Humans, ‘things’ and space : costing hospital infection control interventions

Background: Previous attempts at costing infection control programmes have tended to focus on accounting costs rather than economic costs. For studies using economic costs, estimates tend to be quite crude and probably underestimate the true cost. One of the largest costs of any intervention is staff time, but this cost is difficult to quantify and has been largely ignored in previous attempts. Aim: To design and evaluate the costs of hospital-based infection control interventions or programmes. This article also discusses several issues to consider when costing interventions, and suggests strategies for overcoming these issues. Methods: Previous literature and techniques in both health economics and psychology are reviewed and synthesized. Findings: This article provides a set of generic, transferable costing guidelines. Key principles such as definition of study scope and focus on large costs, as well as pitfalls (e.g. overconfidence and uncertainty), are discussed. Conclusion: These new guidelines can be used by hospital staff and other researchers to cost their infection control programmes and interventions more accurately.

40 years of cancer nursing in Australia : the emergence of a specialty

Over the past 40 years, the nature and scope of cancer nursing practice has been shaped to a large extent by scientific and medical advances, as well as by social, economic and political factors. Nurses’ role in cancer care has evolved from being predominantly functional and dependent in its approach to being a specialty with clearly defined standards of practice underpinned by a growing evidence base and an agreed set of professional performance capabilities. The unique contribution that nurses make to minimising the effects of cancer on a person’s life and improving the patient experience is now well established and Australian cancer nurses are recognised as leaders in the field internationally. Nurses have achieved improved outcomes for people affected by cancer as part of a multidisciplinary team. By being active participants in the Clinical Oncological Society of Australia for at least 30 of the organisation’s 40 year history, Australian cancer nurses have been provided unique opportunities for professional development and inter-professional collaboration. To meet future challenges in delivering quality cancer care, cancer nurses will need to be full partners with consumers and with other health professionals in redesigning health care systems that are more responsive to changes in social, demographic, scientific and technological contexts.

Susceptibility of the critical structural components of railway bridges to the changes in train speed

Modern trains with different axle configurations, speeds and loads are used in railway networks. As a result, one of the most important questions of the mangers involved in bridge managements systems (BMS) is how these changes affect the structural behavior of the critical components of the railway bridges. Although researchers have conducted, many investigations on the dynamic effects of the moving loads on bridges, the influence of the changes in the speed of the train on the demand by capacity ratios of the different critical components of the bridge have not yet been properly studied. This study is important, because different components with different capacities and roles for carrying loads in the structure may be affected differently. To investigate the above phenomenon in this research, a structural model of a simply supported bridge is developed. It will be verified that the dynamic behavior of this bridge is similar to a group of railway bridges in Australia. Demand by capacity ratios of the critical components of the bridge, when it is subjected to a train load with different speeds will be calculated. The results show that the effect of increase or decrease of speed should not be underestimated. The outcome is very significant as it is contrary to what is currently expected, i.e. by reducing the speed of the train, the demand by capacity ratio of components may increase and make the bridge unsafe for carrying live load.

In situ observation of structural changes in polycrystalline silver catalysts by environmental scanning electron microscopy

Morphology changes induced in polycrystalline silver catalysts as a result of heating in either oxygen, water or oxygen-methanol atmospheres have been investigated by environmental scanning electron microscopy (ESEM), FT-Raman spectroscopy and temperature programmed desorption (TPD). The silver catalyst of interest consisted of two distinct particle types, one of which contained a significant concentration of sub-surface hydroxy species (in addition to surface adsorbed atomic oxygen). Heating the sample to 663 K resulted in the production of 'pin-holes' in the silver structure as a consequence of near-surface explosions caused by sub-surface hydroxy recombination. Furthermore, 'pin-holes' were predominantly found in the vicinity of surface defects, such as platelets and edge structures. Reaction between methanol and oxygen also resulted in the formation of 'pin-holes' in the silver surface, which were inherently associated with the catalytic process. A reaction mechanism is suggested that involves the interaction of methanol with sub-surface oxygen species to form sub-surface hydroxy groups. The sub-surface hydroxy species subsequently erupt through the silver surface to again produce 'pin-holes'.

