Was the cold European winter 2009-2010 modified by anthropogenic climate change? An attribution study

An attribution study has been performed to investigate the degree to which the unusually cold European winter 2009-2010 was modified by anthropogenic climate change. Two different methods have been included for the attribution: one based on a large HadGEM3-A ensemble and one based on a statistical surrogate method. Both methods are evaluated by comparing simulated winter temperature means, trends, standard deviations, skewness, return periods, and 5 % quantiles with observations. While the surrogate method performs well, HadGEM3-A in general underestimates the trend in winter by a factor of 2/3. It has a mean cold bias dominated by the mountainous regions and also underestimates the cold 5 % quantile in many regions of Europe. Both methods show that the probability of experiencing a winter as cold as 2009-2010 has been reduced by approximately a factor of two due to anthropogenic changes. The method based on HadGEM3-A ensembles gives somewhat larger changes than the surrogate method because of differences in the definition of the unperturbed climate. The results are based on two diagnostics: the coldest day in winter and the largest continuous area with temperatures colder than twice the local standard deviation. The results are not sensitive to the choice of bias correction except in the mountainous regions. Previous results regarding the behavior of the measures of the changed probability have been extended. The counter-intuitive behavior for heavy-tailed distributions is found to hold for a range of measures and for events that become more rare in a changed climate

Evaluation of the HadGEM3-A simulations in view of detection and attribution of human influence on extreme events in Europe

A detailed analysis is carried out to assess the HadGEM3-A global atmospheric model skill in simulating extreme temperatures, precipitation and storm surges in Europe in the view of their attribution to human influence. The analysis is performed based on an ensemble of 15 atmospheric simulations forced with observed Sea Surface Temperature of the 54 year period 1960-2013. These simulations, together with dual simulations without human influence in the forcing, are intended to be used in weather and climate event attribution. The analysis investigates the main processes leading to extreme events, including atmospheric circulation patterns, their links with temperature extremes, land-atmosphere and troposphere-stratosphere interactions. It also compares observed and simulated variability, trends and generalized extreme value theory parameters for temperature and precipitation. One of the most striking findings is the ability of the model to capture North Atlantic atmospheric weather regimes as obtained from a cluster analysis of sea level pressure fields. The model also reproduces the main observed weather patterns responsible for temperature and precipitation extreme events. However, biases are found in many physical processes. Slightly excessive drying may be the cause of an overestimated summer interannual variability and too intense heat waves, especially in central/northern Europe. However, this does not seem to hinder proper simulation of summer temperature trends. Cold extremes appear well simulated, as well as the underlying blocking frequency and stratosphere-troposphere interactions. Extreme precipitation amounts are overestimated and too variable. The atmospheric conditions leading to storm surges were also examined in the Baltics region. There, simulated weather conditions appear not to be leading to strong enough storm surges, but winds were found in very good agreement with reanalyses. The performance in reproducing atmospheric weather patterns indicates that biases mainly originate from local and regional physical processes. This makes local bias adjustment meaningful for climate change attribution

La thérapie cellulaire de l'insuffisance sphinctérienne urétrale (description d un modèle animal préclinique et comparaison de 3 techniques de tranferts de cellules précurseurs musculaires)

PARIS12-Bib. électronique (940280011) / SudocSudocFranceF

Dysfonction érectile du diabétique et attitudes des médecins généralistes et endocrinologues (enquête auprès de 130 patients)

