306 resultados para comparative genomic hybridization


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Background Contemporary psychotherapy research demonstrates that whilst most clients respond positively to psychological interventions, a small, but significant proportion of clients fail to experience the expected benefits of therapy. Although methodologies exist that enable the identification of successful and unsuccessful therapy, we have a limited understanding of the processes associated with these outcomes. Aim The current study sought to examine the relationship between therapeutic outcome and therapeutic language. Methodology: The therapeutic outcomes of 42 trainee-therapists who provided psychotherapy to 173 clients were tracked with the OQ-45.2 over a 5 year period with the view of identifying the client/ trainee-therapist dyads with the best and poorest outcomes. The 6 best outcome and 6 poorest outcome client/ trainee-therapist dyads were identified in order to examine the characteristics of therapeutic conversations associated with better and poorer therapy outcomes. Therapeutic conversations were analysed with the Narrative Process Coding System. Findings The best outcome client/ trainee-therapist dyads demonstrated significant increases in reflexive conversation over the course of psychotherapy. Implications Examining the practices of the best and poorest outcome client/ trainee-therapist dyads with objective measures of therapy outcome provides an important first step in understanding how therapeutic language may contribute to the greatest therapeutic improvement or deterioration.

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BACKGROUND Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

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Higher education institutions across the world are experiencing a new generation of students, known as millennial learners. They are more technologically literate and digitally connected than previous generations of learners. To meet the teaching and learning needs of these learners, we must offer more deliberate and meaningful learning experiences and opportunities, where students can see the connections between new material and their own experiences and real world applications – an academagogic approach. This study compares the implementation of academagogy for two different groups of millennial learners – one a traditional face-to-face undergraduate Engineering unit, and the other a mixed-mode (online and face-to-face) undergraduate Design unit. The units are discussed in terms of their student evaluation results, both qualitative and quantitative, and in terms of their academic outcomes for students. Conclusions are drawn about the applicability of academagogy as a heuristic for improving teaching and learning across disciplines, as well as its strengths and limitations in terms of student results.

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Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell cycle arrest and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolising enzymes, such as CYP1A1, in breast cells. Lastly, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumours in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

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Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

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In strengthening systems, the CFRP (Carbon Fibre Reinforced Polymer) materials typically have excellent resistance against environmental conditions; however, the performance of adhesives between CFRP and steel is generally affected by various environmental conditions such as marine environment, cold and hot weather. This paper presents the comparative durability study of CFRP strengthened tubular steel structures by using two different adhesives such as MBrace saturant and Araldite K630 under four-point bending. The program consisted of testing twelve CFRP strengthened specimens having treated with epoxy based adhesion promoter, untreated surface and one unstrengthened specimen and conditioned under cold weather for 3 and 6 months to determine the environmental durability. The beams were then loaded to failure in quasi-static manner under four-point bending. The structural responses of CFRP strengthened tubular steel beams were compared in terms of failure load, stiffness and modes of failure. The research findings show that the cold weather immersion had adversely affected the durability of CFRP strengthened steel members. Design factor is also proposed to address the short-terms durability performance under cold weather.

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This study analyzes the management of wastewater pollutants in a number of Chinese industrial sectors from 1998 to 2010. We use decomposition analysis to calculate changes in wastewater pollutant emissions that result from cleaner production processes, end-of-pipe treatment, structural changes in industry, and changes in the scale of production. We focus on one indicator of water quality and three pollutants: chemical oxygen demand (COD), petroleum, cyanide, and volatile phenols. We find that until 2002, COD emissions were mainly reduced through end-of-pipe treatments. Cleaner production processes didn’t begin contributing to COD emissions reductions until the introduction of a 2003 law that enforced their implementation. Petroleum emissions were primarily lowered through cleaner production mechanisms, which have the added benefit of reducing the input cost of intermediate petroleum. Diverse and effective pollution abatement strategies for cyanide and volatile phenols are emerging among industries in China. It will be important for the government to consider differences between industries should they choose to regulate the emissions of specific chemical substances.

