Red blood cells (RBCs) of the Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) in routine testing. RhD-positive (D+) RBC transfusion for Asian-type DEL patients has been proposed but has not been generally adopted due to a lack of direct evidence regarding its safety and underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in Asian-type DEL patients; none of the recipients (0/42; 95% confidence interval, 0%-8.40%) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4,045 serologic D- pregnant women throughout China; alloanti-D was found only in true D- individuals (2.63%, 79/3,009), but not in those with Asian-type DEL (0/1,032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs following transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in Asian-type DEL patients, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as NCT03727230.
In the scenario of mass customization, production is a crucial phase of the whole product life cycle. Production planning and scheduling must therefore evolve and adopt new tools that help to obtain a deeper control of what has to be produced in order to satisfy efficiently customer' needs. This is very important in the clothing and footwear (fashion) industry where customer's taste and choices change rapidly according to fashion dictates. In this paper an application in the footwear sector is presented and tested on a prototype of a new factory -an agile production unit -based on the concepts of agile and flexible production. The planning and scheduling module proposed is mainly focused on the short term in order to respond quickly to market needs and changes in a flexible manner. The module is composed of a finite capacity scheduler integrated with a new software based on the Analytical Hierarchy Process decision support system, which considers all the aspects related to order importance as complexity or urgency and assign each order a priority. This SW is able to take into account many intangible factors, as trademark, that are usually submitted to the subjective judge of the production manager (planner) and is completely configurable according to user' needs. The result of the elaboration, that is the priority value, constitutes a fundamental input for the scheduler in addition to the due date of the order. The scheduler has a daily horizon because it is unnecessary to cover a long-time period if things can change every day following market requirements. The scheduler is configured to create all cycle operations for each single item even in order to manage orders composed of one pair or even one single shoe. This is a fundamental condition under a custom-made production focus. This also allows operation fine control and monitoring of the manufacturing process because the control system can identify exactly where each item at each time is in the system. Concluding, further developments are considered within a more integrated ad extended scenario applied to the automated production system in a new project where the full product life cycle including the customer, retailer shop and suppliers are taken into consideration.
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