[Operating principles, physiological effects and practical issues of high-flow nasal oxygen therapy]. / Principes de fonctionnement, effets physiologiques et aspects pratiques de l'oxygénothérapie à haut débit.

First-line symptomatic treatment of acute respiratory failure (ARF) usually requires standard oxygen therapy, of which the limits have nonetheless led to the development of heated and humidified high-flow nasal oxygen therapy (HFNO). HFNO enables the delivery, through simple nasal cannula, of up to 100% of well-heated and humidified fraction of inspired oxygen (FiO2), at a maximum flow rate of 50 to 70 L/min of gas according to the devices chosen (specific or ventilator). The technical characteristics and operating principles of HFNO (coverage of the patient's spontaneous inspiratory flow, improved conditioning of the inspired gases, comfortable nasal cannula) yield a number of interdependent physiological effects that improve not only oxygenation conditions but also ventilatory mechanics. While it could be indicated in many clinical situations, including first-line hypoxemic ARF, the simplicity of HFNO implementation and the respiratory comfort it procures should in no way minimize the clinical monitoring of patients for whom endotracheal intubation may be required, and should not be unduly delayed.

Covid-19 severe hypoxemic pneumonia: A clinical experience using high-flow nasal oxygen therapy as first-line management.

PURPOSE: To report a French experience in patients admitted to Intensive Care Unit (ICU) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring high fractional concentration of inspired oxygen supported by high flow nasal cannula (HFNC) as first-line therapy. METHODS: Retrospective cohort study conducted in two ICUs of a French university hospital. All consecutive patients admitted during 28-days after the first admission for SARS-CoV-2 pneumonia were screened. Demographic, clinical, respiratory support, specific therapeutics, ICU length-of-stay and survival data were collected. RESULTS: Data of 43 patients were analyzed: mainly men (72%), median age 61 (51-69) years, median body mass index of 28 (25-31) kg/m2, median simplified acute physiology score (SAPS II) of 29 (22-37) and median PaO2/fraction of inspired oxygen (FiO2) (P/F) ratio of 146 (100-189) mmHg. HFNC was initiated at ICU admission in 76% of patients. Median flow was 50 (45-50) L/min and median FiO2 was 0.6 (0.5-0.8). 79% of patients presented at least one comorbidity, mainly hypertension (58%). At day (D) 28, 32% of patients required invasive mechanical ventilation, 3 patients died in ICU. Risk factors for intubation were diabetes (10% vs. 43%, P=0.04) and extensive lesions on chest computed tomography (CT) (P=0.023). Patients with more than 25% of lesions on chest CT were more frequently intubated during ICU stay (P=0.012). At ICU admission (D1), patients with higher SAPS II and Sequential Organ Failure Assessment (SOFA) scores (respectively 39 (28-50) vs. 27 (22-31), P=0.0031 and 5 (2-8) vs. 2 (2-2.2), P=0.0019), and a lower P/F ratio (98 (63-109) vs. 178 (126-206), P=0.0005) were more frequently intubated. Among non-intubated patients, the median lowest P/F was 131 (85-180) mmHg. Four caregivers had to stop working following coronavirus 2 contamination, but did not require hospitalization. CONCLUSION: Our clinical experience supports the use of HFNC as first line-therapy in patients with SARS-COV-2 pneumonia for whom face mask oxygen does not provide adequate respiratory support.

Persistent swallowing disorders after extubation in mechanically ventilated patients in ICU: a two-center prospective study.

