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A study of plant remains from seven archaeological wells at Mas de Vignoles IX, near Nîmes, southern France, was used to shed light on a current gap in the archaeological record caused by erosion and modern agriculture. The analysis also explored the reliability of these sources for palaeoenvironmental and palaeoeconomical information. Significant results on the spatial organization of human habitation, economic activities, and on the environment and its exploitation were obtained for the Middle Neolithic to Roman periods. Furthermore, the Neolithic wells also provided the first early finds of fig seeds in France. The abundance of weed and ruderal plants up to the Iron Age is consistent with data from other studies and their dramatic decrease during the Roman period may have resulted from radical changes in land management. The study marks the first time, in southern France, that a group of wells from a single site have provided a complete record throughout the later prehistoric and Roman periods. [ABSTRACT FROM AUTHOR]

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Heatwaves and soil droughts are increasing in frequency and intensity, leading many tree species to exceed their thermal thresholds, and driving wide-scale forest mortality. Therefore, investigating heat tolerance and canopy temperature regulation mechanisms is essential to understanding and predicting tree vulnerability to hot droughts. We measured the diurnal and seasonal variation in leaf water potential (Ψ), gas exchange (photosynthesis A net and stomatal conductance g s ), canopy temperature (T can ), and heat tolerance (leaf critical temperature T crit and thermal safety margins TSM, i.e., the difference between maximum T can and T crit ) in three oak species in forests along a latitudinal gradient (Quercus petraea in Switzerland, Quercus ilex in France, and Quercus coccifera in Spain) throughout the growing season. Gas exchange and Ψ of all species were strongly reduced by increased air temperature (T air ) and soil drying, resulting in stomatal closure and inhibition of photosynthesis in Q. ilex and Q. coccifera when T air surpassed 30°C and soil moisture dropped below 14%. Across all seasons, T can was mainly above T air but increased strongly (up to 10°C > T air ) when A net was null or negative. Although trees endured extreme T air (up to 42°C), positive TSM were maintained during the growing season due to high T crit in all species (average T crit of 54.7°C) and possibly stomatal decoupling (i.e., A net  ≤0 while g s  >0). Indeed, Q. ilex and Q. coccifera trees maintained low but positive g s (despite null A net ), decreasing Ψ passed embolism thresholds. This may have prevented T can from rising above T crit during extreme heat. Overall, our work highlighted that the mechanisms behind heat tolerance and leaf temperature regulation in oak trees include a combination of high evaporative cooling, large heat tolerance limits, and stomatal decoupling. These processes must be considered to accurately predict plant damages, survival, and mortality during extreme heatwaves., (© 2024 The Author(s). Global Change Biology published by John Wiley & Sons Ltd.)

The article focuses on the Lineus longissimus, also known as the "bootlace worm" or "gusano cordón de bota," which is possibly the longest animal on Earth. It discusses its characteristics, distribution in shallow waters, and its presence in the northern regions of Europe, including the North Sea, the Baltic Sea, and coastal areas of the British Isles, France, Asturias, Galicia, and the Cíes Islands. It article also delves into its anatomy, respiratory system, reproduction, and feeding habits.

What are the consequences of the distribution of economic activities for the groups which constitute urban society? Do these consequences vary with the size of the town? We have answered these questions by examining 93 French towns or agglomerations, with more than 50,000 inhabitants in 1962. For each urban unit, 79 factors were gathered, demography, growth, the division of the active population by economic sectors and by socio-professional categories, education, housing and votes. These 79 variables were the object of a factor analysis and each city was graded in each factor. -- In the agglomerations, the first six factors count for 70% of the variance. In order of importance they are: economic activity and socio-professional categories, age groups and types of families, the work of women votes, migrations and urban growth, size and density of the population. The examination of these factors and the factor scores led to a classification of cities based on socio-professional groups and growth, this classification also took into account, age groups and working women. -- In French provincial towns, following these criteria, there are 20 industrial-worker towns, 27 tertiary non-worker towns (divided into middle class towns arid white-collar towns) and 25 towns in an intermediary situation. The situation of surburban towns is different. [ABSTRACT FROM AUTHOR]

