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Cousminer D.L.,University of Helsinki | Stergiakouli E.,University of Bristol | Berry D.J.,University College London | Ang W.,The University ofWestern Australia | And 50 more authors.
Human Molecular Genetics | Year: 2014

Little is known about genes regulating male puberty. Further, while many identified pubertal timing 1variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9×10-9), amenarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6×10-5) and short adult stature (p = 7.5×10-6) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies. © The Author 2014. Published by Oxford University Press. All rights reserved.


Chittoor G.,The Texas Institute | Farook V.S.,The Texas Institute | Puppala S.,The Texas Institute | Fowler S.P.,University of Texas Health Science Center at San Antonio | And 20 more authors.
Molecular Human Reproduction | Year: 2013

Pretermbirth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility toPTBinMexican Americans (MAs), a minority population in the USA, using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family BirthWeight Study. Only 1302 singleton births from 288 families with information on PTB and significant covariateswere considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An ~10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h2±SE: 0.75±0.20) and significant (P = 4.5 × 10-5), after adjusting for the significant effects of birthweight and birth order.We found significant evidence for linkage of PTB (LOD = 3.6; nominal P = 2.3 ×10-5; empirical P = 1.0× 1010-5) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Knight A.,University of South Australia | Bryan J.,University of South Australia | Wilson C.,University of South Australia | Hodgson J.M.,The University ofWestern Australia | And 2 more authors.
Nutrients | Year: 2016

Evidence from a limited number of randomised controlled intervention trials (RCTs) have shown that a Mediterranean dietary pattern may reduce the risk of cognitive decline and enhance cognitive function among healthy older adults. However, there are currently no data in non-Mediterranean older adult populations. The present study aimed to address this gap by examining the effect of a Mediterranean dietary pattern (MedDiet) for six months on aspects of cognitive function in a randomised controlled intervention trial (the MedLey study) that extended for a duration of 18 months. In the final analysed cohort, a total of 137 men and women (mean age of 72.1 ± 5.0 years) randomly assigned to either a MedDiet or control diet (HabDiet) (i.e., habitual dietary intake), were assessed on a comprehensive neuropsychological test battery, including 11 individual tests. In multivariable-adjusted models, the MedDiet group did not perform significantly better than the HabDiet control group for executive functioning (adjusted mean differences: +2.53, 95% CI −2.59 to 7.65, p = 0.33); speed of processing (adjusted mean differences: +3.24, 95% CI −1.21 to 7.70, p = 0.15); memory (adjusted mean differences: +2.00, 95% CI −3.88 to 7.88, p = 0.50); visual-spatial ability (adjusted mean differences: +0.21, 95% CI −0.38 to 0.81, 0.48); and overall age-related cognitive performance (adjusted mean differences: +7.99, 95% CI −4.00 to 19.9, p = 0.19). In conclusion, this study did not find evidence of a beneficial effect of a MedDiet intervention on cognitive function among healthy older adults. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Lashkari M.,Kerman Graduate University of Technology | Hentz M.G.,Port St. LucieFL | Boykin L.M.,The University ofWestern Australia
PeerJ | Year: 2015

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), vector of citrus greening disease pathogen, Huanglongbing (HLB), is considered the most serious pest of citrus in the world. Prior molecular based studies have hypothesized a link between the D. citri in Iran and the USA (Florida). The purpose of this study was to collect morphometric data fromD. citri populations fromIran (mtCOI haplotype-1), Florida (mtCOI haplotype-1), and Pakistan (mtCOI haplotype-6), to determine whether different mtCOI haplotypes have a relationship to a specific morphometric variation. 240 samples from6 ACP populations (Iran-Jiroft, Chabahar; Florida-Ft. Pierce, Palm Beach Gardens, Port St. Lucie; and Pakistan-Punjab) were collected for comparison.Measurements of 20 morphological characters were selected, measured and analysed using ANOVA and MANOVA. The results indicate differences among the 6 ACP populations (Wilks' lambda = 0.0376, F = 7.29, P < 0.0001). The body length (BL), circumanal ring length (CL), antenna length (AL), forewing length (WL) and Rs vein length of forewing (RL) were the most important characters separating the populations. The cluster analysis showed that the Iran and Florida populations are distinct from each other but separate from the Pakistan population. Thus, three subgroups can be morphologically discriminated within D. citri species in this study, (1) Iran, (2) USA (Florida) and (3) Pakistan population.Morphometric comparisons provided further resolution to the mtCOI haplotypes and distinguished the Florida and Iranian populations. © 2015 Lashkari et al.


Martins I.J.,Edith Cowan University | Martins I.J.,The University ofWestern Australia | Martins I.J.,Mccusker Alzheimers Research Foundation
International Journal of Molecular Sciences | Year: 2015

Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Kemp M.W.,University of Western Australia | Newnham J.P.,University of Western Australia | Challis J.G.,The University ofWestern Australia | Jobe A.H.,University of Western Australia | And 2 more authors.
Human Reproduction Update | Year: 2016

Background: The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation. Methods: Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review. Results: Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings. Conclusions: New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy. © The Author 2015.