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Ghrelin and leptin are key peripherally secreted appetite-regulating hormones in vertebrates. Here we consider the ghrelin gene (GHRL) of birds (class Aves), where it has been reported that ghrelin inhibits rather than augments feeding. Thirty-one bird species were compared, revealing that most species harbour a functional copy of GHRL and the coding region for its derived peptides ghrelin and obestatin. We provide evidence for loss of GHRL in saker and peregrine falcons, and this is likely to result from the insertion of an ERVK retrotransposon in intron 0. We hypothesise that the loss of anorexigenic ghrelin is a predatory adaptation that results in increased food-seeking behaviour and feeding in falcons.

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In 2009, the National Research Council of the National Academies released a report on A New Biology for the 21st Century. The council preferred the term ‘New Biology’ to capture the convergence and integration of the various disciplines of biology. The National Research Council stressed: ‘The essence of the New Biology, as defined by the committee, is integration—re-integration of the many sub-disciplines of biology, and the integration into biology of physicists, chemists, computer scientists, engineers, and mathematicians to create a research community with the capacity to tackle a broad range of scientific and societal problems.’ They define the ‘New Biology’ as ‘integrating life science research with physical science, engineering, computational science, and mathematics’. The National Research Council reflected: 'Biology is at a point of inflection. Years of research have generated detailed information about the components of the complex systems that characterize life––genes, cells, organisms, ecosystems––and this knowledge has begun to fuse into greater understanding of how all those components work together as systems. Powerful tools are allowing biologists to probe complex systems in ever greater detail, from molecular events in individual cells to global biogeochemical cycles. Integration within biology and increasingly fruitful collaboration with physical, earth, and computational scientists, mathematicians, and engineers are making it possible to predict and control the activities of biological systems in ever greater detail.' The National Research Council contended that the New Biology could address a number of pressing challenges. First, it stressed that the New Biology could ‘generate food plants to adapt and grow sustainably in changing environments’. Second, the New Biology could ‘understand and sustain ecosystem function and biodiversity in the face of rapid change’. Third, the New Biology could ‘expand sustainable alternatives to fossil fuels’. Moreover, it was hoped that the New Biology could lead to a better understanding of individual health: ‘The New Biology can accelerate fundamental understanding of the systems that underlie health and the development of the tools and technologies that will in turn lead to more efficient approaches to developing therapeutics and enabling individualized, predictive medicine.’ Biological research has certainly been changing direction in response to changing societal problems. Over the last decade, increasing awareness of the impacts of climate change and dwindling supplies of fossil fuels can be seen to have generated investment in fields such as biofuels, climate-ready crops and storage of agricultural genetic resources. In considering biotechnology’s role in the twenty-first century, biological future-predictor Carlson’s firm Biodesic states: ‘The problems the world faces today – ecosystem responses to global warming, geriatric care in the developed world or infectious diseases in the developing world, the efficient production of more goods using less energy and fewer raw materials – all depend on understanding and then applying biology as a technology.’ This collection considers the roles of intellectual property law in regulating emerging technologies in the biological sciences. Stephen Hilgartner comments that patent law plays a significant part in social negotiations about the shape of emerging technological systems or artefacts: 'Emerging technology – especially in such hotbeds of change as the life sciences, information technology, biomedicine, and nanotechnology – became a site of contention where competing groups pursued incompatible normative visions. Indeed, as people recognized that questions about the shape of technological systems were nothing less than questions about the future shape of societies, science and technology achieved central significance in contemporary democracies. In this context, states face ongoing difficulties trying to mediate these tensions and establish mechanisms for addressing problems of representation and participation in the sociopolitical process that shapes emerging technology.' The introduction to the collection will provide a thumbnail, comparative overview of recent developments in intellectual property and biotechnology – as a foundation to the collection. Section I of this introduction considers recent developments in United States patent law, policy and practice with respect to biotechnology – in particular, highlighting the Myriad Genetics dispute and the decision of the Supreme Court of the United States in Bilski v. Kappos. Section II considers the cross-currents in Canadian jurisprudence in intellectual property and biotechnology. Section III surveys developments in the European Union – and the interpretation of the European Biotechnology Directive. Section IV focuses upon Australia and New Zealand, and considers the policy responses to the controversy of Genetic Technologies Limited’s patents in respect of non-coding DNA and genomic mapping. Section V outlines the parts of the collection and the contents of the chapters.

