A Contribution of the Trivial Connection to Jones Polynomial and Witten's Invariant of 3d Manifolds I

We use the Chern-Simons quantum field theory in order to prove a recently conjectured limitation on the 1/K expansion of the Jones polynomial of a knot and its relation to the Alexander polynomial. This limitation allows us to derive a surgery formula for the loop corrections to the contribution of the trivial connection to Witten's invariant. The 2-loop part of this formula coincides with Walker's surgery formula for Casson-Walker invariant. This proves a conjecture that Casson-Walker invariant is a 2-loop correction to the trivial connection contribution to Witten's invariant of a rational homology sphere. A contribution of the trivial connection to Witten's invariant of a manifold with nontrivial rational homology is calculated for the case of Seifert manifolds.Comment: 28 page

Impaired Sweating Responses to a Passive Whole-body Heat Stress in Individuals with Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), disrupting autonomic function. PURPOSE: The aim of this study was to test the hypothesis that individuals with MS have blunted control of thermoregulatory reflex increases in sweat rate (SR) and cutaneous vasodilation compared to controls during a passive whole-body heat stress (WBH). METHODS: Eighteen individuals with relapsing-remitting MS and 18 healthy controls (CON) participated in the study. Core temperature (Tcore), skin temperature, heart rate, arterial blood pressure (10 min intervals), skin blood flow (laser-Doppler flowmetry: LDF), and SR were continuously measured during normothermic baseline (34 °C water perfusing a tube-lined suit) and WBH (increased Tcore 0.8 °C via 48 °C water perfusing the suit). Following WBH, local heaters were warmed to 42 °C, inducing maximal cutaneous vasodilation at the site of LDF collection. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to mean arterial pressure and expressed as a percentage of maximum. RESULTS: Individuals with MS had attenuated SR responses to WBH (∆SR from baseline: CON: 0.65±0.27; MS: 0.42±0.17 mg/cm2/min, p=0.003), while ∆%CVCmax from baseline was similar between groups (CON: 42±16%; MS: 38±12 %, p=0.39). SR responses were blunted as a function of Tcore in MS (interaction: group*Tcore,p=0.03), of which differences were evident at ∆Tcore 0.7 °C and 0.8 °C (p\u3c0.05). No interaction was observed in ∆%CVCmax. CONCLUSION: Taken together, MS blunts sweating responses, while control of the cutaneous vasculature is preserved in response to WBH

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects