Institute Merieux

Sainte-Foy-lès-Lyon, France

Institute Merieux

Sainte-Foy-lès-Lyon, France
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Calder P.C.,University of Southampton | Boobis A.,Imperial College London | Braun D.,Institute Merieux | Champ C.L.,University of Leeds | And 8 more authors.
Nutrition Research Reviews | Year: 2017

The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers. Copyright © The Authors 2017 This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestrictedre-use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cesari M.,French Institute of Health and Medical Research | Cesari M.,Institut Universitaire de France | Fielding R.A.,Tufts University | Pahor M.,University of Florida | And 18 more authors.
Journal of Cachexia, Sarcopenia and Muscle | Year: 2012

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7-8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject. © 2012 Springer-Verlag.


Albers R.,Unilever | Bourdet-Sicard R.,Danone Inc. | Braun D.,Institute Merieux | Calder P.C.,University of Southampton | And 11 more authors.
British Journal of Nutrition | Year: 2013

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being. © [2013] ILSI Europe.


Calder P.C.,University of Southampton | Ahluwalia N.,University of Paris 13 | Albers R.,Unilever | Bosco N.,Nestlé | And 13 more authors.
British Journal of Nutrition | Year: 2013

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation. Copyright © ILSI Europe 2013.


Zarski J.-P.,Grenoble University Hospital Center | Zarski J.-P.,French Institute of Health and Medical Research | Sturm N.,French Institute of Health and Medical Research | Sturm N.,Grenoble University Hospital Center | And 8 more authors.
Liver International | Year: 2010

Background: The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. Aim: The aim was to evaluate the efficiency of 2 years of treatment with peginterferon α-2a vs α-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. Method: Hundred and five HCV patients with a Metavir fibrosis score≥2 were randomized to receive peginterferon α-2a 180 μg/week (PEG) (n=55) or α-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. Results: There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. Conclusion: Long-term therapy with peginterferon α-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with α-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials. © 2010 John Wiley & Sons A/S.


Gonzalez M.,University of Strasbourg | Jegu J.,University of Strasbourg | Kopferschmitt M.-C.,University of Strasbourg | Donnay C.,University of Strasbourg | And 8 more authors.
Clinical and Experimental Allergy | Year: 2014

Introduction: An increased incidence of asthma has been reported among healthcare workers. The role of quaternary ammonium compounds (QACs), commonly used in cleaning/disinfection products, has not been clearly defined. The aim of this study was to analyse associations between asthma and occupational exposure to disinfectants, especially QACs. Methods: The study was performed on a stratified random sample of the various healthcare departments of 7 healthcare settings. The study included: questionnaire, physical examination and specific IgE assays. Occupational exposure assessment was performed by means of a work questionnaire, workplace studies and a review of products ingredients. Data were analysed by logistic regression. Results: Response rate was 77%; 543 workers (89% female) participated; 37.1% were registered nurses (RNs), 16.4% auxiliary nurses (ANs), 17.3% cleaners; 32.8% were atopic. 335 participants were exposed to QACs. Nursing professionals reported a significantly higher risk of reported physician-diagnosed asthma and, for RNs, of nasal symptoms at work than administrative staff working in healthcare sector. This risk was particularly marked during disinfection tasks and when exposure to QACs. Exposure to QACs increased significantly the risk of reported physician-diagnosed asthma and nasal symptoms at work (adjusted OR = 7.5 and 3.2, respectively). No significant association was found with other exposures such as latex glove use, chlorinated products/bleach or glutaraldehyde. Conclusion: RNs and ANs presented a higher risk of reported asthma than administrative staff. The highest risk was associated with tasks involving dilution of disinfection products by manual mixing, suggesting possible exposure to repeated peaks of concentrated products known to be strong respiratory irritants. Workplace interventions should be conducted to more clearly determine QAC exposure and improve disinfection procedures. © 2013 John Wiley & Sons Ltd.


Xiang Z.,University of Hong Kong | Liu Y.,University of Hong Kong | Zheng J.,University of Hong Kong | Liu M.,Guangzhou Medical College | And 13 more authors.
Cancer Cell | Year: 2014

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) after transplantation remains a serious and life-threatening complication. Herein we showed that the aminobisphosphonate pamidronate-expanded human Vγ9Vδ2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through γ/δ-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2-/-γc-/- mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded Vγ9Vδ2-T cells alone effectively prevented EBV-LPD in Rag2-/-γc-/- mice and induced EBV-LPD regression in EBV+ tumor-bearing Rag2-/-γc-/- mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of Vγ9Vδ2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through Vγ9Vδ2-T cell targeting. © 2014 Elsevier Inc.


Micol R.,Institute Pasteur Paris | Micol R.,University of Paris Descartes | Micol R.,Institute Merieux | Tajahmady A.,Mission nationale dexpertise et daudit hospitaliers | And 10 more authors.
PLoS ONE | Year: 2010

Background: Cryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/μl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients. Methods: A Markov decision tree was used to compare the following strategies at the time of HIV diagnosis: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/μl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US$ 2009) were from Cambodia. Efficacy data were from international literature. Results:In a population in which 81% of patients had a CD4+ count ≤50 cells/ ml and 19% a CD4+ count between 51-100 cells/μl, the proportion alive 1 year after enrolment was 61% (cost $ 472) with no intervention, 70% (cost $ 483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of follow-up, the cost-effectiveness of screening vs. no intervention was US$ 180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated at $1538/LYG if the proportion of patients with CD4+ count ≤50 cells/μl decreased by 75%. Conclusion:In a high endemic area of cryptococcosis and HIV infection, serum CRAG screening and prophylaxis are two cost effective strategies to prevent AIDS associated cryptococcosis in patients with CD4+ count ≤100 cells/μl, at a short-term horizon, screening being more cost-effective but less effective than prophylaxis. Systematic primary prophylaxis may be preferred in patients with CD4+ below 50 cells/μl while systematic serum CRAG screening for early targeted treatment may be preferred in patients with CD4+ between 51-100 cells/μl. © 2010 Micol et al.

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