Improving a GMP manufacturing process is an important goal of a cell therapy lab. We have established an autologous adoptive T cell platform which involves the expansion of antigen specific T cells. ...While successful in manufacturing products for the first 5 patients in our phase 1 clinical trial, we have identified several key manufacturing steps to optimize. Additionally, future clinical trials that will utilize this manufacturing platform require even larger cell numbers. Here we demonstrate development of processes to both scale up our cell manufacturing and utilize both automation and modification of steps in the manufacturing process. We aimed to assess culturing these T cells in larger vessels, as well as potential freezing strategies for our final products while determining the impact these changes have on our product consistency.
PBMCs were isolated from a leukapheresis product from either healthy donors or multiple myeloma patients and cryopreserved. The PBMCs were thawed and seeded into 6-well G-Rex plates, 1L and/or 5L G-Rex vessels followed by stimulation and expansion of T cells. Growth kinetics were monitored in the 6-well plates with cells harvested on days 5, 9, 12, 15 and 19 and evaluated by flow cytometry for CD45, CD3, CD4, and CD8 and viability using 7-AAD. Supernatants were harvested from 6-well plates on days 5, 7, 9, 12, 15, and 19, and from the 1L and 5L cultures on days 7, 9, 12, 15, and 19 and evaluated for metabolites. Final T cells were frozen in vials in either CS5 or CS10. For single cell analysis, cells were thawed and recovered overnight in media. CD8+ and CD4+ cells were magnetically selected. Unstimulated or stimulated cells with either PMA/Ionomycin or CD3/28 were stained and then loaded onto the Adaptive Immune Cell chips, run on the Isolight, and analyzed with the IsoSpeak software.
The viability of the final T cell product was minimally affected by the different freezing media, however it was the PSI of the CD4+ T cells upon stimulation was reduced with CS5 media. Additionally, using the same cell seeding density, the 5L vessel resulted in reduced cell numbers. Based on our data, we hypothesize that the larger the vessel, the more time cells need to reach maximum cell capacity. We also postulate that monitoring of lactate during culture will allow the best timing to harvest the final product. Additionally, the different concentrations of DMSO in frozen samples can affect the polyfunctionality of the product.
Landfill leachate is a type of complex organic wastewater, which can easily cause serious negative impacts on the human health and ecological environment if disposed improperly. Electrochemical ...technology provides an efficient approach to effectively reduce the pollutants in landfill leachate. In this review, the electrochemical standalone processes (electrochemical oxidation, electrochemical reduction, electro-coagulation, electro-Fenton process, three-dimensional electrode process, and ion exchange membrane electrochemical process) and the electrochemical integrated processes (electrochemical-advanced oxidation process (AOP) and biological electrochemical process) for landfill leachate treatment are summarized, which include the performance, mechanism, application, existing problems, and improvement schemes such as cost-effectiveness. The main objective of this review is to help researchers understand the characteristics of electrochemical treatment of landfill leachate and to provide a useful reference for the design of the process and reactor for the harmless treatment of landfill leachate.
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•Electrochemical processes for landfill leachate treatment•Advantages and shortcomings of electrochemical processes•Improvement schemes of electrochemical processes•Future research needs on landfill leachate electrochemical treatment
Problems in manufacturing have always been a hurdle for leadership, engineers, and professionals. They can lead to low productivity, poor quality, high costs, and ultimately loss of customers. ...Problems should be prevented by fair means and following well-established methodologies of continuous process improvement. The present paper addresses this topic, which in both academic and professional literature has been discussed from one single angle–that is, how to use a specific methodology in a certain situation. From that perspective, researchers from academia and consultancy promote the use of a particular method. One of the greatest challenges to researchers and practitioners in manufacturing is to select the right methodology for problem-solving and process improvement. The present paper attempts to address this issue from a literature review perspective. The approach followed is based on the fact that understanding the attributes of process improvement methodologies reported in the open literature and their linkages to the main phases of the continuous improvement process will provide insights on how the selection of the methodologies can be carried out in real manufacturing situations.
Although numerous studies have discussed the importance of the relationship between knowledge management and software process improvement (SPI), a research gap still exists in relation to how the ...specific role of knowledge sharing influences successful SPI implementation. This study advances our knowledge by developing an innovative model for exploring the impact of knowledge sharing on SPI success, the impact of knowledge sharing in specific organizational cultures, and how the support of top management specifically influences the path to SPI success. To empirically test the model, this study adopts the statistical technique of partial least squares (PLS) to analyze 118 samples collected from SPI-certified Taiwanese organizations. The results suggest that clan-type organizational culture has a stronger association with knowledge sharing than hierarchy-type in the context of SPI success. SPI knowledge sharing is found to be a mediator of both clan culture and top management support in the context of SPI success. The findings also include the implication to improve our knowledge about how organizational culture and top management support drive effective knowledge sharing on the way to SPI success.
•SPI relies on human behavior of knowledge sharing, culture & top mgt. support.•This study determines how these factors influence SPI; specifically it shows that.•Clan-type culture is significant to knowledge sharing in SPI context.•How top mgt. support may place influence on the path to SPI success.
Background
We implemented a multi-disciplinary process improvement intervention at our Comprehensive Stroke Center with speech/language pathologists to expedite oral medication delivery in stroke ...patients. Following a failed nursing dysphagia screen, trained neurology physicians screened dysphagia further to approve use of oral medications. We analyzed the safety and efficacy of this intervention.
Methods
We analyzed retrospectively collected data for hospital course, timing of first screen, first oral medication use, and complications (e.g., aspiration pneumonia) in consecutive ischemic stroke patients (9/2019-07/2021). Patients were included if they passed a dysphagia assessment by physicians (Ph), nurses (RN), or speech/language pathologists (SLP). Arrival-to-dysphagia screen and arrival-to-antithrombotic were assessed using restricted mean survival time (RMST).
Results
Of the 789 included patients, 673 were passed by RN, 104 by SLP, and 12 by Ph. Compared to patients passed by SLP, those passed by Ph were younger and had less severe deficits (P < .01 for both). Patients were screened more quickly by Ph than RN or SLP (median 38 vs 182 vs 1330-min post-arrival, P = .0001; 299-min RMST difference vs RN 95%CI 22-575, P = .03; 470-min RMST difference vs SLP 95%CI 175-765, P = .002). This translated to faster oral antithrombotic use for Ph-passed patients (138-min RMST difference vs RN 95%CI 59-216; 332-min RMST difference vs SLP 95%CI 253-411). No patients passed by Ph experienced aspiration pneumonia (0%).
Conclusions
We safely conducted a physician-driven dysphagia screening paradigm which led to faster oral antithrombotic delivery without signal of patient harm. Physician availability to complete dysphagia screens in acute stroke patients was a limitation.
The role of analytics in operations and supply chain management (OSCM) has gained significant importance due to the decision-making complexities in the current business environment. The effectiveness ...of most analytical approaches, in turn, relies on access to timely and accurate data and information. Hence, it is essential for OSCM students to understand the underlying processes and dynamics of information management, for which enterprise resource planning (ERP) systems have become a standard. This case study can be a useful resource for introducing the critical interface between OSCM and information systems. The case study aims to facilitate learning on (1) the limitations of a rudimentary and disconnected information system, (2) the benefits and challenges of ERP implementation, and (3) the important steps to ensure a successful implementation of an ERP system. It provides an interesting context of a fast-growing agribusiness producing regulated products in Canada. The case study has been used in OSCM and management information systems (MIS) courses in two Canadian public Universities. Funding: This work was supported by Mitacs Grants IT28747 and IT32722. Supplemental Material: The Teaching Note and data files are available at https://www.informs.org/Publications/Subscribe/Access-Restricted-Materials .
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