Discrepancies between metabolic activity and DNA content as tool to assess cell proliferation in cancer research

Cell proliferation is a critical and frequently studied feature of molecular biology in cancer research. Therefore, various assays are available using different strategies to measure cell proliferation. Metabolic assays such as AlamarBlue, WST-1, and MTT, which were originally developed to determine cell toxicity, are being used to assess cell numbers. Additionally, proliferative activity can be determined by quantification of DNA content using fluorophores, such as CyQuant and PicoGreen. Referring to data published in high ranking cancer journals, 945 publications applied these assays over the past 14 years to examine the proliferative behaviour of diverse cell types. Within this study, mainly metabolic assays were used to quantify changes in cell growth yet these assays may not accurately reflect cellular proliferation rates due to a miscorrelation of metabolic activity and cell number. Testing this hypothesis, we compared metabolic activity of different cell types, human cancer cells and primary cells, over a time period of 4 days using AlamarBlue and fluorometric assays CyQuant and PicoGreen to determine their DNA content. Our results show certain discrepancies in terms of over-estimation of cell proliferation with respect to the metabolic assay in comparison to DNA binding fluorophores.

Determination of optimal preventive maintenance strategy for serial production lines

A Split System Approach (SSA) based methodology is presented to assist in making optimal Preventive Maintenance decisions for serial production lines. The methodology treats a production line as a complex series system with multiple PM actions over multiple intervals. Both risk related cost and maintenance related cost are factored into the methodology as either deterministic or random variables. This SSA based methodology enables Asset Management (AM) decisions to be optimized considering a variety of factors including failure probability, failure cost, maintenance cost, PM performance, and the type of PM strategy. The application of this new methodology and an evaluation of the effects of these factors on PM decisions are demonstrated using an example. The results of this work show that the performance of a PM strategy can be measured by its Total Expected Cost Index (TECI). The optimal PM interval is dependent on TECI, PM performance and types of PM strategies. These factors are interrelated. Generally it was found that a trade-off between reliability and the number of PM actions needs to be made so that one can minimize Total Expected Cost (TEC) for asset maintenance.

Latitude variation in pancreatic cancer mortality in Australia

Objectives: Ecological studies support the hypothesis that there is an association between vitamin D and pancreatic cancer (PaCa) mortality, but observational studies are somewhat conflicting. We sought to contribute further data to this issue by analyzing the differences in PaCa mortality across the eastern states of Australia and investigating if there is a role of vitamin D-effective ultraviolet radiation (DUVR), which is related to latitude. ---------- Methods: Mortality data from 1968 to 2005 were sourced from the Australian General Record of Incidence and Mortality books. Negative binomial models were fitted to calculate the association between state and PaCa mortality. Clear sky monthly DUVR in each capital city was also modeled. ---------- Results: Mortality from PaCa was 10% higher in southern states than in Queensland, with those in Victoria recording the highest mortality risk (relative risk, 1.13; 95% confidence interval, 1.09-1.17). We found a highly significant association between DUVR and PaCa mortality, with an estimated 1.5% decrease in the risk per 10-kJ/m2 increase in yearly DUVR. ---------- Conclusions: These data show an association between latitude, DUVR, and PaCa mortality. Although this study cannot be used to infer causality, it supports the need for further investigations of a possible role of vitamin D in PaCa etiology.

The skin awareness study : promoting thorough skin self-examination for skin cancer among men 50 years or older

Background: Incidence and mortality from skin cancers including melanoma are highest among men 50 years or older. Thorough skin self-examination may be beneficial to improve skin cancers outcomes.--------- Objectives: To develop and conduct a randomized-controlled trial of a video-based intervention to improve skin self-examination behavior among men 50 years or older.--------- Methods: Pilot work ascertained appropriate targeting of the 12-minute intervention video towards men 50 years or older. Overall, 968 men were recruited and 929 completed baseline telephone assessment. Baseline analysis assessed randomization balance and demographic, skin cancer risk and attitudinal factors associated with conducting a whole-body skin self-examination or receiving a whole-body clinical skin examination by a doctor during the past 12 months.--------- Results: Randomization resulted in well-balanced intervention and control groups. Overall 13% of men reported conducting a thorough skin self-examination using a mirror or the help of another person to check difficult to see areas, while 39% reported having received a whole-body skin examination by a doctor within the past 12 months. Confidence in finding time for and receiving advice or instructions by a doctor to perform a skin self-examination were among the factors associated with thorough skin self-examination at baseline.---------- Conclusions: Men 50 years or older can successfully be recruited to a video-based intervention trial with the aim reduce their burden through skin cancer. Randomization by computer generated randomization list resulted in good balance between control and intervention group and baseline analysis determined factors associated with skin cancer early detection behavior at baseline.

