Serotonin receptor agonists in the acute treatment of migraine. a review on their therapeutic potential

Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute therapy. The serotonin (5-hydroxytryptamine [5-HT]) receptor subtype 1B/1D agonists, called triptans, are nowadays the first-line acute therapy for patients who experience moderate-to-severe migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and cerebrovascular diseases and for those with uncontrolled hypertension. Since the introduction of triptans, no other acute drug class has passed all developmental stages. The research for a new drug lacking vasoconstrictive effects led to the development of lasmiditan, a highly selective 5-HT1F receptor agonist with minimized interactions with other 5-HT receptor subtypes. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood-brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether lasmiditan will become available in the market, and then active triptan comparator studies will assess patients’ preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of lasmiditan leads to medication overuse headache

Functions of innovation systems as a framework to understand sustainable technological change: empirical evidence for earlier claims

Understanding the emergence of innovation systems is recently put central in research analysing the process of technological change. Especially the key-activities that are important for the build up of an innovation system receive much attention. These are labeled ‘functions of innovation systems’. In most cases the authors apply this framework without questioning its validity. This paper builds on five empirical studies, related to renewable energy technologies, to test whether the functions of innovation systems framework is a valid framework to analyse processes of technological change. We test the claim that a specific set of functions is suitable. We also test whether the claim made in previous publications that the interactions between system functions accelerate innovation system emergence and growth is valid. Both claims are confirmed.

The use of FRPs in seismic repair and retrofit: experimental verification

The application of FRPs in the seismic repair and retrofit of structures is addressed. The results from a few tests on full-scale structures, repaired and/or retrofitted with composites, performed at the ELSA laboratory are presented and discussed

Observations and modelling of soil slip-debris flow initiation processes in pyroclastic deposits: the Sarno 1998 event

International audiencePyroclastic soils mantling a wide area of the Campanian Apennines are subjected to recurrent instability phenomena. This study analyses the 5 and 6 May 1998 event which affected the Pizzo d'Alvano (Campania, southern Italy). More than 400 slides affecting shallow pyroclastic deposits were triggered by intense and prolonged but not extreme rainfall. Landslides affected the pyroclastic deposits that cover the steep calcareous ridges and are soil slip-debris flows and rapid mudflows. About 30 main channels were deeply scoured by flows which reached the alluvial fans depositing up to 400 000 m3 of material in the piedmont areas. About 75% of the landslides are associated with morphological discontinuities such as limestone cliffs and roads. The sliding surface is located within the pyroclastic cover, generally at the base of a pumice layer. Geotechnical characterisation of pyroclastic deposits has been accomplished by laboratory and in situ tests. Numerical modelling of seepage processes and stability analyses have been run on four simplified models representing different settings observed at the source areas. Seepage modelling showed the formation of pore pressure pulses in pumice layers and the localised increase of pore pressure in correspondence of stratigraphic discontinuities as response to the rainfall event registered between 28 April and 5 May. Numerical modelling provided pore pressure values for stability analyses and pointed out critical conditions where stratigraphic or morphological discontinuities occur. This study excludes the need of a groundwater flow from the underlying bedrock toward the pyroclastic cover for instabilities to occur

Soil slips and debris flows on terraced slopes

International audienceTerraces cover large areas along the flanks of many alpine and prealpine valleys. Soil slips and soil slips-debris flows are recurrent phenomena along terraced slopes. These landslides cause damages to people, settlements and cultivations. This study investigates the processes related to the triggering of soil slip-debris flows in these settings, analysing those occurred in Valtellina (Central Alps, Italy) on November 2000 after heavy prolonged rainfalls. 260 landslides have been recognised, mostly along the northern valley flank. About 200 soil slips and slumps occurred in terraced areas and a third of them evolved into debris flows. Field work allowed to recognise the settings at soil slip-debris flow source areas. Landslides affected up to 2.5 m of glacial, fluvioglacial and anthropically reworked deposits overlying metamorphic basement. Laboratory and in situ tests allowed to characterise the geotechnical and hydraulic properties of the terrains involved in the initial failure. Several stratigraphic and hydrogeologic factors have been individuated as significant in determining instabilities on terraced slopes. They are the vertical changes of physical soil properties, the presence of buried hollows where groundwater convergence occurs, the rising up of perched groundwater tables, the overflow and lateral infiltration from superficial drainage network, the runoff concentration by means of pathways and the insufficient drainage of retaining walls

