Partial cricotracheal resection for severe pediatric subglottic stenosis: update of the Lausanne experience.

Until recently, severe pediatric subglottic stenosis (SGS) has been treated almost exclusively by laryngotracheoplasty procedures. Even in the most experienced centers, the results of single-stage operations for Cotton's grade III and IV stenoses have been disappointing. This paper reports our experience on 31 partial cricotracheal resections for severe SGS in infants and children. The stenosis was congenital in 6 cases and acquired after prolonged intubation in 25 cases. Twenty-seven patients were tracheotomy-dependent at the time of surgery. Twenty-two cases were classified as grade III and 9 cases as grade IV stenoses according to Cotton. The decannulation rate was 97% (30 of 31 cases) after an open procedure. There were no fatalities and no lesions to the recurrent laryngeal nerves, but there was 1 complete restenosis. Twenty-seven patients show no exertional dyspnea, 3 have a slight stridor with some dyspnea while exercising, and 1 patient is not decannulated. The voice is normal in 21 cases, a dysphonia is present in 9 cases, and the patient with complete restenosis acquired an esophageal voice. Postoperative follow-up is longer than 10 years in 8 cases and longer than 5 years in an additional 6 cases. All patients who reached adulthood show normal growth of the larynx and trachea. Considering the excellent results obtained in this consecutive series of 31 cases, partial cricoid resection with primary thyrotracheal anastomosis should be considered an important treatment option for severe SGS in infants and children.

Lire l'oral : pour une typologie linguistique des représentations écrites de l'oralité (le cas du français)

Cette thèse propose de passer en revue les modalités de la représentation écrite de l'oralité en français. La pratique littéraire constitue le matériau et l'horizon de la théorisation. La problématique - comment l'écrit représente-t-il l'oral ? - est d'abord située et reformulée dans le cadre de la linguistique de la parole (I). Les rapports entre oralité et scripturalité sont ensuite étudiés sous trois angles. L'angle biotechnologique compare la matérialité et l'affordance des signaux graphiques et des signaux acoustiques (II 1). L'examen sémiotique reconnaît dans le français écrit un système dit phonographique dont la fonction est de représenter l'expression des signes du français oral. Sont analysées alors les relations entre les systèmes de signes impliqués, la diversité des actualisations possibles du système phonographique (effets d'écoute), ainsi que diverses sémiotiques analogiques (II 2). On étudie ensuite le rôle de la prosodie dans la lecture. La position adoptée est la suivante : bien qu'elle soit facultative dans l'activité de lecture, la prosodie est spécialement sollicitée par des écrits qu'on peut caractériser linguistiquement. L'interprétation prosodique apporte à ces écrits un surcroît de signification en même temps qu'il produit un mode spécifique de représentation de l'oral appelé effet prosodique (II 3). L'angle sémantique est esquissé finalement : il conduit à dégager deux modalités de représentation supplémentaire. Pour la première, l'oral se situe sur le plan sémantico-référentiel de l'expression écrite (écrire à propos d'oral) ; pour la seconde, l'oral est un extérieur discursif modalisant le dire écrit : l'écrit est reconnu comme énoncé à la manière de l'oral (effet de style oral). - This PhD thesis attempts to review the modalities of orality in written representation. Literary writings act as the material for theorization. First of all, the thesis statement - how does writing represent oral - is situated and then, reformulated within the frame of linguistique de la parole (the linguistic field of speech) (I). The connections between orality and writing are then studied under three angles. The biotechnological angle compares the materiality and the affordance of graphic signs and acoustic signals (II 1). A semiotic examination acknowledges, in French, a phonographical system whose function is to represent the expression of French oral signs. Thus, the relationships between the systems of implicated signs, the diversity of possible actualisations of the phonographic system (voice effects), as well as various analogical semiotics are analysed (II 2). Furthermore, the role of prosody is studied within reading. The stand taken is the following : even though it is optional during a reading activity, prosody is especially sought-after by linguistically characterised writings. The prosodie interpretation brings to these writings a surge of signification while producing a specific mode of oral representation called the prosodie effects (II 3). The semantic angle is finally drawn : it leads to two additional modalities of representation. For the first part, speech is located on the semantic and referential plan of the written expression (writing about speech); as for the second part, spoken language is a discursive exteriority : writing is recognised as an oral-like utterance {oral-like effect).

