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Proteases, especially MMPs, are attractive biomarkers given their central role in both physiological and pathological processes. Distinguishing MMP activity with degradable substrates, however, is a difficult task due to overlapping substrate specificity profiles. Here, we developed a system of peptomers (peptide-peptoid hybrids) to probe the impact of non-natural residues on MMP specificity for a MMP peptide consensus sequence. Peptoids are non-natural, N-substituted glycines with a large side chain diversity. Given the presence of a hallmark proline residue in the P3 position of MMP consensus sequences, we hypothesized that peptoids may offer N-substituted alternatives to generate differential interactions with MMPs. To investigate this hypothesis, peptomer substrates were exposed to five different MMPs, as well as bacterial collagenase, and monitored by fluorescence resonance energy transfer and liquid chromatography-mass spectrometry to determine the rate of cleavage and the composition of degraded fragments, respectively. We found that peptoid residues are well-tolerated in the P3 and P3’ substrate sites and that the identity of the peptoid in these sites displays moderate influence on the rate of cleavage. However, peptoid residues were even better tolerated in the P1 substrate site where activity was more strongly correlated with sidechain identity than sidechain position. All MMPs explored demonstrated similar trends in specificity for the peptomers but exhibited different degrees of variability in proteolytic rate. These kinetic profiles served as “fingerprints” for the proteases and yielded separation by multivariate data analysis. To further demonstrate practical application of this tunability in degradation kinetics, peptomer substrates were tethered into hydrogels and released over distinct timescales. Overall, this work represents a significant step toward the design of probes that maximize differential MMP behavior and presents design rules to tune degradation kinetics with peptoid substitutions, which has promising implications for diagnostic and prognostic applications using array-based sensors.

The estrous cycle is regulated by rhythmic endocrine interactions of the nervous and reproductive systems, which coordinate the hormonal and ovulatory functions of the ovary. Folliculogenesis and follicle progression require the orchestrated response of a variety of cell types to allow the maturation of the follicle and its sequela, ovulation, corpus luteum (CL) formation, and ovulatory wound repair. Little is known about the cell state dynamics of the ovary during the estrous cycle, and the paracrine factors that help coordinate this process. Herein we used single-cell RNA sequencing to evaluate the transcriptome of > 34,000 cells of the adult mouse ovary and describe the transcriptional changes that occur across the normal estrous cycle and other reproductive states to build a comprehensive dynamic atlas of murine ovarian cell types and states.

Introduction Postoperative ileus(POI) and anastomotic leakage(AL) are highly associated but the direction of this link is unknown. Indeed, it has traditionally been stated that AL leads to POI(secondary POI). The objective was to statistically determine the best model of link between POI and AL by comparing different Structural Equation Models(SEM). Methods This is a retrospective analysis of a prospective multicentric database from the Francophone Group for Enhanced Recovery after surgery(GRACE) including patients undergoing colorectal resection or Hartmann reversal between 2014 and 2017. The main outcome measure was the occurrence of postoperative ileus defined by the absence of Gastrointestinal (GI)-3 recovery in or after postoperative day 4 and the occurrence of AL. Results Among the 2227 patients included, 223 patients experienced POI (10 %) and 72 patients experienced anastomotic leakage (3.2 %). In all the models, POI was significantly increased in case of male gender, older age, opioids consumption, right colectomy, chronic obstructive bronchopneumopathy disease and performance of a stoma, and reduced by Enhanced Recovery Programs (ERP) compliance ≥ 70 % and intake of Non-Steroidal Anti-Inflammatory Drugs. Open surgery was not significantly associated with POI in all the models. In contrast, the male gender was the only factor increasing AL in the model drawn with ERP risk factors for AL. In all the models, POI was highly associated with AL and statistical analyses advocate for POI leading to AL. Conclusion The findings of the present large study suggest that the more statistically probable model is the one in which POI come first before AL.

Devenir patient-expert c’est tout d’abord avoir une maladie chronique. Toutefois, ce n’est pas suffisant, c’est egalement avoir suivi une formation a l’education therapeutique du patient et poursuivre le travail avec le diplome : integrer une equipe medicale, developper une experience au sein d’un programme d’education therapeutique dans sa creation, sa dispensation, son evaluation et/ou sa coordination. Dans tous les cas, le patient-expert doit savoir se detacher de son histoire personnelle.

Introduction Limits of Treatment Planning Systems (TPS) dose calculation for photon beams have been widely studied. There are fewer studies on electron beam dose calculation. Fast Electron Monte Carlo (eMC, Varian, Palo Alto, CA) is a clinical dose distribution calculation algorithm for electron beam, based on an advanced variance reduction technique, Macro Monte Carlo (MMC) [1] . Results for complex cases (heterogeneity, irregular surface contour) are limited. A GATE/GEANT4 model of a radiotherapy linac (Varian, TrueBeam) is implemented. The purpose of this study is to evaluate these algorithms by comparing them to film measurements in complex cases. Methods Validation of GATE model is performed on homogenous water phantom. Percentage depth dose curves (PDD) and lateral dose profiles (LDP) are compared with experimental measurement (6 and 9 MeV). Results of dose distribution calculation for eMC and GATE are comparing with Gafchromic EBT3 (Ashland ISP, Wayne, NJ) films, for complex cases including heterogeneities (lung, bone) and irregular surface (step). Normalization are achieved in a homogenous water region for dose profiles at two different depths (at contact and at a distance of the heterogeneity). Global Gamma Index Pass Rate (GIPR) 1D is used to compare the data sets. Results When comparing GATE and measurements, GIPR 2 % / 2 mm for PDD and LDP in homogenous water phantom is 100% for 6 MeV and 9 MeV. GIPR 3 % / 3 mm (threshold >10% D max ) for complexes cases (lung, bone and step) is >98.5% for GATE (6, 9 MeV) except for only one case at 6 MeV (at contact with lung heterogeneity: 82.9%). But, for eMC in lung case, GIPR are 100% for 9 MeV electrons but only 65.6% and 84.4% at 6 MeV at contact and at 10 mm of the heterogeneity, respectively. In presence of bones, GIPR are 100% (6, 9 MeV) except at 9 MeV, at contact of the heterogeneity (69.7%). For irregular surface cases GIPR of eMC vs. films was superior to 95.2% and 99.2% for 6 and 9 MeV respectively. Conclusions GATE model for electron beams is validated in homogeneous water phantom. In presence of surface irregularities (step) satisfactory results are obtained for both GATE and eMC. Nevertheless, when comparing to measurements for heterogeneous media, and in particular after lung (6 MeV) and bones (9 MeV) eMC was limited while GATE was satisfactory in all configurations. The study is currently carried on for more energy (12 and 18 MeV) and clinical cases (face). GATE could be proposed as a 3D dose check solution for complex electron beams.

