Response to ibudilast treatment according to progressive multiple sclerosis disease phenotype

OBJECTIVE: Determine whether a treatment effect of ibudilast on brain atrophy rate differs between participants with primary (PPMS) and secondary (SPMS) progressive multiple sclerosis. BACKGROUND: Progressive forms of MS are both associated with continuous disability progression. Whether PPMS and SPMS differ in treatment response remains unknown. DESIGN/METHODS: SPRINT-MS was a randomized, placebo-controlled 96-week phase 2 trial in both PPMS (n = 134) and SPMS (n = 121) patients. The effect of PPMS and SPMS phenotype on the rate of change of brain atrophy measured by brain parenchymal fraction (BPF) was examined by fitting a three-way interaction linear-mixed model. Adjustment for differences in baseline demographics, disease measures, and brain size was explored. RESULTS: Analysis showed that there was a three-way interaction between the time, treatment effect, and disease phenotype (P \u3c 0.06). After further inspection, the overall treatment effect was primarily driven by patients with PPMS (P \u3c 0.01), and not by patients with SPMS (P = 0.97). This difference may have been due to faster brain atrophy progression seen in the PPMS placebo group compared to SPMS placebo (P \u3c 0.02). Although backward selection (P \u3c 0.05) retained age, T2 lesion volume, RNFL, and longitudinal diffusivity as significant baseline covariates in the linear-mixed model, the adjusted overall treatment effect was still driven by PPMS (P \u3c 0.01). INTERPRETATION: The previously reported overall treatment effect of ibudilast on worsening of brain atrophy in progressive MS appears to be driven by patients with PPMS that may be, in part, because of the faster atrophy progression rates seen in the placebo-treated group

The open-air site of Tolbor 16 (Northern Mongolia): Preliminary results and perspectives.

Numerous questions remain regarding the timing and the context of Upper Paleolithic emergence in Northeast Asia. Available data allow the recognition of a form of Initial Upper Paleolithic (IUP) documented in the Altai circa 45e40 ka 14C BP, and in the Cis- and Transbaikal around �37 ka 14C BP. In Northern Mongolia, a series of assemblages show intriguing similarities with IUP laminar assemblages from South Siberia and suggest long distance contact/movements of population during the first half of MIS3. These contacts are potentially enabled by the main river that drains into Lake Baikal, the Selenga. By cutting through the Sayan and the Yablonovy mountain ranges, the Selenga drainage system provides a potential corridor connecting South Siberia with the plains of Mongolia. The Tolbor 16 site (Ikh Tulberiin Gol, Northern Mongolia) is located circa 13 km from the confluence with the Selenga. The first results presented here suggest that the lithic assemblage and the ornaments discovered at Tolbor 16 document the early appearance of Upper Paleolithic in the region. This newly discovered site offers the possibility to generate high-resolution contextual data on the first appearance of the blade assemblages in Mongolia and to test the ‘Selenga corridor hypothesis’

Evidence for the 125 GeV Higgs boson decaying to a pair of tau leptons

Peer reviewe

Search for massive resonances in dijet systems containing jets tagged as W or Z boson decays in pp collisions at √s=8 TeV

Peer reviewe

Measurement of the t-channel single-top-quark production cross section and of the |V tb| CKM matrix element in pp collisions at √s = 8 TeV

Peer reviewe

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

Peer reviewe

Observation of the diphoton decay of the Higgs boson and measurement of its properties

Peer reviewe

Search for standard model production of four top quarks in the lepton + jets channel in pp collisions at √s = 8 TeV

Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: A search is presented for standard model (SM) production of four top quarks (Formula presented.) in pp collisions in the lepton + jets channel. The data correspond to an integrated luminosity of 19.6 fb−1 recorded at a centre-of-mass energy of 8 TeV with the CMS detector at the CERN LHC. The expected cross section for SM (Formula presented.) production is (Formula presented.). A combination of kinematic reconstruction and multivariate techniques is used to distinguish between the small signal and large background. The data are consistent with expectations of the SM, and an upper limit of 32 fb is set at a 95% confidence level on the cross section for producing four top quarks in the SM, where a limit of 32 ± 17 fb is expected