Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK ) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.

Innovation for Equity in Rural Education : Proceedings of the International Symposium for Innovation in Rural Education

PREFACE The concept of an international symposium on rural education arose from a meeting between members of the SiMERR National Centre, Australia and the NURI Teacher Education Innovation Centre (NURI-TEIC) at Kongju National University, Korea in 2007. Despite the very different national contexts, the teams were struck by the similarities of the challenges facing rural schools in the two countries, and curious about the degree to which these challenges were shared by other countries. At a subsequent meeting in Australia in December 2007, the two centre Directors - Professor John Pegg (SiMERR) and Professor Youn-Kee Im (NURI-TEIC) - agreed on a framework for the first International Symposium for Innovation in Rural Education (ISFIRE). This volume consists of the keynotes and refereed papers presented at ISFIRE 2009. The papers provide insights into rural education in Australia, Bhutan, Canada, Korea, Norway, South Africa and the United States along the following themes: 1. Promoting rural policy initiatives; 2. Nurturing the rural teacher experience; 3. Enhancing rural student experience and growth; 4. Optimising the curriculum; 5. Improving resources in rural schools; and 6. Addressing special issues in rural education. The authors and titles of a further 23 presentations based on refereed abstracts only are listed at the end of this volume. The abstracts for these presentations can be found in the symposium Program. The academics and practitioners who came together for this symposium are passionate about rural education and have dedicated their time and capacities to working for the benefit of rural teachers, students and communities. The papers in this volume offer direction not only for Australia and South Korea, who jointly hosted this symposium, but for all countries in which rural education is contested ground. The keynotes in particular contribute rich perspectives on rural education trends, policies and practices. We hope that this volume generates a greater appreciation of the advantages of rural education and the many innovative approaches being implemented to meet its challenges.

Teachers' motivations for working in rural schools

This paper reports on the analysis of qualitative and quantitative data concerning Australian teachers’ motivations for taking up, remaining in, or leaving teaching positions in rural and regional schools. The data were collected from teachers (n = 2940) as part of the SiMERR National Survey, though the results of the qualitative data analysis were not published with the survey report in 2006. The teachers’ comments provide additional insight into their career decisions, complementing the quantitative findings. Content and frequency analyses of the teachers’ comments reveal individual and collective priorities which together with the statistical evidence can be used to inform policies aimed at addressing the staffing needs of rural schools.

Starting out in STEM : a study of young men and women in first year science, technology, engineering and mathematics courses

In late 2011, first year university students in science, technology, engineering and mathematics (STEM) courses across Australia were invited to participate in the international Interests and Recruitment in Science (IRIS) study. IRIS investigates the influences on young people's decisions to choose university STEM courses and their subsequent experiences of these courses. The study also has a particular focus on the motivations and experiences of young women in courses such as physics, IT and engineering given the low rates of female participation in these fields. Around 3500 students from 30 Australian universities contributed their views on the relative importance of various school and non-school influences on their decisions, as well as insights into their experiences of university STEM courses so far. It is hoped that their contributions will help improve recruitment, retention and gender equity in STEM higher education and careers.

Choosing science : understanding the declines in senior high school science enrolments

'Choosing Science' reports on the most thorough study yet undertaken in Australia to investigate Year 10 students' decisions about whether to take science subjects. The study was well supported by ASTA members, with around 590 teachers and 3800 students participating. It examined teachers' views on the persistent declines in science enrolments, and students' perceptions of school science and aspirations towards further study and careers. The report discusses students' attitudes to science, their enrolment deliberations, sources of advice and recommendations for change. The report identifies the most likely and unlikely contributors to enrolment declines, and makes 10 recommendations.

An interpretative structural modeling based network reconfiguration strategy for power systems

The network reconfiguration is an important stage of restoring a power system after a complete blackout or a local outage. Reasonable planning of the network reconfiguration procedure is essential for rapidly restoring the power system concerned. An approach for evaluating the importance of a line is first proposed based on the line contraction concept. Then, the interpretative structural modeling (ISM) is employed to analyze the relationship among the factors having impacts on the network reconfiguration. The security and speediness of restoring generating units are considered with priority, and a method is next proposed to select the generating unit to be restored by maximizing the restoration benefit with both the generation capacity of the restored generating unit and the importance of the line in the restoration path considered. Both the start-up sequence of generating units and the related restoration paths are optimized together in the proposed method, and in this way the shortcomings of separately solving these two issues in the existing methods are avoided. Finally, the New England 10-unit 39-bus power system and the Guangdong power system in South China are employed to demonstrate the basic features of the proposed method.

Youth off the Streets "Our Place, Walgett Youth and Young Families Project" Project Evaluation.

