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International audience; 11 ATP signaling and surface P2X4 receptors are upregulated selectively in neurons and/or glia in various CNS disorders 12 including anxiety, chronic pain, epilepsy, ischemia, and neurodegenerative diseases. However, the cell-specific functions of 13 P2X4 in pathological contexts remain elusive. To elucidate P2X4 functions, we created a conditional transgenic knock-in 14 P2X4 mouse line (Floxed P2X4mCherryIN) allowing the Cre activity-dependent genetic swapping of the internalization 15 motif of P2X4 by the fluorescent mCherry protein to prevent constitutive endocytosis of P2X4. By combining molecular, 16 cellular, electrophysiological, and behavioral approaches, we characterized two distinct knock-in mouse lines expressing 17 noninternalized P2X4mCherryIN either exclusively in excitatory forebrain neurons or in all cells natively expressing P2X4. 18 The genetic substitution of wild-type P2X4 by noninternalized P2X4mCherryIN in both knock-in mouse models did not 19 alter the sparse distribution and subcellular localization of P2X4 but increased the number of P2X4 receptors at the surface of 20 the targeted cells mimicking the pathological increased surface P2X4 state. Increased surface P2X4 density in the 21 hippocampus of knock-in mice altered LTP and LTD plasticity phenomena at CA1 synapses without affecting basal 22 excitatory transmission. Moreover, these cellular events translated into anxiolytic effects and deficits in spatial memory. Our 23 results show that increased surface density of neuronal P2X4 contributes to synaptic deficits and alterations in anxiety and 24 memory functions consistent with the implication of P2X4 in neuropsychiatric and neurodegenerative disorders. 25 Furthermore, these conditional P2X4mCherryIN knock-in mice will allow exploring the cell-specific roles of P2X4 in 26 various physiological and pathological contexts. 27

We define an intersection product of tropical cycles on matroid varieties (via cutting out the diagonal) and show that it is well-behaved. In particular, this enables us to intersect cycles on moduli spaces of tropical rational marked curves $M_{0,n}$ and $M_{0,n}(\R^r, d)$. This intersection product can be extended to smooth varieties (whose local models are matroid varieties). We also study pull-backs of cycles and rational equivalence., Comment: 23 pages, 5 figures

We use piecewise polynomials to define tropical cocycles generalising the well-known notion of tropical Cartier divisors to higher codimensions. Groups of cocycles are tropical analogues of Chow cohomology groups. We also introduce an intersection product of cocycles with tropical cycles - the counterpart of the classical cap product - and prove that this gives rise to a Poincar\'e duality in some cases., Comment: 15 pages, 3 figures, some more details added

Background Satisfaction is considered a valuable measure of outcome of healthcare processes. Only a few anesthesia-related validated questionnaires are reported. Because their scope is restricted to specific clinical contexts, their use remains limited. The objective of the current study was to develop and validate a self-reported questionnaire, Evaluation du Vecu de l'Anesthesie Generale (EVAN-G), assessing the satisfaction of the perioperative period surrounding general anesthesia. Methods Development of the EVAN-G questionnaire comprised a phase of item generation and a phase of psychometric validation. The patient sample was generated to be proportionally matched to the population of patients undergoing general anesthesia in France. The structure of the questionnaire was identified studying interitem, item-dimension, and interdimension correlations and factor analyses. Data were concurrently gathered to assess external validity. The discriminant validity was determined by comparison of scores across well known patient groups. Reliability was assessed by computation of Cronbach alpha coefficients and by test-retest. Results Eight hundred seventy-four patients were recruited in eight anesthesia departments. The EVAN-G includes 26 items; six specific scores and one global index score are available. Correlations between EVAN-G scores and other concurrent measures supported convergent validity. The EVAN-G correlated poorly with age, American Society of Anesthesiologists physical status, total anesthesia time, and number of previous anesthesias. Significantly higher satisfaction was reported by patients older than 65 yr, belonging to the laryngeal mask group. Reliability and reproducibility were shown. Conclusion The EVAN-G adds important information oriented toward patients' perceptions. The authors' approach provides a novel, valid, and reliable tool that may be used in anesthesia practice.

