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Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection.We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464.Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group.The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women.French Ministry of Health.For the French translation of the abstract see Supplementary Materials section.

Data in-use protection is critical to the data use lifecycle. Trusted execution environments supported by hardware are a key element of a system that provides data protection. The computing model focused on data protection via hardware-attested trusted execution engines is broadly called confidential computing. In this paper, we describe a security analysis of an Intel ISA extension called Intel® Trust Domain Extensions (Intel® TDX) to host confidential compute virtual machine workloads (called Trust Domain Virtual Machines or TD VMs) in the cloud. This paper describes the threat model and security architecture for Intel TDX. We describe the architecture principles, design constraints, and outline open problems that should be solved to increase the utility and scale of confidential computing models.

Background The best methods of labour induction have still been controversial because of an increased risk of uterine rupture, especially in exposed women of labour induction with prostaglandins. We here attempted to determine, after Dinoprostone Vaginal Insert, previous cesarean women (exposed women), compared with nulliparous women (non-exposed women), are more likely 1) to have the dilated cervix (up to 3 cm or more), and 2) to require cesarean after cervix being dilated 3 cm or more. Methods This retrospective observational study included 43 exposed women and 188 non exposed women . A propensity score was calculated to balance the background differences including age, BMI, Bishop. Main findings Exposed women were significantly less likely to reach 3 cm of cervix dilation than non exposed women (62.8 and 67.6% [study] vs. 83 and 81.3% [control] before and after propensy score analysis, respectively (p0.05)). However exposed women were significantly less likely to require cesarean than non exposed women (4.9 vs. 17.2% p = 0.03) after inverse probability of treatment weighting once 3 cm dilation was reached. Conclusion After Dinoprostone Vaginal Insert, women with scarred uterus were less likely to reach 3 cm of cervix dilation but once 3 cm of dilation was achieved, they were less likely to require cesarean.

Background Due to the low resolution of historical imaging technologies, descriptions of Septic Arthritis of Facet Joint (SAFJ) in children are scarce, though severe cases are known. We first aimed to estimate the incidence rate of SAFJ in children; we further aimed to specify SAFJ clinical, imaging and laboratory findings, and identify avenues for appropriate management. Methods A 10-year consecutive SAFJ case series using our imaging center database combined with a 50-year systematic review of literature cases. Results The mean ± SD incidence of pediatric SAFJ was 0.23 ± 0.4/100,000 children-years. The key symptoms were potty refusal (in toddlers) or painful sitting (78%) and lateralized signs (paravertebral tenderness and/or swelling, 88%). SAFJ diagnosis and extension were obtained using magnetic resonance imaging (MRI) (94%), and found an epidural extension in 8/16 cases. The mean duration of antibiotic treatment was 5.1 weeks. The compliance with guidelines was 79% for empiric and 62% for targeted antibiotic therapies. Conclusions SAFJ incidence in children is much greater than expected from the literature. Half of cases were complicated by an epidural infection. Simple clinical symptoms detected as early as the bedside allow a strong suspicion of SAFJ, justifying the use of a first-line MRI to confirm the diagnosis and precisely describe the extension. Focusing on simple clinical signs is key to justify the transfer of a child or the shortening of the delay to obtain an MRI. However, as MRI availability increases in most Western countries, and the capacity for diagnosis increases, the awareness of SAFJ must be spread to avoid missed cases.

Criminal procedure has long set a boundary between public and private in criminal enforcement: generally speaking, enforcement decisions at the post-charging stage are exposed to some degree of public view, while those at the pre-charging stage remain almost entirely secret. The allocation of public and private is, at heart, an allocation of power — and the current allocation is a relic. When private prosecutors were the mainstay of criminal enforcement, public court processes effectively constrained them. But those processes do little to constrain the spaces where enforcement power today resides: in decisions by the servants of a state-run, professionalized enforcement apparatus on whether to investigate, to charge, or to decline charges. This Article challenges criminal procedure’s centuries-old boundary between public and private in criminal enforcement. It argues that the justifications for the boundary are outdated and overstated, and the costs under-noticed. The public/private boundary has served to skew enforcers’ incentives; impoverish insight into enforcement patterns and their causes; weaken traditional channels of accountability (judicial, electoral and internal); and erode public trust. The Article reimagines a new boundary for our time, one that strengthens secrecy in some respects while relaxing it in others, and enables robust oversight of necessarily secret processes. More fundamentally, the Article is a call to center the public/private boundary in accounts of power in the criminal process.

