351 research outputs found

    Agronomical and environmental performances of organic farming in the Seine watershed, France

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    This work suggests that Soil Surface Balance is a robust indicator to compare the performances of organic agriculture with those of conventional agriculture, even strictly following the rules of rational and optimised application of fertilisers. The results of long term nitrogen budget calculation brought us to seriously reconsider the relevance of the need to increase crop yields, and more broadly to reconsider cropping patterns and production systems. In terms of policy levers for mitigating nitrogen contamination of water resources, only the shift to organic farming provides a possible way to reconcile agricultural production and water quality. Further, this view points out the need for specific measures to encourage more mixed farming approach to organic farming on a territorial basis, thus reversing a 50 years trend to regional specialization into either crop or livestock farming

    Use of textile waste as an addition in the elaboration of an ecological concrete block

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    The textile industry has grown significantly in recent years, reaching a global fiber production of 53 million tons which 12 % are recycled; Construction sector has been using more and more recycled materials from different industrial sources, to apply them in their constructions and to reduce CO2 emissions and final energy consumption. The present study aims to study the behavior of concrete blocks of fć= 210 kg/cm2 adding polyester textile waste with 3 %, 6 %, 9 %, 12 % and 15 %; void content, compressive strength and thermal conductivity decrease, and water absorption, acoustic insulation and unit price increase by 3 %, 34 % and 16 % compared to conventional concrete block

    A new agent for the treatment of noninfectious uveitis: rationale and design of three LUMINATE (Lux Uveitis Multicenter Investigation of a New Approach to Treatment) trials of steroid-sparing voclosporin

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    Uveitis is an inflammatory, putative Th1-mediated autoimmune disease that affects various parts of the eye and is a leading cause of visual loss. Currently available therapies are burdened with toxicities and/or lack definitive evidence of efficacy. Voclosporin, a rationally designed novel calcineurin inhibitor, exhibits a favorable safety profile, a strong correlation between pharmacokinetic and pharmacodynamic response, and a wide therapeutic window. The LUMINATE (Lux Uveitis Multicenter Investigation of a New Approach to TrEatment) clinical development program was initiated in 2007 to assess the safety and efficacy of voclosporin for the treatment, maintenance, and control of all forms of noninfectious uveitis. If LUMINATE is successful, voclosporin will become the first Food and Drug Administration-approved corticosteroid-sparing agent for this condition

    Hepatitis C Infection and Kidney Transplant Waiting Time Among End-Stage Renal Disease Patients

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    Kidney transplantation is identified as the ideal approach to managing end-stage renal disease (ESRD), yet access for some groups remains an ongoing concern. Research findings support the notion that hepatitis-C-infected ESRD patients benefit from kidney transplantation compared to those remaining on dialysis. Although the disparity in access to kidney transplantation has been well researched, the association between hepatitis C virus infection and kidney transplant waiting times among ESRD patients was unknown. The purpose of this quantitative retrospective study was to analyze the association between hepatitis C virus infection, blood type, and kidney transplant waiting times among ESRD patients when controlling for age, gender, race, work income, and health insurance coverage. Bronfenbrenner’s ecological systems theory was used as the theoretical foundation for this study. Secondary data were provided by the United Network for Organ Sharing for all kidney transplantations performed between January 1, 2010, and December 31, 2020 for adults 18 years of age and older. Kruskal-Wallis and bivariate regression tests demonstrated a significant association between blood type, age, race, and health insurance coverage and kidney transplant waiting times. The Social change implications are that findings may be used to implement programs to address the disparities limiting access to kidney transplantation among ESRD patients

    Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

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    Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group “PRISM”, tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer''s disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues

    Relating constructs of attention and working memory to social withdrawal in Alzheimer's disease and schizophrenia: issues regarding paradigm selection

    Get PDF
    Central nervous system diseases are not currently diagnosed based on knowledge of biological mechanisms underlying their symptoms. Greater understanding may be offered through an agnostic approach to traditional disease categories, where learning more about shared biological mechanisms across conditions could potentially reclassify sub-groups of patients to allow realisation of more effective treatments. This review represents the output of the collaborative group "PRISM", tasked with considering assay choices for assessment of attention and working memory in a transdiagnostic cohort of Alzheimer's disease and schizophrenia patients exhibiting symptomatic spectra of social withdrawal. A multidimensional analysis of this nature has not been previously attempted. Nominated assays (continuous performance test III, attention network test, digit symbol substitution, N-back, complex span, spatial navigation in a virtual environment) reflected a necessary compromise between the need for broad assessment of the neuropsychological constructs in question with several pragmatic criteria: patient burden, compatibility with neurophysiologic measures and availability of preclinical homologues

    Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration

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    PURPOSE: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. DESIGN: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). PARTICIPANTS: Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. METHODS: Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. MAIN OUTCOME MEASURES: The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. RESULTS: Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. CONCLUSIONS: Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation

    First-in-Human Gene Therapy Trial of AAV8-hCARp.hCNGB3 in Adults and Children With CNGB3-associated Achromatopsia

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    PURPOSE: To assess the safety and efficacy of AAV8-hCARp.hCNGB3 in participants with CNGB3-associated achromatopsia (ACHM). DESIGN: Prospective, phase 1/2 (NCT03001310), open-label, nonrandomized clinical trial. METHODS: The study enrolled 23 adults and children with CNGB3-associated ACHM. In the dose-escalation phase, adult participants were administered 1 of 3 AAV8-hCARp.hCNGB3 dose levels in the worse-seeing eye (up to 0.5 mL). After a maximum tolerated dose was established in adults, an expansion phase was conducted in children ≥3 years old. All participants received topical and oral corticosteroids. Safety and efficacy parameters, including treatment-related adverse events and visual acuity, retinal sensitivity, color vision, and light sensitivity, were assessed for 6 months. RESULTS: AAV8-hCARp.hCNGB3 (11 adults, 12 children) was safe and generally well tolerated. Intraocular inflammation occurred in 9 of 23 participants and was mainly mild or moderate in severity. Severe cases occurred primarily at the highest dose. Two events were considered serious and dose limiting. All intraocular inflammation resolved following topical and systemic steroids. There was no consistent pattern of change from baseline to week 24 for any efficacy assessment. However, favorable changes were observed for individual participants across several assessments, including color vision (n = 6/23), photoaversion (n = 11/20), and vision-related quality-of-life questionnaires (n = 21/23). CONCLUSIONS: AAV8-hCARp.hCNGB3 for CNGB3-associated ACHM demonstrated an acceptable safety and tolerability profile. Improvements in several efficacy parameters indicate that AAV8-hCARp.hCNGB3 gene therapy may provide benefit. These findings, with the development of additional sensitive and quantitative end points, support continued investigation
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