Objectifs : la survenue d'une dysfonction érectile (DE) chez un patient diabétique correspond souvent à une atteinte organique sévère. L'objectif de cette étude était de déterminer si l'attitude des médecins traitants (MT) et des endocrinologues face à la DE des patients diabétiques est adaptée à la gravité potentielle des lésions sous jacentes. Méthodes : un questionnaire a été remis à chaque patient diabétique du service d'endocrinologie du CHU Henri MONDOR afin d'évaluer la fonction érectile, de recueillir les souhaits des patients d'aborder le sujet de la DE, d'évaluer la prise en charge par le MT et l'endocrinologue et d'étudier la différence de prise en charge en fonction du sexe du médecin traitant ou de sa participation au suivi diabétique. Résultats : 130 questionnaires étaient exploitables. L'âge moyen était de 57,5 ans et la durée du diabète de 13,3 ans. Le score érectile moyen (IIEF-5) était de 13,6. Il existait une DE dans 69,4% des cas et 88,4% des patients déclarant une DE souhaitaient un traitement. 8,5% d'entre eux étaient traités pour cela. L'âge et l'ancienneté du diabète à une moindre mesure étaient significativement associés à un accroissement de la DE. Les diabétologues initiaient significativement plus la discussion que le généraliste mais étaient paradoxalement moins actif dans la prise en charge sans toutefois déléguer significativement plus à un spécialiste. Le sujet de la DE avait été abordé avec 25,4% des généralistes et 32,8% des diabétologues. Et dans respectivement 45,2% et 14,3% des cas un traitement a été prescrit. D'autres résultats tendent à montrer que les MT femmes et les MT ne suivant pas le diabète semblent moins impliqués dans la prise en charge de la DE. Conclusion : il existe un défaut de prise en charge de la DE chez le patient diabétique, probablement dû à un défaut de formation des médecinsObjectives : occured of an erectile dysfonction (ED) at a patient diabetic often corresponds to a severe organic attack. The objective of this study was to determine if the attitude of the general practitioners (GP) and of the endocrinologists vis-a-vis of the patients diabetics is adapted to potential gravity. Methods : a questionnaire was given to each patient diabetic of the service of endocrinology of the CHU Henri Mondor in order to evaluate the function erectile, to collect the wishes of the patients to tackle the subject of, to evaluate the catch of load by the GP and the endocrinologist an to study the difference of assumption of responsibility according to the sex of the GP or in its participation in the follow-up diabetic. Results : there was one ED in 69,4% of the cases and 88,4% of the patients declaring one ED wished a treatment. 8,5% of them were treated for that. The age and the seniority of the diabetes to a less measurement were significantly associated an increase in. The diabetologists significantly initiated more the discussion which the general practitioner bute were paradoxically less active in the assumption of responsibility without however delegating significantly more to one specialist. The subject of had been tackled with 25,4% from the general practitioners and 32,8% of the diabetologists. And in respectively 45,2% and 14,3% of the cases a treatment was prescribed. Other results tend to show that the GP women and the GP not following the diabetes seem less implied in the assumption of responsibility of. Conclusion : there is a defect of assumption of responsibility of at the patient diabetic, probably due to a defect of training of the doctorsPARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Développement de thérapies cellulaires pour les complications urinaires et sexuelles de la prostatectomie radicale

Notre travail comporte une partie de chirurgie expérimentale sur animaux par création de modèles d'incontinence urinaire (chez la truie) et le dysfonctionnement érectile (chez le rat) et par évaluation de nouvelles thérapies cellulaires. Dans le modèle de l'incontinence urinaire chez la truie, nous avons montré que l'appareil sphinctérien de la truie se rapproche morphologiquement de celui de l'homme par sa taille, sa forme et sa composition en fibres de type I lui conférant une activité tonique basale mesurable en urodynamique. A l'aide de ce modèle, nous avons envisagé une nouvelle méthode de transfert intra urétral de cellules précurseur musculaires par implantation directe des ficres musculaires (CPM) avec leurs cellules satellites attachées en fourme de bandelette de muscle. Nous avons notamment observé la formation de fibres musculaires striées et un bourgeonnement de terminaisons nerveuses venant au contact de nouvelles plaques motrices. Nous avons conclu donc, que le transfert de CPM par implantation chirurgicale de bandelette musculaire apparaît comme une méthode simple permettant d'obtenir la formation de fibres striées en position ectopique. Et donc, nos résultats fournissent les bases biologiques pour une thérapie cellulaire des pathologies sphinctériennes en général. Dans le modèle de la dysfonction érectile chez le rat, les résultats qu'on a obtenus, suggèrent que le principal mécanisme de la dysfonction érectile après section des nerfs caverneux est plutôt la conséquence de l'apoptose diffuse des cellules conjonctives et des cellules musculaires lisses caverneuses que de l'absence de Nitrique Oxyde. L'injection de cellules médullaires de la moelle osseuse pourrait constituer un traitement curatif de la dysfonction érectile après prostatectomie radicale en remplaçant les cellules apoptotiques.Our work included a part of surgical experiments on animals by creation of models of urinary incontinence (female pig) and model of erectile dysfunction (rat) and by the evaluation of new therapies for these two kinds of pathology. In the model of urinary incontinence of female pig, we showed that the urethral sphincter of the female pig gets closer morphologically to that of the human by its size, its form and its composition in type I fibres which excrete basic tonic activity measurable by urodynamique study. With the help of this model, we envisaged a new method of intra urethral transfer of precursor muscle cells (MPC) directly by surgical implantation of muscle fibres associated with their attached satellites cells in form of muscular band. We notably noticed the formation of striated muscular fibres and sprouting of nervous endings coming in contact of new motor unites. We concluded therefore, that the transfer of MPC by surgical implantation of muscular band appears as a simple method allowing the formation of new striated fibres in an ectopique position. And therefore, our results provide the biological bases for cell therapy for treatment of sphincter pathologies in general.PARIS-EST-Université (770839901) / SudocPARIS12-Bib. électronique (940280011) / SudocSudocFranceF

