Ventilation distribution in rats : part 2 – a comparison of electrical impedance tomography and hyperpolarised helium magnetic resonance imaging

Background: Hyperpolarised helium MRI (He3 MRI) is a new technique that enables imaging of the air distribution within the lungs. This allows accurate determination of the ventilation distribution in vivo. The technique has the disadvantages of requiring an expensive helium isotope, complex apparatus and moving the patient to a compatible MRI scanner. Electrical impedance tomography (EIT) a non-invasive bedside technique that allows constant monitoring of lung impedance, which is dependent on changes in air space capacity in the lung. We have used He3MRI measurements of ventilation distribution as the gold standard for assessment of EIT. Methods: Seven rats were ventilated in supine, prone, left and right lateral position with 70% helium/30% oxygen for EIT measurements and pure helium for He3 MRI. The same ventilator and settings were used for both measurements. Image dimensions, geometric centre and global in homogeneity index were calculated. Results: EIT images were smaller and of lower resolution and contained less anatomical detail than those from He3 MRI. However, both methods could measure positional induced changes in lung ventilation, as assessed by the geometric centre. The global in homogeneity index were comparable between the techniques. Conclusion: EIT is a suitable technique for monitoring ventilation distribution and inhomgeneity as assessed by comparison with He3 MRI.

Sitting-time, physical activity and depressive symptoms in mid-aged women

Background: Associations between sitting-time and physical activity (PA) with depression are unclear. Purpose: To examine concurrent and prospective associations between both sitting-time and PA with prevalent depressive symptoms in mid-aged Australian women. Methods: Data were from 8,950 women, aged 50-55 years in 2001, who completed mail surveys in 2001, 2004, 2007 and 2010. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression questionnaire. Associations between sitting-time (≤4, >4-7, >7 hrs/day) and PA (none, some, meeting guidelines) with depressive symptoms (symptoms/no symptoms) were examined in 2011 in concurrent and lagged mixed effect logistic modeling. Both main effects and interaction models were developed. Results: In main effects modeling, women who sat >7 hrs/day (OR 1.47, 95%CI 1.29-1.67) and women who did no PA (OR 1.99, 95%CI 1.75-2.27) were more likely to have depressive symptoms than women who sat ≤4 hrs/day and who met PA guidelines, respectively. In interaction modeling, the likelihood of depressive symptoms in women who sat >7 hrs/day and did no PA was triple that of women who sat ≤4 hrs/day and met PA guidelines (OR 2.96, 95%CI 2.37-3.69). In prospective main effects and interaction modeling, sitting-time was not associated with depressive symptoms, but women who did no PA were more likely than those who met PA guidelines to have future depressive symptoms (OR 1.26, 95%CI 1.08-1.47). Conclusions: Increasing PA to a level commensurate with PA guidelines can alleviate current depression symptoms and prevent future symptoms in mid-aged women. Reducing sitting-time may ameliorate current symptoms.

Autologous vs. allogenic mesenchymal progenitor cells for the reconstruction of critical-sized segmental tibial bone defects in aged sheep

Mesenchymal progenitor cells (MPCs) represent an attractive cell population for bone tissue engineering. Their special immunological characteristics suggest that MPCs may be used in an allogenic application. The objective of this study was to compare the regenerative potential of autologous vs. allogenic MPCs in an ovine critical-sized segmental defect model. Ovine MPCs were isolated from bone marrow aspirates, expanded and cultured with osteogenic media for two weeks before implantation. Autologous and allogenic transplantation was performed by using the cell-seeded scaffolds, unloaded scaffolds and the application of autologous bone grafts served as control groups (n=6). Bone healing was assessed twelve weeks after surgery by radiology, micro computed tomography, biomechanical testing and histology. Radiology, biomechanical testing and histology revealed no significant difference in bone formation between the autologous and allogenic group. Both cell groups showed more bone formation than the scaffold alone, whereas the biomechanical data showed no significant differences between the cell-groups and the unloaded scaffolds. The results of the study suggest that scaffold based bone tissue engineering using allogenic cells offers the potential for an off the shelf product. Therefore, the results of this study serve as an important baseline for the translation of the assessed concepts into clinical application.

Cryptic diversity and evolutionary relationships among Australian closed-forest Melomys (Rodentia: Muridae) and related Australo-Papuan mosaic-tailed rats

This thesis investigates patterns of evolution in a group of native Australo-Papuan rodents. Past climatic change and associated sea level fluctuations, and fragmentation of wet forests in eastern Australia has facilitated rapid radiation, diversification and speciation in this group. This study adds to our understanding of the evolution of Australia’s rainforest fauna and describes the evolutionary relationships of a new genus of Australian rodent.