Quality issues for the National Bowel Cancer Screening Program (NBCSP)

Purpose: This two-part research project was undertaken as part of the planning process by Queensland Health (QH), Cancer Screening Services Unit (CSSU), Queensland Bowel Cancer Screening Program (QBCSP), in partnership with the National Bowel Cancer Screening Program (NBCSP), to prepare for the implementation of the NBCSP in public sector colonoscopy services in QLD in late 2006. There was no prior information available on the quality of colonoscopy services in Queensland (QLD) and no prior studies that assessed the quality of colonoscopy training in Australia. Furthermore, the NBCSP was introduced without extra funding for colonoscopy service improvement or provision for increases in colonoscopic capacity resulting from the introduction of the NBCSP. The main purpose of the research was to record baseline data on colonoscopy referral and practice in QLD and current training in colonoscopy Australia-wide. It was undertaken from a quality improvement perspective. Implementation of the NBCSP requires that all aspects of the screening pathway, in particular colonoscopy services for the assessment of positive Faecal Occult Blood Tests (FOBTs), will be effective, efficient, equitable and evidence-based. This study examined two important aspects of the continuous quality improvement framework for the NBCSP as they relate to colonoscopy services: (1) evidence-based practice, and (2) quality of colonoscopy training. The Principal Investigator was employed as Senior Project Officer (Training) in the QBCSP during the conduct of this research project. Recommendations from this research have been used to inform the development and implementation of quality improvement initiatives for provision of colonoscopy in the NBCSP, its QLD counterpart the QBCSP and colonoscopy services in QLD, in general. Methods – Part 1 Chart audit of evidence-based practice: The research was undertaken in two parts from 2005-2007. The first part of this research comprised a retrospective chart audit of 1484 colonoscopy records (some 13% of all colonoscopies conducted in public sector facilities in the year 2005) in three QLD colonoscopy services. Whilst some 70% of colonoscopies are currently conducted in the private sector, only public sector colonoscopy facilities provided colonoscopies under the NBCSP. The aim of this study was to compare colonoscopy referral and practice with explicit criteria derived from the National Health & Medical Research Council (NHMRC) (1999) Clinical Practice Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer, and describe the nature of variance with the guidelines. Symptomatic presentations were the most common indication for colonoscopy (60.9%). These comprised per rectal bleeding (31.0%), change of bowel habit (22.1%), abdominal pain (19.6%), iron deficiency anaemia (16.2%), inflammatory bowel disease (8.9%) and other symptoms (11.4%). Surveillance and follow-up colonoscopies accounted for approximately one-third of the remaining colonoscopy workload across sites. Gastroenterologists (GEs) performed relatively more colonoscopies per annum (59.9%) compared to general surgeons (GS) (24.1%), colorectal surgeons (CRS) (9.4%) and general physicians (GPs) (6.5%). Guideline compliance varied with the designation of the colonoscopist. Compliance was lower for CRS (62.9%) compared to GPs (76.0%), GEs (75.0%), GSs (70.9%, p<0.05). Compliance with guideline recommendations for colonoscopic surveillance for family history of colorectal cancer (23.9%), polyps (37.0%) and a past history of bowel cancer (42.7%), was by comparison significantly lower than for symptomatic presentations (94.4%), (p<0.001). Variation with guideline recommendations occurred more frequently for polyp surveillance (earlier than guidelines recommend, 47.9%) and follow-up for past history of bowel cancer (later than recommended, 61.7%, p<0.001). Bowel cancer cases detected at colonoscopy comprised 3.6% of all audited colonoscopies. Incomplete colonoscopies occurred in 4.3% of audited colonoscopies and were more common among women (76.6%). For all colonoscopies audited, the rate of incomplete colonoscopies for GEs was 1.6% (CI 0.9-2.6), GPs 2.0% (CI 0.6-7.2), GS 7.0% (CI 4.8-10.1) and CRS 16.4% (CI 11.2-23.5). 