Thyroxine and reserpine-induced changes in metabolic profiles of rat urine and the therapeutic effect of Liu Wei Di Huang Wan detected by UPLC-HDMS

The promise of metabonomics, a new "omics" technique, to validate Chinese medicines and the compatibility of Chinese formulas has been appreciated. The present study was undertaken to explore the excretion pattern of low molecular mass metabolites in the male Wistar-derived rat model of kidney yin deficiency induced with thyroxine and reserpine as well as the therapeutic effect of Liu Wei Di Huang Wan (LW) and its separated prescriptions, a classic traditional Chinese medicine formula for treating kidney yin deficiency in China. The study utilized ultra-performance liquid chromatography/electrospray ionization synapt high definition mass spectrometry (UPLC/ESI-SYNAPT-HDMS) in both negative and positive electrospray ionization (ESI). At the same time, blood biochemistry was examined to identify specific changes in the kidney yin deficiency. Distinct changes in the pattern of metabolites, as a result of daily administration of thyroxine and reserpine, were observed by UPLC-HDMS combined with a principal component analysis (PCA). The changes in metabolic profiling were restored to their baseline values after treatment with LW according to the PCA score plots. Altogether, the current metabonomic approach based on UPLC-HDMS and orthogonal projection to latent structures discriminate analysis (OPLS-DA) indicated 20 ions (14 in the negative mode, 8 in the positive mode, and 2 in both) as "differentiating metabolites".

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.

Optical data encryption using time-dependent dynamics of refractive index changes in LiNbO3

We present a method for optical encryption of information, based on the time-dependent dynamics of writing and erasure of refractive index changes in a bulk lithium niobate medium. Information is written into the photorefractive crystal with a spatially amplitude modulated laser beam which when overexposed significantly degrades the stored data making it unrecognizable. We show that the degradation can be reversed and that a one-to-one relationship exists between the degradation and recovery rates. It is shown that this simple relationship can be used to determine the erasure time required for decrypting the scrambled index patterns. In addition, this method could be used as a straightforward general technique for determining characteristic writing and erasure rates in photorefractive media.

Age-related changes in cardiac adenosine receptor expression

Adenosine is an important cardioprotective agent that works via several adenosine receptor (ADOR) subtypes to regulate cardiovascular activity. It is well established that functional responses to adenosine decline with age. What is unclear, though, is whether these changes occur at the receptor, second messenger or translational level. In this study we determined the effect of age on cardiac adenosine receptor expression using the housekeeping gene 18S rRNA versus the adenosine A2B receptor gene as internal controls. Absolute quantification showed that no age-related changes occurred in the expression of 18S rRNA or adenosine A2B receptor internal control genes. Subsequently, relative analysis of the adenosine receptor subtypes using 18S rRNA found a significant age-related reduction in the expression of the adenosine A1 receptor (5.5-fold), with no changes in the expression of the adenosine A2A, A2B and A3 receptors. When using the expression of the adenosine A2B receptor as the internal control gene, a significant down regulation of both the adenosine A1 (5.4-fold) and A2A (2.2-fold) receptors with no change in the expression of adenosine A3 receptor was found. Therefore, the high level of expression of the 18S rRNA housekeeping gene was found to mask a significant change in expression of the adenosine A2A receptor with age. Ultimately, these findings show an age-related reduction in adenosine A1 and A2A receptor expression in rat heart.

Changes in health profiles of participants in an Australian police department’s Wellness program

Background: Little is known about the health effects of worksite wellness programs on police department staff. Objective: To examine 1-2 year changes in health profiles of participants in the Queensland Police Service’s wellness program. Methods: Participants underwent yearly physical assessments. Health profile data collected during assessments from 2008 to 2012 were included in the analysis. Data Analysis: Repeated-measures ANOVA was used for continuous outcome variables, related-samples Wilcoxon Signed Rank test for non-normally continuous variables, and McNemar’s test for binary variables. Results: Significant changes in physical measures included decreases in waist circumference and percent body fat, and increases in cardiorespiratory fitness and flexibility (p<0.01). Changes in serum cholesterol, haemoglobin, total cholesterol ratios, HDL, LDL and Triglyceride levels were also significant (p<0.01). Conclusion: Participants’ health profiles mostly improved between cycles although most changes were not clinically significant. As this evaluation used a single-group pre-test post-test design, it provides initial indications that wellness programs can benefit staff in police departments.