summary Long-term water balance investigations are needed to better understand hydrologic systems, especially semi-arid mountainous catchments. These systems exhibit considerable interannual variability in precipitation as well as spatial variation in snow accumulation, soils, and vegetation. This study extended a previous 10-year water balance based on measurements and model simulations to 24 years for the Upper Sheep Creek (USC) catchment, a 26 ha, snow-fed, semi-arid rangeland headwater drainage within the Reynolds Creek Experimental Watershed in southwestern Idaho, USA. Additional analyses afforded by the additional years of data demonstrated that the variability between streamflow and annual precipitation (r 2 = 0.54) could be explained by the timing of precipitation and antecedent moisture conditions. Winter–spring precipitation and soil moisture deficit at the beginning of the water year accounted for 83% of the variability in streamflow, which was almost as accurate as applying the more complex physically-based Simultaneous Heat and Water (SHAW) numerical model (r 2 = 0.85) over the three dominant land cover classes. A conceptual model was formulated based on field observations, numerical simulations and previous studies. Winter precipitation and spring snowmelt must first replenish the deficit within the soil water profile and ground water system before water is delivered to the stream. During this period, surface water and ground water are tightly coupled and their interaction is critical to streamflow generation. Shortly after snow ablation, however, water flux in the root zone becomes decoupled from the ground water system and subsequent precipitation does little to contribute to streamflow for the current year, but serves to offset ET and the soil moisture deficit at the beginning of the following year. This study demonstrates the merits of long-term catchment-scale research to improve our understanding of how climate and land cover interact to control hydrologic dynamics in complex mountainous terrain. Published by Elsevier B.V.

Resume Introduction Les procedures d’angioplastie coronaire sont largement utilisees dans le traitement de la maladie coronarienne. L’implantation de stent dans la paroi vasculaire est associee a l’apparition des processus inflammatoires locaux et a un degre de myonecrose. Cependant, les relations entre la reponse inflammatoire systemique, la myonecrose et les caracteristiques cliniques et procedurales demeurent meconnues. Objectifs (i) Evaluer, apres angioplastie coronaire, la frequence de l’elevation de la troponine I (TnIc) et de la CRP ultrasensible (CRPus) ; (ii) mettre en evidence des facteurs cliniques et proceduraux associes a une elevation de ces biomarqueurs . Methodes Etude prospective unicentrique menee dans une population de malades hospitalises pour angioplastie programmee ou pour syndromes coronariens aigus sans elevation de la TnI. La CRPus et la TnIc ont ete dosees avant, apres et a 24 heures apres la realisation d’une angioplastie. Resultats Trente-quatre patients (64 ± 10,9 ans ; 28 hommes/six femmes) ont ete inclus dans l’etude. Une elevation en postprocedure de la CRPus et de la TnIc est observee respectivement dans 76,4 % (26 patients) et 47 % (16 patients) des cas. Aucune correlation entre la reponse inflammatoire induite par la procedure et la survenue d’une myonecrose n’a pu etre mise en evidence. La complexite angiographique des lesions, le nombre, la longueur totale des stents implantes, la duree de la procedure sont associes a la survenue d’une myonecrose post-angioplastie. En analyse multivariee, seuls l’absence de pretraitement par betabloquants ( p = 0,036, OR = 14,2 CI 95 % 7,69–100) et la duree de la procedure ( p = 0,032, OR = 2,6 CI 95 % 1,35–35) sont des facteurs independants associes a l’augmentation de la TnIc post-angioplastie coronarienne (les betabloquants ont un effet « protecteur » et les procedures longues sont associees plus souvent a une necrose myocytaire). Conclusion La survenue d’une myonecrose est un phenomene frequent apres angioplastie coronaire, en particulier au cours des procedures complexes. La myonecrose ne semble pas conditionnee par le statut inflammatoire, les facteurs de risque cardiovasculaires ou la presentation clinique initiale. Au contraire, la moindre elevation de la troponine, apres angioplastie, observee chez les patients pretraites par betabloqueurs suggere un veritable role pour ces produits dans les phenomenes de protection myocardique. Ces donnees, obtenues dans une cohorte de taille limitee, constituent des elements de reflexion quant a l’eventuel role protecteur des betabloquants. Cette piste reste a confirmer au cours de larges etudes, au mieux randomisees.

