Association of severe myoclonic epilepsy of infancy (SMEI) with probable autoimmune lymphoproliferative syndrome-variant

The paper reported on a case of severe myoclonic epilepsy of infancy (SMEI) associated with a probable autoimmune lymphoproliferative syndrome variant (Dianzani autoimmune lymphoproliferative disease) (DALD). A male patient with typical features of SMEI and a SCN1A gene variant presented in the first year of life with multiple lymph nodes, palpable liver at 2 cm from the costal margin, neutropenia, dysgammaglobulinemia, relative and sometimes absolute lymphocytosis. Subsequently the patient presented with constantly raised IgA in serum and positive antinuclear and thyroid antimicrosomal antibodies. The diagnosis of probable autoimmune lymphoproliferative syndrome was made; arthritis, skin and throat blisters, which appeared subsequently led to the diagnosis of linear IgA disease. On the basis of these unique associations, the Authors hypothesized that autoimmunity may be partly responsible of the severe epileptic symptomatology, perhaps mediated by autoantibodies against sodium channels or by accompanying cytotoxic T-lymphocytes. Corticosteroid treatment ameliorated the epilepsy and laboratory tests. Future studies will be necessary to evaluate the relevance of autoimmunity in SMEI

Are Wnt/β-Catenin and PI3K/AKT/mTORC1 Distinct Pathways in Colorectal Cancer?

Wnt/β-catenin and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathways both are critically involved in colorectal cancer (CRC) development, although they are implicated in the modulation of distinct oncogenic mechanisms. In homeostatic and pathologic conditions, these pathways show a fine regulation based mainly on feedback mechanisms, and are connected at multiple levels involving both upstream and downstream common effectors. The ability of the Wnt/β-catenin and PI3K/AKT/mTORC1 pathways to reciprocally control themselves represents one of the main resistance mechanisms to selective inhibitors in CRC, leading to the hypothesis that in specific settings, particularly in cancer driven by genetic alterations in Wnt/β-catenin signaling, the relationship between Wnt/β-catenin and PI3K/AKT/mTORC1 pathways could be so close that they should be considered as a unique therapeutic target. This review provides an update on the Wnt/β-catenin and PI3K/AKT/mTORC1 pathway interconnections in CRC, describing the main molecular players and the potential implications of combined inhibitors as an approach for CRC chemoprevention and treatment

Molecular determination of epidermal growth factor receptor in normal and neoplastic colorectal mucosa

The epidermal growth factor receptor (EGFr) is considered a major target for treatment of colorectal cancer (CRC). We found a mean EGFr content significantly lower but more activated in colonic neoplastic tissue than in paired normal mucosa. Phosphorylated (pY1068) EGFr detection in CRC may be a better tool than EGFr detection to select patients for targeted therapies

Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

This is the final version of the article. Available from the publisher via the DOI in this record.OBJECTIVES: Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. DESIGN: The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. SETTING AND PARTICIPANTS: Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. OUTCOME MEASURES: PRIMARY OUTCOME: weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. RESULTS: Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). CONCLUSIONS: Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe

A particle filter scheme for multivariate data assimilation into a point-scale snowpack model in an Alpine environment

The accuracy of hydrological predictions in snow-dominated regions deeply depends on the quality of the snowpack simulations, with dynamics that strongly affect the local hydrological regime, especially during the melting period. With the aim of reducing the modelling uncertainty, data assimilation techniques are increasingly being implemented for operational purposes. This study aims to investigate the performance of a multivariate sequential importance resampling – particle filter scheme, designed to jointly assimilate several ground-based snow observations. The system, which relies on a multilayer energy-balance snow model, has been tested at three Alpine sites: Col de Porte (France), Torgnon (Italy), and Weissfluhjoch (Switzerland). The implementation of a multivariate data assimilation scheme faces several challenging issues, which are here addressed and extensively discussed: (1) the effectiveness of the perturbation of the meteorological forcing data in preventing the sample impoverishment; (2) the impact of the parameter perturbation on the filter updating of the snowpack state; the system sensitivity to (3) the frequency of the assimilated observations, and (4) the ensemble size.The perturbation of the meteorological forcing data generally turns out to be insufficient for preventing the sample impoverishment of the particle sample, which is highly limited when jointly perturbating key model parameters. However, the parameter perturbation sharpens the system sensitivity to the frequency of the assimilated observations, which can be successfully relaxed by introducing indirectly estimated information on snow-mass-related variables. The ensemble size is found not to greatly impact the filter performance in this point-scale application.</p