18.6% (n=55) of patients with a documented family history of bowel cancer had colonoscopy performed against guidelines recommendations (for general (category 1) population risk, for reasons of patient request or family history of polyps, rather than for high risk status for colorectal cancer). In general, family history was inadequately documented and subsequently applied to colonoscopy referral and practice. Methods - Part 2 Surveys of quality of colonoscopy training: The second part of the research consisted of Australia-wide anonymous, self-completed surveys of colonoscopy trainers and their trainees to ascertain their opinions on the current apprenticeship model of colonoscopy in Australia and to identify any training needs. Overall, 127 surveys were received from colonoscopy trainers (estimated response rate 30.2%). Approximately 50% of trainers agreed and 27% disagreed that current numbers of training places were adequate to maintain a skilled colonoscopy workforce in preparation for the NBCSP. Approximately 70% of trainers also supported UK-style colonoscopy training within dedicated accredited training centres using a variety of training approaches including simulation. A collaborative approach with the private sector was seen as beneficial by 65% of trainers. Non-gastroenterologists (non-GEs) were more likely than GEs to be of the opinion that simulators are beneficial for colonoscopy training (χ2-test = 5.55, P = 0.026). Approximately 60% of trainers considered that the current requirements for recognition of training in colonoscopy could be insufficient for trainees to gain competence and 80% of those indicated that ≥ 200 colonoscopies were needed. GEs (73.4%) were more likely than non-GEs (36.2%) to be of the opinion that the Conjoint Committee standard is insufficient to gain competence in colonoscopy (χ2-test = 16.97, P = 0.0001). The majority of trainers did not support training either nurses (73%) or GPs in colonoscopy (71%). Only 81 (estimated response rate 17.9%) surveys were received from GS trainees (72.1%), GE trainees (26.3%) and GP trainees (1.2%). The majority were males (75.9%), with a median age 32 years and who had trained in New South Wales (41.0%) or Victoria (30%). Overall, two-thirds (60.8%) of trainees indicated that they deemed the Conjoint Committee standard sufficient to gain competency in colonoscopy. Between specialties, 75.4% of GS trainees indicated that the Conjoint Committee standard for recognition of colonoscopy was sufficient to gain competence in colonoscopy compared to only 38.5% of GE trainees. Measures of competency assessed and recorded by trainees in logbooks centred mainly on caecal intubation (94.7-100%), complications (78.9-100%) and withdrawal time (51-76.2%). Trainees described limited access to colonoscopy training lists due to the time inefficiency of the apprenticeship model and perceived monopolisation of these by GEs and their trainees. Improvements to the current training model suggested by trainees included: more use of simulation, training tools, a United Kingdom (UK)-style training course, concentration on quality indicators, increased access to training lists, accreditation of trainers and interdisciplinary colonoscopy training. Implications for the NBCSP/QBCSP: The introduction of the NBCSP/QBCSP necessitates higher quality colonoscopy services if it is to achieve its ultimate goal of decreasing the incidence of morbidity and mortality associated with bowel cancer in Australia. This will be achieved under a new paradigm for colonoscopy training and implementation of evidence-based practice across the screening pathway and specifically targeting areas highlighted in this thesis. Recommendations for improvement of NBCSP/QBCSP effectiveness and efficiency include the following: 1. Implementation of NBCSP and QBCSP health promotion activities that target men, in particular, to increase FOBT screening uptake. 2. Improved colonoscopy training for trainees and refresher courses or retraining for existing proceduralists to improve completion rates (especially for female NBCSP/QBCSP participants), and polyp and adenoma detection and removal, including newer techniques to detect flat and depressed lesions. 3. Introduction of colonoscopy training initiatives for trainees that are aligned with NBCSP/QBCSP colonoscopy quality indicators, including measurement of training outcomes using objective quality indicators such as caecal intubation, withdrawal time, and adenoma detection rate. 4. Introduction of standardised, interdisciplinary colonoscopy training to reduce apparent differences between specialties with regard to compliance with guideline recommendations, completion rates, and quality of polypectomy. 5. Improved quality of colonoscopy training by adoption of a UK-style training program with centres of excellence, incorporating newer, more objective assessment methods, use of a variety of training tools such as simulation and rotations of trainees between metropolitan, rural, and public and private sector training facilities. 6. Incorporation of NHMRC guidelines into colonoscopy information systems to improve documentation, provide guideline recommendations at the point of care, use of gastroenterology nurse coordinators to facilitate compliance with guidelines and provision of guideline-based colonoscopy referral letters for GPs. 7. Provision of information and education about the NBCSP/QBCSP, bowel cancer risk factors, including family history and polyp surveillance guidelines, for participants, GPs and proceduralists. 8. Improved referral of NBCSP/QBCSP participants found to have a high-risk family history of bowel cancer to appropriate genetics services.

