Genome-wide association study identifies a possible susceptibility locus for endometrial cancer

Background: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. Methods: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). Results: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03–1.16] for the A/G genotype and 1.17 (95% CI, 1.05–1.30) for the G/G genotype (P = 1.6 × 10−4 in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04–1.18) and 1.21 (1.08–1.35), respectively (P = 2.4 × 10−5). Conclusions: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. Impact: This study identified a potential genetic locus for endometrial cancer risk

The life course of Australian researchers : experiences of applying for research funding

The life course of Australian researchers includes regular funding applications, which incur large personal and time costs. We previously estimated that Australian researchers spent 550 years preparing 3,727 proposals for the 2012 NHMRC Project Grant funding round, at an estimated annual salary cost of AU$66 million. Despite the worldwide importance of funding rounds, there is little evidence on what researchers think of the application process. We conducted a web-based survey of Australian researchers (May–July 2013) asking about their experience with NHMRC Project Grants. Almost all researchers (n=224 at 31 May) supported changes to the application (96%) and peer-review (88%) processes; 73% supported the introduction of shorter initial Expressions of Interest; and half (50%) provided extensive comments on the NHMRC processes. Researchers agreed preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. More than half (57%) provided extensive comments on the ongoing personal impact of concurrent grant-writing and holiday seasons on family, children and other relationships. Researchers with experience on Grant Review Panels (34%) or as External Reviewers (78%) reported many sections of the proposals were rarely or never read, which suggests these sections could be cut with no impact on the quality of peer review. Our findings provide evidence on the experience of Australian researchers as applicants. The process of preparing, submitting and reviewing proposals could be streamlined to minimise the burden on applicants and peer reviewers, giving Australian researchers more time to work on actual research and be with their families.

The impact of community health professional contact postpartum on breastfeeding at 3 months : a cross-sectional retrospective study

This study investigated the effect of any health professional contact and the types of contact new mothers received in the first 10 days post-discharge on breastfeeding rates at 3 months. This cross-sectional retrospective self-report survey was distributed to women who birthed in Queensland, Australia between 1st February and 31st May 2010 at 4–5 months postpartum. Data were collected on pregnancy, birth, postpartum care and infant feeding. Logistic regression was used to assess the relationship between health professional contact and breastfeeding at 3 months. Data were analysed by birthing facility sector because of significant differences between sectors in health professional contact. The study cohort consisted of 6,852 women. Women in the public sector were more likely to be visited at home than women birthing in the private sector. Any health professional contact (AOR 1.65 99 % CI 0.98–2.76 public sector, AOR 0.78 99 % CI 0.59–1.03 private sector) and home visits (AOR 1.50 99 % CI 0.89–2.54 public sector, AOR 0.80 99 % CI 0.46–1.39 private sector) were not associated with breastfeeding at 3 months in either sector. A telephone call (AOR 2.07 99 % CI 1.06–4.03) or visit to a general practitioner (GP) (AOR 1.83 99 % CI 1.04–3.21) increased the odds of breastfeeding in public sector women. Health professional contact or home visiting in the first 10 days post-discharge did not have a significant impact on breastfeeding rates at 3 months. Post-discharge telephone contact for all women and opportunities for self-initiated clinic visits for women assessed to be at higher risk of ceasing breastfeeding may be the most effective care.

The Work-Retirement Environment

For most individuals who have the opportunity, paid work is a defining background to achievement in life. Employment has the potential to satisfy economic necessities, educational achievements, professional development, and social and cultural objectives. In many cases, it also assists individuals to define their identity, grow their self esteem, achieve personal ambitions, explore and develop collegial and professional relationships, grow skills and wisdom, and transmit this to the following generations. For many individuals, this process is not now defined and limited by a mandatory retirement date. Individuals are choosing to extend their engagement in the paid workforce and this has its benefits and challenges. This chapter examines these issues in the background of an increasingly ageing population.

