GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

Negligible heat strain in armored vehicle officers wearing personal body armor

Objectives This study evaluated the heat strain experienced by armored vehicle officers (AVOs) wearing personal body armor (PBA) in a sub-tropical climate. Methods Twelve male AVOs, aged 35-58 years, undertook an eight hour shift while wearing PBA. Heart rate and core temperature were monitored continuously. Urine specific gravity (USG) was measured before and after, and with any urination during the shift. Results Heart rate indicated an intermittent and low-intensity nature of the work. USG revealed six AVOs were dehydrated from pre through post shift, and two others became dehydrated. Core temperature averaged 37.4 ± 0.3°C, with maximum's of 37.7 ± 0.2°C. Conclusions Despite increased age, body mass, and poor hydration practices, and Wet-Bulb Globe Temperatures in excess of 30°C; the intermittent nature and low intensity of the work prevented excessive heat strain from developing.

Duration-dependant response of mixed-method pre-cooling for intermittent-sprint exercise in the heat

This study examined the effects of pre-cooling duration on performance and neuromuscular function for self-paced intermittent-sprint shuttle running in the heat. Eight male, team-sport athletes completed two 35-min bouts of intermittent-sprint shuttle running separated by a 15-min recovery on three separate occasions (33°C, 34% relative humidity). Mixed-method pre-cooling was completed for 20 min (COOL20), 10-min (COOL10) or no cooling (CONT) and reapplied for 5-min mid-exercise. Performance was assessed via sprint times, percentage decline and shuttle-running distance covered. Maximal voluntary contractions (MVC), voluntary activation (VA) and evoked twitch properties were recorded pre- and post-intervention and mid- and post-exercise. Core temperature (T c), skin temperature, heart rate, capillary blood metabolites, sweat losses, perceptual exertion and thermal stress were monitored throughout. Venous blood draws pre- and post-exercise were analyzed for muscle damage and inflammation markers. Shuttle-running distances covered were increased 5.2 ± 3.3% following COOL20 (P < 0.05), with no differences observed between COOL10 and CONT (P > 0.05). COOL20 aided in the maintenance of mid- and post-exercise MVC (P < 0.05; d > 0.80), despite no conditional differences in VA (P > 0.05). Pre-exercise T c was reduced by 0.15 ± 0.13°C with COOL20 (P < 0.05; d > 1.10), and remained lower throughout both COOL20 and COOL10 compared to CONT (P < 0.05; d > 0.80). Pre-cooling reduced sweat losses by 0.4 ± 0.3 kg (P < 0.02; d > 1.15), with COOL20 0.2 ± 0.4 kg less than COOL10 (P = 0.19; d = 1.01). Increased pre-cooling duration lowered physiological demands during exercise heat stress and facilitated the maintenance of self-paced intermittent-sprint performance in the heat. Importantly, the dose-response interaction of pre-cooling and sustained neuromuscular responses may explain the improved exercise performance in hot conditions.

The case for good reviewing

After some years of remarkable growth, the scholarly field of Project Management (PM) research currently finds itself in a crucial stage of development. In this editorial, we make an analysis of submissions to PM's premier specialty journal, the International Journal of Project Management over the period 2007–2010, and argue that one of the most important ways in which PM research can further evolve is to pay more attention to the mundane, yet important, act of good reviewing — an activity that we believe has received relatively little attention in the PM community thus far. Let us begin by considering the crucial juncture that, as a scholarly discipline, PM is currently at. On the one hand, the PM research field is characterized by signs of major progress. For one, there has been a strong growth in terms of published output: recent years have seen the publication of three major edited volumes with a central focus on PM, published by top-tier publishers (Cattani et al., 2011, Kenis et al., 2009 and Morris et al., 2011); the PM/temporary organizations literature published in ISI ranked peer-reviewed articles is growing exponentially (Bakker, 2010); and besides some of the long-standing PM specialty journals, the field has recently seen the rise of a number of new journals, including the International Journal of Managing Projects in Business, the International Journal of Project Organisation and Management, and the Journal of Project, Program, and Portfolio Management.

