Genetic testing for haemochromatosis in patients with chondrocalcinosis

Hereditary haemochromatosis (HH) is the most common lethal monogenic human disease, affecting roughly 1 in 300 white northern Europeans. Homozygosity for the C282Y polymorphism within the HFE gene causes more than 80% of cases, with compound heterozygosity of the C282Y and H63D polymorphism also increasing susceptibility to disease. The aim of this study was to determine the frequency of the C282Y and H63D polymorphisms in the disease, and to assess the risk of HH in heterozygotes for the C282Y polymorphism. 128 patients were recruited because of either radiographic chondrocalcinosis (at least bicompartmental knee disease or joints other than the knee involved) or CPPD pseudogout. Genotyping of the HFE C282Y and H63D mutations was performed using PCR/SSP and genotypes for the C282Y polymorphism confirmed by PCR/RFLP. Historical white European control data were used for comparison. Two previously undiagnosed C282Y homozygotes (1.6%), and 16 C282Y heterozygotes (12.5%), including four (3.1%) C282Y/ H63D compound heterozygotes were identified. This represents a significant overrepresentation of C282Y homozygotes (relative risk 3.4, p-0.037), but the number of heterozygotes was not significantly increased. At a cost per test of £1 for each subject, screening all patients with chondrocalcinosis using the above ascertainment criteria costs only £64 for each case of haemochromatosis identified, clearly a highly cost effective test given the early mortality associated with untreated haemochromatosis. Routine screening for haemochromatosis in patients with appreciable chondrocatcinosis is recommended.

Curriculum reform in testing and accountability contexts

Recent international educational developments have important implications for the skills and understandings in curriculum and assessment that teachers develop, both in pre-service and in practice. Global developments in curriculum and assessment reform require teachers to utilise a network of knowledges and develop a repertoire of assessment skills and understandings. In a context of testing, accountability and auditing, data analysis skills are increasingly required to examine pedagogic practices for the development of intervention teaching and learning strategies to improve learning outcomes for all students (Marsh, 2009). However, too often the data are used predominantly for accountability purposes that serve at national levels as a catalyst for measurement, comparison and allocation of funding (Lingard and Sellar, 2013). With increased accountability demands brought about by global competitiveness and programs for international measurement of educational attainment, there has also emerged an increase in the use of testing, which in some countries has become the dominant form of assessment. For example in Australia, national testing of students in Years 3, 5, 7 and 9 began in 2008 under the National Australia Program – Literacy and Numeracy (NAPLAN). The results from this program for each school are published on the My School website (www.myschool.edu.au), increasing the competitive nature of the testing and intensifying the demands on teachers and schools. In particular, there has been a shift in the enacted curriculum in Australia to a focus on literacy and numeracy because the curriculum is tested.

A multimarker approach to diagnose and stratify heart failure

Background We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies. Methods Plasma samples were collected from healthy controls (n = 52) and HF patients (n = 46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13–45, 13–76, 28–76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated. Results Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13–76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13–76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13–76 with NT-proBNP28–76 assays gave the best diagnostic assay performance. Conclusion Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features

Objective National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated Methods A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. Results The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079–0.115%) (one of 1027 patients). Conclusions Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome

Towards development of a rapid and effective non-destructive testing strategy to identify brominated flame retardants in the plastics of consumer products

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants (BFRs) once extensively used in the plastics of a wide range of consumer products. The listing of certain congeners that are constituents of commercial PBDE mixtures (including c-octaBDE) in the Stockholm Convention and tightening regulation of many other BFRs in recent years have created the need for a rapid and effective method of identifying BFR-containing plastics. A three-tiered testing strategy comparing results from non-destructive testing (X-ray fluorescence (XRF)) (n = 1714), a surface wipe test (n = 137) and destructive chemical analysis (n = 48) was undertaken to systematically identify BFRs in a wide range of consumer products. XRF rapidly identified bromine in 92% of products later confirmed to contain BFRs. Surface wipes of products identified tetrabromobisphenol A (TBBPA), c-octaBDE congeners and BDE-209 with relatively high accuracy (> 75%) when confirmed by destructive chemical analysis. A relationship between the amounts of BFRs detected in surface wipes and subsequent destructive testing shows promise in predicting not only the types of BFRs present but also estimating the concentrations present. Information about the types of products that may contain persistent BFRs will assist regulators in implementing policies to further reduce the occurrence of these chemicals in consumer products.

