13 research outputs found

    Reaping the benefits of Business2030

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    Climate activist Greta Thunberg’s Fridays for Future and the Plastic-Free Challenge are just two examples of disruptive social movements that marked the year 2019. These social movements, along with others like them, are relevant to business organizations since they aim to address environmental challenges to meet consumer preferences

    Fixing the business of food. How to align the agrifood sector with the SDGs

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    The Report uncover that in order to support the transformation to more sustainable and healthier food systems, a change in business practices is required, as well as more harmonised and comparable monitoring and reporting standards to support companies as they set ambitious targets in terms of the Four Pillars Framework

    Prognostic Factors Influencing Tumor Response, Locoregional Control and Survival, in Melanoma Patients with Multiple Limb In-transit Metastases Treated with TNF alpha-based Isolated Limb Perfusion

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    Background: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNF alpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNF alpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable close (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNF alpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFa was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNF alpha-based ILP and identify prognostic factors for response, locoregional control and survival. Patients and Methods: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>= 10 nodules :53 cm or fewer nodules with a diameter > 3 cm) in 42.5% of the patients and unresectable in 33%. Forty patients were treated with a TNFa dosage of > 1 mg and 73 with 1 mg. Patients with tumors in the tipper and lower limbs were submitted to ILP via axillary and iliac vessels, respectively. TNF alpha was injected in the arterial line of an extracorporeal circuit at the pre-established close, followed by melphalan (13 and 10 mg/l of limb volume for the upper and lower limbs, respectively) 30 minutes later. Results: Complete responses (CR) and partial responses (PR) were 63% and 24.5%, respectively, with an objective response (OR) of 87.5%. No change (NC) was observed in only 12.5% of the patients. Upon multivariate analysis, only bulky disease maintained its independent value for tumor response with an odds ratio of 4.07 and a p-value of 0.02. The 5-year locoregional disease-free survival was 42.7%. Upon multivariate analysis, the only prognostic factors were stage, age and bulky disease. The 5-year overall survival was 49%. Multivariate analysis showed that only, sex, stage and CR maintained their independent values. Conclusion: TNF alpha-based ILP was proven to be an effective treatment for melanoma patients with in-transit metastases. The TNF alpha dosage of 1 mg was as effective as 3-4 mg, with lower toxicity and cost. We propose that TNF alpha and melphalan-based ILP should be employed for bulky tumors or after failure of melphalan-based ILP

    Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

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    Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) β and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2–specific seroconversion, and enrichment of some shared SARS-CoV-2–associated sequences. No significant age-related or disease severity–related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRβ and TCRδ loci, including some TCRβ sequence–sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection
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