The timing of solid introduction in an ‘obesogenic’ environment : a narrative review of the evidence and methodological issues.

Objective To evaluate the evidence for association between obesity risk outcomes >12 months of age and timing of solid introduction in healthy term infants in developed countries, the large majority of whom are not exclusively breastfed to 6 months of age. Methods Studies included were published 1990-March 2013. Results Twenty-six papers with weight status or obesity prevalence outcomes were identified. Studies were predominantly cohort design, most with important methodological limitations. Ten studies reported a positive association. Of these only two were large good quality studies and both examined the outcome of early (<4 months) solid introduction. None of the four good quality studies that directly evaluated current guidelines provided evidence of any clinically relevant protective effect of solid introduction from 4-5 versus ≥ 6 months of age. Conclusion Overall the introduction of solids prior to 4 months may result in increased risk of childhood obesity but there is little evidence of adverse weight status outcomes associated with introducing solids at 4-6 rather than at 6 months. Implications More and better quality evidence is required to inform guidelines on the ‘when, what and how’ of complementary feeding.

Timing of births and endometrial cancer risk in Swedish women

While a protective long-term effect of parity on endometrial cancer risk is well established, the impact of timing of births is not fully understood. We examined the relationship between endometrial cancer risk and reproductive characteristics in a population-based cohort of 2,674,465 Swedish women, 20–72 years of age. During follow-up from 1973 through 2004, 7,386 endometrial cancers were observed. Compared to uniparous women, nulliparous women had a significantly elevated endometrial cancer risk (hazard ratio [HR] = 1.32, 95% confidence interval [CI], 1.22–1.42). Endometrial cancer risk decreased with increasing parity; compared to uniparous women, women with ≥4 births had a HR=0.66 (95% CI, 0.59–0.74); p-trend < 0.001. Among multiparous women, we observed no relationship of risk with age at first birth after adjustment for other reproductive factors. While we initially observed a decreased risk with later ages at last birth, this appeared to reflect a stronger relationship with time since last birth, with women with shorter times being at lowest risk. In models for multiparous women that included number of births, age at first and last birth, and time since last birth, age at last birth was not associated with endometrial cancer risk, while shorter time since last birth and increased parity were associated with statistically significantly reduced endometrial cancer risks. The HR was 3.95 (95%CI; 2.17–7.20; p-trend=<0.0001) for women with ≥25 years since a last birth compared to women having given birth within 4 years. Our findings support that clearance of initiated cells during delivery may be important in endometrial carcinogenesis. Keywords: endometrial carcinoma, parity, registry, reproductive factors

The impact of litigation risk on the strategic timing of management earnings forecasts

This paper examines whether managers strategically time their earnings forecasts (MEFs) as litigation risk increases. We find as litigation risk increases, the propensity to release a delayed forecast until after the market is closed (AMC) or a Friday decreases but not proportionally more for bad news than for good news. Host costly this behaviour is to investors is questionable as share price returns do not reveal any under-reaction to strategically timed bad news MEF released AMC. We also find evidence consistent with managers timing their MEFs during a natural no-trading period to better disseminate information.

The effects of community attachment and information seeking on displaced disaster victims’ decision making

This paper uses original survey data of the Great East Japan earthquake disaster victims to examine their decision to apply for the temporary housing as well as the timing of application. We assess the effects of victims’ attachment to their locality as well as variation in victims’ information seeking behavior. We additionally consider various factors such as income, age, employment and family structure that are generally considered to affect the decision to choose temporary housing as victims’ solution for their displacement. Empirical results indicate that, ceteris paribus, as the degree of attachment increases, victims are more likely to apply for the temporary housing but attachment does not affect the timing of application. On the other hand, the victims who actively seek information and are able to collect higher quality information are less likely to apply for the temporary housing and if they do apply then they apply relatively later.

Influence of nitrogen fertiliser application and timing on greenhouse gas emissions from a lychee (Litchi chinensis) orchard in humid subtropical Australia

Nitrous oxide emissions from intensive, fertilised agricultural systems have been identified as significant contributors to both Australia's and the global greenhouse gas (GHG) budget. This is expected to increase as rates of agriculture intensification and land use change accelerate to support population growth and food production. Limited data exists on N2O trace gas fluxes from subtropical or tropical tree cropping soils critical for the development of effective mitigation strategies.This study aimed to quantify GHG emissions over two consecutive years (March 2007 to March 2009) from a 30 year (lychee) orchard in the humid subtropical region of Australia. GHG fluxes were measured using a combination of high temporal resolution automated sampling and manually sampled chambers. No fertiliser was added to the plots during the 2007 measurement season. A split application of nitrogen fertiliser (urea) was added at the rate of 265kgNha-1 during the autumn and spring of 2008. Emissions of N2O were influenced by rainfall events and seasonal temperatures during 2007 and the fertilisation events in 2008. Annual N2O emissions from the lychee canopy increased from 1.7kgN2O-Nha-1yr-1 for 2007, to 7.6kgN2O-Nha-1yr-1 following fertiliser application in 2008. This represented an emission factor of 1.56%, corrected for background emissions. The timing of the split application was found to be critical to N2O emissions, with over twice as much lost following an application in spring (2.44%) compared to autumn (EF: 1.10%). This research suggests that avoiding fertiliser application during the hot and moist spring/summer period can reduce N2O losses without compromising yields.

