiological tests) for each of the infections of interest and for any serious bacterial infection. Results After combination of the intermediate and high risk categories, the NICE traffic light system had a test sensitivity of 85.8% (95% confidence interval 83.6% to 87.7%) and specificity of 28.5% (27.8% to 29.3%) for the detection of any serious bacterial infection. Of the 1140 cases of serious bacterial infection, 157 (13.8%) were test negative (in the green zone), and, of these, 108 (68.8%) were urinary tract infections. Adding urine analysis (leucocyte esterase or nitrite positive), reported in 3653 (23.1%) episodes, to the traffic light system improved the test performance: sensitivity 92.1% (89.3% to 94.1%), specificity 22.3% (20.9% to 23.8%), and relative positive likelihood ratio 1.10 (1.06 to 1.14). Conclusion The NICE traffic light system failed to identify a substantial proportion of serious bacterial infections, particularly urinary tract infections. The addition of urine analysis significantly improved test sensitivity, making the traffic light system a more useful triage tool for the detection of serious bacterial infections in young febrile children

Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease a systematic review and meta-analysis

Context: Clinical practice guidelines on the management of mineral and bone disorders due to chronic kidney disease recommend specific treatment target levels for serum phosphorus, parathyroid hormone, and calcium. Objective: To assess the quality of evidence for the association between levels of serum phosphorus, parathyroid hormone, and calcium and risks of death, cardiovascular mortality, and nonfatal cardiovascular events in individuals with chronic kidney disease. Data Sources: The databases of MEDLINE (1948 to December 2010) and EMBASE (1947 to December 2010) were searched without language restriction. Hand searches also were conducted of the reference lists of primary studies, review articles, and clinical guidelines along with full-text review of any citation that appeared relevant. Study Selection: Of 8380 citations identified in the original search, 47 cohort studies (N=327 644 patients) met the inclusion criteria. Data Extraction: The characteristics of study design, participants, exposures, and covariates together with the outcomes of all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular events at different levels of serum phosphorus, parathyroid hormone, and calcium were analyzed within studies. Data were summarized across studies (when possible) using random-effects meta-regression. Data Synthesis: The risk of death increased 18% for every 1-mg/dL increase in serum phosphorus (relative risk [RR], 1.18 [95% confidence interval {CI}, 1.12-1.25]). There was no significant association between all-cause mortality and serum level of parathyroid hormone (RR per 100-pg/mL increase, 1.01 [95% CI, 1.00-1.02]) or serum level of calcium (RR per 1-mg/dL increase, 1.08 [95% CI, 1.00-1.16]). Data for the association between serum level of phosphorus, parathyroid hormone, and calcium and cardiovascular death were each available in only 1 adequately adjusted cohort study. Lack of adjustment for confounding variables was not a major limitation of the available studies. Conclusions: The evidentiary basis for a strong, consistent, and independent association between serum levels of calcium and parathyroid hormone and the risk of death and cardiovascular events in chronic kidney disease is poor. There appears to be an association between higher serum levels of phosphorus and mortality in this population. ©2011 American Medical Association. All rights reserved

Elevated Liver Enzymes and Mortality in Older Individuals: A Prospective Cohort Study

Aim of the study: The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)]. Methods: We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up. Results: Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30). Conclusions: In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age

Precalibrating an intermediate complexity climate model

Credible climate predictions require a rational quantification of uncertainty, but full Bayesian calibration requires detailed estimates of prior probability distributions and covariances, which are difficult to obtain in practice. We describe a simplified procedure, termed precalibration, which provides an approximate quantification of uncertainty in climate prediction, and requires only that uncontroversially implausible values of certain inputs and outputs are identified. The method is applied to intermediate-complexity model simulations of the Atlantic meridional overturning circulation (AMOC) and confirms the existence of a cliff-edge catastrophe in freshwaterforcing input space. When uncertainty in 14 further parameters is taken into account, an implausible, AMOC-off, region remains as a robust feature of the model dynamics, but its location is found to depend strongly on values of the other parameters

Cardiac testing for coronary artery disease in potential kidney transplant recipients.