Bomb disposal in the tropics : a cocktail of metabolic and environmental heat

Bomb technicians perform their work while encapsulated in explosive ordnance disposal (EOD) suits. Designed primarily for safety, these suits have an unintended consequence of impairing the body’s natural mechanisms for heat dissipation. Purpose: To quantify the heat strain encountered during an EOD operational scenario in the tropical north of Australia. Methods: All active police male bomb technicians, located in a tropical region of Australia (n=4, experience 7 ± 2.1 yrs, age 34 ± 2 yrs, height 182.3 ± 5.4 cm, body mass 95 ± 4 kg, VO2max 46 ± 5.7 ml.kg-1.min-1) undertook an operational scenario wearing the Med-Eng EOD 9 suit and helmet (~32 kg). The climatic conditions ranged between 27.1–31.8°C ambient temperature, 66-88% relative humidity, and 30.7-34.3°C wet bulb globe temperature. The scenario involved searching a two story non air-conditioned building for a target; carrying and positioning equipment for taking an X-ray; carrying and positioning equipment to disrupt the target; and finally clearing the site. Core temperature and heart rate were continuously monitored, and were used to calculate a physiological strain index (PSI). Urine specific gravity (USG) assessed hydration status and heat associated symptomology were also recorded. Results: The scenario was completed in 121 ± 22 mins (23.4 ± 0.4% work, 76.5 ± 0.4% rest/recovery). Maximum core temperature (38.4 ± 0.2°C), heart rate (173 ± 5.4 bpm, 94 ± 3.3% max), PSI (7.1 ± 0.4) and USG (1.031 ± 0.002) were all elevated after the simulated operation. Heat associated symptomology highlighted that moderate-severe levels of fatigue and thirst were universally experienced, muscle weakness and heat sensations experienced by 75%, and one bomb technician reported confusion and light-headedness. Conclusion: All bomb technicians demonstrated moderate-high levels of heat strain, evidenced by elevated heart rate, core body temperature and PSI. Severe levels of dehydration and noteworthy heat-related symptoms further highlight the risks to health and safety faced by bomb technicians operating in tropical locations.

Neighbourhood disadvantage, individual-level socioeconomic position, and self-reported chronic arthritis : a cross-sectional multilevel study

Objective: To examine the association between individual- and neighborhood-level disadvantage and self-reported arthritis. Methods: We used data from a population-based cross-sectional study conducted in 2007 among 10,757 men and women ages 40–65 years, selected from 200 neighborhoods in Brisbane, Queensland, Australia using a stratified 2-stage cluster design. Data were collected using a mail survey (68.5% response). Neighborhood disadvantage was measured using a census-based composite index, and individual disadvantage was measured using self-reported education, household income, and occupation. Arthritis was indicated by self-report. Data were analyzed using multilevel modeling. Results: The overall rate of self-reported arthritis was 23% (95% confidence interval [95% CI] 22–24). After adjustment for sociodemographic factors, arthritis prevalence was greatest for women (odds ratio [OR] 1.5, 95% CI 1.4–1.7) and in those ages 60–65 years (OR 4.4, 95% CI 3.7–5.2), those with a diploma/associate diploma (OR 1.3, 95% CI 1.1–1.6), those who were permanently unable to work (OR 4.0, 95% CI 3.1–5.3), and those with a household income <$25,999 (OR 2.1, 95% CI 1.7–2.6). Independent of individual-level factors, residents of the most disadvantaged neighborhoods were 42% (OR 1.4, 95% CI 1.2–1.7) more likely than those in the least disadvantaged neighborhoods to self-report arthritis. Cross-level interactions between neighborhood disadvantage and education, occupation, and household income were not significant. Conclusion: Arthritis prevalence is greater in more socially disadvantaged neighborhoods. These are the first multilevel data to examine the relationship between individual- and neighborhood-level disadvantage upon arthritis and have important implications for policy, health promotion, and other intervention strategies designed to reduce the rates of arthritis, indicating that intervention efforts may need to focus on both people and places.

An ensemble method for predicting subnuclear localizations from primary protein structures

Background Predicting protein subnuclear localization is a challenging problem. Some previous works based on non-sequence information including Gene Ontology annotations and kernel fusion have respective limitations. The aim of this work is twofold: one is to propose a novel individual feature extraction method; another is to develop an ensemble method to improve prediction performance using comprehensive information represented in the form of high dimensional feature vector obtained by 11 feature extraction methods. Methodology/Principal Findings A novel two-stage multiclass support vector machine is proposed to predict protein subnuclear localizations. It only considers those feature extraction methods based on amino acid classifications and physicochemical properties. In order to speed up our system, an automatic search method for the kernel parameter is used. The prediction performance of our method is evaluated on four datasets: Lei dataset, multi-localization dataset, SNL9 dataset and a new independent dataset. The overall accuracy of prediction for 6 localizations on Lei dataset is 75.2% and that for 9 localizations on SNL9 dataset is 72.1% in the leave-one-out cross validation, 71.7% for the multi-localization dataset and 69.8% for the new independent dataset, respectively. Comparisons with those existing methods show that our method performs better for both single-localization and multi-localization proteins and achieves more balanced sensitivities and specificities on large-size and small-size subcellular localizations. The overall accuracy improvements are 4.0% and 4.7% for single-localization proteins and 6.5% for multi-localization proteins. The reliability and stability of our classification model are further confirmed by permutation analysis. Conclusions It can be concluded that our method is effective and valuable for predicting protein subnuclear localizations. A web server has been designed to implement the proposed method. It is freely available at http://bioinformatics.awowshop.com/snlpr​ed_page.php.

