Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Forest Management Cooperatives and Their Development Under Uncertain Conditions: A Comprehensive Analysis Using an Actor-Centered Institutionalism Approach

The change in forest ownership structures, the resulting fragmentation of forest properties and restitution processes have led to the emergence of organizations in Europe that are able to deal with these challenges. Changes in the timber selling process due to decisions of the German Federal Competition Authority have led first to uncertain conditions for forest management cooperatives (FMCs) and their members in the federal state of Baden-Wuerttemberg. In the course of this change, some FMCs have questioned their status quo while others have evolved under uncertain conditions. This paper aims to provide an overview of factors determining the further development of forest management cooperatives under uncertain conditions following the categories of actor-centered institutionalism (ACI). To be able to conduct a comprehensive political analysis of the changes taking place in the timber selling process, the ACI approach is used in conjunction with path dependency as the theoretical framework for this paper. Methodologically, it is based on a qualitative analysis of field protocols from four regional conferences in Baden-Wuerttemberg, Germany, involving a total of 140 participants in 2017. The results highlight that individual actors, the economic and social capabilities of FMCs, the existing constellations and interactions determine further developments under uncertainty. Legal certainty and in some cases the withdrawal of the state determine positively the dealing with uncertain situations. Foresters and their direction essentially determine the development. Furthermore, FMCs highlight that the cooperation with municipal foresters has a positive impact that will help deal with uncertainty in the future. A clear interest of cooperation and long-standing relationships also determine further developments under uncertain conditions