981 resultados para Positive Definite Functions


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Recent developments in wearable ECG technology have seen renewed interest in the use of Heart Rate Variability (HRV) feedback for stress management. Yet, little is know about the efficacy of such interventions. Positive reappraisal is an emotion regulation strategy that involves changing the way a situation is construed to decrease emotional impact. We sought to test the effectiveness of an intervention that used feedback on HRV data to prompt positive reappraisal during a stressful work task. Participants (N=122) completed two 20-minute trials of an inbox activity. In-between the first and the second trial participants were assigned to the waitlist control condition, a positive reappraisal via psycho-education condition, or a positive reappraisal via HRV feedback condition. Results revealed that using HRV data to frame a positive reappraisal message is more effective than using psycho-education (or no intervention)–especially for increasing positive mood and reducing arousal.

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The establishment and continuity of two international comparative assessments of science learning—the IEA’s TIMSS project and the OECD’s PISA project—have meant that there are now high-status reference points for other national and more local approaches to assessing the efficacy of science teaching and learning. Both projects, albeit with very different senses of what the outcome of science learning should be, have contributed positively and negatively to the current state of assessment of school science. The TIMSS project looks back at the science that is commonly included in the curricula of the participating countries. It is thus not about established school science nor about innovations in it. PISA is highly innovative looking, prospectively forward to see how students can use their science learning in everyday life situations. In this chapter some of these positives and negatives are discussed.

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Gemcitabine is indicated in combination with cisplatin as first-line therapy for solid tumours including non-small cell lung cancer (NSCLC), bladder cancer and mesothelioma. Gemcitabine is an analogue of pyrimidine cytosine and functions as an anti-metabolite. Structurally, however, gemcitabine has similarities to 5-aza-2-deoxycytidine (decitabine/Dacogen®), a DNA methyltransferase inhibitor (DNMTi). NSCLC, mesothelioma and prostate cancer cell lines were treated with decitabine and gemcitabine. Reactivation of epigenetically silenced genes was examined by RT-PCR/qPCR. DNA methyltransferase activity in nuclear extracts and recombinant proteins was measured using a DNA methyltransferase assay, and alterations in DNA methylation status were examined using methylation-specific PCR (MS-PCR) and pyrosequencing. We observe a reactivation of several epigenetically silenced genes including GSTP1, IGFBP3 and RASSF1A. Gemcitabine functionally inhibited DNA methyltransferase activity in both nuclear extracts and recombinant proteins. Gemcitabine dramatically destabilised DNMT1 protein. However, DNA CpG methylation was for the most part unaffected by gemcitabine. In conclusion, gemcitabine both inhibits and destabilises DNA methyltransferases and reactivates epigenetically silenced genes having activity equivalent to decitabine at concentrations significantly lower than those achieved in the treatment of patients with solid tumours. This property may contribute to the anticancer activity of gemcitabine.

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Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

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Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201-995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1-5. Although elevated plasma somatostatin levels may be detected in 14-15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [111In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer. Copyright © 2001 S. Karger AG, Basel.

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Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. © 2004 Blackwell Publishing Ltd.

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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.

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We present the treatment rationale and study design of the MetLung phase III study. This study will investigate onartuzumab (MetMAb) in combination with erlotinib compared with erlotinib alone, as second- or third-line treatment, in patients with advanced non-small-cell lung cancer (NSCLC) who are Met-positive by immunohistochemistry. Approximately 490 patients (245 per treatment arm) will receive erlotinib (150 mg oral daily) plus onartuzumab or placebo (15 mg/kg intravenous every 3 weeks) until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death. The efficacy objectives of this study are to compare overall survival (OS) (primary endpoint), progression-free survival, and response rates between the 2 treatment arms. In addition, safety, quality of life, pharmacokinetics, and translational research will be investigated across treatment arms. If the primary objective (OS) is achieved, this study will provide robust results toward an alternative treatment option for patients with Met-positive second- or third-line NSCLC. © 2012 Elsevier Inc. All Rights Reserved.

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Information and Communications Technology (ICT) has spread rapidly in Australia. Mobile phones, which increasingly have advanced capabilities including Internet access, mobile television and multimedia storage, are owned by 22% of Australian children aged 9-11 years and 73% of those aged 12-14 years (Australian Bureau of Statistics, 2012b), as well as by over 90% of Australians aged 15 years and over(Australian Communications and Media Authority (ACMA), 2010). Nearly 80% of Australian households have access to the Internet and 73% have a broadband Internet connection, ensuring that Internet access is typically reliable and high-speed (Australian Bureau of Statistics, 2012a). Ninety percent of Australian children aged 5-14 years (comprising 79% of 5-8 year olds; 96% of 9-11 year olds; and 98% of 12-14 year olds) reported having accessed the Internet during 2011-2012, a significant increase from 79% in 2008-2009 (Australian Bureau of Statistics, 2012b). Approximately 90% of 5-14 year olds have accessed the Internet both from home and from school, with close to 49% accessing the Internet from other places (Australian Bureau of Statistics, 2012b). Young people often make use of borrowed Internet access (e.g. in friends’ homes), commercial access (e.g. cybercafés), public access (e.g. libraries), and mobile device access in areas offering free Wi-Fi (Lim, 2009).