Patients with chronic kidney disease (CKD) are at increased risk of coronary artery disease (CAD) and adverse cardiac events. Screening for CAD is therefore an important part of preoperative evaluation for kidney transplant candidates. There is significant interest in the role of non-invasive cardiac investigations and their ability to identify patients at high risk of CAD.  We investigated the accuracy of non-invasive cardiac screening tests compared with coronary angiography to detect CAD in patients who are potential kidney transplant recipients. MEDLINE and EMBASE searches (inception to November 2010) were performed to identify studies that assessed the diagnostic accuracy of non-invasive screening tests, using coronary angiography as the reference standard. We also conducted citation tracking via Web of Science and handsearched reference lists of identified primary studies and review articles.   We included in this review all diagnostic cross sectional, cohort and randomised studies of test accuracy that compared the results of any cardiac test with coronary angiography (the reference standard) relating to patients considered as potential candidates for kidney transplantation or kidney-pancreas transplantation at the time diagnostic tests were performed.  We used a hierarchical modelling strategy to produce summary receiver operating characteristic (SROC) curves, and pooled estimates of sensitivity and specificity. Sensitivity analyses to determine test accuracy were performed if only studies that had full verification or applied a threshold of ≥ 70% stenosis on coronary angiography for the diagnosis of significant CAD were included. The following screening investigations included in the meta-analysis were: dobutamine stress echocardiography (DSE) (13 studies), myocardial perfusion scintigraphy (MPS) (nine studies), echocardiography (three studies), exercise stress electrocardiography (two studies), resting electrocardiography (three studies), and one study each of electron beam computed tomography (EBCT), exercise ventriculography, carotid intimal media thickness (CIMT) and digital subtraction fluorography (DSF). Sufficient studies were present to allow hierarchical summary receiver operating characteristic (HSROC) analysis for DSE and MPS. When including all available studies, both DSE and MPS had moderate sensitivity and specificity in detecting coronary artery stenosis in patients who are kidney transplant candidates [DSE (13 studies) - pooled sensitivity 0.79 (95% CI 0.67 to 0.88), pooled specificity 0.89 (95% CI 0.81 to 0.94); MPS (nine studies) - pooled sensitivity 0.74 (95% CI 0.54 to 0.87), pooled specificity 0.70 (95% CI 0.51 to 0.84)]. When limiting to studies which defined coronary artery stenosis using a reference threshold of ≥ 70% stenosis on coronary angiography, there was little change in these pooled estimates of accuracy [DSE (9 studies) - pooled sensitivity 0.76 (95% CI 0.60 to 0.87), specificity 0.88 (95% CI 0.78 to 0.94); MPS (7 studies) - pooled sensitivity 0.67 (95% CI 0.48 to 0.82), pooled specificity 0.77 (95% CI 0.61 to 0.88)]. There was evidence that DSE had improved accuracy over MPS (P = 0.02) when all studies were included in the analysis, but this was not significant when we excluded studies which did not avoid partial verification or use a reference standard threshold of ≥70% stenosis (P = 0.09).   DSE may perform better than MPS but additional studies directly comparing these cardiac screening tests are needed. Absence of significant CAD may not necessarily correlate with cardiac-event free survival following transplantation. Further research should focus on assessing the ability of functional tests to predict postoperative outcome

Spectropolarimetry of Supernovae

Overwhelming evidence has accumulated in recent years that supernova explosions are intrinsically 3-dimensional phenomena with significant departures from spherical symmetry. We review the evidence derived from spectropolarimetry that has established several key results: virtually all supernovae are significantly aspherical near maximum light; core-collapse supernovae behave differently than thermonuclear (Type Ia) supernovae; the asphericity of core-collapse supernovae is stronger in the inner layers showing that the explosion process itself is strongly aspherical; core-collapse supernovae tend to establish a preferred direction of asymmetry; the asphericity is stronger in the outer layers of thermonuclear supernovae providing constraints on the burning process. We emphasize the utility of the Q/U plane as a diagnostic tool and revisit SN 1987A and SN 1993J in a contemporary context. An axially-symmetric geometry can explain many basic features of core-collapse supernovae, but significant departures from axial symmetry are needed to explain most events. We introduce a spectropolarimetry type to classify the range of behavior observed in polarized supernovae. Understanding asymmetries in supernovae is important for phenomena as diverse as the origins of gamma-ray bursts and the cosmological applications of Type Ia supernovae in studies of the dark energy content of the universe.Comment: Draft of Annual Review article prior to final copy editing; 85 pages, 13 figures, 1 tabl