This article examines information leakage when trading in distributed ledgers. We show how the lack of time priority in the period between the publication of a transaction and its validation by miners or designated participants can expose a transaction’s footprint to the market, resulting in potential front-running and manipulation. We propose a cryptographic approach for solving information leakage problems in distributed ledgers that relies on using a hash (or fingerprint) to secure time priority, followed by a second communication that reveals more features of the underlying market transaction—in effect using a transaction’s fingerprint to hide its footprint. Solving the information leakage problem greatly expands the potential applications of private distributed ledger technology to include trading.

Background and Aims Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. Methods 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. Results All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10–0.55; P

Based on a field research conducted with 213 people who identify themselves as participants of 15M movement in Spain, this article focuses on the representation of a civic (horizontal) public square movement, 15M, by a civil (vertical) political party, Podemos. Parting from this example, the question of public square movements’ aftermath and representation is problematized. The overarching argument of this discussion is that the alternatives for change coming from those advocating for a form of representation led from above cannot represent the spaces of social and political transformation opened up by collective presences such as 15M.

This paper examines information leakage in distributed ledgers. We show how the lack of time priority in the period between the publication of a transaction and its validation by miners or designated participants can expose a transaction’s “footprint” to the market, resulting in potential front-running and manipulation. We propose a cryptology-based approach for solving information leakage problems in distributed ledgers that relies on using a “hash” (or mathematical identifier) to secure time-priority followed by a second communication revealing more features of the underlying market transaction. Solving the information leakage problem greatly expands the potential applications of private distributed ledger technology.

La reglementation sanitaire francaise applicable aux eaux potables est codifiee dans le Code de la sante publique et prevoit que le controle sanitaire reglementaire est exerce par le prefet; il comprend notamment l’inspection des installations.Parmi les priorites retenues en 2007 par la Ddass de la Gironde, devenue ARS en avril 2010, figurait la realisation d’une action specifique de controle contradictoire, specifique sur les conditions d’ame nagement et d’entretien des installations de production et de distribution d’eau potable en utilisant un questionnaire d’enquete. L’action entreprise en Gironde a consiste, d’une part, a verifier les conditions d’application des arretes prefectoraux instaurant les perimetres de protection des captages et, d’autre part, a inspecter les installations de production et de distribution d’eau. Elle avait aussi deux objectifs complementaires : de mettre a jour les informations techniques detenues par la Ddass et de sensibiliser les collectivites et les exploitants a l’entretien des ouvrages, au risque de malveillance et a sa prevention, a la securite des produits chimiques, a la securite electrique.Les controles realises de 2007 a 2010 ont conduit a visiter 82 des 373 captages publics (22 %) et 62 des 256 installations publiques de traitement (24 %) d’eau potable de la Gironde. Les 155 remarques formulees concernant les captages ont porte principalement pour 27 % d’entre elles sur la conception des tetes d’ouvrages, 25 % sur la cloture et 14 % sur l’etancheite des ouvrages. Les 147 remarques concernant les installations de traitement et/ou de stockage ont quant a elles porte principalement sur la conception et la surveillance des installations vis-a-vis de la malveillance (28 %), la conception des installations (25 %) et la securite des produits chimiques (17 %). Les obligations prevues par la reglementation francaise concernant les points souleves dans le present article relevent plus de l’obligation de resultat que de l’obligation de moyens, le domaine n’etant que tres peu encadre par le droit europeen. Un partage de culture dans ce domaine est necessaire, en particulier pour tirer des enseignements des erreurs du passe, valoriser les bonnes experiences, a defaut de disposer de reglementations, guides techniques, codes de bonnes pratiques adaptes.