Background, objectives The extent of microvascular obstruction (MVO) during myocardial infarction referred to as the "no-reflow phenomenon", may determine myocardial damage. Our study aimed to investigate the incidence and the influencing factors of MVO in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous intervention (PCI). Patients, methods Using contrast-enhanced MRI, microvascular obstruction was defined as early hypoenhancement. Contrast defects were scored from 0 (no hypoenhancement) to 3 (strong hypoenhancement). 50 patients (56±11 years) with STEMI underwent PCI. Contrast-enhanced MRI (6±2 days after STEMI) and biochemical parameters were evaluated. Results Microvascular obstruction (score 1 to 3) was observed in 90% of the patients and major microvascular obstruction (score 2–3) in 54%. In univariate analysis, leukocytes and CRP levels were associated with MVO, whereas pre-infarction angina and prior medication by aspirin or calcium channel antagonist appeared protective. Microvascular obstruction intensity positively correlated with baseline inflammation status assessed by C-reactive protein and leukocytes (rho=0.43 and rho=0.44; p =0.003), the peak of CK (rho=0.56; p =0.01) or Troponin I (rho=0.59; p =0.01) and negatively correlated with LVEF (rho=−0.44; p =0.002). Multivariate analysis identified the absence of pre-infarction angina as the only independent predictor for microvascular obstruction (odds ratio, 8.35, 95% confidence interval 1.27–54.71; p =0.027). Conclusion MRI-detected microvascular obstruction has a high incidence in patients with STEMI treated by primary PCI and determines post-MI LVEF even in patients with post PCI TIMI 3 flow score. Pre-infarction angina appears to be an independent determinant of the extent of MVO detected by MRI.

Resume L'association thienopyridine–aspirine a permis le developpement de l'angioplastie coronaire en diminuant le risque de thrombose de stent. A distance des procedures de revascularisation, une reponse plaquettaire inadaptee au traitement par clopidogrel est associee a un accroissement du risque de recidive thrombotique. En l'absence de consensus sur les techniques de depistage appropriees, la comparaison des differentes methodes disponibles est une etape indispensable au depistage des patients les plus a risque. Objectifs (i) evaluer la prevalence d'une resistance biologique au clopidogrel au sein d'une population de patients prise en charge en USIC pour SCA (ii) identifier les facteurs associes a l'existence d'une « resistance biologique » au clopidogrel (iii) evaluer la concordance des deux principales methodes, l'agregometrie plaquettaire a l'ADP et l'etude en cytometrie en flux de la phosphorylation de la proteine VASP. Patients, materiel et methodes Patients admis en USIC pour SCA avec ou sans sus-decalage du segment ST (n = 27). Un traitement par clopidogrel 300 mg puis 75 mg/j est institue en complement d'un traitement par aspirine. Une tritherapie antiplaquettaire (antiGPIIbIIIa) est instauree chez les patients les plus a risque. La mesure de l'agregabilite plaquettaire (agregation a l'ADP (5 et 10 et 20 microM), l'analyse quantitative de la phosphorylation de la proteine VASP sont realises avant tout traitement par clopidogrel (j0) et apres cinq jours au moins de traitement (j5). Cette methode permet de calculer un index de reactivite plaquettaire (IRP). Une « resistance biologique » au clopidogrel est definie dans ce travail par une reactivite plaquettaire residuelle superieure a 67,3 % a j5 (valeur moyenne –2SD de l'IRP mesuree chez les patients non traites) ou par une diminution inferieure a 30 % de l'agregabilite plaquettaire entre j0 et j5. Resultats Une diminution significative de l'IRP et des agregations plaquettaires est observee apres cinq jours de traitement par clopidogrel (p

Resume Les indications des stimulateurs cardiaques et des defibrillateurs automatiques s'elargissent. La connaissance des principes de leur fonctionnement devient un imperatif pour la prise en charge en urgence des patients qui en sont porteurs. Les principaux dysfonctionnements de ces materiels sont lies a une depletion de pile, une rupture de sonde ou d'isolant, un deplacement de sonde, un defaut de programmation, une augmentation des seuils de stimulation ou de defibrillation, mais il en existe d'autres comme l'infection ou la migration de sonde. Pour evaluer le dispositif, il faut recueillir les elements cliniques, puis les caracteristiques techniques de l'appareil mentionnees sur la carte delivree au moment de l'implantation. En urgence, l'analyse du fonctionnement des stimulateurs repose sur l'electrocardiogramme sans, puis avec application d'un aimant, celle des defibrillateurs sur le caractere approprie ou non des chocs electriques. Un defibrillateur qui delivre un choc inapproprie est inhibe par apposition d'un aimant sur son boitier. Toute interference electromagnetique expose au risque de deprogrammation et de panne des dispositifs implantables, et justifie une surveillance permanente du rythme cardiaque. D'autres complications (infection, deplacement de sondes…) exigent des traitements specifiques.

Resume La ketamine est un anesthesique general connu depuis longtemps. Le role des recepteurs N-methyl-D-aspartate dans la douleur nociceptive a entraine un regain d’interet des antagonistes des recepteurs NMDA comme la ketamine. De nombreuses etudes animales sur la ketamine et la tolerance aux morphiniques ont montre des resultats prometteurs. Les recentes donnees experimentales animales et cliniques ont clairement mis en evidence que le processus douloureux est lie a un equilibre entre des systemes pronociceptifs et antinociceptifs. Aussi, la douleur ressentie n’est pas uniquement le fait de l’influx nociceptif mais resulte aussi de processus de sensibilisation centrale. Nous avons analyse dans cette mise au point les donnees experimentales et cliniques et discute de l’efficacite de faibles doses de ketamine dans la prise en charge de la douleur aigue lors d’administration isolee ou en association avec d’autres substances antalgiques comme la morphine. Les faibles doses de ketamine comprennent un bolus intraveineux (0,1 a 0,5 mg/kg) suivi d’une perfusion a debit continu de 1 a 2 mcg/kg/min pendant 24 a 48 heures. Ces doses de ketamine ameliorent la douleur postoperatoire en diminuant la composante hyperalgesique et limite la tolerance morphinique ce qui s’accompagne d’une baisse de la consommation en analgesiques tout en ameliorant la qualite de l’analgesie. Les effets secondaires psychodysleptiques diminuent avec les faibles doses de ketamine. Cela suggere que l’administration de faibles doses de ketamine est sure et utile dans la prise en charge de la douleur postoperatoire quand elle est utilisee comme adjuvant aux anesthesiques locaux, morphiniques et autres substances analgesiques.