Effects of seagrasses and algae of the Caulerpa family on hydrodynamics and particle-trapping rates

The widespread decline of seagrass beds within the Mediterranean often results in the replacement of seagrasses by opportunistic green algae of the Caulerpa family. Because Caulerpa beds have a different height, stiffness and density compared to seagrasses, these changes in habitat type modify the interaction of the seafloor with hydrodynamics, influencing key processes such as sediment resuspension and particle trapping. Here, we compare the effects on hydrodynamics and particle trapping of Caulerpa taxifolia, C. racemosa, and C. prolifera with the Mediterranean seagrasses Cymodocea nodosa and Posidonia oceanica. All macrophyte canopies reduced near-bed volumetric flow rates compared to bare sediment, vertical profiles of turbulent kinetic energy revealed peak values around the top of the canopies, and maximum values of Reynolds stress increased by a factor of between 1.4 (C. nodosa) and 324.1 (P. oceanica) when vegetation was present. All canopies enhanced particle retention rates compared to bare sediment. The experimental C. prolifera canopy was the most effective at particle retention (m2 habitat); however, C. racemosa had the largest particle retention capacity per structure surface area. Hence, in terms of enhancing particle trapping and reducing hydrodynamic forces at the sediment surface, Caulerpa beds provided a similar or enhanced function compared to P.oceanica and C. nodosa. However, strong seasonality in the leaf area index of C. racemosa and C. taxifolia within the Mediterranean, combined with a weak rhizome structure, suggests that sediments maybe unprotected during winter storms, when most erosion occurs. Hence, replacement of seagrass beds with Caulerpa is likely to have a major influence on annual sediment dynamics at ecosystem scales.This research was funded by the European Network of Excellence ‘‘Marine Biodiversity and Ecosystem Function’’ (MarBEF); FP6, EC contract no. 505446 and a grant from the Fundacio ´n BBVA. EPM was supported by a European Union Marie Curie host fellowship for transfer of knowledge, MTKD-CT-2004-509254, the Spanish national project EVAMARIA (CTM2005-00395/MAR) and the regional government of Andalusia project FUNDIV(P07-RNM-2516)

Impact of woody encroachment on soil organic carbon and nitrogen in abandoned agricultural lands along a rainfall gradient in Italy

Land use changes represent one of the most important components of global environmental change andhave a strong influence on carbon cycling. As a consequence of changes in economy during the last century, areas of marginal agriculture have been abandoned leading to secondary successions. The encroachment of woody plants into grasslands, pastures and croplands is generally thought to increase the carbon stored in these ecosystems even though there are evidences for a decrease in soil carbon stocks after land use change. In this paper, we investigate the effects of woody plant invasion on soil carbon and nitrogen stocks along a precipitation gradient (200–2,500 mm) using original data from paired experiment in Italian Alps and Sicily and data from literature (Guo and Gifford Glob Change Biol 8(4):345–360, 2002). We found a clear negative relationship (-0.05% C mm-1) between changes in soil organic carbon and precipitation explaining 70% of the variation in soil Cstocks after recolonization: dry sites gain carbon (up to? 67%) while wet sites lose carbon (up to -45%). In our data set, there seem to be two threshold values for soil carbon accumulation: the first one is 900 mm of mean annual rainfall, which separates the negative from the positive ratio values; the second one is 750 mm, which divides the positive values in two groups of sites. Most interestingly, this threshold of 750 mm corresponds exactly to a bioclimatic threshold: sites with\750 mm mean annual rainfall is classified as thermo-mediterranean sites, while the ones [750 mm are classified as mesomediterranean sites. This suggests that apart from rainfall also temperature values have an important influence on soil carbon accumulation after abandonment. Moreover, our results confirmed that the correlation between rainfall and trend in soil organic carbon may be related to nitrogen dynamics: carbon losses may occur only if there is a substantial decrease in soil nitrogen stock which occurs in wetter sites probably because of the higher leaching

Sensitivity of snow models to the accuracy of meteorological forcings in mountain environments

Snow models are usually evaluated at sites providing high-quality meteorological data, so that the uncertainty in the meteorological input data can be neglected when assessing model performances. However, high-quality input data are rarely available in mountain areas and, in practical applications, the meteorological forcing used to drive snow models is typically derived from spatial interpolation of the available in situ data or from reanalyses, whose accuracy can be considerably lower. In order to fully characterize the performances of a snow model, the model sensitivity to errors in the input data should be quantified. In this study we test the ability of six snow models to reproduce snow water equivalent, snow density and snow depth when they are forced by meteorological input data with gradually lower accuracy. The SNOWPACK, GEOTOP, HTESSEL, UTOPIA, SMASH and S3M snow models are forced, first, with high-quality measurements performed at the experimental site of Torgnon, located at 2160ma.s.l. in the Italian Alps (control run). Then, the models are forced by data at gradually lower temporal and/or spatial resolution, obtained by (i) sampling the original Torgnon 30 min time series at 3, 6, and 12 h, (ii) spatially interpolating neighbouring in situ station measurements and (iii) extracting information from GLDAS, ERA5 and ERA-Interim reanalyses at the grid point closest to the Torgnon site. Since the selected models are characterized by different degrees of complexity, from highly sophisticated multi-layer snow models to simple, empirical, single-layer snow schemes, we also discuss the results of these experiments in relation to the model complexity. The results show that, when forced by accurate 30 min resolution weather station data, the single-layer, intermediatecomplexity snow models HTESSEL and UTOPIA provide similar skills to the more sophisticated multi-layer model SNOWPACK, and these three models show better agreement with observations and more robust performances over different seasons compared to the lower-complexity models SMASH and S3M. All models forced by 3-hourly data provide similar skills to the control run, while the use of 6- A nd 12-hourly temporal resolution forcings may lead to a reduction in model performances if the incoming shortwave radiation is not properly represented. The SMASH model generally shows low sensitivity to the temporal degradation of the input data. Spatially interpolated data from neighbouring stations and reanalyses are found to be adequate forcings, provided that temperature and precipitation variables are not affected by large biases over the considered period. However, a simple bias-adjustment technique applied to ERA-Interim temperatures allowed all models to achieve similar performances to the control run. Regardless of their complexity, all models show weaknesses in the representation of the snow density

Main Belt Asteroids with WISE/NEOWISE I: Preliminary Albedos and Diameters

We present initial results from the Wide-field Infrared Survey Explorer (WISE), a four-band all-sky thermal infrared survey that produces data well suited to measuring the physical properties of asteroids, and the NEOWISE enhancement to the WISE mission allowing for detailed study of Solar system objects. Using a NEATM thermal model fitting routine we compute diameters for over 100,000 Main Belt asteroids from their IR thermal flux, with errors better than 10%. We then incorporate literature values of visible measurements (in the form of the H absolute magnitude) to determine albedos. Using these data we investigate the albedo and diameter distributions of the Main Belt. As observed previously, we find a change in the average albedo when comparing the inner, middle, and outer portions of the Main Belt. We also confirm that the albedo distribution of each region is strongly bimodal. We observe groupings of objects with similar albedos in regions of the Main Belt associated with dynamical breakup families. Asteroid families typically show a characteristic albedo for all members, but there are notable exceptions to this. This paper is the first look at the Main Belt asteroids in the WISE data, and only represents the preliminary, observed raw size and albedo distributions for the populations considered. These distributions are subject to survey biases inherent to the NEOWISE dataset and cannot yet be interpreted as describing the true populations; the debiased size and albedo distributions will be the subject of the next paper in this series.Comment: Accepted to ApJ. Online table to also appear on the publisher's websit

Il coralligeno toscano: distribuzione, struttura dei popolamenti e monitoraggio mediante utilizzo di differenti indici di qualit\ue0 ecologica.

Coralligenous reefs are one of the main habitat of the Mediterranean Sea for distribution, biodiversity and role in the carbon cycle. Distribution and ecological quality of coralligenous reefs must be assessed under the Marine Strategy Framework Directive. The present work aimed at assess the distribution of coralligenous reefs in Tuscany waters, describing their structure and evaluating their ecological quality through different ecological quality indices. In Tuscany waters, coralligenous reefs are distributed on rocky cliffs between 25-30 m and 50-60 m of depth. The ecological quality resulted always sufficient with values of the indices higher on the islands than on the continental coasts