Application of an appearance-based intervention to improve sun protection outcomes of outdoor workers in Queensland, Australia

Outdoor workers are exposed to high levels of ultraviolet radiation (UVR) and may thus be at greater risk to experience UVR-related health effects such as skin cancer, sun burn, and cataracts. A number of intervention trials (n=14) have aimed to improve outdoor workers’ work-related sun protection cognitions and behaviours. Only one study however has reported the use of UV-photography as part of a multi-component intervention. This study was performed in the USA and showed long-term (12 months) improvements in work-related sun protection behaviours. Intervention effects of the other studies have varied greatly, depending on the population studied, intervention applied, and measurement of effect. Previous studies have not assessed whether: - Interventions are similarly effective for workers in stringent and less stringent policy organisations; - Policy effect is translated into workers’ leisure time protection; - Implemented interventions are effective in the long-term; - The facial UV-photograph technique is effective in Australian male outdoor workers without a large additional intervention package, and; - Such interventions will also affect workers’ leisure time sun-related cognitions and behaviours. Therefore, the present Protection of Outdoor Workers from Environmental Radiation [POWER]-study aimed to fill these gaps and had the objectives of: a) assessing outdoor workers’ sun-related cognitions and behaviours at work and during leisure time in stringent and less stringent sun protection policy environments; b) assessing the effect of an appearance-based intervention on workers’ risk perceptions, intentions and behaviours over time; c) assessing whether the intervention was equally effective within the two policy settings; and d) assessing the immediate post-intervention effect. Effectiveness was described in terms of changes in sun-related risk perceptions and intentions (as these factors were shown to be main precursors of behaviour change in many health promotion theories) and behaviour. The study purposefully selected and recruited two organisations with a large outdoor worker contingent in Queensland, Australia within a 40 kilometre radius of Brisbane. The two organisations differed in the stringency of implementation and reinforcement of their organisational sun protection policy. Data were collected from 154 male predominantly Australian born outdoor workers with an average age of 37 years and predominantly medium to fair skin (83%). Sun-related cognitions and behaviours of workers were assessed using self-report questionnaires at baseline and six to twelve months later. Variation in follow-up time was due to a time difference in the recruitment of the two organisations. Participants within each organisation were assigned to an intervention or control group. The intervention group participants received a one-off personalised Skin Cancer Risk Assessment Tool [SCRAT]-letter and a facial UV-photograph with detailed verbal information. This was followed by an immediate post-intervention questionnaire within three months of the start of the study. The control group only received the baseline and follow-up questionnaire. Data were analysed using a variety of techniques including: descriptive analyses, parametric and non-parametric tests, and generalised estimating equations. A 15% proportional difference observed was deemed of clinical significance, with the addition of reported statistical significance (p<0.05) where applicable. Objective 1: Assess and compare the current sun-related risk perceptions, intentions, behaviours, and policy awareness of outdoor workers in stringent and less stringent sun protection policy settings. Workers within the two organisations (stringent n=89 and less stringent n=65) were similar in their knowledge about skin cancer, self efficacy, attitudes, and social norms regarding sun protection at work and during leisure time. Participants were predominantly in favour of sun protection. Results highlighted that compared to workers in a less stringent policy organisation working for an organisation with stringent sun protection policies and practices resulted in more desirable sun protection intentions (less willing to tan p=0.03) ; actual behaviours at work (sufficient use of upper and lower body protection, headgear, and sunglasses (p<0.001 for all comparisons), and greater policy awareness (awareness of repercussions if Personal Protective Equipment (PPE) was not used, p<0.001)). However the effect of the work-related sun protection policy was found not to extend to leisure time sun protection. Objective 2: Compare changes in sun-related risk perceptions, intentions, and behaviours between the intervention and control group. The effect of the intervention was minimal and mainly resulted in a clinically significant reduction in work-related self-perceived risk of developing skin cancer in the intervention compared to the control group (16% and 32% for intervention and control group, respectively estimated their risk higher compared to other outdoor workers: , p=0.11). No other clinical significant effects were observed at 12 months follow-up. Objective 3: Assess whether the intervention was equally effective in the stringent sun protection policy organisation and the less stringent sun protection policy organisation. The appearance-based intervention resulted in a clinically significant improvement in the stringent policy intervention group participants’ intention to protect from the sun at work (workplace*time interaction, p=0.01). In addition to a reduction in their willingness to tan both at work (will tan at baseline: 17% and 61%, p=0.06, at follow-up: 54% and 33%, p=0.07, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p<0.001) and during leisure time (will tan at baseline: 42% and 78%, p=0.01, at follow-up: 50% and 63%, p=0.43, stringent and less stringent policy intervention group respectively. The workplace*time interaction was significant p=0.01) over the course of the study compared to the less stringent policy intervention group. However, no changes in actual sun protection behaviours were found. Objective 4: Examine the effect of the intervention on level of alarm and concern regarding the health of the skin as well as sun protection behaviours in both organisations. The immediate post-intervention results showed that the stringent policy organisation participants indicated to be less alarmed (p=0.04) and concerned (p<0.01) about the health of their skin and less likely to show the facial UV-photograph to others (family p=0.03) compared to the less stringent policy participants. A clinically significantly larger proportion of participants from the stringent policy organisation reported they worried more about skin cancer (65%) and skin freckling (43%) compared to those in the less stringent policy organisation (46%,and 23% respectively , after seeing the UV-photograph). In summary the results of this study suggest that the having a stringent work-related sun protection policy was significantly related to for work-time sun protection practices, but did not extend to leisure time sun protection. This could reflect the insufficient level of sun protection found in the general Australian population during leisure time. Alternatively, reactance caused by being restricted in personal decisions through work-time policy could have contributed to lower leisure time sun protection. Finally, other factors could have also contributed to the less than optimal leisure time sun protection behaviours reported, such as unmeasured personal or cultural barriers. All these factors combined may have lead to reduced willingness to take proper preventive action during leisure time exposure. The intervention did not result in any measurable difference between the intervention and control groups in sun protection behaviours in this population, potentially due to the long lag time between the implementation of the intervention and assessment at 12-months follow-up. In addition, high levels of sun protection behaviours were found at baseline (ceiling effect) which left little room for improvement. Further, this study did not assess sunscreen use, which was the predominant behaviour assessed in previous effective appearance-based interventions trials. Additionally, previous trials were mainly conducted in female populations, whilst the POWER-study’s population was all male. The observed immediate post-intervention result could be due to more emphasis being placed on sun protection and risks related to sun exposure in the stringent policy organisation. Therefore participants from the stringent policy organisation could have been more aware of harmful effects of UVR and hence, by knowing that they usually protect adequately, not be as alarmed or concerned as the participants from the less stringent policy organisation. In conclusion, a facial UV-photograph and SCRAT-letter information alone may not achieve large changes in sun-related cognitions and behaviour, especially of assessed 6-12 months after the intervention was implemented and in workers who are already quite well protected. Differences found between workers in the present study appear to be more attributable to organisational policy. However, against a background of organisational policy, this intervention may be a useful addition to sun-related workplace health and safety programs. The study findings have been interpreted while respecting a number of limitations. These have included non-random allocation of participants due to pre-organised allocation of participants to study group in one organisation and difficulty in separating participants from either study group. Due to the transient nature of the outdoor worker population, only 105 of 154 workers available at baseline could be reached for follow-up. (attrition rate=32%). In addition the discrepancy in the time to follow-up assessment between the two organisations was a limitation of the current study. Given the caveats of this research, the following recommendations were made for future research: - Consensus should be reached to define "outdoor worker" in terms of time spent outside at work as well as in the way sun protection behaviours are measured and reported. - Future studies should implement and assess the value of the facial UV-photographs in a wide range of outdoor worker organisations and countries. - More timely and frequent follow-up assessments should be implemented in intervention studies to determine the intervention effect and to identify the best timing of booster sessions to optimise results. - Future research should continue to aim to target outdoor workers’ leisure time cognitions and behaviours and improve these if possible. Overall, policy appears to be an important factor in workers’ compliance with work-time use of sun protection. Given the evidence generated by this research, organisations employing outdoor workers should consider stringent implementation and reinforcement of a sun protection policy. Finally, more research is needed to improve ways to generate desirable behaviour in this population during leisure time.

