Environments for Healthy Living (EFHL) Griffith Birth Cohort Study : background and methods

The health of an individual is determined by the interaction of genetic and individual factors with wider social and environmental elements. Public health approaches to improving the health of disadvantaged populations will be most effective if they optimise influences at each of these levels, particularly in the early part of the life course. In order to better ascertain the relative contribution of these multi-level determinants there is a need for robust studies, longitudinal and prospective in nature, that examine individual, familial, social and environmental exposures. This paper describes the study background and methods, as it has been implemented in an Australian birth cohort study, Environments for Healthy Living (EFHL): The Griffith Study of Population Health. EFHL is a prospective, multi-level, multi-year longitudinal birth cohort study, designed to collect information from before birth through to adulthood across a spectrum of eco-epidemiological factors, including genetic material from cord-blood samples at birth, individual and familial factors, to spatial data on the living environment. EFHL commenced the pilot phase of recruitment in 2006 and open recruitment in 2007, with a target sample size of 4000 mother/infant dyads. Detailed information on each participant is obtained at birth, 12-months, 3-years, 5-years and subsequent three to five yearly intervals. The findings of this research will provide detailed evidence on the relative contribution of multi-level determinants of health, which can be used to inform social policy and intervention strategies that will facilitate healthy behaviours and choices across sub-populations.

Familial recurrence risks for multiple sclerosis in Australia

BACKGROUND: Genetic susceptibility to multiple sclerosis (MS) has been recognised for many years. Considerable data exist from the northern hemisphere regarding the familial recurrence risks for MS, but there are few data for the southern hemisphere and regions at lower latitude such as Australia. To investigate the interaction between environmental and genetic causative factors in MS, the authors undertook a familial recurrence risk study in three latitudinally distinct regions of Australia. METHODS: Immediate and extended family pedigrees have been collected for three cohorts of people with MS in Queensland, Victoria and Tasmania spanning 15° of latitude. Age of onset data from Queensland were utilised to estimate age-adjusted recurrence rates. RESULTS: Recurrence risks in Australia were significantly lower than in studies from northern hemisphere populations. The age-adjusted risk for siblings across Australia was 2.13% compared with 3.5% for the northern hemisphere. A similar pattern was seen for other relatives. The risks to relatives were proportional to the population risks for each site, and hence the sibling recurrence-risk ratio (λ(s)) was similar across all sites. DISCUSSION: The familial recurrence risk of MS in Australia is lower than in previously reported studies. This is directly related to the lower population prevalence of MS. The overall genetic susceptibility in Australia as measured by the λ(s) is similar to the northern hemisphere, suggesting that the difference in population risk is explained largely by environmental factors rather than by genetic admixture.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Mutations in cardiac T-Box Factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy

The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up.

A portrayal of new entrants into the Australian economy (Entrepreneurial individuals and ventures)

This paper provides a descriptive overview of the venture creation in Australia, those who participate in it and the types of firms they build. Findings of interest in this paper include: • The majority of business founders (89 per cent) state the motivation to start a new business is opportunity-driven rather than necessity driven. • The extent of under-representation of women business founders in Australia appears to be lower than international comparisons and has decreased over time. • Australian business founders tend to possess significant ‘human capital’ many are university-educated, and large shares have different types of experience that may benefit the start-up. • The major industries for start-up activities are Retailing; various service industries (Business Consulting; Health, Education and Social; other Consumer services); Construction, Manufacturing, and Agriculture. • A large proportion of CAUSEE respondents (49 per cent nascent firms and 46 per cent young firms) are members of start-up teams, which is similar to international comparisons.

Illustrating outcomes for Australian nascent and young firm entrepreneurial activity

This paper examines the outcomes of nascent and young entrepreneurial firms in Australia. Findings of interest in this paper include: • After three years similar proportions of nascent firms reach an operational state (31 per cent), i.e. sales regularly exceed costs, compared with those that have terminated (35 per cent), and those who are still trying to achieve venture creation (34 per cent). This outcome closely mirrors the outcomes in the US PSED study. • The young firm sample shows that these new ventures remain more robust to firm closure. The vast majority of young firms (78 per cent) continue to be active in the market the last time they participated in CAUSEE. • The annual termination rate for young firms is 9 per cent at most, and 14 per cent cumulatively, while cumulatively only 8 per cent of young firms experience a drop-off in activity to be considered as having uncertain status. • The average number of employees in Nascent Firms is one person, the average number of Young Firm employees increases from two at first sampling to three after three years. • While the founders of exiting Nascent Firms are more likely to return to their old job upon termination of their business, Young Firm founders move on to new jobs. Regardless the majority of exiting firm founders rate their experience as positive and are prepared to attempt business creation in the future.

Innovation and change in new ventures

This paper examines the innovativeness of nascent and young entrepreneurial firms in Australia. Findings of interest in this paper include: • The vast majority of new ventures offer some degree of innovation in some aspect of their business, be it the product, the process, their market selection or their marketing approach. • With close to 75 per cent claiming they do more than taking mere imitations to the market, novelty in the product/service is the type of innovation most commonly offered by start-up firms. • The innovativeness of start-ups varies by industry. Construction start-ups stand out as particularly low in innovation across all indicators, while Manufacturing stands out the most in the positive direction. • Team start-ups other than spouse teams have higher novelty, as do ventures started by founders with prior start-up experience. • There is no association between the founders’ level of education and the novelty of the ventures they (try to) create.

