RESPOND: a programme to prevent secondary falls in older people presenting to the emergency department with a fall: protocol for an economic evaluation.

Background: Falls remain common for community-dwelling older people and impose a substantial economic burden to the healthcare system. RESPOND is a novel falls prevention programme that aims to reduce secondary falls and fall injuries among older people who present to a hospital emergency department (ED) with a fall. The present protocol describes a prospective economic evaluation examining the incremental cost-effectiveness of the RESPOND programme, compared with usual care practice, from the Australian health system perspective.

Long-term Outcomes of the Western Australian Trial of Screening for Abdominal Aortic Aneurysms: Secondary Analysis of a Randomized Clinical Trial.

Importance: Mortality from ruptured abdominal aortic aneurysms (AAAs) remains high. The benefit of screening older men for AAAs needs to be assessed in a range of health care settings.

Objective: To assess the influence of screening for AAAs in men aged 64 to 83 years on mortality from AAAs.

The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D₂ Dopamine Receptor (D2L-R) Acts as an Intracellular Retention Signal.

This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D₂ dopamine receptor (D2L-R) confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR) located within the insert could act as an RXR-type endoplasmic reticulum (ER) retention signal. Arginine residues (R) within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E), either individually or in clusters, thus generating single, double, and triple D2L-R mutants.

A common variant association study reveals novel susceptibility loci for low HDL-cholesterol levels in ethnic Arabs.

The genetic susceptibility to acquiring low high density lipoprotein-cholesterol (LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high-density Axiom Genome-Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations (SNPs) to genotype 5495 individuals in a two-phase study involving discovery and validation sets of experiments.

Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation.

Introduction: Preoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes.

A comparison of outcomes among hospital survivors with and without severe comorbidity admitted to the intensive care unit.

Little is known about the experiences of patients with severe comorbidity discharged from Intensive Care Units (ICUs). This project aimed to determine the effects of an ICU stay for patients with severe comorbidity by comparing 1) quality of life (QOL), 2) the symptom profile of hospital survivors and 3) health service use after hospital discharge for patients admitted to ICU with and without severe comorbidity. A case-control study was used.

Resident-to-resident physical aggression leading to injury in nursing homes: a systematic review.

Background: resident-to-resident aggression (RRA) is an understudied form of elder abuse in nursing homes.

Objective: the purpose of this systematic review was to examine the published research on the frequency, nature, contributing factors and outcomes of RRA in nursing homes.

Methods: in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, this review examined all original, peer-reviewed research published in English, French, German, Italian or Spanish between 1st January 1949 and 31st December 2013 describing incidents of RRA in nursing homes.

Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease.

Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast.

Short-term n-3 fatty acid supplementation but not aspirin increases plasma proresolving mediators of inflammation.

Resolution of inflammation is an active process involving specialized proresolving mediators (SPM) formed from the n-3 fatty acids. This study examined the effect of n-3 fatty acid supplementation and aspirin on plasma SPMs in healthy humans. Healthy volunteers (n = 21) were supplemented with n-3 fatty acids (2.

EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia.

The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees.

CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.

Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (CTSH) affects disease mechanisms and progression in T1D.

In older men, lower plasma 25-hydroxyvitamin D is associated with reduced incidence of prostate, but not colorectal or lung cancer.

Context And Objective: Prostate, colorectal and lung cancers are common in men. In this study, we aimed to determine whether vitamin D status is associated with the incidence of these cancers in older men.

Design: Prospective cohort study.

Incidence and survival for Merkel cell carcinoma in Queensland, Australia, 1993-2010.

Importance: Merkel cell carcinoma (MCC) is an uncommon but highly invasive form of skin cancer. The mechanisms that cause MCC are yet to be fully determined.

Objectives: To compare the incidence and survival rates of MCC in Queensland, Australia, known to be a high-risk area, with MCC incidence and survival elsewhere in the world.

PRMT2 and RORγ expression are associated with breast cancer survival outcomes.

Protein arginine methyltransferases (PRMTs) methylate arginine residues on histones and target transcription factors that play critical roles in many cellular processes, including gene transcription, mRNA splicing, proliferation, and differentiation. Recent studies have linked PRMT-dependent epigenetic marks and modifications to carcinogenesis and metastasis in cancer. However, the role of PRMT2-dependent signaling in breast cancer remains obscure.

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

Background: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF.