The Project: • YOTS is a major youth specific agency established in 1991. It is a non-denominational, non-discriminatory and not-for-profit organisation, providing a wide range of services and offering a full continuum of care. It seeks to build on the strengths and positive aspects of marginalised young people and communities. • The 'Our Place, Walgett Youth and Young Families Project' further develops an existing YOTS capacity to provide services to Aboriginal young people. • The project adopted an action-research and community development model in which YOTS worked in partnership with the Youth Sub-committee of the Walgett Interagency. • Specific goals/objectives of the program were to: Coordinate youth and young family activities in partnership with local services and the community to build self-esteem, pride, resilience, motivation and skills; Contribute to the prevention and reduction of homelessness, unstable and unsafe housing and disruptive mobility (Walgett/Redfern) in youth and young families; Increase and improve collaborative engagement between youth and family focused services; and, research, adapt and implement Australian and international best-practice homelessness prevention/reduction initiatives to contribute to new models of practice relevant to rural and regional areas. • The project centred around an out-reach model that focused on providing a safe space with relevant structured activities coordinated by YOTS youth and family workers. Through community and service provider consultation, it was proposed that local services could coordinate strategies and activities and run them, where possible, from the centre, providing ease of access in a safe and supportive context. • Specific activities included: Implementing regular meetings with the stakeholders and community representatives; Developing a Terms of Reference for YOTS presence in the Walgett community; Undertaking a community consultation prior to finalising program activities; Implementing a range of recreational activities (sports, music, arts and crafts) early on in the activity; Implementing young family support initiatives; implementing a volunteering program, including volunteer support to young families through intergenerational volunteering; running a series of Culture and Healing Camps in partnership with local Elders and other services; Running a series of Music Camps; Providing alternative education support and referrals in partnership with local schools; Researching, identifying and adapting other best-practice models.

Antibodies against human herpesvirus 8 in black South African patients with cancer

Background Infection with human herpesvirus 8 (HHV-8) has been consistently linked to Kaposi's sarcoma, but its mode of transmission, association with other cancers, and interaction with the human immunodeficiency virus type 1 (HIV-1) are largely unknown. Methods Between January 1992 and December 1997, we interviewed 3591 black patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 in 3344 of the patients. Antibodies against HHV-8 were detected with an indirect immunofluorescence assay. The intensity of the fluorescent signal correlated well with the titers of antibodies (P<0.001). The relations among the presence of anti–HHV-8 antibodies, sociodemographic and behavioral factors, type of cancer, and the presence or absence of coexistent HIV-1 infection were examined with the use of unconditional logistic-regression models. Results Among the 3293 subjects with cancers other than Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 32 percent, which did not differ significantly from the standardized seroprevalence among black blood donors. Among these 3293 patients, the prevalence of antibodies against HHV-8 increased with increasing age (P<0.001) and an increasing number of sexual partners (P=0.05) and decreased with increasing years of education (P=0.007); it was not strongly associated with HIV-1 infection. Anti–HHV-8 antibodies were more frequent among black than white blood donors (P<0.001). Among the 51 patients with Kaposi's sarcoma, the standardized seroprevalence of antibodies against HHV-8 was 83 percent, significantly higher than the prevalence among those without Kaposi's sarcoma (P<0.001). For 16 other specific types of cancer, including multiple myeloma (108 cases) and prostate cancer (202 cases), the variation in the standardized seroprevalence of antibodies against HHV-8 was not remarkable. At a given intensity of fluorescence of anti–HHV-8 antibodies, Kaposi's sarcoma was more frequent among HIV-1–positive patients than among those who were HIV-1–negative (P<0.001). Conclusions Among black patients with cancer in South Africa, the seroprevalence of anti–HHV-8 antibodies is high and is specifically associated with Kaposi's sarcoma, particularly at high titers.

Impact of Mobility Constraints on Epidemic Broadcast in DTNs

In this paper, we investigate the effect of mobility constraints on epidemic broad-cast mechanisms in DTNs (Delay-Tolerant Networks). Major factors affecting epidemic broadcast performances are its forwarding algorithm and node mobility. The impact of forwarding algorithm and node mobility on epidemic broadcast mechanisms has been actively studied in the literature, but those studies use generally unconstrained mobility models. The objective of this paper is therefore to quantitatively investigate the effect of mobility constraints on epidemic broadcast mechanisms. We evaluate the performances of P-BCAST (PUSH-based BroadCast), SA-BCAST (Self-Adaptive BroadCast), and HP-BCAST (History-based P-BCAST) with a random waypoint mobility model with mobility constraints.

