Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten.

Testicular tumors are the most common malignancy of young men and tumors affecting the testis are caused by somatic mutations in germ or germ-like cells. The PI3K pathway is constitutively activated in about one third of testicular cancers. To investigate the role of the PI3K pathway in transforming stem-like cells in the testis, we investigated tumors derived from mice with post-natal, constitutive activation of PI3K signaling and homozygous deletion of tumor suppressor Pten, targeted to nestin expressing cells.

Diagnosis and analysis of unexplained cases of childhood encephalitis in Australia using metatranscriptomic sequencing.

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study.

Invasive atypical non-typhoidal serovars in The Gambia.

Invasive non-typhoidal (iNTS) disease continues to be a significant public health problem in sub-Saharan Africa. Common clinical misdiagnosis, antimicrobial resistance, high case fatality and lack of a vaccine make iNTS a priority for global health research. Using whole genome sequence analysis of 164 invasive isolates obtained through population-based surveillance between 2008 and 2016, we conducted genomic analysis of the serovars causing invasive diseases in rural Gambia.

Ximmer: a system for improving accuracy and consistency of CNV calling from exome data.

Background: While exome and targeted next-generation DNA sequencing are primarily used for detecting single nucleotide changes and small indels, detection of copy number variants (CNVs) can provide highly valuable additional information from the data. Although there are dozens of exome CNV detection methods available, these are often difficult to use, and accuracy varies unpredictably between and within datasets.

Findings: We present Ximmer, a tool that supports an end-to-end process for evaluating, tuning, and running analysis methods for detection of CNVs in germline samples.

The costs of diabetes among Australians aged 45-64 years from 2015 to 2030: projections of lost productive life years (PLYs), lost personal income, lost taxation revenue, extra welfare payments and lost gross domestic product from Health&WealthMOD2030.

Objectives: To project the number of people aged 45-64 years with lost productive life years (PLYs) due to diabetes and related costs (lost income, extra welfare payments, lost taxation revenue); and lost gross domestic product (GDP) attributable to diabetes in Australia from 2015 to 2030.

Design: A simulation study of how the number of people aged 45-64 years with diabetes increases over time (based on population growth and disease trend data) and the economic losses incurred by individuals and the government. Cross-sectional outputs of a microsimulation model (Health&WealthMOD2030) which used the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers 2003 and 2009 as a base population and integrated outputs from two microsimulation models (Static Incomes Model and Australian Population and Policy Simulation Model), Treasury's population and labour force projections, and chronic disease trends data.

DNA methylation mediated up-regulation of TERRA non-coding RNA is coincident with elongated telomeres in the human placenta.

Study Question: What factors regulate elongated telomere length in the human placenta?

Summary Answer: Hypomethylation of TERRA promoters in the human placenta is associated with high TERRA expression, however, no clear mechanistic link between these phenomena and elongated telomere length in the human placenta was found.

What Is Known Already: Human placenta tissue and trophoblasts show longer telomere lengths compared to gestational age-matched somatic cells. However, telomerase (hTERT) expression and activity in the placenta is low, suggesting a role for an alternative lengthening of telomeres (ALT).

Economic costs of chronic disease through lost productive life years (PLYs) among Australians aged 45-64 years from 2015 to 2030: results from a microsimulation model.

Objectives: To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030.

Design, Setting And Participants: Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45-64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003).

Blood cultures in newborns and children: optimising an everyday test.

Effective use of blood cultures is a key component of the management of septic newborns and children. The technical and practical aspects of paediatric practice and the heightened susceptibility of children to infection because of immunological immaturity make automatic extrapolation of adult data difficult and potentially unfounded.