A mega-analysis of genome-wide association studies for major depressive disorder

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 x 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 x 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Factors affecting entry-level Internet technology adoption by small business in Australia : evidence from three cases

The adoption of Internet technologies by the small business sector (SMEs)The adoption of Internet technologies by the small business sector is important to their on-going survival. Yet, given the opportunities and benefits that Internet technologies can provide it has been shown that Australian small businesses are relatively slow in adopting them. This paper develops a model from recent literature on the facilitators and inhibitors to the adoption of Internet technologies by small business. Cross-case analysis of findings from three case studies are presented. Findings indicate that perceived lack of business benefit, mistrust of the IT industry and lack of understanding of Internet technologies are major inhibitors to Internet adoption by small business.

The association between maternal infant feeding practices and child weight at 11-17 months in first-time Australian mothers

Introduction: Emerging evidence reveals that early feeding practices are associated with child food intake, eating behaviour and weight status. This cross-sectional analysis examined the association between maternal infant feeding practices/beliefs and child weight in Australian infants aged 11-17 months. Methods: Participants were 293 first-time mothers of healthy term infants (144 boys, mean age 14±1 months) enrolled in the NOURISH RCT. Mothers self-reported infant feeding practices and beliefs using the Infant Feeding Questionnaire (Baughcum, 2001). Anthropometric data were also measured at baseline (infants aged 4 months). Multiple regression analysis was used, adjusting for infant age, gender, birth weight, infant feeding mode (breast vs. formula), maternal perceptions of infant weight status, pre-pregnancy weight, weight concern, age and education. Results: The average child weight-for-age z-score (WAZ) was 0.62±0.83 (range:-1.56 to 2.94) and the mean change in WAZ (WAZ change) from 4 to 14 months was 0.62±0.69 (range:-1.50 to 2.76). Feeding practices/beliefs partly explained child WAZ (R2=0.28) and WAZ change (R2=0.13) in the adjusted models. While child weight status at 14 months was inversely associated with responsive feeding (e.g. baby feeds whenever she wants, feeding to stop baby being unsettled) (β=-0.104, p=0.06) and maternal concern about the child becoming underweight (β=-0.224, p<0.001), it was positively associated with mother’s concern about child overweight (β=0.197, p<0.05). Birth weight, infant’s age, maternal weight concern and perceiving her child as overweight were significant covariates. WAZ change was only significantly associated with responsive feeding (β=-0.147, p<0.05). Conclusion: Responsive feeding may be an important strategy to promote healthy child weight.

Associations between parenting behaviours and feeding beliefs of first-time Australian mothers in the NOURISH obesity prevention trial

Purpose: Parenting style and early feeding practices have been linked to child intake, eating behaviour and weight status. The purpose of this study was to examine associations between general maternal parenting behaviours and feeding beliefs in Australian mothers of 11-17 month-old children. Methods: This cross-sectional analysis included 223 first-time mothers and their children (49% male, mean age 14 [sd 1] months) enrolled in the control group of the NOURISH trial. Mothers self-reported their feeding beliefs and parenting behaviours (overprotection, irritability, warmth, autonomy-encouraging) using modified questions from the Infant Feeding Questionnaire (Baughcum, 2001) and the Longitudinal Study of Australian Children. Multiple regression analyses were conducted, using feeding beliefs (four factors) as dependent and parenting behaviours as independent variables while adjusting for child gender, age, weight-for-age z-score and maternal age, education level, feeding mode (breast vs. non-breast), and perception of own pre-pregnancy and child weight status. Results/Findings: Two of four parenting behaviours were significantly associated with feeding beliefs. Maternal warmth was inversely associated with concerns that the child would become underweight (β=-0.156, p=0.022) and positively associated with mothers’ awareness of child’s hunger/satiety cues (β=0.303, p<0.001). Mothers’ overprotection was positively associated with concerns that the child would become underweight (β=0.213, p=0.001); become overweight (β=0.174, p=0.005); and mother’s responsive feeding (β=0.135, p=0.057). Weight-for-age z-score, mothers’ perception of their child and own weight status, education, feeding mode, and child’s age were significant covariates. Conclusions: Feeding occurs within the broader parenting context. Improving early feeding beliefs and practices may require addressing mother’s approaches to parenting, especially warmth and overprotection.