Language affects length of stay in emergency departments in Queensland public hospitals

BACKGROUND: A long length of stay (LOS) in the emergency department (ED) associated with overcrowding has been found to adversely affect the quality of ED care. The objective of this study is to determine whether patients who speak a language other than English at home have a longer LOS in EDs compared to those whose speak only English at home. METHODS: A secondary data analysis of a Queensland state-wide hospital EDs dataset (Emergency Department Information System) was conducted for the period, 1 January 2008 to 31 December 2010. RESULTS: The interpreter requirement was the highest among Vietnamese speakers (23.1%) followed by Chinese (19.8%) and Arabic speakers (18.7%). There were significant differences in the distributions of the departure statuses among the language groups (Chi-squared=3236.88, P<0.001). Compared with English speakers, the Beta coeffi cient for the LOS in the EDs measured in minutes was among Vietnamese, 26.3 (95%CI: 22.1–30.5); Arabic, 10.3 (95%CI: 7.3–13.2); Spanish, 9.4 (95%CI: 7.1–11.7); Chinese, 8.6 (95%CI: 2.6–14.6); Hindi, 4.0 (95%CI: 2.2–5.7); Italian, 3.5 (95%CI: 1.6–5.4); and German, 2.7 (95%CI: 1.0–4.4). The fi nal regression model explained 17% of the variability in LOS. CONCLUSION: There is a close relationship between the language spoken at home and the LOS at EDs, indicating that language could be an important predictor of prolonged LOS in EDs and improving language services might reduce LOS and ease overcrowding in EDs in Queensland's public hospitals.

Numerical analysis of shape transition in graphene nanoribbons

Graphene nanoribbon (GNR) with free edges can exhibit non-flat morphologies due to pre-existing edge stress. Using molecular dynamics (MD) simulations, we investigate the free-edge effect on the shape transition in GNRs with different edge types, including regular (armchair and zigzag), armchair terminated with hydrogen and reconstructed armchair. The results show that initial edge stress and energy are dependent on the edge configurations. It is confirmed that pre-strain on the free edges is a possible way to limit the random shape transition of GNRs. In addition, the influence of surface attachment on the shape transition is also investigated in this work. It is found that surface attachment can lead to periodic ripples in GNRs, dependent on the initial edge configurations.

Human milk xanthine oxidase and neonatal salivary nucleotide precursors generate hydrogen peroxide; a novel pathway with potential role in regulating oral microflora

Background: Xanthine oxidase (XO) is a complex molybdeno-flavoprotein occurring with high activity in the milk fat globule membrane (MFGM) in all mammalian milk and is involved in the final stage of degradation of purine nucleotides. It catalyzes the sequential oxidation of hypoxanthine to xanthine and uric acid, accompanied by production of hydrogen peroxide and superoxide anion. Human saliva has been extensively described for its composition of proteins, electrolytes, cortisol, melatonin and some metabolites such as amino acids, but little is known about nucleotide metabolites. Method: Saliva was collected with swabs from babies; at full-term 1-4 days, 6-weeks, 6-months and 12-months. Unstimulated fasting (morning) saliva samples were collected directly from 77 adults. Breast milk was collected from 24 new mothers. Saliva was extracted from swabs and ultra-filtered. Nucleotide metabolites were analyzed by RP-HPLC with UV-photodiode array and ESI-MS/MS. XO activity was measured as peroxide production from hypoxanthine. Bacterial inhibition over time was assessed using CFU/mL or OD. Results: Median concentrations (μmol/L) of salivary nucleobases and nucleosides for neonates/6-weeks/6-months/12-months/adult respectively were: uracil 5.3/0.8/1.4/0.7/0.8, hypoxanthine 27/7.0/1.1/0.8/2.0, xanthine 19/7.0/2.0/2.0/2.0, adenosine 12/7.0/0.9/0.8/0.1, inosine 11/5.0/0.3/0.4/0.2, guanosine 7.0/6.0/0.5/0.4/0.1, uridine 12/0.8/0.3/0.9/0.4. Deoxynucleosides and dihydropyrimidines concentrations were essentially negligible. XO activity (Vmax:mean ± SD) in breast milk was 8.9 ± 6.2 μmol/min/L and endogenous peroxide was 27 ± 12 μmol/L; mixing breast milk with neonate saliva generated ~40 μmol/L peroxide,which inhibited Staphylococcus aureus. Conclusions: Salivary metabolites, particularly xanthine/hypoxanthine, are high in neonates, transitioning to low adult levels between 6-weeks to 6-months (p < 0.001). Peroxide occurs in breast milk and is boosted during suckling as an antibacterial system.

