Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

Cyclooxygenase-2 (COX-2), the prostaglandin (PG)-synthesizing enzyme overexpressed in colorectal cancer (CRC), has pleiotropic, cancer-promoting effects. COX-2 inhibitors (CIBs) interfere with many cancer-associated processes and show promising antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the WNT pathway, the key driver of colonic carcinogenesis. Our data indicates a substantial cell line-specificity of APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the WNT pathway by APHS suggests one potential common mechanism behind the antineoplastic effects of COX-2 inhibition

A novel skin cancer prevention strategy: Preservice teachers\u27 perceptions of a sun safety intervention and experiences in schools

Issue addressed: Teachers play a vital role in developing children\u27s sun protection routines however upskilling preservice teachers (PSTs) while at university has not yet been trialled as a targeted skin cancer prevention strategy. Hence, this study investigated PSTs perceptions and experiences of sun safety following a brief pilot intervention and placement in primary schools in Western Australia. Methods: This study used a triangulation mixed methods design. Participants (n = 161) completed a post intervention survey which was analysed quantitatively. A random sub-sample was invited to participate in focus groups (three groups, n = 21) and one-on-one interviews (n = 4). This data was transcribed and uploaded in NVIVO software for thematic analysis. Results: Participants felt the intervention increased their awareness of the dangers of overexposure to ultraviolet radiation (UVR) with many feeling more knowledgeable, skilled and confident to teach sun safety in school settings. Most reported clear sun safety messages in their placement schools. However, only 34.4 % reported they had been briefed on the school\u27s sun safety procedures. There was consensus among PSTs that sun protection in primary schools needs to be improved to maximise the protection of children from harmful UVR overexposure. Participants supported a need for consistent sun protection messaging across primary schools with greater emphasis on education rather than compliance management to sun protection. Conclusion: Enhancing existing teacher education programs to include more rigorous curriculum content and pedagogical approaches to sun protection education is a novel skin cancer prevention strategy and could feasibly support PSTs self-efficacy to effectively deliver sun safety curriculum in Australian schools

Estimating fatality rates in occupational light vehicle users using vehicle registration and crash data

Objective: To estimate occupational light vehicle (OLV) fatality numbers using vehicle registration and crash data and compare these with previous estimates based on workers\u27 compensation data. Method: New South Wales (NSW) Roads and Traffic Authority (RTA) vehicle registration and crash data were obtained for 2004. NSW is the only Australian jurisdiction with mandatory work-use registration, which was used as a proxy for work-relatedness. OLV fatality rates based on registration data as the denominator were calculated and comparisons made with published 2003/04 fatalities based on workers\u27 compensation data. Results: Thirty-four NSW RTA OLV-user fatalities were identified, a rate of 4.5 deaths per 100,000 organisationally registered OLV, whereas the Australian Safety and Compensation Council (ASCC), reported 28 OLV deaths Australia-wide. Conclusions: More OLV user fatalities were identified from vehicle registration-based data than those based on workers\u27 compensation estimates and the data are likely to provide an improved estimate of fatalities specific to OLV use. Implications: OLV-use is an important cause of traumatic fatalities that would be better identified through the use of vehicle-registration data, which provides a stronger evidence base from which to develop policy responses

The Role of Effective Communication to Enhance Participation in Screening Mammography: A New Zealand Case

Changes in the organisation of health care have dominated policy initiatives over the past two decades in many countries. An increasing reliance on public health initiatives to prevent or detect disease early has resulted in an increase in programs that screen for cancer in the community. In turn, this accentuates the need to persuasively communicate the value of such initiatives to encourage continued participation. Merely placing screening programs into a community setting is not sufficient to ensure that adequate numbers will voluntarily participate regularly to achieve anticipated cost and mortality savings in the population. In this research the influence of managing communication in a public screening mammography program was investigated. The results revealed that significant opportunities were overlooked for reassurance and information during the physical mammography process. In turn, this highlights the influence of constraints imposed by the structure of the screening program and the resources allocated to the process. This research suggests that it is important to address multiple influences, including ethnic differences, when asking questions about the effectiveness of public health policy, particularly when considering the choices women make about ongoing participation in breast screening programs

Determinants of non attendance to mammography program in a region with high voluntary health insurance coverage

<p>Abstract</p> <p>Background</p> <p>High participation rates are needed to ensure that breast cancer screening programs effectively reduce mortality. We identified the determinants of non-participation in a public breast cancer screening program.</p> <p>Methods</p> <p>In this case-control study, 274 women aged 50 to 64 years included in a population-based mammography screening program were personally interviewed. Socio-demographic characteristics, health beliefs, health service utilization, insurance coverage, prior mammography and other preventive activities were examined.</p> <p>Results</p> <p>Of the 192 cases and 194 controls contacted, 101 and 173, respectively, were subsequently interviewed. Factors related to non-participation in the breast cancer screening program included higher education (odds ratio [OR] = 5.28; 95% confidence interval [CI95%] = 1.57–17.68), annual dental checks-ups (OR = 1.81; CI95%1.08–3.03), prior mammography at a private health center (OR = 7.27; CI95% 3.97–13.32), gynecologist recommendation of mammography (OR = 2.2; CI95%1.3–3.8), number of visits to a gynecologist (median visits by cases = 1.2, versus controls = 0.92, P = 0.001), and supplemental private insurance (OR = 5.62; CI95% = 3.28–9.6). Among women who had not received a prior mammogram or who had done so at a public center, perceived barriers were the main factors related to non-participation. Among women who had previously received mammograms at a private center, supplemental private health insurance also influenced non-participation. Benign breast symptoms increased the likelihood of participation.</p> <p>Conclusion</p> <p>Our data indicate that factors related to the type of insurance coverage (such as prior mammography at a private health center and supplemental private insurance) influenced non-participation in the screening program.</p