Introduction La candidose invasive neonatale (CIN) est une cause importante de morbi-mortalite chez le nouveau-ne, avec un risque important de sequelles. Plusieurs etudes ont montre que le dosage de (1,3)-beta-D-glucane (BDG) etait utile au diagnostic de candidose invasive chez l’adulte et l’enfant mais peu d’etudes ont ete conduites chez le nouveau-ne. Notre objectif etait d’evaluer les performances du BDG pour le diagnostic de CIN. Materiels et methodes En septembre 2017, nous avons effectue une recherche bibliographique systematique sur MEDLINE et Google Scholar afin d’identifier les etudes ayant evalue les performances du BDG (Fungitell®) pour le diagnostic de CIN en comparaison a tout test de reference incluant une hemoculture fongique. Nous avons egalement recherche dans les references des etudes incluses ainsi que dans les listes des etudes ayant citees les etudes incluses. Deux relecteurs ont selectionne les etudes et evalue leur qualite methodologique grâce a la grille QUADAS-2. La meta-analyse de performances diagnostiques (sensibilite, specificite, rapports de vraisemblance) a ete faite au seuil de 80 pg/mL en utilisant le modele hierarchique bivarie. Resultats Cette revue systematique de la litterature nous a permis d’identifier 6 etudes, incluant au total 359 nouveau-nes. Les etudes etaient globalement de bonne qualite methodologique ; il y avait toutefois frequemment un risque de biais de selection. La majorite des etudes ont utilise des criteres EORTC/MSG modifies pour etablir le diagnostic de CIN. Au seuil de 80 pg/mL, la meta-analyse a montre les indices de performances diagnostiques suivant : sensibilite 85 % (intervalle de confiance a 95 % : 68–94), specificite 69 % (IC95 % : 50–83), rapport de vraisemblance positif 2,7 (IC95 % : 1,5–5,0) et rapport de vraisemblance negatif 0,22 (IC95 % : 0,09–0,54). Conclusion Le BDG a une sensibilite elevee et un rapport de vraisemblance negatif bas et pourrait donc etre utilise en routine pour ecarter de maniere fiable le diagnostic de CIN. Des etudes complementaires portant sur un plus grand nombre de nouveau-nes a risque sont necessaires pour confirmer ces resultats.

Patients with alcoholic liver disease (ALD) have vitamin A (VA) deficiency and an enhanced immune response associated with disease severity. All-trans retinoic acid (ATRA), a VA-active metabolite, has anti-inflammatory effects and its deficiency could contribute to the exacerbated proinflammatory reaction. The aim of this study was to investigate the effects of ATRA/VA deficiency and supplementation on the monocyte response in ALD.Vitamin A and ATRA plasma levels were quantified in ALD patients and healthy subjects (HS). The in vitro effect of ATRA on lipopolysaccharide (LPS)-induced TNF-α production by human peripheral blood mononuclear cells (PBMC) was assessed by ELISA and RT-PCR. The activation pattern of peritoneal macrophages (PerMΦ) and circulating monocytes isolated from VA-deficient mice and ALD patients, respectively, was evaluated by flow cytometry, quantification of TNF-α and NO2 production.Alcoholic liver disease patients (n = 85) showed plasmatic VA deficiency that was correlated with scores of severity and with the hepatic venous pressure gradient. ATRA levels correlated significantly with VA levels. In vitro, ATRA pretreatment decreased the overproduction of TNF-α by LPS-stimulated PBMC of ALD patients. In vivo, VA deficiency in mice was associated with increased activation of PerMΦ, while oral ATRA supplementation normalized it.For the first time, we show that VA/ATRA deficiencies in ALD patients are associated with disease severity. Furthermore, our data strongly suggest that the VA deficiency observed in ALD patients might participate in the pathophysiology of the disease by priming immune cells, and that ATRA supplementation could downregulate the deleterious proinflammatory state in cirrhosis and might thus be of therapeutic use.

Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathways are not clearly elucidated. Activation of interleukin 1β (IL-1β) and immunomodulation via MyD88, the first signaling molecule in the ST2 pathway, seem to be involved. Because IL-33, the ST2 ligand, is an IL-1 family member and acts as an alarmin, we explored the ST2 pathway in human and mouse AP. Soluble ST2 was assayed by enzyme-linked immunosorbent assay (ELISA) in plasma of 44 patients admitted for AP. The levels of soluble ST2 increased early during AP and correlated with parameters of severity. Under two different experimental models of AP (ie, choline-deficient-ethionine-supplemented diet and cerulein injections), ST2-deficient mice (Il1rl1(-/-)) presented with more severe disease than wild-type mice, with increased activation of mast cells. In vitro, Il1rl1(-/-) bone-marrow-derived mast cells exhibited exacerbated degranulation, compared with the wild type. Flow cytometry identified mast cells as the main peritoneal population expressing ST2. Using immunohistochemistry and ELISA, we showed constitutive expression of IL-33 in murine pancreas and its release during experimental AP. Correlated with AP severity, increased soluble ST2 levels evoke involvement of the ST2 pathway in human AP. Furthermore, our experimental data suggest a protective role for ST2 during AP, highlighting the potential regulatory role of mast cells and the possibility of the ST2 pathway as a new therapeutic target in AP.

Resume Objectif Analyser les differents facteurs influencant le taux d’accouchement reel et theorique apres fecondation in vitro. Patients et methodes Etude retrospective de 1001 couples entres dans un cycle de FIV/ICSI entre 2004 et 2006 avec analyse des succes (accouchement) et des echecs, en tenant compte des abandons. Resultats Globalement, les taux cumulatifs theoriques apres n tentatives sont de 23,9 %, 40,5 %, 51,4 %, 62,2 % pour des taux reels de 23,9 %, 36 %, 41,2 % et 44,4 %. Les succes diminuent a partir de 35 ans et s’effondre au-dela de 38 ans. Concernant la reserve ovarienne, on note que, dans la classe d’âge 35 a 38 ans, les taux actuariels reels sont satisfaisants des lors que la reponse ovarienne a ete correcte (plus de quatre ovocytes). Dans la classe d’âge au-dela de 38 ans, les resultats sont catastrophiques des lors qu’il y a eu une mauvaise reponse (moins de cinq ovocytes). Seuls les patientes ayant une tres bonne reponse (plus de huit ovocytes) ont des chances d’accouchement notables. L’analyse multivariee montre un impact majeur de l’âge (OR = 0,17 [0,09–0,32]) dans la classe 38 a 39 ans versus celles de moins de 30 ans. Dans les indications ovulatoires, le taux de succes est meilleur (OR = 1,61 IC : 1,05–2,47, p = 0,03). Le nombre d’embryons transferes a un impact fort dans le resultat final (OR par embryon supplementaire = 1,62 IC 1,32–1,99, p Discussion et conclusion L’impact de l’âge sur les taux cumulatifs d’accouchement en AMP est indeniable et, pour les femmes de plus de 35 ans, ceux de la reponse a la stimulation et au nombre d’embryons transferes.

La reglementation sanitaire francaise applicable aux piscines, autres que celles reservees a l’usage personnel d’une famille, est codifiee dans le code de la Sante Publique et prevoit que le controle sanitaire reglementaire est effectue a la diligence de l’ARS qui peut realiser les prelevements ou confier leur realisation au laboratoire agree charge du controle sanitaire des eaux.Dans ce contexte, en 2009, la realisation par l’ARS d’Aquitaine de visites techniques de 50 piscines publiques et privees fonctionnant toute l’annee en Gironde a ete retenue comme un axe prioritaire par l’ex-DDASS de la Gironde dans le but de :•mettre a jour les informations techniques detenues par l’ARS sur les piscines, en particulier celles qui figurent dans les dossiers de declaration ;•rappeler aux gestionnaires de ces etablissements le contexte technique reglementaire auquel ils sont soumis au titre du code de la Sante Publique ;•dresser le constat de la situation au niveau de chaque etablissement et plus globalement au niveau de l’ensemble des etablissements controles. D’entree, il a ete decide de ne pas controler les regles de securite (cette action ne relevant pas des attributions de l’ARS), ni de dresser un bilan des resultats des analyses de controle sanitaire realisees mensuellement sur ces etablissements, ou de tenter de croiser ces resultats avec les constats realises en matiere de conception et d’entretien.Les controles realises de 2009 a 2010 ont conduit a soulever 214 points majeurs figurant dans les 50 lettres envoyees aux gestionnaires des etablissements enquetes et portent sur le non-respect de regle de conception, mais aussi, dans un certain nombre de cas sur l’entretien des installations, la tenue du carnet sanitaire et l’information du public. Globalement, les 214 points majeurs souleves se repartissent en 15 thematiques. A eux seuls cinq themes « d’inspection » representent plus de deux tiers des remarques formulees (146/214 = 68,2 %) : le stockage des produits chimiques (21 remarques), le mauvais raccordement sur les reseaux eaux usees/eaux pluviales (24 remarques), la mauvaise realisation des analyses d’autosurveillance ou mauvaise tenue du carnet sanitaire (24 remarques), l’entretien insuffisant des installations (28 remarques) et les problemes de conception ou d’entretien des installations de traitement de l’eau des bassins (49 remarques). La realisation de l’enquete a permis de rappeler aux exploitants la necessite de veiller au respect de regles qui ne coutent que peu ou pas d’argent comme l’affichage reglementaire, la tenue du carnet sanitaire, la realisation de tests de terrain, la regularisation administrative des etablissements, l’utilisation de reactifs de traitement homologues et un entretien soutenu des installations.La publication du present article de synthese est de nature a sensibiliser les maitres d’ouvrage, concepteurs et exploitants de ces etablissements dont l’encadrement reglementaire date, pour une grande part, de 1981 et qui n’est pas concerne par l’application de directives europeennes.