Abstract: Species of the genus Cystoseira are particularly hard to discriminate, due to the complexity of their morphology, which can be influenced by their phenological state and ecological parameters. Our study emphasized on the relevance of two kinds of analytical tools, (1) LC/ESI-MS n and (2) 1H HR-MAS NMR, also called in vivo NMR, to identify Cystoseira specimens at the specific level and discuss their taxonomy. For these analyses, samples were collected at several locations in Brittany (France), where Cystoseira baccata, C. foeniculacea, C. humilis, C. nodicaulis and C. tamariscifolia were previously reported. To validate our chemical procedure, the sequence of the ITS2 has been obtained for each species to investigate their phylogenetic relationships at a molecular level. Our study highlighted the consistency of the two physico-chemical methods, compared to “classical” molecular approach, in studying taxonomy within the genus Cystoseira. Especially, LC/ESI-MS n and phylogenetic analyses converged into the discrimination of two taxonomical groups among the 5 species. The occurrence of some specific signals in the 1H HR-MAS NMR spectra and/or some characteristic chemical compounds during LC/ESI-MS n analysis could be regarded as discriminating factors. LC/ESI-MS n and 1H HR-MAS NMR turned out to be two relevant and innovative techniques to discriminate taxonomically this complex genus. [ABSTRACT FROM AUTHOR]

This research investigates the renewed interest in autism, the stigmatization of persons with autism and the need to better measure such stigmatization. Two studies were thus conducted on 101 and 104 participants in order to validate the French version of the Multidimensional Attitude Scale toward persons with disabilities, and examine the moderating effects of age, gender and contact on such attitudes. Both the exploratory and confirmatory factor analyses yielded a four-dimensional scale, indicating that the observed data fit with the theoretical model and that the sub-scale show an acceptable internal consistency. Results on moderating effect were less clear cut. The discussion deals with the measurement of attitudes toward people with autism as well as the role of social contact. [ABSTRACT FROM AUTHOR]

Leydetite, monoclinic Fe(UO2)(SO4)2(H2O)11(IMA 2012–065), is a new supergene uranyl sulfate from Mas d''Alary, Lodève, Hérault, France. It forms yellow to greenish, tabular, transparent to translucent crystals up to 2 mm in size. Crystals have a vitreous lustre. Leydetite has a perfect cleavage on (001). The streak is yellowish white. Mohs hardness is ∼2. The mineral does not fluoresce under long- or short-wavelength UV radiation. Leydetite is colourless in transmitted light, non-pleochroic, biaxial, with α = 1.513(2), γ = 1.522(2) (further optical properties could not be measured). The measured chemical composition of leydetite, FeO 9.28, MgO 0.37, Al2O30.26, CuO 0.14, UO340.19, SO321.91, SiO20.18, H2O 27.67, total 100 wt.%, leads to the empirical formula (based on 21 O a.p.f.u.), (Fe0.93Mg0.07Al0.04Cu0.01)Σ1.05(U1.01O2)(S1.96Si0.02)Σ1.98O8(H2O)11. Leydetite is monoclinic, space group C2/c, with a= 11.3203(3), b= 7.7293(2), c= 21.8145(8) Å, β = 102.402(3)°, V= 1864.18(10) Å3, Z= 4, and Dcalc= 2.55 g cm–3. The six strongest reflections in the X-ray powder diffraction pattern are [dobsin Å (I) (hkl)]: 10.625 (100) (002), 6.277 (1) (111), 5.321 (66) (004), 3.549 (5) (006), 2.663 (4) (008), 2.131 (2) (0 0 10). The crystal structure has been refined from single-crystal X-ray diffraction data to R1= 0.0224 for 5211 observed reflections with [I> 3σ(I)]. Leydetite possesses a sheet structure based upon the protasite anion topology. The sheet consists of UO7bipyramids, which share four of their equatorial vertices with SO4tetrahedra. Each SO4tetrahedron, in turn, shares two of its vertices with UO7bipyramids. The remaining unshared equatorial vertex of the bipyramid is occupied by H2O, which extends hydrogen bonds within the sheet to one of a free vertex of the SO4tetrahedron. Sheets are stacked perpendicular to the cdirection. In the interlayer, Fe2+ions and H2O groups link to the sheets on either side via a network of hydrogen bonds. Leydetite is isostructural with the synthetic compound Mg(UO2)(SO4)2(H2O)11. The name of the new mineral honours Jean Claude Leydet (born 1961), an amateur mineralogist from Brest (France), who discovered the new mineral. [ABSTRACT FROM AUTHOR]

We tested the potential of High-Resolution MAS NMR spectroscopy to study 20 samples of Emmental cheeses from 7 different geographical regions. Principal component analysis (PCA) and discriminant analysis (DA) were used to analyze the data set of 1H HRMAS NMR spectra and succeeded in grouping the studied samples according to their geographical origins.