Resume Objectifs Les pathologies allergiques etant peu decrites en pre-hospitalier, nous avons souhaite en evaluer les modes de presentation, la frequence et les modalites de prise en charge. Methode Etude retrospective incluant les dossiers medicaux concernant les interventions primaires de notre SMUR. Deux periodes ont ete definies en fonction de la mise en place dans le service d’une procedure therapeutique « allergie » : P 1 (1 er juillet 2000 – 30 novembre 2001) et P 2 (1 er decembre 2001 – 30 juin 2003) correspondant respectivement aux dossiers des patients pris en charge avant et apres la mise en place de la procedure. Elements analyses : differents tableaux cliniques, therapeutiques administrees, devenir des patients, impact de la procedure therapeutique sur les pratiques medicales. Resultats Les situations cliniques les plus souvent rencontrees sont l’urticaire superficielle et l’urticaire profonde sans atteinte ORL. Les traitements prescrits sont en adequation avec les donnees de la litterature pour les pathologies les plus graves. Les corticoides sont, meme pour les pathologies les moins importantes, tres largement utilises au detriment des antiH1, meme si l’utilisation de ces derniers augmentent nettement entre les deux periodes. Les patients sont orientes dans 63,3 % des cas vers un service d’Urgences. La procedure therapeutique est respectee dans 25,4 % des situations en periode 2. Conclusion Les SMUR sont rarement confrontes a la pathologie allergique et la prise en charge est peu homogene. Des recommandations s’appuyant sur la litterature sont necessaires pour harmoniser les pratiques.

5-fluorouracil, an antimetabolite agent, has been widely used since 1957 for treatment of varied types of cancer such as gastro-intestinal, pancreas, breast, lung, head and neck malignancies. Cardiotoxicity of 5-fluorouracil is rare and was first described in 1975. It can induce severe complications and involve vital prognosis in the short-term. These complications are less known by cardiologists than medical oncologists. The following clinical case represents a potentially serious and rare case of completely reversible cardiogenic shock in a patient with a colo-rectal cancer. A better knowledge of these complications could reduce cases of death by an earlier diagnosis, and a better evaluation of patients with high cardiotoxicity risk.

Objective: To investigate the effects of IV lidocaine on spontaneous and evoked pain (allodynia and hyperalgesia) due to peripheral nerve injury (postherpetic neuralgia or nerve trauma) using quantitative sensory testing. Method: The authors randomized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day (mean 737 mg/day). Results: Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection. The drug also decreased mechanical dynamic allodynia and static (punctate) mechanical allodynia/hyperalgesia, but not thermal allodynia and hyperalgesia. The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia. Conclusions: These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury. Patients with mechanical allodynia may be good candidates for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers.

SummaryBackground and objective: Intubation of the trachea has been a risky cross-contamination procedure over the past decade because no perfect decontamination procedures exist. Infectious agents found on laryngoscopic devices have the potential for devastating spread of the human immunodeficiency virus, hepatitis viruses B and C and transmissible non-conventional agents. The purpose of this prospective observational study was to assess the quality of endotracheal intubation with disposable laryngoscope blades, under normal intubating conditions.Methods: Anaesthetists were asked to complete daily questionnaires regarding the difficulty of intubation experienced using the Vital View® disposable laryngoscope blade (Vital Signs Inc, Totowa, NC, USA). The choice of the type of blade (conventional or disposable blade) for the first attempt at intubation depended only on the operating room assignment. Glottic visualization during laryngoscopy was assessed by the modified Cormack and Lehane classification. Difficult tracheal intubation was evaluated by the intubation difficulty scale (>5, procedure involving moderate to major difficulty).Results: The anaesthetic staff recorded 219 intubations. One hundred-and-nineteen of first attempts at laryngoscopy were with disposable blades (DB group) and another 100 with conventional blades (CB group). There were no significant differences between the two groups for Cormack and Lehane score 3, for intubation difficulty scale scores >5 and for intubation difficulty scale score 0. There were 12 blade changes before successful intubation.Conclusions: In routine use, the Vital View® disposable laryngoscope blade appears to be an efficient device because it does not modify the ease of endotracheal intubation in most cases. Nonetheless, it may be advisable to maintain conventional laryngoscopes in reserve for difficult intubations.

