Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families : evidence for common founders and independent mutations

Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families from Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem-repeat markers; however, the data provide evidence to indicate that there were at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents.

Good and bad Sharia : Australia's mixed response to Islamic law

Reflecting on the legal consequences of globalisation in the 21st century, Twining predicted that societies in the West would have to 'wrestle with the extent to which the state should recognise, make concessions to, or even enforce norms and values embedded in different religions, cultures or traditions'. This is borne out as the direction across the common law world moves towards entrenching legal pluralism. The concessions each nation has made to minorities with different religions, cultures and traditions have varied. The special character of Islam, as a comprehensive blueprint for life in which law and religion unite, has meant that the negotiations for a special place for Muslims within each common law jurisdiction has been at the forefront of new legal ordering possibilities. This is the crux of the pluralism debate. Cautiously, Australians have watched the, at times histrionic, discourse in Canada and Great Britain on official recognition for Islamic law.

Regulating Prostitution: Controlling Women's Lives'

The chapter argues that the women who compose the majority of street prostitutes in Great Britain are currently subject to an interlocking system of regulation that variously defines them as criminal offenders, threats to public health, victims of child abuse, and vulnerable women who must be compelled under the threat of punishment to seek welfare help. Each label or approach to the street prostitute involves a set of interventions aimed at changing or working with different aspects of the women's lives. This produces an interlocking system of regulation, because the interventions are not mutually exclusive. A street prostitute can be defined as both a victim and an offender and as both a patient in need of medical help and a threat to public health. This comprehensive system of regulation means that a street prostitute faces not only a wide range of criminal justice dispositions, but also mandatory participation in programs in which her relationships and the choices she makes in her life outside of prostitution are subject to scrutiny and intervention. Given that street prostitutes are mostly poor women seeking economic survival in a profession that makes them vulnerable to victimization, the current regulatory system is an attempt to control a small group of poor women regarding their choices and relationships as they struggle to survive poverty. Whereas in the 1980s in Great Britain, a woman involved in street prostitution may have faced only a fine, now she is subject to a more extensive range of criminal justice actions accompanied by various government interventions designed to remake her life.

Occupational Access and Wage Discrimination

This article presents a study on the quantification of the level of occupational access and wage discrimination in Great Britain. The traditional approach to quantifying the level of sex discrimination is to distinguish gender differences in productive characteristics from the unequal treatment of characteristics according to gender. The role of inter- versus intra-occupational effects in determining the magnitude of wage differences between men and women was examined. The econometric results provided estimates of the wage differential in six broad occupational classifications together with an aggregate picture of how important the occupational distribution of females is in explaining their lower average wage. In summary, the results of the study suggest that the vast majority of the male and female wage differential arises from intra-occupation effects. The results provide evidence to suggest that occupational segregation is not a major contributor to the observed male/female wage differential.

Refugees from Vietnam

"Refugees from Vietnam" sets out to identify the social policy issues that arise when mass settlement of refugees takes place, particularly in an unfamiliar social context. It also tries to offer ways forward which would allow the resettlement process to be more successful from the viewpoint of the refugees and of the host community. The refugee group chosen as a case study for this book was that group of refugees who fled from Vietnam as "the boat people" and arrived in Britain and many other Western countries between 1979 and 1981. Since 1979 the author has been involved in the resettlement in the UK of refugees from Vietnam. She has written a number of articles on this topic. She is also the author of the book "Illiteracy and the Offender.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Genome-wide search for markers associated with bovine spongiform encephalopathy

A genome-wide search for markers associated with BSE incidence was performed by using Transmission-Disequilibrium Tests (TDTs). Significant segregation distortion, i.e., unequal transmission probabilities of alleles within a locus, was found for three marker loci on Chromosomes (Chrs) 5, 10, and 20. Although TDTs are robust to false associations owing to hidden population substructures, it cannot distinguish segregation distortion caused by a true association between a marker and bovine spongiform encephalopathy (BSE) from a population-wide distortion. An interaction test and a segregation distortion analysis in half-sib controls were used to disentangle these two alternative hypotheses. None of the markers showed any significant interaction between allele transmission rates and disease status, and only the marker on Chr 10 showed a significant segregation distortion in control individuals. Nevertheless, the control group may have been a mixture of resistant and susceptible but unchallenged individuals. When new genotypes were generated in the vicinity of these three markers, evidence for an association with BSE was confirmed for the locus on Chr 5.