To better identify the responses of phytoplankton blooms to warming conditions as expected in a climate change context, an in situ mesocosm experiment was carried out in a coastal Mediterranean lagoon (Thau Lagoon, South of France) in April 2018. Our objective was to assess both the direct and indirect effects of warming on phytoplankton, particularly those mediated by top-down control. Four treatments were applied: 1) natural planktonic community with ambient water temperature (C); 2) natural planktonic community at +3°C elevated temperature (T); 3) exclusion of larger zooplankton (> 200 μm; mesozooplankton) leaving microzooplankton predominant with ambient water temperature (MicroZ); and 4) exclusion of larger zooplankton (> 200 μm; mesozooplankton) at +3°C elevated temperature (TMicroZ). Warming strongly depressed the amplitude of the phytoplankton bloom as the chlorophyll a concentration was twice lower in the T treatment. This decline under warmer conditions was most likely imputed to increase top-down control by zooplankton. However, removal of mesozooplankton resulted in an opposite trend, with a higher bloom amplitude observed under warmer conditions (MicroZ vs. TMicroZ) pointing at a strong interplay between micro- and mesozooplankton and the effect of warming for the spring phytoplankton blooms. Furthermore, both warming and mesozooplankton exclusion induced shifts in phytoplankton community composition during bloom and post-bloom periods, favoring dinoflagellates and small green algae at the expense of diatoms and prymnesiophytes. Moreover, warming altered phytoplankton succession by promoting an early bloom of small green flagellates, and a late bloom of diatoms. Our findings clearly highlighted the sensitivity of phytoplankton blooms amplitudes, community composition and succession patterns to temperature increases, as well as the key role of initial zooplankton community composition to elicit opposite response in bloom dynamics. It also points out that warmer conditions might favor dinoflagellates and small green algae, irrespective of zooplankton community composition, with potential implications for food web dynamics and energy transfer efficiency under future ocean condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Trombetta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To allow health professionals to monitor and anticipate demands for emergency care in the Île-de-France region of France., Materials and Methods: Data from emergency departments and emergency medical services are automatically processed on a daily basis and visualized through an interactive online dashboard. Forecasting methods are used to provide 7 days predictions., Results: The dashboard displays data at regional and departmental levels or for 5 different age categories. It features summary statistics, historical values, predictions, comparisons to previous years, and monitoring of common reasons for care and outcomes., Discussion: A large number of health professionals have already requested access to the dashboard (n = 606). Although the quality of data transmitted may vary slightly, the dashboard has already helped improve health situational awareness and anticipation., Conclusions: The high access demand to the dashboard demonstrates the operational usefulness of real-time visualization of multisource data coupled with advanced analytics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background & Aims: Significant progress has been made in the management of pancreatic ductal adenocarcinoma (PDAC) in recent years. In this population-based study, we aimed to compare incidence, therapeutic strategies, and survival outcomes of PDAC patients in France over a decade., Methods: This study was performed using a nationwide French database. All patients receiving care for PDAC during years 2009, 2014 and 2018 were included. Treatment modalities and survival outcomes were analyzed., Results: A total of 8143/8771/10494 patients were considered in 2009/2014/2018, respectively. Incidence increased mainly among patients aged >60 years. In localized PDAC, the proportion of patients receiving best supportive care (BSC) only decreased at 43.6/36.4/32.4 % and 27.8/29.1/34.3 % received chemo(radio)therapy alone. The rate of upfront surgery remained stable while 3/8/18 % of operated patients received neoadjuvant therapy. Median overall survival (OS) was 7.0/7.9/8.5 months in the overall population. Among treated patients, 1-year OS was 61.4/67.7/68.8 % and 30.3/36.3/38.8 % for localized and metastatic PDAC, respectively., Conclusions: This study confirms the rising incidence of PDAC. Improved outcomes were seen in localized PDAC, with a wider use of chemotherapy and neoadjuvant strategies, and in treated metastatic patients. A modest survival gain was seen overall, hindered by the still high rate of patients receiving BSC only., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

