Neurophysiological and Autonomic Dynamics of Threat Processing During Sustained Social Fear Generalization.

Survival in rapidly changing environments requires that organisms learn to predict noxious outcomes based on situational cues. One key facet of successful threat prediction is generalization from a specific predictive cue to similar cues, ensuring that a cue-outcome contingency is applied beyond the original learning environment. Generalization has also been observed in laboratory studies of human aversive conditioning: Most behavioral and physiological processes generalize responses from a stimulus paired with threat, (the CS+), to unpaired stimuli, with response magnitudes varying as a function of stimulus similarity. In contrast, work focusing on sensory responses in visual cortex has found a sharpening pattern, in which responses to stimuli closely resembling the CS+ are maximally suppressed, potentially reflecting lateral inhibitory interactions with the CS+ representation. Originally demonstrated with simple visual cues, changes in visuocortical tuning have also been observed in threat generalization learning across facial identity cues. It is however unclear to what extent these visuocortical changes represent transient or sustained effects and if generalization learning requires prior conditioning to the CS+. The present study addressed these questions using EEG and pupillometry in a paradigm involving several hundreds of trials of aversive generalization learning along a gradient of facial identities. Visuocortical ssVEP sharpening occurred after dozens of trials of generalization learning without prior differential conditioning, but diminished as learning progressed further. By contrast, generalization of EEG alpha power suppression, pupil dilation, and self-reported valence and arousal ratings was seen throughout the experimental session. Findings are consistent with models of threat processing emphasizing the role of changing visucocortical and attention dynamics in the formation, curation, and shaping of fear memories as observers continue learning about stimulus-outcome contingencies.

FRENCH versus ESI: comparison between two nurse triage emergency scales with referent scenarios.

OBJECTIVES: Acute triage is needed to prioritize care and achieve optimal resource allocation in busy emergency departments. The main objective is to compare the FRench Emergency Nurse Classification in Hospital scale (FRENCH) to the American scale Emergency Severity Index (ESI). Secondary objectives are to compare for each scale the over and under-triage, the triage matching to the gold standard and the inter-individual sorting reproducibility between the nurses. METHODS: This is a prospective observational study conducting among the nursing staffs and nursing students, selected from Caen University College Hospital and Lisieux Hospital Center emergency departments between two months. Each group individually rank 60 referent clinical cases composed by scales designers. An assessment of scale practicality is collected after for each tool. The collected parameters are analyzed by a Cohen kappa concordance test (κ). RESULTS: With 8151 triage results of gold standard scenarios sorting in two scales by the same nurses, the FRENCH scale seems to give better triage results than the US ESI scale (nurse: FRENCH 60% and ESI 53%, p = 0.003 ; nursing students: FRENCH 49% and ESI 42%, p < 0.001). In the two groups ESI has also a big tendency to under-sort (p = 0.01), particularly for the most severe patients (p < 0.01). The interobserver sorting concordance for any experience gives good results for the FRENCH and the ESI without any difference (nurses : FRENCH KPQ=0.72 ESI KPQ=0.78; p = 0.32 ; students KPQ=0.44 KPQ=0.55; p = 0.22). CONCLUSION: The ESI and FRENCH scales comparison on 8151 sorting results shows direct validity in favor of FRENCH one and similar interobserver agreement for both scales.

Manipulating Reward Sensitivity Using Reward Circuit-Targeted Transcranial Magnetic Stimulation.

BACKGROUND: The reward circuit is important for motivation and learning, and dysregulations of the reward circuit are prominent in anhedonic depression. Noninvasive interventions that can selectively target the reward circuit may hold promise for the treatment of anhedonia. METHODS: We tested a novel transcranial magnetic stimulation intervention for modulating the reward circuit. A total of 35 healthy individuals participated in a crossover controlled study targeting the reward circuit or a control site with intermittent theta burst stimulation (iTBS), an excitatory form of transcranial magnetic stimulation. Individual reward circuit targets were defined based upon functional magnetic resonance imaging functional connectivity with the ventral striatum, yielding targets in the rostromedial prefrontal cortex (rmPFC). Reward circuit function was assessed at baseline using functional magnetic resonance imaging, and reward circuit modulation was assessed using an event-related potential referred to as the reward positivity, which has been shown to reliably track reward sensitivity, as well as individual differences in depression and risk for depression. RESULTS: Relative to control iTBS, rmPFC iTBS enhanced the reward positivity. This effect was moderated by reward function, suggesting greater enhancements in individuals with lower reward function. This effect was also moderated by rmPFC-ventral striatum connectivity insofar as iTBS reached the rmPFC, suggesting that efficacy relies jointly on the strength of the rmPFC-ventral striatum pathway and ability of transcranial magnetic stimulation to target the rmPFC. CONCLUSIONS: These data suggest that the reward circuit can be modulated by rmPFC iTBS, and amenability to such modulations is related to measures of reward circuit function. This provides the first step toward a novel noninvasive treatment of disorders of the reward circuit.