Performance measurement and continuous improvement : are they linked to manufacturing strategy?

To maintain or achieve competitiveness and profitability, a manufacturing firm or enterprise must respond to a range of challenges, including rapid improvements in technology; declining employment and output; globalisation of markets and environmental requirements. In addition, substantial changes in government policy have had important impacts in many countries, as have the increasing levels of global trade. Manufacturing enterprises need to have a clear understanding of what their customers want and why customers purchase their products rather than purchase from their competitors. They need to fully understand the aims of the business in terms of its customers, market segments, product attributes, geographical markets and performance. Continuous Improvement (CI) methods have become widely adopted and regarded as providing an important component of increased company competitiveness. This article examines the extent to which continuous improvement activities have contributed to the different areas of business performance.

Enhancing the capacity of oncology nurses to provide supportive care for patients with advanced cancer : evaluation of an educational intervention

Aim: This study aimed to enhance the capacity of oncology nurses to provide supportive care for patients with advanced cancer who have dependent children. ---------- Method: This was a pilot study of an educational intervention comprising a study-developed self-directed learning manual, supported by a day-long communication skills training workshop. Evaluation pre- and post-training included measures of stress and burnout, self-reports of confidence and attitudes, responses to clinical vignettes and video-taped interviews with simulated patients.---------- Results: Nurses found the educational intervention highly acceptable, and reported increased confidence in their ability to provide information and support for parents, and to initiate discussion about emotional issues. There were significant improvements in general communication skills and skills specific to this training, as well as reduced use of blocking.---------- Conclusion: Brief communication skills training supplemented with tailored educational resources can enhance confidence skills and knowledge of oncology nurses regarding their supportive care of parents with advanced cancer.

Accommodating the diverse cultural needs of cancer patients and their families in palliative care

Cultural issues have become an increasingly important consideration in healthcare. Such cultural issues, however, are underresearched in Australia, especially in palliative care. This study has sought to address this gap, exploring the social construction of cultural issues in palliative care by oncology nurses. A grounded theory approach was used. Semistructured interviews with 7 Australian oncology nurses provided the data for the study. The core category emerging from the study was that of accommodating cultural needs whereby to meet patients' specific cultural requirements, nurses actively found ways to accommodate the needs of patients and their families. This process often included compromise and negotiation whereby limits were set. In addition, the use of cross-cultural communication strategies emerged from the data as an important feature of cultural care. A series of subcategories were also identified as factors that could influence the process by which nurses would accommodate cultural needs.

Do strategy choices matter for nascent firms? A study on effectuation and causation impacts on new ventures outcomes