Resume Objectifs. – Evaluer les connaissances et l’attitude theoriques du personnel medical et paramedical hospitalier concernant la prise en charge des arrets cardiaques (AC). Methode. – Un questionnaire anonyme, fonde sur l’enseignement dispense pour l’attestation de formation aux premiers secours (AFPS) a ete distribue au personnel medical et paramedical d’un l’hopital de 450 lits. Le questionnaire a porte sur la presence d’une formation anterieure concernant l’AC, sur la reconnaissance et la prise en charge d’un AC, sur les connaissances et l’experience en ce qui concerne les gestes de secourisme et la presence d’un chariot d’urgence en salle. Resultats. – Cinq cent soixante et onze personnes ont repondu au questionnaire sur 996 distribues (57 %) dont 158 personnes dans le groupe medical (Med) et 413 dans le groupe paramedical (Pmed). Soixante et onze pour cent des personnes du groupe « Med » et 64 % du groupe «Pmed » ont recu au moins une fois une formation concernant l’AC. Devant une perte de connaissance l’absence de mouvements ventilatoires spontanes a ete explicitement recherchee par 55 % des personnes du groupe « Med » et 19 % du groupe « Pmed ». Un pouls carotidien ou femoral a ete explicitement recherche par 70 % des personnes dans le groupe « Med » et 18 % dans le groupe « Pmed ». Devant un AC, 50 % des personnes du groupe « Med » degageaient les voies aeriennes, 75 % debutaient une ventilation artificielle et 86 %, un MCE et 42 % alertaient des secours. Pour le groupe « Pmed », nous avons retrouve respectivement 29, 47 %, 64 et 60 %. Dans le groupe « Med » 81 % des personnes pensaient savoir ventiler et 82 % ont ventile au moins une fois, 88 % pensaient savoir masser et 85 % ont masse au moins une fois. Dans le groupe « Pmed », nous avons retrouve respectivement 67, 76, 73 et 78 %. Soixante-quatre pour cent des personnes du groupe « Med » savaient qu’il existait un chariot d’urgence dans leur service contre 89 % pour le groupe « Pmed ». Conclusion. – Ce travail a montre que les connaissances theoriques concernant la prise en charge des AC du personnel paramedical et medical de notre hopital etaient insuffisantes au regard des recommandations nationales et internationales. L’analyse de cette etude a ete rendue difficile par le faible pourcentage de repondants et une probable surestimation des connaissances.

Early recovery after surgery provides patients with all means to counteract or minimize the deleterious effects of surgery. This concept is suitable for a surgical procedure (e.g., colorectal surgery) and comes in the form of a clinical pathway that covers three periods (pre-, intra- and postoperative). The purpose of this Expert panel guideline is firstly to assess the impact of each parameter usually included in the rehabilitation programs on 6 foreseeable consequences of colorectal surgery: surgical stress, postoperative ileus, water and energy imbalance, postoperative immobility, sleep alterations and postoperative complications; secondly, to validate the usefulness of each as criteria of efficiency criteria for success of rehabilitation programs. Two main criteria were selected to evaluate the impact of each parameter: the length of stay and frequency of postoperative complications. Lack of information in the literature forced experts to assess some parameters with criteria (duration of postoperative ileus or quality of analgesia) that mainly surrogate a positive impact for the implementation of an early recovery program. After literature analysis, 19 parameters were identified as potentially interfering with at least one of the foreseeable consequences of colorectal surgery. GRADE® methodology was applied to determine a level of evidence and strength of recommendation. After synthesis of the work of experts using GRADE® method on 19 parameters, 35 recommendations were produced by the organizing committee. The recommendations were submitted and amended by a group of reviewers. After three rounds of Delphi quotes, strong agreement was obtained for 28 recommendations (80%) and weak agreement for seven recommendations. A consensus was reached among anesthesiologists and surgeons on a number of approaches that are likely not sufficiently applied for rehabilitation programs in colorectal surgery such as: preoperative intake of carbohydrates; intraoperative hemodynamic optimization; oral feeding resume before ha24; gum chewing after surgery; patient out of bed and walking at D1. The panel also clarified the value and place of such approaches such as: patient information; preoperative immunonutrition; laparoscopic surgery; antibiotic prophylaxis; prevention of hypothermia; systematic prevention of nausea and vomiting; morphine-sparing analgesic techniques; indications and techniques for bladder catheterization. The panel also confirmed the futility of approaches such as: bowel preparation for colon surgery; maintain of the nasogastric tube; surgical drainage for colonic surgery.

Background: Bispectral index (BIS) monitoring has been found to decrease the requirements for propofol, sevoflurane and desflurane and to improve recovery. We wanted to assess the effect of BIS monitoring on intraoperative isoflurane utilisation, and the early recovery profile. Methods: Eighty patients undergoing various surgical procedures were studied. In the first phase of the study, patients were anaesthetised without the use of BIS, the anaesthetists being blinded to the BIS readings, and isoflurane being administered according to standard clinical practice (control group). In a second phase, isoflurane was titrated to maintain a BIS value between 40 and 60 during surgery, and then 60–70 during 15 min prior to the end of surgery (BIS group). Isoflurane consumption was measured. Recovery times and the time to achieve a modified Aldrete score of 9 were recorded. Results: Despite similar mean BIS levels during maintenance of anaesthesia, the cumulative time spent with BIS values between 40 and 60 during maintenance of anaesthesia was significantly longer in the BIS group as compared with the control group (P

UNLABELLED We evaluated the effect of perioperative administration of two doses of morphine for postoperative analgesia after remifentanil-based anesthesia. The prospective, randomized study included 245 patients from 33 centers. All patients were scheduled for abdominal or urological surgery lasting more than 1 h. General anesthesia used remifentanil as the perioperative opioid (1 microg/kg as a bolus then, 0.5 microg/kg as a continuous infusion). A morphine bolus of 0. 15 mg/kg (0.15-mg group) or 0.25 mg/kg (0.25-mg group) was administered 30 min before the end of surgery. In the postanesthesia care unit, pain scores for patients were evaluated by using behavioral pain scores of 1-3, verbal pain scores of 0-3, and visual analog scale scores of 0-10). Postoperative analgesia was obtained by a morphine titration (3 mg every 5 min). Demographic and surgery characteristics were similar in both groups. The delay for first demand of morphine was similar in the 0.15-mg and the 0.25-mg groups (26 [9-60] and 30 [10-60] min, respectively). The frequency of morphine titration was similar in both groups (75% and 66%, respectively). The amount of morphine used in the postanesthesia care unit was smaller in the 0.25-mg group (0.16 [0.0-1.25] vs 0.10 [0.0-0.56] mg/kg; P = 0.008). In the 0.25-mg group, the behavioral pain score was lower at 15 min, the verbal pain score was lower at 60 min (P < 0.001), and similar at 30 min. The visual analog scale pain score at 30 min and 60 min was similar in both groups. The incidence of minor side effects was similar in both groups. However, three cases of postoperative respiratory depression occurred in the 0.25-mg group compared with no cases in the 0.15-mg group. In conclusion, perioperative administration of morphine alone does not provide entirely adequate immediate postoperative pain control after remifentanil-based anesthesia in major surgery. IMPLICATIONS The administration of 0.15 or 0.25 mg/kg perioperative morphine during remifentanil-based anesthesia for major surgery does not preclude additional morphine administration in the postanesthesia care unit. The larger dose of 0.25 mg/kg slightly improves postoperative analgesia; however, it may be responsible for postoperative respiratory depression.