DNA marker technology, being an alternative to classical hybrid selection approach, is a rapid method for identifying genes and loci associated with breeding-important traits at the early stages of ontogenesis, and, consequently, represents an approach for intensifying the breeding process. This review presents an overview of the studies on the identification of the economically important traits in the pear genome, as well as the development and use of marker-assisted selection (MAS) techniques. To date, a number of genetic factors have been identified in the pear genome, including the resistance to diseases and pests, namely, the resistance to European pear scab (V. pirina Aderh) and Asian pear scab (V. nashicola), to black spot (Alternaria alternata (Fr.) Keissler) and brown spot (Stemphylium vesicarium) disease, fire blight (Erwinia amylovora), pear psylla (Cacopsylla pyri), pear slug (Caliroacerasi), pear blister mite (Eriophyes pyri), self-incompatibility locus, and dwarf trait gene. Major genes and quantitative trait loci (QTLs) for the fruit quality characteristics have also been identified, namely those controlling fruit skin color and fruit russeting, fruit size and weight, taste, the level of ethylene production, and harvest time. It should be noted that Russian studies in this field are limited to the validation and use of MAS techniques developed abroad. According to the experience of Japanese researchers, the use of MAS for several key traits had considerably increased the efficiency of breeding process. Despite the currently limited list of MAS techniques for pears, the high pace of genome research guarantees fairly rapid development of new methods in the future. In combination with new breeding technologies (NBT), the use of MAS for pear is a promising trend in breeding. [ABSTRACT FROM AUTHOR]

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Copyright of Revista de Psicoterapia is the property of Revista de Psiquiatria y Psicologia Humanista, S.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An increasing number of cities are interested in deep geothermal energy in order to increase the share of renewable energies in their district heating networks. To reduce the risks related to deep geothermal energy operations, reliable digital models are needed: they make it possible to predict the depth of aquifers away from borehole locations, and their thermal and hydrological evolution by supporting detailed water and heat flow simulations. This paper presents a 3D geomodel developed for this purpose in the southern Paris Basin of France in the Orléans area. The 3D geomodel integrates various data such as reprocessed and interpreted seismic lines, well data, and a pre-existing larger-scale and lower-resolution 3D geological model. The resulting 3D geomodel gives a new and reliable representation of the main aquifers underlying the study area. Within the framework of the project, hydrological and thermal simulations were then performed based on this 3D geomodel. Other environmental investigations (e.g. CO2 storage) and teaching/communication activities could also benefit from the dataset. Measurement(s) geological features Technology Type(s) 3D geomodelling integration Sample Characteristic - Location Southern Paris Basin (France) [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkylated substances (PFAS) are a large group of toxic compounds which have been widely used in industrial and consumer applications, from where they can migrate into the environment. They can pose a risk to human health because they have been associated with several diseases. To obtain more information on the risk of PFAS in fast food packaging materials, several PFAS (perfluorocarboxylic acids or PFCAs (n = 16), perfluorosulfonic acids or PFSAs (n = 14), and a miscellaneous group constituted by sulfonamides (n = 5) and fluorotelomer phosphate esters or PAPs (n = 5)) were quantified in food contact materials (FCMs) from fast-food restaurants in France. Perfluorohexanoic acid (PFHxA), 6:2 fluorotelomer sulfonic acid (6:2 FTS) and 6:2/6:2 fluorotelomer phosphate diester (6:2/6:2 diPAP) were detected in all samples. PFCAs with shorter chain lengths (C 4 -C 6 ) showed the highest concentrations compared to median (C 7 -C 10 ) and longer chain length PFCAs (C 11 -C 18 ). However, they had lower detection frequencies (DFs) (except for PFHxA, DF = 100%) with values of 36 and 34% for C 4 and C 5 PFCAs, respectively. The DF of longer chain length PFCAs was higher, especially those of the median chain length PFCAs (C 8 -C 10 , with DF = 79-98%). Analytes from the PFSA group with high DFs (70-98%) were perfluorobutane sulfonic acid (PFBS), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS, linear and branched) and 10:2 fluorotelomer sulfonic acid (10:2 FTS), with concentrations similar to some analytes from the PFCA group. 4:2 Fluorotelomer phosphate monoester (4:2 mPAP), 8:2 fluorotelomer phosphate monoester (8:2 mPAP) and 8:2/8:2 fluorotelomer phosphate diester (8:2/8:2 diPAP) were found with the highest concentrations (<0.006-42.7 ng g -1 , <0.001-2.7 ng g -1 and <0.001-287 ng g -1 , respectively) and the highest DFs (ranged 68-94%). Some correlations between analytes were found, indicating similar degradation routes or a common origin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The objective was to establish new diagnostic criteria for undernutrition for the French population, concordant for children aged <18 years and adults aged <70 years, easy to use by health professionals and applicable whatever the situation (in and outpatients). A multi-disciplinary working and a reading group were involved. The procedure was divided into four phases: (1) systematic review and synthesis of the literature; (2) writing of the initial version of the guidelines; (3) reading and (4) finalisation. The literature search included international guidelines, meta-analyses, systematic reviews and randomised control trials from January 2007 to 31 July 2018. A two-step approach was selected: diagnosing undernutrition and then grading its severity. For diagnosis at least one phenotypic criterion associated with at least one aetiologic criterion were required for both children and adults. Phenotypic criteria for children were weight loss, Body Mass Index (BMI) < International Obesity Task Force curve 18·5, weight stagnation, reduction of muscle mass/function; for adults: weight loss, BMI < 18·5 and reduction of muscle mass/function. Aetiological criteria for children and adults were reduction in dietary intake, reduced absorption and hypercatabolism. Phenotypic metrics were used in both children and adults for grading severity (moderate or severe). These new French recommendations integrate the proposals of recent international recommendations combining aetiologic with phenotypic criteria, but for the first time, they are concordant for children and adults. The WHO threshold of 18·5 for BMI was kept as phenotypic criteria because epidemiological data show an increased mortality for that threshold. [ABSTRACT FROM AUTHOR]

The study aimed to examine physiological responses of firefighters performing a firefighting simulation test (FST) and to determine the relationship between physical fitness parameters and FST performance. Aerobic fitness, muscular strength, muscular endurance, and anaerobic capabilities were evaluated in 37 firefighters (21-profesionals and 16-volunteers firefighters). Furthermore, participants carried out the FST during which we measured performance, respiratory gas exchange, heart rate (HR), perceived exertion and blood lactate concentrations. Males were significantly faster than females for all tasks of the FST (p < 0.01); however, final performance score (16.5 ± 2.9 and 14.5 ± 2.6 points for males and females, respectively), HR (94.0 ± 2.0% and 93.7 ± 2.3% of HRmax) and perceived exertion (8.1 ± 0.9 and 7.1 ± 1.3) were not significantly different. Prediction of FST performance by LASSO regression revealed a model that included mainly aerobic capacity and maximal strength. In conclusion, FST challenged both aerobic and anaerobic energy metabolisms for both males and females and requires various physiological abilities to perform. Practitioner Summary: For the safety of firefighters and victims, firefighters must meet minimum physical requirements. 37 firefighters performed physical tests and a new firefighting test implemented for the recruitment of firefighters in France. The results revealed that this test is strenuous and that performance is associated with cardiorespiratory fitness and muscular strength. Abbreviations: V̇O2: oxygen consumption; V̇CO2: carbon dioxyde production; V̇E: expired ventilation; RER: respiratory exchange ratio; FST: firefighting simulation test; MAS: maximal aerobic speed; HR: heart rate; RPE: rating of perceived exertion; MVC: maximum voluntary contraction; IMTP: isometric mid-thigh pull; TTE: time to exhaustion; Ppeak: peak power; Pmean: mean power; LASSO: least absolute shrinkage and selection operator; La-: blood lactate concentration. [ABSTRACT FROM AUTHOR]

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Introduction: Obstructive sleep apnea (OSA) is a frequent condition. In the absence of treatment, OSA is associated with a higher risk of traffic accidents and a large variety of diseases. The objectives of this study were to describe the characteristics of patients treated for OSA in France and assess the time trends in treatment. Methods: The French National Health Data System is an individual database with data on all healthcare reimbursements for the entire French population. Based on this database, we included all patients aged 20 years or over who were treated with continuous positive airway pressure (CPAP) or mandibular advancement splint (MAS) between 2009 and 2018. Negative binomial models, adjusted for age, were used to assess time trends in treatment prevalence and incidence rates. Results: In 2017, 2.3% of French adults aged ≥20 years were treated with CPAP (men: 3.3%; women: 1.3%). The highest prevalence was observed in people aged 70–74 years (5.0%). From 2009 to 2018, the annual prevalence of CPAP increased 3-fold and the annual incidence 1.9-fold. During the same period, the rate of patients reimbursed for MAS (first prescription or renewal) was multiplied by 7.6. The proportion of patients treated with CPAP in 2017 who were no longer treated in the subsequent year was 6.9%. Discussion: The sharp increase in the incidence of OSA treatment probably reflects a better recognition of the disease in France. However, the prevalence of OSA treatment remains lower than expected based on the international literature. Further studies are needed to identify the obstacles to an optimal management of individuals with OSA in France. [ABSTRACT FROM AUTHOR]