Meuleners L.B.,Curtin University Australia | Fraser M.L.,Curtin University Australia | Ng J.,The University ofWestern Australia | Morlet N.,Curtin University Australia
Age and Ageing | Year: 2014

Background: cataract is a leading cause of reversible vision impairment and may increase falls in older adults. Objective: to assess the risk of an injury due to a fall among adults aged 60+, 2 years before first-eye cataract surgery, between first-eye surgery and second-eye surgery and 2 years after second-eye surgery. Design: a retrospective cohort study. Setting: Western Australian Hospital Morbidity Data System and the Western Australian Death Registry. Subjects: there were 28,396 individuals aged 60+ years who underwent bilateral cataract surgery in Western Australia between 2001 and 2008. Methods: Poisson regression analysis based on generalised estimating equations compared the frequency of falls 2 years before first-eye cataract surgery, between first-and second-eye surgery and 2 years after second-eye cataract surgery after accounting for potential confounders. Results: the risk of an injurious fall that required hospitalisation doubled (risk ratio: 2.14, 95% confidence interval: 1.82 to 2.51) between first-and second-eye cataract surgery compared with the 2 years before first-eye surgery. There was a 34% increase in the number of injurious falls that required hospitalisation in the 2 years after second-eye cataract surgery compared with the 2 years before first-eye surgery (risk ratio: 1.34, 95% confidence interval: 1.16-1.55). Conclusions: there was an increased risk of injurious falls after first-and second-eye cataract surgery which has implications for the timely provision of second-eye surgery as well as appropriate refractive management between surgeries. © The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society.


Black L.J.,Curtin University Australia | Jacoby P.,The University ofWestern Australia | Nowson C.A.,Deakin University | Daly R.M.,Deakin University | Lucas R.M.,Australian National University
Nutrients | Year: 2016

Despite concerns about vitamin D deficiency in the Australian population, little is known about the prevalence and predictors of vitamin D-containing supplement use. We described the use of vitamin D-containing supplements, and investigated associations between supplemental vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, using a single 24-h dietary recall from the 2011–2013 Australian Health Survey (n = 12,153; ages ≥ 2 years). Multiple regression models were used to investigate predictors of vitamin D-containing supplement use in adults, and associations between dose and serum 25(OH)D concentrations/vitamin D sufficiency (≥50 nmol/L), adjusting for potential confounders. The prevalence of vitamin D-containing supplement use was 10%, 6% and 19% in children, adolescents and adults, respectively. Predictors of vitamin D-containing supplement use in adults included being female, advancing age, higher educational attainment, higher socio-economic status, not smoking, and greater physical activity. After adjusting for potential confounders, a 40 IU (1 µg) increase in vitamin D intake from supplements was associated with an increase of 0.41 nmol/L in serum 25(OH)D concentrations (95% CI 0.35, 0.47; p < 0.001). However, the prevalence of vitamin D-containing supplement use was generally low in the Australian population, particularly for single vitamin D supplements, with most supplement users obtaining only low levels of vitamin D from other supplement types. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


Lim J.K.,The University ofWestern Australia | Lehane B.M.,The University ofWestern Australia
Frontiers in Offshore Geotechnics III - Proceedings of the 3rd International Symposium on Frontiers in Offshore Geotechnics, ISFOG 2015 | Year: 2015

The compelling evidence for displacement pile set-up (i.e. capacity gains over time after installation) of shaft friction in sand has led to increasing attempts to incorporate time effects in design practice as well as in probabilistic analyses and numerical modelling. The progression is, however, based on a range of dubious inferences from case history data and trends that display a wide degree of scatter. The existing database of field tests indicates that the majority of the reported cases of set-up were assessed from dynamic load tests and static re-tests and, as a consequence, the interpreted degree of set-up differs from that of a virgin pile. In addition, these cases are usually characterised under the assumption that shaft friction increases vary with the logarithm of time. Recent research also reveals that the jacking procedures commonly employed in pile experiments (to model driven piles) lead to a different ageing behaviour to driven piles. Some of these difficulties are highlighted in this paper with the aim of reflecting current understanding of the phenomenon of pile set-up in sand. © 2015 Taylor and Francis Group, London.


Truong P.,The University ofWestern Australia | Lehane B.M.,The University ofWestern Australia
Frontiers in Offshore Geotechnics III - Proceedings of the 3rd International Symposium on Frontiers in Offshore Geotechnics, ISFOG 2015 | Year: 2015

Current design standards for piles in sand are based on research conducted over 30 years ago with limited testing data and consideration of cyclic effects. With a global increase in the use of monopiles as foundations for offshore and near-shore structures to sustain long term cyclic environmental loads, there is now a need to improve understanding of the behaviour of piles under lateral cyclic loading. This paper addresses the shortage of test data by presenting results from a series of lateral cyclic loading tests conducted in medium dense sand in the centrifuge. These results are compared with data from recent publications to improve insights into the effects of cyclic load characteristics and soil density on the pile head displacement, pile bending moments, soil-pile stiffness and soil reaction (p − y curves). © 2015 Taylor and Francis Group, London.

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