Understanding the experience of social housing pathways

This report is part of an Australian Housing and Urban Research Institute (AHURI) Inquiry examining how social housing pathways could be reimagined to provide more effective assistance for low-income households in Australia. This research sets out to understand the ways in which individuals and households experience pathways into, within and out of the Australian social housing system

Ethical issues in the use of in-depth interviews: literature review and discussion

This paper reports a literature review on the topic of ethical issues in in-depth interviews. The review returned three types of article: general discussion, issues in particular studies, and studies of interview-based research ethics. Whilst many of the issues discussed in these articles are generic to research ethics, such as confidentiality, they often had particular manifestations in this type of research. For example, privacy was a significant problem as interviews sometimes probe unexpected areas. For similar reasons, it is difficult to give full information of the nature of a particular interview at the outset, hence informed consent is problematic. Where a pair is interviewed (such as carer and cared-for) there are major difficulties in maintaining confidentiality and protecting privacy. The potential for interviews to harm participants emotionally is noted in some papers, although this is often set against potential therapeutic benefit. As well as these generic issues, there are some ethical issues fairly specific to in-depth interviews. The problem of dual role is noted in many papers. It can take many forms: an interviewer might be nurse and researcher, scientist and counsellor, or reporter and evangelist. There are other specific issues such as taking sides in an interview, and protecting vulnerable groups. Little specific study of the ethics of in-depth interviews has taken place. However, that which has shows some important findings. For example, one study shows participants are not averse to discussing painful issues provided they feel the study is worthwhile. Some papers make recommendations for researchers. One such is that they should consider using a model of continuous (or process) consent rather than viewing consent as occurring once, at signature, prior to the interview. However, there is a need for further study of this area, both philosophical and empirical

Diagnostic test accuracy and cost‐effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To estimate the sensitivity and specificity of each technique for determining 1p/19q codeletion status in glioma, with a view to determining the most sensitive and specific technique(s)

MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review

BACKGROUND: The DNA repair protein O6 methylguanine-DNA methyltransferase (MGMT) causes resistance of tumour cells to alkylating agents. It is a predictive biomarker in high grade gliomas treated with temozolomide, however there is no consensus on which test method, methylation sites, and cut-off values to use. METHODS: We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; where MGMT status was determined in tumour tissue, and assessed by one or more technique; and where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios. Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS: Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS: We cannot draw strong conclusions about use of frozen tissue versus formalin-fixed paraffin embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and Pyrosequencing at CpG sites ranging from 72 to 95. A cut-off threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies. 190 studies were identified presenting hazard ratios from survival analysis in patients in which MGMT methylation was measured by one technique only

EGFRvIII upregulates DNA mismatch repair resulting in increased temozolomide sensitivity of MGMT promoter methylated glioblastoma

The oncogene epidermal growth factor receptor variant III (EGFRvIII) is frequently expressed in glioblastomas (GBM) but its impact on therapy response is still under controversial debate. Here we wanted to test if EGFRvIII influences the sensitivity towards the alkylating agent temozolomide (TMZ). Therefore, we retrospectively analyzed the survival of 336 GBM patients, demonstrating that under standard treatment, which includes TMZ, EGFRvIII expression is associated with prolonged survival, but only in patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated tumors. Using isogenic GBM cell lines with endogenous EGFRvIII expression we could demonstrate that EGFRvIII increases TMZ sensitivity and results in enhanced numbers of DNA double-strand breaks and a pronounced S/G2-phase arrest after TMZ treatment. We observed a higher expression of DNA mismatch repair (MMR) proteins in EGFRvIII+ cells and patient tumor samples, which was most pronounced for MSH2 and MSH6. EGFRvIII-specific knockdown reduced MMR protein expression thereby increasing TMZ resistance. Subsequent functional kinome profiling revealed an increased activation of p38- and ERK1/2-dependent signaling in EGFRvIII expressing cells, which regulates MMR protein expression downstream of EGFRvIII. In summary, our results demonstrate that the oncoprotein EGFRvIII sensitizes a fraction of GBM to current standard of care treatment through the upregulation of DNA MMR

A multi-region assessment of population rates of cardiac catheterization and yield of high-risk coronary artery disease

