A genome-wide study of Hardy–Weinberg equilibrium with next generation sequence data

Statistical tests for Hardy–Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes. Observed disequilibrium is, in about 60% of the cases, due to heterozygote excess. We suggest that most excess disequilibrium can be explained by sequencing problems, and hypothesize mechanisms that can explain exceptional heterozygosities. We report higher rates of disequilibrium for the MHC region on chromosome 6, regions flanking centromeres and p-arms of acrocentric chromosomes. We also detected long-range haplotypes and areas with incidental high disequilibrium. We report disequilibrium to be related to read depth, with variants having extreme read depths being more likely to be out of equilibrium. Disequilibrium rates were found to be 11 times higher in segmental duplications and simple tandem repeat regions. The variants with significant disequilibrium are seen to be concentrated in these areas. For next generation sequence data, Hardy–Weinberg disequilibrium seems to be a major indicator for copy number variation.Peer ReviewedPostprint (published version

Bacillus Calmette-Guérin-related cold thigh abscess as an unusual cause of thigh swelling in infants following BCG vaccine administration: a case series

<p>Abstract</p> <p>Introduction</p> <p>Thigh swelling in an infant can be a symptom of a simple benign condition or a life-threatening condition. We observed a cluster of thigh swelling episodes in infants in which the cause was Bacillus Calmette-Guérin-related cold thigh abscess. We report this unusual case series to raise awareness about this diagnosis.</p> <p>Case presentations</p> <p>We performed a retrospective review of five infants (four boys and one girl) who presented with Bacillus Calmette-Guérin-related left thigh abscess. The swelling was noticed by the parents at a mean period of three months prior to presentation. The ages at presentation were five, five, eight and nine months for the boys, and six months for the girl. All of the patients were healthy Saudi infants, and received the Bacillus Calmette-Guérin vaccine at birth. Clinically, all of the patients were well and did not demonstrate signs of systemic infection. All patients underwent needle aspiration, with subsequent incision and drainage in four of the five cases. The cultures obtained from the abscess fluids were the key to establishing the diagnosis. Only three patients (60%) received antituberculosis drugs. Wound healing lasted for a mean period of approximately seven months. Two-year follow-up was unremarkable for all of our patients.</p> <p>Conclusions</p> <p>Technical errors continue to be significant in the development of vaccine-related complications. Bacillus Calmette-Guérin-related cold thigh abscess is an extremely rare entity.</p

Studies on dental erosion: An in vivo-in vitro model of endogenous dental erosion - its application to testing protection by fluoride gel application

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The objective in this study was to develop an in vivo-in vitro model of endogenous erosion, with a view to exploring the potential for some degree of its control by the use of topical fluoride gel application to teeth. Methods: Six volunteers each wore a small clasp retained palatal acrylic appliance to which six sterilized enamel tiles were bonded. Three tiles on each appliance were coated extra-orally with either 1.23 per cent acidulated phosphate fluoride (APF) or 2.2 per cent sodium fluoride (NaF) neutral gel for four minutes prior to multiple periods of exposure to the simulated gastric acid, cumulating in 16, 36, 80 and 150 minutes of exposure. Impressions of the enamel tiles prior to and following acid exposure permitted dies to be prepared. These were sectioned through the exposed areas and examined under a stereomicroscope to assess maximum depths of erosion. Results: The depth of erosive demineralization of enamel was found to be greatly reduced with increased frequency of APF gel application. The reduction in enamel loss was less following topical application of NaF gel. Conclusions: It was concluded that fluoride gels significantly reduced enamel erosion using this in vivo-in vitro model and therefore, if prescribed appropriately, should help reduce tooth tissue loss from endogenous erosion.L Jones, D Lekkas, D Hunt, J McIntyre and W Rafi

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Hypoglycemia in Non-Diabetic In-Patients: Clinical or Criminal?

