The Making of Domestic Violence Policy by the Australian Commonwealth Government and the Government of the State of New South Wales between 1970 and 1985: An Analytical Narrative of Feminist Policy Activism

This thesis is a study of the processes by which domestic violence, as framed by Australian feminists from the early 1970s, was inserted into the policy agenda of governments, and developed into a comprehensive body of policy. The thesis covers the period between 1970 and 1985. Acknowledging the federal nature of the Australian polity, it examines these processes that unfolded within both the Australian Commonwealth government and the government of New South Wales. The thesis provides a political history of domestic violence policy making in the identified period. It shows that policy responses to women escaping violent partners included both immediate measures (such as protection and justice strategies) and more long-term measures to attempt to secure the conditions for women's financial, legal and personal autonomy. The elements found to have been most significant in shaping the development of such policies were the roles and identities of the participant players, including the driving role of the women suffering partner violence; the lack of contest in the early stages of policy achievement with established professionals in related fields; the uniquely 'hybrid' role and positioning of refuge feminists; and the degree of integration and continuity which characterised the domestic violence policy process. The thesis also investigates the relationship between domestic violence policy making and the broader women's policy enterprise. It demonstrates the care with which those involved avoided the dangers of sensationalism and tokenism while striving for an appropriate policy response. The thesis pays particular attention to the circumstances in which feminists in the early 1970s experienced their 'discovery' of domestic violence. It demonstrates the significance of social and economic circumstances in shaping the political options of feminists in the thesis period and those preceding it, and the extent to which policy possibilities are shaped by representations of the nature and functions of policy itself. Finally, the thesis investigates the relationship between the strategic processes undertaken and the policy outcomes produced, finding that policies achieved in the thesis period complemented and in some ways transcended accepted policy practice in the relevant period

Validation of the MEK5 and ERK5 pathway as targets for therapy in prostate cancer and analysis of the ERK5 signalling complex

Extracellular signal-regulated protein kinase 5 (ERK5) is a member of the mitogen activated protein (MAP) kinase family which is specifically activated by mitogen/extracellular signal regulated kinase kinase-5 (MEK5). Over recent years, abnormal MEK5/ERK5 signalling has been shown to be important in prostate carcinogenesis with increased levels of ERK5 immunoreactivity being associated with Gleason sum score (p<0.0001), bone metastases (p=0.0044) and locally advanced disease at diagnosis (p=0.0023). In addition PC3 cells over-expressing ERK5 displayed enhanced proliferation, migration and invasion. Taken together, these data suggest MEK5/ERK5 pathway to be biological important in prostate cancer and a potential target in invasive prostate cancer. Using siRNA to target ERK5 expression, I found that reduced ERK5 expression significantly inhibited cellular proliferation, motility and invasion in prostate cancer PC3 cells when compared to the controls, (p<0.005). Our group has previously reported upregulated ERK5 expression in primary human prostate cancer specimens. In this study, I was able to validate these results and demonstrate moderate-strong levels of cytoplasmic staining in 63% cases of PIN/PIA. High levels of cytoplasmic (55%) and nucleur (73%) immunoreactivity was also shown in a range of metastatic prostate tumours (n=11). A number of similarities and interactions between ERK5 and ERK1/2 have recently been identified and there is suggestion that ERK5 may in fact regulate some of the cellular functions originally attributed to ERK1/2. Potential ‘cross-talk’ between ERK5 and ERK1/2 signalling was investigated using siRNA for each individual isoform of ERK1/2. ERK1 knockdown resulted in increased ERK5 activation in addition to prolonged ERK2 phosphorylation. Proliferation studies were also performed in PC3 cells, the results of which support published data that ERK1 acts as a negative regulator and ERK2 as a positive regulator of cell proliferation. ERK5 has been shown to regulate the activity of several transcription factors and recent evidence suggests that ERK5 may be heat shock protein (HSP) 90 dependent. To further investigate the ERK5 signalling network and its interacting proteins, I performed mass spectrometry-based quantitative proteomics using SILAC labelled cells. Results from this study support the theory that HSP90 does associate with ERK5 however contrary to published data my results show that it is not involved in ERK5 activation. Our results validate the importance of the MEK5-ERK5 signalling pathway as a potential target for therapy in prostate cancer and highlight a novel functional and biochemical relationship between ERK1 and HSP 90 with ERK5 signalling

Characterization of the Covalently Bound Anionic Flavin Radical in Monoamine Oxidase A by Electron Paramagnetic Resonance