Like Man, Like Woman: Roman Women, Gender Qualities and Conjugal Relationships at the Turn of the First Century

Modern scholarship often discusses Roman women in terms of their difference from their male counterparts, frequently defining them as 'other'. This book shows how Roman male writers at the turn of the first century actually described women as not so different from men: the same qualities and abilities pertaining to the domains of parenthood, intellect and morals are ascribed by writers to women as well as to men. There are two voices, however: a traditional, ideal voice and an individual, realistic voice. This creates a duality of representations of women, which recurs across literary genres and reflects a duality of mentality. How can we interpret the paradoxical information about Roman women given by the male-authored texts? How does this duality of mentality inform us about gender roles and gender hierarchy? This work analyses well-known, as well as overlooked, passages from the writings of Pliny the Younger, Tacitus, Suetonius, Quintilian, Statius, Martial and Juvenal and sheds new light on Roman views of women and their abilities, on the notions of private and public and on conjugal relationships. In the process, the famous sixth satire of Juvenal is revisited and its topic reassessed, providing further insights into the complex issues of gender roles, marriage and emotions. By contrasting representations of women across a broad spectrum of literary genres, this book provides consistent findings that have wide significance for the study of Latin literature and the social history of the late first and early second centuries.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. METHODS: In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. FINDINGS: Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). INTERPRETATION: The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. FUNDING: Merck KGaA, Darmstadt, Germany.

Auditory verbal hallucinations of epileptic origin.

Complex auditory hallucinations are often characterized by hearing voices and are then called auditory verbal hallucinations (AVHs). While AVHs have been extensively investigated in psychiatric patients suffering from schizophrenia, reports from neurological patients are rare and, in most cases, incomplete. Here, we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by analyzing the phenomenology of AVHs and patients' neuropsychological and lesion profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9 patients suffering AVHs were identified and studied by means of a semistructured interview, neuropsychological tests, and multimodal imaging, relying on a combination of functional and structural neuroimaging data and surface and intracranial EEG. We found that AVHs in patients with epilepsy were associated with prevalent language deficits and damage to posterior language areas and basal language areas in the left temporal cortex. Auditory verbal hallucinations, most of the times, consisted in hearing a single voice of the same gender and language as the patient and had specific spatial features, being, most of the times, perceived in the external space, contralateral to the lesion. We argue that the consistent location of AVHs in the contralesional external space, the prominence of associated language deficits, and the prevalence of lesions to the posterior temporal language areas characterize AVHs of neurological origin, distinguishing them from those of psychiatric origin.

Left recurrent laryngeal nerve palsy associated with silicosis.

Left recurrent laryngeal nerve palsy usually results from invasion or compression of the nerve caused by diseases localized within the aortopulmonary window. This study reports the case of a 76-yr-old male with vocal cord paralysis due to lymph node involvement by silicosis. This rare entity was identified by video-mediastinoscopy, which revealed a granulomatous and fibrosed recurrent lymph node encasing the nerve. The nerve was dissected and released from scar tissues. Progressive clinical improvement was observed followed by total and durable recovery of the voice after 15 weeks follow-up.

Treatment of velopharyngeal insufficiency by autologous fat injection.

Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation pharyngoplasty, using different implants, have all been used to address this trouble. We hereby present our results following rhinopharyngeal autologous fat injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between 2004 and 2007. The degree of hypernasal speech was evaluated pre- and postoperatively by a speech therapist and an ENT specialist and quantified by an acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with preoperative speech therapy (average, 8 years). The mean value of the nasalance score was 37% preoperatively and 23% postoperatively (p = 0.015). The hypernasality was reduced postoperatively in all patients (1-3 degrees of the Borel-Maisonny score). There were no major complications, two minor complications (one hematoma, one cervical pain). The autologous fat injection is a simple, safe, minimally invasive procedure. It proves to be efficient in cases of mild velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

ConnectomeViewer - Multi-Modal Multi-Level Network Visualization and Analysis.

