Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Exploring retinal and functional markers of diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most debilitating complications of diabetes. DPN is a major cause of foot ulceration and lower limb amputation. Early diagnosis and management is a key factor in reducing morbidity and mortality. Current techniques for clinical assessment of DPN are relatively insensitive for detecting early disease or involve invasive procedures such as skin biopsies. There is a need for less painful, non-invasive and safe evaluation methods. Eye care professionals already play an important role in the management of diabetic retinopathy; however recent studies have indicated that the eye may also be an important site for the diagnosis and monitoring of neuropathy. Corneal nerve morphology has been shown to be a promising marker of diabetic neuropathy occurring elsewhere in the body, and emerging evidence tentatively suggests that retinal anatomical markers and a range of functional visual indicators could similarly provide useful information regarding neural damage in diabetes – although this line of research is, as yet, less well established. This review outlines the growing body of evidence supporting a potential diagnostic role for retinal structure and visual functional markers in the diagnosis and monitoring of peripheral neuropathy in diabetes.

Visualisation modelling in 3D of an alluvial aquifer system at a valley-wide scale to understand groundwater status : Lockyer, QLD

Visualisation provides a method to efficiently convey and understand the complex nature and processes of groundwater systems. This technique has been applied to the Lockyer Valley to aid in comprehending the current condition of the system. The Lockyer Valley in southeast Queensland hosts intensive irrigated agriculture sourcing groundwater from alluvial aquifers. The valley is around 3000 km2 in area and the alluvial deposits are typically 1-3 km wide and to 20-35 m deep in the main channels, reducing in size in subcatchments. The configuration of the alluvium is of a series of elongate “fingers”. In this roughly circular valley recharge to the alluvial aquifers is largely from seasonal storm events, on the surrounding ranges. The ranges are overlain by basaltic aquifers of Tertiary age, which overall are quite transmissive. Both runoff from these ranges and infiltration into the basalts provided ephemeral flow to the streams of the valley. Throughout the valley there are over 5,000 bores extracting alluvial groundwater, plus lesser numbers extracting from underlying sandstone bedrock. Although there are approximately 2500 monitoring bores, the only regularly monitored area is the formally declared management zone in the lower one third. This zone has a calibrated Modflow model (Durick and Bleakly, 2000); a broader valley Modflow model was developed in 2002 (KBR), but did not have extensive extraction data for detailed calibration. Another Modflow model focused on a central area river confluence (Wilson, 2005) with some local production data and pumping test results. A recent subcatchment simulation model incorporates a network of bores with short-period automated hydrographic measurements (Dvoracek and Cox, 2008). The above simulation models were all based on conceptual hydrogeological models of differing scale and detail.

Associations among smoking status, lifestyle and lipoprotein subclasses

BACKGROUND: The relationship between cigarette smoking and cardiovascular disease is well established, yet the underlying mechanisms remain unclear. Although smokers have a more atherogenic lipid profile, this may be mediated by other lifestyle-related factors. Analysis of lipoprotein subclasses by the use of nuclear magnetic resonance spectroscopy (NMR) may improve characterisation of lipoprotein abnormalities. OBJECTIVE: We used NMR spectroscopy to investigate the relationships between smoking status, lifestyle-related risk factors, and lipoproteins in a contemporary cohort. METHODS: A total of 612 participants (360 women) aged 40–69 years at baseline (199021994) enrolled in the Melbourne Collaborative Cohort Study had plasma lipoproteins measured with NMR. Data were analysed separately by sex. RESULTS: After adjusting for lifestyle-related risk factors, including alcohol and dietary intake, physical activity, and weight, mean total low-density lipoprotein (LDL) particle concentration was greater for female smokers than nonsmokers. Both medium- and small-LDL particle concentrations contributed to this difference. Total high-density lipoprotein (HDL) and large-HDL particle concentrations were lower for female smokers than nonsmokers. The proportion with low HDL particle number was greater for female smokers than nonsmokers. For men, there were few smoking-related differences in lipoprotein measures. CONCLUSION: Female smokers have a more atherogenic lipoprotein profile than nonsmokers. This difference is independent of other lifestyle-related risk factors. Lipoprotein profiles did not differ greatly between male smokers and nonsmokers.

Discrimination or Differential Involvement? A Review of the Research Exploring the Impact of Indigenous Status on Sentencing

Existing court data suggest that adult Indigenous offenders are more likely than non-Indigenous defendants to be sentenced to prison but once imprisoned generally receive shorter terms. Using findings from international and Australian multivariate statistical analyses, this paper reviews the three key hypotheses advanced as plausible explanations for these differences: 1) differential involvement, 2) negative discrimination, 3) positive discrimination. Overall, prior research shows strong support for the differential involvement thesis, some support for positive discrimination and little foundation for negative discrimination in the sentencing of Indigenous defendants. Where discrimination is found, we argue that this may be explained by the lack of a more complete set of control variables in researchers’ multivariate models.

Business process management education in academia: Status, challenges, and recommendations

In response to the growing proliferation of Business Process Management (BPM) in industry and the demand this creates for BPM expertise, universities across the globe are at various stages of incorporating knowledge and skills in their teaching offerings. However, there are still only a handful of institutions that offer specialized education in BPM in a systematic and in-depth manner. This article is based on a global educators’ panel discussion held at the 2009 European Conference on Information Systems in Verona, Italy. The article presents the BPM programs of five universities from Australia, Europe, Africa, and North America, describing the BPM content covered, program and course structures, and challenges and lessons learned. The article also provides a comparative content analysis of BPM education programs illustrating a heterogeneous view of BPM. The examples presented demonstrate how different courses and programs can be developed to meet the educational goals of a university department, program, or school. This article contributes insights on how best to continuously sustain and reshape BPM education to ensure it remains dynamic, responsive, and sustainable in light of the evolving and ever-changing marketplace demands for BPM expertise.