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In his book, The Emperor of All Maladies, Siddhartha Mukherjee writes a history of cancer — "It is a chronicle of an ancient disease — once a clandestine, 'whispered-about' illness — that has metamorphosed into a lethal shape-shifting entity imbued with such penetrating metaphorical, medical, scientific, and political potency that cancer is often described as the defining plague of our generation." Increasingly, an important theme in the history of cancer is the role of law, particularly in the field of intellectual property law. It is striking that a number of contemporary policy debates over intellectual property and public health have concerned cancer research, diagnosis, and treatment. In the area of access to essential medicines, there has been much debate over Novartis’ patent application in respect of Glivec, a treatment for leukaemia. India’s Supreme Court held that the Swiss company’s patent application violated a safeguard provision in India’s patent law designed to stop evergreening. In the field of tobacco control, the Australian Government introduced plain packaging for tobacco products in order to address the health burdens associated with the tobacco epidemic. This regime was successfully defended in the High Court of Australia. In the area of intellectual property and biotechnology, there have been significant disputes over the Utah biotechnology company Myriad Genetics and its patents in respect of genetic testing for BRCA1 and BRCA2, which are related to breast cancer and ovarian cancer. The Federal Court of Australia handed down a decision on the validity of Myriad Genetics’ patent in respect of genetic testing for BRCA1 in February 2013. The Supreme Court of the United States heard a challenge to the validity of Myriad Genetics’ patents in this area in April 2013, and handed down a judgment in July 2013. Such disputes have involved tensions between intellectual property rights, and public health. This article focuses upon one of these important test cases involving intellectual property, public health, and cancer research. In June 2010, Cancer Voices Australia and Yvonne D’Arcy brought an action in the Federal Court of Australia against the validity of a BRCA1 patent — held by Myriad Genetics Inc, the Centre de Recherche du Chul, the Cancer Institute of Japan and Genetic Technologies Limited. Yvonne D’Arcy — a Brisbane woman who has had treatment for breast cancer — maintained: "I believe that what they are doing is morally and ethically corrupt and that big companies should not control any parts of the human body." She observed: "For my daughter, I've had her have [sic] mammograms, etc, because of me but I would still like her to be able to have the test to see if the mutation gene is in there from me." The applicants made the following arguments: "Genes and the information represented by human gene sequences are products of nature universally present in each individual, and the information content of a human gene sequence is fixed. Genetic variations or mutations are products of nature. The isolation of the BRCA1 gene mutation from the human body constitutes no more than a medical or scientific discovery of a naturally occurring phenomenon and does not give rise to a patentable invention." The applicants also argued that "the alleged invention is not a patentable invention in that, so far as claimed in claims 1–3, it is not a manner of manufacture within the meaning of s 6 of the Statute of Monopolies". The applicants suggested that "the alleged invention is a mere discovery". Moreover, the applicants contended that "the alleged invention of each of claims 1-3 is not a patentable invention because they are claims for biological processes for the generation of human beings". The applicants, though, later dropped the argument that the patent claims related to biological processes for the generation of human beings. In February 2013, Nicholas J of the Federal Court of Australia considered the case brought by Cancer Voices Australia and Yvonne D’Arcy against Myriad Genetics. The judge presented the issues in the case, as follows: "The issue that arises in this case is of considerable importance. It relates to the patentability of genes, or gene sequences, and the practice of 'gene patenting'. Briefly stated, the issue to be decided is whether under the Patents Act 1990 (Cth) a valid patent may be granted for a claim that covers naturally occurring nucleic acid — either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) — that has been 'isolated'". In this context, the word "isolated" implies that naturally occurring nucleic acid found in the cells of the human body, whether it be DNA or RNA, has been removed from the cellular environment in which it naturally exists and separated from other cellular components also found there. The genes found in the human body are made of nucleic acid. The particular gene with which the patent in suit is concerned (BRCA1) is a human breast and ovarian cancer disposing gene. Various mutations that may be present in this gene have been linked to various forms of cancer including breast cancer and ovarian cancer.' The judge held in this particular case that Myriad Genetics’ patent claims were a "manner of manufacture" under s 6 of the Statute of Monopolies and s 18(1)(a) of the Patents Act 1990 (Cth). The matter is currently under appeal in the Full Court of the Federal Court of Australia. This article interprets the dispute over Myriad Genetics in light of the scholarly work of Nobel Laureate Professor Joseph Stiglitz on inequality. Such work has significant explanatory power in the context of intellectual property and biotechnology. First, Stiglitz has contended that "societal inequality was a result not just of the laws of economics, but also of how we shape the economy — through politics, including through almost every aspect of our legal system". Stiglitz is concerned that "our intellectual property regime … contributes needlessly to the gravest form of inequality." He maintains: "The right to life should not be contingent on the ability to pay." Second, Stiglitz worries that "some of the most iniquitous aspects of inequality creation within our economic system are a result of 'rent-seeking': profits, and inequality, generated by manipulating social or political conditions to get a larger share of the economic pie, rather than increasing the size of that pie". He observes that "the most iniquitous aspect of this wealth appropriation arises when the wealth that goes to the top comes at the expense of the bottom." Third, Stiglitz comments: "When the legal regime governing intellectual property rights is designed poorly, it facilitates rent-seeking" and "the result is that there is actually less innovation and more inequality." He is concerned that intellectual property regimes "create monopoly rents that impede access to health both create inequality and hamper growth more generally." Finally, Stiglitz has recommended: "Government-financed research, foundations, and the prize system … are alternatives, with major advantages, and without the inequality-increasing disadvantages of the current intellectual property rights system.’" This article provides a critical analysis of the Australian litigation and debate surrounding Myriad Genetics’ patents in respect of genetic testing for BRCA1. First, it considers the ruling of Nicholas J in the Federal Court of Australia that Myriad Genetics’ patent was a manner of manufacture as it related to an artificially created state of affairs, and not mere products of nature. Second, it examines the policy debate over gene patents in Australia, and its relevance to the litigation involving Myriad Genetics. Third, it examines comparative law, and contrasts the ruling by Nicholas J in the Federal Court of Australia with developments in the United States, Canada, and the European Union. Fourth, this piece considers the reaction to the decision of Nicholas at first instance in Australia. Fifth, the article assesses the prospects of an appeal to the Full Federal Court of Australia over the Myriad Genetics’ patents. Finally, this article observes that, whatever happens in respect of litigation against Myriad Genetics, there remains controversy over Genetic Technologies Limited. The Melbourne firm has been aggressively licensing and enforcing its related patents on non-coding DNA and genomic mapping.

