Successful induction of ovulation and completed pregnancy using recombinant human luteinizing hormone and follicle stimulating hormone in a woman with Kallmann's syndrome

The induction of ovulation in women with hypogonado-trophic hypogonadism requires follicle stimulating hormone (FSH) for follicular growth and both FSH and luteinizing hormone (LH) to induce optimal follicular steroidogenesis. The development of human recombinant FSH and LH means that individually tailored doses of both hormones can be used with the aim of inducing unifollicular ovulation. This report describes the use of recombinant human FSH and LH for the induction of ovulation and conception in the second cycle of treatment, and subsequently a successfully completed pregnancy in a woman with Kallmann's syndrom

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

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

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

Posidonia oceanica restoration, a relevant strategy after boat anchoring degradation?

Trabajo presentado al 7th Mediterranean Symposium on Marine Vegetation, celebrado en Génova (Italia), los días 19 y 20 de septiembre de 2022.The anchoring of large pleasure boats constitutes one of the main threats in shallow marine habitats and particularly for seagrass beds. In the Mediterranean, this activity has seen constant development during the last decades, causing major physical disturbances in Posidonia oceanica meadows and associated ecosystem services, notably in terms of climate change mitigation (i.e. carbon fixation and sequestration capacities). In this context, the aims of the present study are to estimate the impact of these anchoring activities on P. oceanica meadows in a particularly highlyfrequented area (Sant’Amanza gulf, SE Corsica Island) and to set up a strategy to restore this major carbon sink. Since the last decade, time-series of marine habitat maps revealed an important regression of P. oceanica meadows, with a loss of 72.9 ha, corresponding to 11% of the meadow surface and 9% decline in the total carbon fixation and sequestration performed each year. Moreover, in the most impacted part of the bay (Balistra bay), a loss of 16.6 ha (28%) has been recorded between 2011 and 2022. Following recent enforcement of anchoring regulation, prohibiting the anchoring of large units (greater than 24 m), and the lockdown linked to the COVID-19 pandemic, anchorages in the seagrass reduced by 92%, between 2018 and 2022. Natural recovery was observed at the edge of the meadow (plagiotropic rhizomes) but this growth is slow and the areas to recover are large. As a result, a transplant experiment, from cuttings harvested from the adjacent meadows, was initiated in the spring 2021. Four restoration techniques are being tested in the some pilot sites and the development of these transplants will be monitored and compared to the natural recovery.This research has been co-financed by INTERREG program (GIREPAM), Collectivity of Corsica Corse (PADDUC-CHANGE), SETEC Foundation, Environment Office of Corsica and the French Office of Biodiversity (RenforC program)

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

Stakeholders’ attitudes about the transplantations of the mediterranean seagrass posidonia oceanica as a habitat restoration measure after anthropogenic impacts: A q methodology approach

Anthropogenic impacts on Posidonia oceanica meadows have led to a decline of this ecosystem throughout the Mediterranean. Transplantations have often been prescribed as a compensation measure to mitigate the impacts caused by coastal maritime works. Here a Q methodology approach was used to investigate the stakeholders’ attitudes in four case studies of P. oceanica transplants realized in Italian waters. Twenty-two respondents were asked to score 37 statements, and the resultant Q-sorting was analyzed via an inverse PCA using the KADE software. Four discourses, corresponding to the significant axes in the factorial analysis were identified: science and conservation (F1), oriented at a rigorous scientific approach; engineering and industry (F2), oriented at the economic development; environmentalism and participation (F3), oriented at the conservation of seagrass meadows; and transplantation-oriented (F4), oriented at the realization of transplants as compensation measures. The main conflicts and agreements between discourses are assessed and discussed, based on the analysis of the distinguishing statements that contributed to consensus or disagreement among discourses. The benefits of the Q methodology in the identification and mediation of conflicts in the four case studies are discussed, and its potential as a powerful aid in the development of a good environmental governance is acknowledged

Marine Invasion in the Mediterranean Sea: The Role of Abiotic Factors When There Is No Biological Resistance

The tropical red alga Womersleyella setacea (Rhodomelaceae, Rhodophyta) is causing increasing concern in the Mediterranean Sea because of its invasive behavior. After its introduction it has colonized most Mediterranean areas, but the mechanism underlying its acclimatization and invasion process remains unknown. To understand this process, we decided i) to assess in situ the seasonal biomass and phenological patterns of populations inhabiting the Mediterranean Sea in relation to the main environmental factors, and ii) to experimentally determine if the tolerance of W. setacea to different light and temperature conditions can explain its colonization success, as well as its bathymetric distribution range. The bathymetric distribution, biomass, and phenology of W. setacea were studied at two localities, and related to irradiance and temperature values recorded in situ. Laboratory experiments were set up to study survival, growth and reproduction under contrasting light and temperature conditions in the short, mid, and long term.Results showed that, in the studied area, the bathymetric distribution of W. setacea is restricted to a depth belt between 25 and 40 m deep, reaching maximum biomass values (126 g dw m−2) at 30 m depth. In concordance, although in the short term W. setacea survived and grew in a large range of environmental conditions, its life requirements for the mid and long term were dim light levels and low temperatures. Biomass of Womersleyella setacea did not show any clear seasonal pattern, though minimum values were reported in spring. Reproductive structures were always absent. Bearing in mind that no herbivores feed on Womersleyella setacea and that its thermal preferences are more characteristic of temperate than of tropical seaweeds, low light (50 µmol photon m−2 s−1) and low temperature (12°C) levels are critical for W. setacea survival and growth, thus probably determining its spread and bathymetric distribution across the Mediterranean Sea

Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model

The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer

Cases of albinism and leucism in amphibians in Italy : new reports

Findings of abnormally pigmented amphibian individuals provide interesting insights on intraspecific phenotypic variability as well as on variation among populations inhabiting different habitats. Amphibian coloration is determined by chromatophores (specific epidermal cells), and a variety of abnormalities related to them have been reported. In this study we reported cases of albinism and leucism in six species of Italian amphibians, including some endemic species. For some taxa, like Hydromantes sarrabusensis, H. flavus, H. supramontis and Bufo viridis, we describe the first observations of albinism and leucism