Background & Aims In decompensated cirrhosis, the early innate immune response to the Toll-like receptor 4 (TLR4) agonist, lipopolysaccharides (LPS), is characterized by a hyper-production of pro-inflammatory cytokines and hypo-production of the anti-inflammatory cytokine IL-10. In LPS-stimulated non-cirrhotic immune cells, the constitutively active glycogen synthase kinase (GSK) 3 favors pro- vs. anti-inflammatory cytokines, by acting on gene induction. However, in these cells, TLR4 dampens its own pro-inflammatory response by inducing early (within minutes) AKT-mediated phosphorylation of GSK3β (one of two GSK3 isoforms) on Ser9. Phosphorylation of GSK3β (Ser9) inhibits its activity, decreases pro-inflammatory cytokines, and increases IL-10. Thus, we investigated the role of GSK3 in LPS-induced cytokine production by peripheral blood mononuclear cells (PBMCs) or monocytes from patients with advanced cirrhosis and normal subjects. Methods Cells were pre-incubated with or without GSK3 inhibitor (SB216763 or lithium chloride) for 1h and then stimulated with LPS. Cytokine production was assessed at mRNA and secreted proteins levels, by real-time RT-PCR at 1h and ELISA at 20h, respectively. GSK3β phosphorylation was assessed using Western blotting. Results In cirrhotic and normal PBMCs pretreated with GSK3 inhibitors, LPS-induced production of pro-inflammatory proteins TNF-α and IL-12p40 was significantly decreased while that of IL-10 was increased. LPS-induced, AKT-mediated phosphorylation of GSK3β on Ser9 found in normal monocytes, was abolished in cirrhotic cells. Conclusions GSK3 is involved in the early TLR4-mediated pro-inflammatory response in patients with decompensated cirrhosis. This was associated with a defect in AKT-mediated GSK3β phosphorylation resulting in unrestricted ‘pro-inflammatory' activity of the enzyme.

Practical Applications Summary In Footprints on a Blockchain: Trading and Information Leakage in Distributed Ledgers , from the Summer 2017 issue of The Journal of Trading , authors Rune Tevasvold Aune , Adam Krellenstein (both of Symbiont ) Maureen O’Hara ( Cornell University School of Management ) and Ouziel Slama (formerly of Symbiont and now with Legolas ), describe a creative solution to a potential limitation to the use of distributed ledger technology in financial market contexts. This complication relates to the disclosure of proprietary trading information that could be used to “front-run” certain investors. The authors outline a solution to this problem, which involves the use of a cryptographic hash to indicate prioritization of transactions. This solution could facilitate widespread usage of blockchain technology in a variety of financial contexts.

Understanding and manipulating pancreatic beta-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human beta-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to redifferentiate into beta-cells. To directly test whether cultured beta-cells dedifferentiate, we applied genetic lineage tracing in mice. Differentiated beta-cells were heritably labeled using the Cre-lox system, and their fate in culture was followed. We provide evidence that mouse beta-cells can undergo dedifferentiation in vitro into an insulin-, pdx1-, and glut2-negative state. However, dedifferentiated beta-cells only rarely proliferate under standard culture conditions and are eventually eliminated from cultures. Thus, the predominant mesenchymal cells seen in cultures of mouse islets are not of a beta-cell origin.

Percutaneous biopsy is the reference diagnostic procedure for adult musculoskeletal tumors. Its place in pediatrics is controversial and open biopsy remains recommended. To assess diagnostic performance and feasibility of percutaneous biopsy performed on children and young adults for suspected malignant bone tumors. We conducted a 5-year retrospective study including patients ≤21 years who underwent a bone biopsy for a suspected malignant bone tumor. We assessed diagnostic yield (percentage of analyzable biopsies), accuracy (percentage of accurate diagnoses among all analyzable biopsies) and efficacy (percentage of accurate diagnoses among all biopsies), costs, anesthetic requirements and sample availability for biomedical research. Patients diagnosed with an open biopsy were used to compare diagnostic performances, anesthetic requirements and costs. We included 90 percutaneous and 27 open biopsies in 117 patients. For percutaneous biopsy, diagnostic yield was 95.5% (95% confidence interval [CI] 88.8–98.7%), accuracy was 96.2% (95% CI 86.8–99.5%) and efficacy was 89.3% (95% CI 78.1–96.0%). There was no statistical difference with open biopsy (Fisher exact test, P > 0.05). Mean costs were reduced with percutaneous biopsy: €1,937 (standard deviation [SD] €2,408) versus €6,362 (SD €5,033; Mann-Whitney, P

