Development of a robotic cluster for automated and scalable cell therapy manufacturing

The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. Here, we present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster's expansion module was demonstrated by expanding human CD8+ T cells. The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

In de logistiek leven we van communicatie : Communiceren in de logistieke sector: wat wordt verwacht van een beginnend logisticus?

Wat verwacht de beroepspraktijk van logistieke starters als het gaat om communicatieve competentie? In een exploratieve studie is in beeld gebracht welke rol communicatie speelt in de werkzaamheden van de logistieke starter, welke communicatieve producten de logistieke starter moet beheersen, welke kwaliteitseisen de leidinggevenden daaraan stellen en hoe belangrijk communicatief competent zijn is in de beroepspraktijk. Dit onderzoek maakt deel uit van een groter verkennend onderzoek van het lectoraat Human Communication Development van de HAN naar de communicatieve aspecten van FEM-afgestudeerden in diverse sectoren (accountancy, logistiek en rechten). Dit artikel beschrijft de resultaten van het onderzoek in de logistieke praktijk. Deze resultaten hebben geleid tot aanscherping van de Body of Knowledge and Skills (BoKS) op het gebied van communicatie voor logistici. Deze BoKS ondersteunt HRM-professionals en onderwijsontwikkelaars bij het gericht verbeteren van de communicatieve competentie van (aankomend) logistieke professionals

De communicatief competente professional in de ogen van managers: Een kwalitatieve exploratie als input voor curriculumontwikkeling

The communicative competent professional from a managerial perspective. A qualitative exploration is input for curriculum development. Research indicates that the communicative performance of starting professionals does not always match managers' expectations, although managers rate communication as important for their professional success. lnstitutes of higher education have the task of designing educational programmes that prepare students to meet the professional challenges concerning their communication. This article explores what managers themselves define as good professional communication. Their practical definitions of communicative competence were investigated through 44 semi-structured interviews in four professional business contexts (accountancy, communication, legal, and logistics). The research focused on the communicative competence of starting professionals and revealed (1) that communication is inextricably bound with the start¡ng professionals' work, (2) what specific genres starting professionals use, (3) that the quality requirements managers impose concern both text craftsmanship and contextual awareness and, (4) that managers rate communicative competence as important for organisations and starting professionals themselves. This implies that professional communication should play a prominent role in the curriculum with more focus on strategic communication awareness in relation to professional practically-oriented tasks. This will prepare students more effectively to meet managers' expectations regarding communication

Detection of Microchimerism by Minor Histocompatibility Antigen HA-1 Allele-Specific Nested Polymerase Chain Reaction

AbstractMinor histocompatibility antigens (mHags) can induce T-cell reactivities with important consequences for the graft-versus-leukemia effect and the development of graft-versus-host disease in HLA-matched stem cell transplantation settings. Recently, mHag-specific T cells were also demonstrated in multiparous woman and in solid organ transplant recipients. Microchimeric cells have been detected in the latter settings. To study whether microchimerism is instrumental in the induction and/or maintenance of mHag T cells, we developed an HA-1 allele-specific nested polymerase chain reaction. To optimize and validate the reliability of this method at different levels of microchimerism, serial dilutions of HA-1H cells titrated into HA-1R cells were tested. We demonstrated that the HA-1H allele can be reliably and consistently detected at concentrations as low as 1:105 without losing specificity. The developed HA-1-specific nested polymerase chain reaction is an important tool that facilitates the detection of HA-1 microchimerism in various clinical specimens and that promotes investigation of the effects of microchimerism on induction of mHag-specific T cells in the various settings of immunization

Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy

Clinical responses of solid tumors after allogeneic human leukocyte antigen-matched stem cell transplantation (SCT) often coincide with severe graft-versus-host disease (GVHD). Targeting minor histocompatibility antigens (mHags) with hematopoiesis- and cancer-restricted expression, for example, HA-1, may allow boosting the antitumor effect of allogeneic SCT without risking severe GVHD. The mHag HA-1 is aberrantly expressed in cancers of most entities. However, an estimated 30% to 40% of solid tumors do not express HA-1 (ie, are HA-1(neg)) and cannot be targeted by HA-1-specific immunotherapy. Here, we investigated the transcriptional regulation of HA-1 gene expression in cancer. We found that DNA hypermethylation in the HA-1 promoter region is closely associated with the absence of HA-1 gene expression in solid tumor cell lines. Moreover, we detected HA-1 promoter hypermethylation in primary cancers. The hypomethylating agent 5-aza-2'-deoxycytidine induced HA-1 expression only in HA-1(neg) tumor cells and sensitized them for recognition by HA-1-specific cytotoxic T lymphocytes. Contrarily, the histone deacetylation inhibitor trichostatin A induced HA-1 expression both in some HA-1(neg) tumor cell lines and in normal nonhematopoietic cells. Our data suggest that promoter hypermethylation contributes to the HA-1 gene regulation in tumors. Hypomethylating drugs might extend the safe applicability of HA-1 as an immunotherapeutic target on solid tumors after allogeneic SC

Replication Data for: SARS-CoV-2 Omicron Variant of Concern in Seychelles: Introduction and Spread

This is a replication dataset for the manuscript titled: "SARS-CoV-2 Omicron Variant of Concern in Seychelles: Introduction and Spread." The study is part of a regional collaborative COVID-19 public health rapid response initiative overseen by WHO-AFRO and Africa-CDC do decribe the SARS-CoV-2 genomic epidemiology in Africa. Data package includes R and python scripts used to analyze data: Figure1.R - This r code plots the Seychelles government intervention levels, number of daily COVID-19 cases, the temporal patterns of SARS CoV-2 Lineages in Seychelles. Figure2.R - This r code plots the Omicron lineages phylogenetic tree of BA.1-like, BA.1-like, BA.1-like, BA.1-like lineages. Figure3.R Figure4.R - This r code plots the number of transition events between Seychelles and the rest of world. SuppFig1.R - This r code plots the number of daily COVID-19 cases from March 2020 to September 2022 and highlights the period when Omicron VOC was circulating. SuppFig2.R - This r code plots the number of transition events between discrete locations i.e within Seychelles AncestralChanges.py </ol