BACKGROUND: Persistent swallowing disorders (SD) are non-pulmonary complications of mechanical ventilation (MV). However, there are few clinical studies on persistent SD in critically ill patients undergoing tracheal intubation for MV. The aim of the present study was to assess the incidence and characteristics of clinical manifestations associated with persistent SD. METHODS: We prospectively evaluated in patients requiring more than 7 days of invasive MV the incidence and characteristics of clinical manifestations related to persistent SD. For this purpose, quality of swallowing was assessed within 24 h after extubation by an experienced physical therapist not directly involved in patient management. Swallowing assessment consisted in a specific standardized test combining a swallowing test and a full clinical evaluation of the cranial nerves involved in swallowing. In patients with SD on the first test, a second test was done within 48 h in order to discriminate between transient and persistent SD. RESULTS: Among the 482 patients mechanically ventilated more than 7 days, 138 were enrolled in this study. The first test performed 24 h after extubation revealed SD in 35 patients (25%). According to the second test performed 48 h later, SD were considered transient in 21 (15%) and persistent in 14 (10%) cases. Patients with persistent SD were older (66 ± 16 vs 58 ± 15 years), had lower bodyweight at admission (76 ± 15 vs 87 ± 23 kg) and received less often neuromuscular blocking agents (36% vs 66%) compared to patients without or with only transient SD. Patients with persistent SD had longer duration of Intensive Care Unit (ICU) stay after first extubation and longer delay to oral feeding than patients without or with only transient SD, respectively, 11 ± 9 vs 7 ± 6 days and 23 ± 33 vs 5 ± 7 days. CONCLUSIONS: Based on a specific standardized clinical test, 25% of patients mechanically ventilated more than 7 days exhibited clinical manifestations of SD. However, SD were considered as persistent after extubation in only 10% of them. Persistent SD were associated with longer duration of ICU stay after extubation and longer time of enteral feeding. TRIAL REGISTRATION: The study is registered with Clinical Trials (NCT01360580).

Landau Velocity for Collective Quantum Hall Breakdown in Bilayer Graphene.

Breakdown of the quantum Hall effect (QHE) is commonly associated with an electric field approaching the inter-Landau-level (LL) Zener field, the ratio of the Landau gap and the cyclotron radius. Eluded in semiconducting heterostructures, in spite of extensive investigation, the intrinsic Zener limit is reported here using high-mobility bilayer graphene and high-frequency current noise. We show that collective excitations arising from electron-electron interactions are essential. Beyond a noiseless ballistic QHE regime a large super-Poissonian shot noise signals the breakdown via inter-LL scattering. The breakdown is ultimately limited by collective excitations in a regime where phonon and impurity scattering are quenched. The breakdown mechanism can be described by a Landau critical velocity as it bears strong similarities with the roton mechanism of superfluids. In addition, we show that breakdown is a precursor of an electric-field induced QHE-metal transition.

[Mindfulness-based-relapse prevention (MBRP): Evaluation of the impact of a group of Mindfulness Therapy in alcohol relapse prevention for alcohol use disorders]. / Résultats préliminaires d'un groupe de pleine conscience (Mindfulness) chez des patients alcoolo-dépendants.

UNLABELLED: For several years, the learning of mindfulness has developed in a psychological intervention perspective, particularly in the field of addiction. Presently, the management of addictions with substances is centered on two questions: the motivation in the change of behaviour and in a significant change in alcohol consumption. Concerning alcohol dependence, the evolution of behaviour is variable and characterized by forgiveness episodes and relapses. Over many years, a treatment for the abuse of substance associated with techniques based on full consciousness (Kabat-Zinn, 1990; Segal et al., 2002) Mindfulness-based relapse prevention (MBRP) was developed by Marlatt et al. (2011). The prevention of the relapse therapy, based on full consciousness, is a program of eight sessions integrating techniques of "mindfulness" into the techniques of prevention of the relapse. However, not much research has focused on the MBRP, the publication of the manual regarding this intervention is too recent (Bowen S et al., 2011). OBJECTIVE: We are interested in the active mechanisms, which are at stake in the MBRP. Indeed, the meditation acts presents many mechanisms in the addicting disorders. Our non-controlled research was based on a protocol in order to evaluate the alcohol consummation, mindfulness, impulsiveness, automatic thoughts, anxiety and abilities to cope. The first results are interesting: reduction of alcohol consummation, increase of mindfulness, reduction of trigger relapse, increasing cognitive flexibility and high degree of satisfaction among participants. METHODOLOGY: An intervention MBRP was proposed to 26 patients who were assigned to three groups. They were questioned about their alcohol consumption and assessed by a protocol of seven evaluations before and after the group MBRP: Five Facets Mindfulness (FFMQ), Impulsive Behavior Scale (UPPS), Acceptance and Action Questionnaire (AAQ II), State Trait Anxiety Inventory (STAI-A, STAI-B), Questionnaire of the automatic thoughts (QPA), and The Drug-Taking Confidence Questionnaire (DTCQ-8). This study exposes the preliminary results of an intervention for substance use disorders called mindfulness-based relapse prevention (mbrp) administered to five groups of alcohol dependent patients in a psychiatric department and a department of alcohol science in France. RESULTS: The results show maintained abstinence and a moderation leading to abstinence for the still consuming patients. According to our evaluations, we obtained several significant results after the therapy, despite our small cohort: patients accepted their thoughts and feelings better (FFMQ-judgment); the tendency to give in to the impulses decreased (urgency-UPPS), and their tolerance to anxiety increased (STAI-YA-YB). Moreover, this study appears to confirm that the MBRP program allows an improvement of self-efficiency. The study continues in order to confirm these results on a larger sample and to explore the long-term results, so as to propose a new work-tool for patients and caregivers.

Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein.

Rabies virus glycoprotein (RVG) can pseudotype lentiviral vectors, although at a lower efficiency to that of vesicular stomatitis virus glycoprotein (VSVG). Transduction with VSVG-pseudotyped vectors of rodent central nervous system (CNS) leads to local neurotropic gene transfer, whereas with RVG-pseudotyped vectors additional disperse transduction of neurons located at distal efferent sites occurs via axonal retrograde transport. Attempts to produce high-titre RVG-pseudotyped lentiviral vectors for preclinical and clinical trials has to date been problematic. We have constructed several chimeric RVG/VSVG glycoproteins and found that a construct bearing the external/transmembrane domain of RVG and the cytoplasmic domain of VSVG shows increased incorporation onto HIV-1 lentiviral particles and has increased infectivity in vitro in 293T cells and in differentiated neuronal cell lines of human, rat and murine origin. Stereotactic application of vector pseudotyped with this RVG/VSVG chimera in the rat striatum resulted in efficient gene transfer at the site of injection showing both neuronal and glial tropism. Distal neuronal transduction in the substantia nigra, thalamus and olfactory bulb via retrograde axonal transport also occurs after intrastriatal administration of chimera-pseudotyped vectors at similar levels to that observed with a RVG-pseudotyped vector. This is the first report of distal transduction in the olfactory bulb. The enhanced pseudotyping with this envelope should enable easier production of higher-titre pseudotyped lentiviral vectors that exhibit efficient local and dispersed neuronal transduction in the CNS.

Glass transition of a particle in a random potential, front selection in nonlinear renormalization group, and entropic phenomena in Liouville and sinh-Gordon models.

We study via renormalization group (RG), numerics, exact bounds, and qualitative arguments the equilibrium Gibbs measure of a particle in a d-dimensional Gaussian random potential with translationally invariant logarithmic spatial correlations. We show that for any d>/=1 it exhibits a transition at T=T(c)>0. The low-temperature glass phase has a nontrivial structure, being dominated by a few distant states (with replica symmetry breaking phenomenology). In finite dimension this transition exists only in this "marginal glass" case (energy fluctuation exponent straight theta=0) and disappears if correlations grow faster (single ground-state dominance straight theta>0) or slower (high-temperature phase). The associated extremal statistics problem for correlated energy landscapes exhibits universal features which we describe using a nonlinear Kolmogorov (KPP) RG equation. These include the tails of the distribution of the minimal energy (or free energy) and the finite-size corrections, which are universal. The glass transition is closely related to Derrida's random energy models. In d=2, the connection between this problem and Liouville and sinh-Gordon models is discussed. The glass transition of the particle exhibits interesting similarities with the weak- to strong-coupling transition in Liouville (c=1 barrier) and with a transition that we conjecture for the sinh-Gordon model, with correspondence in some exact results and RG analysis. Glassy freezing of the particle is associated with the generation under RG of new local operators and of nonsmooth configurations in Liouville. Applications to Dirac fermions in random magnetic fields at criticality reveal a peculiar "quasilocalized" regime (corresponding to the glass phase for the particle), where eigenfunctions are concentrated over a finite number of distant regions, and allow us to recover the multifractal spectrum in the delocalized regime.

