Incidence and Survival for Merkel Cell Carcinoma in Queensland, Australia, 1993-2010

Importance: Merkel cell carcinoma (MCC) is an uncommon but highly invasive form of skin cancer. The mechanisms that cause MCC are yet to be fully determined. Objectives To compare the incidence and survival rates of MCC in Queensland, Australia, known to be a high-risk area, with MCC incidence and survival elsewhere in the world. We also analyzed incidence trends and differences in survival by key demographic and clinical characteristics. Design, Setting, and Participants: Retrospective cohort study of population-based administrative data for MCC collected by the Queensland Cancer Registry and supplemented with detailed histopathologic data. Deidentified records were obtained of all Queensland residents diagnosed as having MCC during the period from 1993 to 2010. A subsample of histopathologic records were reviewed by a senior dermatopathologist to determine the potential for misclassification. A total of 879 eligible cases of MCC were included in the study. Main Outcomes and Measures: Incidence rates were directly age standardized to the 2000 United States Standard Population. Trends were examined using Joinpoint software with results expressed in terms of the annual percentage change. The period method was used to calculate 5-year relative survival, and adjusted hazard ratios were obtained from multivariate Poisson models.Results: There were 340 cases of MCC diagnosed in Queensland between 2006 and 2010, corresponding to an incidence rate of 1.6 per 100 000 population. Men (2.5 per 100 000) had higher incidence than women (0.9 per 100 000), and rates peaked at 20.7 per 100 000 for persons 80 years or older. The overall incidence of MCC increased by an average of 2.6% per year from 1993 onwards. Relative survival was 41% after 5 years, with significantly better survival found for those younger than 70 years at diagnosis (56%-60%), those with tumors on the face or ears (51%), and those with stage I lesions (49%). Conclusions and Relevance: Incidence rates for MCC in Queensland are at least double those of any that have been previously published elsewhere in the world. It is likely that Queensland’s combination of a predominantly white population, outdoor lifestyle, and exposure to sunlight has played a role in this unwanted result. Interventions are required to increase awareness of MCC among clinicians and the public

Personalised electronic messages to improve sun protection in young adults

The incidence of all skin cancers, including melanoma, continues to rise. It is well known that ultraviolet (UV) radiation is the main environmental risk factor for skin cancer, and excessive exposure at a young age increases the risk of developing skin cancer. The aim of this study was to determine the acceptability and feasibility of delivering sun protection messages via electronic media such as short message services (SMS) to people 18-40 years, and explore factors associated with their acceptability. Overall, 80% of participants agreed that they would like to receive some form of sun protection advice; of these, 20% prefer to receive it via SMS and 42% via email. Willingness to receive electronic messages about the UV index was associated with being unsure about whether a suntanned person would look healthy and greater use of sun protection in the past. Careful attention to message framing and timing of message delivery and focus on short-term effects of sun exposure such as sunburn and skin ageing should increase the acceptability of such messages to young people. We conclude that sun protection messages delivered to young adults via electronic media appear feasible and acceptable

Outdoor workers and sun protection strategies: Two case study examples in Queensland, Australia

Introduction: Outdoor workers are at risk of developing skin cancer because they are exposed to high levels of harmful ultraviolet radiation. The Outdoor Workers Sun Protection Project investigated sun protection strategies for high risk outdoor workers in rural and regional Australia. Methods: Fourteen workplaces (recruitment rate 37%) across four industries in rural and regional Queensland, Australia were recruited to the OWSPP. In 2011–2012, data were collected using pre- and post-intervention interviews and discussion groups. This article presents two workplaces as case study examples. Results: The flat organisational structure of workplace 1 supported the implementation of the Sun Safety Action Plan (SSAP), whilst the hierarchical organisational nature of workplace 2 delayed implementation of the SSAP. Neither workplace had an existing sun protection policy but both workplaces adopted one. An effect related to the researchers’ presence was seen in workplace 1 and to a lesser degree in workplace 2. Overt reciprocity was seen between management and workers in workplace 1 but this was not so evident in workplace 2. In both workplaces, the role of the workplace champion was pivotal to SSAP progression. Conclusions: These two case studies highlight a number of contextually bound workplace characteristics related to sun safety. These issues are (1) the structure of workplace, (2) policy, (3) an effect related to the researchers’ presence, (4) the workplace champion and (5) reciprocity. There are several recommendations from this article. Workplace health promotion strategies for sun safety need to be contextualised to individual workplaces to take advantage of the strengths of the workplace and to build capacity