Une evaluation quantitative des douleurs neuropathiques centrales et des deficits sensitifs associes a la syringomyelie a ete realisee pour etudier les relations possibles entre la douleur et les deficits. Douze patients (7 hommes, 5 femmes) âges en moyenne de 40,7 ans±11,8 ans (27–63 ans), presentant une syringomyelie associee a une malformation de Chiari type 1 (9 cas), plus rarement liee a une scoliose ou a un traumatisme (2 cas) ont ete inclus. Une evaluation de l’intensite et de l’etendue de la douleur spontanee et de l’allodynie tactile a ete realisee, couplee a une determination des seuils de detection et de douleur a des stimulations mecaniques (poils de Von Frey), des seuils de detection et de douleur au chaud et au froid (thermotest), des seuils vibratoires (vibrametre), et de l’etendue des deficits thermiques. Cette evaluation a mis en evidence dans tous les cas des anomalies des seuils de detection et de douleur au chaud et au froid, s’etendant sur 1 a 18 dermatomes. Une IRM avec coupes axiales et longitudinales a mise en evidence une bonne correlation entre l’extension paramediane de la fente et la lateralisation des deficits. La douleur spontanee (16 territoires douloureux etudies) etait le plus souvent localisee dans une aire de deficit thermique (11 cas), mais aucune correlation n’a ete retrouvee entre son intensite et l’importance des deficits. En outre, les douleurs spontanees et surtout provoquees, etaient frequemment localisees dans des territoires peu deficitaires ou adjacents au deficit. Ces donnees indiquent l’interet de l’evaluation quantative des troubles de la sensibilite chez les patients syringomyeliques, en suggerant notamment que les douleurs neuropathiques centrales ne sont pas correlees a l’importance de la desafferentation.

Caudal anaesthesia is indicated for surgical procedures lasting less than 90 min. Fentanyl and clonidine are known to prolong postoperative caudal analgesia, but there are no data on their effect on duration of surgical analgesia. We evaluated if the addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia after single shot caudal block in children in a randomized, double-blind study. We studied 64 children, aged 6-108 months, undergoing bilateral correction of vesicoureteral reflux which was expected to last more than 90 min. Patients were allocated to one of four groups: group O received 1 ml kg-1 of a mixture of 0.25% bupivacaine with epinephrine and 1% lidocaine in equal parts; group F received the same mixture of local anaesthetics in addition to fentanyl 1 microgram kg-1; group C received the same mixture of local anaesthetics in addition to clonidine 1.5 micrograms kg-1; and group C + F received the same mixture of local anaesthetics in addition to fentanyl 0.5 microgram kg-1 and clonidine 0.75 microgram kg-1. Single shot caudal block was sufficient in only 57% of children in group O compared with 93% in groups C and F and 86% in group C + F (P = 0.035). Global assessment of anaesthesia, defined as the time from caudal injection to the first administration of analgesic (either during or after surgery), was significantly longer in the three groups of children who received additives compared with local anaesthetics alone (P = 0.035), but there were no differences between the three additive groups. Vomiting was observed only in children who received fentanyl. Addition of clonidine or fentanyl to local anaesthetics prolonged the duration of surgical analgesia of caudal block, allowing single shot caudal anaesthesia to be recommended for surgery lasting 90-150 minutes. Clonidine had some advantages over fentanyl as it did not produce clinically significant side effects.

Compartment syndromes are well recognized following major trauma. However, although uncommon, they may occur following athletic activity. We report a case of acute exertional peroneal compartmental syndrome in a 32-year-old that developed following horse riding. Because of the ignorance of pathology, a regional analgesia was carried out resulting in delayed diagnosis. Postoperative electromyography showed the absence of a fibula nerve compound action potential. At one-year follow-up visit following decompressive fasciotomy, muscular strength of the muscles of the anterior tibial compartment almost returned to normal. The presentation of this case of compartmental syndrome following horse riding allows to discuss the place of the regional anaesthesia. Because this anaesthesia technique can delay the diagnosis and the surgical treatment, it should not be used in first intention in the treatment of severe pain associated with compartmental syndrome.

This document describes the two membranes containment systems developed by the company Gaztransport & Technigaz for the transportation at sea of liquefied natural gas (LNG) and applied by several shipyards in Europe, United States, Japan and Korea. The merits of both containment systems are underlined with respect to the competition for operating flexibility as well as safety during LNG carrier operation. Finally, the merits of both containment systems in terms of construction and coasts are presented.

The authors conducted brief assessments in an outclinic setting to identify the functional properties of severe tantrums in three preschool-age boys with language delays. For one child, tantrums were sensitive to positive reinforcement in the form of access to preferred tangible stimuli (toys and preferred food). For a second child, tantrums also were sensitive to positive reinforcement but in the form of maternal attention and access to preferred stimuli (toys). The third child's tantrums were multiply controlled. For each participant, alternative communicative responses were identified and reinforced as replacements for tantrums. Results showed that brief functional analyses of tantrums serve as viable assessment options in outclinic settings. Further, identification of the functional properties of tantrums allowed for selection of replacement behaviors, which may be particularly useful for children with communication delays.

Resume Depuis 1980, date d'apparition du defibrillateur automatique implantable (DAI), un nombre croissant d'appareils a ete mis en place chez les patients a haut risque de mort subite par tachycardie ou fibrillation ventriculaire. Les progres technologiques et la miniaturisation ont permis de simplifier les techniques d'implantation du DAI. Celle par voie endoveineuse s'est pratiquement substitutee a celle par thoracotomie. La mise en place du dispositif s'effectue habituellement sous anesthesie generale. L'atteinte cardiaque sous-jacente et l'etat general du patient determinent le choix des medicaments, la technique anesthesique et l'ampleur du monitorage. Un mois apres l'implantation, l'electrophysiologiste confirme la programmation adequate du generateur en induisant chez le patient prealablement anesthesie une fibrillation ventriculaire, puis en s'assurant de sa resolution par le DAI. L'anesthesiste peut etre egalement confronte a la prise en charge de patients ayant un DAI. En pareil cas, les recommandations suivantes peuvent etre formulees : le port de gants est conseille au personnel entrant en contact avec le patient, afin d'eviter tout risque d'electrisation ; l'anesthesiste doit disposer d'un aimant pour desactiver le defibrillateur, ainsi que d'un defibrillateur transthoracique ; si celui-ci est utilise, les palettes externes sont a orienter perpendiculairement a l'axe reliant les electrodes internes ; le DAI doit etre de preference desactive pendant l'utilisation d'un bistouri electrique ou la realisation d'un electrochoc ; dans les cas difficiles, la collaboration avec un cardiologue s'avere souvent necessaire.

A 61-year-old man has been implanted with a Ventritex Profile MD V-186 HV3 ICD for ischemic cardiomyopathy with sustained inducible VT. Three years later, this patient received several inappropriate shocks during the device's interrogation. These shocks provoked ventricular fibrillation. They were caused by a failing soldering between the system random accessory memory (SRAM) module and the hybrid circuit of the device. The device was explanted in emergency.

Simbol‐X is an X‐Ray telescope operating in formation flight. It means that its optical performances will strongly depend on the drift of the two spacecrafts and its ability to measure these drifts for image reconstruction. We built a dynamical ray tracing code to study the impact of these parameters on the optical performance of Simbol‐X (see Chauvin et al., these proceedings). Using the simulation tool we have developed, we have conducted detailed analyses of the impact of different parameters on the imaging performance of the Simbol‐X telescope.

We have developed a simulation tool for a Wolter I telescope operating in formation flight. The aim is to understand and predict the behavior of the Simbol‐X instrument. As the geometry is variable, formation flight introduces new challenges and complex implications. Our code, based on Monte Carlo ray tracing, computes the full photon trajectories up to the detector plane, along with the relative drifts of the two spacecrafts. It takes into account angle and energy dependent interactions of the photons with the mirrors and applies to any grazing incidence telescope. The resulting images of simulated sources from 0.1 keV to 100 keV allow us to optimize the configuration of the instrument and to assess the performance of the Simbol‐X telescope.

Summary Background Early wheezing in infants is a potential risk factor for persistence of asthma into adulthood. Moreover, a personal or familial history of atopy are risk factors associated with persistence of pre-existing wheezing during childhood. However, their relative importance remains unclear. Objectives Firstly to determine the critical thresholds of common biological markers of atopy in wheezy infants associated with persistence of wheezing into childhood and secondly to rank these biological markers together with clinical parameters according to the strength of their association with wheezing persistence. Methods A cohort of infants less than 30 months old with recurrent wheezing was established in order to assess severity of respiratory symptoms and to look for the presence of atopy. At the age of 6 years, they were re-evaluated regarding remission of wheezing over the previous 12-months period. Results Data were available for 219 subjects. In 27% of them, wheezing persisted at 6 years of age. Critical biological thresholds associated with the risk of wheezing persistence were: (1) a blood eosinophilia count 470/mm3 (defining eosinophilia), and (2) a total serum IgE level 45 IU/mL (defining elevated IgE) during infancy. A multiple component factorial analysis identified a dimension associating eosinophilia, elevated IgE and allergic sensitization on the one hand with persistent wheezing at 6 years of age on the other (λ=0.15). According to a segmentation analysis, the main discriminative parameter of wheezing persistence was eosinophilia. Thus a lack of eosinophilia alone could account for 91% of infants in remission, and when combined with absence of allergic sensitization, remission was correctly discriminated in 96.9% of the study population. Conclusion Our data strongly suggest that the lack of eosinophilia in wheezy infants without ongoing infection could predict future remission of wheezing in a large majority of cases.

Long-term water balance investigations are needed to better understand hydrologic systems, especially semi-arid mountainous catchments. This study extended a previous 10-year water balance to 23 years for the Upper Sheep Creek (USC) catchment, a 26 ha, snow-fed, semi-arid rangeland headwater drainage within the Reynolds Creek Experimental Watershed in southwestern Idaho, USA. The ten-year water balance study at USC identified that runoff from the catchment was correlated (r2 = 0.52) to precipitation above a critical threshold of approximately 450 mm of precipitation necessary to generate runoff and that a strong relationship existed between simulated percolation beyond the root zone and measured runoff. The results from the current long-term study, however, indicate that thresholds and trends between these hydrologic quantities are strongly dependent on both antecedent and current hydroclimatic conditions. The influence of the system variability on runoff was captured reasonably well by simulations performed by the SHAW model, with r2 between runoff and simulated percolation beyond the root-zone as high as 0.96. This study will serve as a basis for post-treatment comparison for USC where a prescribed fire was conducted in the fall of 2007.