The Tashi project 2004-2010 : developing methods for creating theatre works that fully engage children aged between 3 and 10

Over a seven-year period, Mark Radvan directed a suite of children’s theatre productions adapted from the original Tashi stories by Australian writers Anna and Barbara Fienberg. The Tashi Project’s repertoire of plays performed to over 40,000 children aged between 3 and 10 years old, and their carers, in seasons at the Out of the Box Festival, at Brisbane Powerhouse and in venues across Australia in two interstate tours in 2009 and 2010. The project investigated how best to combine an exploration of theatrical forms and conventions, with a performance style evolved in a specially developed training program and a deliberate positioning of young children as audiences capable of sophisticated readings of action, symbol, theme and character. The results of this project show that when brought into appropriate relationship with the theatre artists, young children aged 3-5 can engage with sophisticated narrative forms, and with the right contextual framing they enjoy heightened dramatic and emotional tension, bringing to the event sustained and highly engaged concentration. Older children aged 6-10 also bring sustained and heightened engagement to the same stories, providing that other more sophisticated dramatic elements are woven into the construction of the performances, such as character, theme and style.

PP39 Mental health outcomes of abortion for young women aged 18-23 years, findings from an Australian longitudinal birth cohort study

Background: Few longitudinal studies have examined the mental health outcomes of women after abortion and the results are controversial. Despite falling birth rates, teenage pregnancies remain high and over half (53%) of teenage and a third (36%) of young adult (20_24 years) pregnancies are aborted. Recent findings from a NewZealand longitudinal birth cohort linked abortion and subsequent psychiatric disorders in young women. Limited Australian data is available examining this association. Methods: Data were taken from the Mater-University Study of Pregnancy (MUSP). Running since 1981, this is a prospective birth cohort study of 7223 mothers and children. At the 21-year follow-up 3775 (52.3% of the original cohort) participants were surveyed, of these 1132 young women had complete data on pregnancy outcomes and psychiatric diagnoses from a structured interview. Binary logistic regression examined the association between five lifetime psychiatric disorders (nicotine, alcohol, cannabis, affective and anxiety disorders) and ever having an abortion or birth. Analyses adjusted for age, concurrent and maternal sociodemographic factors, and factors related to adolescent behaviour, previous mental health and family functioning. Results: A quarter of the young women (n_261) reported at least one pregnancy and 32.6% had an abortion. Abortion was significantly associated with age-adjusted OR for all the lifetime disorders. After full adjustment abortion remained significantly associated with nicotine (OR_2.1, 1.2_3.6) and alcohol disorders (OR_2.0, 1.3_3.3). Conclusion: The findings suggest that abortion in young women is independently associated with an increased risk of nicotine and alcohol disorders.

Metabolomic analysis characterizes tissue specific indomethacin-induced metabolic perturbations of rats

In this study, the promising metabolomic approach integrating with ingenuity pathway analysis (IPA) was applied to characterize the tissue specific metabolic perturbation of rats that was induced by indomethacin. The selective pattern recognition analyses were applied to analyze global metabolic profiling of urine of rats treated by indomethacin at an acute dosage of reference that has been proven to induce tissue disorders in rats, evaluated throughout the time-course of -24-72 h. The results preliminarily revealed that modifications of amino acid metabolism, fatty acid metabolism and energetically associated metabolic pathways accounted for metabolic perturbation of the rats that was induced by indomethacin. Furthermore, IPA was applied to deeply analyze the biomarkers and their relations with the metabolic perturbations evidenced by pattern recognition analyses. Specific biochemical functions affected by indomethacin suggested that there is an important correlation of its effects in kidney and liver metabolism, based on the determined metabolites and their pathway-based analysis. The IPA correlation of the three major biomarkers, identified as creatinine, prostaglandin E2 and guanosine, suggested that the administration of indomethacin induced certain levels of toxicity in the kidneys and liver. The changes in the levels of biomarker metabolites allowed the phenotypical determination of the metabolic perturbations induced by indomethacin in a time-dependent manner.

Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

This paper was designed to study metabonomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula for treatment of jaundice and liver disorders in China. Urinary samples from control, alcohol- and YCHT-treated rats were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) in positive ionization mode. The total ion chromatograms obtained from the control, alcohol- and YCHT-treated rats were easily distinguishable using a multivariate statistical analysis method such as the principal components analysis (PCA). The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the control and YCHT-treated rats. The positive ions m/z 664.3126 (9.00 min) was elevated in urine of alcohol-treated rats, whereas, ions m/z 155.3547 (10.96 min) and 708.2932 (9.01 min) were at a lower concentration compared with that in urine of control rats, however, these ions did not indicate a statistical difference between control rats and YCHT-treated rats. The ion m/z 664.3126 was found to correspond to ceramide (d18:1/25:0), providing further support for an involvement of the sphingomyelin signaling pathway in alcohol hepatotoxicity and the intervention effects of YCHT.

Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods

BACKGROUND & AIMS Metabolomics is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could provide valuable insights into the mechanisms of diseases. The aim of this study was to elucidate the changes in endogenous metabolites and to phenotype the metabolic profiling of d-galactosamine (GalN)-inducing acute hepatitis in rats by UPLC-ESI MS. METHODS The systemic biochemical actions of GalN administration (ip, 400 mg/kg) have been investigated in male wistar rats using conventional clinical chemistry, liver histopathology and metabolomic analysis of UPLC- ESI MS of urine. The urine was collected predose (-24 to 0 h) and 0-24, 24-48, 48-72, 72-96 h post-dose. Mass spectrometry of the urine was analysed visually and via conjunction with multivariate data analysis. RESULTS Results demonstrated that there was a time-dependent biochemical effect of GalN dosed on the levels of a range of low-molecular-weight metabolites in urine, which was correlated with developing phase of the GalN-inducing acute hepatitis. Urinary excretion of beta-hydroxybutanoic acid and citric acid was decreased following GalN dosing, whereas that of glycocholic acid, indole-3-acetic acid, sphinganine, n-acetyl-l-phenylalanine, cholic acid and creatinine excretion was increased, which suggests that several key metabolic pathways such as energy metabolism, lipid metabolism and amino acid metabolism were perturbed by GalN. CONCLUSION This metabolomic investigation demonstrates that this robust non-invasive tool offers insight into the metabolic states of diseases.

Patellar tendinopathy in junior basketball players : a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years

Anterior knee pain is a common presenting complaint amongst adolescent athletes. We hypothesised that patellar tendinopathy may occur at a younger age than is generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to 18-year-old female (n=64) and male (n=70) basketball players and 29 control swimmers (17 female, 12 male) clinically and with ultrasonography. We found that of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds (11% in males, 2% in females). Twenty-six percent of the basketball players' patellar tendons contained an ultrasonographic hypoechoic region. Ultrasonographic abnormality was more prevalent in the oldest tertile of players (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic hypoechoic region nevertheless. This study indicates that patellar tendinopathy can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon abnormality is 3 times as common as clinical symptoms

Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, λHR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 Pstl RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by χ2 analysis (P > 0.2). Linkage analysis of a family (data from 16 family members, 10 of whom were hypertensive), informative for both markers, without an age-of-onset correction, and assuming dominant inheritance of hypertension, complete penetrance and a disease frequency of 20%, did not indicate linkage of REN with hypertension, but gave a positive, although not significant, logarithm of the odds for linkage score of 0.784 at a recombination fraction of 0 for AT3 linkage to hypertension. In conclusion, the present study could find no evidence for an association of a REN HindIII RFLP with essential hypertension or for a linkage of the locus defined by this RFLP in a family segregating for hypertension. In the case of an AT3 Pstl RFLP, although association analysis was negative, linkage analysis suggested possible involvement (odds of 6:1 in favour) of a gene located near the 1q23 locus with hypertension in one informative family.

Get real : the development, implementation and evaluation of an intervention for primary aged children with High Functioning Autism

