Renormalization of Poincare Transformations in Hamiltonian Semiclassical Field Theory

Semiclassical Hamiltonian field theory is investigated from the axiomatic point of view. A notion of a semiclassical state is introduced. An "elementary" semiclassical state is specified by a set of classical field configuration and quantum state in this external field. "Composed" semiclassical states viewed as formal superpositions of "elementary" states are nontrivial only if the Maslov isotropic condition is satisfied; the inner product of "composed" semiclassical states is degenerate. The mathematical proof of Poincare invariance of semiclassical field theory is obtained for "elementary" and "composed" semiclassical states. The notion of semiclassical field is introduced; its Poincare invariance is also mathematically proved.Comment: LaTeX, 40 pages; short version of hep-th/010307

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Interstitial Cystitis / Bladder Pain Syndrome: factors predicting the clinical course of the disease

Introduction. Etiology of the Bladder pain syndrome/Interstitial cystitis (BPS/IC) remains completely unknown. BPS/ IC is a chronic disease in which bladder biopsy specimens show varying degrees of inflammation`s severity, detrusor fibrosis and mastocytosis. With BPS/IC, cellular mechanisms of inflammation and processes leading to tissue damage and fibrosis are still not entirely clear. However, the results of studies have shown that fibrosis and mastocytosis of the detrusor are associated with the need for various types of treatment and suggest the failure of standard therapy.Purpose of research. The aim of the study is to determine the relationship between the anatomical capacity of the bladder and detrusor fibrosis with the clinical course of BPS/IC.Materials and methods. 110 patients with BPS/IC were examined from 2010 to 2014 in the University Urological Clinic MSMU, A.I. Evdokimov Moscow State University of Medicine and Dentistry. Patients` pain severity was assessed by a 10-point Visual Analogue Pain scale (VAS). Clinical manifestations of the disease were assessed using international questionnaires: an index of symptoms and quality of life of patients with interstitial cystitis (Interstitial Cystitis Symptom and Problem Indexes; ICSI, ICPI) and scales of symptoms of pelvic pain, urgency and frequency of urination (the Urine and Frequency Questionnaire, PUF), Female Sexual Dysfunction Index (FSDI), Hospital Anxiety and Depression Scale. All patients underwent cystoscopy with general anesthesia for therapeutic and diagnostic purposes. Bladder biopsy was performed in 36 patients (33%) for the treatment of other bladder`s diseases, as well as for the degree`s pathological assessment of the inflammatory process and the severity of detrusor fibrosis.Results. In 65% of patients, the anatomical capacity of the bladder was 200-350 ml, and in 5% of cases, its reduction to 100 ml was found. The average capacity of the bladder was 297 ± 90.2 ml. The results of the study suggest a significant decrease in the anatomical capacity of the bladder due to progressive inflammation and fibrosis in the bladder`s wall an essential factor affecting the clinical course of the BPS/IC, causing the severity of the organ-specific symptoms of the disease. A direct correlation was found between the indicators of the nature of alterative changes in urothelia, the severity of inflammatory infiltration and the severity of pain, symptoms of dysuria, in particular, frequency of urination and imperative urges, quality of life and mental health. The severity of fibrosis, the presence of perineuritis and mastocytosis are directly dependent on the duration of the disease.Conclusions. Reduced bladder capacity and detrusor fibrosis are markers of bladder damage in BPS/IC. These changes are characteristic of a certain patients` subgroup who require endovesical treatment, unlike patients with a systemic phenotype and comorbid conditions

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)