BACKGROUND AND AIM: We wished to establish the frequency of unexpected hypoglycemia observed in non diabetic patients outside the intensive care unit and to determine if they have a plausible clinical explanation. METHODS: We analysed data for 2010 from three distinct sources to identify non diabetic hypoglycaemic patients: bedside and laboratory blood glucose measurements; medication records for those treatments (high-strength glucose solution and glucagon) commonly given to reverse hypoglycemia; and diagnostic codes for hypoglycemia. We excluded from the denominator admissions of patients with a diagnosis of diabetes or prescribed diabetic medication. Case notes of patients identified were reviewed. We used capture-recapture methods to establish the likely frequency of hypoglycemia in non-diabetic in-patients outside intensive care unit at different cut-off points for hypoglycemia. We also recorded co-morbidities that might have given rise to hypoglycemia. RESULTS: Among the 37,898 admissions, the triggers identified 71 hypoglycaemic episodes at a cut-off of 3.3 mmol/l. Estimated frequency at 3.3 mmol/l was 50(CI 33-93), at 3.0 mmol/l, 36(CI 24-64), at 2.7 mmol/l, 13(CI 11-19), at 2.5 mmol/l, 11(CI 9-15) and at 2.2 mmol/l, 8(CI 7-11) per 10,000 admissions. Admissions of patients aged above 65 years were approximately 50% more likely to have an episode of hypoglycemia. Most were associated with important co-morbidities. CONCLUSION: Significant non-diabetic hypoglycemia in hospital in-patients (at or below 2.7 mmol/l) outside critical care is rare. It is sufficiently rare for occurrences to merit case-note review and diagnostic blood tests, unless an obvious explanation is found

Koilocytes indicate a role for human papilloma virus in breast cancer

Background: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. Methods: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. Results: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). Interpretation: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.6 page(s

Patient-reported GP health assessments rather than individual cardiovascular risk burden are associated with the engagement in lifestyle changes: Population-based survey in South Australia

© 2019 The Author(s). Background: Little is known about whether a more comprehensive health assessment, performed by a general practitioner (GP) during a clinical encounter, could influence patients' lifestyle. We aimed to investigate whether health assessments, performed by GPs, are more important than the presence of cardiovascular disease (CVD) or cardiometabolic risk factors (obesity, diabetes, hypertension, dyslipidaemia) for engagement in lifestyle change. Methods: Cross-sectional, population-based survey conducted in South Australia (September-December 2017) using face-To-face interviews and self-reported data of 2977 individuals aged 15+ years. The main outcome was engagement in four lifestyle changes: 1) increasing fruit/vegetable intake, 2) increasing physical activity level, 3) reducing alcohol consumption, and 4) attempts to stop smoking. Health assessments performed by a GP in the last 12 months included clinical/laboratory investigations (weight/waist circumference, blood pressure, glucose levels, lipid levels) and questions about lifestyle/wellbeing (current diet, physical activity, smoking status, alcohol intake, mental health, sleeping problems). Results were restricted to individuals aged 35+ years because of the low prevalence of CVD or their risk factors among younger participants. Logistic regression was used in all associations, adjusted for sociodemographic, lifestyle, mental health, and clinical variables. Results: Of the 2384 investigated adults (mean age 57.3 ± 13.9 years; 51.9% females), 10.2% had CVD and 49.1% at least one cardiometabolic risk factor. Clinical/laboratory assessments performed by the GP were 2-3 times more frequent than assessments of lifestyle, mental health status, or sleeping problems, especially among those with CVD. Individuals with CVD or a cardiometabolic risk factor were no more likely to be increasing their fruit/vegetable consumption (33.6%), physical activity level (40.9%), reducing alcohol consumption (31.1%), or trying to quit smoking (34.0%) than 'healthy' participants. However, lifestyle changes were between 30 and 100% more likely when GPs performed three or more health assessments (either clinical/laboratory or questions about lifestyle/wellbeing) than when individuals did not visit the GP or when GPs performed no any assessment during these clinical encounters (p < 0.05 in all cases). Conclusion: More frequent and comprehensive CVD-related assessments by GPs were more important in promoting a healthier lifestyle than the presence of CVD or cardiometabolic risk factors by themselves

Preparation and thermal conductivity of CuO nanofluid via a wet chemical method

In this article, a wet chemical method was developed to prepare stable CuO nanofluids. The influences of synthesis parameters, such as kinds and amounts of copper salts, reaction time, were studied. The thermal conductivities of CuO nanofluids were also investigated. The results showed that different copper salts resulted in different particle morphology. The concentration of copper acetate and reaction time affected the size and shape of clusters of primary nanoparticles. Nanofluids with different microstructures could be obtained by changing the synthesis parameters. The thermal conductivities of CuO nanofluids increased with the increase of particle loading