Two-dimensional anisotropic non-Fermi-liquid phase of coupled Luttinger liquids.

Using bosonization techniques, we show that strong forward scattering interactions between one-dimensional spinless Luttinger liquids (LL) can stabilize a phase where charge-density wave, superconducting, and transverse single particle hopping perturbations are irrelevant. This new phase retains its LL-like properties in the directions of the chains, but with relations between exponents modified by the transverse interactions, whereas it is a perfect insulator in the transverse direction. The mechanism that stabilizes this phase is strong transverse charge-density wave fluctuations at incommensurate wave vector, which frustrates crystal formation by preventing lock-in of the in-chain density waves.

[Anomalies of the T wave following treatment of complete chronic left branch block by massage of the carotid sinus or injection of adenosine triphosphate]. / Anomalies de l'onde T après effacement d'un bloc complet de la branche gauche d'allure chronique par massage du sinus carotidien ou injection d'adénosine triphosphorique.

We studied the T wave during normal conduction in 25 patients aged 42 to 81 years (average 62 +/- 5) during sinus rhythm and complete left bundle branch block which regressed transiently after carotid sinus massage (22 cases) or injection of adenosine triphosphate (5 cases). Six patients had angina pectoris; coronary arteriography in 3 of the other 19 patients was normal. The reversion to normal intraventricular conduction was obtained with a lengthening of the ventricular cycle in all patients. The T wave axis with narrow QRS complexes was between + 70 degrees and -140 degrees (normal T axis in 11/25 patients); in the horizontal plane, the T wave was negative in V2 in 4 patients, in V2-V4 in 12 patients, in V2-V6 in 7 patients and in V4 in 1 patient. The amplitude of inversion in V2 varied from 0.1 to 1.5 mV; there was no significant difference between the patients with angina (0.50 +/- 0.31) and the remainder (0.43 +/- 0.16). In normal conduction, the T wave changes were more common in the horizontal plane (24/25 patients: 96%) than in the frontal plane (14/25 patients, 56%). The high incidence of abnormalities of ventricular repolarisation after regression of complete left bundle branch block does not appear to be related to coronary artery disease. Another explanation is proposed because of the analogy with the changes observed after terminating right ventricular pacing and after regression of a Wolff-Parkinson-White syndrome. An abnormality of initial ventricular depolarisation--common to left bundle branch block, the Wolff syndrome and right ventricular pacing--could be responsible for these T wave changes during normal conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of infectious secretions in the transmission of rhinovirus.

In a series of studies aimed at investigating the role of environmental surfaces in the transmission of certain respiratory virus infections, it was shown that small amounts of nasal mucus containing rhinovirus (infectious mucus) can spread from fingertips to door knobs, faucet handles, or other environmental surfaces and remain infectious for many hours. These surfaces can serve as a reservoir of virus and may provide sufficient infectious material to contaminate hands. Recent studies have shown that once virus is on the fingers, it may be transferred to the nasal and conjunctival mucosa by means of autoinoculation. It has been estimated that as little as 1.0 plaque-forming unit can produce an infection in a susceptible human. In the present experiments, the amount of rhinovirus transmitted from fingers contaminated with infectious mucus to environmental surfaces and from there onto the fingers of a volunteer who touched the contaminated objects was quantitated, and the efficiency of transfer was studied. From 3 to 1,800 plaque-forming units of rhinovirus were recovered from the fingertips of volunteers (recipients) who handled either a door knob or a faucet that had previously been manipulated by another volunteer (donor) whose fingers were contaminated with infectious mucus. The average amount of rhinovirus recovered from the fingers of the recipients was approximately 13.5% of the amount recoverable from the fingers of the donor. In experiments in which there was direct hand-to-hand contact between donor and recipient, about 6.7% of the virus present on the fingertips of donors was recoverable from the recipients.