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Objectives Actigraphy can reliably assess sleep in healthy adults and be used to estimate total sleep time in suspected obstructive sleep apnoea (OSA) patients. We compared sleep quality for Continuous Positive Air Pressure (CPAP) treated OSA patients and controls, evaluating the impact of stopping CPAP for one night. Methods 11 men, aged 51–75 years (m = 65.6 years), compliant CPAP users, treated for 1–19 years (m = 7.8 years) wore Cambridge Neurotechnology Ltd actiwatches for one night while using CPAP and for one night sleeping without CPAP. A control group of 11 healthy men, aged 63–74 years (m = 64.1 years) slept normally whilst wearing an actiwatch. Subsequent daytime sleepiness was recorded using Karolinska sleepiness scores (KSS). Results Actimetry showed no significant differences between actual sleep time, sleep efficiency, sleep disturbance index or number of wake bouts when comparing OSA participants using CPAP, with controls; there was no difference in subsequent daytime sleepiness, control KSS = 4.21, OSA KSS = 4.17. Without CPAP there was no significant difference in sleep length or sleep onset latency compared with using CPAP, but there was a significant impact on sleep quality as shown by: increased sleep disturbance index from 7.9 to 13.8 [t(10) = 3.510, P < 0.05], decreased percent of actual sleep from 92.05% to 86.15% [t(10) = 3.51, P < 0.05], decreased sleep efficiency from 86.6% to 81% [t(10) = 2.204, P < 0.05] and increased number of wake bouts from 29 to 42.5 [t(10) = 3.877, P < 0.05]. Daytime sleepiness became significantly worse increasing from KSS 4.17 to 6.27 [t(10) = )4.96, P < 0.05]. Conclusion There was no disparity in sleep quality or KSS scores between CPAP treated OSA patients and healthy controls of a similar age. Treated OSA patients obtained quality sleep with no elevated day time sleepiness. However, cessation of treatment for one night caused sleep quality to deteriorate despite a comparable sleep time; the deterioration in sleep quality could explain the increase in daytime sleepiness. OSA patients need to know that even short-term noncompliance with CPAP treatment significantly impairs sleep quality, leading to excessive sleepiness during monotonous tasks such as driving. Actigraphy successfully identified nights of non-compliance in treated OSA patients; but did not differentiate between the sleep of CPAP treated OSA patients and healthy controls.

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Kate Nayton, Elaine Fielding and Elizabeth Beattie describe how they developed a successful program to educate hospital staff about dementia care. The program may soon be trialled in other acute care facilities.

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The monstrous landscape and the revenge of nature are recurring motifs in Australian cinema. In the horror genre, the idea of the monstrous landscape emerges from, and builds upon, an established tradition in Australian cinema in which landscape functions not just as a setting for action, but also as a character in its own right. Rather than a picturesque wilderness or countryside, or a serene natural world untainted by civilisation – representations common in landscape cinema celebrating positive aspects of the Australian ‘outback’ – the monstrous landscape is a dangerous, malevolent and threatening force. Drawing upon themes also common in Australian Gothic narratives such as entrapment in a hostile environment, isolation and fear of the unknown (Turcotte, 1988, see also Jonathan Rayner’s essay in this volume), the monstrous landscape acts according to its own logic indecipherable to non-Indigenous Australians and is represented in terms of its alien-ness and inhuman horror.

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In Chronic Kidney Disease (CKD), management of diet is important in prevention of disease progression and symptom management, however evidence on nutrition prescription is limited. Recent international CKD guidelines and literature was reviewed to address the following question “What is the appropriate nutrition prescription to achieve positive outcomes in adult patients with chronic kidney disease?” Databases included in the search were Medline and CINAHL using EBSCOhost search engine, Embase and the Cochrane Database of Systematic Reviews published from 2000 to 2009. International guidelines pertaining to nutrition prescription in CKD were also reviewed from 2000 to 2013. Three hundred and eleven papers and eight guidelines were reviewed by three reviewers. Evidence was graded as per the National Health and Medical Research Council of Australia criteria. The evidence from thirty six papers was tabulated under the following headings: protein, weight loss, enteral support, vitamin D, sodium, fat, fibre, oral nutrition supplements, nutrition counselling, including protein and phosphate, nutrients in peritoneal dialysis solution and intradialytic parenteral nutrition, and was compared to international guidelines. While more evidence based studies are warranted, the customary nutrition prescription remains satisfactory with the exception of Vitamin D and phosphate. In these two areas, additional research is urgently needed given the potential of adverse outcomes for the CKD patient.

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It is widely acknowledged that effective asset management requires an interdisciplinary approach, in which synergies should exist between traditional disciplines such as: accounting, engineering, finance, humanities, logistics, and information systems technologies. Asset management is also an important, yet complex business practice. Business process modelling is proposed as an approach to manage the complexity of asset management through the modelling of asset management processes. A sound foundation for the systematic application and analysis of business process modelling in asset management is, however, yet to be developed. Fundamentally, a business process consists of activities (termed functions), events/states, and control flow logic. As both events/states and control flow logic are somewhat dependent on the functions themselves, it is a logical step to first identify the functions within a process. This research addresses the current gap in knowledge by developing a method to identify functions common to various industry types (termed core functions). This lays the foundation to extract such functions, so as to identify both commonalities and variation points in asset management processes. This method describes the use of a manual text mining and a taxonomy approach. An example is presented.