Affective state and voice : cross-cultural assessment of speaking behavior and voice sound characteristics : a normative multicenter study of 577 + 36 healthy subjects

BACKGROUND: Human speech is greatly influenced by the speakers' affective state, such as sadness, happiness, grief, guilt, fear, anger, aggression, faintheartedness, shame, sexual arousal, love, amongst others. Attentive listeners discover a lot about the affective state of their dialog partners with no great effort, and without having to talk about it explicitly during a conversation or on the phone. On the other hand, speech dysfunctions, such as slow, delayed or monotonous speech, are prominent features of affective disorders. METHODS: This project was comprised of four studies with healthy volunteers from Bristol (English: n = 117), Lausanne (French: n = 128), Zurich (German: n = 208), and Valencia (Spanish: n = 124). All samples were stratified according to gender, age, and education. The specific study design with different types of spoken text along with repeated assessments at 14-day intervals allowed us to estimate the 'natural' variation of speech parameters over time, and to analyze the sensitivity of speech parameters with respect to form and content of spoken text. Additionally, our project included a longitudinal self-assessment study with university students from Zurich (n = 18) and unemployed adults from Valencia (n = 18) in order to test the feasibility of the speech analysis method in home environments. RESULTS: The normative data showed that speaking behavior and voice sound characteristics can be quantified in a reproducible and language-independent way. The high resolution of the method was verified by a computerized assignment of speech parameter patterns to languages at a success rate of 90%, while the correct assignment to texts was 70%. In the longitudinal self-assessment study we calculated individual 'baselines' for each test person along with deviations thereof. The significance of such deviations was assessed through the normative reference data. CONCLUSIONS: Our data provided gender-, age-, and language-specific thresholds that allow one to reliably distinguish between 'natural fluctuations' and 'significant changes'. The longitudinal self-assessment study with repeated assessments at 1-day intervals over 14 days demonstrated the feasibility and efficiency of the speech analysis method in home environments, thus clearing the way to a broader range of applications in psychiatry. © 2014 S. Karger AG, Basel.

Cricotracheal resection for adult and pediatric subglottic stenoses: Similarities and differences

Since the mid-1970s thoracic surgeons have used cricotracheal resection (CTR) in the adult population. Similar positive results have from then on been reported by different investigators using this technique. In contrast, otolaryngologists have typically used an anterior midline approach to the larynx and trachea for their laryngotracheal reconstructions (LTRs), both in adults and children. The fear of injury to the recurrent laryngeal nerve (RLN), the risk of a dehiscence of the anastomosis, and the interference with normal growth of the larynx in the pediatric age group were the main reasons put forward for not using a CTR for the cure of subglottic stenosis. In this article, we describe the similarities and differences in CTRs performed for adult and pediatric cases. The high rate (>90%) of success for severe pediatric SGS using CTR compares most favorably with LTR, which is still used in most otolaryngology departments. The reasons lie in the full resection of the stenosis and the restoration of a steady cartilaginous framework of the larynx and trachea with full mucosal lining on both sides of the anastomosis. Furthermore, CTR can be associated with a Rethi procedure for the cure of combined posterior glottic and subglottic stenoses. Good results from series of two different centers suggest that CTR will become the treatment of choice for pediatric severe SGS, as is presently the case in the adult population.

Clinical consequences of sensitisation to minor histocompatibility antigens before allogeneic bone marrow transplantation.

To study sensitisation to minor histocompatibility antigens (mHag) before and after BMT, we measured antidonor CTL activity in five patients who had rejected their graft, and in a control group of 10 leukemic patients who engrafted without complications. All patients were transplanted with marrow from an HLA-identical sibling. Fourteen patients were conditioned with cyclophosphamide (120 mg/kg) and TBI (1350 cGy) and received a T cell-depleted graft, while one patient with aplastic anaemia received cyclophosphamide alone and unmanipulated marrow. Before transplantation, anti-donor CTL activity was detected in two of the 15 patients. These patients rejected their grafts at days 21 and 58, respectively. In the other three patients who rejected their grafts at days 41, 60 and 250, CTL activity was found only after transplantation. In contrast, no anti-donor CTLs could be detected at any time in the 10 patients who engrafted permanently. We have identified some of the mHags recognised during graft rejection by cloning and subsequent specificity analysis of the recipient CTLs. In the patient who rejected at day 41 without detectable immunisation before BMT, the response was directed against HA-1, a minor antigen known to play a role in GVHD. In the other combinations, a significant part of the CTL activity was directed against the male antigen H-Y. In the patient who rejected the marrow of her HLA-identical brother at day 250, two clones recognised H-Y, while five others recognised at least three distinct autosomal mHags. This patient had an HLA-identical sister who expressed only one autosomal mHag that had been recognised by one single T cell clone. After re-transplantation with the marrow of this second donor, the CTL activity could no longer be detected and the patient engrafted without further complications.

