The effects of PVP(FE(III)) catalyst and polymer molecular weight on gene delivery via biodegradable crosslinked polyethylenimine

Human gene therapy has faced many setbacks due to the immunogenicity and oncogenity of viruses. Safe and efficient alternative gene delivery vehicles are needed to implement gene therapy in clinical practice. Polymeric vectors are an attractive option due to their availability, simple chemistry, and low toxicity and immunogenicity. Our group has previously reported biodegradable polyethylenimines (PEI) that show high transfection efficiency and low toxicity by cross-linking 800 Da PEI with diacrylate cross-linkers using Michael addition. However, the synthesis was difficult to control, inconsistent, and resulted in polymers with a narrow range of molecular weights. In the present work, we utilized a heterogenous PVP(Fe(III)) catalyst to provide a more controllable PEI crosslinking reaction and wider range of biodegradable PEIs. The biodegradable PEIs reported here have molecular weights ranging from 1.2 kDa to 48 kDa, are nontoxic in MDA-MB-231 cells, and show low toxicity in HeLa cells. At their respective optimal polymer:DNA ratios, these biodegradable PEIs demonstrated about 2-5-fold higher transfection efficiency and 2-7-fold higher cellular uptake, compared unmodified 25 kDa PEI. The biodegradable PEIs show similar DNA condensation properties as unmodified PEI but more readily unpackage DNA, based on ethidium bromide exclusion and heparan sulfate competitive displacement assays, which could contribute to their improved transfection efficiency. Overall, the synthesis reported here provides a more robust, controlled reaction to produce cross-linked biodegradable PEIs that show enhanced gene delivery, low toxicity, and high cellular uptake and can potentially be used for future in vivo studies.

Abstracting and correlating heterogeneous events to detect complex scenarios

The research presented in this thesis addresses inherent problems in signaturebased intrusion detection systems (IDSs) operating in heterogeneous environments. The research proposes a solution to address the difficulties associated with multistep attack scenario specification and detection for such environments. The research has focused on two distinct problems: the representation of events derived from heterogeneous sources and multi-step attack specification and detection. The first part of the research investigates the application of an event abstraction model to event logs collected from a heterogeneous environment. The event abstraction model comprises a hierarchy of events derived from different log sources such as system audit data, application logs, captured network traffic, and intrusion detection system alerts. Unlike existing event abstraction models where low-level information may be discarded during the abstraction process, the event abstraction model presented in this work preserves all low-level information as well as providing high-level information in the form of abstract events. The event abstraction model presented in this work was designed independently of any particular IDS and thus may be used by any IDS, intrusion forensic tools, or monitoring tools. The second part of the research investigates the use of unification for multi-step attack scenario specification and detection. Multi-step attack scenarios are hard to specify and detect as they often involve the correlation of events from multiple sources which may be affected by time uncertainty. The unification algorithm provides a simple and straightforward scenario matching mechanism by using variable instantiation where variables represent events as defined in the event abstraction model. The third part of the research looks into the solution to address time uncertainty. Clock synchronisation is crucial for detecting multi-step attack scenarios which involve logs from multiple hosts. Issues involving time uncertainty have been largely neglected by intrusion detection research. The system presented in this research introduces two techniques for addressing time uncertainty issues: clock skew compensation and clock drift modelling using linear regression. An off-line IDS prototype for detecting multi-step attacks has been implemented. The prototype comprises two modules: implementation of the abstract event system architecture (AESA) and of the scenario detection module. The scenario detection module implements our signature language developed based on the Python programming language syntax and the unification-based scenario detection engine. The prototype has been evaluated using a publicly available dataset of real attack traffic and event logs and a synthetic dataset. The distinct features of the public dataset are the fact that it contains multi-step attacks which involve multiple hosts with clock skew and clock drift. These features allow us to demonstrate the application and the advantages of the contributions of this research. All instances of multi-step attacks in the dataset have been correctly identified even though there exists a significant clock skew and drift in the dataset. Future work identified by this research would be to develop a refined unification algorithm suitable for processing streams of events to enable an on-line detection. In terms of time uncertainty, identified future work would be to develop mechanisms which allows automatic clock skew and clock drift identification and correction. The immediate application of the research presented in this thesis is the framework of an off-line IDS which processes events from heterogeneous sources using abstraction and which can detect multi-step attack scenarios which may involve time uncertainty.

