Novel genetic markers for chronic kidney disease in a geographically isolated population of Indigenous Australians: Individual and multiple phenotype genome-wide association study.

Background: Chronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations.

Computed tomography scan radiation and brain cancer incidence.

Background: Computed tomography (CT) scans make substantial contributions to low-dose ionizing radiation exposures, raising concerns about excess cancers caused by diagnostic radiation.

Methods: Deidentified medicare records for all Australians aged 0-19 years between 1985-2005 were linked to national death and cancer registrations to 2012. The National Cancer Institute CT program was used to estimate radiation doses to the brain from CT exposures in 1985-2005, Poisson regression was used to model the dependence of brain cancer incidence on brain radiation dose, which lagged by 2 years to minimize reverse causation bias.

Cohort profile: The Australian Paediatric Exposure to Radiation Cohort (Aust-PERC).

Although the carcinogenic effects of high-dose radiation are well-established, the risks at low doses, such as from diagnostic X-rays, are less well understood. Children are susceptible to radiation induced cancers, and in the last decade, several cohort studies have reported increased cancer risks following computed tomography (CT) scans in childhood. However, cohort studies can be limited by insufficient follow-up, indication bias, reverse causation, or by lack of organ doses from CT scans or other exposures.

Ct Dosimetry for The Australian Cohort Data Linkage Study.

Children undergoing computed tomography (CT) scans have an increased risk of cancer in subsequent years, but it is unclear how much of the excess risk is due to reverse causation bias or confounding, rather than to causal effects of ionising radiation. An examination of the relationship between excess cancer risk and organ dose can help to resolve these uncertainties. Accordingly, we have estimated doses to 33 different organs arising from over 900 000 CT scans between 1985 and 2005 in our previously described cohort of almost 12 million Australians aged 0-19 years.

CT scans in childhood predict subsequent brain cancer: Finite mixture modelling can help separate reverse causation scans from those that may be causal.

Background: Excess brain cancers observed after computed tomography (CT) scans could be caused by ionizing radiation. However, as scans are often used to investigate symptoms of brain cancer, excess cancers could also be due to reverse causation bias. We used finite mixture models (FMM) to differentiate CT exposures that are plausibly causal from those due to reverse causation.

Analysis of the (PAR4) Single Nucleotide Polymorphism () in an Indigenous Australian Population.

The gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, , that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of the allele indicate it may be an important determinant in the ethnic differences that exist in thrombosis and hemostasis, and for patient outcomes to PAR antagonist anti-platelet therapies.

New Genetic Loci Associated With Chronic Kidney Disease in an Indigenous Australian Population.

The common occurrence of renal disease in Australian Aboriginal populations such as Tiwi Islanders may be determined by environmental and genetic factors. To explore genetic contributions, we performed a genome-wide association study (GWAS) of urinary albumin creatinine ratio (ACR) in a sample of 249 Tiwi individuals with genotype data from a 370K single nucleotide polymorphism (SNP) array. A principal component analysis (PCA) of the 249 individual Tiwi cohort and samples from 11 populations included in phase III of the HapMap Project indicated that Tiwi Islanders are a relatively distinct and unique population with no close genetic relationships to the other ethnic groups.

Diagnostic Nuclear Medicine for Paediatric Patients in Australia: Assessing the Individual's Dose Burden.

We report data for all Australians aged 0-19 y who underwent publicly funded nuclear medicine studies between 1985 and 2005, inclusive. Radiation doses were estimated for individual patients for 95 different types of studies. There were 374 848 occasions of service for 277 511 patients with a collective effective dose of 1123 Sievert (Sv).

Exposure to ionizing radiation and brain cancer incidence: The Life Span Study cohort.

Background: Ionizing radiation is a cause of cancer. This paper examines the effects of radiation dose and age at exposure on the incidence of brain cancer using data from the Life Span Study (LSS) of atomic bomb survivors.

Methods: The Radiation Effects Research Foundation website provides demographic details of the LSS population, estimated radiation doses at time of bomb in 1945, person years of follow-up and incident cancers from 1958 to 1998.