Principal Topic : Nascent entrepreneurship has drawn the attention of scholars in the last few years (Davidsson, 2006, Wagner, 2004). However, most studies have asked why firms are created focussing on questions such as what are the characteristics (Delmar and Davidsson, 2000) and motivations (Carter, Gartner, Shaver & Reynolds, 2004) of nascent entrepreneurs, or what are the success factors in venture creation (Davidsson & Honig; 2003; Delmar and Shane, 2004). In contrast, the question of how companies emerge is still in its infancy. On a theoretical side, effectuation, developed by Sarasvathy (2001) offers one view of the strategies that may be at work during the venture creation process. Causation, the theorized inverse to effectuation, may be described as a rational reasoning method to create a company. After a comprehensive market analysis to discover opportunities, the entrepreneur will select the alternative with the higher expected return and implement it through the use of a business plan. In contrast, effectuation suggests that the future entrepreneur will develop her new venture in a more iterative way by selecting possibilities through flexibility and interaction with the market, affordability of loss of resources and time invested, development of pre-commitments and alliances from stakeholders. Another contrasting point is that causation is ''goal driven'' while an effectual approach is ''mean driven'' (Sarasvathy, 2001) One of the predictions of effectuation theory is effectuation is more likely to be used by entrepreneurs early in the venture creation process (Sarasvathy, 2001). However, this temporal aspect and the impact of the effectuation strategy on the venture outcomes has so far not been systematically and empirically tested on large samples. The reason behind this research gap is twofold. Firstly, few studies collect longitudinal data on emerging ventures at an early enough stage of development to avoid severe survivor bias. Second, the studies that collect such data have not included validated measures of effectuation. The research we are conducting attempts to partially fill this gap by combining an empirical investigation on a large sample of nascent and young firms with the effectuation/causation continuum as a basis (Sarasvathy, 2001). The objectives are to understand the strategies used by the firms during the creation process and measure their impacts on the firm outcomes. Methodology/Key Propositions : This study draws its data from the first wave of the CAUSEE project where 28,383 Australian households were randomly contacted by phone using a specific methodology to capture emerging firms (Davidsson, Steffens, Gordon, Reynolds, 2008). This screening led to the identification of 594 nascent ventures (i.e., firms that are not operating yet) and 514 young firms (i.e., firms that have started operating from 2004) that were willing to participate in the study. Comprehensive phone interviews were conducted with these 1108 ventures. In a likewise comprehensive follow-up 12 months later, 80% of the eligible cases completed the interview. The questionnaire contains specific sections designed to distinguish effectual and causal processes, innovation, gestation activities, business idea changes and ventures outcomes. The effectuation questions are based on the components of effectuation strategy as described by Sarasvathy (2001) namely: flexibility, affordable loss and pre-commitment from stakeholders. Results from two rounds of pre-testing informed the design of the instrument included in the main survey. The first two waves of data have will be used to test and compare the use of effectuation in the venture creation process. To increase the robustness of the results, temporal use of effectuation will be tested both directly and indirectly. 1. By comparing the use of effectuation in nascent and young firms from wave 1 to 2, we will be able to find out how effectuation is affected by time over a 12-month duration and if the stage of venture development has an impact on its use. 2. By comparing nascent ventures early in the creation process versus nascent ventures late in the creation process. Early versus late can be determined with the help of time-stamped gestation activity questions included in the survey. This will help us to determine the change on a small time scale during the creation phase of the venture. 3. By comparing nascent firms to young (already operational) firms. 4. By comparing young firms becoming operational in 2006 with those first becoming operational in 2004. Results and Implications : Wave 1 and 2 data have been completed and wave 2 is currently being checked and 'cleaned'. Analysis work will commence in September, 2009. This paper is expected to contribute to the body of knowledge on effectuation by measuring quantitatively its use and impact on nascent and young firms activities at different stages of their development. In addition, this study will also increase the understanding of the venture creation process by comparing over time nascent and young firms from a large sample of randomly selected ventures. We acknowledge the results from this study will be preliminary and will have to be interpreted with caution as the changes identified may be due to several factors and may not only be attributed to the use/not use of effectuation. Meanwhile, we believe that this study is important to the field of entrepreneurship as it provides some much needed insights on the processes used by nascent and young firms during their creation and early operating stages.

How boards strategise : a strategy as practice view

While board involvement in strategy is seen as increasingly important, our understanding of how boards fulfil this role is limited. This article draws on indepth qualitative research with directors and senior managers to develop a Strategy as Practice view on how boards "do" strategy. Two different but complementary strategising practices - Procedural Strategising and Interactive Strategising - are identified and elaborated in terms of their underlying micro-activities. The internal boardroom factors that affect the relative emphasis on these strategies practices - the strategic stance of the board, board power and perceive legitimacy of each practice - are also identified and discussed. These findings are then integrated into a typology of board strategising. A key implication of this paper is that boards need to consciously choose the nature and extent of their involvement in strategy.

