Merging Data with Modeling: An Example from Fatigue.

It is well known that errors are inevitable in experimental observations, but it is equally unavoidable to eliminate errors in modeling the process leading to the experimental observations. If estimation and prediction are to be done with reasonable accuracy, the accumulated errors must be adequately managed. Research in fatigue is challenging because modeling can be quite complex.

Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis: Long-term follow-up of a Phase II randomised clinical trial with a cerebrospinal fluid sub-study.

Background: Evobrutinib - an oral, central nervous system (CNS)-penetrant, and highly selective Bruton's tyrosine kinase inhibitor - has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS.

Objective: Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal fluid (CSF) sub-study.

Methods: In the 48-week double-blind period (DBP), patients received evobrutinib 25 mg once-daily, 75 mg once-daily, 75 mg twice-daily or placebo (switched to evobrutinib 25 mg once-daily after week 24).

The effect of disease modifying therapies on fatigue in multiple sclerosis.

Introduction: Fatigue is one of the most common and debilitating symptoms in people with multiple sclerosis (PwMS). Disease-modifying therapies (DMTs) are currently the gold standard in the treatment of MS and their effectiveness has been assessed through randomized clinical trials (RCTs). However, there is limited evidence on the impact of DMTs on fatigue in (PwMS).

Static and group-based trajectory analyses of factors associated with non-adherence in patients with multiple sclerosis newly-initiating once- or twice-daily oral disease-modifying therapy.

Background: Increased understanding of adherence may facilitate optimal targeting of interventions.

Objective: To utilize group-based trajectory modeling (GBTM) to understand longitudinal patterns of adherence and factors associated with non-adherence in patients with multiple sclerosis (MS) newly-initiating once-/twice-daily oral disease-modifying therapy (DMT) (fingolimod, dimethyl fumarate, or teriflunomide).

Methods: Commercial plan data were analyzed using proportion of days covered (PDC) to evaluate factors associated with non-adherence.

Algebra of diffeomorphism-invariant observables in Jackiw-Teitelboim gravity.

In this paper we use the covariant Peierls bracket to compute the algebra of a sizable number of diffeomorphism-invariant observables in classical Jackiw-Teitelboim gravity coupled to fairly arbitrary matter. We then show that many recent results, including the construction of traversable wormholes, the existence of a family of SL(2 ℝ) algebras acting on the matter fields, and the calculation of the scrambling time, can be recast as simple consequences of this algebra. We also use it to clarify the question of when the creation of an excitation deep in the bulk increases or decreases the boundary energy, which is of crucial importance for the "typical state" versions of the firewall paradox.