Factors associated with common mental disorders during the transition to adulthood : do emerging adults and ‘early starters’ differ? Findings from an Australian birth cohort study

Background: Despite increasing diversity in pathways to adulthood, choices available to young people are influenced by environmental, familial and individual factors, namely access to socioeconomic resources, family support and mental and physical health status. Young people from families with higher socioeconomic position (SEP) are more likely to pursue tertiary education and delay entry to adulthood, whereas those from low socioeconomic backgrounds are less likely to attain higher education or training, and more likely to partner and become parents early. The first group are commonly termed ‘emerging adults’ and the latter group ‘early starters’. Mental health disorders during this transition can seriously disrupt psychological, social and academic development as well as employment prospects. Depression, anxiety and most substance use disorders have early onset during adolescence and early adulthood with approximately three quarters of lifetime psychiatric disorders having emerged by 24 years of age. Aims: This thesis aimed to explore the relationships between mental health, sociodemographic factors and family functioning during the transition to adulthood. Four areas were investigated: 1) The key differences between emerging adults and ‘early starters’, were examined and focused on a series of social, economic, and demographic factors as well as DSM-IV diagnoses; 2) Methodological issues associated with the measurement of depression and anxiety in young adults were explored by comparing a quantitative measure of symptoms of anxiety and depression (Achenbach’s YSR and YASR internalising scales) with DSM-IV diagnosed depression and anxiety. 3) The association between family SEP and DSM-IV depression and anxiety was examined in relation to the different pathways to adulthood. 4) Finally, the association between pregnancy loss, abortion and miscarriage, and DSM-IV diagnoses of common psychiatric disorders was assessed in young women who reported early parenting, experiencing a pregnancy loss, or who had never been pregnant. Methods: Data were taken from the Mater University Study of Pregnancy (MUSP), a large birth cohort started in 1981 in Brisbane, Australia. 7223 mothers and their children were assessed five times, at 6 months, 5, 14 and 21 years after birth. Over 3700 young adults, aged 18 to 23 years, were interviewed at the 21-year phase. Respondents completed an extensive series of self-reported questionnaires and a computerised structured psychiatric interview. Three outcomes were assessed at the 21-year phase. Mental health disorders diagnosed by a computerised structured psychiatric interview (CIDI-Auto), the prevalence of DSM-IV depression, anxiety and substance use disorders within the previous 12-month, during the transition (between ages of 18 and 23 years) or lifetime were examined. The primary outcome “current stage in the transition to adulthood” was developed using a measure conceptually constructed from the literature. The measure was based on important demographic markers, and these defined four independent groups: emerging adults (single with no children and living with parents), and three categories of ‘early starter’, singles (with no children or partner, living independently), those with a partner (married or cohabitating but without children) and parents. Early pregnancy loss was assessed using a measure that also defined four independent groups and was based on pregnancy outcomes in the young women This categorised the young women into those who were never pregnant, women who gave birth to a live child, and women who reported some form of pregnancy loss, either an abortion or a spontaneous miscarriage. A series of analyses were undertaken to test the study aims. Potential confounding and mediating factors were prospectively measured between the child’s birth and the 21-year phase. Binomial and multinomial logistic regression was used to estimate the risk of relevant outcomes, and the associations were reported as odds ratios (OR) and 95% confidence intervals (95%CI). Key findings: The thesis makes a number of important contributions to our understanding of the transition to adulthood, particularly in relation to the mental health consequences associated with different pathways. Firstly, findings from the thesis clearly showed that young people who parented or partnered early fared worse across most of the economic and social factors as well as the common mental disorders when compared to emerging adults. That is, young people who became early parents were also more