OBJECTIVE To quantify the effect of body temperature and sepsis on energy expenditure in head-injured patients. DESIGN Prospective, nonrandomized, observational study. SETTING Neurosurgical intensive care unit. PATIENTS Severe head-injured patients. INTERVENTIONS Use of an indirect calorimeter to measure energy expenditure. MEASUREMENTS AND MAIN RESULTS Mean arterial pressure (MAP), heart rate (HR), body temperature, and mean hourly energy expenditure were recorded. Twenty-four patients had 1,919 hourly measures of the above parameters. The measurement periods were divided into four groups, according to the anesthetic agents used for sedation: fentanyl and midazolam (group FM); fentanyl, midazolam, and curarization (group C); thiopental (group T); and no sedation (group NS). The energy expenditure/basal energy expenditure ratio (EE/BEE) was significantly lower in group T (1.20 +/- 0.15) than in group FM (1.32 +/- 0.24) or group C (1.32 +/- 0.20) and was significantly higher in group NS (1.60 +/- 0.33). There was a significant correlation between body temperature and EE/BEE (p < .0001, r2 = .27) only in sedated patients. Using the equation of the regression line to correct energy expenditure for differences in body temperatures between groups, the difference in energy expenditure between groups with sedation disappeared. This finding suggested that the low energy expenditure under thiopental was due only to hypothermia. Sepsis significantly increased energy expenditure independently of fever. There was a weak but statistically significant correlation between energy expenditure and HR (p

Transcranial Doppler is used to estimate changes in cerebral blood flow, but the effect of hemodilution on cerebral blood flow velocity (CBFV) in anesthetized patients has not been evaluated.The aim of this study was to measure the effect of isovolemic hemodilution on CBFV and lumbar cerebrospinal fluid pressure (PCSF) in anesthetized patients without change in other physiological variables that may affect CBFV. Patients under-going hemodilution were compared with a control group undergoing no hemodilution. With hemodilution, hematocrit decreased from 38% +/- 3% to 30% +/- 2%, arterial oxygen content (CaO2) decreased from 17.5 +/- 1.3 to 13.9 +/- 0.9 mL/dL, and CBFV increased from 50 +/- 10 to 58 +/- 10 cm/s. An equivalent of cerebral arterial O2 transport calculated as CaO2 x CBFV did not significantly change. Over the same time interval, there were no changes in the control group. There was no statistically significant change in PCSF, pulsatility index, PaCO (2), blood pressure, heart rate, or body temperature in either group. We conclude that CBFV reflects cerebral blood flow changes after hemodilution. Implications: Hemodilution increases cerebral blood flow but may change the cerebral artery diameter, which could confound perioperative measurement of cerebral blood flow velocity. This study found transcranial Doppler ultrasonography to accurately assess the effects of hemodilution on the cerebral circulation, but the hematocrit should be taken into account to fully understand perioperative cerebral blood flow velocity changes. (Anesth Analg 1998;86:320-4)

We introduce the notion of families of n-marked smooth rational tropical curves over smooth tropical varieties and establish a one-to-one correspondence between (equivalence classes of) these families and morphisms from smooth tropical varieties into the moduli space of n-marked abstract rational tropical curves., Comment: 24 pages, 3 figures Second version: Generalisations and corrections (e.g. a general tropical fibre product) Third version: Minor changes and corrections (version as published in Canadian Journal of Mathematics)

