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Supplemental Methods. Supplemental Table 1: ââ,¬â€¹Genomic Data Characterization by Center. Supplemental Table 2: ââ,¬â€¹Gene Panels Submitted by Each Center. Figure S1: Number of putative germline SNPs per sample, before and after uniform germline filtering. Figure S2ââ,¬â€¹. Distribution of total somatic mutation burden per sample stratified by sequencing panel. Figure S3: ââ,¬â€¹Log-scale comparison of mutation frequencies at hotspot sites between GENIE (data aggregated from all sequencing panels) and cancerhotspots.org (CHS) using a binomial test. Figure S4:ââ,¬â€¹ Comparison of mutation frequencies at hotspot sites in each GENIE sequencing panel with cancerhotspots.org (CHS) using a binomial test.

Table S4

AACR GENIE Data Guide

International audience; Dans cet article, nous présentons les résultats d’un programme de recherche-action participative en France sur l’exercice des droits de l’homme et la prise de décision assistée et substitutive, inspiré de la Convention Internationale relative aux droits des personnes handicapées (« CIDPH »). Réunissant des personnes ayant le vécu du handicap, des universitaires et des professionnels de la santé et de l’aide sociale, le projet utilise la méthode de la « construction par l’expérience du problème public » pour transformer l’expérience en expertise collective. Cela a permis d’explorer le soutien dont les personnes en situation de vulnérabilité, pour lesquels la capacité à exercer les droits s’est affaiblie, ont besoin pour prendre des décisions dans leur vie quotidienne et participer de manière significative au débat public. Le lien entre la conscience/connaissance des droits et leur exercice est discuté. Nous défendons la nécessité d’équilibrer les positions des différents contributeurs dans la recherche-action participative, de manière raisonnée, en reconnaissant la participation scientifique et citoyenne de tous les acteurs.

Introduction L’endoscopie est une activite complexe, regie par des recommandations de bonnes pratiques et textes de lois et surtout multidisciplinaire integrant de nombreuses interactions fonctionnelles notamment avec la pharmacie a usage interieur (PUI). Dans le contexte actuel de securisation des actes lies aux soins et d’amelioration continue de la qualite, il paraissait important de realiser un travail plus specifique sur l’activite d’endoscopie digestive de notre etablissement. L’objectif principal de ce travail est d’ameliorer la prise en charge des patients en endoscopie digestive au travers de l’identification des risques prioritaires du secteur. Materiels et methode La methode d’Analyse Preliminaire des Risques (APR) a ete choisie. L’APR a ete realisee sur le parcours patient necessitant un examen endoscopique programme sous anesthesie generale en HGE, mode d’entree le plus frequent dans ce secteur. Des observations dans les unites, la synthese des evenements indesirables signales et une revue de la bibliographie ont permis la construction du processus, la definition des dangers generiques, la cartographie des scenarios. Ces differents elements ont ensuite ete discutes et valides par un groupe de travail pluriprofessionnel incluant la cadre de sante et medecin referent du secteur, une infirmiere (IDE) et aide-soignant de salle, une IDE de programmation, un anesthesiste, une ingenieur gestionnaire de risques et une interne en pharmacie. Une criticite a ete attribuee a chaque evenement redoute a l’aide des echelles de cotation institutionnelles afin d’isoler les risques prioritaires et reflechir a des actions d’ameliorations. Resultats et discussion Quatre seances de 2 h ont ete organisees. Le parcours patient a ete decoupe en 5 phases, 21 fonctions et 56 sous-systemes. Le groupe de travail a identifie 152 situations dangereuses dont 54 de priorite 1 qui ont fait l’objet d’une analyse approfondie immediate avec notamment la gestion des dispositifs medicaux steriles (DMS) et la prescription des protocoles de soins qui sont ressorties avec une criticite elevee. La mise en œuvre de 7 actions cles a permis de minimiser les risques identifies dans 37 scenarios critiques. Ces actions d’amelioration sont principalement des actions de prevention et portent sur la reorganisation de la programmation des examens, la gestion des consommables et du materiel, l’actualisation des protocoles de soins et leur informatisation, l’interruption de taches. Conclusion Cette etude a permis aux professionnels de sante d’identifier les risques lies a leur activite au travers d’une demarche collective pluriprofessionnelle indispensable. De plus, au travers de cette analyse de risques, des problematiques transversales en lien avec la tracabilite, l’achat et la dispensation des DMS courants et implantables ont ete mis en exergue sur cette activite. Ceci a declenche sur ce point un travail de fond institutionnel avec la PUI integrant l’ensemble des secteurs d’endoscopie de notre etablissement. De plus, un travail specifique entre le secteur d’endoscopie digestive et le service d’informatisation de la PUI a ete lancee afin de permettre la prescription de protocoles de soins complets et ce des la consultation d’anesthesie.