Introduction: The field of Connectomic research is growing rapidly, resulting from methodological advances in structural neuroimaging on many spatial scales. Especially progress in Diffusion MRI data acquisition and processing made available macroscopic structural connectivity maps in vivo through Connectome Mapping Pipelines (Hagmann et al, 2008) into so-called Connectomes (Hagmann 2005, Sporns et al, 2005). They exhibit both spatial and topological information that constrain functional imaging studies and are relevant in their interpretation. The need for a special-purpose software tool for both clinical researchers and neuroscientists to support investigations of such connectome data has grown. Methods: We developed the ConnectomeViewer, a powerful, extensible software tool for visualization and analysis in connectomic research. It uses the novel defined container-like Connectome File Format, specifying networks (GraphML), surfaces (Gifti), volumes (Nifti), track data (TrackVis) and metadata. Usage of Python as programming language allows it to by cross-platform and have access to a multitude of scientific libraries. Results: Using a flexible plugin architecture, it is possible to enhance functionality for specific purposes easily. Following features are already implemented: * Ready usage of libraries, e.g. for complex network analysis (NetworkX) and data plotting (Matplotlib). More brain connectivity measures will be implemented in a future release (Rubinov et al, 2009). * 3D View of networks with node positioning based on corresponding ROI surface patch. Other layouts possible. * Picking functionality to select nodes, select edges, get more node information (ConnectomeWiki), toggle surface representations * Interactive thresholding and modality selection of edge properties using filters * Arbitrary metadata can be stored for networks, thereby allowing e.g. group-based analysis or meta-analysis. * Python Shell for scripting. Application data is exposed and can be modified or used for further post-processing. * Visualization pipelines using filters and modules can be composed with Mayavi (Ramachandran et al, 2008). * Interface to TrackVis to visualize track data. Selected nodes are converted to ROIs for fiber filtering The Connectome Mapping Pipeline (Hagmann et al, 2008) processed 20 healthy subjects into an average Connectome dataset. The Figures show the ConnectomeViewer user interface using this dataset. Connections are shown that occur in all 20 subjects. The dataset is freely available from the homepage (connectomeviewer.org). Conclusions: The ConnectomeViewer is a cross-platform, open-source software tool that provides extensive visualization and analysis capabilities for connectomic research. It has a modular architecture, integrates relevant datatypes and is completely scriptable. Visit www.connectomics.org to get involved as user or developer.

Partial cricotracheal resection in children weighing less than 10 kilograms.

OBJECTIVES: To assess the long-term outcome, safety, and efficacy of partial cricotracheal resection (PCTR) for subglottic stenosis in a group of children and infants weighing less than 10 kg at the time of the surgery. STUDY DESIGN: Historical cohort study. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: Thirty-six children weighing less than 10 kg at the time of the surgery were compared to a group of 65 children who weighed more than 10 kg. The Kaplan Meier method and Cox regression were carried out to detect differences in decannulation time and rates and to examine the influence of various parameters (i.e., comorbidities, type of surgery, and complications requiring revision surgery) at the time of decannulation. Evaluation of the long-term outcome was based on questionnaires assessing breathing, voice, and swallowing. RESULTS: Decannulation rate was 92 percent (33/36) for the group of children weighing less than 10 kg. No significant differences were found between the two body weight groups with respect to the aforementioned covariates. The median follow-up period was nine years (range, 1-23 yrs). Questionnaire responses revealed completely normal breathing and swallowing in 72 percent and 90 percent of the children, respectively. Seventy-one percent of the patients considered their voice to be rough or weak. CONCLUSION: PCTR in infants and children weighing less than 10 kg is a safe and efficient technique with similar long-term results when compared to results seen in older and heavier children.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

Partial Cricotracheal Resection in Children: Potential Pitfalls and Avoidance of Complications.