The basic current-carrying mechanism through a superconducting weak link embedded in a resistive environment undergoes a continuous crossover, as the voltage increases, from Josephson Cooper pair transfer exciting electromagnetic modes in the environment to multiple Andreev reflections leading to the creation of quasiparticles. We corroborate these ideas through measurements of the dc current-voltage characteristics of superconducting atomic contacts containing channels of arbitrary and adjustable transmission. We present a simple model, in the spirit of the classical resistively shunted junction model, that accounts well for the observed characteristics.

In the field of cardiac pacing, the past year has not been marked by the publication of decisive scientific works, but several important publications have continued to witness the dynamism of this discipline. Selecting the significant facts in 2006 was not easy. Yet, in the following lines, we have integrated them in the dynamic of this speciality. The validation of the concept of resynchronization is now definitively accepted, and its actual place in the strategy of treatment of heart failure is clearer. With the issue of the systematic adjunction of an anti-tachycardia function, we reach the meeting point between cardiac pacing, arrhythmology and heart failure.

Percutaneous coronary intervention (PCI) is widely used actually for the treatment of coronary disease. Stent implantation in the vessel wall is associated with local healing processes and some myonecrosis. However, little is known about the relationships between systemic inflammatory response, myonecrosis and the patient's and procedural characteristics.(i) To evaluate the level of C-Reactive Protein (hsCRP) and cardiac troponin I (cTnI) elevation after PCI; (ii) to determine the patient's and procedural factors associated with those elevations.This is a prospective monocentric study carried out in patients hospitalised for elective PCI or for ACS without cTnI elevation. CRP and cTnI were assessed before, after and 24 hours after the procedure.Thirty-four patients (mean age 64+/-10.9 years; sex ratio 28 males/six females) were included. hsCRP increased in 26 patients (76.4%) and cTnI in 16 patients (47%) after PCI. cTnI elevation did not correlate with inflammatory response. Whereas none of the studied parameters were statistically linked with hsCRP increase, cTnI elevation was significantly associated with AHA-ACC B(2)/C type lesion, the number and the total length of stents implanted, the duration of procedure and treatment by betablockers. Multivariate analysis showed that the independent predictors of cTnI elevation were procedure duration (p=0.032 OR=14.2 CI 95% 7.69-100) and the absence of pretreatment with betablockers (p=0.036, OR=2,6 CI 95% 1.35-35).cTnI elevation following PCI is very frequent and related with the duration of the procedure. Our data suggest a protective role of betablockers in the occurrence of cTnI elevation after PCI. Confirmation of the protective role of betablockers in larger cohort is mandatory.

Although antiplatelet therapy with ASA-clopidogrel reduces the risk of cardiovascular episodes after PCI, a substantial number of events occur during follow-up. Sustained platelet reactivity under dual antiplatelet therapy was recently associated with increased risk of recurrent atherothrombotic events after PCI. Whereas it appears significant to determine clopidogrel responsiveness, the accurate platelet function assay is still under investigation.(i) to determine the proportion of "low-responders" or "resistants" patients during coronary syndrome (ii) to identify determinants of interindividual variability response to clopidogrel (iii) to compare aggregometry and VASP phosphorylation measured by flow cytometry. Patients were treated by clopidogrel (300 mg loading dose and 75 mg maintenance dose) and ASA (160 mg) (N=27). Additional treatment by GPIIbIIIa antagonists was given to high-risk patients (N=9). Platelet function was monitored by ADP aggregometry (5, 10, 20 microM) and VASP phosphorylation before any treatment by clopidogrel (d0) and at least five days after (d5). The platelet reactivity index (PRI), expressed as percentage, is the difference in VASP fluorescence intensity between resting (+ PGE1) and activated (ADP) platelets. At d5, low responsiveness to clopidogrel was defined by either (i) a PRI67.3% corresponding to the mean value -2SD measured in untreated patients (dO) (ii) or an absolute change (delta d0-d5) in aggregation (ADP 10 microM)to 30%.PRI, platelet aggregometry to ADP was significantly reduced following clopidogrel treatment (P0.01). A wide inter-individual variability to clopidogrel was observed at d5 (PRI from 11 to 83%). Whatever the platelet function used, a large proportion of patients were detected as "low-responders" (37% by VASP, 44% by ADP aggregometry). Absolute change in ADP aggregation was correlated to the variation of PRI (R = 0.559; P = 0.02). Contrary to ADP aggregometry, PRI was not influenced by GPIIbIIIa antagonists or prior administration of ASA. However, the conformity of the two methods to evaluate clopidogrel responsiveness was only 66%. No differences in platelet aggregometry could be observed at d5 between "low" and "good-responders" defined by VASP analysis. At d5, a higher PRI value could be detected in male and patients with history of dyslipemia.During coronary syndrome, impaired platelet responsiveness to clopidogrel was observed in a large proportion of patients whatever the platelet function assay used. VASP analysis was found insensitive to GPIIbIIIa or aspirin administration. Possible mechanisms linking clopidogrel "resistance" measured by VASP assay and enhanced thrombogenicity remain to be characterized. Indeed, clopidogrel "resistance" defined by VASP analysis was not associated with higher platelet aggregation.

We have probed the current-phase relation of an atomic contact placed with a tunnel junction in a small superconducting loop. The measurements are in quantitative agreement with the predictions of a resistively shunted SQUID model in which the Josephson coupling of the contact is calculated using the independently determined transmissions of its conduction channels., Comment: to be published in Physical Review Letters

We have measured the effect of microwave irradiation on the dc current-voltage characteristics of superconducting atomic contacts. The interaction of the external field with the ac supercurrents leads to replicas of the supercurrent peak, the well known Shapiro resonances. The observation of supplementary fractional resonances for contacts containing highly transmitting conduction channels reveals their non-sinusoidal current-phase relation. The resonances sit on a background current which is itself deeply modified, as a result of photon assisted multiple Andreev reflections. The results provide firm support for the full quantum theory of transport between two superconductors based on the concept of Andreev bound states.