Evaluation of brief dietary questions to estimate vegetable and fruit consumption – using serum carotenoids and red-cell folate

Objective: To evaluate responses to self-administered brief questions regarding consumption of vegetables and fruit by comparison with blood levels of serum carotenoids and red-cell folate. Design: A cross-sectional study in which participants reported their usual intake of fruit and vegetables in servings per day, and serum levels of five carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and red-cell folate were measured. Serum carotenoid levels were determined by high-performance liquid chromatography, and red-cell folate by an automated immunoassay system. Settings and subjects: Between October and December 2000, a sample of 1598 adults aged 25 years and over, from six randomly selected urban centres in Queensland, Australia, were examined as part of a national study conducted to determine the prevalence of diabetes and associated cardiovascular risk factors. Results: Statistically significant (P<0.01) associations with vegetable and fruit intake (categorised into groups: ≤1 serving, 2–3 servings and ≥4 servings per day) were observed for α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and red-cell folate. The mean level of these carotenoids and of red-cell folate increased with increasing frequency of reported servings of vegetables and fruit, both before and after adjusting for potential confounding factors. A significant association with lycopene was observed only for vegetable intake before adjusting for confounders. Conclusions: These data indicate that brief questions may be a simple and valuable tool for monitoring vegetable and fruit intake in this population.

A flexible protection scheme for an islanded Multi-Microgrid

Multi-Microgrids (MMGs) have been proposed to connect distributed generators (DG), microgrids (MG), and medium-voltage (MV) loads with the distribution system. A flexible protection scheme that enables an islanded MMG to continue operation during fault conditions is yet to be developed. In this paper, a protection scheme for an islanded MMG that utilises MG controllers and communication links is proposed. The MMG model used includes two MGs connected to the distribution system. Each MG consists of diesel, wind, and photovoltaic (PV) microsources. The effectiveness of the proposed protection scheme is evaluated by simulation.

An improved protection strategy for microgrids

Microgrids (MG) enable the integration of low capacity renewable energy resources with distribution systems. A recently proposed protection scheme for MGs utilising undervoltage, High Impedance Fault (HIF) detection, directional protection modules, and communication links significantly reduces the fault clearing time compared to previous schemes. In this paper, the effect of replacing undervoltage protection with differential protection in a scheme that also contains HIF and directional protection modules is studied. The MG model used in this study includes a diesel, wind, and two photovoltaic (PV) microsources. The alternative protection schemes are evaluated by simulation. It is found that the protection scheme consisting of differential, HIF detection, and directional protection modules is more effective compared to the alternative in protecting the MG from some fault conditions such as the phase-A-to-ground, phase-B-to-C, and phase-B-to-C-to-ground.

Keep ahead of the workforce development curve through the establishment of standardised training for rail incident investigators

The Australasian rail industry lacks a consistently accepted standard of minimal training necessary to perform rail incident investigations. Current Australasian courses do not offer the breadth of development required for a comprehensive career pathway in incident investigation (Biggs, Banks & Dovan, 2012; Short, Kains & Harris, 2010).

Hearing loss and a supportive tactile signal in a navigation system : effects on driving behavior and eye movements

An on-road study was conducted to evaluate a complementary tactile navigation signal on driving behaviour and eye movements for drivers with hearing loss (HL) compared to drivers with normal hearing (NH). 32 participants (16 HL and 16 NH) performed two preprogrammed navigation tasks. In one, participants received only visual information, while the other also included a vibration in the seat to guide them in the correct direction. SMI glasses were used for eye tracking, recording the point of gaze within the scene. Analysis was performed on predefined regions. A questionnaire examined participant's experience of the navigation systems. Hearing loss was associated with lower speed, higher satisfaction with the tactile signal and more glances in the rear view mirror. Additionally, tactile support led to less time spent viewing the navigation display.

The research lottery : the pressures on the Australian grant system

NHMRC Project Grants and ARC Discovery Grants are two of the major sources of funding for new ideas in Australian science. Many scientists rely on them for their job or the jobs of their staff. They are highly competitive with only around 1 in 5 applications winning funding. To increase the chances of winning funding, scientists spend a long time writing carefully crafted applications, generally at the sacrifice of their research output. And the pressures on the system and our scientists are only going to get worse.

Oral immunization with a novel lipid-based adjuvant protects against genital Chlamydia infection

Oral immunization is attractive as a delivery route because it is needle-free and useful for rapid mass vaccination programs to target pandemics or bioterrorism. This potential has not been realized for human vaccination, due to the requirement of large antigen doses and toxic (to humans) adjuvants to overcome the induction of oral tolerance and potential degradation of antigens in the stomach. To date, only oral vaccines based on live attenuated organisms have been approved for human use. In this study we describe the use of a lipid-based delivery system/adjuvant, Lipid C, for oral immunization to protect mice against genital tract chlamydial infection. Lipid C is formulated from food-grade purified and fractionated triglycerides. Bacterial shedding following vaginal challenge with Chlamydia muridarum was reduced by 50% in female mice orally immunized with the chlamydial major outer membrane protein (MOMP) formulated in Lipid C, protection equivalent to that seen in animals immunized with MOMP admixed with both cholera toxin (CT) and CpG oligodeoxynucleotides (CpG-ODN). Protection was further enhanced when MOMP, CT and CpG were all combined in the Lipid C matrix. Protection correlated with production of gamma interferon (IFN) by splenic T cells, a serum MOMP-specific IgG response and low but detectable levels of MOMP-specific IgA in vaginal lavage.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

BACKGROUND Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.

The impact of funding deadlines on personal workloads, stress and family relationships : a qualitative study of Australian researchers

Objective To examine the impact of applying for funding on personal workloads, stress and family relationships. Design Qualitative study of researchers preparing grant proposals. Setting Web-based survey on applying for the annual National Health and Medical Research Council (NHMRC) Project Grant scheme. Participants Australian researchers (n=215). Results Almost all agreed that preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. Almost all researchers agreed that they became stressed by the workload (93%) and restricted their holidays during the grant writing season (88%). Most researchers agreed that they submitted proposals because chance is involved in being successful (75%), due to performance requirements at their institution (60%) and pressure from their colleagues to submit proposals (53%). Almost all researchers supported changes to the current processes to submit proposals (95%) and peer review (90%). Most researchers (59%) provided extensive comments on the impact of writing proposals on their work life and home life. Six major work life themes were: (1) top priority; (2) career development; (3) stress at work; (4) benefits at work; (5) time spent at work and (6) pressure from colleagues. Six major home life themes were: (1) restricting family holidays; (2) time spent on work at home; (3) impact on children; (4) stress at home; (5) impact on family and friends and (6) impact on partner. Additional impacts on the mental health and well-being of researchers were identified. Conclusions The process of preparing grant proposals for a single annual deadline is stressful, time consuming and conflicts with family responsibilities. The timing of the funding cycle could be shifted to minimise applicant burden, give Australian researchers more time to work on actual research and to be with their families.

Higher uptake of long-acting reversible and permanent methods of contraception by Australian women living in rural and remote areas

Objectives: To examine factors associated with the uptake of i) long-acting reversible, ii) permanent and iii) traditional contraceptive methods among Australian women. Methods: Participants in the Australian Longitudinal Study on Women's Health born in 1973–78 reported on their contraceptive use at three surveys: 2003, 2006 and 2009. The participants were 5,849 women aged 25–30 in 2003 randomly sampled from Medicare. The main outcome measure was current contraceptive method at age 28–33 years categorised as long-acting reversible methods (implant, IUD, injection), permanent (tubal ligation, vasectomy), and traditional methods (oral contraceptive pills, condoms, withdrawal, safe period). Results: Compared to women living in major cities, women in inner regional areas were more likely to use long-acting (OR=1.26, 95%CI 1.03–1.55) or permanent methods (OR=1.43, 95%CI 1.17–1.76). Women living in outer regional/remote areas were more likely than women living in cities to use long-acting (OR=1.65, 95%CI 1.31–2.08) or permanent methods (OR=1.69, 95%CI 1.43–2.14). Conclusions: Location of residence is an important factor in women's choices about long-acting and permanent contraception in addition to the number and age of their children. Implications: Further research is needed to understand the role of geographical location in women's access to contraceptive options in Australia.

RMAA safety performance : how does it compare with Greenfield projects?

Gross value of cons truction work in the repair , maintenance, minor alte ration and addition (RMAA) sector in Hong Kong has expanded dramatically by 58% from 1998 to 2007, accounting for over 53% of the whole construction market in 2007. Unfortunately, the portion of industrial accidents arising from this sector also increased substantially during the same period. It is important to improve the safety performance of the RMAA sector. This paper has set out the objectives to examine safety statistics of RMAA works; to compare them with those of green field projects; and more importantly, to highlight potential hurdles en countered in the process of comparison and finally to provide effective recommendations for overcoming these impediments. To strive for continuous safety improvement of RMAA works, comparable safety statistics should be compiled for this sector.