Electrophysiological and phenomenological effects of short-term immersion in an altered sensory environment.

We examined the spontaneous cerebral electrophysiology and phenomenology during short-term perceptual deprivation consisting of an edgeless visual field combined with monotonous auditory input that eliminated potential grounding cues (multimodal Ganzfeld). Subjects (N = 22) were instructed to self-report perceptual fading using a button press. Relaxed wakefulness with closed eyes and viewing of a time-varying stimulus array served as control conditions. The power of parieto-occipital alpha rhythms during perceptual deprivation was midway between the eyes-closed and eyes-open conditions, with a state-specific frequency acceleration. Oscillatory alpha power remained enhanced in the multimodal Ganzfeld relative to viewing time-varying signals, despite no indication of diminished brain arousal. Subjects experienced a range of perceptual phenomena while in the altered sensory environment and individuals with faster alpha oscillations self-reported a greater number of fading episodes. We suggest that alpha-band electroencephalogram (EEG) dynamics signal internally oriented mentation in response to brief perceptual deprivation.

Perceptual phenomena in destructured sensory fields: Probing the brain's intrinsic functional architectures.

Destructured sensory fields, involving homogenous stimulation with little or no time-varying structure, provide a fertile ground for testing hypotheses about predictive coding in the human brain. Extended exposure to sensory patterns that deviate substantially from the statistics of natural environments can elicit a bewildering range of perceptual phenomena, up to and including vivid oneiric imagery. We illustrate how this large variety of perceptual effects can be understood as the experiential counterpart of auto-generated neuronal dynamics, unconstrained by parameters that tune the waking sensorium. We synthesize the literature on autonomous neuronal activity across multiple spatiotemporal scales with generative models of brain function and evidence from artificial neural architectures. Perception, we argue, emerges from a process of non-random sampling from an intrinsic distribution of hypotheses rather than a direct transfer of information from the world. The imagery that occurs in altered sensory environments is explained as the outcome of an iterative search through internal world models in which the structural typology of percepts reflects the brain's intrinsic functional architectures.

Genesis, goals and achievements of Long-Term Ecological Research at the global scale: A critical review of ILTER and future directions.

Since its founding in 1993 the International Long-term Ecological Research Network (ILTER) has gone through pronounced development phases. The current network comprises 44 active member LTER networks representing 700 LTER Sites and ~80 LTSER Platforms across all continents, active in the fields of ecosystem, critical zone and socio-ecological research. The critical challenges and most important achievements of the initial phase have now become state-of-the-art in networking for excellent science. At the same time increasing integration, accelerating technology, networking of resources and a strong pull for more socially relevant scientific information have been modifying the mission and goals of ILTER. This article provides a critical review of ILTER's mission, goals, development and impacts. Major characteristics, tools, services, partnerships and selected examples of relative strengths relevant for advancing ILTER are presented. We elaborate on the tradeoffs between the needs of the scientific community and stakeholder expectations. The embedding of ILTER in an increasingly collaborative landscape of global environmental observation and ecological research networks and infrastructures is also reflected by developments of pioneering regional and national LTER networks such as SAEON in South Africa, CERN/CEOBEX in China, TERN in Australia or eLTER RI in Europe. The primary role of ILTER is currently seen as a mechanism to investigate ecosystem structure, function, and services in response to a wide range of environmental forcings using long-term, place-based research. We suggest four main fields of activities and advancements for the next decade through development/delivery of a: (1) Global multi-disciplinary community of researchers and research institutes; (2) Strategic global framework and strong partnerships in ecosystem observation and research; (3) Global Research Infrastructure (GRI); and (4) a scientific knowledge factory for societally relevant information on sustainable use of natural resources.

[Ipsilateral dual kidney transplantation: a monocentric experience about 15 cases and literature review]. / Bi-transplantation rénale par abord ipsilatéral: expérience d'un centre à propos de 15 patients opérés consécutivement et revue de la littérature.