It was recently suggested that partially reduced monoamine oxidase (MAO) A contains an equilibrium mixture of an anionic flavin radical and a tyrosyl radical (Rigby, S. E.; et al. J. Biol. Chem. 2005, 280, 4627-4632). These observations formed the basis for a revised radical mechanism for MAO. In contrast, an earlier study of MAO B only found evidence for an anionic flavin radical (DeRose, V. J.; et al. Biochemistry 1996, 35, 11085-11091). To resolve the discrepancy, we have performed continuous-wave electron paramagnetic resonance at 94 GHz (W-band) on the radical form of MAO A. A comparison with D-amino acid oxidase (DAAO) demonstrates that both enzymes only contain anionic flavin radicals. Pulsed electron-nuclear double resonance spectra of the two enzymes recorded at 9 GHz (X-band) reveal distinct hyperfine coupling patterns for the two flavins. Density functional theory calculations show that these differences can be understood in terms of the difference at C8 of the isoalloxazine ring. DAAO contains a noncovalently bound flavin whereas MAO A contains a flavin covalently bound to a cysteinyl residue at C8. The similar electronic structures and hydrophobic environments of MAO and DAAO, and the similar structural motifs of their substrates suggest that a direct hydride transfer catalytic mechanism established for DAAO (Umhau, S.; et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 12463-12468) should be considered for MAO

The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement

Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe

Methicillin-resistant Staphylococcus aureus acquisition in healthcare workers with cystic fibrosis: a retrospective cross-sectional study.

Background People with cystic fibrosis (CF) may work in healthcare settings risking nosocomial pathogen acquisition. The aim of this study was to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection in adult healthcare workers with CF (HCWcf). Methods Data was collected in this observational study on MRSA acquisition from 405 CF patients attending an adult CF centre in Australia between 2001–2012. Demographic and clinical characteristics were compared between HCWcf and non-HCWcf. A sub-analysis was subsequently performed to compare demographic and clinical characteristics between those patients (HCWcf versus non-HCWcf) that acquired MRSA. We also investigated rates of chronic MRSA infection and the outcome of eradication treatment in HCWcf. Results A higher proportion of HCWcf acquired MRSA [n = 10/21] compared to non-HCWcf [n = 40/255] (P &lt;0.001). The odds of MRSA acquisition were 8.4 (95 % CI, 3.0 – 23.4) times greater in HCWcf than non-HCWcf. HCWcf with MRSA were older (P = 0.02) and had better lung function (P = 0.009), yet hospitalisation rates were similar compared to non-HCWcf with MRSA. Chronic MRSA infection developed in 36/50 CF patients (HCWcf, n = 6; non-HCWcf, n = 30), with eradication therapy achieved in 5/6 (83 %) HCWcf. Conclusions The rate of MRSA incidence was highest in HCWcf and the workplace is a possible source of acquisition. Vocational guidance should include the potential for MRSA acquisition for CF patients considering healthcare professions

Item response analysis of the Positive and Negative Syndrome Scale

<p>Abstract</p> <p>Background</p> <p>Statistical models based on item response theory were used to examine (a) the performance of individual Positive and Negative Syndrome Scale (PANSS) items and their options, (b) the effectiveness of various subscales to discriminate among individual differences in symptom severity, and (c) the appropriateness of cutoff scores recently recommended by Andreasen and her colleagues (2005) to establish symptom remission.</p> <p>Methods</p> <p>Option characteristic curves were estimated using a nonparametric item response model to examine the probability of endorsing each of 7 options within each of 30 PANSS items as a function of standardized, overall symptom severity. Our data were baseline PANSS scores from 9205 patients with schizophrenia or schizoaffective disorder who were enrolled between 1995 and 2003 in either a large, naturalistic, observational study or else in 1 of 12 randomized, double-blind, clinical trials comparing olanzapine to other antipsychotic drugs.</p> <p>Results</p> <p>Our analyses show that the majority of items forming the Positive and Negative subscales of the PANSS perform very well. We also identified key areas for improvement or revision in items and options within the General Psychopathology subscale. The Positive and Negative subscale scores are not only more discriminating of individual differences in symptom severity than the General Psychopathology subscale score, but are also more efficient on average than the 30-item total score. Of the 8 items recently recommended to establish symptom remission, 1 performed markedly different from the 7 others and should either be deleted or rescored requiring that patients achieve a lower score of 2 (rather than 3) to signal remission.</p> <p>Conclusion</p> <p>This first item response analysis of the PANSS supports its sound psychometric properties; most PANSS items were either very good or good at assessing overall severity of illness. These analyses did identify some items which might be further improved for measuring individual severity differences or for defining remission thresholds. Findings also suggest that the Positive and Negative subscales are more sensitive to change than the PANSS total score and, thus, may constitute a "mini PANSS" that may be more reliable, require shorter administration and training time, and possibly reduce sample sizes needed for future research.</p

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease : UK collaborative randomised trial

ABSTRACT Objective To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). Design Multicentre, pragmatic randomised trial (with parallel preference groups). Setting 21 hospitals in the United Kingdom. Participants 357 randomised participants (178 surgical,179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. Intervention The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. Main outcome measures The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. Main results Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. Conclusion At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. Trial registration ISRCTN15517081This study was funded by the NIHR Health Technology Assessment Programme (as part of project no. 97/10/99) and the full project report is published in Health Technology Assessment 2008;12:1/181. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewe