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Background: Purified cannabidiol (CBD) was administered to highly refractory patients with Dravet (DS) or Lennox–Gastaut (LGS) syndromes in an ongoing expanded access program (EAP). Herein, we report interim results on CBD safety and seizure outcomes in patients treated for a 12-month period. Material and Methods: Thirty centers were enrolled from December 2018 to December 2019 within the open-label prospective EAP up to a maximum of 25 mg/kg per day. Adverse effects and liver function tests were assessed after 2 weeks; 1, 3, and 6 months of treatment; and periodically thereafter. Seizure endpoints were the percentage of patients with ≥50 and 100% reduction in seizures compared to baseline. Results: A total of 93 patients were enrolled and included in the safety analysis. Eighty-two patients [27 (32.9%) DS, 55 (67.1%) LGS] with at least 3 months of treatment have been included in the effectiveness analysis; median previously failed antiseizure medications was eight. Pediatric and adult patients were uniformly represented in the cohort. At 3-month follow-up, compared to the 28-day baseline period, the percentage of patients with at least a 50% reduction in seizure frequency was 40.2% (plus 1.2% seizure-free). Retention rate was similar according to diagnosis, while we found an increased number of patients remaining under treatment in the adult group. CBD was mostly coadministered with valproic acid (62.2%) and clobazam (41.5%). In the safety dataset, 29 (31.2%) dropped out: reasons were lack of efficacy [16 (17.2%)] and adverse events (AEs) [12 (12.9%)], and one met withdrawal criteria (1.1%). Most reported AEs were somnolence (22.6%) and diarrhea (11.9%), followed by transaminase elevation and loss of appetite. Conclusions: CBD is associated with improved seizure control also in a considerable proportion of highly refractory patients with DS and LGS independently from clobazam use. Overall, CBD safety and effectiveness are not dose-related in this cohort.

The aim of this research was the micromorphological and mineralogical characterization of calcrete outcrops located in central Morocco, with particular focus on microstructure development and palygorskite formation processes. Two study sites in the Al Haouz Plain (ca 30. km west to Marrakech city) were identified, in an area dominated by Quaternary sedimentary formations including layers cemented by carbonate and widespread calcareous crusts at the surface. The calcrete samples were examined by means of polarizing microscopy from thin sections, scanning electron microscopy / energy-dispersive X-ray spectroscopy (SEM/EDX) from undisturbed samples, and X-ray diffraction (XRD) methods. The matrix of the calcrete material cementing the schist fragments composed of abundant calcite was associated mainly with palygorskite, quartz, and to a lesser extent illite/mica, feldspar, and chlorite. SEM observations indicated that palygorskite mainly occurred as fibres, fibre bundles and networks mainly grown on and/or enclosing calcite rhombohedrons. The EDX spectra of the palygorskite fibres exhibited strong silicon (Si) peaks followed by Al, Mg and Fe peaks. The EDX analysis of calcite rhombohedric crystals exhibited a strong Ca peak, followed by weak peaks of Si, Mg, Al and Fe possibly due to nearby or overlapped palygorskite crystals. One main palygorskite neoformation process was described. Palygorskite was authigenically formed (neoformed) during and after precipitation of calcite from percolating soil solutions in a near-surface setting. Peculiar sub-rounded microstructural units, here designated as pedogenic ooids/pisoids (according to the size), were determined in the matrix of the studied calcretes, associated to pendants and clay-rich rims surrounding them

OBJECTIVE: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. METHODS: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. RESULTS: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. CONCLUSIONS: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

Atmospheric vapor pressure deficit (VPD) is the main environmental driver of plant transpiration (TR). Because TR is concomitant with CO2 fixation and drives water use, breeding for specific modalities of TR response to VPD could enable increasing yields under a large spectrum of water availabilities. Two main bottlenecks currently limit the potential of this approach: i) effective high-throughput screening for these eco-physiological responses and ii) assigning genotypes with specific responses to appropriate production environment based on local weather. To address i) we developed a system for screening TR responses to VPD independent from confounding variation in temperature, enabling the identification of a substantial diversity among 54 wheat genotypes. Two main behaviors were identified, with the most contrasting genotypes exhibiting either an “aggressive” water use strategy (high slopes of linear TR responses to VPD) or a “water-saving” one (a segmented relationship whereby TR does not increase anymore starting from a VPD threshold). To address ii), we used a crop simulation modeling approach that we tested for the divergent conditions of Tunisia, a Mediterranean country where wheat drought tolerance is key for local food security. The analysis found that in the productive north, genotypes with aggressive water use would lead to yield increases of up to 15% with marginal gains in the rest of the country, as a result of using water that would be otherwise lost to evaporation. In contrast, due to photosynthetic limitations, water-saving genotypes would lead to yield penalties in the north but to major yield gains in the drought-prone center and south with gains as high as 30% in the food insecure region of Sidi Bouzid, where the Tunisian revolution started. Overall, this work indicates that highly contrasted drought tolerance strategies are needed even for small and globally drought-prone Mediterranean countries as a result of local context dependencies.

Vengono illustrati i processi di formazione e la distribuzione geografica in Turchia dei Calcisols, spesso associati ai Leptosols.

Chromic and Rhodic Luvisols, otherwise known as the Red Mediterranean Soils or the Terra Rossa, show marked textural differences and genetic peculiarities within their profile.

Land planning and land restoration in drylands affected by desertification require a good understanding of the active geomorphic processes, their intensities and spatial patterns. Traditional Soil and Land Suitability maps do not incorporate this information and may be partially inadequate in that regard, because they necessarily give a 'static' representation of the land. The geomorphology of the study area (Feriana district, Central Western Tunisia) is complex, including relict landforms, such as Quaternary pediments, fossil sand dunes, and the evidence of ancient endorheic systems. On the other hand the area is characterized by active and intense geomorphic processes: water and wind erosion, aeolian deposition, and localized present-day endorheism accompanied by water logging and salt accumulation processes. The soils reflect the imprints of multiple past and present pedogenic and geomorphic processes.In this study a Geomorphologic and a Pedo-morphologic Map were produced to provide the local decision makers with cartographic tools to best plan land use options and land restoration. The Maps were drawn at the 1:50,000 scale based on detailed photo-interpretation and on dedicated field surveys

The aim of this study was to evaluate the potential of MODIS normalized difference vegetation index hypertemporal data analysis for assessing Mediterranean pasture conditions in North Western Sardinia (Italy). During the seasons 2006 to 2007 and 2007 to 2008, field observations were carried out to classify 67 pasture sites in three condition classes based on expert knowledge. The local net primary productivity scaling (LNS) method was applied, and its potential for discriminating the pasture condition classes was evaluated by logistic regression models (LRM). Yearly and average LNS maps were generated for the period 2000 to 2008, and analyzed to identify areas that exhibited persistently low LNS values (hotspots). The LNS method proved useful to discriminate pastures in different conditions (LRM bootstrapped Nagelkerke pseudo R2 = 0.52). The analysis of persistence of low LNS values allow identifying regional hotspots of degradation. A qualitative evaluation of the main hotspots on aerial photographs revealed that approximately 62% of the hotspots were clearly characterized by pasture degradation patterns, whereas the remaining were associated to highly fragmented landscapes or to errors in the land cover map. This result emphasizes the importance of using multiscale approaches by integrating the LNS regional assessment with high spatial resolution remote sensing data analysis. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE).

This paper reviews the design and functionality of the 24 MW 170 GHz electron cyclotron heating and current drive system being planned for the ITER Tokamak. The sub-systems (power supplies, gyrotrons, transmission lines and launcher antennas) are described based on present day technologies, while on-going R&D provides component and sub-system testing with the possibility of increasing the reliability of the overall EC system. Modifications to the steering ranges of the launching antennas are under investigation that can improve the functional capabilities of the EC system without increasing cost and relaxing the engineering constraints.

A field experiment was carried out to assess biomass and nitrogen status in Mediterranean pastures by means of hyperspectral high resolution field radiometric data. Spectral and agronomic measurements were collected at three different pasture growth stages and in grazed–ungrazed plots distributed over an area of 14 ha. Reflectance-based vegetation indices such as simple ratio indices (SR[i,j]) and normalized difference vegetation indices (NDVI[i,j]) were calculated using all combinations of two wavelengths i and j in the spectral range 400–1000 nm. The performances of these indices in predicting green biomass (GBM, t ha−1), leaf area index (LAI, m2 m−2), nitrogen content (N, kg ha−1) and nitrogen concentration (NC, %) were evaluated by linear regression analysis using the cross validated coefficient of determination () and root mean squared error (RMSECV). SR involving bands in near-infrared (i = 770–930 nm) and in the red edge (j = 720–740 nm) yielded the best performance for GBM (, RMSECV = 2.35 t ha−1), LAI (, RMSECV = 0.37 m2 m−2), and N (, RMSECV = 7.36 kg ha−1). The best model performances for NC (, RMSECV = 0.35%) were obtained using SR involving near-infrared bands (i = 775–820 nm) and longer wavelengths of the red edge (j = 740–770 nm). The defined indices lead to significant improvements in model predictive capability compared to the traditional SR [near-infrared, red] and NDVI [near-infrared, red] and to broad-band indices. The possibility of exploiting these results gathered at field level with high resolution spectral data (FWHM 3.5 nm) also at landscape level by means of hyperspectral airborne or satellite sensors was explored. Model performances resulted extremely sensitive to band position, suggesting the importance of using hyperspectral sensors with contiguous spectral bands.

The identification of Morphopedoscape Units allowed a more rational land evaluation for an agro-pastoral activity planning and a desertification combating in an inner region of Tunisia.