The importance of gestation process dynamics

Principal Topic In this paper we seek to highlight the important intermediate role that the gestation process plays in entrepreneurship by examining its key antecedents and its consequences for new venture emergence. In doing so we take a behavioural perspective and argue that it is not only what a nascent venture is, but what it does (Katz & Gartner, 1988; Shane & Delmar, 2004; Reynolds, 2007) and when it does it during start-up (Reynolds & Miller, 1992; Lichtenstein, Carter, Dooley & Gartner, 2007) that is important. To extend an analogy from biological development, what we suggest is that the way a new venture is nurtured is just as fundamental as its nature. Much prior research has focused on the nature of new ventures and attempted to attribute variations in outcomes directly to the impact resource endowments and investments have. While there is little doubt that venture resource attributes such as human capital, and specifically prior entrepreneurial experience (Alsos & Kolvereid, 1998), access to social (Davidsson & Honig, 2003) and financial capital have an influence. Resource attributes themselves are distal from successful start-up endeavours and remain inanimate if not for the actions of the nascent venture. The key contribution we make is to shift focus from whether or not actions are taken, but when these actions happen and how that is situated in the overall gestation process. Thus, we suggest that it is gestation process dynamics, or when gestation actions occur, that is more proximal to venture outcomes and we focus on this. Recently scholars have highlighted the complexity that exists in the start-up or gestation process, be it temporal or contextual (Liao, Welsch & Tan, 2005; Lichtenstein et al. 2007). There is great variation in how long a start-up process might take (Reynolds & Miller, 1992), some processes require less action than others (Carter, Gartner & Reynolds, 1996), and the overall intensity of the start-up effort is also deemed important (Reynolds, 2007). And, despite some evidence that particular activities are more influential than others (Delmar & Shane, 2003), the order in which events may happen is, until now, largely indeterminate as regard its influence on success (Liao & Welsch, 2008). We suggest that it is this complexity of the intervening gestation process that attenuates the effect of resource endowment and has resulted in mixed findings in previous research. Thus, in order to reduce complexity we shall take a holistic view of the gestation process and argue that it is its’ dynamic properties that determine nascent venture attempt outcomes. Importantly, we acknowledge that particular gestation processes of themselves would not guarantee successful start-up, but it is more correctly the fit between the process dynamics and the ventures attributes (Davidsson, 2005) that is influential. So we aim to examine process dynamics by comparing sub-groups of venture types by resource attributes. Thus, as an initial step toward unpacking the complexity of the gestation process, this paper aims to establish the importance of its role as an intermediary between attributes of the nascent venture and the emergence of that venture. Here, we make a contribution by empirically examining gestation process dynamics and their fit with venture attributes. We do this by firstly, examining that nature of the influence that venture attributes such as human and social capital have on the dynamics of the gestation process, and secondly by investigating the effect that gestation process dynamics have on venture creation outcomes. Methodology and Propositions In order to explore the importance that gestation processes dynamics have in nascent entrepreneurship we conduct an empirical study of ventures start-ups. Data is drawn from a screened random sample of 625 Australian nascent business ventures prior to them achieving consistent outcomes in the market. This data was collected during 2007/8 and 2008/9 as part of the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE) project (Davidsson et al., 2008). CAUSEE is a longitudinal panel study conducted over four years, sourcing information from annually administered telephone surveys. Importantly for our study, this methodology allows for the capture and tracking of active nascent venture creation as it happens, thus reducing hindsight and selection biases. In addition, improved tests of causality may be made given that outcome measures are temporally removed from preceding events. The data analysed in this paper represents the first two of these four years, and for the first time has access to follow-up outcome measures for these venture attempts: where 260 were successful, 126 were abandoned, and 191 are still in progress. With regards to venture attributes as gestation process antecedents, we examine specific human capital measured as successful prior experience in entrepreneurship, and direct social capital of the venture as ‘team start-ups’. In assessing gestation process dynamics we follow Lichtenstein et al. (2007) to suggest that the rate, concentration and timing of gestation activities may be used to summarise the complexity dynamics of that process. In addition, we extend this set of measures to include the interaction of discovery and exploitation by way of changes made to the venture idea. Those ventures with successful prior experience or those who conduct symbiotic parallel start-up attempts may be able to, or be forced to, leave their gestation action until later and still derive a successful outcome. In addition access to direct social capital may provide the support upon which the venture may draw in order to persevere in the face of adversity, turning a seemingly futile start-up attempt into a success. On the other hand prior experience may engender the foresight to terminate a venture attempt early should it be seen to be going nowhere. The temporal nature of these conjectures highlight the importance that process dynamics play and will be examined in this research Statistical models are developed to examine gestation process dynamics. We use multivariate general linear modelling to analyse how human and social capital factors influence gestation process dynamics. In turn, we use event history models and stratified Cox regression to assess the influence that gestation process dynamics have on venture outcomes. Results and Implications What entrepreneurs do is of interest to both scholars and practitioners’ alike. Thus the results of this research are important since they focus on nascent behaviour and its outcomes. While venture attributes themselves may be influential this is of little actionable assistance to practitioners. For example it is unhelpful to say to the prospective first time entrepreneur “you’ll be more successful if you have lots of prior experience in firm start-ups”. This research attempts to close this relevance gap by addressing what gestation behaviours might be appropriate, when actions best be focused, and most importantly in what circumstances. Further, we make a contribution to the entrepreneurship literature, examining the role that gestation process dynamics play in outcomes, by specifically attributing these to the nature of the venture itself. This extension is to the best of our knowledge new to the research field.