Objective The purpose of this study was to evaluate the benefits of intraoperative autotransfusion of autologous blood on the conservation of allogenic blood, including cost-effectiveness and the consequences for hemoglobin level and coagulation tests. Methods The Hoemonetics Cell Saver 4 autotransfusion system (Hoemonetics Corporation, MA) was used when the estimated blood loss was equal to or more than 500 ml. A total of 472 patients undergoing intracranial surgery were included in the study. Results Ninety patients (19%) received transfusions either with autologous blood or allogenic blood. Fifty-five patients (61%) received only autologous blood transfusions, 10 patients (11%) received both autologous and allogenic blood transfusions, and 25 patients (28%) received only allogenic blood transfusions. The amount of autologous blood transfused was 600 +/- 590 ml (range, 230-3000 ml). The amount of allogenic blood transfused was 3 +/- 3 units (range, 2-15 units). Autologous blood represented 68% of all blood products transfused. Mild abnormalities during coagulation tests occurred without clinical bleeding. Conclusion Autologous blood transfusions were demonstrated to be safe in patients undergoing intracranial surgery and to be more cost-effective than allogenic blood transfusions. Intraoperative autologous blood transfusions may be used alone in more than half of the patients requiring transfusions during intracranial surgery and decrease the amount of allogenic blood used. Improvements in the monitoring for the need of performing this technique, as well as preoperative blood donations, would decrease the amount of allogenic blood transfused.

The pharmacokinetics of pefloxacin (PF) were investigated in a population of 74 intensive care unit patients receiving 400 mg bid as 1-hr infusion using (i) Bayesian estimation (BE) of individual patient parameters followed by multiple linear regression (MLR) analysis and (ii) NONMEM analysis. The data consisted of 3 to 9 PF plasma levels per patient measured over 1 to 3 dosage intervals (total 113) according to four different limited (suboptimal) sampling 3-point protocols. Twenty-nine covariates (including 15 comedications) were considered to explain the interpatient variability. Predicted PF CL for a patient with median covariates values was similar in both BE/MLR and NONMEM analysis (4.02 and 3.92 L/hr, respectively). Bilirubin level and age were identified as the major determinants of PF CL by both approaches with similar predicted magnitude of effects (about 40 and 30% decrease of median CL, respectively). Confounding effects were observed between creatinine clearance (26% decrease of PF CL in the BE/MLR model), simplified acute physiology score (a global score based on 14 biological and clinical variables) (18% decrease of median CL in the NONMEM model) and age (entered in both models) which were highly correlated in our data base. However, both models predicted similar PF CL for actual subpopulations by using actual covariate values. Finally, the NONMEM analysis allowed identification of an effect of weight on CL (decrease of CL for weight65 kg) whereas the BE/MLR analysis predicted an increase of CL in patients treated with phenobarbital. In conclusion, both approaches allowed identification of the major risk factors of PF pharmacokinetics in ICU patients. Their potential use at different stages of drug development is discussed.

UNLABELLED Delayed recovery has been advocated to limit the postoperative stress linked to awakening from anesthesia, but data on this subject are lacking. In this study, we measured oxygen consumption (V(O2)) and plasma catecholamine concentrations as markers of postoperative stress. We tested the hypothesis that delayed recovery and extubation would attenuate metabolic changes after intracranial surgery. Thirty patients were included in a prospective, open study and were randomized into two groups. In Group I, the patients were tracheally extubated as soon as possible after surgery. In Group II, the patients were sedated with propofol for 2 h after surgery. V(O2), catecholamine concentration, mean arterial pressure (MAP), and heart rate (HR) were measured during anesthesia, at extubation, and 30 min after extubation. V(O2) and noradrenaline on extubation and mean V(O2) during recovery were significantly higher in Group II than in Group I (V(O2) for Group I: preextubation 215 +/- 46 mL/min, recovery 198 +/- 38 mL/min; for Group II: preextubation 320 +/- 75 mL/min, recovery 268 +/- 49 mL/min; noradrenaline on extubation for Group I: 207 +/- 76 pg/mL, for Group II: 374 +/- 236 pg/ mL). Extubation induced a significant increase in MAP. MAP, HR, and adrenaline values were not statistically different between groups. In conclusion, delayed recovery after neurosurgery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence from general anesthesia. IMPLICATIONS In this study, we tested the hypothesis that delayed recovery after neurosurgery would attenuate the consequences of recovery from general anesthesia. As markers of stress, oxygen consumption and noradrenaline blood levels were higher after delayed versus early recovery. Thus, delayed recovery cannot be recommended as a mechanism of limiting the metabolic and hemodynamic consequences from emergence after neurosurgery.