Quantitative and qualitative changes in gene expression patterns characterize the activity of plaques in multiple sclerosis

Multiple sclerosis (MS) is a complex autoimmune disorder of the CNS with both genetic and environmental contributing factors. Clinical symptoms are broadly characterized by initial onset, and progressive debilitating neurological impairment. In this study, RNA from MS chronic active and MS acute lesions was extracted, and compared with patient matched normal white matter by fluorescent cDNA microarray hybridization analysis. This resulted in the identification of 139 genes that were differentially regulated in MS plaque tissue compared to normal tissue. Of these, 69 genes showed a common pattern of expression in the chronic active and acute plaque tissues investigated (Pvalue<0.0001, ρ=0.73, by Spearman's ρ analysis); while 70 transcripts were uniquely differentially expressed (≥1.5-fold) in either acute or chronic active tissues. These results included known markers of MS such as the myelin basic protein (MBP) and glutathione S-transferase (GST) M1, nerve growth factors, such as nerve injury-induced protein 1 (NINJ1), X-ray and excision DNA repair factors (XRCC9 and ERCC5) and X-linked genes such as the ribosomal protein, RPS4X. Primers were then designed for seven array-selected genes, including transferrin (TF), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), GSTP1, crystallin, alpha-B (CRYAB), phosphomannomutase 1 (PMM1) and tubulin β-5 (TBB5), and real time quantitative (Q)-PCR analysis was performed. The results of comparative Q-PCR analysis correlated significantly with those obtained by array analysis (r=0.75, Pvalue<0.01, by Pearson's bivariate correlation). Both chronic active and acute plaques shared the majority of factors identified suggesting that quantitative, rather than gross qualitative differences in gene expression pattern may define the progression from acute to chronic active plaques in MS.

Analysis of organic aerosols collected on filters by Aerosol Mass Spectrometry for source identification

Aerosol mass spectrometers (AMS) are powerful tools in the analysis of the chemical composition of airborne particles, particularly organic aerosols which are gaining increasing attention. However, the advantages of AMS in providing on-line data can be outweighed by the difficulties involved in its use in field measurements at multiple sites. In contrast to the on-line measurement by AMS, a method which involves sample collection on filters followed by subsequent analysis by AMS could significantly broaden the scope of AMS application. We report the application of such an approach to field studies at multiple sites. An AMS was deployed at 5 urban schools to determine the sources of the organic aerosols at the schools directly. PM1 aerosols were also collected on filters at these and 20 other urban schools. The filters were extracted with water and the extract run through a nebulizer to generate the aerosols, which were analysed by an AMS. The mass spectra from the samples collected on filters at the 5 schools were found to have excellent correlations with those obtained directly by AMS, with r2 ranging from 0.89 to 0.98. Filter recoveries varied between the schools from 40 -115%, possibly indicating that this method provides qualitative rather than quantitative information. The stability of the organic aerosols on Teflon filters was demonstrated by analysing samples stored for up to two years. Application of the procedure to the remaining 20 schools showed that secondary organic aerosols were the main source of aerosols at the majority of the schools. Overall, this procedure provides accurate representation of the mass spectra of ambient organic aerosols and could facilitate rapid data acquisition at multiple sites where AMS could not be deployed for logistical reasons.

Phenotypic changes in artemisinin-resistant plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition

The appearance of Plasmodium falciparum parasites with decreased in vivo sensitivity but no measurable in vitro resistance to artemisinin has raised the urgent need to characterize the artemisinin resistance phenotype. Changes in the temporary growth arrest (dormancy) profile of parasites may be one aspect of this phenotype. In this study, we investigated the link between dormancy and resistance, using artelinic acid (AL)-resistant parasites. Our results demonstrate that the AL resistance phenotype has (i) decreased sensitivity of mature-stage parasites, (ii) decreased sensitivity of the ring stage to the induction of dormancy, and (iii) a faster recovery from dormancy.

The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice.