Rapid referral for headache management from emergency department to headache centre. four years data

Background: Headache is one of the most common reason for medical consultation to emergency department (ED). The inappropriate use of ED for non-emergency conditions is a problem in terms of overcrowding of emergency facilities, unnecessary testing and treatment, increased medical costs, burden on medical service providers and weaker relationships between patient and primary care provider. The aim of this study was to analyze the different stages of ED management of headache to identify those deficiencies that can be overcome by a fast referral to a headache clinic. Methods: The study is a retrospective analysis of the electronic medical records of patients discharged from an academic ED between January 1, 2015 and December 31, 2018 and referred to the tertiary level headache centre of the same hospital. We analyzed all aspects related to the permanence in ED and also assessed whether there was a match between the diagnosis made in ED and ours. Results: Among our sample of 244 patients, 76.2% were admitted as "green tag", 75% underwent a head computed tomography, 19.3% received a neurological consultation, 43% did not receive any pharmacological treatment and 62.7% still had headache at discharge. The length of stay in ED was associated with reporting the first aura ever (p = 0.014) and whether patients received consultations (p < 0.001). The concordance analysis shown a significant moderate agreement only for the diagnosis of migraine and only between triage and headache centre. Conclusions: Most patients who went to ED complaining of headache received the same treatment regardless of their diagnosis and in many cases the headache had not yet resolved at the time of discharge. Given the many shortcomings in headache management in ED, rapid referral to the headache centre is of paramount importance to help the patient achieve a definiteve diagnosis and appropriate treatment

A new device hypothesis for water extraction from air and basic air condition system in developing countries

This work proposes a new device for air treatment with dehumidification and water recovery/storage, with possible mitigation of indoor environmental conditions. The system is based on Peltier cells coupled with a horizontal earth‐to‐air heat exchanger, it is proposed as an easy‐to-implement alternative to the heat pumps and air handling units currently used on the market, in terms of cost, ease of installation, and maintenance. The process provides the water collection from the cooling of warm‐humid air through a process that leads to condensation and water vapor separation. The airflow generated by a fan splits into two dual flows that lap the two surfaces of the Peltier cells, one flow laps the cold surfaces undergoing sensible, latent cooling with dehumidification; the other flow laps the hot surfaces and heats up. The airflow undergoes thermal pre‐treatment through the underground horizontal geothermal pipe that precedes the Peltier cells. In the water storage tank, which also works as a mixing chamber, the two air streams are mixed to regulate the outlet temperature. The system can be stand‐alone if equipped with a photovoltaic panel and a micro wind turbine, able to be used in places where electricity is absent. The system, with different configurations, is modeled in the African city Kigali, in Rwanda

q-Analogue of Shock Soliton Solution

By using Jackson's q-exponential function we introduce the generating function, the recursive formulas and the second order q-differential equation for the q-Hermite polynomials. This allows us to solve the q-heat equation in terms of q-Kampe de Feriet polynomials with arbitrary N moving zeroes, and to find operator solution for the Initial Value Problem for the q-heat equation. By the q-analog of the Cole-Hopf transformation we construct the q-Burgers type nonlinear heat equation with quadratic dispersion and the cubic nonlinearity. In q -> 1 limit it reduces to the standard Burgers equation. Exact solutions for the q-Burgers equation in the form of moving poles, singular and regular q-shock soliton solutions are found.Comment: 13 pages, 5 figure

Discrete derivatives and symmetries of difference equations

We show on the example of the discrete heat equation that for any given discrete derivative we can construct a nontrivial Leibniz rule suitable to find the symmetries of discrete equations. In this way we obtain a symmetry Lie algebra, defined in terms of shift operators, isomorphic to that of the continuous heat equation.Comment: submitted to J.Phys. A 10 Latex page