OBJECTIVE: Our study aimed to support the viability of the concept of Ipsilateral Dual Kidney Transplantation (DKT) by presenting our initial experience and proposing a review of the literature in this subject. METHODS: Fifteen ipsilateral DKT were performed at Nice University Hospital between August 2010 and March 2012. We have described our skin incision preferences, the vascular anastomoses, and the uretero-vesical reimplantation. We have analyzed the operative duration, the cold ischemia time (CIT) of both transplants, the blood transfusion volume, the intraoperative and postoperative complications, the time to diuresis recovery, the hospital stay, and the kinetics of the creatinine clearance until the third postoperative month. We have compared our results with those of the literature. RESULTS: The average CIT of the first transplant (T1) was 17.5 ± 3.3 hours, and that of the second (T2) was 18.4 ± 3.3 hours. The mean operating time was 234 ± 67 minutes. Patients received an average of 2 units of blood during surgery [0-4] and 1.8 units in the postoperative period [0-15]. The complications rate was 26.7% and included an intraoperative T2 artery thrombosis and 3 postoperative complications consistent with a hematoma, a T2 ureteric necrosis and a T2 venous thrombosis. Two transplants were lost (6.7%) and one death (6.7%) was reported on day 40. The average length of hospital stay was 20.9 ± 7.8 days. The mean creatinine clearance values were 12.6 mL/min at D2, 35.6 mL/min at D7, 44.9 mL/min on discharge, and 48.2 mL/min at D90. CONCLUSION: Our results supported the viability of the dual kidney transplantation concept. Furthermore the ipsilateral approach shortened the procedure and limited the surgical trauma by preserving the contralateral iliac fossa, without compromising renal function recovery or increasing morbidity.

New measurements of high-momentum nucleons and short-range structures in nuclei.

We present new measurements of electron scattering from high-momentum nucleons in nuclei. These data allow an improved determination of the strength of two-nucleon correlations for several nuclei, including light nuclei where clustering effects can, for the first time, be examined. The data also include the kinematic region where three-nucleon correlations are expected to dominate.

Probing quark-gluon interactions with transverse polarized scattering.

We have extracted QCD matrix elements from our data on doubly polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element d˜2, which arises strictly from quark-gluon interactions, to be unambiguously nonzero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.

Scaling of the F2 structure function in nuclei and quark distributions at x>1.

We present new data on electron scattering from a range of nuclei taken in Hall C at Jefferson Lab. For heavy nuclei, we observe a rapid falloff in the cross section for x>1, which is sensitive to short-range contributions to the nuclear wave function, and in deep inelastic scattering corresponds to probing extremely high momentum quarks. This result agrees with higher energy muon scattering measurements, but is in sharp contrast to neutrino scattering measurements which suggested a dramatic enhancement in the distribution of the "superfast" quarks probed at x>1. The falloff at x>1 is noticeably stronger in 2H and 3He, but nearly identical for all heavier nuclei.

New measurements of the European Muon Collaboration effect in very light nuclei.

New Jefferson Lab data are presented on the nuclear dependence of the inclusive cross section from (2)H, (3)He, (4)He, (9)Be and (12)C for 0.3 < x < 0.9, Q(2) approximately 3-6 GeV(2). These data represent the first measurement of the EMC effect for (3)He at large x and a significant improvement for (4)He. The data do not support previous A-dependent or density-dependent fits to the EMC effect and suggest that the nuclear dependence of the quark distributions may depend on the local nuclear environment.

[Original presentation of relapsing polychondritis: four cases]. / Manifestations originales au cours de la polychondrite atrophiante: à propos de quatre cas.

INTRODUCTION: The diagnosis of relapsing polychondritis is difficult as various manifestations may be encountered aside the characteristic episodes of recurrent chondritis. CASE REPORTS: From the retrospective analysis of the medical charts of patients presenting with relapsing polychondritis seen at Nîmes hospital between 1995 to 2006, four were selected for their original extra-cartilaginous manifestations. Case 1: relapsing polychondritis was diagnosed at the time of a thromboembolic event associated with a right uveitis, left temporomandibular arthritis and bilateral sensorineural deafness. Case 2: relapsing polychondritis occurred in a patient with history of bilateral sensorineural deafness with punctuated keratitis followed by a relapsing cutaneous leucocytoclastic vasculitis. Case 3: relapsing polychondritis associated with recurrent thromboembolic disease and a Sweet's syndrome and case 4: relapsing polychondritis presenting with a febrile erythema. CONCLUSION: The reported observations highlight the difficulty of the initial diagnosis of relapsing chondritis and the variety of the extra-chondritis manifestations that could be observed in this disease.

Effects of postoperative ketamine infusion on pain control and feeding behaviour in bitches undergoing mastectomy.

OBJECTIVES: To determine if ketamine administered to bitches at the end of a mastectomy, followed by a six-hour constant rate infusion (CRI), improved postoperative opioid analgesia and feeding behaviour. METHODS: The bitches were randomised into three groups: the placebo group received 0.09 ml/kg isotonic saline intravenously followed by a six-hour CRI of 0.5 ml/kg/hour, the low-dose ketamine received 150 microg/kg ketamine intravenously followed by a six-hour CRI of 2 microg/kg/minute and the high-dose ketamine group received 700 microg/kg ketamine intravenously followed by a six-hour CRI of 10 microg/kg/minute. Any additional opioids given were recorded at the time of extubation and at intervals after extubation. Food intake was evaluated eight (T8) and 20 (T20) hours after extubation by measuring the per cent coverage of basal energy requirements (BER). RESULTS: No significant difference was observed for opioid requirements between the three groups. The mean percentages of BER coverage did not differ significantly at T8 but the difference between the high-dose and low-dose ketamine groups (P=0.014), and the high-dose ketamine and placebo groups (P=0.038) was significant at T20. CLINICAL SIGNIFICANCE: This study demonstrated that 700 microg/kg ketamine given intravenously postoperatively followed by a six-hour ketamine CRI of 10 microg/kg/minute improved patient feeding behaviour.

Proton spin structure in the resonance region.

We have examined the spin structure of the proton in the region of the nucleon resonances (1.085 GeV

Correlated strength in the nuclear spectral function.

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment locates by direct measurement the correlated strength predicted by theory.

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Severe autoimmune hemolytic anemia following rituximab therapy in a patient with a lymphoproliferative disorder.

Rituximab (chimeric anti-CD20 IgG1 monoclonal antibody) is effective in the treatment of relapsed/refractory low-grade lymphomas of B-cell origin as well as in diffuse large B-cell lymphoma. Several reports also demonstrated the efficacy of rituximab for the treatment of autoimmune cytopenia, especially for cold agglutinin disease. We report the first case, to our knowledge, of rituximab-related autoimmune hemolytic anemia. The pathophysiological mechanisms remain unknown, although the drug could act through massive cytokines liberation after destruction of CD20 positive cells by rituximab.

Evaluation of imipenem 1.5 g daily in febrile patients with short duration neutropenia after chemotherapy for non-leukemic hematologic malignancies and solid tumors: personal experience and review of the literature.

Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir (n = 44), was 67/mm3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli. The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms (p = 0.007) and of infected sites (p = 0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment ofthe febrile patients with post chemotherapy neutropenia of short duration.

Hepatic intra-arterial injection of 1,25-dihydroxyvitamin D3 in lipiodol: Pilot study in patients with hepatocellular carcinoma.

1,25-dihydroxycholecalciferol [1,25-(OH)2 D3] has been shown to have antiproliferative effects in a wide variety of cancer cell lines. In vivo studies, although often limited by the development of hypercalcemia, have also shown the potential usefulness of 1,25-(OH)2 D3 in inhibiting tumor growth. The potential usefulness of the drug has been hampered by the development of hypercalcemia. This pilot clinical study was designed to evaluate the preclinical results that have shown, locoregional administration of 1,25-(OH)2 D3 in lipiodol can prevent the development of hypercalcemia. Eight patients with refractory HCC were given a single intrahepatic arterial dose (50, 75 or 100 microg) of 1,25-(OH)2 D3 dissolved in 5 ml of lipiodol. Following this, for 4 weeks serum calcium, 1,25-(OH)2 D3, alpha-fetoprotein and a range of biochemical indices were monitored. While, in 3 patients the calcium levels exceeded the normal range, even at these extremely high doses, non of the patients developed grade 3 hypercalcemia. 1,25-(OH)2 D3 administration also led to transient stabilization of serum alpha-fetoprotein in these patients. The data obtained support the hypothesis that, in patients with HCC, locoregional delivery of 1,25-(OH)2 D3 in lipiodol can allow administration of supra-pharmacological doses of the drug without the development of hypercalcemia.