Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

What factors influence nurses’ assessment practices? Development of the Barriers to Nurses’ use of Physical Assessment Scale

Aim To develop and psychometrically test the Barriers to Nurses’ use of Physical Assessment Scale. Background There is growing evidence of failure to recognise hospitalised patients at risk of clinical deterioration, in part due to inadequate physical assessment by nurses. Yet, little is known about the barriers to nurses’ use of physical assessment in the acute hospital setting and no validated scales have been published. Design Instrument development study. Method Scale development was based on a comprehensive literature review, focus groups, expert review and psychometric evaluation. The scale was administered to 434 acute care registered nurses working at a large Australian teaching hospital between June and July 2013. Psychometric analysis included factor analysis, model fit statistics and reliability testing. Results The final scale was reduced to 38 items representing seven factors, together accounting for 57.7% of the variance: (1) reliance on others and technology, (2) lack of time and interruptions, (3) ward culture, (4) lack of confidence, (5) lack of nursing role models, (6) lack of influence on patient care, and; (7) specialty area. Internal reliability ranged from .70 to .86. Conclusion Findings provide initial evidence for the validity and reliability of the Barriers to Nurses’ use of Physical Assessment Scale and point to the importance of understanding the organisational determinants of nurses’ assessment practices. The new scale has potential clinical and research applications to support nursing assessment in acute care settings.

Reliability and validity of physical fitness field tests for adults aged 55 to 70 years

The aim of this study was to examine the reliability and validity of field tests for assessing physical function in mid-aged and young-old people (55-70 y). Tests were selected that required minimal space and equipment and could be implemented in multiple field settings such as a general practitioner's office. Nineteen participants completed 2 field and I laboratory testing sessions. Intra-class correlations showed good reliability for the tests of upper body strength (lift and reach, R=.66), lower body strength (sit to stand, R=.80) and functional capacity (Canadian Step Test, R=.92), but not for leg power (single timed chair rise, R=.28). There was also good reliability for the balance test during 3 stances: parallel (94.7% agreement), semi-tandem (73.7%), and tandem (52.6%). Comparison of field test results with objective laboratory measures found good validity for the sit to stand (cf 1RM leg press, Pearson r=.68, p <.05), and for the step test (cf PWC140, r = -.60, p <.001), but not for the lift and reach (cf 1RM bench press, r=.43, p >.05), balance (r=-.13, -.18, .23) and rate of force development tests (r=-.28). It was concluded that the lower body strength and cardiovascular function tests were appropriate for use in field settings with mid-aged and young-old adults.

Children's understanding of the concept of physical activity

This study evaluated 4th-grade students' understanding of the concept of physical activity and assessed the effects of two interventions to enhance the students' understanding of this concept. Students were randomly assigned to 1 of 3 conditions: the video group (n = 40) watched a 5-min video describing physical activity; the verbal group (n = 42) listened to a generic description of physical activity; the control group received no instruction (n = 45). Students completed a 17-item checklist testing their understanding of the concept of physical activity. Compared to controls, students in the verbal and video group demonstrated significantly higher checklist scores, with the video group scoring significantly higher than the verbal group. Only 35.6% of the controls, compared to 52.4% and 70.0% of the verbal and video groups respectively, could classify greater than or equal to 15 of the checklist items correctly, The results indicate that, without intervention, children have a limited understanding of the concept of physical activity.

Better health outcomes for people with physical disabilities in China through audits of mobility related access : a research and implementation need

