Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial

INTRODUCTION In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts. © 2013 by the International Association for the Study of Lung Cancer.

An ICT Implementation Strategy for Primary Schools in Fiji

Information and Communication Technology (ICT) has been embraced with hope and optimism in both developing and developed countries. While in the developed countries most citizens have access to one or many of the devices which utilize this technology (e.g. desktop, laptop, tablet, mobile phone), in developing countries this “luxury” can only be afforded by a privileged few. The use of these technologies in primary schools in developing countries is low. This is due to the fact that there are other bigger issues that some of these countries have to grapple with such as meeting the basic health and education needs of its citizens. Quality primary education and global development partnerships are two of the eight Millennium Development Goals of the United Nations (UNDP, 2012). Many Governments, NGO’s, service organizations, and individuals in developing countries are always looking at ways in which the disparity (not just in terms of ICT) can be narrowed. There has to be a greater collaboration between stakeholders in developing and developed countries (Mutonyi & Norton, 2007). How do stakeholders from developed countries engage with partners in developing countries to deliver meaningful and relevant outcomes for primary school students using ICT? As a first step getting the key stakeholders on side is critical. In the Fijian context, schools are managed and run by committees who are members of the community. Therefore, getting the committee on side together with the head-teachers and teachers is critical. Conversations about teaching and learning with technology can then follow with greater ease. The sustainability of any innovative approaches is also an essential element of this equation. Through this lens, this chapter investigates how ICT can be implemented in primary schools in Fiji. It proposes a three-layered approach which focuses on: (1) the community, school leadership, and teachers; (2) content, pedagogy, and technology, and (3) sustainability.

Expanding Emergency Department capacity : a multisite study

Objectives: To i) identify predictors of admission, and ii) describe outcomes for patients who arrived via ambulance to three Australian public Emergency Departments (EDs), before and after the opening of 41 additional ED beds within the area. Methods: A retrospective, comparative, cohort study using deterministically linked health data collected between 3 September 2006 and 2 September 2008. Data included ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay and in-hospital mortality. Logistic regression analysis was undertaken to identify predictors of hospital admission. Results: One third of all 286,037 ED presentations were via ambulance (n= 79,196) and 40.3% required admission. After increasing emergency capacity, the only outcome measure to improve was in-hospital mortality. Ambulance offload delay, time to see doctor, ED length of stay (ED LOS), admission requirement, access block, hospital length of stay did not improve. Strong predictors of admission before and after increased capacity included: age over 65 years, Australian Triage Scale (ATS) category 1-3, diagnoses of circulatory or respiratory conditions and ED LOS > 4 hours. With additional capacity the odds ratios for these predictors increased for age >65 and ED LOS > 4 hours and decreased for triage category and ED diagnoses. Conclusions: Expanding ED capacity from 81 to 122 beds within a health service area impacted favourably on mortality outcomes but not on time-related service outcomes such as ambulance offload time, time to see doctor and ED LOS. To improve all service outcomes, when altering (increasing/decreasing) ED bed numbers, the whole healthcare system needs to be considered.

Taxonomy, ecology, and control of hypsipyla shoot borers of meliaceae

Hypsipyla grandella and Hypsipyla robusta are serious pests of species of the subfamily Swietenioideae of the family Meliaceae in virtually every moist tropical region of the world. An international workshop reviewed the ecology and control of Hypsipyla shoot borers of Meliaceae, identified promising control methods, and set priorities for future research. The conclusions of the workshop are presented with specific recommendations for research in aspects of the taxonomy, biology, and ecology of Hypsipyla, and pest management options that use host plant resistance and chemical, biological, and silvicultural control

Intravascular device administration sets: Replacement after standard versus prolonged use in hospitalised patients--a study protocol for a randomised controlled trial (The RSVP Trial)

Introduction Vascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload. Methods and analysis This is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.

Authentically ambiguous, credibly anonymous: Perceptually reframing the personal narrative towards effective persuasion in aggressive human rights contexts

Testing the strategies of discourse and materiality, this practice-based and practice-led research experiments with how anonymous storytelling by vulnerable communities, like that of the sexual minorities and their allies in Malaysia, can better speak to their human rights issues without further subjecting them to personal attacks and targetted persecution. The research identifies the critical role of the voice in lending authenticity and credibility to first person narratives; and contextual credibility as a form of credibility which personal stories naturally aspire to achieve with audiences. Adopting a discursive view of persuasion and recognising too that the power of persuasion may in effect lie with those who receive these stories rather than with those who tell them, the insights and knowledge gained from the research informed the development of the field output, Persuasive Storytelling by Vulnerable Communities in Aggressive Contexts: A Human Rights Communication Framework.

Aging-in-place: Perspectives from the construction industry

Older adults report a desire to remain within the preferred environment for as long as possible. This desire is referred to as aging-in-place. Aging-in-place integrates housing and care options. Factors affecting the ability to remain within the preferred environment include current home designs, access to housing choices, social support networks, and community services, to name a few. Research supports physical and psychosocial benefits of aging-in-place for the individual. Home modifications have the potential to influence the quality of life in a number of positive directions that range from personal mobility to community engagement. Modifications range from minor to significant. Financial resources, contractor interest and expertise, consumer awareness and consumer opportunity affect the degree of change. Increasingly, construction professionals express an interest in learning more about aging-in place. Queries ranged from obtaining a greater understanding of the meaning of the concept, impact of demographic change on housing stock, and increased awareness of universal design features. This paper presents findings from a survey administered to current members of the Canadian Home Builders’ Association – Calgary Regional Office. Within this presentation, we report findings on members understanding of demographic change and the effect of this change on the current and future housing stock. We discuss perceived barriers and benefits of the development of business models to support aging-in-place. Finally, we conclude with discussion of educational support to enhance the understanding of aging-in-place.