706 research outputs found

    Analyse a posteriori d'une démarche d'observatoire dans un contexte conflictuel : cas de l'irrigation en Charente

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    La situation de l'irrigation en Poitou-Charentes est emblématique des tensions entre le monde agricole et la société. Pour dépasser ces conflits, un observatoire alliant système d'information et action collective a été mis en place en Charente à l'initiative d'un collectif regroupant responsables politiques, chercheurs et conseillers agricoles. Cet article a pour objectif de restituer l'analyse des différentes perspectives et attentes des acteurs ayant participé à l'élaboration de l'observatoire. L'analyse proposée s'appuie sur une enquête réalisée en 2006 auprès des acteurs concernés. Il en ressort un cadre que nous proposons d'utiliser lors de la conception d'observatoires afin d'expliciter la diversité des attentes des parties prenantes et de faciliter l'élaboration d'un accord préalable à leur mise en ½uvre. / Irrigation in Poitou-Charentes exemplifies the tensions that exist between agriculture and other societal sectors. To overcome these conflicts, a Community Information System (CIS) for the purpose of both data management and community development has been set up in Charente by a group of policymakers, researchers and agricultural advisers. This paper describes our analysis of the differences among participants in the development of this CIS in terms of their points of view and expectations. Drawing on an analysis of a set of interviews conducted with these stakeholders in 2006, we propose a framework for use during the initial design phase of a CIS to make stakeholder expectations explicit and to promote a shared understanding prior to setting up a CIS

    Preclinical evaluation of the gorilla-derived HAdV-B AdV-lumc007 oncolytic adenovirus 'GoraVir' for the treatment of pancreatic ductal adenocarcinoma

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    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, and immune-suppressive tumour microenvironment. Oncolytic virotherapy has emerged as a new treatment modality which uses tumour-specific viruses to eliminate cancerous cells. Non-human primate adenoviruses of the human adenovirus B (HAdV-B) species have demonstrated considerable lytic potential in human cancer cells as well as limited preexisting neutralizing immunity in humans. Previously, we have generated a new oncolytic derivative of the gorilla-derived HAdV-B AdV-lumc007 named ‘GoraVir’. Here, we show that GoraVir displays oncolytic efficacy in pancreatic cancer cells and pancreatic-cancer-associated fibroblasts. Moreover, it retains its lytic potential in monoculture and co-culture spheroids. In addition, we established the ubiquitously expressed complement receptor CD46 as the main entry receptor for GoraVir. Finally, a single intratumoural dose of GoraVir was shown to delay tumour growth in a BxPC-3 xenograft model at 10 days post-treatment. Collectively, these data demonstrate that the new gorilla-derived oncolytic adenovirus is a potent oncolytic vector candidate that targets both pancreatic cancer cells and tumour-adjacent stroma. Cellular mechanisms in basic and clinical gastroenterology and hepatolog

    Heart failure and the risk of stroke: the Rotterdam Study

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    Patients with heart failure used to have an increased risk of stroke, but this may have changed with current treatment regimens. We assessed the association between heart failure and the risk of stroke in a population-based cohort that was followed since 1990. The study uses the cohort of the Rotterdam Study and is based on 7,546 participants who at baseline (1990–1993) were aged 55 years or over and free from stroke. The associations between heart failure and risk of stroke were assessed using time-dependent Cox proportional hazards models, adjusted for cardiovascular risk factors (smoking, diabetes mellitus, BMI, ankle brachial index, blood pressure, atrial fibrillation, myocardial infarction and relevant medication). At baseline, 233 participants had heart failure. During an average follow-up time of 9.7 years, 1,014 persons developed heart failure, and 827 strokes (470 ischemic, 75 hemorrhagic, 282 unclassified) occurred. The risk of ischemic stroke was more than five-fold increased in the first month after diagnosis of heart failure (age and sex adjusted HR 5.79, 95% CI 2.15–15.62), but attenuated over time (age and sex adjusted HR 3.50 [95% CI 1.96–6.25] after 1–6 months and 0.83 [95% CI 0.53–1.29] after 0.5–6 years). Additional adjustment for cardiovascular risk factors only marginally attenuated these risks. In conclusion, the risk of ischemic stroke is strongly increased shortly after the diagnosis of heart failure but returns to normal within 6 months after onset of heart failure

    Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: Results from a randomized controlled trial (CONTRAST)

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    Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a prespecified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [20.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (22.52% [24.72 to 20.31]; P = 0.02 and 249 ng/mL [2103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [20.4 to 14.5]; P = 0.06). In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance

    Swallowing dysfunction in cancer patients

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    Purpose Dysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer. Methods The literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references. Results A wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer. Conclusions Swallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed

    Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography

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    Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden

    Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study

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    AIMS: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. METHODS: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. RESULTS: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (10 g per day, after adjusting for a range of confounding factors. CONCLUSION: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT

    Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

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    BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study
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