Introducción. El interferón gama (IFNγ) es la citocina más potente para controlar la infección por Mycobacterium tuberculosis, el agente etiológico de la tuberculosis humana. Los pacientes con tuberculosis activa presentan reducción de los niveles de IFNγ, lo cual parece explicar la inmunidad poco efectiva contra el bacilo. La disminución de su expresión o alteraciones funcionales de los factores transactivadores del promotor del gen de IFNγ, podrían explicar la reducción de los niveles de IFNγ enlos pacientes con tuberculosis. Objetivo. Determinar la asociación de variantes genéticas en los factores de transcripción TBET,STAT1, STAT4 y HLX con sensibilidad o resistencia a tuberculosis pulmonar. Materiales y métodos. Se seleccionaron ocho polimorfismos de un solo nucleótido (Single-NucleotidePolymorphism, SNP) y se estableció su genotipo, en 466 pacientes con tuberculosis pulmonar y 300 controles sanos en Colombia; además, se hizo un análisis de asociación alélica y genética. Resultados. Los resultados indican que los SNP de los factores de transcripción estudiados no están asociados con tuberculosis; sin embargo, el polimorfismo rs11650354 en TBET puede estar implicado en la disminución de riesgo de tuberculosis. El genotipo TT de TBET se asoció significativamente con protección contra tuberculosis usando un modelo genético recesivo (OR=0,089; CI95%: 0,01-0,73;p=0,0069); sin embargo, la corrección mediante pruebas múltiples de ajuste abolió esta asociación (Empirical P Value, EMP2=0,61). Conclusión. En este estudio se sugiere un efecto de la variante rs11650354 de TBET sobre la resistencia a la tuberculosis en la población colombiana. Es necesario desarrollar un estudio de replicación usando muestras adicionales para confirmar esta asociación sugestiva. doi: http://dx.doi.org/10.7705/biomedica.v33i2.790

The recent demonstration that aromatase is expressed at higher levels in endometriosis implants than in normal endometrium has led to pilot studies using inhibitor aromatasis in patients with endometriosis. We conducted a systematic review of the literature and studied the efficacy of aromatase inhibitors on endometriosis. There were seventeen studies (case reports/series) evaluating outcomes of aromatase inhibitors. Studies suggest that aromatase inhibitors alone or co-administered with progestins, oral contraceptives or gonadotrophin releasing hormone (GnRH) agonist could reduce pain and endometriosis. There is only one randomized controlled trial comparing aromatase inhibitor+GnRH agonist and GnRH agonist and one study with eighty patients. Side-effects profiles of aromatase inhibitor regimens are favorable; it does not appear a significant bone loss. Aromatase inhibitors seem to have a promising effect on endometriosis but randomized controlled trials are needed to prove their effects and their safety.

Described as a myeloproliferative disorder mainly affecting elderly women, recent reports now confirm the occurrence of essential thrombocythemia at younger ages, which questions treatment during pregnancy. We report a further case of uneventful full term pregnancy with the use of interferon-α for maternal essential thrombocythemia which suggests that interferon-α could be considered as an effective and safe treatment during pregnancy for women with essential thrombocythemia. Further studies are warranted to determine whether interferon-α is the optimal therapeutic option during pregnancy for this patient population.

Julien Charles revient dans cet ouvrage sur une partie des resultats issus de son travail de these, dont le titre etait : « Une participation eprouvante. Enquetes sur l’autogestion, le management participatif, la participation citoyenne et l’empowerment ». Au croisement des sociologies critique et pragmatique, l’auteur aborde la notion de participation. Pour definir cette derniere, il reprend la definition des dictionnaires : l’« action de prendre part a quelque chose », ce terme est donc a c...