China has 85 million people with disabilities, 30% of whom have a physical disability(1). Up to 2006, overall disability rates increased by 0.5% per year, more for males and in rural areas, and rates of physical disability increased by 11.2% per year(2). With population ageing the proportion of people with disability will increase even faster. In May 2014 the 67th World Health Assembly adopted a resolution endorsing the WHO Global Disability Action Plan 2014–2021. One of its three objectives is “to remove barriers and improve access to health services and programmes”. Access to transport contributes to positive health outcomes both directly and indirectly (e.g. access to economic opportunities, which is associated with better health)(3). However, once people with physical disabilities leave their dwellings they are confronted with physical barriers to their mobility, ranging from the condition/provision of paths to the cost/availability of transport and access to buildings. In addition, their mobility restrictions increase their vulnerability as road users, exposing them to a higher risk of injury through road crashes. QUT's School of Public Health and Social Work (PHSW) and and Centre for Accident Research and Road Safety-Queensland (CARRS-Q) CARRS-Q have been collaborating on development of a combined disability audit and road safety access tool that can identify transport barriers and safety issues along the routes taken by people with disabilities, to enable prioritisation of actions to address these issues. There are also spin-off benefits for other road users from addressing the rising toll of disability through road crashes in China(4). The tool has undergone initial proof-of-concept testing in India and Viet Nam, and is currently being assessed in Cambodia and Laos. Given the rapid development of China, increases in rates of physical disability and the impacts of an ageing population, it is proposed to establish collaborative research through the Australia-China Centre for Public Health to (1) tailor the combined road safety audit and disability access tool for use in China; (2) evaluate its use on a sample of routes; (3) develop plans for changes to the routes in consultation with local authorities; (4) evaluate the effectiveness of implemented changes in terms of access and health. 1. Zheng, Q, et al, 2014. Health and Quality of Life Outcomes, 12:25. 2. Zheng, X, et al, 2011. Bull World Health Org, 89:788–797. 3. Götschi, T & Kahlmeier, S, 2011. Integrated Transport, Health, and Sustainability Assessment (INTHESA): Final Report. Institute of Social and Preventive Medicine, University of Zurich. 4. Lin, T, et al, 2013. J Public Health, 35:541–547.

Stability analysis and implementation of Power-Hardware-in-the-Loop for power system testing

This project develops the required guidelines to assure stable and accurate operation of Power-Hardware-in-the-Loop implementations. The proposals of this research have been theoretically analyzed and practically examined using a Real-Time Digital Simulator. In this research, the interaction between software simulated power network and the physical power system has been studied. The conditions for different operating regimes have been derived and the corresponding analyses have been presented.

ISPCAN child abuse screening tool children's version (ICAST-C): Instrument development and multi-national pilot testing

Objective To develop a child victimization survey among a diverse group of child protection experts and examine the performance of the instrument through a set of international pilot studies. Methods The initial draft of the instrument was developed after input from scientists and practitioners representing 40 countries. Volunteers from the larger group of scientists participating in the Delphi review of the ICAST P and R reviewed the ICAST C by email in 2 rounds resulting in a final instrument. The ICAST C was then translated and back translated into six languages and field tested in four countries using a convenience sample of 571 children 12–17 years of age selected from schools and classrooms to which the investigators had easy access. Results The final ICAST C Home has 38 items and the ICAST C Institution has 44 items. These items serve as screeners and positive endorsements are followed by queries for frequency and perpetrator. Half of respondents were boys (49%). Endorsement for various forms of victimization ranged from 0 to 51%. Many children report violence exposure (51%), physical victimization (55%), psychological victimization (66%), sexual victimization (18%), and neglect in their homes (37%) in the last year. High rates of physical victimization (57%), psychological victimization (59%), and sexual victimization (22%) were also reported in schools in the last year. Internal consistency was moderate to high (alpha between .685 and .855) and missing data low (less than 1.5% for all but one item). Conclusions In pilot testing, the ICAST C identifies high rates of child victimization in all domains. Rates of missing data are low, and internal consistency is moderate to high. Pilot testing demonstrated the feasibility of using child self-report as one strategy to assess child victimization. Practice implications The ICAST C is a multi-national, multi-lingual, consensus-based survey instrument. It is available in six languages for international research to estimate child victimization. Assessing the prevalence of child victimization is critical in understanding the scope of the problem, setting national and local priorities, and garnering support for program and policy development aimed at child protection.