Changes in Outdoor Workers' Sun-Related Attitudes, Beliefs, and Behaviors: A Pre–Post Workplace Intervention

Objective: To evaluate changes in outdoor workers' sun-related attitudes, beliefs, and behaviors in response to a health promotion intervention using a participatory action research process. Methods: Fourteen workplaces across four outdoor industry types worked collaboratively with the project team to develop tailored sun protection action plans. Workers were assessed before and after the 18-month intervention. Results: Outdoor workers reported increases in workplace support for sun protection (P < 0.01) and personal use of sun protection (P < 0.01). More workers reported seeking natural shade (+20%) and wearing more personal protective equipment, including broad-brimmed hats (+25%), long-sleeved collared shirts (+19%), and long trousers (+16%). The proportion of workers reporting sunburn over the past 12 months was lower at postintervention (-14%) (P = 0.03); however, the intensity of reported sunburn increased. Conclusions: This intervention was successful in increasing workers' sun protective attitudes, beliefs, and behaviors

Psychological distress and quality of life in lung cancer: The role of health-related stigma, illness appraisals and social constraints

Objective: Health-related stigma is associated with negative psychological and quality of life outcomes in lung cancer patients. This study describes the impact of stigma on lung cancer patients\u27 psychological distress and quality of life and explores the role of social constraints and illness appraisal as mediators of effect. Methods: A self-administered cross-sectional survey examined psychological distress and quality of life in 151 people (59% response rate) diagnosed with lung cancer from Queensland and New South Wales. Health-related stigma, social constraints and illness appraisals were assessed as predictors of adjustment outcomes. Results: Forty-nine percent of patients reported elevated anxiety; 41% were depressed; and 51% had high global distress. Health-related stigma was significantly related to global psychological distress and quality of life with greater stigma and shame related to poorer outcomes. These effects were mediated by illness appraisals and social constraints. Conclusions: Health-related stigma appears to contribute to poorer adjustment by constraining interpersonal discussions about cancer and heightening feelings of threat. There is a need for the development and evaluation of interventions to ameliorate the negative effects of health-related stigma among lung cancer patients

An Integrated-Photonics Optical-Frequency Synthesizer

Integrated-photonics microchips now enable a range of advanced functionalities for high-coherence applications such as data transmission, highly optimized physical sensors, and harnessing quantum states, but with cost, efficiency, and portability much beyond tabletop experiments. Through high-volume semiconductor processing built around advanced materials there exists an opportunity for integrated devices to impact applications cutting across disciplines of basic science and technology. Here we show how to synthesize the absolute frequency of a lightwave signal, using integrated photonics to implement lasers, system interconnects, and nonlinear frequency comb generation. The laser frequency output of our synthesizer is programmed by a microwave clock across 4 THz near 1550 nm with 1 Hz resolution and traceability to the SI second. This is accomplished with a heterogeneously integrated III/V-Si tunable laser, which is guided by dual dissipative-Kerr-soliton frequency combs fabricated on silicon chips. Through out-of-loop measurements of the phase-coherent, microwave-to-optical link, we verify that the fractional-frequency instability of the integrated photonics synthesizer matches the $7.0*10^{-13}$ reference-clock instability for a 1 second acquisition, and constrain any synthesis error to $7.7*10^{-15}$ while stepping the synthesizer across the telecommunication C band. Any application of an optical frequency source would be enabled by the precision optical synthesis presented here. Building on the ubiquitous capability in the microwave domain, our results demonstrate a first path to synthesis with integrated photonics, leveraging low-cost, low-power, and compact features that will be critical for its widespread use.Comment: 10 pages, 6 figure