ISPCAN child abuse screening tool children's version (ICAST-C): Instrument development and multi-national pilot testing

Objective To develop a child victimization survey among a diverse group of child protection experts and examine the performance of the instrument through a set of international pilot studies. Methods The initial draft of the instrument was developed after input from scientists and practitioners representing 40 countries. Volunteers from the larger group of scientists participating in the Delphi review of the ICAST P and R reviewed the ICAST C by email in 2 rounds resulting in a final instrument. The ICAST C was then translated and back translated into six languages and field tested in four countries using a convenience sample of 571 children 12–17 years of age selected from schools and classrooms to which the investigators had easy access. Results The final ICAST C Home has 38 items and the ICAST C Institution has 44 items. These items serve as screeners and positive endorsements are followed by queries for frequency and perpetrator. Half of respondents were boys (49%). Endorsement for various forms of victimization ranged from 0 to 51%. Many children report violence exposure (51%), physical victimization (55%), psychological victimization (66%), sexual victimization (18%), and neglect in their homes (37%) in the last year. High rates of physical victimization (57%), psychological victimization (59%), and sexual victimization (22%) were also reported in schools in the last year. Internal consistency was moderate to high (alpha between .685 and .855) and missing data low (less than 1.5% for all but one item). Conclusions In pilot testing, the ICAST C identifies high rates of child victimization in all domains. Rates of missing data are low, and internal consistency is moderate to high. Pilot testing demonstrated the feasibility of using child self-report as one strategy to assess child victimization. Practice implications The ICAST C is a multi-national, multi-lingual, consensus-based survey instrument. It is available in six languages for international research to estimate child victimization. Assessing the prevalence of child victimization is critical in understanding the scope of the problem, setting national and local priorities, and garnering support for program and policy development aimed at child protection.

Design and flight testing of an integrated solar powered UAV and WSN for greenhouse gas monitoring emissions in agricultural farms

There is an increased interest in measuring the amount of greenhouse gases produced by farming practices . This paper describes an integrated solar powered Unmanned Air Vehicles (UAV) and Wireless Sensor Network (WSN) gas sensing system for greenhouse gas emissions in agricultural lands. The system uses a generic gas sensing system for CH4 and CO2 concentrations using metal oxide (MoX) and non-dispersive infrared sensors, and a new solar cell encapsulation method to power the unmanned aerial system (UAS)as well as a data management platform to store, analyze and share the information with operators and external users. The system was successfully field tested at ground and low altitudes, collecting, storing and transmitting data in real time to a central node for analysis and 3D mapping. The system can be used in a wide range of outdoor applications at a relatively low operational cost. In particular, agricultural environments are increasingly subject to emissions mitigation policies. Accurate measurements of CH4 and CO2 with its temporal and spatial variability can provide farm managers key information to plan agricultural practices. A video of the bench and flight test performed can be seen in the following link: https://www.youtube.com/watch?v=Bwas7stYIxQ

Acute liver failure in children : a regional experience

Objective: To review the outcome of acute liver failure (ALF) and the effect of liver transplantation in children in Australia. Methodology: A retrospective review was conducted of all paediatric patients referred with acute liver failure between 1985 and 2000 to the Queensland Liver Transplant Service, a paediatric liver transplant centre based at the Royal Children's Hospital, Brisbane, that is one of three paediatric transplant centres in Australia. Results: Twenty-six patients were referred with ALF. Four patients did not require transplantation and recovered with medical therapy while two were excluded because of irreversible neurological changes and died. Of the 20 patients considered for transplant, three refused for social and/or religious reasons, with 17 patients listed for transplantation. One patient recovered spontaneously and one died before receiving a transplant. There were 15 transplants of which 40% (6/15) were < 2 years old. Sixty-seven per cent (10/15) survived > 1 month after transplantation. Forty per cent (6/15) survived more than 6 months after transplant. There were only four long term survivors after transplant for ALF (27%). Overall, 27% (6/22) of patients referred with ALF survived. Of the 16 patients that died, 44% (7/16) were from neurological causes. Most of these were from cerebral oedema but two patients transplanted for valproate hepatotoxicity died from neurological disease despite good graft function. Conclusions: Irreversible neurological disease remains a major cause of death in children with ALF. We recommend better patient selection and early referral and transfer to a transplant centre before onset of irreversible neurological disease to optimize outcome of children transplanted for ALF.