The NOURISH randomised control trial : positive feeding practices and food preferences in early childhood - a primary prevention program for childhood obesity

Background Primary prevention of childhood overweight is an international priority. In Australia 20-25% of 2-8 year olds are already overweight. These children are at substantially increased the risk of becoming overweight adults, with attendant increased risk of morbidity and mortality. Early feeding practices determine infant exposure to food (type, amount, frequency) and include responses (eg coercion) to infant feeding behaviour (eg. food refusal). There is correlational evidence linking parenting style and early feeding practices to child eating behaviour and weight status. A focus on early feeding is consistent with the national focus on early childhood as the foundation for life-long health and well being. The NOURISH trial aims to implement and evaluate a community-based intervention to promote early feeding practices that will foster healthy food preferences and intake and preserve the innate capacity to self-regulate food intake in young children. Methods/Design This randomised controlled trial (RCT) aims to recruit 820 first-time mothers and their healthy term infants. A consecutive sample of eligible mothers will be approached postnatally at major maternity hospitals in Brisbane and Adelaide. Initial consent will be for re-contact for full enrolment when the infants are 4-7 months old. Individual mother- infant dyads will be randomised to usual care or the intervention. The intervention will provide anticipatory guidance via two modules of six fortnightly parent education and peer support group sessions, each followed by six months of regular maintenance contact. The modules will commence when the infants are aged 4-7 and 13-16 months to coincide with establishment of solid feeding, and autonomy and independence, respectively. Outcome measures will be assessed at baseline, with follow up at nine and 18 months. These will include infant intake (type and amount of foods), food preferences, feeding behaviour and growth and self-reported maternal feeding practices and parenting practices and efficacy. Covariates will include sociodemographics, infant feeding mode and temperament, maternal weight status and weight concern and child care exposure. Discussion Despite the strong rationale to focus on parents’ early feeding practices as a key determinant of child food preferences, intake and self-regulatory capacity, prospective longitudinal and intervention studies are rare. This trial will be amongst to provide Level II evidence regarding the impact of an intervention (commencing prior to age 12 months) on children’s eating patterns and behaviours. Trial Registration: ACTRN12608000056392

Self-referencing and consumer evaluations of larger-sized female models : a weight locus of control perspective

In two experiments, we show that the beliefs women have about the controllability of their weight (i.e., weight locus of control) influences their responses to advertisements featuring a larger-sized female model or a slim female model. Further, we examine self-referencing as a mechanism for these effects. Specifically, people who believe they can control their weight (“internals”), respond most favorably to slim models in advertising, and this favorable response is mediated by self-referencing. In contrast, people who feel powerless about their weight (“externals”), self-reference larger-sized models, but only prefer larger-sized models when the advertisement is for a non-fattening product. For fattening products, they exhibit a similar preference for larger-sized models and slim models. Together, these experiments shed light on the effect of model body size and the role of weight locus of control in influencing consumer attitudes.

Estimating total cross sections from neutron-nucleus collisions using a simple functional form

Total cross sections for neutron scattering from nuclei, with energies ranging from 10 to 600 MeV and from many nuclei spanning the mass range 6Li to 238U, have been analyzed using a simple, three-parameter, functional form. The calculated cross sections are compared with results obtained by using microscopic (g-folding) optical potentials as well as with experimental data. The functional form reproduces those total cross sections very well. When allowance is made for Ramsauer-like effects in the scattering, the parameters of the functional form required vary smoothly with energy and target mass. They too can be represented by functions of energy and mass.

The effectiveness of using a simple ARIA based geographical classification to identify road crash patterns in rural and urban areas of Queensland

Research has noted a ‘pronounced pattern of increase with increasing remoteness' of death rates in road crashes. However, crash characteristics by remoteness are not commonly or consistently reported, with definitions of rural and urban often relying on proxy representations such as prevailing speed limit. The current paper seeks to evaluate the efficacy of the Accessibility / Remoteness Index of Australia (ARIA+) to identifying trends in road crashes. ARIA+ does not rely on road-specific measures and uses distances to populated centres to attribute a score to an area, which can in turn be grouped into 5 classifications of increasing remoteness. The current paper uses applications of these classifications at the broad level of Australian Bureau of Statistics' Statistical Local Areas, thus avoiding precise crash locating or dedicated mapping software. Analyses used Queensland road crash database details for all 31,346 crashes resulting in a fatality or hospitalisation occurring between 1st July, 2001 and 30th June 2006 inclusive. Results showed that this simplified application of ARIA+ aligned with previous definitions such as speed limit, while also providing further delineation. Differences in crash contributing factors were noted with increasing remoteness such as a greater representation of alcohol and ‘excessive speed for circumstances.' Other factors such as the predominance of younger drivers in crashes differed little by remoteness classification. The results are discussed in terms of the utility of remoteness as a graduated rather than binary (rural/urban) construct and the potential for combining ARIA crash data with census and hospital datasets.

Longitudinal patterns of weight in women diagnosed with breast cancer [Conference Abstract]

Introduction: Weight gain is a common concern following breast cancer and has been associated with negative health outcomes. As such, prevention of weight gain is of clinical interest. This work describes weight change between 6- and 18-months following a breast cancer diagnosis and explores the personal, treatment and behavioural characteristics associated with gains in weight. Methods: Body mass index was objectively assessed, at three-monthly intervals, on a population-based sample of women newly diagnosed with unilateral breast cancer (n=185). Changes in BMI between 6- and 18-months post-diagnosis were calculated, with gains of one or more being considered clinically detrimental to future health. Results: Approximately 60% of participants were overweight or obese at 6-months post-diagnosis. While BMI remained relatively stable across the testing period (range=27.3-27.8), 24% of participants experienced clinically relevant gains in BMI (median gains=1.9). Following adjustment for potential confounders, younger age (<45 years; Odds ratio, OR=9.8), being morbidly obese at baseline (OR=4.6) and receiving hormone therapy (OR=4.8) were characteristics associated with an increased odds (p<0.05) of gaining BMI. Other characteristics associated with gains in BMI were more extensive surgery and having a history of smoking, although these relationships were not supported statistically. In contrast, caring for younger children was associated with reduced risk of gaining BMI (OR=0.3, p=0.20). Conclusions: Clinically relevant weight gain between 6- and 18-months post-breast cancer diagnosis is an issue for one in four women, with certain subgroups being particularly susceptible. However, the majority of women diagnosed with breast cancer are overweight or obese and gains in body weight are common. Thus, interventions that address the importance of achieving and sustaining a healthy body weight, delivered to all women with breast cancer, may have greater public health impact than interventions targeting any specific breast cancer subgroup.

Development and validation of 3-Minute Nutrition Screening (3-MinNS) tool for acute hospital patients in Singapore

It is important to detect and treat malnutrition in hospital patients so as to improve clinical outcome and reduce hospital stay. The aim of this study was to develop and validate a nutrition screening tool with a simple and quick scoring system for acute hospital patients in Singapore. In this study, 818 newly admitted patients aged above 18 years old were screened using five parameters that contribute to the risk of malnutrition. A dietitian blinded to the nutrition screening score assessed the same patients using the reference standard, Subjective Global Assessment (SGA) within 48 hours. The sensitivity and specificity were established using the Receiver Operator Characteristics (ROC) curve and the best cutoff scores determined. The nutrition parameter with the largest Area Under the ROC Curve (AUC) was chosen as the final screening tool, which was named 3-Minute Nutrition Screening (3-MinNS). The combination of the parameters weight loss, intake and muscle wastage (3-MinNS), gave the largest AUC when compared with SGA. Using 3-MinNS, the best cutoff point to identify malnourished patients is three (sensitivity 86%, specificity 83%). The cutoff score to identify subjects at risk of severe malnutrition is five (sensitivity 93%, specificity 86%). 3-Minute Nutrition Screening is a valid, simple and rapid tool to identify patients at risk of malnutrition in Singapore acute hospital patients. It is able to differentiate patients at risk of moderate malnutrition and severe malnutrition for prioritization and management purposes.