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Objective: Due to a strong genotype-phenotype correlation, the timing of prophylactic thyroidectomy in rearranged during transfection (RET) gene mutation carriers is usually dictated by genetic analysis., Subjects and Methods: We report a nationwide retrospective study of the clinical data of 77 French patients from 19 families with a mutation in codon 790 of the RET proto-oncogene., Results: The average age at diagnosis was 35.6 years ± 20.5. Thirty-nine patients were women. Fifty-five patients underwent operations for the treatment of medullary thyroid carcinoma (MTC) at the mean age of 38 years (4-82 years). The mean follow-up duration was 89 months. TNM staging was as follows: T0NxMx in 19, TxNxMx in 1, T1NxMx in 22, T1N1Mx in 8, T2N1Mx in 1 and T3N1Mx in four patients. In the T1/x-Nx group, 96% were considered cured after surgery. In the N1 group (n=13), six patients had multifocal disease and five patients were cured. Age and gender were not significant predictors of remission. Twenty-two patients did not undergo an operation (age 1.5-78 years); among them, 11 patients had a mean basal calcitonin (CT) level of 9.8 pg/ml (2-24) after 53 months of follow-up. One patient had been operated on for phaeochromocytoma (PHEO), and their CT level remained normal for 262 months., Conclusions: This study confirms that RET 790 mutation is associated with a non-aggressive form of multiple endocrine neoplasia type 2, as 28% of the patients were followed up without thyroidectomy, 25% had been thyroidectomised with no tumour being detected and even patients with MTC had slow-evolving disease. Moreover, only one patient had PHEO, and no-one had primary hyperparathyroidism.

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

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Multiple endocrine neoplasia type 2 (MEN2) is an hereditary disease with a prevalence of 1/5000. Three phenotypic variants have been identified: MEN2A associates medullary thyroid carcinoma (MTC) to pheochromocytoma in about 20-50% of cases and to primary hyperparathyroidism in 5-20% of cases; MEN2B associates MTC to pheochromocytoma in 50% of cases, to marphanoid habitus and to mucosal and digestive ganglioneuromatosis whereas in familial isolated medullary thyroid carcinoma (FMTC), the other components of the disease are absent. In MEN2, natural history of the disease and a common embryologic origin (neural crest) may explain the phenotypes observed in the organ involved, beginning from the stage of hyperplasia to adenoma and cancer. MEN2 is an inherited autosomal dominant disease with a complete penetrance, related to germline mutation in the proto-oncogene RET. MTC represent the most frequent circumstance of diagnosis. Pheochromocytoma and HPT may reveal the disease unfrequently and are systematically associated to undiagnosed MTC which is present yet. Analysis of the RET gene allows to confirm the diagnosis of MEN2 by identifying the causal germline mutation. Management of MEN2 patients include thyroidectomy associated to cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved, and selective resection of pathologic parathyroid glands for HPT. Familial genetic screening detects at risk subjects who will develop the disease and allows to manage them at the earliest stage of the disease by perform early or prophylactic thyroidectomy such giving them the best chance of cure. Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC, thus pointing the necessity of a complete thyroid surgery for index cases with MTC and the earliest thyroidectomy for screened at risk subjects.

Objective: Genetic diagnosis available since 1993 established germinal mutations of the RET proto-oncogene at codon 634 as the main cause of inherited medullary thyroid carcinoma (MTC). International guidelines established in 1999 recommend that children with such mutations undergo a total thyroidectomy before age 5, with unspecified cervical neck dissection. Since 1993, only 41 of 275 thyroidectomies reported in RET 634 children were performed before age 5 (15%). The aim of this study was to evaluate the implementation of these guidelines in a single centre., Design and Patients: Genetic diagnosis was proposed to the parents of all eight children born after 1992 from two RET 634 families. Total thyroidectomy was proposed before age 5 if the child carried a mutation., Results: Genetic diagnosis was performed in all the children (aged 1-3) and thyroidectomy in the five who carried a mutation (aged 2-5). Cervical lymph node dissection varied from lymphadenectomy of central and lateral compartments in the eldest child to pickings in the youngest. There was no permanent hypoparathyroidism or recurrent nerve paralysis. C-cell hyperplasia, medullary thyroid carcinoma and lymph node metastasis were present in 5/5, 3/5 and 0/5, respectively. Undetectable pentagastrin-stimulated CT levels were achieved and maintained postoperatively in all five children (average follow-up 3.6 years)., Conclusions: MEN 2 guidelines on thyroidectomy can be efficiently and safely implemented by a multidisciplinary team operating in a single centre. The lack of guidelines on cervical neck dissection remains a problem; this could be solved by determining an age under which this procedure would be deemed unnecessary.

