Children from high- and low-risk areas of Italy have incidence rates of T1D that are closer to those of their native regions than to those of German children, indicating that genetic factors play a predominant role in the pathogenesis of T1D.
Treatment with CD19-directed CAR T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune-effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30-40% of patients treated with axicabtagene ciloleucel (axi-cel), usually within the first 4 weeks post dosing, and usually responding well to steroids. Here, we describe a case of progressive central neurotoxicity occurring 9 months post axi-cel in a patient with r/r LBCL having undergone a prior alloHCT. Despite extensive systemic and intrathecal immunosuppression neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T cell DNA copy numbers and higly elevated levels of IL-1 and IL-6 were found in the CSF as clinical symptoms emerged, and CAR T cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected devastating late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.
The difference between the production cost and selling price of the products may be viewed as a criterion that determines an organization's competitiveness and market success. In such circumstances, it is necessary to impact these criteria in order to maximize this difference. The selling products' price, in modern market conditions, is a category which may not be significantly affected. So organizations have one option, which is the production cost reduction. This is the motive for business organizations and the imperative of each organization. The key parameters that influence the costs of production and therefore influence the competitiveness of organizations are the parameters of production machines and processes used to create products. To define optimal parameter values for production machines and processes that will reduce production costs and increase competitiveness of production organizations, the authors have developed a new mathematical model. The model is based on application of the ABC classification method to classify production line processes based on their costs and an application of a genetic algorithm to find the optimal values of production machine parameters used in these processes. It has been applied in three different modern production line processes; the costs obtained by the model application have been compared with the real production costs.
Abstract. The evaluation and enhancement of business processes in any organization in an uncertain environment presents one of the main requirements of ISO 9000:2008 and has a key effect on competitive advantage and long-term sustainability. The aim of this paper can be defined as the identification and discussion of some of the most important business processes of seaports and the performances of business processes and their key performance indicators (KPIs). The complexity and importance of the treated problem call for analytic methods rather than intuitive decisions. The existing decision variables of the considered problem are described by linguistic expressions which are modelled by triangular fuzzy numbers (TFNs). In this paper, the modified fuzzy extended analytic hierarchy process (FAHP) is proposed. The assessment of the relative importance of each pair of performances and their key performance indicators are stated as a fuzzy group decision-making problem. By using the modified fuzzy extended analytic hierarchy process, the fuzzy rank of business processes of a seaport is obtained. The model is tested through an illustrative example with real-life data, where the obtained data suggest measures which should enhance business strategy and improve key performance indicators. The future improvement is based on benchmark and knowledge sharing.
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