Signals for CP-Violation in Scalar Tau Pair Production at Muon Colliders

We discuss signals for CP-violation in $\mu^+ \mu^- \to \tilde \tau_i^- \tilde \tau_j^+$, where $i,j = 1,2$ label the two scalar $\tau$ mass eigenstates. We assume that these reactions can proceed through the production and decay of the heavy neutral Higgs bosons present in supersymmetric models. CP-violation in the Higgs sector can be probed through a rate asymmetry even with unpolarized beams, while the CP-odd phase associated with the $\tilde \tau$ mass matrix can be probed only if the polarization of at least one beam can be varied. These asymmetries might be ${\cal O}(1)$.Comment: 9 pages, LaTeX with equations.sty, 3 PS figures (included

High Cleavage Efficiency of a 2A Peptide Derived from Porcine Teschovirus-1 in Human Cell Lines, Zebrafish and Mice

When expression of more than one gene is required in cells, bicistronic or multicistronic expression vectors have been used. Among various strategies employed to construct bicistronic or multicistronic vectors, an internal ribosomal entry site (IRES) has been widely used. Due to the large size and difference in expression levels between genes before and after IRES, however, a new strategy was required to replace IRES. A self-cleaving 2A peptide could be a good candidate to replace IRES because of its small size and high cleavage efficiency between genes upstream and downstream of the 2A peptide. Despite the advantages of the 2A peptides, its use is not widespread because (i) there are no publicly available cloning vectors harboring a 2A peptide gene and (ii) comprehensive comparison of cleavage efficiency among various 2A peptides reported to date has not been performed in different contexts. Here, we generated four expression plasmids each harboring different 2A peptides derived from the foot-and-mouth disease virus, equine rhinitis A virus, Thosea asigna virus and porcine teschovirus-1, respectively, and evaluated their cleavage efficiency in three commonly used human cell lines, zebrafish embryos and adult mice. Western blotting and confocal microscopic analyses revealed that among the four 2As, the one derived from porcine teschovirus-1 (P2A) has the highest cleavage efficiency in all the contexts examined. We anticipate that the 2A-harboring cloning vectors we generated and the highest efficiency of the P2A peptide we demonstrated would help biomedical researchers easily adopt the 2A technology when bicistronic or multicistronic expression is required

Heat shock protein 70-mediated sensitization of cells to apoptosis by Carboxyl-Terminal Modulator Protein

<p>Abstract</p> <p>Background</p> <p>The serine/threonine protein kinase B (PKB/Akt) is involved in insulin signaling, cellular survival, and transformation. Carboxyl-terminal modulator protein (CTMP) has been identified as a novel PKB binding partner in a yeast two-hybrid screen, and appears to be a negative PKB regulator with tumor suppressor-like properties. In the present study we investigate novel mechanisms by which CTMP plays a role in apoptosis process.</p> <p>Results</p> <p>CTMP is localized to mitochondria. Furthermore, CTMP becomes phosphorylated following the treatment of cells with pervanadate, an insulin-mimetic. Two serine residues (Ser37 and Ser38) were identified as novel <it>in vivo </it>phosphorylation sites of CTMP. Association of CTMP and heat shock protein 70 (Hsp70) inhibits the formation of complexes containing apoptotic protease activating factor 1 and Hsp70. Overexpression of CTMP increased the sensitivity of cells to apoptosis, most likely due to the inhibition of Hsp70 function.</p> <p>Conclusion</p> <p>Our data suggest that phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to Hsp70. In addition to its role in PKB inhibition, CTMP may therefore play a key role in mitochondria-mediated apoptosis by localizing to mitochondria.</p