Student success : the identification and support of first year university students at risk of attrition

The engagement behaviour of 1,524 student-enrolments (“students”) in five first year units was monitored and 608 (39.9%) were classified as “at risk” using the criterion of not submitting or failing their first assignment. Of these, 327 (53.8%) were successfully contacted (i.e., spoken to by phone) and provided with advice and/or referral to learning and personal support services while the remaining 281 (46.2%) could not be contacted. Nine hundred and sixteen students (60.1%) were classified as “not at risk.” Overall, the at risk group who were contacted achieved significantly higher end-of-semester final grades than, and persisted (completed the unit) at more than twice the rate of, the at risk group who were not contacted. There were variations among the units which were explained by the timing of the first assignment, specific teaching-learning processes and the structure of the curriculum. Implications for curriculum design and supporting first year students within a personal, social and academic framework are discussed.

Early outcomes of patella resurfacing in total knee arthroplasty

Background Patella resurfacing in total knee arthroplasty is a contentious issue. The literature suggests that resurfacing of the patella is based on surgeon preference, and little is known about the role and timing of resurfacing and how this affects outcomes. Methods We analyzed 134,799 total knee arthroplasties using data from the Australian Orthopaedic Association National Joint Replacement Registry. Hazards ratios (HRs) were used to compare rates of early revision between patella resurfacing at the primary procedure (the resurfacing group, R) and primary arthroplasty without resurfacing (no-resurfacing group, NR). We also analyzed the outcomes of NR that were revised for isolated patella addition. Results At 5 years, the R group showed a lower revision rate than the NR group: cumulative per cent revision (CPR) 3.1% and 4.0%, respectively (HR = 0.75, p < 0.001). Revisions for patellofemoral pain were more common in the NR group (17%) than in the R group (1%), and “patella only” revisions were more common in the NR group (29%) than in the R group (6%). Non-resurfaced knees revised for isolated patella addition had a higher revision rate than patella resurfacing at the primary procedure, with a 4-year CPR of 15% and 2.8%, respectively (HR = 4.1, p < 0.001). Interpretation Rates of early revision of primary total knees were higher when the patella was not resurfaced, and suggest that surgeons may be inclined to resurface later if there is patellofemoral pain. However, 15% of non-resurfaced knees revised for patella addition are re-revised by 4 years. Our results suggest an early beneficial outcome for patella resurfacing at primary arthroplasty based on revision rates up to 5 years.

Drivers of adoption for successive generation of high-tech products

To understand the diffusion of high technology products such as PCs, digital cameras and DVD players it is necessary to consider the dynamics of successive generations of technology. From the consumer’s perspective, these technology changes may manifest themselves as either a new generation product substituting for the old (for instance digital cameras) or as multiple generations of a single product (for example PCs). To date, research has been confined to aggregate level sales models. These models consider the demand relationship between one generation of a product and a successor generation. However, they do not give insights into the disaggregate-level decisions by individual households – whether to adopt the newer generation, and if so, when. This paper makes two contributions. It is the first large scale empirical study to collect household data for successive generations of technologies in an effort to understand the drivers of adoption. Second, in contrast to traditional analysis in diffusion research that conceptualizes technology substitution as an “adoption of innovation” type process, we propose that from a consumer’s perspective, technology substitution combines elements of both adoption (adopting the new generation technology) and replacement (replacing generation I product with generation II). Key Propositions In some cases, successive generations are clear “substitutes” for the earlier generation (e.g. PCs Pentium I to II to III ). More commonly the new generation II technology is a “partial substitute” for existing generation I technology (e.g. DVD players and VCRs). Some consumers will purchase generation II products as substitutes for their generation I product, while other consumers will purchase generation II products as additional products to be used as well as their generation I product. We propose that substitute generation II purchases combine elements of both adoption and replacement, but additional generation II purchases are solely adoption-driven process. Moreover, drawing on adoption theory consumer innovativeness is the most important consumer characteristic for adoption timing of new products. Hence, we hypothesize consumer innovativeness to influence the timing of both additional and substitute generation II purchases but to have a stronger impact on additional generation II purchases. We further propose that substitute generation II purchases act partially as a replacement purchase for the generation I product. Thus, we hypothesize that households with older generation I products will make substitute generation II purchases earlier. Methods We employ Cox hazard modeling to study factors influencing the timing of a household’s adoption of generation II products. A separate hazard model is conducted for additional and substitute purchases. The age of the generation I product is calculated based on the most recent household purchase of that product. Control variables include size and income of household, age and education of decision-maker. Results and Implications Our preliminary results confirm both our hypotheses. Consumer innovativeness has a strong influence on both additional purchases and substitute purchases. Also consistent with our hypotheses, the age of the generation I product has a dramatic influence for substitute purchases of VCR/DVD players and a strong influence for PCs/notebooks. Yet, also as hypothesized, there was no influence on additional purchases. This implies that there is a clear distinction between additional and substitute purchases of generation II products, each with different drivers. For substitute purchases, product age is a key driver. Therefore marketers of high technology products can utilize data on generation I product age (e.g. from warranty or loyalty programs) to target customers who are more likely to make a purchase.