Introduction The Diabetes Prevention Program has been translated to community settings with varying success. Although primary care referrals are used for identifying and enrolling eligible patients in the Diabetes Prevention Program, little is known about the effects of strategies to facilitate and sustain eligible patient referrals using electronic health record systems. Methods To facilitate and sustain patient referrals, a modification to the electronic health record system was made and combined with provider education in 6 federally qualified health centers in the Bronx, New York. Referral data from April 2012 through November 2014 were analyzed using segmented regression analysis. Results Patient referrals increased significantly after the modification of the electronic health record system and implementation of the provider education intervention. Before the electronic system modification, 0 to 2 patients were referred per month. During the following year (September 2013 through August 2014), which included the provider education intervention, referrals increased to 1 to 9 per month and continued to increase to 5 to 11 per month from September through November 2014. Conclusions Modification of an electronic health record system coupled with a provider education intervention shows promise as a strategy to identify and refer eligible patients to community-based Diabetes Prevention Programs. Further refinement of the electronic system for facilitating referrals and follow-up of eligible patients should be explored.

Objectif de l’etude A cote des traitements de reference (chirurgie, radiofrequence), la radiotherapie induit desormais un taux de sterilisation de 90 % des lesions de moins de 5 cm, et d’environ 80 % des lesions de plus 5 cm, justifiant une comparaison therapeutique. Materiel et methode Les dossiers de patients atteints d’un carcinome hepatocellulaire unifocal traite par chemoembolisation (TACE) et irradiation si les patients etaient ineligibles a un traitement de reference, par comparaison a ceux traites par chirurgie, ont ete analyses retrospectivement (analyse statistique : test de Student, analyse uni- et multifactorielle). Resultats Cent-soixante-dix-huit dossiers ont ete analyses, 68 associations de radiotherapie et chemoembolisation et 110 chirurgies, chez 78 % d’hommes, d’âge moyen 66 ans (39–89 ans), atteints d’une cirrhose hepatique sous-jacente pour 52 %, d’une tumeur de taille moyenne de 50 mm (16–220 mm), de moins de 50 mm pour 103, avec une duree moyenne du suivi 33 mois. Le taux de reponse complete apres l’association de radiotherapie et chemoembolisation etait de 92 % si la lesion etait de moins de 5 cm contre 80 % sinon. En cas de lesion de moins de 5 cm, l’âge moyen etait comparable, la cirrhose hepatique plus frequente si le patient recevait une association de radiotherapie et chemoembolisation (p Conclusion L’analyse de cette cohorte de 178 patients atteints d’un carcinome hepatocellulaire unifocal de score Child A a montre que le taux de reponse complete apres l’associations de radiotherapie et chemoembolisation etait eleve. Quelle que soit la taille de la lesion, il n’y avait aucune difference en analyse multifactorielle entre les deux traitements. Ces resultats justifient la mise en place d’un essai randomise comparant l’association de radiotherapie et chemoembolisation et la resection chirurgicale, pour tous les patients, particulierement en cas de tumeur unique de plus de 5 cm.