Transglutaminase (TG) enzymes and protein crosslinking have long been implicated in the formation of mineralized tissues. The aim of this study was to analyze the expression, activity and function of TGs in differentiating osteoblasts to gain further insight into the role of extracellular matrix protein crosslinking in bone formation. MC3T3-E1 (subclone 14) pre-osteoblast cultures were treated with ascorbic acid and β-glycerophosphate to induce cell differentiation and matrix mineralization. Expression of TG isoforms was analyzed by RT-PCR. TG activity was assessed during osteoblast differentiation by in vitro biochemical assays and by in situ labeling of live cell cultures. We demonstrate that MC3T3-E1/C14 osteoblasts express two TG isoforms—TG2 and FXIIIA. Abundant TG activity was observed during cell differentiation which increased significantly after thrombin treatment, a result confirming the presence of FXIIIA in the cultures. Ascorbic acid treatment, which stimulated collagen secretion and assembly, also stimulated externalization of TG activity, likely from FXIIIA which was externalized upon this treatment as analyzed by immunofluoresence microscopy. Inhibition of TG activity in the cultures by cystamine resulted in complete abrogation of mineralization, attributable to decreased matrix accumulation and an arrested state of osteoblast differentiation as measured by decreased levels of bone sialoprotein, osteocalcin and alkaline phosphatase. Additional functional studies and substrate characterization showed that TG activity was required for the formation of a fibronectin–collagen network during the early stages of matrix formation and assembly. This network, in turn, appeared to be essential for further matrix production and progression of the osteoblast differentiation program, and ultimately for mineralization.

Despite the general in vitro susceptibility of Staphylococcus aureus isolates that cause infectious bovine mastitis, the pathogen remains difficult to eradicate with the available antibiotics. The capacity to survive intracellularly has been proposed as a factor contributing to the persistence of S. aureus in the bovine mammary gland. The costs associated with the use of cows or goats to assess the in vivo efficacy of new antibacterial compounds constitute a major drawback. Therefore, in the present study, a mouse model of intramammary infection has been characterized for in vivo testing of new experimental drugs. An inoculum of 100 CFU of S. aureus per gland caused an important level of infection with minimal tissue damage as observed at 24 h post-inoculation. By microscopy, polymorphonuclear neutrophil cell infiltration of the infected mammary glands was observed to increase over time. At 12-24 h of infection, the pathogen was primarily found alive and dividing in neutrophils and occasionally within mammary epithelial cells. Intramuscular or intravenous injections of cephapirin at t = 0 and 10 h reduced the number of CFU/g of gland in a dose-dependent manner. In conclusion, the mouse model of infectious mastitis proposed here is suitable for primary evaluation of experimental drugs after parenteral treatment of intramammary infection with a pathogen such as S. aureus that presents both intracellular and extracellular phases of growth.

Background We describe the first reported case of uterine perforation by a cystoperitoneal shunt. The mechanism of this unusual complication is unclear. Case A 17-year-old patient had a cystoperitoneal shunt for a porencephalic cyst. She presented with recurrent watery vaginal discharge. A pelvic ultrasound examination showed that the uterus had been perforated by the distal tip of the shunt. The cystoperitoneal shunt was converted to a ventriculo-atrial shunt, and the vaginal discharge subsequently resolved. Conclusion The appearance of light and clear vaginal discharge in a patient with a cystoperitoneal shunt raises the possibility of uterine perforation. This can be confirmed by ultrasound and analysis of the discharge. Removal of the shunt leads to spontaneous closure of the uterine defect.