Initial prototype testing of Ray's Night Out: A new mobile app targeting risky drinking in young people

Background Risky single occasion drinking (RSOD; 4 or more drinks in <6 h) more than doubles the risk of injury in young people (15 - 25 years). The potential role of smartphone apps in reducing RSOD in young people is yet to be explored. Objective: To describe the initial prototype testing of ‘Ray's Night Out’, a new iPhone app targeting RSOD in young people. Method Quantitative and qualitative methods were used to evaluate the quality, perceived utility, and acceptability of the app among nine young people (19e23 years). Results Participants reported Ray's Night Out had good to excellent levels of functionality and visual appeal, acceptable to good levels of entertainment, interest and information, and acceptable levels of customization and interactivity. Young people thought the app had high levels of youth appeal, would prompt users to think about their alcohol use limits, but was unlikely to motivate a change in alcohol use in its current form. Qualitative data provided several suggestions for improving the app. Conclusion Following revision, Ray's Night Out could provide an effective intervention for RSOD in non help-seeking young people. A randomized controlled trial is currently underway to test the final prototype of the app.

Rank regression for accelerated failure time model with clustered and censored data

For clustered survival data, the traditional Gehan-type estimator is asymptotically equivalent to using only the between-cluster ranks, and the within-cluster ranks are ignored. The contribution of this paper is two fold: - (i) incorporating within-cluster ranks in censored data analysis, and; - (ii) applying the induced smoothing of Brown and Wang (2005, Biometrika) for computational convenience. Asymptotic properties of the resulting estimating functions are given. We also carry out numerical studies to assess the performance of the proposed approach and conclude that the proposed approach can lead to much improved estimators when strong clustering effects exist. A dataset from a litter-matched tumorigenesis experiment is used for illustration.

Differences between Black and White South Africans in product failure attributions, anger and complaint behaviour

The purpose of this research is to extend an understanding of how Black and White South African consumers' causal attributions for major household appliance performance failures impact on their anger and subsequent complaint behaviour. A survey was administered to Black and White South African consumers who were dissatisfied with the performance of a major household appliance item. Respondents resided in a major metropolitan area. The findings showed that, compared to Whites, the Black South Africans felt a low but significantly higher external locus of causality and lower control, and experienced a higher level of anger regarding product failure. The level of anger determined the decision to take complaint action, but racial group determined the type of action taken. Blacks complained more actively to retailers and engaged more in private complaint action than Whites. These findings may show that Black South Africans are developing a more individualistic orientation as consumers. Therefore, researchers should consider the effect of cultural swapping when researching consumer behaviour in multi-cultural countries. Implications for retailers in terms of complaint handling are indicated.

Direct shear testing on unsaturated silty soils to investigate the effects of drying and wetting on shear strength parameters at low suction

A modified conventional direct shear device was used to measure unsaturated shear strength of two silty soils at low suction values (0 ~ 50 kPa) that were achieved by following drying and wetting paths of soil water characteristic curves (SWCCs). The results revealed that the internal friction angle of the soils was not significantly affected by either the suction or the drying wetting SWCCs. The apparent cohesion of soil increased with a decreasing rate as suction increased. Shear stress-shear displacement curves obtained from soil specimens subjected to the same net normal stress and different suction values showed a higher initial stiffness and a greater peak stress as suction increased. A soil in wetting exhibited slightly higher peak shear stress and more contractive volume change behavior than that of soil in drying at the same net normal stress and suction.

Blast response and failure analysis of a segmented buried tunnel

Underground tunnels are vulnerable to terrorist attacks which can cause collapse of the tunnel structures or at least extensive damage, requiring lengthy repairs. This paper treats the blast impact on a reinforced concrete segmental tunnel buried in soil under a number of parametric conditions; soil properties, soil cover, distance of explosive from the tunnel centreline and explosive weight and analyses the possible failure patterns. A fully coupled Fluid Structure Interaction (FSI) technique incorporating the Arbitrary Lagrangian-Eulerian (ALE) method is used in this study. Results indicate that the tunnel in saturated soil is more vulnerable to severe damage than that buried in either partially saturated soil or dry soil. The tunnel is also more vulnerable to surface explosions which occur directly above the centre of the tunnel than those that occur at any equivalent distances in the ground away from the tunnel centre. The research findings provide useful information on modeling, analysis, overall tunnel response and failure patterns of segmented tunnels subjected to blast loads. This information will guide future development and application of research in this field.

Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac diseases. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immunoreactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

Social audit failure: Legal liability of external auditors

In this chapter, we look at the step beyond reporting, to the external audit or assurance function. The role of any audit engagement is to provide a professional opinion on a set of financial or non-financial assertions reported by an organization's management, based on an agreed evaluative framework. Any such opinion is not a guarantee that the underlying report is free from fraud or misstatement. Where an audit opinion on financial statements is incorrect, this is referred to as an audit failure. Specifically, the textbook definition of audit failure has two components: that the financial statements contain a serious error and that the auditor has failed to detect the error due to the auditor's failure during the audit process.