Introduction La candidose invasive (CI) est une cause importante de morbi-mortalite chez le nouveau-ne, en particulier chez le premature. Plusieurs etudes ont montre que le dosage de (1,3)-beta-D-glucane (BDG) etait utile au diagnostic de CI chez l’adulte, mais peu d’etudes ont ete conduites chez le nouveau-ne. Notre objectif etait d’evaluer les performances diagnostiques du BDG chez des nouveau-nes suspects de CI. Materiels et methodes Nous avons mene une etude retrospective monocentrique dans les secteurs de neonatologie (pediatrie, soins intensifs et reanimation) d’un CHU pediatrique francais entre 2011 et 2016. Les patients eligibles etaient les nouveau-nes suspects de CI sur la base de criteres cliniques de sepsis et de facteurs de risque de CI et chez qui un dosage plasmatique quantitatif de BDG avait ete realise (Fungitell, Etats-Unis). Le seuil de positivite pour le BDG etait de 80 pg/mL. Le protocole de prise en charge de ces patients incluait egalement la realisation systematique d’hemocultures. Les patients ont ensuite ete classes en CI « prouvee », « probable » ou « possible », sur la base des criteres EORTC/MSG de 2008 (test de reference). Les patients avec CI « prouvee » et « probable » ont ete regroupes comme positifs pour l’analyse statistique. Resultats Parmi les 13 nouveau-nes inclus pour analyse (âge gestationnel median de 27 + 2 semaines d’amenorrhee et poids de naissance median de 1020 g), le diagnostic de CI a ete retenu chez 9 (5 CI prouvees et 4 CI probables ; 8 CI a Candida albicans et 1 CI a Candida glabrata ) et exclu chez 4. Au total, 10 patients avaient un taux de BDG ≥ 80 pg/mL. L’elevation du BDG etait associee a la presence de CI de maniere statistiquement significative ( p = 0,014 au test exact de Fisher). La sensibilite et la specificite du BDG etaient respectivement de 100 % (IC95 % : 66 a 100 %) et 75 % (IC95 % : 19 a 99 %). Les valeurs predictives positive et negative du BDG etaient respectivement de 90 % (IC95 % : 56 a 100 %) et 100 % (IC95 % : 29 a 100 %). Conclusion D’apres cette etude retrospective monocentrique portant sur des nouveau-nes a haut risque de CI, le BDG semble avoir une sensibilite et une valeur predictive negative elevees. Des etudes complementaires portant sur un plus grand nombre de nouveau-nes a risque sont necessaires pour determiner si le dosage de BDG peut etre utilise en routine pour ecarter de maniere fiable ce diagnostic.

Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathways are not clearly elucidated. Activation of interleukin 1β (IL-1β) and immunomodulation via MyD88, the first signaling molecule in the ST2 pathway, seem to be involved. Because IL-33, the ST2 ligand, is an IL-1 family member and acts as an alarmin, we explored the ST2 pathway in human and mouse AP. Soluble ST2 was assayed by enzyme-linked immunosorbent assay (ELISA) in plasma of 44 patients admitted for AP. The levels of soluble ST2 increased early during AP and correlated with parameters of severity. Under two different experimental models of AP (ie, choline-deficient-ethionine-supplemented diet and cerulein injections), ST2-deficient mice (Il1rl1(-/-)) presented with more severe disease than wild-type mice, with increased activation of mast cells. In vitro, Il1rl1(-/-) bone-marrow-derived mast cells exhibited exacerbated degranulation, compared with the wild type. Flow cytometry identified mast cells as the main peritoneal population expressing ST2. Using immunohistochemistry and ELISA, we showed constitutive expression of IL-33 in murine pancreas and its release during experimental AP. Correlated with AP severity, increased soluble ST2 levels evoke involvement of the ST2 pathway in human AP. Furthermore, our experimental data suggest a protective role for ST2 during AP, highlighting the potential regulatory role of mast cells and the possibility of the ST2 pathway as a new therapeutic target in AP.

We show how to simulate intermittency patterns of multiplicity fluctuations in rapidity for any multiparticle production process. The simulation uses an “upside-down” mechanism mixing a random cascading process with a multi-poissonian statistical noise. As an example, we discuss the analysis problems at very small rapidity bin, such as the modifications due to finite multiplicity or number of cascading steps (partial intermittency).