Cognitive performance in high-altitude Andean residents compared with low-altitude populations: from childhood to older age.

Objectives: To assess cognition in populations born and living at high altitude (HA; 3,700 m) and low altitude (LA; 500 m) in Bolivia, who were similar for both socioeconomic status and genetic ancestry. To determine whether HA hypoxia influences cognitive decline across the life span.

Method: In total, 191 healthy participants aged 4 to 85 years were assessed at HA (N = 94; 33; 35% male) and LA (N = 97; 46, 47% male) on a battery of cognitive tasks: fluid intelligence, attention, short- and long-term memory, and psychomotor speed.

Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.

Traditional medicinal herb Andrographis paniculata is known to possess anti-tumor activity, and its potential active compound is the diterpenoid lactone andrographolide (ANGL). In this study, we have found that ANGL inhibits tumor growth in nude mice bearing xenografted Hep3B cancer cells, concomitant with a reduction in tumor vessel counts. ANGL inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenic responses in vitro and neoangiogenesis in vivo.

Breast cancer prognosis predicted by nuclear receptor-coregulator networks.

Although molecular signatures based on transcript expression in breast cancer samples have provided new insights into breast cancer classification and prognosis, there are acknowledged limitations in current signatures. To provide rational, pathway-based signatures of disrupted physiology in cancer tissues that may be relevant to prognosis, this study has directly quantitated changed gene expression, between normal breast and cancer tissue, as a basis for signature development. The nuclear receptor (NR) family of transcription factors, and their coregulators, are fundamental regulators of every aspect of metazoan life, and were rigorously quantified in normal breast tissues and ERα positive and ERα negative breast cancers.

Comparison of sequence variants in transcriptomic control regions across 17 mouse genomes.

The laboratory mouse is the most widely used mammalian model organism in biomedical research, so a thorough annotation of functional variation in the mouse genome would be of significant value. In this study, we compared sequence variation in a comprehensive list of functional elements (e.g.

Analysis of the human mitochondrial transcriptome using directional deep sequencing and parallel analysis of RNA ends.

RNA sequencing using next-generation technologies provides comprehensive coverage of transcriptomes at a much greater depth than conventional transcriptomic methods. The human mitochondrial genome is relatively small, and sequencing its transcriptome provides a valuable method to investigate changes in RNA metabolism in great detail. Here we describe two methods that use next-generation technologies to investigate mitochondrial RNAs.

Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals.

Sexuality, body image and relationships following burns: analysis of BSHS-B outcome measures.

Background: The Burns Specific Health Scale - Brief (BSHS-B) was analyzed to investigate the longitudinal impact of burns on sexuality and body image. Four sub-domains of the BSHS-B domains were of particular interest: sexuality, body image, affect and relationships, and as such were investigated for correlation between all of the sub-scales of the BSHS-B.

Methods: A total of 1846 observations from 865 Western Australian burn patient BSHS-B questionnaires were analyzed.

Challenges of diagnostic exome sequencing in an inbred founder population.

Exome sequencing was used as a diagnostic tool in a Roma/Gypsy family with three subjects (one deceased) affected by lissencephaly with cerebellar hypoplasia (LCH), a clinically and genetically heterogeneous diagnostic category. Data analysis identified high levels of unreported inbreeding, with multiple rare/novel "deleterious" variants occurring in the homozygous state in the affected individuals. Step-wise filtering was facilitated by the inclusion of parental samples in the analysis and the availability of ethnically matched control exome data.

Occupational exposure to solar radiation in Australia: who is exposed and what protection do they use?

Objective: Solar ultraviolet radiation (UVR) exposure is widely recognised as a leading cause of skin cancer, with outdoor workers being particularly at risk. Little is known on a national level about how many workers are exposed to solar radiation, the circumstances in which they are exposed, or their use of protective measures.

Methods: The Australian Work Exposures Study (AWES) was a cross-sectional telephone survey of 5,023 Australian workers aged 18 to 65.

Cigarette smoking and pancreatic cancer risk: more to the story than just pack-years.

Purpose: Cigarette smoking is an established risk factor for pancreatic adenocarcinoma. However, few studies have thoroughly investigated the effects of independent smoking dimensions (duration, intensity, cumulative dose and time since quitting) on risk estimates. We analysed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, with the aim of determining which smoking component is primarily important to pancreatic cancer risk.