Cigarette smoking and endometrial cancer risk: the modifying effect of obesity.

The objective of this study was to evaluate the association between cigarette smoking and endometrial cancer risk by investigating potential modifying effects of menopausal status, obesity, and exogenous hormones. We pooled data from three case-control studies with the same study design conducted in Italy and Switzerland between 1982 and 2006. Overall, 1446 incident endometrial cancers and 4076 hospital controls were enrolled. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models, conditioned on study and centre, and adjusted for age, period of interview, age at menarche, parity, and body mass index. In comparison with never smokers, current smokers showed reduced endometrial cancer risk (OR: 0.80; 95% CI: 0.66-0.96), with a 28% decrease in risk for smoking >/=20 cigarettes/day. The association did not vary according to menopausal status, oral contraceptive use, or hormone replacement therapy. However, heterogeneity emerged according to body mass index among postmenopausal women, with obese women showing the greatest risk reduction for current smoking (OR: 0.47; 95% CI: 0.27-0.81). In postmenopausal women, obesity turned out to be an important modifier of the association between cigarette smoking and the risk of endometrial cancer. This finding calls for caution in interpreting the favorable effects of cigarette smoking, considering the toxic and carcinogenic effects of tobacco.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Nuclear receptor PPARS function in stem cell differentiation and bone physiology