Objectifs Une large proportion de patients atteints d’un nodule unique de carcinome hepatocellulaire ne peut pas beneficier d’un traitement potentiellement curatif (transplantation hepatique, resection chirurgicale ou radiofrequence). La chimio-embolisation intra-arterielle hepatique (TACE) est un traitement palliatif, donnant un taux de reponse complete de moins de 20 % et un taux de reponse complete de plus de 12 mois de moins de 5 %, avec une duree mediane de survie de 20 mois. Dans ce travail, nous avons evalue l’efficacite de l’association de TACE et de radiotherapie conformationnelle dans une grande serie de patients. Patients et methodes De 2000 a 2014, 86 patients consecutifs ont ete traites pour un carcinome hepatocellulaire unifocal, le plus souvent de moins de 100 mm, par un schema (RTF3) associant une TACE (doxorubicine, 50 mg, j1) et une radiotherapie conformationnelle debutee entre j10 et j15, initialement de 54 Gy, puis de 60 Gy en 18 a 20 fractions, avec une scanographie quadridimentionnelle ou un gating , initialement tridimensionnelle, puis avec modulation d’intensite ou stereotaxique. Le suivi des patients a ete clinique, biologique et par imagerie (une scanographie et une IRM hepatiques le premier mois apres le traitement, puis a 3 mois, puis tous les 3 a 6 mois pendant 5 ans). Resultats Les resultats sont actuellement disponibles pour les 35 premiers patients (ils seront actualises et presentes pour les 86 patients lors du congres). Il s’agissait de 28 hommes et sept femmes, d’âge moyen de 72,8 ans, atteints pour 32 d’une cirrhose de score de Child-Pugh A ; la tumeur etait en moyenne de 48,9 mm (10–150 mm). Le taux de reponse complete selon les criteres RECIST (Response Evaluation Criteria in Solid Tumors) etait de 80 % (95 % pour les nodules moins de 50 mm et 60 % pour ceux de plus de 50 mm) avec un taux de recidive locale, faible, de 11 %. Les probabilites de survie globale etaient de 79 %, 59 % et 44 %, respectivement a 1 an, 2 ans et 3 ans, avec une duree mediane de survie, inhabituellement elevee, de 37,4 mois. Cinq patients (14 %) ont souffert d’une toxicite de grade 3 (trois ascites, une hemorragie digestive), ou 4 (une hemorragie digestive), sans qu’il soit possible d’imputer avec certitude ces complications a la radiotherapie. En analyse multifactorielle, seule une concentration pre therapeutique d’alpha-fœtoproteine de plus de 200 ng/mL representait un facteur independant de pronostic defavorable. Conclusions L’efficacite (taux de controle local survie globale eleves) et la bonne tolerance de cette association de TACE et de radiotherapie conformationnelle (schema RTF3) ont permis de choisir ce schema comme bras experimental lors de l’elaboration de l’essai randomise de phase IIb, TACERTE, etude nationale en cours qui compare la repetition d’une TACE (bras controle) et le schema RTF3.

Beta-cell replacement represents the ultimate cure for type 1 diabetes, however it is limited by availability of organ donors. Adult human islets are difficult to propagate in culture, and efforts to expand them result in dedifferentiation. Here we describe conditions for expansion of adult human islet cells, as well as a way for their redifferentiation. Most cells in islets isolated from human pancreata were induced to replicate within the first week of culture in expansion medium. Cells were propagated for 16 population doublings, without a change in replication rate or noticeable cell mortality, representing an expansion of over 65,000-fold. Replication was accompanied by a decrease in expression of key beta-cell genes. Shift of the cells to differentiation medium containing betacellulin resulted in redifferentiation, as manifested by restoration of beta-cell gene expression and insulin content. These methods may allow transplantation of functional islet cells from single donors into multiple recipients.

Objectifs Evaluer l’efficacite et la securite de la microbiopsie (MBO) dans le diagnostic des tumeurs osseuses malignes pediatriques. Materiels et Methodes Analyse retrospective des dossiers des patients âges de moins de 21 ans diagnostiques par MBO entre 2008 et 2012. Rendement et Efficacite diagnostiques definis comme: 1)-pourcentage de biopsie analysable, 2)-pourcentage de diagnostic confirme par la chirurgie. Resultats principaux 117 patients (mediane 13 ans [1 ; 21]) analyses. 90(77%) MBO et 27(23%) biopsies chirurgicales. Rendement et Efficacite diagnostiques des MBO respectivement de 95.5% et 96.2%, sans difference significative avec la biopsie chirurgicale. Nombre moyen d’echantillons=5,9. 77 MBO (85%) sont realisees sous AL avec sedation minime et 13 (14%) sous AG. Geste realise en HdJ dans 70% des cas. Aucune complication severe rapportee. 91.7% des patients inclus dans des essais cliniques ont beneficie d’une congelation de materiel, avec 70.7% des echantillons comportant plus de 30% de cellules tumorales permettant donc les etudes biologiques ancillaires. Couts moyens de la MBO=1,523€ contre 6,362€ pour la biopsie chirurgicale (p Conclusion La biopsie percutanee est une technique performante pour le diagnostic des tumeurs osseuses malignes de l’enfant.

504 INSULIN RESISTANCE CONFERS A HIGHER RISK OF PORTAL HYPERTENSION, CIRRHOSIS AND EARLY MORTALITY TO ALCOHOLIC LIVER DISEASE PATIENTS E. Trepo, D. Degre, A. Lemmers, T. Gustot, A. Gerkens, S. Evrard, R. Ouziel, P. Deltenre, M. Adler, J. Deviere, C. Moreno. Department Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Laboratory of Experimental Gastroenterology, Universite Libre de Bruxelles, Brussels, Hopital de Jolimont, Haine-Saint-Paul, Belgium E-mail: christophe.moreno@erasme.ulb.ac.be