What it means to be green : an examination of early stage environmental and sustainability focused firms

This paper examines ‘green’ entrepreneurial nascent and young firms in Australia. Findings of interest in this paper include: • Green entrepreneurs are more likely to be highly educated and have an extended depth of experience within their industry and are more likely to have started a business prior to their current venture. • Green entrepreneurs exhibit increased levels of innovation, with an increased focus on new & high technology, R&D and the development of proprietary technology. • Green entrepreneurs are most likely to be based upon a product rather than a service and have a higher emphasis upon growth when compared with non-green entrepreneurs. • Green entrepreneurial firms tend to have a longer venture creation process and draw financial resources from a larger number of sources and rely more upon equity as a means of financing their venture.

New venture internationalisation

This paper investigates the international background and international activities of Australian start-up firms. Findings of interest in this paper include: • Due to their small scale, young age and distant location firm founders then to favour the domestic market rather that engage internationally. • Firms that do engage internationally tend to do so at the very early stages of venture creation. • Firms that do engage in exporting activities tend to rely on intermediaries rather than more direct forms of export actions.

Capturing gazelles : features of high potential firms and new venture growth

This paper investigates the characteristics of ventures which have the potential to reach high growth and compares this with ‘everyday’ new ventures. Findings of interest in this paper include: • HP firms are characterised by higher human capital, are more likely to have a team of founders, are more likely to be product based. • HP firms are more likely to achieve more extreme levels of growth (both positive and negative). • HP ventures that make a loss are more likely to do so early in the venture process. Those that do hold on show that there can higher levels of loss made later on in firm development. HP firms have higher resource needs, in terms of seeking external finance, but are no more likely to receive external finance than regular firms.

Unpacking the venture creation process

This paper investigates the dimensions of time and effort and how these factors impact on the venture creation process in Australia. Findings of interest in this paper include: • First and foremost business planning is used as a thinking tool within the boundaries of the firm. • Business planning is more strongly associated with firms that are more ambitious, being built by teams, draw on more experience or education. • Industry characteristics in part drive the duration required for venture creation. Manufacturing and Agriculture based firms seemingly take longer timeframes than other industries. Extended venture creation times frames are also associated with firms that aim to bring more novel concepts to market.

Identifying important success factors in new venture creation

This paper seeks to uncover the factors that lead to a successful entrepreneurial experience and or venture. Findings of interest in this paper include: • A venture’s initial aspirations are a double edged sword. Ambition may lead to improved performance by striving to reach harder goals. Harder goals are more difficult therefore this may lead to some dissatisfaction, and possibly abandonment of the venture. • Venture legitimacy is important to establish where possible. Firms that formalize their legal form are more successful, as are those set up a shop-front in order to makes sales. • Increased use of technology and higher levels of novelty does not guarantee success early on. Firms of this nature have longer processes, and attempting to create brand new markets is difficult to achieve. At the same time developing your own technology and securing this intellectual property is important for success. • Having goals to work towards and business planning may be useful, but only if the plan is actively revised. Just having a business plan does not matter. Business plans are more useful as a thinking tool than as a blueprint for action. It is the process of thinking through while reviewing the plan that provides the benefit, not following its instruction to the letter.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Career implications of multi-layered institutional settings

Project work has grown significantly in volume and recognition in recent decades as projects have ‘become a common form of work organization in all sectors of the economy’ (Lindgren & Packendorff, 2006: 841). This increase in project-based work is just one of the many changes that have been affecting the nature of work, the employment relationship and the associated conceptualization and experience of careers (Baruch, 2004b; Söderlund & Bredin, 2006). A career can be defined as a process of development along a path of work experience and roles in one or more organizations (Baruch & Rosenstein, 1992), and careers involving project-based work take place within multi layered institutional settings. Projects are generally undertaken by small temporary organizations (Ekstedt, Lundin, Söderholm & Wirdenius, 1999; Pettigrew, 2003; Söderlund, 2012) which in turn may form part of larger, permanent entities; involve people drawn from a number of disciplines and organizations; or be formed as partnerships, joint ventures or strategic alliances between two or more organizations (Scott, 2007).

The effect of surface tension and kinetic undercooling on a radially-symmetric melting problem

The addition of surface tension to the classical Stefan problem for melting a sphere causes the solution to blow up at a finite time before complete melting takes place. This singular behaviour is characterised by the speed of the solid-melt interface and the flux of heat at the interface both becoming unbounded in the blow-up limit. In this paper, we use numerical simulation for a particular energy-conserving one-phase version of the problem to show that kinetic undercooling regularises this blow-up, so that the model with both surface tension and kinetic undercooling has solutions that are regular right up to complete melting. By examining the regime in which the dimensionless kinetic undercooling parameter is small, our results demonstrate how physically realistic solutions to this Stefan problem are consistent with observations of abrupt melting of nanoscaled particles.