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This article considers the origins and the development of the defence of experimental use in patent law - the ’freedom to tinker'. It explores the impact of such an exemption upon a number of important industries - such as agriculture, biotechnology, and pharmaceutical drugs. This article takes a comparative approach in its analysis of patent law and experimental use. It highlights the competing norms, and lack of harmonization between a number of jurisdictions - including the United States, the European Union, and Australia. Section 2 provides a critique of the development of the common law defence of experimental use in the United States. It considers a series of precedents - including Roche Products Inc v Bolar Pharmaceuticals, Madey v Duke University, Integra Lifesciences I Ltd v Merck KgaA, and Applera v MJ Research. Section 3 explores the operation of patent law and experimental use in European jurisdictions. It looks at a number of significant precedents in the United Kingdom, the Netherlands, France, Italy, and Germany. Section 4 considers the policy debate in a number of forums over the defence of experimental use in Australia. It examines the controversy over Genetic Technologies Limited asking research organisations to obtain a licence in respect of its patents associated with non-coding DNA and genomic mapping. It also considers the inquiries of the Australian Law Reform Commission and the Advisory Council on Intellectual Property, as well as the impact of the TRIPS Agreement and the Australia-United States Free Trade Agreement. The conclusion contends that there is a need for a broad-based defence of experimental use for all the member states of the Organisation for Economic Co-operation and Development.

