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Second Challenge (second + challenge)
Selected AbstractsStatistical methods for the evaluation of health effects of prenatal mercury exposureENVIRONMETRICS, Issue 2 2003Esben Budtz-Jørgensen Abstract Environmental risk assessment based on epidemiological data puts stringent demands on the statistical procedures. First, convincing evidence has to be established that there is a risk at all. In practice this endeavor requires prudent use of the observational epidemiological information with delicate balancing between utilizing the information optimally but not over-interpreting it. If a case for an environmental risk has been made, the second challenge is to provide useful input that regulatory authorities can use to set standards. This article surveys some of these issues in the concrete case of neurobehavioral effects in Faroese children prenatally exposed to methylmercury. A selection of modern, appropriate methods has been applied in the analysis of this material that may be considered typical of environmental epidemiology today. In particular we emphasize the potential of structural equation models for improving standard multiple regression analysis of complex environmental epidemiology data. Copyright © 2003 John Wiley & Sons, Ltd. [source] Relative resistance of Pacific salmon to infectious salmon anaemia virusJOURNAL OF FISH DISEASES, Issue 9 2003J B Rolland Abstract Infectious salmon anaemia (ISA) is a major disease of Atlantic salmon, Salmo salar, caused by an orthomyxovirus (ISAV). Increases in global aquaculture and the international movement of fish made it important to determine if Pacific salmon are at risk. Steelhead trout, Oncorhynchus mykiss, and chum, O. keta, Chinook, O. tshawytscha, coho, O. kisutch, and Atlantic salmon were injected intraperitoneally with a high, medium, or low dose of a Norwegian strain of ISAV. In a second challenge, the same species, except chum salmon, were injected with a high dose of either a Canadian or the Norwegian strain. Average cumulative mortality of Atlantic salmon in trial 1 was 12% in the high dose group, 20% in the medium dose group and 16% in the low dose group. The average cumulative mortality of Atlantic salmon in trial 2 was 98%. No signs typical of ISA and no ISAV-related mortality occurred among any of the groups of Oncorhynchus spp. in either experiment, although ISAV was reisolated from some fish sampled at intervals post-challenge. The results indicate that while Oncorhynchus spp. are quite resistant to ISAV relative to Atlantic salmon, the potential for ISAV to adapt to Oncorhynchus spp. should not be ignored. [source] An Assay for Evoked Locomotor Behavior in Drosophila Reveals a Role for Integrins in Ethanol Sensitivity and Rapid Ethanol ToleranceALCOHOLISM, Issue 10 2009Poonam Bhandari Background:, Ethanol induces similar behavioral responses in mammals and the fruit fly, Drosophila melanogaster. By coupling assays for ethanol-related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of the Drosophila model for investigating genes involved in ethanol-related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response. Methods:, We established eRING (ethanol Rapid Iterative Negative Geotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e., startle-induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol-related behaviors. Results:, Negative geotaxis measured in eRING assays was dose-dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across 4 control strains, but internal ethanol concentrations were indistinguishable in the 4 strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations in amnesiac and hangover, genes known to influence these traits. Additionally, mutations in the , integrin gene myospheroid and the , integrin gene scab increased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations. Conclusions:, The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the function of , and , integrins in flies. [source] Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for treatment of cows with experimentally induced Escherichia coli mastitisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2002M. Rantala Efficacy and pharmacokinetics of enrofloxacin and flunixin meglumine for treatment of cows with experimentally induced Escherichia coli mastitis. J. vet. Pharmacol. Therap.25, 251,258. The efficacy of flunixin alone and together with enrofloxacin in treatment of experimental Escherichia coli mastitis was compared using six cows. The cross-over study design was used. Pharmacokinetics of flunixin and enrofloxacin were also studied in these diseased cows. The response of each cow was similar after the first and second challenge and the individual reaction seemed to explain the severity of clinical signs. The most important predictive factor for outcome of E. coli mastitis was a heavy drop in milk yield. Treatment with enrofloxacin and flunixin enhanced elimination of bacteria, but the difference from those receiving flunixin alone was not significant. Two cows, which had received no antimicrobial treatment (Group 1), were killed on day 4 postchallenge. One cow was killed after the first and the other after the second challenge. Cows receiving combination therapy produced 0.9 L more milk per day during the study period than cows which had only received flunixin (P< 0.05). Based on our findings, antimicrobial treatment might be beneficial in the treatment of high-yielding cows in early lactation. The absorption of enrofloxacin was delayed after subcutaneous administration, the mean apparent elimination half-life being about 23 h, whereas after i.v. administration elimination t1/2 was only 1.5 h. The majority of the antimicrobial activity in milk originated from the active metabolite, ciprofloxacin, which could be measured throughout the 120-h follow-up period after the last subcutaneous administration. No differences were present in the pharmacokinetic parameters of flunixin between treatment groups: mean elimination half-life was 5.7,6.2 h, volume of distribution 0.43,0.49 L/kg and clearance 0.13,0.14 L h/kg. No flunixin or merely traces were detected in milk: one of the three cows had a concentration of 0.019 mg/L 8 h after administration. [source] Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bitesMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2001R. J. Probst Summary Leishmaniasis research needs a near-human model for investigations of natural infection processes, immunological responses and evaluation of treatments. Therefore, we developed a reproducible system using Leishmania major Yakimoff & Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Macaca mulatta (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of experimentally infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of presumed Indian origin (Leishmania naïve) were exposed to bites of female sandflies that had been infected with L. major by membrane-feeding on human blood seeded with amastigotes isolated from hamster footpad lesions. Infection rates of membrane-fed sandflies averaged >,85% seven days after the infective feed, with uniformly high numbers of promastigotes in the stomodaeal valve region of the sandfly gut. Nodules and ulcerating dermal lesions developed on 7/8 monkeys 2,4 weeks post-bite and persisted for 3,7 months. Monkeys also developed satellite lesions beyond the area of sandfly bites on the head, but not on the chest. Three re-challenged monkeys developed lesions that healed faster than lesions from their primary challenges. After infection, monkeys developed delayed type hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens (LSTA) and, when tested by ELISA and IFA, showed significant post-infection antibody titres which typically rose for ,170 days and then gradually receded during the next 100 days following the first challenge. After the second challenge, antibody titres spiked higher within ,50 days and receded more rapidly. In contrast, four rhesus macaques of Chinese origin developed no lesions following infected sandfly bites, although they raised antibodies and LSTA reactions, indicating subclinical infection. [source] Promoting evidence-based psychosocial care for cancer patients,PSYCHO-ONCOLOGY, Issue 1 2009Paul B. Jacobsen Abstract With numerous studies demonstrating that psychosocial care reduces distress and improves quality of life, practitioners have an obligation to treat cancer patients in a manner consistent with this evidence. Although the rationale is straightforward, major challenges exist in achieving the goal of translating research into clinical practice. One challenge has been the nature of the evidence, with many studies of psychosocial interventions characterized by poor methodological quality, absence of eligibility criteria specifying heightened distress, and minimal consideration of dissemination potential. A second challenge has been to make practitioners aware of relevant evidence. Targeted efforts at dissemination, such as the issuance of clinical practice guidelines and evidence-based recommendations and the distribution of intervention materials via the Internet, appear to be more effective than passive efforts in providing practitioners with useful information. Perhaps the most challenging aspect has been to persuade practitioners to change how they practice. One approach currently under development would allow practitioners and health-care organizations to perform self-evaluations of the quality of their psychosocial care based on review of medical records. Feedback showing quality of care to be less than optimal is likely to motivate change, especially if the quality indicators assessed are considered to be important and reliable and point to specific actions that can be taken. The use of evidence to promote changes in clinical practice represents one of the major ways in which the field of psycho-oncology can fully realize its potential to positively affect the lives of people with cancer. Copyright © 2008 John Wiley & Sons, Ltd. [source] Integrating art as a trans-boundary element in a radical innovation frameworkR & D MANAGEMENT, Issue 1 2010Christian Stüer Companies have learned that radical innovations (RIs) are a prerequisite to grow organically. However, companies struggle to identify and introduce RIs, as their inherent high uncertainties and novelty challenge established organisations and management routines. To address the first challenge, companies need to take a holistic approach and design a trans-boundary environment of creativity, trans-disciplinary and entrepreneurial spirit. This environment attracts and retains visionary people, fosters generation of new opportunities and cultivates adaptability. By adapting evaluation metrics for RI, setting up flexible processes, and promoting trans-disciplinary exchange, the second challenge can be addressed. Increased research has concentrated on several aspects of RI lately, but so far a combining framework is missing. Our paper bridges this gap by developing an improved theoretical framework, enhancing the existing literature and introducing art as a method to advance trans-disciplinary interchange. In a case-study approach, we have applied our framework to the research and development department of Vodafone Research and Development, Germany, as they integrate art methodically in their research and development process. Analysing their RI capabilities, we identify the trans-disciplinary exchange with artists as a novel initiator and driver of RI, which has not yet been adequately considered. [source] Emerging strategies for exploiting cannabinoid receptor agonists as medicinesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009Roger G Pertwee Mandarin translation of abstract Medicines that activate cannabinoid CB1 and CB2 receptor are already in the clinic. These are Cesamet® (nabilone), Marinol® (dronabinol; ,9 -tetrahydrocannabinol) and Sativex® (,9 -tetrahydrocannabinol with cannabidiol). The first two of these medicines can be prescribed to reduce chemotherapy-induced nausea and vomiting. Marinol® can also be prescribed to stimulate appetite, while Sativex® is prescribed for the symptomatic relief of neuropathic pain in adults with multiple sclerosis and as an adjunctive analgesic treatment for adult patients with advanced cancer. One challenge now is to identify additional therapeutic targets for cannabinoid receptor agonists, and a number of potential clinical applications for such agonists are mentioned in this review. A second challenge is to develop strategies that will improve the efficacy and/or the benefit-to-risk ratio of a cannabinoid receptor agonist. This review focuses on five strategies that have the potential to meet either or both of these objectives. These are strategies that involve: (i) targeting cannabinoid receptors located outside the blood-brain barrier; (ii) targeting cannabinoid receptors expressed by a particular tissue; (iii) targeting up-regulated cannabinoid receptors; (iv) targeting cannabinoid CB2 receptors; or (v) ,multi-targeting'. Preclinical data that justify additional research directed at evaluating the clinical importance of each of these strategies are also discussed. Mandarin translation of abstract [source] | ||||||||||