Cancer data and Aboriginal disparities (CanDAD)-developing an Advanced Cancer Data System for Aboriginal people in South Australia: a mixed methods research protocol

Introduction: In Australia, Aboriginal and Torres Strait Islander People carry a greater burden of cancerrelated mortality than non-Aboriginal Australians. The Cancer Data and Aboriginal Disparities Project aims to develop and test an integrated, comprehensive cancer monitoring and surveillance system capable of incorporating epidemiological and narrative data to address disparities and advocate for clinical system change. Methods and analysis: The Advanced Cancer Data System will integrate routinely collected unit record data from the South Australian Population Cancer Registry and a range of other data sources for a retrospective cohort of indigenous people with cancers diagnosed from 1990 to 2010. A randomly drawn non- Aboriginal cohort will be matched by primary cancer site, sex, age and year at diagnosis. Cross-tabulations and regression analyses will examine the extent to which demographic attributes, cancer stage and survival vary between the cohorts. Narratives from Aboriginal people with cancer, their families, carers and service providers will be collected and analysed using patient pathway mapping and thematic analysis. Statements from the narratives will structure both a concept mapping process of rating, sorting and prioritising issues, focusing on issues of importance and feasibility, and the development of a real-time Aboriginal Cancer Measure of Experience for ongoing linkage with epidemiological data in the Advanced Cancer Data System. Aboriginal Community engagement underpins this Project. Ethics and dissemination: The research has been approved by relevant local and national ethics committees. Findings will be disseminated in local and international peer-reviewed journals and conference presentations. In addition, the research will provide data for knowledge translation activities across the partner organisations and feed directly into the Statewide Cancer Control Plan. It will provide a mechanism for monitoring and evaluating the implementation of the recommendations in these documents.Paul Henry Yerrell, David Roder, Margaret Cargo, Rachel Reilly, David Banham, Jasmine May Micklem, Kim Morey, Harold Bundamurra Stewart, Janet Stajic, Michael Norris, Alex Brown, On behalf of the CanDAD Aboriginal Community Reference Group and CanDAD Investigator

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome

BACKGROUND AND OBJECTIVES: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome. Panel sequencing has a number of limitations when compared with whole exome sequencing. We employed whole exome sequencing to detect monogenic causes of steroid-resistant nephrotic syndrome in an international cohort of 300 families. DESIGN, SETTING, PARTIIPANTS AND MEASUREMENTS: Three hundred thirty-five individuals with steroid-resistant nephrotic syndrome from 300 families were recruited from April of 1998 to June of 2016. Age of onset was restricted to <25 years of age. Exome data were evaluated for 33 known monogenic steroid-resistant nephrotic syndrome genes. RESULTS: In 74 of 300 families (25%), we identified a causative mutation in one of 20 genes known to cause steroid-resistant nephrotic syndrome. In 11 families (3.7%), we detected a mutation in a gene that causes a phenocopy of steroid-resistant nephrotic syndrome. This is consistent with our previously published identification of mutations using a panel approach. We detected a causative mutation in a known steroid-resistant nephrotic syndrome gene in 38% of consanguineous families and in 13% of nonconsanguineous families, and 48% of children with congenital nephrotic syndrome. A total of 68 different mutations were detected in 20 of 33 steroid-resistant nephrotic syndrome genes. Fifteen of these mutations were novel. NPHS1, PLCE1, NPHS2, and SMARCAL1 were the most common genes in which we detected a mutation. In another 28% of families, we detected mutations in one or more candidate genes for steroid-resistant nephrotic syndrome. CONCLUSIONS: Whole exome sequencing is a sensitive approach toward diagnosis of monogenic causes of steroid-resistant nephrotic syndrome. A molecular genetic diagnosis of steroid-resistant nephrotic syndrome may have important consequences for the management of treatment and kidney transplantation in steroid-resistant nephrotic syndrome

Unboxing mutations: Connecting mutation types with evolutionary consequences

A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types (e.g., SNPs, translocations and inversions). To do this we must simultaneously consider different mutation types in an evolutionary framework. Here, we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance in a given scenario. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance

The accuracy of radon and thoron progeny concentrations measured through air filtration

© 2014 Elsevier Ltd. The accuracy and the optimization of determining radon and thoron progeny concentrations in air using air filtration followed by alpha activity measurements were investigated in details. The effects of radon and thoron concentrations, filtering duration and the choice of measuring intervals on relative standard deviations were analyzed. Obtaining satisfactory results by this method should be expected only in the case of high radon and thoron progeny concentrations in air. The optimization process also showed up to be dependent on the progeny concentration. Determinant of the system matrix and its effect on the sensitivity of the results were investigated

Hit probability of a disk shaped detector with particles with a finite range emitted by a point-like source

An analytical analysis of the geometrical efficiency of a circular detector for particles with a finite range, emitted from a point-like source, is given. Several different cases were determined, depending on the particle range, radius of the detector and the position of the source with respect to the detector. These cases were analyzed separately and different expressions for calculating the hit probability were obtained for each of them. Results were compared with Monte Carlo calculations and good agreement was found. The problem considered here might be relevant for alpha-particle detection under specific conditions. © 2011 Elsevier Ltd

Theoretical calculation of radon emanation fraction

Emanation fraction of radon atoms created in a granular material was estimated using Monte Carlo method. Two models based on different arrangements of grains were considered: one of them representing simple cubic structure and the other one based on face centered cubic structure. As it was expected, the structure that provided higher density of grain packing (FCCS) gave lower values of radon emanation fraction. Both models showed that the probability of radon embedding in the neighboring grains would approach zero for large values of grain radius. Assuming homogenous distribution of 226Ra within the whole grain volume, radon emanation fraction decreased with increasing grain radius while it showed the opposite behavior in the case of surface distribution of 226Ra. The order of magnitude of radon emanation fraction decreased from 10-2% (for grain radius of few micrometers) to 10 -4% (for grain radius larger than few millimeters) when homogenous distribution of 226Ra was considered. If the distribution of 226Ra was assumed only within the surface layer of a grain, emanation increased from less than 1% (obtained for grain size of few micrometers) to almost 25% (for large grain radius). The effect of moisture on the emanation fraction was confirmed by examining the case of water filling the space among the grains. Radon emanation was also considered analytically and the results were compared with Monte Carlo calculations. © 2014 Elsevier B.V. All rights reserved