The MRI assessment of intraurethrally - delivered muscle precursor cells using anionic magnetic nanoparticles

International audienceAutografting of cultured myogenic precursor cells (MPC) is a therapeutic strategy for muscle disorders, including striated urethral sphincter insufficiency. Implantation of myofibers with their satellite cells into the urethra is a recently described method of MPC transfer aimed at generating a new sphincter in incontinent patients. In this study, we magnetically labeled muscle implants with dextran-free anionic iron oxide nanoparticles (AMNP). The aim was to evaluate the biocompatibility of the labeling procedure and its utility for non-invasive MRI follow-up of cell therapy in a female pig model. After adsorption of AMNP to the implant surface, various cell types, including MPC, were magnetically labeled within the implants. Magnetic labeling did not affect cell proliferation or differentiation. Autograft detection in vivo by 0.3-T MRI was possible for up to 1 month. Ex vivo, Perl's, anti-desmin and anti-myosin heavy chain staining confirmed the co-localization of AMNP and regenerated myofibers. AMNP labeling was thus useful for locating myofiber implant autografts in vivo and for ex vivo monitoring of the biology of this cell transfer method

The pathophysiology of pelvic floor disorders: evidence from a histomorphologic study of the perineum and a mouse model of rectal prolapse

The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain deficient in urokinase-type plasminogen activator (uPA−/−) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA−/− mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA−/− mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders

Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage.

International audienceIntroduction. Animal models of urinary incontinence and erectile dysfunction following radical prostatectomy (RP) are lacking. Aims. To develop an animal model of combined post-RP urethral sphincter and erectile dysfunctions, and noninvasive methods to assess erectile function (EF) and urinary sphincter function (USF) during prolonged follow-up. Methods. In the main experiments, 60 male Sprague Dawley rats were randomized to a sham operation (N = 30) or electrocautery of both sides of the striated urethral sphincter (N = 30). EF and USF were evaluated preoperatively and on postoperative days 7, 15, 30, 60, and 90. Sphincter and penile tissue samples were evaluated histologically on days 7 (N = 10) and 30 (N = 10) to detect apoptosis (TUNEL assays) and fibrosis (Trichrome Masson staining). Main Outcome Measures. To assess EF, we measured systemic and penile blood flow using penile laser Doppler and penile rigidity using a durometer before and after apomorphine injection. USF was assessed based on the retrograde leak point pressure (LPPr). Results. Apomorphine increased baseline Doppler flow by 180% (95% confidence interval, 156-202%) and penile hardness from 3.49 ± 0.5 to 7.16 ± 0.82 Shore A units but did not change systemic arterial flow. Mean LPPr was 76.8 ± 6.18 mm Hg at baseline and decreased by 50% after injury, with no response to apomorphine on day 7. EF and USF impairments persisted up to 90 days post injury. Histology showed penile apoptosis on day 7 and extensive urethral sphincter and penile fibrosis on day 30. Our data did not allow us to determine whether the impairment in erectile response to apomorphine preponderantly reflected arterial penile insufficiency or veno-occlusive dysfunction. Conclusion. Electrocautery of the striated urethral sphincter caused severe and lasting impairment of EF and USF that could be monitored repeatedly using minimally invasive methods. This new animal model may hold potential for developing new treatments designed to correct post-RP impairments. Khodari M, Souktani R, Le Coz O, Bedretdinova D, Figeac F, Acquistapace A, Lesault PF, Cognet J, Rodriguez AM, and Yiou R. Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage. J Sex Med 2012;9:2827-2837