Background: According to the French regulation, stroke units (SU) include both an intensive (I-SU) and a non-intensive (NI-SU) component. Their standard operating procedures have been detailed in governmental directives in 2003 and 2007., Objectives: To evaluate (i) resources available in French SU, (ii) differences between regions, and between France and the 2 close European countries of similar size, and (iii) to identify avenues for improvement., Methods: We performed a survey of all French SU, with an online questionnaire, to evaluate available resources and activity. We compared the 17 French regions, and France, with Germany and Italy. We used 2019 as year of reference., Results: The 138 French SU, shared 911 I-SU beds; 123 SU (89.1%) answered the questionnaire. The number of I-SU beds per million inhabitants was 13.6 for the whole country, with important differences between regions, ranging from 7.0 (Reunion Island) to 20.9 (Occitanie region). Per million inhabitants, France had fewer I-SU beds than Germany and Italy (13.5 vs. 29.9 and 23.2 respectively), and fewer thrombectomy centres (0.6 vs. 1.8 and 1.0). Per million inhabitants, France had also lower thrombolysis (203 vs. 402) and thrombectomy (104 vs. 194) rates than Germany, but, compared with Italy, similar thrombolysis rates (203 vs. 202) and higher thrombectomy rates (104 vs. 81)., Conclusion: There are still avenues for improvement in acute stroke care in France, especially concerning the number and regional repartition of I-SU beds, and access to reperfusion therapies., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the presence of ret and trk proto-oncogene rearrangements in thyroid tumors., Design and Methods: High-molecular-weight DNA was extracted from 36 thyroid tumors (1 multinodular goiter, 14 follicular adenomas, 16 papillary carcinomas, 1 lymph node metastasis of a papillary carcinoma, 1 follicular carcinoma, and 3 medullary carcinomas) and 22 adjacent tissues. Southern blot analysis was performed after digestion with EcoR1 or BamH1, using specific probes for ret and trk., Results: Only 2 ret rearrangements were found in 2 papillary carcinomas (overall frequency: 6%; papillary carcinoma frequency: 13%). All normal or tumor samples were negative for the presence of a trk rearrangement., Conclusions: The previous data from the literature are highly conflicting, ranging from 0 to 30% of activation. Our results could be, therefore, classified as medium between these extreme values. It seems, therefore, that genetic and/or geographical factors could play a role in ret and trk proto-oncogene activation.

Multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B), and familial medullary thyroid carcinoma (FMTC) are three dominantly inherited disorders linked to the same disease locus on chromosome 10. Two types of germline mutation of the RET proto-onco-gene, which codes for a transmembrane tyrosine kinase, are associated with MEN 2. Missense mutations at cysteine residues in the extra-cytoplasmic domain are exclusively associated with MEN 2A and FMTC. In MEN 2B patients, a single point mutation at codon 918 has recently been characterized, leading to the replacement of a methionine by a threonine within the RET tyrosine kinase domain. We now report the identification of a mutation at codon 918 in the germline of 16 patients out of 18 unrelated MEN 2B families analyzed. In these families we have been able to demonstrate that, in five cases, the mutation arose de novo, and that, in one kindred, it was coinherited with the disease. These results indicate that a unique mutation at codon 918 of the RET gene is the most prevalent genetic defect causing MEN 2B, but also that rare MEN 2B cases are associated with different mutations yet to be defined.

Constitutional mutations of the RET proto-oncogene have been identified in multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) families. We sequenced RET exons 10 and 11 in 86 unrelated patients with an inherited predisposition to MTC (excluding MEN 2B). Germ-line mutations were identified in 93% of the MEN 2A families and 67% of the FMTC families tested. All were missense mutations affecting one of three cysteines in the extracellular domain of the RET tyrosine kinase receptor. The prevalence of phaeochromocytoma and hyperparathyroidism was significantly higher in families with a mutation of cysteine 634. These data confirm the preferential localisation of MEN 2A and FMTC associated mutations and the strong correlation between clinical manifestations and the position of RET mutation. Although direct sequencing of RET exons 10 and 11 allows the identification of a constitutional mutation in a large proportion of MEN 2A and FMTC families, our data sustain the existence of other MTC predisposing mutations elsewhere in RET coding or regulating region.

Based on the theory of social representations, this study aims to identify the main determinants to participation in colorectal cancer screening. Six focus groups (N = 29 participants belonging to the general population) were conducted, followed by a theoretical thematic analysis. Screening obstacles are a lack of test's accessibility, a low preoccupation for prevention and the negative image of colorectal cancer. Conversely, screening facilitators are the ease of the new test, being encouraged to get screened and appointment reminder. This study advances understanding of adherence to screening by addressing the beliefs and knowledge surrounding it. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery.

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Background: FOLFIRINOX has shown promising results in locally advanced (LAPA) or borderline resectable (BRPA) pancreatic adenocarcinoma. We report here a cohort of patients treated with this regimen from the AGEO group.Methods: This is a retrospective multicentre study. We included all consecutive patients with non-pre-treated LAPA or BRPA treated with FOLFIRINOX.Results: We included 330 patients (57.9% male, 65.4% <65 years, 96.4% PS <2). Disease was classified as BRPA in 31.1% or LAPA in 68.9%. Objective response rate with FOLFIRINOX was 29.5% and stable disease 51%. Subsequent CRT was performed in 46.4% of patients and 23.9% had curative intent surgery. Resection rates were 42.1% for BRPA and 15.5% for LAPA. Main G3/4 toxicities were fatigue (15%), neutropenia (12%) and neuropathy (G2/3 35%). After a median follow-up of 26.7 months, median OS (mOS) and PFS were 21.4 and 12.4 months, respectively. For patients treated by FOLFIRINOX alone, or FOLFIRINOX followed by CRT, or FOLFIRINOX + /- CRT + surgery, mOS was 16.8 months, 21.8 months and not reached, respectively (p < 0.0001).Conclusions: FOLFIRINOX for LAPA and BRPA seems to be effective with a manageable toxicity profile. These promising results in "real-life" patients now have to be confirmed in a Phase 3 randomised trial. [ABSTRACT FROM AUTHOR]

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Objectives: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia.Trial Design: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial.Participants: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days.Intervention and Comparator: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication.Main Outcomes: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected.Randomization: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not).Blinding (masking): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacy data, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1).Trial Status: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021.Trial Registration: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

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Copyright of Hydrogeology Journal is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: to describe, using data from a cancer registry in a well-defined French population, the therapeutic strategies and survival of patients with metastatic colon cancer (mCC)., Methods: all patients with synchronous mCC diagnosed within the 2005-2014 period recorded in the digestive cancers registry of Burgundy were included., Results: 1286 mCC patients were included (57% male), of which 34.5% did not receive any antitumor treatment. Both, advanced age (≥75 years) and the Charlson comorbidity score ≥2 were significantly associated with the absence of antitumor treatment. Among the patients treated with chemotherapy, 59 and 33% received at least two and three lines, respectively. Most patients treated with chemotherapy (68%) did not receive first-line targeted therapy. Of patients aged ≥75 years, 57% received no chemotherapy and 56% of treated patients had first-line treatment only., Conclusion: this population-based study shows that more than one-third of patients with mCC receive no chemotherapy and that only 59% of treated patients receive treatment beyond the first line. This study also highlights the fact that more than half of patients ≥75 years do not get any antitumor treatment. In patients <75 years, the proportion of patients receiving chemotherapy and/or undergoing curative intent surgery tended to increase over time., Competing Interests: Declaration of Competing Interest L. Mas declare no competing interests. J.B. Bachet has received personal fees from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier, Shire, and nonfinancial support from Amgen, Merck Serono, and Roche. V. Jooste declare no competing interests. C. Lepage has received personal fees from Advanced Accelerator Application, Merck Serono, and nonfinancial support from Amgen, Pierre Fabre, Merck Serono and Ipsen. A.M. Bouvier declare no competing interests., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)