OBJECTIVES: To delineate the various factors contributing to failure or delay in decannulation after partial cricotracheal resection (PCTR) in children. STUDY DESIGN: Case series. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: A retrospective case review of 100 children who underwent PCTR between 1978 and 2008 for severe subglottic stenosis using an ongoing database. RESULTS: Ninety of 100 (90%) patients were decannulated. Six patients needed secondary tracheostomy. The results of the preoperative evaluation showed grade II stenosis in four patients, grade III in 64 patients, and grade IV in 32 patients. The overall decannulation rate was 100 percent in grade II, 95 percent in grade III, and 78 percent in grade IV stenosis. Fourteen (14%) patients required revision open surgery. The most common cause of revision surgery was posterior glottic stenosis. Partial anastomotic dehiscence was seen in four patients. Delayed decannulation (>1 year) occurred in nine patients. Overall mortality rate in the whole series was 6 percent. No deaths were directly related to the surgery. No iatrogenic recurrent laryngeal nerve injury was present in the entire series. CONCLUSION: Comorbidities and associated syndromes should be addressed before PCTR is planned to improve the final postoperative outcome in terms of decannulation. Perioperative morbidity due to anastomotic dehiscence, to a certain extent, can be avoided by intraoperative judgment in the selection of double-stage surgery when more than five tracheal rings need to be resected. Subglottic stenosis with glottic involvement continues to pose a difficult challenge to pediatric otolaryngologists, often necessitating revision procedures.

Assimilation des expériences problématiques: une étude de cas de psychothérapie psychodynamique limitée dans le temps [Assimilation of problematic experiences: a case study on short-term dynamic psychotherapy].

The assimilation model is a qualitative and integrative approach that enables to study change processes that occur in psychotherapy. According to Stiles, this model conceives the individual's personality as constituent of different voices; the concept of voice is used to describe traces left by past experiences. During the psychotherapy, we can observe the progressive integration of the problematic voices into the patient's personality. We applied the assimilation model to a 34-session-long case of an effective short-term dynamic psychotherapy. We've chosen eight sessions we transcribed and analyzed by establishing points of contact between the case and the theory. The results are presented and discussed in terms of the evolution of the main voices in the patient.

The parties' voices in a therapeutic interview

Drawing on a dialogical approach inspired by Bakhtin, we start from the assumptionthat a concrete discussion is an intermingling between dialogue in praesentia and dialogue inabsentia, and we refer to the notion of 'enunciative positioning' to account for the variousrelations that a speaker may express towards the voices that he or she invokes. Our data arebased on a first therapeutic interview between a therapist, a mother and a child in a counselingcenter for children and adolescents. We identify the various voices invoked in this interviewand show that three levels of discursive process were involved: (a) the speakers invokedabsent speakers; (b) at the same time they developed their own discourse on the basis of theirinterlocutors' discourse which (c) itself drew on absent speakers or voices. We highlight thevarious discursive processes through which the speakers integrate their own voice into absentvoices, or integrate a distant voice so that it loses its property of being a distant (andborrowed) voice. As a theoretical and methodological contribution to dialogism, our resultsshow that absent voices and their specific intermingling with hic et nunc exchanges were amajor resource for therapeutic changes.

Emotion expression in body action and posture

Emotion communication research strongly focuses on the face and voice as expressive modalities, leaving the rest of the body relatively understudied. Contrary to the early assumption that body movement only indicates emotional intensity, recent studies show that body movement and posture also convey emotion specific information. However, a deeper understanding of the underlying mechanisms is hampered by a lack of production studies informed by a theoretical framework. In this research we adopted the Body Action and Posture (BAP) coding system to examine the types and patterns of body movement that are employed by 10 professional actors to portray a set of 12 emotions. We investigated to what extent these expression patterns support explicit or implicit predictions from basic emotion theory, bi-dimensional theory, and componential appraisal theory. The overall results showed partial support for the different theoretical approaches. They revealed that several patterns of body movement systematically occur in portrayals of specific emotions, allowing emotion differentiation. While a few emotions were prototypically encoded by one particular pattern, most emotions were variably expressed by multiple patterns, many of which can be explained as reflecting functional components of emotion such as modes of appraisal and action readiness. It is concluded that further work in this largely underdeveloped area should be guided by an appropriate theoretical framework to allow a more systematic design of experiments and clear hypothesis testing.