likely to experience recent anxiety (OR=2.0, 95%CI 1.5-2.8) and depression (OR=1.7, 95%CI 1.1-2.7) than were emerging adults after taking into account a range of confounding factors. Singles and those partnering early also had higher rates of lifetime anxiety and depression than emerging adults. Young people who partnered early, but were without children, had decreased odds of recent depression; this may be due to the protective effect of early marriage against depression. It was also found that young people who form families early had an increased risk of cigarette smoking (parents OR=3.7, 95%CI 2.9-4.8) compared to emerging adults, but not heavy alcohol (parents OR=0.4, 95%CI 0.3-0.6) or recent illicit drug use. The high rates of cigarette smoking and tobacco use disorders in ‘early starters’ were explained by common risk factors related to early adversity and lower SEP. Having a child and early marriage may well function as a ‘turning point’ for some young people, it is not clear whether this is due to a conscious decision to disengage from a previous ‘substance using’ lifestyle or simply that they no longer have the time to devote to such activities because of child caring. In relation to the methodological issues associated with assessing common mental disorders in young adults, it was found that although the Achenbach empirical internalising scales successfully predicted both later DSM-IV depression (YSR OR=2.3, 95%CI 1.7-3.1) and concurrently diagnosed depression (YASR OR=6.9, 95%CI 5.0- 9.5) and anxiety (YASR OR=5.1, 95%CI 3.8- 6.7), the scales discriminated poorly between young people with or without DSM-IV diagnosed mood disorder. Sensitivity values (the proportion of true positives) for the internalising scales were surprisingly low. Only a third of young people with current DSM-IV depression (range for each of the scales was between 34% to 42%) were correctly identified as cases by the YASR internalising scales, and only a quarter with current anxiety disorder (range of 23% to 31%) were correctly identified. Also, use of the DSM-oriented scales increased sensitivity only marginally (for depression between 2-8%, and anxiety between 2-6%) above the standard Achenbach scales. This is despite the fact that the DSM-oriented scales were originally developed to overcome the poor prediction of DSM-IV diagnoses by the Achenbach scales. The internalising scales, both standard and DSM-oriented, were much more effective at identifying young people with comorbid depression and anxiety, with OR’s 10.1 to 21.7 depending on the internalising scale used. SEP is an important predictor of both an early transition to adulthood and the experience of anxiety during that time Family income during adolescence was a strong predictor of early parenting and partnering before age 24 but not early independent living. Compared to families in the upper quintile, young people from families with low income were nearly twice as likely to live with a partner and four times more likely to become parents (OR ranged from 2.6 to 4.0). This association remained after adjusting for current employment and education level. Children raised in low income families were 30% more likely to have an anxiety disorder (OR=1.3, 95%CI 0.9-1.9), but not depression, as young adults when compared to children from wealthier families. Emerging adults and ‘early starters’ from low income families did not differ in their likelihood of having a later anxiety disorder. Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis) [abortion OR=3.6, 95%CI 2.0-6.7 and miscarriage OR=2.6, 95%CI 1.2-5.4]. Abortion was associated with alcohol use disorder (OR=2.1, 95%CI 1.3- 3.5) and 12-month depression (OR=1.9, 95%CI 1.1- 3.1). These finding suggest that the association identified by Fergusson et al between abortion and later psychiatric disorders in young women may be due to pregnancy loss and not to abortion, per se. Conclusion: Findings from this thesis support the view that young people who parent or partner early have a greater burden of depression and anxiety when compared to emerging adults. As well, young women experiencing pregnancy loss, from either abortion or miscarriage, are more likely to experience depression and anxiety than are those who give birth to a live infant or who have never been pregnant. Depression, anxiety and substance use disorders often go unrecognised and untreated in young people; this is especially true in young people from lower SEP. Early identification of these common mental health disorders is important, as depression and anxiety experienced during the transition to adulthood have been found to seriously disrupt an individual’s social, educational and economic prospects in later life.