National Aboriginal and Torres Strait Islander women's health strategy

The Strategy presented in this report was developed through the Australian Women’s Health Network Talking Circle in 2009-2010. Over 400 Aboriginal and Torres Strait Islander women were involved in the consultations. The Action Areas and Recommendations presented in this Strategy were raised and discussed by the women who contributed to the Talking Circle. This Strategy is not intended to replace any other national or state/territory identified priorities or needs. Instead, this Strategy supplements other work. Aboriginal and Torres Strait Islander women experience extremely poor health outcomes. They have a right to determine for themselves what their health system will look like. This Strategy is part of that process. If Aboriginal and Torres Strait Islander women continue to have their sense of identity marginalised and eroded, they will continue to have the poorest health of any group of women in Australian society.

Interventions for preventing and managing radiation-induced skin reactions in cancer patients (Protocol)

To assess the effects of any interventions which aim to prevent or manage radiation-induced skin reactions in people with cancer.

Effects of starting strategy on 5-min cycling time-trial performance

The importance of pacing for middle-distance performance is well recognized, yet previous research has produced equivocal results. Twenty-six trained male cyclists (O2peak 62.8 ± 5.9 ml · kg-1 · min-1; maximal aerobic power output 340 ± 43 W; mean ± s) performed three cycling time-trials where the total external work (102.7 ± 13.7 kJ) for each trial was identical to the best of two 5-min habituation trials. Markers of aerobic and anaerobic metabolism were assessed in 12 participants. Power output during the first quarter of the time-trials was fixed to control external mechanical work done (25.7 ± 3.4 kJ) and induce fast-, even-, and slow-starting strategies (60, 75, and 90 s, respectively). Finishing times for the fast-start time-trial (4:53 ± 0:11 min:s) were shorter than for the even-start (5:04 ± 0:11 min:s; 95% CI = 5 to 18 s, effect size = 0.65, P < 0.001) and slow-start time-trial (5:09 ± 0:11 min:s; 95% CI = 7 to 24 s, effect size = 1.00, P < 0.001). Mean O2 during the fast-start trials (4.31 ± 0.51 litres · min-1) was 0.18 ± 0.19 litres · min-1 (95% CI = 0.07 to 0.30 litres · min-1, effect size = 0.94, P = 0.003) higher than the even- and 0.18 ± 0.20 litres · min-1 (95% CI = 0.5 to 0.30 litres · min-1, effect size = 0.86, P = 0.007) higher than the slow-start time-trial. Oxygen deficit was greatest during the first quarter of the fast-start trial but was lower than the even- and slow-start trials during the second quarter of the trial. Blood lactate and pH were similar between the three trials. In conclusion, performance during a 5-min cycling time-trial was improved with the adoption of a fast- rather than an even- or slow-starting strategy.

The meaning of cancer for Australian Aboriginal women : changing the focus of cancer nursing

Aim: The purpose of the study was to explore why Aboriginal women participate in cancer screening programs but appear reluctant to following-up results, or accept medical advice about treatment. Methods: Interpretive ethnography, a qualitative methodology, was used to explore Aboriginal women’s perception of cancer, and the cultural context in which meaning was constructed and influenced treatment decision. Data collection, which occurred over two years, involved fieldwork, participant-observation, face-to-face interviews and focus groups, in two rural Aboriginal communities. Forty eight interviews were recorded from a cross section of the communities, including cancer survivors and patients, family members, health care providers and other women from the community. Results: Key findings were that Aboriginal women’s had a fearful and fatalistic attitude toward cancer, doubted the efficacy of treatment and carried an enduring ambivalence toward the authority of whiteman’s medicine. The women faced a dilemma of wanting access to cancer treatment options but feared entering hospital or clinics not attuned to their cultural needs. Conclusion: The findings highlight the need for a culture-centred approach that decentres the authority of conventional services and instead gives prominence to Aboriginal cultural values as a focal point in cancer control. It should be the responsibility of cancer nurses and others to engage with their local Aboriginal communities to build relationships that foster an exchange of learning about cultural differences that make a difference to how cancer control is practiced.