<p>Abstract</p> <p>Background</p> <p>There is variation in cardiac catheterization utilization across jurisdictions. Previous work from Alberta, Canada, showed no evidence of a plateau in the yield of high-risk disease at cardiac catheterization rates as high as 600 per 100,000 population suggesting that the optimal rate is higher. This work aims 1) To determine if a previously demonstrated linear relationship between the yield of high-risk coronary disease and cardiac catheterization rates persists with contemporary data and 2) to explore whether the linear relationship exists in other jurisdictions.</p> <p>Methods</p> <p>Detailed clinical information on all patients undergoing cardiac catheterization in 3 Canadian provinces was available through the Alberta Provincial Project for Outcomes Assessment in Coronary Heart (APPROACH) disease and partner initiatives in British Columbia and Nova Scotia. Population rates of catheterization and high-risk coronary disease detection for each health region in these three provinces, and age-adjusted rates produced using direct standardization. A mixed effects regression analysis was performed to assess the relationship between catheterization rate and high-risk coronary disease detection.</p> <p>Results</p> <p>In the contemporary Alberta data, we found a linear relationship between the population catheterization rate and the high-risk yield. Although the yield was slightly less in time period 2 (2002-2006) than in time period 1(1995-2001), there was no statistical evidence of a plateau. The linear relationship between catheterization rate and high-risk yield was similarly demonstrated in British Columbia and Nova Scotia and appears to extend, without a plateau in yield, to rates over 800 procedures per 100,000 population.</p> <p>Conclusions</p> <p>Our study demonstrates a consistent finding, over time and across jurisdictions, of linearly increasing detection of high-risk CAD as population rates of cardiac catheterization increase. This internationally-relevant finding can inform country-level planning of invasive cardiac care services.</p

Long-Term Effect of Participation in an Early Exercise and Education Program on Clinical Outcomes and Cost Implications, in Patients with TIA and Minor, Non-Disabling Stroke

Participation in exercise and education programs following transient ischemic attack (TIA) or minor stroke may decrease cardiovascular disease risk. The purpose of this study was to assess the long-term effect (3.5 years) of an exercise and education program administered soon after TIA or minor stroke diagnosis on clinical outcome measures (stroke classification and number, patient deaths, hospital/emergency department admission) and cost implications obtained from standard hospital records. Hospital records were screened for 60 adults (male, n = 31; 71 ± 10 years), diagnosed with TIA or non-disabling stroke, who had previously been randomised and completed either an 8-week exercise and education program, or usual care control. Follow-up clinical outcomes and cost implications were obtained 3.5 ± 0.3 years post-exercise. Participants randomised to the exercise and education program had significantly fewer recurrent stroke/TIAs (n = 3 vs. n = 13, Cohen’s d = 0.79) than the control group (P ≤ 0.003). Similar finding were reported for patient deaths (n = 0 vs. n = 4, d = 0.53), and hospital admissions (n = 48 vs. n = 102, d = 0.54), although these findings were only approaching statistical significance. The relative risk (mean; 95%CI) of death, stroke/TIAs and hospital admissions were 0.11 (0.01 to 1.98), 0.23 (0.07 to 0.72) and 0.79 (0.57 to 1.09), respectively. Hospital admission costs were significantly lower for the exercise group ($9041 ± 15,080 NZD [~$6000 ± 10,000 USD]) than the control group ($21,750 ± 22,973 NZD [~$14,000 ± 15,000 USD]) during the follow-up period (P &lt; 0.05, d = 0.69). The present study demonstrates the long-term patient benefit and economic importance of providing secondary prevention, exercise and education programs for patients with TIA and minor stroke. URL: http://www.anzctr.org.au/; Trial Registration Number: ACTRN12611000630910

Application of 4,5-diaminofluorescein to reliably measure nitric oxide released from endothelial cells in vitro

Here we describe in more depth the previously published application of the fluorescent probe 4,5-diaminofluorescein (DAF-2) in order to reliably measure low levels of nitric oxide (NO) as released from human endothelial cells in vitro. The used approach is based on the following considerations a) use low concentrations of DAF-2 (0.1 µM) in order to reduce the contribution of DAF-2 auto-fluorescence to the measured total fluorescence, and b) subtract the DAF-2 auto-fluorescence from the measured total fluorescence. The advantage of this method is the reliable quantification of NO in a biological system in the nanomolar range once thoroughly validated. Here we focus in addition to the previous publication (Leikert et al., FEBS Lett 2001, 506:131-134) on aspects of validation procedures as well as limitations and pitfalls of this method

PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

<p>Abstract</p> <p>Background</p> <p>Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the <it>PLCL1 </it>(phospholipase c-like 1) locus. Carriers of the major A allele of the most significant polymorphism, rs7595412, have around 17% larger hip BS than non-carriers. We therefore hypothesized that this polymorphism may also influence postmenopausal complications.</p> <p>Methods</p> <p>The effects of rs7595412 on hip BS, bone mineral density (BMD), vertebral fractures, serum Crosslaps and osteocalcin levels were analyzed in 1,191 postmenopausal Danish women.</p> <p>Results</p> <p>This polymorphism had no influence on hip and spine BS as well as on femur and spine BMD. Women carrying at least one copy of the A allele had lower levels of serum osteocalcin as compared with those homozygous for the G allele (p = 0.03) whereas no effect on serum Crosslaps was detected. Furthermore, women homozygous for the A allele were more affected by vertebral fractures than those carrying at least one copy of the G allele (p = 0.04).</p> <p>Conclusions</p> <p>In postmenopausal women, our results suggest that the <it>PLCL1 </it>rs7595412 polymorphism has no obvious effect on hip BS or BMD but may be nominally associated with increased proportion of vertebral fracture and increased levels of osteocalcin.</p

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure