Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline

Background: While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS. Objective: To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project. Methods: An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings. Results: We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM). Conclusion: Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages. Keywords: Autologous haematopoietic stem cell transplantation (AHSCT), multiple sclerosis, registry study, treatment recommendation

State Spaces -- The Locale Way

Verification of imperative programs means reasoning about modifications of a program state. So proper representation of state spaces is crucial for the usability of a corresponding verification environment. In this paper we discuss various existing state space models under different aspects like strong typing, modularity and scalability. We also propose a variant based on the locale infrastructure of Isabelle. Thus we manage to combine the advantages of previous formulations (without suffering from their disadvantages), and gain extra flexibility in composing state space components (inherited from the modularity of locales)

Investigation of Degradation Effects of DMFC MEAs in the First Few Days of Operation

The selection of fuel cell-components like GDL, membrane, catalyst etc. and also the operating conditions are important issues to reach high power density and superior reliability. However, degradation of the cell performance is a factor which hampers the fast commercialization of DMFCs. In DMFC investigations a dramatic loss in performance can often be detected even in the first few days of operation. The motivation of this investigation is to classify the degradation mechanisms. Performance degradation of fuel cells is partly reversible and partly irreversible. Different MEAs were investigated in single cell measurements with respect to their performance during the first days of operation. To characterize the processes in the cell U/I characteristics, EIS measurements and water balances were used. The investigations show that the conditions for a favorable water management changes with time which has major impact on the cell performance. A large part of the decline in performance can be avoided by changing operating conditions or by using modified MEAs. However, due to the irreversible part of degradation the decline in performance can not be avoided totally