International audience; Background: Intraperitoneal mesh implantation is often associated with formation of adhesion to the mesh. This experimental study examines the potential of minimally invasive pneumoperitoneal-MRI to assess these adhesions in a preclinical context. Methods: Uncoated polyethylene terephthalate meshes were placed intraperitoneally in rats, in regard to the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Examinations were performed 2-weeks post mesh implantation using a rodent dedicated high field MRI. Respiratory-triggered T2 weighted images were acquired prior to and after intraperitoneal injection of ~8-10mL gas to induce a mechanical stress on the abdominal wall. Results Adhesions are occasionally seen in sham operated rats as opposed to rats receiving polyethylene terephthalate meshes. On high-resolution images, meshes can be detected due to their characteristic net-shape. Angers.. However, evidence of adherence is only found if intraperitoneal gas injection is performed, when a ~1-cm elevation of the abdominal wall is observed. When adherence occurs between the mesh and the caecum, the latter remains in contact with the wall. Looser adherences between visceral tissue and meshes are also observed. Conclusions T2-weighted pneumoperitoneal-MR imaging is a powerful tool for assessing adherence after intraperitoneal mesh implantation. According to the mini-invasive procedure adopted here, this approach may allow a temporal follow-up of adherence fate.

Interferon gamma (IFNγ) is the most potent cytokine involved in the control of Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB). Patients with active TB present reduced levels of IFNγ, which may explain the lack of effective immunity against Mtb in these patients. The diminished expression of or functional alterations in trans-acting factors that regulate IFNγ gene expression may explain the reduced levels of IFNγ in TB patients.To investigate the relationships of genetic variants in the transcription factors TBET, STAT1, STAT4, and HLX to susceptibility/resistance to pulmonary TB.Eight candidate single-nucleotide polymorphisms (SNPs) were selected, and genotyped in 466 unrelated pulmonary TB patients and 300 healthy controls from Colombia, and the allelic and genetic associations with TB were analyzed.The results indicate that no SNP in the transcription factors studied is associated with TB. However, polymorphism rs11650354 in the TBET gene may be associated with a decreased risk of TB; the TT genotype was significantly associated with TB protection in a recessive genetic model (OR=0.089, 95% CI: 0.01-0.73, p=0.0069), although this association was not maintained after multiple test correction (EMP2= 0.61).In this study, the rs11650354 variant of TBET was suggested to promote resistance to TB in a Colombian population. A future replication case-control study using additional samples will be necessary to confirm this suggestive association.

Background: Hereditary C1-inhibitor (C1-Inh) deficiency is associated with ‘bradykinin-mediated angio-oedema’ (BK-AO) and is believed not to be associated with urticaria. Acquired AO has been related to oestrogen contraceptives. Objective: To demonstrate that AO precipitated by oestrogens and characterized by nonfunctional C1-Inh is mediated by BK and to evaluate the occurrence of urticaria in these patients. Methods: A retrospective evaluation of patients referred for AO related to oestrogen was undertaken. Circulating C1-Inh, high molecular weight kininogen (HK) and enzymes involved in the metabolism of bradykinin were investigated. Results: Fifteen patients were included. HK cleavage concurrent to oestrogen intake was demonstrated in 10 patients with available plasma. Eight patients reported recurrent or chronic urticaria. Discontinuation of the contraceptive resulted in a return to native C1-Inh and HK in all cases studied and to normal kininogenase activity in all but one. The clinical manifestations completely disappeared in 6 patients and improved in 7 after the withdrawal of oestrogen. Conclusion: Patients display extensive cleavage of HK in the plasma, which supports that AO precipitated by oestrogen contraception is BK-mediated. Recurrent urticaria may have been underestimated in this context. The presence of recurrent urticaria should not systematically rule out the diagnosis of BK-AO when the history is suggestive.

Objective To report the obstetric outcome after expectant management for a right cornual heterotopic pregnancy. Design Case report. Setting University hospital. Patient(s) A 33-year-old salpingectomized woman with an 8-year history of primary infertility who conceived after in utero transfer of two embryos obtained by in vitro fertilization. Intervention(s) Expectant management and close ultrasonographic and clinical monitoring. Main Outcome Measure(s) Obstetric outcome. Result(s) The intrauterine pregnancy proceeded unremarkably. A caesarean section was performed for dystocia and allowed the delivery of a healthy 4170 g male infant. The examination of the uterus showed a prerupture of the right uterine horn. Conclusion(s) Expectant management for cornual heterotopic pregnancy could be considered a successful option in a symptom-free patient where the ectopic embryo has a limited craniocaudal length with no cardiac activity. Our case also suggests that elective cesarean section could be the optimal mode of delivery for rare cases of successful management for cornual heterotopic pregnancy, regardless of the therapeutic option chosen for the cornual pregnancy, due to the theoretical increase risk of uterine rupture during labor.