Incentive mechanisms in infrastructure projects : A case-based comparison between Australia and the Netherlands

Despite a general belief that incentive mechanisms can improve value for money during procurement and performance during project execution, empirical research on the actual effects is nascent. This research focuses on the design and implementation of incentive mechanisms in four different infrastructure projects: two road reconstructions in the Netherlands and two building constructions in Australia. Based on an analytical framework of key motivation drivers, a cross cases analysis is conducted in view of performance on the contract assumptions, selection phase, execution phase and project contract performance. It was identified that despite significant differences in the project characteristics, results indicate that they experience similar contextual drivers on the incentive effectiveness. High value was placed on risk allocation and relationship building in the selection and construction phase. The differences can be explained from both contextual and project related characteristics. Although there are limitations with this research in drawing generalizations across two sets of case projects, the results provide a strong base to explore the nature of incentive systems across different geographical and contextual boundaries in future research.

Brownfield re-development : Perceptions and risk mitigation strategies

Scarcity of large parcels of land in well-serviced areas has motivated people to re-develop brownfield land. Most of brownfield land has high risk of contamination from wide range of industrial activities such as gas works, factories, railway land and waste tips. In addition, people who live in brownfield re-development areas may be exposed to health hazards. This paper discusses public perceptions on the brownfield sites and also the risk and mitigation strategy to promote brownfield re-development. Data is gathered from face to face survey of fifty respondents who work in Brisbane Central Business District (CBD) and interview with an expert on remediation of contaminated land. From this preliminary study, it is found that majority of the population are not aware of any brownfield sites near their residence and those who are aware showed very little concern on their proximity to the site. Further discussion on the paper based on a simple cross tabulation analysis. The main risk mitigation strategy of re-development of brownfield site is by updating the registration through Environmental Management Register (EMR) and Contaminated Land Register (CLR). In addition, insurance may offer to cover cost overruns on remediation cost.

Generator coherency and area detection in large power systems

This paper provides a new general approach for defining coherent generators in power systems based on the coherency in low frequency inter-area modes. The disturbance is considered to be distributed in the network by applying random load changes which is the random walk representation of real loads instead of a single fault and coherent generators are obtained by spectrum analysis of the generators velocity variations. In order to find the coherent areas and their borders in the inter-connected networks, non-generating buses are assigned to each group of coherent generator using similar coherency detection techniques. The method is evaluated on two test systems and coherent generators and areas are obtained for different operating points to provide a more accurate grouping approach which is valid across a range of realistic operating points of the system.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Marked association of a RFLP for the low density lipoprotein receptor gene with obesity in essential hypertensives

RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage disequilibrium between each other. Cross-sectional analysis of a bi-alleleic ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in similar frequency between a group of 84 Caucasian essential hypertensive (HT) and a group of 96 normotensive subjects whose parents each had a similar blood pressure status at age > or = 50. After subdividing HTs into lean and obese, however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26 kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P = 0.004). The difference in genotype frequencies was even more striking (chi 2 = 23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with obesity in HT.

Unpacking ‘lessons learned’ : investigating failures and considering alternative solutions

One of the most common ways to share project knowledge is to capture the positive and negative aspects of projects in the form of lessons learned (LL). If effectively used, this process can assist project managers in reusing project knowledge and preventing future projects from repeating mistakes. Nevertheless, the process of capturing, storing, reviewing and reusing LL often remains suboptimal. Despite the potential for rich knowledge capture, lessons are often documented as simple, line-item statements devoid of context. Findings from an empirical investigation across four cases revealed a range of reasons related to the perceived quality, process and visibility of LL that lead to their limited use and application. Drawn from the cross-case analysis, this paper investigates an integrated approach to LL involving the use of a collaborative Web-based tool, which is easily accessible, intelligible and user-friendly, allowing more effective sharing of project knowledge and overcoming existing problems with LL.

