Effectiveness of delayed-release dimethyl fumarate on patient-reported outcomes and clinical measures in patients with relapsing-remitting multiple sclerosis in a real-world clinical setting: PROTEC.

Ensaio clínico PROTEC, Protocolo nº 109MS408Abstract BACKGROUND: Patient-reported outcomes (PRO) and clinical outcomes give a broad assessment of relapsing-remitting multiple sclerosis (RRMS) disease. OBJECTIVE: The aim is to evaluate the effectiveness of delayed-release dimethyl fumarate (DMF) on disease activity and PROs in patients with RRMS in the clinic. METHODS: PROTEC, a phase 4, open-label, 12-month observational study, assessed annualized relapse rate (ARR), proportion of patients relapsed, and changes in PROs. Newly diagnosed and early MS (≤3.5 EDSS and ≤1 relapse in the prior year) patient subgroups were evaluated. RESULTS: Unadjusted ARR at 12 months post-DMF versus 12 months before DMF initiation was 75% lower (0.161 vs. 0.643, p < 0.0001) overall (n = 1105) and 84%, 77%, and 71% lower in newly diagnosed, ≤3.5 EDSS, and ≤1 relapse subgroups, respectively. Overall, 88% of patients were relapse-free 12 months after DMF initiation (84%, newly diagnosed; 88%, ≤3.5 EDSS; 88%, ≤1 relapse). PRO measures for fatigue, treatment satisfaction, daily living, and work improved significantly over 12 months of DMF versus baseline. CONCLUSION: At 12 months after versus 12 months before DMF initiation, ARR was significantly lower, the majority of patients were relapse-free, and multiple PRO measures showed improvement (overall and for subgroups), suggesting that DMF is effective based on clinical outcomes and from a patient perspective.Clinical trial: A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes (PROTEC), NCT01930708,info:eu-repo/semantics/publishedVersio

How to account for irrigation withdrawals in a watershed model

In agricultural areas, the downstream flow can be highly influenced by human activities during low-flow periods, especially during dam releases and irrigation withdrawals. Irrigation is indeed the major use of freshwater in the world. This study aims at precisely taking these factors into account in a watershed model. The Soil and Water Assessment Tool (SWAT+) agro-hydrological model was chosen for its capacity to model crop dynamics and management. Two different crop models were compared in terms of their ability to estimate water needs and actual irrigation. The first crop model is based on air temperature as the main determining factor for growth, whereas the second relies on high-resolution data from the Sentinel-2 satellite to monitor plant growth. Both are applied at the plot scale in a watershed of 800 km2 that is characterized by irrigation withdrawals. Results show that including remote sensing data leads to more realistic modeled emergence dates for summer crops. However, both approaches have proven to be able to reproduce the evolution of daily irrigation withdrawals throughout the year. As a result, both approaches allowed us to simulate the downstream flow with a good daily accuracy, especially during low-flow periods.</p

A Plasmodium membrane receptor platform integrates cues for egress and invasion in blood forms and activation of transmission stages

Critical events in the life cycle of malaria-causing parasites depend on cyclic guanosine monophosphate homeostasis by guanylyl cyclases (GCs) and phosphodiesterases, including merozoite egress or invasion of erythrocytes and gametocyte activation. These processes rely on a single GCalpha, but in the absence of known signaling receptors, how this pathway integrates distinct triggers is unknown. We show that temperature-dependent epistatic interactions between phosphodiesterases counterbalance GCalpha basal activity preventing gametocyte activation before mosquito blood feed. GCalpha interacts with two multipass membrane cofactors in schizonts and gametocytes: UGO (unique GC organizer) and SLF (signaling linking factor). While SLF regulates GCalpha basal activity, UGO is essential for GCalpha up-regulation in response to natural signals inducing merozoite egress and gametocyte activation. This work identifies a GC membrane receptor platform that senses signals triggering processes specific to an intracellular parasitic lifestyle, including host cell egress and invasion to ensure intraerythrocytic amplification and transmission to mosquitoes

Measurement of double-differential cross sections for top quark pair production in pp collisions at [Formula: see text][Formula: see text] and impact on parton distribution functions.

Normalized double-differential cross sections for top quark pair ([Formula: see text]) production are measured in pp collisions at a centre-of-mass energy of 8[Formula: see text] with the CMS experiment at the LHC. The analyzed data correspond to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton [Formula: see text] final state. The [Formula: see text] cross section is determined as a function of various pairs of observables characterizing the kinematics of the top quark and [Formula: see text] system. The data are compared to calculations using perturbative quantum chromodynamics at next-to-leading and approximate next-to-next-to-leading orders. They are also compared to predictions of Monte Carlo event generators that complement fixed-order computations with parton showers, hadronization, and multiple-parton interactions. Overall agreement is observed with the predictions, which is improved when the latest global sets of proton parton distribution functions are used. The inclusion of the measured [Formula: see text] cross sections in a fit of parametrized parton distribution functions is shown to have significant impact on the gluon distribution

Measurement of prompt and nonprompt [Formula: see text] production in [Formula: see text] and [Formula: see text] collisions at [Formula: see text].

This paper reports the measurement of [Formula: see text] meson production in proton-proton ([Formula: see text]) and proton-lead ([Formula: see text]) collisions at a center-of-mass energy per nucleon pair of [Formula: see text] by the CMS experiment at the LHC. The data samples used in the analysis correspond to integrated luminosities of 28[Formula: see text] and 35[Formula: see text] for [Formula: see text] and [Formula: see text] collisions, respectively. Prompt and nonprompt [Formula: see text] mesons, the latter produced in the decay of [Formula: see text] hadrons, are measured in their dimuon decay channels. Differential cross sections are measured in the transverse momentum range of [Formula: see text], and center-of-mass rapidity ranges of [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]). The nuclear modification factor, [Formula: see text], is measured as a function of both [Formula: see text] and [Formula: see text]. Small modifications to the [Formula: see text] cross sections are observed in [Formula: see text] relative to [Formula: see text] collisions. The ratio of [Formula: see text] production cross sections in [Formula: see text]-going and Pb-going directions, [Formula: see text], studied as functions of [Formula: see text] and [Formula: see text], shows a significant decrease for increasing transverse energy deposited at large pseudorapidities. These results, which cover a wide kinematic range, provide new insight on the role of cold nuclear matter effects on prompt and nonprompt [Formula: see text] production

Measurement of the WZ production cross section in pp collisions at [Formula: see text] and 8[Formula: see text] and search for anomalous triple gauge couplings at [Formula: see text].

The WZ production cross section is measured by the CMS experiment at the CERN LHC in proton-proton collision data samples corresponding to integrated luminosities of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see text] at [Formula: see text]. The measurements are performed using the fully-leptonic WZ decay modes with electrons and muons in the final state. The measured cross sections for [Formula: see text] are [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text]. Differential cross sections with respect to the [Formula: see text] boson [Formula: see text], the leading jet [Formula: see text], and the number of jets are obtained using the [Formula: see text] data. The results are consistent with standard model predictions and constraints on anomalous triple gauge couplings are obtained