In adult, bone remodeling is a permanent process, reaching an annual turnover of about 10% of the skeleton. Bone remodeling requires the sequential and coordinated actions of the hematopoietic origin osteoclasts, to remove bone and the mesenchymal origin osteoblasts to replace it. An increased level of bone resorption is the primary cause of age-related bone loss often resulting in osteopenia, and is the major cause of osteoporosis.¦Peroxisome proliferator-activated receptors (PPARs), which are expressed in three isotypes, PPARa, PPARp and PPARy, are ligand-activated transcription factors that control many cellular and metabolic processes, more particularly linked to lipid metabolism. In bone, previous works has shown that PPARy inhibits osteogenesis by favoring adipogenesis from common mesenchymal progenitors. In addition, the pro-osteoclastogenesis activity of PPARy results in an increased bone resorption. Accordingly, treatment with PPARy agonist such as the anti-diabetic drug TZD causes bone loss and accumulation of marrow adiposity in mice as well as in postmenopausal women. The aim of the present thesis work was to elucidate the PPARs functions in bone physiology.¦The initial characterization of the PPARP" bone phenotype mainly revealed a decreased BMD. In vitro studies exploring the potency of mesenchymal stem cells to differentiate in osteoblast showed no differences depending on the genotype. However, we could demonstrate an effect of PPARp in partially inhibiting osteoclastogenesis. These results are further sustained by a study made in collaboration with the group of Dr Kronke, which showed an impressive protection against ovariectomy-generated bone loss when the females are treated with a PPARp agonist.¦Observations in PPARy null mice are more complex. The lab has recently been able to generate mice carrying a total deletion of PPARy. Intriguingly, the exploration of the bone phenotype of these mice revealed paradoxical findings. Whereas short bones such as vertebrae exhibit an elevated BMD as expected, long bones (tibia and femur) are clearly osteoporotic. According to their activity when set in culture, osteoblast differentiation normally occurs. Indeed the phenotype can be mainly attributed to a high density of osteoclasts in the cortical bone of PPARy null mice, associated to large bone resorption areas.¦Our explorations suggest a mechanism that involves regulatory processes linking osteoclastogenesis to adipogenesis, the latter being totally absent in PPARy null mice. Indeed, the lack of adipose tissue creates a favorable niche for osteoclastogenesis since conditioned medium made from differentiated adipocyte 3T3L1 inhibited osteoclastogenesis from both PPARy-/- and WT cells. Thus, adipokines deficiency in PPARy-/- mice contributes to de- repress osteoclastogenesis. Using specific blocking antibody, we further identified adiponectin as the major player among dozens of adipokines. Using flow cytometry assay, we explored the levels at which the osteoclastic commitment was perturbed in the bone marrow of PPARy-/- mice. Intriguingly, we observe a general decrease for hematopoietic stem cell and lineage progenitors but increased proportion of osteoclast progenitor in PPARy-/- bone marrow. The general decrease of HSC in the bone marrow is however largely compensated by an important extra-medullary hematopoeisis, taking place in the liver and in the spleen.¦These specific characteristics emphasize the key role of PPARy on a cross road of osteogenesis, adipogenesis and hematopoiesis/osteoclastogenesis. They underline the complexity of the bone marrow niche, and demonstrate the inter-dependance of different cell types in defining bone homeostasis, that may be overseen when experimental design single out pure cell populations.¦Chez l'adulte, même après la fin de la croissance, le renouvellement des os se poursuit et porte sur environ 10% de l'ensemble du squelette adulte, par année. Ce renouvellement implique à la fois des mécanismes séquentiels et coordonnés des ostéoclastes d'origine hématopoïetique, qui dégradent l'os, et des ostéoblastes d'origine mésenchymale, qui permettent la régénération de l'os. La perte en densité osseuse due à l'âge entraîne un fort niveau de résorption, conduisant souvent à une ostéopénie, elle-même cause de l'ostéoporose.¦Les trois isotypes PPAR (Peroxisome proliferator-activated receptor, PPARa, PPARp, et PPARy) sont des récepteurs nucléaires qui contrôlent de nombreux mécanismes cellulaires et métaboliques, plus particulièrement liés au métabolisme lipidique. Au niveau osseux, des travaux précédents ont montré que PPARy inhibe l'ostéoblastogenèse en favorisant la formation d'adipocytes à partir de la cellule progénitrice commune. De plus, l'activité pro- ostéoclastogénique de PPARy induit une résorption osseuse accrue. Condormément à ces observations, les patients diabétiques traités par les thiazolidinediones qui agissent sur PPARy, ont un risque accrue d'ostéoporose liée à une perte osseuse accrue et un accroissement de l'adiposité au niveau de la moelle osseuse. Dans ce contexte, l'objectif de mon travail de thèse a été d'élucider le rôle des PPAR dans la physiologie osseuse, en s'appuyant sur le phénotype des souris porteuses de mutation pour PPAR.¦La caractérisation initiale des os des souris porteuses d'une délétion de ΡΡΑΕφ a principalement révélé une diminution de la densité minérale osseuse (DMO). Alors que l'ostéogenèse n'est pas significativement altérée chez ces souris, l'ostéoclastogenèse est elle augmentée, suggérant un rôle modérateur de ce processus par ΡΡΑΕΙβ. Ces résultats sont par ailleurs soutenus par une étude menée par le groupe du Dr Krônke en collaboration avec notre groupe, et qui monte une protection très importante des souris traitées par un activateur de PPARP contre l'ostéoporose provoquée par l'ovariectomie.¦Les observations concernant PPARy donnent des résultats plus complexes. Le laboratoire a en effet été capable récemment de générer des souris portant une délétion totale de PPARy. Alors que les os courts chez ces souris présentent une augmentation de la DMO, comme attendu, les os longs sont clairement ostéoporotiques. Ce phénotype corrèle avec une densité élevée d'ostéoclastes dans l'os cortical de ces os longs. Deux processus semblent contribuer à ce phénotype. En premier lieu, nous démontrons qu'un milieu conditionné provenant de cultures de cellules 3T3-L1 différenciées en adipocytes contiennent une forte activité inhibitrice d'osteoclastogenesis. L'utilisation d'anticorps neutralisant permet d'identifier l'adiponectine comme l'un des facteurs principaux de cette inhibition. Les souris PPARy étant totalement dépourvues d'adipocytes et donc de tissu adipeux, la sécrétion locale d'adiponectine dans la moelle osseuse est donc également absente, entraînant une désinhibition de l'ostéoclastogenèse. En second lieu, des analyses par FACS révèle une proportion accrue des cellules progénitrices d'ostéoclastes dans la moelle osseuse. Cela s'accompagne par une diminution globale des cellules souches hématopoïétiques, qui est cependant largement compensée par une importante hématopoëise extra-médullaire, dans le foie comme dans la rate.¦L'ensemble de notre travail montre toute l'importance de PPARy au carrefour de l'ostéogenèse, adipogenèse, et hématopoëise/osteoclastogenèse. Il souligne la complexité de la niche que représente la moelle osseuse et démontre l'inter-dépendance des différents types cellulaires définissant l'homéostasie osseuse, complexité qui peut facilement être masqué lorsque le travail expérimental se concentre sur le comportement d'un type cellulaire donné.

Ranking of HMA Moisture Sensitivity Tests in Iowa, RB00-012, 2012

Several agencies specify AASHTO T283 as the primary test for field acceptance of moisture susceptibility in hot mix asphalt. When used in this application, logistical difficulties challenge its practicality, while repeatability is routinely scrutinized by contractors. An alternative test is needed which can effectively demonstrate the ability to screen mixtures based on expected performance. The ideal replacement can be validated with field performance, is repeatable, and allows for prompt reporting of results. Dynamic modulus, flow number, AASHTO T283, Hamburg wheel tracking device (HWTD), and the moisture induced sensitivity test (MIST) were performed on plant produced surface mixes in Iowa. Follow-up distress surveys were used to rank the mixes by their performance. The rankings indicate both the quantity of swelling from MIST conditioning and submersed flow number matched the performance ranking of all but one mixture. Hamburg testing parameters also appear effective, namely the stripping inflection point and the ratio between stripping slope and the creep slope. Dynamic modulus testing was ineffective, followed by AASHTO T283 and ratios produced from flow number results of conditioned samples.

Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.

BACKGROUND: The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. METHODS: A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. RESULTS: 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). CONCLUSION: This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.

Correlates of insomnia in patients with social phobia: role of depression and anxiety.

The severity of insomnia and the relationships between social fear, anxiety, depression and insomnia were examined in 179 patients with social phobia. Two-thirds of our sample had insomnia. Depression, anxiety, social anxiety, and insomnia were positively correlated. General and social anxiety contributed to insomnia when accounting for depression.

Prise en soins de la schizophrénie chez la personne âgée

Care of the elderly schizophrenic patient : Despite the development of new aetiopathological models the treatment of late-life schizophrenia is still based essentially on antipsychotic medication. The absence of research specifically targeting late-life schizophrenics limits the value of recommendations on indication, dosage and treatment alternatives, particularly as the latter have scant regard for the age of schizophrenia onset (early, late, very late onset), for the various comorbidities and the polymedication so common in the elderly. The use of atypical neuroleptics at adapted doses should be combined with biopsychosocial care and treatment of psychiatric and somatic comorbidities. The choice of an adapted treatment is often conditioned, especially if early schizophrenia is con sidered, by many years of treatment and side effects which may limit compliance when the evolution itself has been unfavourable with persistent, sometimes handi capping residual symptoms. Moreover, schizophrenia is complicated by cognitive disorders for which the best therapeutic approach in the elderly remains uncertain.

Sign language in Landau-Kleffner syndrome.

This article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau-Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.

Depositional models of lacustrine evaporites in the SE margin of the Ebro basin (Paleogene, NE Spain)

