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Rituximab has been used to treat MS patients in Iceland for over a decade. However, long-term effect of rituximab on leukocyte populations has not yet been elucidated. By retrospective analysis of flow cytometric data from 349 patients visiting the neurological ward at The National University Hospital of Iceland from 2012 to 2023 for rituximab treatment, the long-term effect of rituximab and whether the effect was dose dependent (1000mg vs 500mg) was evaluated. No difference was detected in efficacy of B cell depletion in patients treated with 500mg as an initial dose of rituximab when compared to 1000mg. Long-term use of rituximab led to an increase in T cell count (p=0,0015) in patients receiving 3-8 doses of rituximab (1.5-8 years of treatment). The increase occurred in both CD4 + (p=0,0028) and CD8 + T cells (p=0,0015) and led to a decrease in the CD4/CD8 ratio (p=0,004). The most notable difference lies in reshaping the balance between näive and effector CD8 + T cells. The clinical implications of long-term treatment with rituximab and its effect on the T cell pool needs to be explored further. Since no difference in B cell depletion was detected between the two patient groups, 1000mg as an initial dose might be excessive, suggesting a personalized dosing regimen might have therapeutic and financial advantages., Competing Interests: SB and GB received support from the Icelandic student innovation fund. BL has received honoraria from Takeda, Pfizer and CSL Behring and has received payment from the Icelandic Medicines Agency for expert testimony. BL is the president of the Scandinavian Society for Immunology, Executive director of clinical research and associated services at Landspitali, Associate editor for the Scandinavian Journal of Immunology and a member of the board at Heilsustofnun Rehabilitation and Health Clinic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Björnsson, Sigurgrímsdóttir, Maggadóttir, Einarsdóttir, Sveinsson, Hjaltason, Sigurðardóttir, Lúðvíksson and Brynjólfsson.)

When is it fitting for an agent to feel guilt over an outcome, and for others to be morally indignant with her over it? A popular answer requires that the outcome happened because of the agent, or that the agent was a cause of the outcome. This paper reviews some of what makes this causal-explanatory view attractive before turning to two kinds of problem cases: cases of collective harms and cases of fungible switching. These, it is argued, motivate a related but importantly different answer. What is required for fitting guilt and indignation is that the agent is relevantly implicated in that outcome: that the agent's morally substandard responsiveness to reasons, or substandard caring, is relevantly involved in a normal explanation of it. This answer, it is further argued, makes sense because when an agent's substandard caring is so involved, the outcome provides a lesson against such caring, a lesson central to the function of guilt and indignation., (© The Author(s) 2021.)

The studies we report indicate that it is possible to manipulate explicit ascriptions of consciousness by manipulating whether an agent's behavior is deterministically caused. In addition, we explore whether this impact of determinism on consciousness is direct, or whether it is mediated by notions linked to agency - notions like moral responsibility, free will, deliberate choice, and sensitivity to moral reasons. We provide evidence of mediation. This result extends work on attributions of consciousness and their connection to attributions of agency by Adam Arico, Brian Fiala, and Shaun Nichols and supports it against recent criticisms., Competing Interests: Disclosure Statement No potential conflict of interest was reported by the authors.