Sectionalizing strategies for minimizing outage durations of critical loads in parallel power system restoration with bi-level programming

Fast restoration of critical loads and non-black-start generators can significantly reduce the economic losses caused by power system blackouts. In a parallel power system restoration scenario, the sectionalization of restoration subsystems plays a very important role in determining the pickup of critical loads before synchronization. Most existing research mainly focuses on the startup of non-black-start generators. The restoration of critical loads, especially the loads with cold load characteristics, has not yet been addressed in optimizing the subsystem divisions. As a result, sectionalized restoration subsystems cannot achieve the best coordination between the pickup of loads and the ramping of generators. In order to generate sectionalizing strategies considering the pickup of critical loads in parallel power system restoration scenarios, an optimization model considering power system constraints, the characteristics of the cold load pickup and the features of generator startup is proposed in this paper. A bi-level programming approach is employed to solve the proposed sectionalizing model. In the upper level the optimal sectionalizing problem for the restoration subsystems is addressed, while in the lower level the objective is to minimize the outage durations of critical loads. The proposed sectionalizing model has been validated by the New-England 39-bus system and the IEEE 118-bus system. Further comparisons with some existing methods are carried out as well.

Mutation of perinatal myosin heavy chain

Veugelers et al. (July 29 issue)1 report on patients with the trismus–pseudocamptodactyly syndrome as having a “Carney complex variant.” Among more than 500 patients with the Carney complex in our database, there are none with the trismus–pseudocamptodactyly syndrome.2,3...

Legal duties following the discharge of mental health patients

In the recent decision of Hunter and New England Local Health District v McKenna; Hunter and New England Local Health District v Simon, the High Court of Australia held that a hospital and its medical staff owed no common law duty of care to third parties claiming for mental harm, against the background of statutory powers to detain mentally ill patients. This conclusion was based in part on the statutory framework and in part on the inconsistency which would arise if such a duty was imposed. If such a duty was imposed in these circumstances, the consequence may be that doctors would generally detain rather than discharge mentally ill persons to avoid the foreseeable risk of harm to others. Such an approach would be inconsistent with the policy of the mental health legislation , which favours personal liberty and discharge rather than detention unless no other care of a less restrictive kind is appropriate and reasonably available.

Factors potentiating the risk of sudden infant death syndrome associated with the prone position

Background. In several studies the sudden infant death syndrome (SIDS) has been significantly associated with sleeping in the prone position. It is not known how the prone position increases the risk of SIDS. Methods. We analyzed data from a case-control study (58 infants with SIDS and 120 control infants) and a prospective cohort study (22 infants with SIDS and 213 control infants) in Tasmania. Interactions were examined in matched analyses with a multiplicative model of interaction. Results. In the case-control study, SIDS was significantly associated with sleeping in the prone position, as compared with other positions (unadjusted odds ratio, 4.5; 95 percent confidence interval, 2.1 to 9.6). The strength of this association was increased among infants who slept on natural-fiber mattresses (P = 0.05), infants who were swaddled (P = 0.09), infants who slept in heated rooms (P = 0.006), and infants who had had a recent illness (P = 0.02). These variables had no significant effect on infants who did not sleep in the prone position. A history of recent illness was significantly associated with SIDS among infants who slept prone (odds ratio, 5.7; 95 percent confidence interval, 1.8 to 19) but not among infants who slept in other positions (odds ratio, 0.83). In the cohort study, the risk of SIDS was greater among infants who slept prone on natural-fiber mattresses (odds ratio, 6.6; 95 percent confidence interval, 1.3 to 33) than among infants who slept prone on other types of mattresses (odds ratio, 1.8). Conclusions. When infants sleep prone, the elevated risk of SIDS is increased by each of four factors: the use of natural-fiber mattresses, swaddling, recent illness, and the use of heating in bedrooms.

Book Review "Selling sex: a hidden history of prostitution", R. Frances, UNSW Press, Sydney, 2007

In the opening pages of Selling Sex we are introduced to 'Joy', a statue of a young female sex worker which stood in East Sydney for eighteen months during 1995- 1997. Following complaints by local residents, the statue was removed from public view and returned to its owner. Evidently, Joy was considered a reminder of the community's 'bad old days', when it was better known for prostitution than restaurants. In a nation in which almost every sizable community has proudly erected monuments to military men, the removal of Joy reveals much about labour and gender relations in Australia. For Frances, the removal of Joy is symbolic, our historical treatment of sex workers having parallels with our treatment of the convicts. This work sets out to give these women (male prostitutes do not figure in this history) a voice and break with the stereotypes of 'abandoned whores' or 'sad victims'. It also sets out to place the sex industry in the broader national and international context in which it has historically operated...