An important evaporitic sedimentation occurred during the Paleogene (Eocene to lower Oligocene) in the Barberà sector of the southeastern margin of the Tertiary Ebro Basin. This sedimentation took place in shallow lacustrine environments and was controlled by a number of factors: 1) the tectonic structuration of the margin; 2) the high calcium sulphate content in the meteoric waters coming from the marginal reliefs; 3) the semiarid climate; and 4) the development of large alluvial fans along the basin margin, which also conditioned the location of the saline lakes. The evaporites are currently composed of secondary gypsum in surface and anhydrite at depth. There are, however, vestiges of the local presence of sodium sulphates. The evaporite units, with individual thicknesses ranging between 50 and 100 m, are intercalated within various lithostratigraphic formations and exhibit a paleogeographical pattern. The units located closer to the basin margin are characterized by a massive gypsum lithofacies (originally, bioturbated gypsum) bearing chert, and also by meganodular gypsum locally (originally, meganodules of anhydrite) in association with red lutites and clastic intercalations (gypsarenites, sandstones and conglomerates). Chert, which is only linked to the thickest gypsum layers, seems to be an early diagenetic, lacustrine product. Cyclicity in these proximal units indicates the progressive development of lowsalinity, lacustrine bodies on red mud flats. At the top of some cycles, exposure episodes commonly resulted in dissolution, erosion, and the formation of edaphic features. In contrast, the units located in a more distal position with regard to the basin margin are formed by an alternation of banded-nodular gypsum and laminated gypsum layers in association with grey lutites and few clastic intercalations. These distal units formed in saline lakes with a higher ionic concentration. Exposure episodes in these lakes resulted in the formation of synsedimentary anhydrite and sabkha cycles. In some of these units, however, outer rims characterized by a lithofacies association similar to that of the proximal units occur (nodular gypsum, massive gypsum and chert nodules).

Matriconditioning integrated with gibberellic acid to hasten seed germination and improve stand establishment of pepper and tomato

Emergence and stand establishment of tomato (Lycopersicon lycopersicum (L.) (Karsten ex Farw) and pepper (Capsicum annus L.) seeds are often slow and erratic, particularly under stress conditions. Field emergence trials sometimes have not responded to priming in pepper. This study examined the combined effects of matriconditioning and gibberellin application on the germination and stand establishment of pepper and tomato seeds. Pepper and tomato seeds were conditioned with a solid carrier, Micro Cel E, in the presence of gibberellic acid (GA) for 1, 2 , 3 and 4 days at 15 and 25ºC. The results showed that, in all cases, even under stress conditions, the combination of matriconditioning with GA was effective in improving germination and emergence of pepper and tomato. The germination time was, in average, reduced by 2 to 3 days by primed seeds. Thus, matriconditioning, during which germination is suspended, provides an unique means to rapidly and efficiently digest the endosperm by GA-induced enzymes and reduce the mechanical restraints of endosperm thus providing energy to start and sustain embryo growth.

Regulation of peptidase activity in a three-dimensional aggregate model of brain tumor vasculature.

The abnormal vascular system of brain cancers inappropriately expresses membrane proteins, including proteolytic enzymes, ultimately resulting in blood extravasation. The production of inflammatory mediators, such as cytokines and nitric oxide, and tumor hypoxia have been implicated in these effects. We have previously shown that the activity of aminopeptidase A is increased in the abnormal vascular system of human and rat brain tumors. To study the mechanisms regulating the activities of peptidases in cerebral vasculature in brain tumors, we have developed a three-dimensional model of differentiated rat brain cells in aggregate cultures in which rat brain microvessels were incorporated. The secretion of interleukin-6 (IL-6) in the culture medium of aggregates was used as an indicator of inflammatory activation. Addition to these aggregates of C6 glioma cell medium (C6-CM) conditioned under hypoxic or normoxic conditions or serum mimicked tumor-dependent hypoxia or conditions of dysfunction of brain tumor vasculature. Hypoxic and normoxic C6-CM, but not serum, regulated peptidase activity in aggregates, and in particular it increased the activity of aminopeptidase A determined using histoenzymography. Serum, but not C6-CM, increased IL-6 production, but did not increase aminopeptidase A activity in aggregates. Thus soluble glioma-derived factors, but not serum-derived factors, induce dysfunctions of cerebral vasculature by directly regulating the activity of peptidases, not involving inflammatory activation. Tumor hypoxia is not necessary to modulate peptidase activity.

The meaning of marriage for men during the transition to fatherhood : the Swiss context

In Europe, Switzerland presents an unusual pattern of marriage with a very high proportion of couples who begin to cohabit without being married, but with a very low proportion of nonmarital births. A lot of couples marry before the conception of the child or during the pregnancy. In this article we focus on the point of view of men vis-agrave-vis the marriage and its meanings. Qualitative investigations show that men strongly desire marriage for several reasons, from their desire to participate in child rearing to the fear of having their paternity denied by Swiss institutions