Children with Autism Spectrum Disorder experience difficulty in communication and in understanding the social world which can have negative consequences for their relationships, in managing emotions, and generally dealing with the challenges of everyday life. This thesis examines the effectiveness of the Active and Reflective components of the Get REAL program through the assessment of the detailed coding of video-recorded observations and longitudinal quantitative analysis. The aim of Get REAL is to increase the social, emotional, and cognitive learning of children with High Functioning Autism (HFA). Get REAL is a group program designed specifically for use in inclusive primary school settings. The Get REAL program was designed in response to the mixed success of generalisation of learning to new contexts of existing social skills programs. The theoretical foundation of Get REAL is based upon pedagogical theory and learning theory to facilitate transfer of learning, combined with experiential, individualised, evaluative and organisational approaches. This thesis is by publication and consists of four refereed journal papers; 1 accepted for publication and 3 that are under review. Paper 1 describes the development and theoretical basis of the Get REAL program and provides detail of the program structure and learning cycle. The focus of Paper 1 reflects the first question of interest in the thesis which is about the extent to which learning derived from participation in the program can be generalised to other contexts. Participants are 16 children with HFA ranging in age from 8-13 years. Results provided support for the generalisability of learning from Get REAL to home and school evidenced by parent and teacher data collected pre and post participation in Get REAL. Following establishment of the generalisation of learning from Get REAL, Papers 2 and 3 focus on the Active and Reflective components of the program in order to examine how individual and group learning takes place. Participants (N = 12) in the program are video-taped during the Active and Reflective Sessions. Using identical coding protocols of video data, improvements in prosocial behaviour and diminishing of inappropriate behaviours were apparent with the exception of perspective taking. Data also revealed that 2 of the participants had atypical trajectories. An in-depth case study analysis was then conducted with these 2 participants in Paper 4. Data included reports from health care and education professionals within the school and externally (e.g., paediatrician) and identified the multi-faceted nature of care needed for children with comorbid diagnoses and extremely challenging family circumstances as a complex task to effect change. Results of this research support the effectiveness of the Get REAL program in promoting pro social behaviours such as improvements in engaging with others and emotional regulation, and in diminishing unwanted behaviours such as conduct problems. Further, the gains made by the participating children were found to be generalisable beyond Get REAL to home and other school settings. The research contained in the thesis adds to current knowledge about how learning can take place for children with HFA. Results show that an experiential learning framework with a focus on social cognition, together with explicit teaching, scaffolded with video feedback, are key ingredients for the generalisation of social learning to broader contexts.

Nurses' experiences of practice and political reform in long-term aged care in Australia : implications for the retention of nursing personnel

Keywords gerontological nursing;health care reform;health policy;long-term care;recruitment and retention Aim  The aim of the study was to explore registered nurses’ experiences in long-term aged care in light of the political reform of aged care services in Australia. Background  In Australia, the aged care industry has undergone a lengthy period of political and structural reform. Despite reviews into various aspects of these reforms, there has been little consideration of the effect these are having on the practice experiences and retention of nursing staff in long-term care. Methods  In this critical hermeneutic study, 14 nurses from long-term care facilities in Australia were interviewed about their experiences during the reform period. Results  The data revealed a sense of tension and conflict between nurses’ traditional values, roles and responsibilities and those supported by the reforms. Nurses struggled to renegotiate both their practice roles and values as the reforms were implemented and the system evolved. Nursing management support was an important aspect in mediating the effect of reforms on nursing staff. Conclusion  This research highlights both the tensions experienced by nurses in long-term aged care in Australia and the need to renegotiate nursing roles, responsibilities and values within an evolving care system. This research supports a role for sensitive and proactive nursing management during periods of industry reform as a retention strategy for qualified nursing personnel.

Searching for value : the influence of policy and reform on nurses’ sense of value in long-term aged care in Australia.

Contemporary literature on long-term aged care focuses heavily on issues associated with the recruitment and retention of nursing staff, such as job satisfaction and attitudes towards caring for older people. This paper aims to highlight one aspect of a larger study of registered nurses' experiences in long-term aged care in Australia and the influence that government policy and reform has in shaping that experience. This insight into aspects of nurses' everyday experience also contributes to a broader understanding of job satisfaction in long-term care. Findings from this study suggest that registered nurses experience tension in their search for value in their practice, which incorporates professional, political and social mediators of value and worth. These issues are discussed in relation to the impact of policy and reform on nurses' sense of value in long-term aged care and highlight the need for sensitive policy initiatives that support issues of value in nursing practice.

The interface of acute and aged care : the role of the nurse in a provincial area

Objective This study was to investigate issues that arose from pre-admission to post-discharge, for people in Toowoomba, Queensland over the age of 65 admitted to an acute facility. This paper concentrates on a significant concern that emerged from the large amount of data collected during this project, that is,the role of the nurse in the continuum of health care involving elderly people. Method The study involved a multi-site, multi-agency and multi-method (qualitative and quantitative) approach. Data was collected from regional service providers, the Department of Health and Aged Care (DHAC), the Australian Bureau of Statistics (ABS), Home and Community Care (HACC), the Aged Care Assessment Team (ACAT), elderly people who had been discharged from regional hospitals and their carers, residents of regional aged care facilities, area health professionals and elderly regional hospital inpatients. Results The data indicated that nurses in this provincial area currently play a limited role in preadmission planning, being mostly concerned with elective surgery, especially joint replacements. While nurses deliver the majority of care during hospitalisation, they do not appear to be cognizant of the needs of the elderly regarding post-acute discharge. Conclusion The recent introduction of the model of nurse case management in the acute sector appears to be a positive development that will streamline and optimise the health care of the elderly across the continuum in the Toowoomba area. The paper recommends some strategies, such as discharge liaison nurses based in Emergency Departments and the expansion of the nurse case management role, which would optimise care for the elderly person at the interface of care.