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This study uses the reverse salient methodology to contrast subsystems in video game consoles in order to discover, characterize, and forecast the most significant technology gap. We build on the current methodologies (Performance Gap and Time Gap) for measuring the magnitude of Reverse Salience, by showing the effectiveness of Performance Gap Ratio (PGR). The three subject subsystems in this analysis are the CPU Score, GPU core frequency, and video memory bandwidth. CPU Score is a metric developed for this project, which is the product of the core frequency, number of parallel cores, and instruction size. We measure the Performance Gap of each subsystem against concurrently available PC hardware on the market. Using PGR, we normalize the evolution of these technologies for comparative analysis. The results indicate that while CPU performance has historically been the Reverse Salient, video memory bandwidth has taken over as the quickest growing technology gap in the current generation. Finally, we create a technology forecasting model that shows how much the video RAM bandwidth gap will grow through 2019 should the current trend continue. This analysis can assist console developers in assigning resources to the next generation of platforms, which will ultimately result in longer hardware life cycles.

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Purpose The aim of this paper is to empirically explore antecedents of local food purchase intention in two food producing countries with different cultural backgrounds. Design/methodology/approach An online survey was employed to collect data from consumers located in Chile (n=283) and Australia (n=300). A proposed model is tested with structural equation modelling (SEM). Findings Attitude towards consuming local food is a strong and direct driver of intentions to purchase local food in both countries. Attitude toward supporting local agri-businesses and consumer ethnocentrism are found to positively impact attitude towards consuming local food in both countries. Attitude towards local agri-businesses also has a direct effect on intentions to purchase local food in Australia, but not in Chile. Interestingly, subjective norms are not found to affect intentions to consume local food in either country. Research limitations/implications The paper examines factors affecting the attitude toward and behavioural intention regarding local food consumption and develops an extended model of local food consumption. An outcome of this new model is the inclusion of personal variables, which influence local food purchasing behaviour. Practical implications Producers and retailers need to develop campaigns explaining how consuming local food supports local businesses and farmers, which will reinforce personal values associated with local consumption. Originality/value This is the first study to demonstrate that positive attitudes toward local foods are important drivers of local food purchase behaviour, independent of the cultural characteristics or level of economic development within a country.

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A key feature of the current era of Australian schooling is the dominance of publically available student, school and teacher performance data. Our paper examines the intersection of data on teachers’ postgraduate qualifications and students’ end of schooling outcomes in 26 Catholic Systemic Secondary Schools and 18 Catholic Independent Secondary Schools throughout the State of Queensland. We introduce and justify taking up a new socially-just measurement model of students’ end of schooling outcomes, called the ‘Tracking and Academic Management Index’, otherwise known as ‘TAMI’. Additional analysis is focused on the outcomes of top-end students vis-à-vis all students who are encouraged to remain in institutionalised education of one form or another for the two final years of senior secondary schooling. These findings of the correlations between Catholic teachers’ postgraduate qualifications and students’ end of schooling outcomes are also compared with teachers’ postgraduate qualifications and students’ end of schooling outcomes across 174 Queensland Government Secondary Schools and 58 Queensland Independent Secondary Schools from the same data collection period. The findings raise important questions about the transference of teachers’ postgraduate qualifications for progressing students’ end of schooling outcomes as well as the performance of Queensland Catholic Systemic Secondary Schools and Queensland Catholic Independent Secondary Schools during a particular era of education.

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Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.