Translocation of an intrauterine device (IUD) to the sigmoid colon lumen is an extremely rare presentation of an ectopic IUD that usually results in fever and gastrointestinal symptoms. We report the exceptional case of an asymptomatic IUD translocation to the sigmoid colon lumen secondary to uterine perforation.A CT-scan was carried out during the follow-up of a 53-year-old woman with a metastatic epidermoid carcinoma of the tongue evolving over the previous eight years. It incidentally revealed the presence of an IUD in the sigmoid colon lumen. The patient being completely asymptomatic and at the terminal stage of her disease, removal of the device by means of a surgical or endoscopic procedure was not attempted. The patient died four months later due to lung cancer; during that period of time the IUD located in the colon remained asymptomatic.Asymptomatic migration of IUD to the sigmoid colon lumen can occur. Except when the patient's condition does not allow it, as in the case reported, removal of the IUD is indicated because of the risk of fistula formation and colon perforation with a high ensuing morbidity. This case report highlights the need for follow-up of patients wearing an IUD.

The most important knowledge in the area of biology currently consists of raw text documents. Bibliographic databases of biomedical articles can be searched, but an efficient procedure should evaluate the relevance of documents to biology. In genetics, this challenge is even trickier, because of the lack of consistency in genes' naming tradition. We aim to define a good approach for collecting relevant abstracts for biology and for studied species and genes. Our approach relies on defining best queries, detecting and filtering best sources.

Patients suffering from dementia are at risk of developing some behavior problems during the evolution of the disease. Therefore, it seems important to rule out, from the outset, all physical, psychiatric, metabolic or pharmacological causes in every cognitively impaired patient with disruptive behavior. Before using any medication to treat the patient, it is advisable to attempt a non pharmacological approach. This article offers some advice to the benefit of the caregivers faced with their close ones' behavioral problems. In spite of the best non pharmacological approach, medication can be necessary in order to control and monitor the disruptive behavior. It is imperative to have a thorough knowledge of the psychotropic medications, their impact and possible side effects.

The demented patient's caregivers often feel powerless when confronted with the loss of autonomy and seek advice. The family physician's implication is an important asset to help solve the difficulties associated with the evolution of the disease. This article addresses the most frequent problems encountered and suggests ways to adapt the patient's environment to compensate for cognitive deficits and to improve safety.