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Sun protection for adolescents at school in Aotearoa/New Zealand

Skin cancer is a substantial public health issue in New Zealand (NZ) with exposure to solar ultraviolet radiation (UVR) being the major modifiable risk. Excessive UVR during adolescence can have a lasting effect on long-term cancer risk. Additionally, risky behaviours can continue to adulthood. The aspirational-shared aim of the series of studies included in this thesis is to identify and assess processes and actions to help to reduce excessive exposure of UVR during adolescence for young people, thereby potentially contributing to reducing the burden of skin cancer. There were four studies undertaken as part of this PhD, chosen specifically to address knowledge gaps with respect to this cohort in NZ and internationally. The first study was a systematic review using Effective Public Health Practice Project guidelines to review the quality of interventions targeting adolescents and delivered in secondary schools. In total 13 interventions were identified and received quality ratings of ‘strong’ (n=0), ‘moderate’ (5) or weak (8). Most interventions were health-based, emphasising the association between UVR exposure and skin cancer. These have limited success in changing behaviour. Two promising interventions were identified as potentially relevant. Both moved beyond presenting didactic education in the classroom. The first was an appearance-based intervention using facial ageing technology. The second was an environmental intervention with the provision of a real time ultraviolet index (UVI) display meter in the playground. Subsequently, the second and third studies assessed the feasibility and/or piloting of two separate interventions based on those identified in the review. The first was a classroom-based appearance intervention using ultraviolet filtering photographic technology, and the second a UVI display meter in a school sports setting. The classroom-based intervention was well accepted by students, however, it was resource intensive and so in its current format would not be practical for a population-based intervention. Unfortunately, ethical issues surrounding research with adolescents impeded the second study. In combination with the potential expense of repeated calibration of the UVI display meter, there was insufficient support to pursue a full Randomised Controlled Trial (RCT) in the current format. As National Sporting Organisations (NSO) are the governing organisations for many school sports, the fourth study was an audit, using both desk top review and semi-structured interviews, of NSO sun protection policies. Only two NSOs in NZ have a sun protection policy. Schools are the obvious choice for addressing sun protection in adolescents. Furthermore, the school setting for this thesis is wider than the ‘in school’ environment, specifically with respect to participating in schools sports. There is no ‘one size fits all’ solution to sun protection for adolescents. It is not always feasible to provide a sun protective environment, so often there is no choice but for young people to engage in personal sun protection practices. Healthy policies and environments that either mandate or encourage young people to use appropriate sun protection are essential. Even this will not be entirely effective, and young people themselves need to be convinced that sun protection is important and necessary for them to engage in

Sun protection for adolescents at school in Aotearoa/New Zealand

Skin cancer is a substantial public health issue in New Zealand (NZ) with exposure to solar ultraviolet radiation (UVR) being the major modifiable risk. Excessive UVR during adolescence can have a lasting effect on long-term cancer risk. Additionally, risky behaviours can continue to adulthood. The aspirational-shared aim of the series of studies included in this thesis is to identify and assess processes and actions to help to reduce excessive exposure of UVR during adolescence for young people, thereby potentially contributing to reducing the burden of skin cancer. There were four studies undertaken as part of this PhD, chosen specifically to address knowledge gaps with respect to this cohort in NZ and internationally. The first study was a systematic review using Effective Public Health Practice Project guidelines to review the quality of interventions targeting adolescents and delivered in secondary schools. In total 13 interventions were identified and received quality ratings of ‘strong’ (n=0), ‘moderate’ (5) or weak (8). Most interventions were health-based, emphasising the association between UVR exposure and skin cancer. These have limited success in changing behaviour. Two promising interventions were identified as potentially relevant. Both moved beyond presenting didactic education in the classroom. The first was an appearance-based intervention using facial ageing technology. The second was an environmental intervention with the provision of a real time ultraviolet index (UVI) display meter in the playground. Subsequently, the second and third studies assessed the feasibility and/or piloting of two separate interventions based on those identified in the review. The first was a classroom-based appearance intervention using ultraviolet filtering photographic technology, and the second a UVI display meter in a school sports setting. The classroom-based intervention was well accepted by students, however, it was resource intensive and so in its current format would not be practical for a population-based intervention. Unfortunately, ethical issues surrounding research with adolescents impeded the second study. In combination with the potential expense of repeated calibration of the UVI display meter, there was insufficient support to pursue a full Randomised Controlled Trial (RCT) in the current format. As National Sporting Organisations (NSO) are the governing organisations for many school sports, the fourth study was an audit, using both desk top review and semi-structured interviews, of NSO sun protection policies. Only two NSOs in NZ have a sun protection policy. Schools are the obvious choice for addressing sun protection in adolescents. Furthermore, the school setting for this thesis is wider than the ‘in school’ environment, specifically with respect to participating in schools sports. There is no ‘one size fits all’ solution to sun protection for adolescents. It is not always feasible to provide a sun protective environment, so often there is no choice but for young people to engage in personal sun protection practices. Healthy policies and environments that either mandate or encourage young people to use appropriate sun protection are essential. Even this will not be entirely effective, and young people themselves need to be convinced that sun protection is important and necessary for them to engage in