Understanding the impact of legislative changes on child car seating and restraint practices in regional Queensland

Road crashes contribute to a significant amount of child mortality and morbidity in Australia. In fact, passenger injuries contribute to the majority of child crash road trauma. A number of factors contribute to child injury and death in motor vehicles, including inappropriate seating position, inappropriate choice of restraint, and incorrect installation and use of child restraints. Prior to March 2010, child restraint legislation in Queensland only required children twelve months and younger to be seated in a properly adjusted and fastened child restraint. This legislation left older infants and young children potentially suboptimally protected. From March 2010, new legislation specified seating position and type of child restraint required, depending on the age of the child. This research was underpinned by the Health Belief Model (HBM), which explores health related behaviour, behaviour change, environmental factors influencing behaviour change (including legislative changes) and is flexible enough to be used in relation to parents' health practices for their children, rather than parent health directly. This thesis investigates the extent to which the changes to child restraint legislation have led parents in regional areas of Queensland to use appropriate restraint practices for their children and determines the extent to which the constructs of the HBM, parental perceptions, barriers and environmental factors contribute to the appropriateness of child seating and restraint use. Study One included three sets of observations taken in two regional cities of Queensland prior to the legislative amendment, during an educative period of six months, and after the enactment of the legislation. Each child's seating position and restraint type were recorded. Results showed that the proportion of children observed occupying the front seat decreased by 15.6 per cent with the announcement the legislation. There was no decrease in front seat use at the enactment of the legislation. The proportion of children observed using dedicated child restraints increased by 8.8 per cent with the announcement of the legislation when there was one child in the vehicle. Further, there was a 10.1 per cent increase in the proportion of children observed using a seat belt that fit with the announcement when there was one child in the vehicle and with the enactment of the legislation regardless of the number of children in the vehicle (21.8 per cent for one child, 39.7 per cent for two children and 40.2 per cent for three or more children). Study Two comprised initial intercept interviews, later followed up by telephone, with parents with children aged eight years and younger at the announcement and telephone interviews at the enactment of the legislation in one regional city in Queensland. Parents reported their child restraint practices, and opinions, knowledge and understanding of the requirements of the new legislation. Parent responses were analysed in terms of the constructs in the HBM. When asked which seating position their child 'usually' used, parents reported child front seat use was nil (0.0 per cent) and did not change with the enactment of the legislative amendment. However, when parents were asked whether they allowed children to use the front seat at some point within the six months prior to the interview, reported child front seat use was 7 (5.4 per cent) children at T2 and 10 (9.6 per cent) at T3. Reported use of age-appropriate child restraints did not increase with the enactment of the legislation (p = 0.77, ns). Parents reported restraint practices were classed as either appropriate or inappropriate. Parents who reported appropriate restraint practices were those whose children were sitting in optimal restraints and seating positions for their age according to the requirements of the legislation. Parents who reported inappropriate restraint practices were those who had one or more children who were suboptimally restrained or seated for their age according to the requirements of the legislation. Neither parents' perceptions about their susceptibility of being in a crash nor the likelihood of severity of child injury if involved in a crash yielded significant differences in the appropriateness of reported parent restraint practices over time with the enactment of the legislation. A trend in the data suggested parents perceived a benefit to using appropriate restraint practices was to avoid fines and demerit points. Over 75 per cent of parents who agreed that child restraints provide better protection for children than an adult seat belt reported appropriately seating and restraining their children (2 (1) = 8.093, p<.05). The self-efficacy measure regarding parents' confidence in installing a child restraint showed a significant association with appropriate parental restraint practices (2 (1) = 7.036, p<.05). Results suggested that some parents may have misinterpreted the announcement of the legislative amendment as the announcement of the enforcement of the legislation instead. Some parents who correctly reported details of the legislation did not report appropriate child restraint practices. This finding shows that parents' knowledge of the legislative amendment does not necessarily have an impact on their behaviour to appropriately seat and restrain children. The results of these studies have important implications for road safety and the prevention of road-related injury and death to children in Queensland. Firstly, parents reported feeling unsure of how to install restraints, which suggests that there may be children travelling in restraints that have not been installed correctly, putting them at risk. Interventions to alert and encourage parents to seek advice when unsure about the correct installation of child restraints could be considered. Secondly, some parents in this study although they were using the most appropriate restraint for their children, reported using a type that was not the most appropriate restraint for the child's age according to the legislation. This suggests that intervention may be effective in helping parents make a more accurate choice of the most appropriate type of restraint to use with children, especially as the child ages and child restraint requirements change. Further research could be conducted to ascertain the most effective methods of informing and motivating parents to use the most appropriate restraints and seating positions for their children, as these results show a concerning disparity between reported restraint practices and those that were observed.

Changes to airborne pollen counts across Europe

A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO levels may be influential.