From Polymorph Screening to Dissolution Testing - Solid Phase Analysis during Pharmaceutical Development and Manufacturing

Solid materials can exist in different physical structures without a change in chemical composition. This phenomenon, known as polymorphism, has several implications on pharmaceutical development and manufacturing. Various solid forms of a drug can possess different physical and chemical properties, which may affect processing characteristics and stability, as well as the performance of a drug in the human body. Therefore, knowledge and control of the solid forms is fundamental to maintain safety and high quality of pharmaceuticals. During manufacture, harsh conditions can give rise to unexpected solid phase transformations and therefore change the behavior of the drug. Traditionally, pharmaceutical production has relied on time-consuming off-line analysis of production batches and finished products. This has led to poor understanding of processes and drug products. Therefore, new powerful methods that enable real time monitoring of pharmaceuticals during manufacturing processes are greatly needed. The aim of this thesis was to apply spectroscopic techniques to solid phase analysis within different stages of drug development and manufacturing, and thus, provide a molecular level insight into the behavior of active pharmaceutical ingredients (APIs) during processing. Applications to polymorph screening and different unit operations were developed and studied. A new approach to dissolution testing, which involves simultaneous measurement of drug concentration in the dissolution medium and in-situ solid phase analysis of the dissolving sample, was introduced and studied. Solid phase analysis was successfully performed during different stages, enabling a molecular level insight into the occurring phenomena. Near-infrared (NIR) spectroscopy was utilized in screening of polymorphs and processing-induced transformations (PITs). Polymorph screening was also studied with NIR and Raman spectroscopy in tandem. Quantitative solid phase analysis during fluidized bed drying was performed with in-line NIR and Raman spectroscopy and partial least squares (PLS) regression, and different dehydration mechanisms were studied using in-situ spectroscopy and partial least squares discriminant analysis (PLS-DA). In-situ solid phase analysis with Raman spectroscopy during dissolution testing enabled analysis of dissolution as a whole, and provided a scientific explanation for changes in the dissolution rate. It was concluded that the methods applied and studied provide better process understanding and knowledge of the drug products, and therefore, a way to achieve better quality.

Biodegradation of 1080: Testing soils in south-eastern Australia for sodium fluoroacetate-degrading micro-organisms

Sodium fluoroacetate (1080) is a vertebrate poison commonly used for the control of vertebrate pests in Australia. Long-term environmental persistence of 1080 from baiting operations has likely nontarget species and environmental impacts and is a matter of public concern. Defluorinating micro-organisms have been detected in soils of Western and central Australia, and Queensland, but not in south-eastern Australia. The presence or absence of defluorinating micro-organisms in soils from south-eastern Australia will assist in determining whether long-term environmental persistence of 1080 is or is not occurring. Soils from the Central West Slopes and Plains and Central Tablelands of New South Wales were sampled to investigate the presence and capability of 1080 defluorinating soil micro-organisms. Thirty-one species of micro-organisms were isolated from soils from each site after 10 days incubation in a 20 mM 1080 solution. Of these, 13 isolates showed measurable defluorinating ability when grown in a 1080 and sterile soil suspension. Two species, the bacteria Micromonospora, and the actinomycete Streptosporangium, have not been previously reported for their defluorinating ability. These results indicate that defluorinating micro-organisms are present in soils in south-eastern Australia, which adds weight to other studies that found that 1080 is subject to microbiological degradative processes following removal from the bait substrate. Soil micro-organism defluorination, in combination with physical breakdown and uptake by plants, indicates that fluoroacetate in soils and natural water ways is unlikely to persist. This has implications for the better informed use of 1080 in pest animal management programmes in south-eastern Australia.

A network forensics tool for precise data packet capture and replay in cyber-physical systems

Network data packet capture and replay capabilities are basic requirements for forensic analysis of faults and security-related anomalies, as well as for testing and development. Cyber-physical networks, in which data packets are used to monitor and control physical devices, must operate within strict timing constraints, in order to match the hardware devices' characteristics. Standard network monitoring tools are unsuitable for such systems because they cannot guarantee to capture all data packets, may introduce their own traffic into the network, and cannot reliably reproduce the original timing of data packets. Here we present a high-speed network forensics tool specifically designed for capturing and replaying data traffic in Supervisory Control and Data Acquisition systems. Unlike general-purpose "packet capture" tools it does not affect the observed network's data traffic and guarantees that the original packet ordering is preserved. Most importantly, it allows replay of network traffic precisely matching its original timing. The tool was implemented by developing novel user interface and back-end software for a special-purpose network interface card. Experimental results show a clear improvement in data capture and replay capabilities over standard network monitoring methods and general-purpose forensics solutions.