Cost effectiveness of patient education for the prevention of falls in hospital : economic evaluation from a randomized controlled trial

Background Falls are one of the most frequently occurring adverse events that impact upon the recovery of older hospital inpatients. Falls can threaten both immediate and longer-term health and independence. There is need to identify cost-effective means for preventing falls in hospitals. Hospital-based falls prevention interventions tested in randomized trials have not yet been subjected to economic evaluation. Methods Incremental cost-effectiveness analysis was undertaken from the health service provider perspective, over the period of hospitalization (time horizon) using the Australian Dollar (A$) at 2008 values. Analyses were based on data from a randomized trial among n = 1,206 acute and rehabilitation inpatients. Decision tree modeling with three-way sensitivity analyses were conducted using burden of disease estimates developed from trial data and previous research. The intervention was a multimedia patient education program provided with trained health professional follow-up shown to reduce falls among cognitively intact hospital patients. Results The short-term cost to a health service of one cognitively intact patient being a faller could be as high as A$14,591 (2008). The education program cost A$526 (2008) to prevent one cognitively intact patient becoming a faller and A$294 (2008) to prevent one fall based on primary trial data. These estimates were unstable due to high variability in the hospital costs accrued by individual patients involved in the trial. There was a 52% probability the complete program was both more effective and less costly (from the health service perspective) than providing usual care alone. Decision tree modeling sensitivity analyses identified that when provided in real life contexts, the program would be both more effective in preventing falls among cognitively intact inpatients and cost saving where the proportion of these patients who would otherwise fall under usual care conditions is at least 4.0%. Conclusions This economic evaluation was designed to assist health care providers decide in what circumstances this intervention should be provided. If the proportion of cognitively intact patients falling on a ward under usual care conditions is 4% or greater, then provision of the complete program in addition to usual care will likely both prevent falls and reduce costs for a health service.

A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays

Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS −786 T > C, the allele frequencies were 0.87 (T allele) and 0.13 (C allele). Conclusions Our PCR-RFLP method is a simple, cost-effective and time-saving method. It can be used to successfully genotype subjects for the MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants simultaneously with 100% concordance from DNA sequencing data. This method can be routinely used for rapid investigation of the MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants.

Two-dimensional graphene heterojunctions: The tunable mechanical properties

We report the mechanical properties of different two-dimensional carbon heterojunctions (HJs) made from graphene and various stable graphene allotropes, including α-, β-, γ- and 6612-graphyne (GY), and graphdiyne (GDY). It is found that all HJs exhibit a brittle behaviour except the one with α-GY, which however shows a hardening process due to the formation of triple carbon rings. Such hardening process has greatly deferred the failure of the structure. The yielding of the HJs is usually initiated at the interface between graphene and graphene allotropes, and monoatomic carbon rings are normally formed after yielding. By varying the locations of graphene (either in the middle or at the two ends of the HJs), similar mechanical properties have been obtained, suggesting insignificant impacts from location of graphene allotropes. Whereas, changing the types and percentages of the graphene allotropes, the HJs exhibit vastly different mechanical properties. In general, with the increasing graphene percentage, the yield strain decreases and the effective Young’s modulus increases. Meanwhile, the yield stress appears irrelevant with the graphene percentage. This study provides a fundamental understanding of the tensile properties of the heterojunctions that are crucial for the design and engineering of their mechanical properties, in order to facilitate their emerging future applications in nanoscale devices, such as flexible/stretchable electronics.

Early life predictors of preschool overweight and obesity : a case–control study in Sri Lanka

Background Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease risk factors. Our aim was to assess the early life risk factors associated with overweight and obesity among preschool children. Methods In this case–control study, from the 1087 preschool children measured, age, sex and ethnicity matched 71 cases and 71 controls were recruited. Cases and controls were defined according to the WHO 2006 growth standards. The birth and growth characteristics were extracted from the child health development records. Infant feeding practices and maternal factors were obtained from the mother. Rapid weight gain was defined as an increase in weight-for-age Z score (WHO standards) above 0.67 SD from birth to 2 years. The magnitude and significant difference in mean values of the variables associated with overweight and obesity were evaluated using logistic regressions and paired t-test, respectively. Results Cases had significantly shorter duration (months) of breastfeeding (19.4, 24.6, p = 0.003), and smaller duration (months) of exclusive breastfeeding (3.7, 5.1, p = 0.001) compared to controls. Rapid weight gain (OR = 6.3, 95% CI = 2.04–19.49), first born status (OR = 3.6, 95% CI = 1.17-10.91) and pre-pregnancy obesity (OR = 4.0, 95% CI = 1.46-10.76) were positively associated with overweight and obesity. Breastfeeding more than 2 years (OR = 0.2, 95% CI = 0.06-0.57) was negatively associated with overweight and obesity. Conclusion Rapid weight gain within first two years, first–born status and pre-pregnancy obesity of the mother contributed for preschool obesity. Our results suggest that intervention may be indicated earlier in infancy and during the toddler and preschool years to tackle the increasing prevalence of obesity.