Project management office a knowledge broker in project-based organisations

Current research into project management offices (PMOs) has stressed the PMOs' potential to act as knowledge brokers between projects, and between project and top management. Nonetheless, the literature does not provide sufficient evidence of the brokering role of PMOs. The research reported here aims to examine PMO's functions from a knowledge sharing perspective and explore whether or not these functions reflect the knowledge sharing needs of project managers (PMs). These issues are investigated through a cross-case analysis of seven organisations. The main contribution is insight into how PMs share knowledge and awareness of the need to structure PMOs to align with PMs' nature, needs and expectations in order to improve knowledge sharing in PBOs. Finally, some practical steps for helping PMOs to better adapt their functions to the needs of PMs and their learning and knowledge sharing style are proposed.

Brief screening for psychosis-like experiences

Objective Psychotic-like experiences (PLEs) are common, and are markers of poor mental health. This study examined the internal structure of a screening test, the Community Assessment of Psychic Experiences-Positive scale (CAPE-P) in a young Australian sample. Method A cross-sectional online survey, which included the CAPE-P, was completed by 1610 university students aged between 18 and 25 years. Confirmatory factor analyses compared 1-, 4-, and 5-factor models, and examined effects of omitting selected items. Results A 3-factor model, omitting items on magical thinking, grandiosity, paranormal beliefs and a cross-loading item produced the best fit. The resultant 15-item CAPE (CAPE-P15) had three subscales - Persecutory Ideation, Perceptual Abnormalities and Bizarre Experiences, all with high levels of internal consistency. Conclusion The CAPE-P15 shows promise as a measure of positive, psychosis-like experiences, but further validation of this measure is required in community samples.

Student focus and prioritization of design parameters in first-year engineering design projects

BACKGROUND Research on engineering design is a core area of concern within engineering education and a fundamental understanding of how engineering students approach and undertake design is necessary in order to develop effective design models and pedagogies. Understanding the factors related to design experiences in education and how they affect student practice can help educators as well as designers to leverage these factors as part of the design process. PURPOSE This study investigated the design practices of first-year engineering students’ and their experiences with a first-year engineering course design project. The research questions that guided the investigation were: 1. From a student perspective, what design parameters or criteria are most important? 2. How does this perspective impact subsequent student design practice throughout the design process? DESIGN/METHOD The authors employed qualitative multi-case study methods (Miles & Huberman, 1994) in order to the answer the research questions. Participant teams were observed and video recorded during team design meetings in which they researched the background for the design problem, brainstormed and sketched possible solutions, as well as built prototypes and final models of their design solutions as part of a course design project. Analysis focused on explanation building (Yin, 2009) and utilized within-case and cross-case analysis (Miles & Huberman, 1994). RESULTS We found that students focused disproportionally on the functional parameter, i.e. the physical implementation of their solution, and the possible/applicable parameter, i.e. a possible and applicable solution that benefited the user, in comparison to other given parameters such as safety and innovativeness. In addition, we found that individual teams focused on the functional and possible/ applicable parameters in early design phases such as brainstorming/ ideation and sketching. When prompted to discuss these non-salient parameters (from the student perspective) in the final design report, student design teams often used a post-hoc justification to support how the final designs fit the parameters that they did not initially consider. CONCLUSIONS This study suggests is that student design teams become fixated on (and consequently prioritize) certain parameters they interpret as important because they feel these parameters were described more explicitly in terms how they were met and assessed. Students fail to consider other parameters, perceived to be less directly assessable, unless prompted to do so. Failure to consider other parameters in the early design phases subsequently affects their approach in design phases as well. Case studies examining students’ study strategies within three Australian Universities illustrate similarities with some student approaches to design.