The changing use of pediatric CT in Australia.

Background: Despite the medical benefits of CT, there are concerns about increased cancer risks following CT scans in childhood.

Objective: To assess Australian temporal trends in pediatric CT scans funded through Medicare over the period 1985 to 2005, as well as changes in the types of CT scanners used.

Materials And Methods: We studied de-identified electronic records of Medicare-funded services, including CT scans, that were available for children and adults younger than 20 years between 1985 and 2005.

Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages.

Chlamydia trachomatis causes sexually transmitted infections and the blinding disease trachoma. Current data on C. trachomatis phylogeny show that there is only a single trachoma-causing clade, which is distinct from the lineages causing urogenital tract (UGT) and lymphogranuloma venerum diseases.

Short-term risk of colorectal cancer in individuals with lynch syndrome: a meta-analysis.

Purpose: For carriers of germline mutations in DNA mismatch repair genes, the most relevant statistic for cancer prevention is colorectal cancer (Lynch syndrome) risk, particularly in the short term.

Methods: We conducted a meta-analysis of all independent published Lynch syndrome studies reporting age- and sex-dependent colorectal cancer risks. We estimated 5-year colorectal cancer risk over different age groups, separately for male and female mutation carriers, and number needed to screen to prevent one death.

Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians.

Objective: To assess the cancer risk in children and adolescents following exposure to low dose ionising radiation from diagnostic computed tomography (CT) scans.

Design: Population based, cohort, data linkage study in Australia. COHORT MEMBERS: 10.

Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life.

Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood.

Understanding mortality in the 1918-1919 influenza pandemic in England and Wales.

Background: The causes of recurrent waves in the 1918-1919 influenza pandemic are not fully understood.

Objectives: To identify the risk factors for influenza onset, spread and mortality in waves 1, 2 and 3 (summer, autumn and winter) in England and Wales in 1918-1919.

Methods: Influenza mortality rates for 333 population units and putative risk factors were analysed by correlation and by regressions weighted by population size and adjusted for spatial trends.

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9.

Background: The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?

Methods: We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.

Understanding influenza transmission, immunity and pandemic threats.

The current pandemic threat can be best understood within an ecological framework that takes account of the history of past pandemics caused by influenza A, the relationships between pandemic and seasonal spread of influenza viruses, and the importance of immunity and behavioural responses in human populations. Isolated populations without recent exposure to seasonal influenza seem more susceptible to new pandemic viruses, and much collateral evidence suggests that this is due to immunity directed against epitopes shared between pandemic and previously circulating strains of inter-pandemic influenza A virus. In the highly connected modern world, most populations are regularly exposed to non-pandemic viruses, which can even boost immunity without causing influenza symptoms.

Review. The changing face of kuru: a personal perspective.

The epidemic of kuru is now known to have been transmitted among the Fore by ritual consumption of infected organs from deceased relatives. As cannibalism was suppressed by government patrol officers during the 1950s, most transmission had ceased by 1957, when the kuru research programme first commenced. As predicted in the 1960s, the epidemic has waned, with progressive ageing of kuru-affected cohorts over the years to 2007.

Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: a randomized controlled trial.

Background: For children at high risk of chronic suppurative otitis media (CSOM), strategies to prevent acute otitis media with perforation (AOMwiP) may reduce progression to CSOM.

Methods: In a double blind study in northern Australia, 103 Aboriginal infants with first detection of OME were randomised to receive either amoxicillin (50 mg/kg/d BD) or placebo for 24 weeks, or until bilateral aerated middle ears were diagnosed at two successive monthly examinations (success). Standardised clinical assessments and international standards for microbiology were used.

A biological model for influenza transmission: pandemic planning implications of asymptomatic infection and immunity.

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R(0) from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R(0).

In vivo penicillin MIC drift to extremely high resistance in Serotype 14 Streptococcus pneumoniae persistently colonizing the nasopharynx of an infant with chronic suppurative lung disease: a case study.

This is the first report of in vivo pneumococcal penicillin MIC drift from 4.0 to 16.0 mg/liter, possibly associated with alterations in the pbp1a gene.