Towards a dignified and sustainable electricity generation sector in Australia : a comparative review of three models

Electricity is the cornerstone of modern life. It is essential to economic stability and growth, jobs and improved living standards. Electricity is also the fundamental ingredient for a dignified life; it is the source of such basic human requirements as cooked food, a comfortable living temperature and essential health care. For these reasons, it is unimaginable that today's economies could function without electricity and the modern energy services that it delivers. Somewhat ironically, however, the current approach to electricity generation also contributes to two of the gravest and most persistent problems threatening the livelihood of humans. These problems are anthropogenic climate change and sustained human poverty. To address these challenges, the global electricity sector must reduce its reliance on fossil fuel sources. In this context, the object of this research is twofold. Initially it is to consider the design of the Renewable Energy (Electricity) Act 2000 (Cth) (Renewable Electricity Act), which represents Australia's primary regulatory approach to increase the production of renewable sourced electricity. This analysis is conducted by reference to the regulatory models that exist in Germany and Great Britain. Within this context, this thesis then evaluates whether the Renewable Electricity Act is designed effectively to contribute to a more sustainable and dignified electricity generation sector in Australia. On the basis of the appraisal of the Renewable Electricity Act, this thesis contends that while certain aspects of the regulatory regime have merit, ultimately its design does not represent an effective and coherent regulatory approach to increase the production of renewable sourced electricity. In this regard, this thesis proposes a number of recommendations to reform the existing regime. These recommendations are not intended to provide instantaneous or simple solutions to the current regulatory regime. Instead, the purpose of these recommendations is to establish the legal foundations for an effective regulatory regime that is designed to increase the production of renewable sourced electricity in Australia in order to contribute to a more sustainable and dignified approach to electricity production.

Platinum-based chemotherapy in metastatic breast cancer : the Leicester (UK) experience

Aims: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. Materials and methods: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n = 23), or cisplatin-etoposide (PE) (n = 19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m 2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m 2), and cisplatin (50 mg/m 2) all on day 1; and cisplatin (75 mg/m 2) and etoposide (100 mg/m 2) on day 1 and (100 mg/m 2) orally twice a day on days 2-3. Results: The response rate for 40 evaluable patients (MVP: n = 23; PE: n = 17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n = 19; PE: n = 18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer. © 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Cultural Policy

The development of cultural policy during the twentieth century is underscored by three key developments. First, the formation of the Arts Council of Great Britain in 1946, first headed by the Cambridge economist Lord Keynes, saw the scaffolding developed for ongoing government support for the arts. In doing so, it established the principle of an “arm’s length” relationship between the government of the day and individual artists, through the development of independent arts boards engaged in the peer review of creative works. Second, the formation of the Fifth Republic in France in 1958 saw the creation of a Ministry of Culture, headed by the writer André Malraux. Malraux and his successors have seen three major tasks for a national cultural policy: government support for the creation of new artistic and cultural works; the promotion and maintenance of cultural heritage; and enabling equitable access to creative works and creative opportunities through all segments of society. Finally, at a global level, agencies such as UNESCO have sought to promote national cultural policies as an element of national sovereignty, particularly in the developing world, and this has involved addressing sources of structural inequality in the distribution of global cultural and communications resources...

Teaching colour theory online : challenges, opportunities and experiences [Abstract]

Over the past decade, various paradigm shifts and challenges have rapidly changed learning and teaching in higher education including meeting student expectation for more engaging, more interactive learning experiences, the increased focus in the tertiary sector to deliver content online, and dealing with the complexities of fast-changing technologies. Rising to these challenges and responding to them is a complex and multi-faceted task. This paper discusses a case study undertaken applying a framework drawn from engineering education teaching and learning methods using the concept of academagogy, which is learner-centric, actively empowering students in building effective learning and engages facilitators in meaningful teaching and delivery methods.