Background Post-partum haemorrhage is the world9s leading cause of maternal mortality. In 2001, the report of the expert committee on maternal mortality stood a disturbing picture of French practices with nearly two thirds of deaths from haemorrhage considered preventable. We present here the results of a clinical audit on the subject of evaluation and improvement of our daily practices in the management of postpartum haemorrhage. Methods This is a before and after study conducted in the department of Obstetrics and Gynaecology of Angers University Hospital. As a first time and retrospectively, we analysed all records of patients who experienced a postpartum haemorrhage between July and December 2005 (excluding caesarean section). Following the recommendations for clinical practice (RCP) issued by the CNGOF in 2004, we established a specification defining the sequence of optimal management of haemorrhage. The following major items were discussed: timing of support, total blood loss, active management of the third stage of labour, vaginal examination, uterine massage, use of oxytocin or sulprostone and time of administration, clarity of the information listed in the file and present the summary sheet dedicated to the management of bleeding. In a second step, during a meeting of compulsory service, the results were analysed and discussed with all stakeholders in the delivery room (obstetrician-gynaecologist senior and junior, midwives, anaesthesiologists) and CNGOF recommendations were recalled and detailed areas for improvement were highlighted and solutions to optimise our practices have been introduced. Finally, prospectively and to assess the impact of this meeting, we, on the same criteria, analysed the records of patients who experienced post-partum haemorrhage between January and April 2007. Overall results 1st period: 75 cases of bleeding>500 ml (500–8000 ml, average: 1091 ml), 65.33% of systematic intraveinous prophylactic injection of 10 UI of oxytocin (49/75), 88% of examination of uterine cavity (66/75), 49.33% of instrumental examination of genital tract, 76% of oxytocin administration (57/75), 16% of sulprostone administration (12/75) with an average delay of 34 min of administration (13–58 min), 29.33% abstracts met (22/75). 2nd period: 63 cases of bleeding>500 ml (500–2000 ml, average: 1022 ml), 90% of systematic intraveinous prophylactic injection of 10 UI of oxytocin (57/63), 95% examination of uterine cavity (60/63), 93.65% of instrumental examination of genital tract (59/63), 92.06% Syntocinon injection (58/63), 25.4% of the use of sulprostone (16/63), mean time: 23 min (7–48 min), 81% of filled summaries (51/63). Discussion/conclusion This study shows the importance of the meetings of awareness and the major impact of self-criticism. Through corrective actions simple and inexpensive, the management of post-partum haemorrhage delivery has become in our department, standard with over 90% of supported consistent with PRC 2004. Contexte L9hemorragie du post-partum represente la premiere cause mondiale de mortalite maternelle. En 2001, le rapport du comite d9experts sur la mortalite maternelle dressait un tableau inquietant des pratiques francaises avec pres de deux tiers des deces par hemorragie consideres comme evitables. Une remise en question de nos pratiques s9averait alors necessaire. Nous presentons ici les resultats d9un audit clinique ayant pour theme l9evaluation et l9amelioration de nos pratiques quotidiennes dans la prise en charge de l9hemorragie de la delivrance. Materiel et methode Il s9agit d9une etude de type « avant-apres » realise au sein du Pole de Gynecologie-Obstetrique du CHU d9Angers. Dans un premier temps et de maniere retrospective, nous avons analyse l9ensemble des dossiers des patientes ayant presente une hemorragie de la delivrance entre juillet et decembre 2005 (hors cesarienne). Suivant les recommandations pour la pratique clinique (RPC) emises par le CNGOF en 2004, nous avons etabli un cahier des charges definissant la sequence optimale de prise en charge d9une hemorragie. Il Nos actes quotidiens ont ete ensuite compares avec les RPC. Les principaux items suivants ont ete etudies: chronologie de la prise en charge, pertes sanguines totales, delivrance dirigee, realisation d9une revision uterine et d9un examen sous valves, massage uterin, recours aux ocytociques ou a la sulprostone et delai d9administration, clarte des informations recensees dans le dossier et presence de la feuille-resume dediee a la gestion de l9hemorragie. Dans un deuxieme temps, au cours d9une reunion de service obligatoire, les resultats ont ete analyses et commentes avec tous les intervenants de la salle d9accouchement (Gynecologue-obstetriciens, internes en formation, sages-femmes, anesthesistes-reanimateurs) et les recommandations du CNGOF ont ete rappelees et detaillees, les points a ameliorer ont ete mis en exergue et des solutions visant a optimiser nos pratiques ont ete instaurees. Enfin, de maniere prospective et afin d’evaluer l9impact de cette reunion de sensibilisation, nous avons, sur les memes criteres, analyse les dossiers des patientes ayant presente une hemorragie entre janvier et avril 2007. Il s9agit alors de mettre en evidence une amelioration de nos pratiques. Resultats globaux 1ere periode: 75 cas d9hemorragie > a 500 ml (500–8000 ml, moyenne: 1091 ml), 65.33% de delivrance dirigee (49/75), 88% de revision uterine (66/75), 49.33% d9examen sous valves, 76% d9injection de syntocinon (57/75), 16% de recours a la sulprostone (12/75) avec un delai moyen d9administration de 34 minutes (13–58min), 29.33% feuilles-resumes remplies (22/75). 2eme periode: 63 cas d9hemorragie > a 500 ml (500–2000 ml, moyenne: 1022 ml), 90% de delivrance dirigee (57/63), 95% de revision uterine (60/63), 93.65% d9examen sous valve (59/63), 92.06% d9injection de syntocinon (58/63), 25.4% de recours a la sulprostone (16/63), delai moyen d9administration 23 minutes (7–48 min), 81% de feuilles-resumes remplies (51/63). Discussion/conclusion Cette etude montre l9importance des reunions de sensibilisation et l9impact majeur de l9autocritique. Au moyen d9actions correctrices simples et peu couteuses, la prise en charge des hemorragies de la delivrance est devenue, dans notre centre, standardisee avec plus de 90% de prises en charge conformes aux RPC de 2004.