388 resultados para Including therapeutic trials


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Purpose While a number of universities in Australia have embraced concepts such as project/problem‐based learning and design of innovative learning environments for engineering education, there has been a lack of national guidance on including sustainability as a “critical literacy” into all engineering streams. This paper was presented at the 2004 International Conference on Engineering Education in Sustainable Development (EESD) in Barcelona, Spain, outlining a current initiative that is seeking to address the “critical literacy” dilemma. Design/methodology/approach The paper presents the positive steps taken by Australia's peak engineering body, the Institution of Engineers Australia (EA), in considering accreditation requirements for university engineering courses and its responsibility to ensure the inclusion of sustainability education material. It then describes a current initiative called the “Engineering Sustainable Solutions Program – Critical Literacies for Engineers Portfolio” (ESSP‐CL), which is being developed by The Natural Edge Project (TNEP) in partnership with EA and Unesco. Findings Content for the module was gathered from around the world, drawing on research from the publication The Natural Advantage of Nations: Business Opportunities, Innovation, and Governance in the Twenty‐first Century. Parts of the first draft of the ESSP‐CL have been trialled at Griffith University, Queensland, Australia with first year environmental engineering students, in May 2004. Further trials are now proceeding with a number of other universities and organisations nationally and internationally. Practical implications It is intended that ESSP‐CL will be a valuable resource to universities, professional development activities or other education facilities nationally and internationally. Originality/value This paper fulfils an identified information/resources need.

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Analytical expressions are derived for the mean and variance, of estimates of the bispectrum of a real-time series assuming a cosinusoidal model. The effects of spectral leakage, inherent in discrete Fourier transform operation when the modes present in the signal have a nonintegral number of wavelengths in the record, are included in the analysis. A single phase-coupled triad of modes can cause the bispectrum to have a nonzero mean value over the entire region of computation owing to leakage. The variance of bispectral estimates in the presence of leakage has contributions from individual modes and from triads of phase-coupled modes. Time-domain windowing reduces the leakage. The theoretical expressions for the mean and variance of bispectral estimates are derived in terms of a function dependent on an arbitrary symmetric time-domain window applied to the record. the number of data, and the statistics of the phase coupling among triads of modes. The theoretical results are verified by numerical simulations for simple test cases and applied to laboratory data to examine phase coupling in a hypothesis testing framework

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Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

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Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

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Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

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Previous research has emphasised the importance of active citizenship in the early years for the development of a tolerant and cohesive Australian society. This paper presents findings related to young children’s beliefs about exclusion based on gender and race. The findings draw from a larger study exploring the development of children’s moral and social values and teachers’ beliefs and practices related to teaching for moral development, in the early years of school in Australia. This current study examined reasoning about exclusion in early childhood with children aged 5-8 years. One hundred children from seven schools (Preparatory to Grade 3) answered questions relating to two scenarios in which the children had to make a decision about whether to include others of different gender or race in their play. The majority of children believed that others should be included in their play, regardless of their gender or race. When asked to explain, the children primarily gave reasons related to moral concern and fairness. Children were then asked whether they would continue to include or exclude if their friends (social consensus) or teachers (authority) suggested otherwise. The majority of children maintained their beliefs when beliefs to the contrary were voiced by their peers and teachers. The implications of these responses are discussed.

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Intensive Case Management (ICM) is widely claimed to be an evidence-based and cost effective program for people with high levels of disability as a result of mental illness. However, the findings of recent randomized controlled trials comparing ICM with ‘usual services’ suggest that both clinical and cost effectiveness of ICM may be weakening. Possible reasons for this, including fidelity of implementation, researcher allegiance effects and changes in the wider service environment within which ICM is provided, are considered. The implications for service delivery and research are discussed.

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Abstract OBJECTIVE: Depression, anxiety and alcohol misuse frequently co-occur. While there is an extensive literature reporting on the efficacy of psychological treatments that target depression, anxiety or alcohol misuse separately, less research has examined treatments that address these disorders when they co-occur. We conducted a systematic review to determine whether psychological interventions that target alcohol misuse among people with co-occurring depressive or anxiety disorders are effective. DATA SOURCES: We systematically searched the PubMed and PsychINFO databases from inception to March 2010. Individual searches in alcohol, depression and anxiety were conducted, and were limited to 'human' published 'randomized controlled trials' or 'sequential allocation' articles written in English. STUDY SELECTION: We identified randomized controlled trials that compared manual guided psychological interventions for alcohol misuse among individuals with depressive or anxiety disorders. Of 1540 articles identified, eight met inclusion criteria for the review. DATA EXTRACTION: From each study, we recorded alcohol and mental health outcomes, and other relevant clinical factors including age, gender ratio, follow-up length and drop-out rates. Quality of studies was also assessed. DATA SYNTHESIS: Motivational interviewing and cognitive-behavioral interventions were associated with significant reductions in alcohol consumption and depressive and/or anxiety symptoms. Although brief interventions were associated with significant improvements in both mental health and alcohol use variables, longer interventions produced even better outcomes. CONCLUSIONS: There is accumulating evidence for the effectiveness of motivational interviewing and cognitive behavior therapy for people with co-occurring alcohol and depressive or anxiety disorders.

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This paper discusses the challenges of making a case for the adoption of low cost railway level crossings in Australia. Several issues are discussed in this paper including legal issues associated with the treatment of low-exposure passive crossings with low cost level crossing warning devices (LCLCWDs); principles of operation and deployment for LCLCWDs; and technical and human factors aspects of safety and availability. The Cooperative Research Centre (CRC) for Rail Innovation’s affordable level crossings project aims to address a number of these technical and human factors issues through research and field trials.

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Raman spectroscopy complimented with infrared spectroscopy has been used to study the rare earth based mineral decrespignyite (Y,REE)4Cu(CO3)4Cl(OH)5•2(H2O) and compared with the Raman spectra of a series of selected natural halogenated carbonates from different origins including bastnasite, parisite and northupite. The Raman spectrum of decrespignyite displays three bands are at 1056, 1070 and 1088 cm-1 attributed to the CO32- symmetric stretching vibration. The observation of three symmetric stretching vibrations is very unusual. The position of CO32- symmetric stretching vibration varies with mineral composition. Raman bands of decrespignyite show bands at 1391, 1414, 1489 and 1547 cm-1. Raman spectra of bastnasite, parisite and northupite show a single band at 1433, 1420 and 1554 cm-1 assigned to the ν3 (CO3)2- antisymmetric stretching mode. The observation of additional Raman bands for the ν3 modes for some halogenated carbonates is significant in that it shows distortion of the carbonate anion in the mineral structure. Four Raman bands are observed at 791, 815, 837 and 849 cm-1and assigned to the (CO3)2- ν2 bending modes. Raman bands are observed for decrespignyite at 694, 718 and 746 cm-1 and are assigned to the (CO3)2- ν4 bending modes. Raman bands are observed for the carbonate ν4 in phase bending modes at 722 cm-1 for bastnasite, 736 and 684 cm-1 for parisite, 714 cm-1 for northupite. Multiple bands are observed in the OH stretching region for decrespignyite, bastnasite and parisite indicating the presence of water and OH units in the mineral structure.