The implications of educational and methodological background for the career success of Nobel Laureates : an investigation of major awards

Nobel laureates have achieved the highest recognition in academia, reaching the boundaries of human knowledge and understanding. Owing to past research, we have a good understanding of the career patterns behind their performance. Yet, we have only limited understanding of the factors driving their recognition with respect to major institutionalized scientific honours. We therefore look at the award life cycle achievements of the 1901–2000 Nobel laureates in physics, chemistry, and physiology or medicine. The results show that Nobelists with a theoretical orientation achieved more awards than laureates with an empirical orientation. Moreover, it seems their educational background shapes their future recognition. Researchers educated in Great Britain and the US tend to attract more awards than other Nobelists, although there are career pattern differences. Among those, laureates educated at Cambridge or Harvard are more successful in Chemistry, those from Columbia and Cambridge excel in Physics, while Columbia educated laureates dominate in Physiology or Medicine.

Australian horror movies and the American market

In Australian cinema since the mid-2000s, horror has become a popular and at times commercially viable genre for low-budget and emerging filmmakers targeting international markets. While the annual horror film output of Australia pales in comparison to that of other Anglophone nations like the United States, Great Britain, and Canada, it has produced several significant titles that have performed moderately well at the international box office, from Wolf Creek (Greg McLean, 2005) to Daybreakers (Michael and Peter Spierig, 2009). Yet as part of a broader tradition of Anglophone horror cinema, many Australian horror movies have been heavily influenced by US and to a lesser extent British horror films. Furthermore, Australian horror film production is largely an internationally-oriented sector that relies on its relationships with overseas distributors and often investors. Consequently, the content and style of Australian horror movies have regularly been tailored for international markets. As a direct consequence some filmmakers have sought to trade on the “Australianness” of their product, others have attempted to pass off their films as faux-American, while others still have attempted to develop placeless films effaced of national reference points. This chapter examines local production as part of a broader tradition of Anglophone horror cinema, the influence of US horror movies, and the limitations of the domestic marketplace. The article concludes with an analysis of how the lure of the US market influences Australian filmmakers’ textual strategies.

The management of venereal disease in New South Wales, 1871 to 1916

Practical techniques to manage the dangers associated with sexually transmitted diseases have varied considerably both cross culturally and historically. Adopting a Foucauldian perspective, this article examines sociohistorical aspects of the governance of venereal disease in New South Wales between 1871 and 1916. Public debates and official documents are analysed to identify strategic shifts in practices associated with venereal disease management , especially in relation to prostitution. Particular attention is paid to the development of contagious disease legislation and its role in the regulation of venereal disease . It is argued that during the period in question, two distinct governmental regimes of disease control can be identified. In the first, medical policing managed venereal disease through the mobilisation of repressive controls, requiring the isolation and detention of polluting bodies. In the second, liberal governance adopted pedagogic practices to train populations perceived as either healthy or unhealthy. It is further argued that as liberal strategies of governance came to dominate the management of venereal disease , the association of prostitution with venereal disease began to weaken. Instead, authorities became increasingly concerned with populations whose behaviour was not traditionally linked with venereal disease , such as the young and the sexually inexperienced.

Nurses’ views on the implementation of Individualised Medication Administration Guides in patients with dysphagia in care homes

As conditions such as stroke, cancer, Parkinson's disease and Huntingdon's chorea are commonly found in care homes between 15% and 30% of residents in care homes have been found to have difficulties in swallowing their medicines.To address the difficulties associated with administering medicines to patients who cannot swallow (with dysphagia), Individualised Medication Administration Guides (I-MAGs) were introduced by a specialised pharmacist in Care for Elderly wards in a general hospital in East Anglia. The guides contained detailed information about how to administer each medication and they were individualised to the needs of the patient. The I-MAGs were printed in green forms and attached to the medication chart in order to be used in conjunction with it. The ward nurses reported an increase in their confidence when administering medication when I-MAGs were present in the ward. Some patients with I-MAG were discharged to care homes where the I-MAG might have been equally useful. However, the design of such guides is not known to be suitable for care homes environment where they have never been used before. This study aims to explore the opinions of nurses and carers within care homes on the relevance and acceptability of individualised medication administration guides for patients with dysphagia (PWD).