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Chiara Lupi,1 Simona Guerzoni,2 Andrea Negro,3 Silvia Benemei1 1Headache Centre, Careggi University Hospital, Department of Health Sciences, University of Florence, Florence, Italy; 2Medical Toxicology Unit, Headache and Drug Abuse Centre, Department of Biomedical, Metabolic and Neural Sciences, University of Modena e Reggio Emilia, Modena, Italy; 3Department of Clinical and Molecular Medicine, Regional Referral Headache Centre, Sant’Andrea Hospital, Sapienza University, Rome Abstract: In the last 15 years relevant efforts have been made to demonstrate that calcitonin gene-related peptide (CGRP) antagonism is a valuable and druggable mechanism for treatment or prevention of migraine. Galcanezumab is one of the antibodies developed and studied to prevent migraine by targeting CGRP. The scope of this review is to report data currently available on galcanezumab. According to available data, galcanezumab is safe and efficacious in preventing migraine in episodic migraine patients, also reducing disability and functional impairment due to the disorder. In September 2018, galcanezumab was approved in the USA for the prevention of migraine in adults. The placement of galcanezumab into the current therapeutic scenario will be a revolution for migraine patients, and probably in a less near future also for patients affected by other primary headaches. Keywords: calcitonin gene-related peptide, headache, LY2951742, monoclonal antibody prophylaxis, CGRP

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In this article a model of water diffusion within a bonded assembly will be set up. It will be fed by experimental tests which will allow to characterize the diffusive properties of a bonded assembly by taking into account the presence of interphases. For this purpose, specimens will be instrumented with Fresnel fiber optic sensors. These sensors allow a local measurement of the water content of a polymer material during wet ageing. Once these measurements are performed, the model, which will be called "gradient model", will then allow to calculate and represent the water content field at the core and at the interphases of an epoxy/metal bonded assembly. This model will be confronted with gravimetric tests in order to verify its good performance on the calculation of the global water content of an assembly. [ABSTRACT FROM AUTHOR]

The durability of bonded structures in wet environments is the subject of a large number of studies. The long-term behaviour of these structures is affected and driven by the water diffusion within the adhesive. The literature highlights that the creation of interphases, particular area where chemical and physical bonds are established between the adhesive and the substrate, play an important role in water diffusion kinetics. The aim of this study is to provide amethod to characterize the mean water diffusive properties of the interphases of a bonded assembly in immersion. This approach includes global gravimetric tests of an assembly and an analytical model to characterize its water diffusive parameters. The model divides the bonded joint into two separate layers: one layer representing the adhesive and the other the interfacial area. The water content of each layer can then be estimated using analytical equations. Diffusion parameters are then deduced from these water contents. A greater and faster water diffusion within the interfacial zone has been highlighted. The approach presented here allows to quantify it. [ABSTRACT FROM AUTHOR]

Background and purpose: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. Methods: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire‐based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. Results: In all, 1161 patients completed the study. Twenty‐eight per cent of participants were aware that they suffered from migraine. Sixty‐four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X‐ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty‐eight per cent of patients had received symptomatic migraine‐specific medications and 29% at least one migraine preventive medication. Conclusions: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations. [ABSTRACT FROM AUTHOR]

We consider three layer optical waveguides and present a method to measure simultaneously the refractive index and the thickness of each layer with m-lines spectroscopy. We establish the three layer waveguide modal dispersion equations and describe a numerical method to solve these equations. The accuracy of the method is evaluated by numerical simulations with noisy data and experimentally demonstrated using a PZT thin film placed between two ZnO layers. [ABSTRACT FROM AUTHOR]

The Middle Pleistocene Transition represents an important reorganization of climate that switched from a 41‐kyr periodicity to a quasiperiodic 100‐kyr cycle. Here, we have investigated this time interval using calcareous nannofossils from a midlatitude well‐preserved sedimentary record from the Ocean Drilling Program Site 1209 in the North West Pacific Ocean. We studied samples from 1.45 to 0.45 Ma, looking for significant changes in the nannofossil assemblages. Micropaleontological data were processed using an information theoretic model comparison that deconvolutes variations in nannofossil assemblages using different predictors. The major findings are that calcareous nannofossils permit the detection of discrete events during the Middle Pleistocene Transition. They display three different associations belonging, respectively, to the 41‐kyr world, the transition, and the 100‐kyr world. The statistical approach demonstrated that nannofossils responded abruptly at the boundaries of the transition developing in two rapid steps superimposed on a more gradual process. Moreover, a strong decrease in the genus Reticulofenestra and the beginning of the Gephyrocapsa caribbeanica acme permitted us to pinpoint climate events within the Middle Pleistocene Transition. Finally, through the nannofossil paleoecology, we documented an anomalous long‐term warming trend that could be related to an intensification of the Walker circulation and the stabilization of long‐term conditions like La Niña at the midlatitudes of the NW Pacific during the Middle Pleistocene Transition. Key Points: Three different intervals across MPT are defined by nannofossils, and the acme of Gephyrocapsa caribbeanica marks the end of the MPTStatistical framework indicates that at the MPT boundaries the nannofossil response was abrupt and superimposed on a gradual trendThe Walker circulation and the ENSO played a fundamental role at Pacific midlatitudes, during the MPT [ABSTRACT FROM AUTHOR]

Background:Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed.Methods:To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS).Results:In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses.Conclusions:BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies. [ABSTRACT FROM AUTHOR]