Research capacity and culture in podiatry : early observations within Queensland Health

Background Research is a major driver of health care improvement and evidence-based practice is becoming the foundation of health care delivery. For health professions to develop within emerging models of health care delivery, it would seem imperative to develop and monitor the research capacity and evidence-based literacy of the health care workforce. This observational paper aims to report the research capacity levels of statewide populations of public-sector podiatrists at two different time points twelve-months apart. Methods The Research Capacity & Culture (RCC) survey was electronically distributed to all Queensland Health (Australia) employed podiatrists in January 2011 (n = 58) and January 2012 (n = 60). The RCC is a validated tool designed to measure indicators of research skill in health professionals. Participants rate skill levels against each individual, team and organisation statement on a 10-point scale (one = lowest, ten = highest). Chi-squared and Mann Whitney U tests were used to determine any differences between the results of the two survey samples. A minimum significance of p < 0.05 was used throughout. Results Thirty-seven (64%) podiatrists responded to the 2011 survey and 33 (55%) the 2012 survey. The 2011 survey respondents reported low skill levels (Median < 4) on most aspects of individual research aspects, except for their ability to locate and critically review research literature (Median > 6). Whereas, most reported their organisation’s skills to perform and support research at much higher levels (Median > 6). The 2012 survey respondents reported significantly higher skill ratings compared to the 2011 survey in individuals’ ability to secure research funding, submit ethics applications, and provide research advice, plus, in their organisation’s skills to support, fund, monitor, mentor and engage universities to partner their research (p < 0.05). Conclusions This study appears to report the research capacity levels of the largest populations of podiatrists published. The 2011 survey findings indicate podiatrists have similarly low research capacity skill levels to those reported in the allied health literature. The 2012 survey, compared to the 2011 survey, suggests podiatrists perceived higher skills and support to initiate research in 2012. This improvement coincided with the implementation of research capacity building strategies.

Evaluation of the alkaline comet assay and urinary 3-methyladenine excretion for monitoring DNA damage in melanoma patients treated with dacarbazine and tamoxifen

Purpose: To develop, using dacarbazine as a model, reliable techniques for measuring DNA damage and repair as pharmacodynamic endpoints for patients receiving chemotherapy. Methods: A group of 39 patients with malignant melanoma were treated with dacarbazine 1 g/m2 i.v. every 21 days. Tamoxifen 20 mg daily was commenced 24 h after the first infusion and continued until 3 weeks after the last cycle of chemotherapy. DNA strand breaks formed during dacarbazine-induced DNA damage and repair were measured in individual cells by the alkaline comet assay. DNA methyl adducts were quantified by measuring urinary 3-methyladenine (3-MeA) excretion using immunoaffinity ELISA. Venous blood was taken on cycles 1 and 2 for separation of peripheral blood lymphocytes (PBLs) for measurement of DNA strand breaks. Results: Wide interpatient variation in PBL DNA strand breaks occurred following chemotherapy, with a peak at 4 h (median 26.6 h, interquartile range 14.75- 40.5 h) and incomplete repair by 24 h. Similarly, there was a range of 3-MeA excretion with peak levels 4-10 h after chemotherapy (median 33 nmol/h, interquartile range 20.448.65 nmol/h). Peak 3-MeA excretion was positively correlated with DNA strand breaks at 4 h (Spearman's correlation coefficient, r = 0.39, P = 0.036) and 24 h (r = 0.46, P = 0.01). Drug-induced emesis correlated with PBL DNA strand breaks (Mann Whitney U-test, P = 0.03) but not with peak 3-MeA excretion. Conclusions: DNA damage and repair following cytotoxic chemotherapy can be measured in vivo by the alkaline comet assay and by urinary 3-MeA excretion in patients receiving chemotherapy.

Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

A preliminary study into the environmental and economic consequences of a sugar factory depithing operation

Bagasse stockpile operations have the potential to lead to adverse environmental and social impacts. Dust releases can cause occupational health and safety concerns for factory workers and dust emissions impact on the surrounding community. Preliminary modelling showed that bagasse depithing would likely reduce the environmental risks, particularly dust emissions, associated with large-scale bagasse stockpiling operations. Dust emission properties were measured and used for dispersion modelling with favourable outcomes. Modelling showed a 70% reduction in peak ground level concentrations of PM10 dust (particles with an aerodynamic diameter less than 10 μm) from operations on depithed bagasse stockpiles compared to similar operations on stockpiles of whole bagasse. However, the costs of a depithing operation at a sugar factory were estimated to be approximately $2.1 million in capital expenditure to process 100 000 t/y of bagasse and operating costs were 200 000 p.a. The total capital cost for a 10 000 t/y operation was approximately $1.6 million. The cost of depithing based on a discounted cash flow analysis was $5.50 per tonne of bagasse for the 100 000 t/y scenario. This may make depithing prohibitively expensive in many situations if installed exclusively as a dust control measure.

"The Stratified Record upon Which We Set Our Feet" : The Spatial Turn and the Multilayering of History, Geography, and Geology

In Thomas Mann’s tetralogy of the 1930s and 1940s, Joseph and His Brothers, the narrator declares history is not only “that which has happened and that which goes on happening in time,” but it is also “the stratified record upon which we set our feet, the ground beneath us.” By opening up history to its spatial, geographical, and geological dimensions Mann both predicts and encapsulates the twentieth-century’s “spatial turn,” a critical shift that divested geography of its largely passive role as history’s “stage” and brought to the fore intersections between the humanities and the earth sciences. In this paper, I draw out the relationships between history, narrative, geography, and geology revealed by this spatial turn and the questions these pose for thinking about the disciplinary relationship between geography and the humanities. As Mann’s statement exemplifies, the spatial turn itself has often been captured most strikingly in fiction, and I would argue nowhere more so than in Graham Swift’s Waterland (1983) and Anne Michaels’s Fugitive Pieces (1996), both of which present space, place, and landscape as having a palpable influence on history and memory. The geographical/geological line that runs through both Waterland and Fugitive Pieces continues through Tim Robinson’s non-fictional, two-volume “topographical” history Stones of Aran. Robinson’s Stones of Aran—which is not history, not geography, and not literature, and yet is all three—constructs an imaginative geography that renders inseparable geography, geology, history, memory, and the act of writing.

A natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer : a phase III double-blind randomised controlled trial

Purpose To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation induced skin reactions (RISR). Methods and Materials A total of 174 patients were randomised and participated in the study. Patients either received Cream 1 (the natural oil-based emulsion containing allantoin) or Cream 2 (aqueous cream). Skin toxicity, pain, itching and skin-related quality of life scores were collected for up to four weeks after radiation treatment. Results Patients who received Cream 1 had a significantly lower average level of Common Toxicity Criteria at week 3 (p<0.05), but had statistically higher average levels of skin toxicity at weeks 7, 8 and 9 (all p<0.001). Similar results were observed when skin toxicity was analysed by grades. With regards to pain, patients in the Cream 2 group had a significantly higher average level of worst pain (p<0.05) and itching (p=0.046) compared to the Cream 1 group at week 3, however these differences were not observed at other weeks. In addition, there was a strong trend for Cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison to Cream 1 (p=0.056). Overall, more participants in the Cream 1 group were required to use another topical treatment at weeks 8 (p=0.049) and 9 (p=0.01). Conclusion The natural oil-based emulsion containing allantoin appears to have similar effects for managing skin toxicity compared to aqueous cream up to week 5, however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream appears to be a more preferred option.

Improving combustion stability in sugar factory boilers

Reliable operation of a sugar factory boiler station is essential for efficient and timely processing of the cane supply. Sugar factory boilers have to contend with changes in fuel quality caused by variations in performance of the extraction station, different cane varieties and associated agronomic factors along with fluctuations in factory steam demand. These variations can affect the stability of combustion in boiler furnaces leading to reductions in boiler steam output and large furnace pressure fluctuations that can cause serious damage. This paper investigates the causes of unstable combustion, discusses aspects of boiler design that make a boiler more susceptible to unstable combustion and uses modelling to evaluate different options for improving combustion stability.

Management of a high grade pan stage schedule to reduce the steam consumption

MOST PAN stages in Australian factories use only five or six batch pans for the high grade massecuite production and operate these in a fairly rigid repeating production schedule. It is common that some of the pans are of large dropping capacity e.g. 150 to 240 t. Because of the relatively small number and large sizes of the pans, steam consumption varies widely through the schedule, often by ±30% about the mean value. Large fluctuations in steam consumption have implications for the steam generation/condensate management of the factory and the evaporators when bleed vapour is used. One of the objectives of a project to develop a supervisory control system for a pan stage is to (a) reduce the average steam consumption and (b) reduce the variation in the steam consumption. The operation of each of the high grade pans within the schedule at Macknade Mill was analysed to determine the idle (or buffer) time, time allocations for essential but unproductive operations (e.g. pan turn round, charging, slow ramping up of steam rates on pan start etc.), and productive time i.e. the time during boil-on of liquor and molasses feed. Empirical models were developed for each high grade pan on the stage to define the interdependence of the production rate and the evaporation rate for the different phases of each pan’s cycle. The data were analysed in a spreadsheet model to try to reduce and smooth the total steam consumption. This paper reports on the methodology developed in the model and the results of the investigations for the pan stage at Macknade Mill. It was found that the operation of the schedule severely restricted the ability to reduce the average steam consumption and smooth the steam flows. While longer cycle times provide increased flexibility the steam consumption profile was changed only slightly. The ability to cut massecuite on the run among pans, or the use of a high grade seed vessel, would assist in reducing the average steam consumption and the magnitude of the variations in steam flow.

Improving boiler performance with modified boiler control systems

For timely processing of the crop, sugar factories need boiler stations that can reliably produce steam when fired with fuel of variable quality. The control systems installed on most sugar factory boilers have changed little in the last thirty years and in some cases the default control system response to changes in fuel and/or fuel quality is not correct and operator intervention is required to prevent factory stoppages or reductions in crushing rate caused by poor combustion. Some factories have recently modified their boiler control systems for improved combustion performance and reduced maintenance costs. This paper describes testing carried out to evaluate some of these control system modifications and identifies boiler control system changes that can be applied more widely in the sugar industry.

Can larger cemented femoral components reduce periprosthetic fractures?

Introduction The risk for late periprosthetic fractures is higher in patients treated for a neck of femur fracture compared to those treated for osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated if a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite sawbone model. Method A biomechanical composite sawbone model was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented stem were implanted by an experienced surgeon, in 7 sawbones each and loaded at 40 deg/s internal rotation until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874). Data are non-parametric and tested with Mann-Whitney U-test. Results The mean torque load to fracture was 154.1 NM (SD 4.4) for the 44-1 stem and 229 NM (SD10.9) for the 44-4 stem (p = 0.01). The mean fracture energy was 9.6 J (SD1.2) for the 44-1 stem and 17.2 J (SD2.0) for the 44-4 stem (p = 0.14). Conclusion the use of a large body polished tapered cemented stem for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hypermethylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P, 0.05 and Mann-Whitney test P, 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 (P, 0.01) and 0.63 (P, 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC. © the authors.