Breath Testing by Fourier Transform Infrared Spectroscopy for Solvent Intoxication Diagnostics

Technical or contaminated ethanol products are sometimes ingested either accidentally or on purpose. Typical misused products are black-market liquor and automotive products, e.g., windshield washer fluids. In addition to less toxic solvents, these liquids may contain the deadly methanol. Symptoms of even lethal solvent poisoning are often non-specific at the early stage. The present series of studies was carried out to develop a method for solvent intoxication breath diagnostics to speed up the diagnosis procedure conventionally based on blood tests. Especially in the case of methanol ingestion, the analysis method should be sufficiently sensitive and accurate to determine the presence of even small amounts of methanol from the mixture of ethanol and other less-toxic components. In addition to the studies on the FT-IR method, the Dräger 7110 evidential breath analyzer was examined to determine its ability to reveal a coexisting toxic solvent. An industrial Fourier transform infrared analyzer was modified for breath testing. The sample cell fittings were widened and the cell size reduced in order to get an alveolar sample directly from a single exhalation. The performance and the feasibility of the Gasmet FT-IR analyzer were tested in clinical settings and in the laboratory. Actual human breath screening studies were carried out with healthy volunteers, inebriated homeless men, emergency room patients and methanol-intoxicated patients. A number of the breath analysis results were compared to blood test results in order to approximate the blood-breath relationship. In the laboratory experiments, the analytical performance of the Gasmet FT-IR analyzer and Dräger 7110 evidential breath analyzer was evaluated by means of artificial samples resembling exhaled breath. The investigations demonstrated that a successful breath ethanol analysis by Dräger 7110 evidential breath analyzer could exclude any significant methanol intoxication. In contrast, the device did not detect very high levels of acetone, 1-propanol and 2-propanol in simulated breath. The Dräger 7110 evidential breath ethanol analyzer was not equipped to recognize the interfering component. According to the studies the Gasmet FT-IR analyzer was adequately sensitive, selective and accurate for solvent intoxication diagnostics. In addition to diagnostics, the fast breath solvent analysis proved feasible for controlling the ethanol and methanol concentration during haemodialysis treatment. Because of the simplicity of the sampling and analysis procedure, non-laboratory personnel, such as police officers or social workers, could also operate the analyzer for screening purposes.

Statistical Methods for Accelerated Life Testing with Particular Reference to Resin Impregnated Paper Bushings

Electrical failure of insulation is known to be an extremal random process wherein nominally identical pro-rated specimens of equipment insulation, at constant stress fail at inordinately different times even under laboratory test conditions. In order to be able to estimate the life of power equipment, it is necessary to run long duration ageing experiments under accelerated stresses, to acquire and analyze insulation specific failure data. In the present work, Resin Impregnated Paper (RIP) a relatively new insulation system of choice used in transformer bushings, is taken as an example. The failure data has been processed using proven statistical methods, both graphical and analytical. The physical model governing insulation failure at constant accelerated stress has been assumed to be based on temperature dependent inverse power law model.

In situ approach for testing the enantiopurity of chiral amines and amino alcohols by H-1 NMR

An in situ approach involving a simple mix and shake method for testing the enantiopurity of primary, secondary and tertiary chiral amines and their derivatives, chiral amino alcohols, by H-1-NMR spectroscopy is developed. The protocol involves the in situ formation of chiral ammonium borate salt from a mixture of C-2 symmetric chiral BINOL, trialkoxyborane and chiral amines. The proposed concept was demonstrated convincingly on a large number of chiral and pro-chiral amines and amino alcohols, and also aids the precise measurement of enantiomeric excess. The protocol can be completed in a couple of minutes directly in the NMR sample tube, without the need for any physical separation.