Pathogenicity of Plesiomonas shigelloides : interactions with eukaryotic host cells in vitro

Diarrhoea is one of the leading causes of morbidity and mortality in populations in developing countries and is a significant health issue throughout the world. Despite the frequency and the severity of the diarrhoeal disease, mechanisms of pathogenesis for many of the causative agents have been poorly characterised. Although implicated in a number of intestinal and extra-intestinal infections in humans, Plesiomonas shigelloides generally has been dismissed as an enteropathogen due to the lack of clearly demonstrated virulence-associated properties such as production of cytotoxins and enterotoxins or invasive abilities. However, evidence from a number of sources has indicated that this species may be the cause of a number of clinical infections. The work described in this thesis seeks to resolve this discrepancy by investigating the pathogenic potential of P. shigelloides using in vitro cell models. The focus of this research centres on how this organism interacts with human host cells in an experimental model. Very little is known about the pathogenic potential of P. shigel/oides and its mechanisms in human infections and disease. However, disease manifestations mimic those of other related microorganisms. Chapter 2 reviews microbial pathogenesis in general, with an emphasis on understanding the mechanisms resulting from infection with bacterial pathogens and the alterations in host cell biology. In addition, this review analyses the pathogenic status of a poorly-defined enteropathogen, P. shigelloides. Key stages of pathogenicity must occur in order for a bacterial pathogen to cause disease. Such stages include bacterial adherence to host tissue, bacterial entry into host tissues (usually required), multiplication within host tissues, evasion of host defence mechanisms and the causation of damage. In this study, these key strategies in infection and disease were sought to help assess the pathogenic potential of P. shigelloides (Chapter 3). Twelve isolates of P. shigelloides, obtained from clinical cases of gastroenteritis, were used to infect monolayers of human intestinal epithelial cells in vitro. Ultrastructural analysis demonstrated that P. shigelloides was able to adhere to the microvilli at the apical surface of the epithelial cells and also to the plasma membranes of both apical and basal surfaces. Furthermore, it was demonstrated that these isolates were able to enter intestinal epithelial cells. Internalised bacteria often were confined within vacuoles surrounded by single or multiple membranes. Observation of bacteria within membranebound vacuoles suggests that uptake of P. shigelloides into intestinal epithelial cells occurs via a process morphologically comparable to phagocytosis. Bacterial cells also were observed free in the host cell cytoplasm, indicating that P. shige/loides is able to escape from the surrounding vacuolar membrane and exist within the cytosol of the host. Plesiomonas shigelloides has not only been implicated in gastrointestinal infections, but also in a range of non-intestinal infections such as cholecystitis, proctitis, septicaemia and meningitis. The mechanisms by which P. shigelloides causes these infections are not understood. Previous research was unable to ascertain the pathogenic potential of P. shigel/oides using cells of non-intestinal origin (HEp-2 cells derived from a human larynx carcinoma and Hela cells derived from a cervical carcinoma). However, with the recent findings (from this study) that P. shigelloides can adhere to and enter intestinal cells, it was hypothesised, that P. shigel/oides would be able to enter Hela and HEp-2 cells. Six clinical isolates of P. shigelloides, which previously have been shown to be invasive to intestinally derived Caco-2 cells (Chapter 3) were used to study interactions with Hela and HEp-2 cells (Chapter 4). These isolates were shown to adhere to and enter both nonintestinal host cell lines. Plesiomonas shigelloides were observed within vacuoles surrounded by single and multiple membranes, as well as free in the host cell cytosol, similar to infection by P. shigelloides of Caco-2 cells. Comparisons of the number of bacteria adhered to and present intracellularly within Hela, HEp-2 and Caco-2 cells revealed a preference of P. shigelloides for Caco-2 cells. This study conclusively showed for the first time that P. shigelloides is able to enter HEp-2 and Hela cells, demonstrating the potential ability to cause an infection and/or disease of extra-intestinal sites in humans. Further high resolution ultrastructural analysis of the mechanisms involved in P. shigelloides adherence to intestinal epithelial cells (Chapter 5) revealed numerous prominent surface features which appeared to be involved in the binding of P. shige/loides to host cells. These surface structures varied in morphology from small bumps across the bacterial cell surface to much longer filaments. Evidence that flagella might play a role in bacterial adherence also was found. The hypothesis that filamentous appendages are morphologically expressed when in contact with host cells also was tested. Observations of bacteria free in the host cell cytosol suggests that P. shigelloides is able to lyse free from the initial vacuolar compartment. The vacuoles containing P. shigel/oides within host cells have not been characterised and the point at which P. shigelloides escapes from the surrounding vacuolar compartment has not been determined. A cytochemical detection assay for acid phosphatase, an enzymatic marker for lysosomes, was used to analyse the co-localisation of bacteria-containing vacuoles and acid phosphatase activity (Chapter 6). Acid phosphatase activity was not detected in these bacteria-containing vacuoles. However, the surface of many intracellular and extracellular bacteria demonstrated high levels of acid phosphatase activity, leading to the proposal of a new virulence factor for P. shigelloides. For many pathogens, the efficiency with which they adhere to and enter host cells is dependant upon the bacterial phase of growth. Such dependency reflects the timing of expression of particular virulence factors important for bacterial pathogenesis. In previous studies (Chapter 3 to Chapter 6), an overnight culture of P. shigelloides was used to investigate a number of interactions, however, it was unknown whether this allowed expression of bacterial factors to permit efficient P. shigelloides attachment and entry into human cells. In this study (Chapter 7), a number of clinical and environmental P. shigelloides isolates were investigated to determine whether adherence and entry into host cells in vitro was more efficient during exponential-phase or stationary-phase bacterial growth. An increase in the number of adherent and intracellular bacteria was demonstrated when bacteria were inoculated into host cell cultures in exponential phase cultures. This was demonstrated clearly for 3 out of 4 isolates examined. In addition, an increase in the morphological expression of filamentous appendages, a suggested virulence factor for P. shigel/oides, was observed for bacteria in exponential growth phase. These observations suggest that virulence determinants for P. shigel/oides may be more efficiently expressed when bacteria are in exponential growth phase. This study demonstrated also, for the first time, that environmental water isolates of P. shigelloides were able to adhere to and enter human intestinal cells in vitro. These isolates were seen to enter Caco-2 host cells through a process comparable to the clinical isolates examined. These findings support the hypothesis of a water transmission route for P. shigelloides infections. The results presented in this thesis contribute significantly to our understanding of the pathogenic mechanisms involved in P. shigelloides infections and disease. Several of the factors involved in P. shigelloides pathogenesis have homologues in other pathogens of the human intestine, namely Vibrio, Aeromonas, Salmonella, Shigella species and diarrhoeaassociated strains of Escherichia coli. This study emphasises the relevance of research into Plesiomonas as a means of furthering our understanding of bacterial virulence in general. As well it provides tantalising clues on normal and pathogenic host cell mechanisms.