Is the association between temperature and mortality modified by age, gender and socio-economic status?

Background: A number of studies have examined the relationship between high ambient temperature and mortality. Recently, concern has arisen about whether this relationship is modified by socio-demographic factors. However, data for this type of study is relatively scarce in subtropical/tropical regions where people are well accustomed to warm temperatures. Objective: To investigate whether the relationship between daily mean temperature and daily all-cause mortality is modified by age, gender and socio-economic status (SES) in Brisbane, Australia. Methods: We obtained daily mean temperature and all-cause mortality data for Brisbane, Australia during 1996–2004. A generalised additive model was fitted to assess the percentage increase in all deaths with every one degree increment above the threshold temperature. Different age, gender and SES groups were included in the model as categorical variables and their modification effects were estimated separately. Results: A total of 53,316 non-external deaths were included during the study period. There was a clear increasing trend in the harmful effect of high temperature on mortality with age. The effect estimate among women was more than 20 times that among men. We did not find an SES effect on the percent increase associated with temperature. Conclusions: The effects of high temperature on all deaths were modified by age and gender but not by SES in Brisbane, Australia.

The association between MC1R genotype and BRAF mutation status in cutaneous melanoma : findings from an Australian population

There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.

Whitefly Transmission and Efficient ssDNA Accumulation of Bean Golden Mosaic Geminivirus Require Functional Coat Protein

Bean golden mosaic geminivirus (BGMV) has a bipartite genome composed of two circular ssDNA components (DNA-A and DNA-B) and is transmitted by the whitefly, Bemisia tabaci. DNA-A encodes the viral replication proteins and the coat protein. To determine the role of BGMV coat protein systemic infection and whitefly transmission, two deletions and a restriction fragment inversion were introduced into the BGMV coat protein gene. All three coat protein mutants produced systemic infections when coinoculated with DNA-B onto Phaseolus vulgaris using electric discharge particle acceleration "particle gun." However, they were not sap transmissible and coat protein was not detected in mutant-infected plants. In addition, none of the mutants were transmitted by whiteflies. With all three mutants, ssDNA accumulation of DNA-A and DNA-B was reduced 25- to 50-fold and 3- to 10-fold, respectively, as compared to that of wild-type DNA. No effect on dsDNA-A accumulation was detected and there was 2- to 5-fold increase in dsDNA-B accumulation. Recombinants between the mutated DNA-A and DNA-B forms were identified when the inoculated coat protein mutant was linearized in the common region.

Trends in impaired driving in Australia in 2010 : a status report

This paper reviews the status of alcohol, drugs and traffic safety in Australia, with particular emphasis on developments in the period 2008-2010. Australian jurisdictions have made impressive improvements in road safety since the early 1970s. Enforcement and public education campaigns that specifically target drink driving have been successful, with resultant long-term reduction in alcohol-related fatalities. There is a high level of community disapproval of drink driving and strong support for countermeasures. Many best-practice countermeasures targeting impaired driving are in place, including general prevention/ deterrence programs such as random breath testing (RBT), random roadside drug testing legal alcohol limits, responsible service of alcohol programs, public education and advertising campaigns and designated driver programs, and offender management programs such as driver licensing penalties and fines, alcohol ignition interlocks and vehicle impoundment for high risk drink drivers, and offender education programs. There continue to be enhancements occurring, particularly in the areas of drug-impaired driving and offender management, but also in addressing the fundamental policy and legislative framework to address impaired driving (e.g., a current national debate about lowering the permissible blood alcohol for all drivers from 0.05 to 0.02 or 0.00 gm/100 ml BAC). However, there are major challenges that may be impacting on programs targeting impaired driving, including the rapid development of a binge drinking culture among young Australians, the extension of trading hours of licensed premises, continued problems with secondary supply of alcohol to minors, and increases in the marketing of alcopops and ready-to-drink spirit-based beverages. This paper addresses the question: Are impaired driving countermeasures in Australia continuing to achieve reductions in road traumas and rates of offending, or are they plateauing? If they are plateauing, is this due to declining effectiveness of countermeasures or the need to ‘hold the line’ against societal influences encouraging impaired driving?

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Physical and functional interaction of the archaeal single-stranded DNA-binding protein SSB with RNA polymerase

Archaeal transcription utilizes a complex multisubunit RNA polymerase and the basal transcription factors TBP and TF(II)B, closely resembling its eukaryal counterpart. We have uncovered a tight physical and functional interaction between RNA polymerase and the single-stranded DNA-binding protein SSB in Sulfolobus solfataricus. SSB stimulates transcription from promoters in vitro under TBP-limiting conditions and supports transcription in the absence of TBP. SSB also rescues transcription from repression by reconstituted chromatin. We demonstrate the potential for promoter melting by SSB, suggesting a plausible basis for the stimulation of transcription. This stimulation requires both the single-stranded DNA-binding domain and the acidic C-terminal tail of the SSB. The tail forms a stable interaction with RNA polymerase. These data reveal an unexpected role for single-stranded DNA-binding proteins in transcription in archaea.