Monte Carlo modelling of X-ray absorptiometry and its application to body composition studies

This thesis applies Monte Carlo techniques to the study of X-ray absorptiometric methods of bone mineral measurement. These studies seek to obtain information that can be used in efforts to improve the accuracy of the bone mineral measurements. A Monte Carlo computer code for X-ray photon transport at diagnostic energies has been developed from first principles. This development was undertaken as there was no readily available code which included electron binding energy corrections for incoherent scattering and one of the objectives of the project was to study the effects of inclusion of these corrections in Monte Carlo models. The code includes the main Monte Carlo program plus utilities for dealing with input data. A number of geometrical subroutines which can be used to construct complex geometries have also been written. The accuracy of the Monte Carlo code has been evaluated against the predictions of theory and the results of experiments. The results show a high correlation with theoretical predictions. In comparisons of model results with those of direct experimental measurements, agreement to within the model and experimental variances is obtained. The code is an accurate and valid modelling tool. A study of the significance of inclusion of electron binding energy corrections for incoherent scatter in the Monte Carlo code has been made. The results show this significance to be very dependent upon the type of application. The most significant effect is a reduction of low angle scatter flux for high atomic number scatterers. To effectively apply the Monte Carlo code to the study of bone mineral density measurement by photon absorptiometry the results must be considered in the context of a theoretical framework for the extraction of energy dependent information from planar X-ray beams. Such a theoretical framework is developed and the two-dimensional nature of tissue decomposition based on attenuation measurements alone is explained. This theoretical framework forms the basis for analytical models of bone mineral measurement by dual energy X-ray photon absorptiometry techniques. Monte Carlo models of dual energy X-ray absorptiometry (DEXA) have been established. These models have been used to study the contribution of scattered radiation to the measurements. It has been demonstrated that the measurement geometry has a significant effect upon the scatter contribution to the detected signal. For the geometry of the models studied in this work the scatter has no significant effect upon the results of the measurements. The model has also been used to study a proposed technique which involves dual energy X-ray transmission measurements plus a linear measurement of the distance along the ray path. This is designated as the DPA( +) technique. The addition of the linear measurement enables the tissue decomposition to be extended to three components. Bone mineral, fat and lean soft tissue are the components considered here. The results of the model demonstrate that the measurement of bone mineral using this technique is stable over a wide range of soft tissue compositions and hence would indicate the potential to overcome a major problem of the two component DEXA technique. However, the results also show that the accuracy of the DPA( +) technique is highly dependent upon the composition of the non-mineral components of bone and has poorer precision (approximately twice the coefficient of variation) than the standard DEXA measurements. These factors may limit the usefulness of the technique. These studies illustrate the value of Monte Carlo computer modelling of quantitative X-ray measurement techniques. The Monte Carlo models of bone densitometry measurement have:- 1. demonstrated the significant effects of the measurement geometry upon the contribution of scattered radiation to the measurements, 2. demonstrated that the statistical precision of the proposed DPA( +) three tissue component technique is poorer than that of the standard DEXA two tissue component technique, 3. demonstrated that the proposed DPA(+) technique has difficulty providing accurate simultaneous measurement of body composition in terms of a three component model of fat, lean soft tissue and bone mineral,4. and provided a knowledge base for input to decisions about development (or otherwise) of a physical prototype DPA( +) imaging system. The Monte Carlo computer code, data, utilities and associated models represent a set of significant, accurate and valid modelling tools for quantitative studies of physical problems in the fields of diagnostic radiology and radiography.

Excess length of stay due to central line–associated bloodstream infection in intensive care units in Argentina, Brazil, and Mexico

Objective.To estimate the excess length of stay in an intensive care unit (ICU) due to a central line–associated bloodstream infection (CLABSI), using a multistate model that accounts for the timing of infection. Design.A cohort of 3,560 patients followed up for 36,806 days in ICUs. Setting.Eleven ICUs in 3 Latin American countries: Argentina, Brazil, and Mexico. Patients.All patients admitted to the ICU during a defined time period with a central line in place for more than 24 hours. Results.The average excess length of stay due to a CLABSI increased in 10 of 11 ICUs and varied from −1.23 days to 4.69 days. A reduction in length of stay in Mexico was probably caused by an increased risk of death due to CLABSI, leading to shorter times to death. Adjusting for patient age and Average Severity of Illness Score tended to increase the estimated excess length of stays due to CLABSI. Conclusions.CLABSIs are associated with an excess length of ICU stay. The average excess length of stay varies between ICUs, most likely because of the case‐mix of admissions and differences in the ways that hospitals deal with infections.

The provision of patient personal hygiene in the intensive care unit : a descriptive exploratory study of bed-bathing practice

Background/objectives The provision of the patient bed-bath is a fundamental nursing care activity yet few quantitative data and no qualitative data are available on registered nurses’ (RNs) clinical practice in this domain in the intensive care unit (ICU). The aim of this study was to describe ICU RNs current practice with respect to the timing, frequency and duration of the patient bed-bath and the cleansing and emollient agents used. Methods The study utilised a two-phase sequential explanatory mixed method design. Phase one used a questionnaire to survey RNs and phase two employed semi-structured focus group (FG) interviews with RNs. Data was collected over 28 days across four Australian metropolitan ICUs. Ethical approval was granted from the relevant hospital and university human research ethics committees. RNs were asked to complete a questionnaire following each episode of care (i.e. bed-bath) and then to attend one of three FG interviews: RNs with less than 2 years ICU experience; RNs with 2–5 years ICU experience; and RNs with greater than 5 years ICU experience. Results During the 28-day study period the four ICUs had 77.25 beds open. In phase one a total of 539 questionnaires were returned, representing 30.5% of episodes of patient bed-baths (based on 1767 bed occupancy and one bed-bath per patient per day). In 349 bed-bath episodes 54.7% patients were mechanically ventilated. The bed-bath was given between 02.00 and 06.00 h in 161 episodes (30%), took 15–30 min to complete (n = 195, 36.2%) and was completed within the last 8 h in 304 episodes (56.8%). Cleansing agents used were predominantly pH balanced soap or liquid soap and water (n = 379, 71%) in comparison to chlorhexidine impregnated sponges/cloths (n = 86, 16.1%) or other agents such as pre-packaged washcloths (n = 65, 12.2%). In 347 episodes (64.4%) emollients were not applied after the bed-bath. In phase two 12 FGs were conducted (three FGs at each ICU) with a total of 42 RN participants. Thematic analysis of FG transcripts across the three levels of RN ICU experience highlighted a transition of patient hygiene practice philosophy from shades of grey – falling in line for inexperienced clinicians to experienced clinicians concrete beliefs about patient bed-bath needs. Conclusions This study identified variation in process and products used in patient hygiene practices in four ICUs. Further study to improve patient outcomes is required to determine the appropriate timing of patient hygiene activities and cleansing agents used to improve skin integrity.