Impaired metabolic reactivity to oxidative stress in early psychosis patients.

Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.

Les commissions d'enquête parlementaires. Cadre juridique d'une procédure politique. Étude de droit suisse fédéral et cantonal

SECTION III PLAN Cette étude sera divisée en six chapitres. Le premier retracera l'évolution historique des enquêtes parlementaires, aux niveaux fédéral et cantonal. Ce survol servira de cadre empirique pour les discussions plus spécifiques qui le suivront. A cette occasion, une attention particulière sera accordée au principe de séparation des pouvoirs et aux fonctions que cette institution remplit au sein de notre système démocratique. L'objet de l'enquête sera défini de manière plus détaillée dans un chapitre second. Il s'agira d'étudier l'étendue du champ d'investigation ouvert aux députés, afin de déterminer si certaines thématiques sont, dès l'abord, soustraites à leur compétence. La troisième partie de ce travail portera sur l'établissement des faits. Les diverses possibilités s'offrant aux parlementaires pour élucider les événements litigieux seront répertoriées puis analysées, afin d'évaluer leur importance réelle dans la pratique des commissions. A ces moyens d'investigation seront opposées les garanties de procédure reconnues au représentant du Gouvernement et aux personnes concernées par l'enquête. Le quatrième chapitre s'intéressera ainsi au droit d'être entendu et aux règles assurant l'équité de la procédure. Le cinquième chapitre sera le complément procédural des deux précédents. Il s'intéressera aux diverses voies de droit, judiciaires ou non, permettant d'obtenir un contrôle sur les travaux de la commission. Il sera conçu comme un catalogue des moyens de redressement qu'un particulier ou une autorité peuvent utiliser, lorsqu'une contestation les oppose aux parlementaires enquêteurs. Ce chapitre donnera aussi l'occasion d'étudier certains mécanismes introduits par la récente révision de l'organisation judiciaire fédérale. Enfin, le sixième et dernier chapitre traitera des problèmes de coordination posés par la poursuite, parallèlement aux recherches parlementaires, de procédures concurrentes portant sur le même objet. Un concours sera tour à tour envisagé avec une instruction pénale puis avec des procédures internes à l'administration, telles qu'une procédure disciplinaire ou une enquête administrative.

Le régime des plans d'affectation : en particulier le plan de quartier

Le plan de quartier (Gestaltungsplan) occupe une position singulière parmi les plans d'affectation. Il oscille en effet entre deux régimes distincts : celui du plan de zones, dont il partage la nature juridique, et celui de l'autorisation de construire, que son caractère détaillé préfigure dans une large mesure. Bien qu'il soit couramment utilisé par les communes, le plan de quartier pose de nombreuses questions et mérite à ce titre de faire l'objet d'une étude approfondie. C'est ce à quoi s'emploie le présent ouvrage. Il aborde les questions pratiques et théoriques qui se posent en relation avec cet instrument : sa nature juridique, son contenu, la procédure à laquelle il est soumis et les diverses limites qui s'imposent à son auteur, de même que la forme et la licéité des arrangements qui peuvent être conclus à l'occasion de son adoption. La réflexion développée en lien avec le plan de quartier est également élargie aux autres plans d'affectation afin de proposer une vision globale, cohérente et critique du système de planification et des possibilités d'évolution qu'il recèle. Cet ouvrage a pour vocation de satisfaire le profane dans une même mesure que le spécialiste. Il présente des informations générales sur le fonctionnement de l'aménagement du territoire au sens large et les principes qui le sous-tendent, mais contient aussi des développements plus pointus destinés au lecteur désireux de pénétrer au coeur de la problématique. La systématique suivie permet d'accéder aisément aux divers sujets traités, présentés dans un ordre logique et chronologique - les chemins de traverse que dessinent les renvois proposant pour leur part un itinéraire intellectuel alternatif. Quant aux nombreuses références doctrinales et jurisprudentielles, elles permettent à chacun de prolonger la réflexion sur l'une ou l'autre des thématiques abordées.

Inexperienced sonographers can successfully visualize and assess a three-dimensional image of the fetal face using a standardized ultrasound protocol.

Introduction: A standardized three-dimensional ultrasonographic (3DUS) protocol is described that allows fetal face reconstruction. Ability to identify cleft lip with 3DUS using this protocol was assessed by operators with minimal 3DUS experience. Material and Methods: 260 stored volumes of fetal face were analyzed using a standardized protocol by operators with different levels of competence in 3DUS. The outcomes studied were: (1) the performance of post-processing 3D face volumes for the detection of facial clefts; (2) the ability of a resident with minimal 3DUS experience to reconstruct the acquired facial volumes, and (3) the time needed to reconstruct each plane to allow proper diagnosis of a cleft. Results: The three orthogonal planes of the fetal face (axial, sagittal and coronal) were adequately reconstructed with similar performance when acquired by a maternal-fetal medicine specialist or by residents with minimal experience (72 vs. 76%, p = 0.629). The learning curve for manipulation of 3DUS volumes of the fetal face corresponds to 30 cases and is independent of the operator's level of experience. Discussion: The learning curve for the standardized protocol we describe is short, even for inexperienced sonographers. This technique might decrease the length of anatomy ultrasounds and improve the ability to visualize fetal face anomalies.

Congenital high airway obstruction syndrome and airway reconstruction: an evolving paradigm.

OBJECTIVES: To refine the classic definition of, and provide a working definition for, congenital high airway obstruction syndrome (CHAOS) and to discuss the various aspects of long-term airway reconstruction, including the range of laryngeal anomalies and the various techniques for reconstruction. DESIGN: Retrospective chart review. PATIENTS: Four children (age range, 2-8 years) with CHAOS who presented to a single tertiary care children's hospital for pediatric airway reconstruction between 1995 and 2000. CONCLUSIONS: To date, CHAOS remains poorly described in the otolaryngologic literature. We propose the following working definition for pediatric cases of CHAOS: any neonate who needs a surgical airway within 1 hour of birth owing to high upper airway (ie, glottic, subglottic, or upper tracheal) obstruction and who cannot be tracheally intubated other than through a persistent tracheoesophageal fistula. Therefore, CHAOS has 3 possible presentations: (1) complete laryngeal atresia without an esophageal fistula, (2) complete laryngeal atresia with a tracheoesophageal fistula, and (3) near-complete high upper airway obstruction. Management of the airway, particularly in regard to long-term reconstruction, in children with CHAOS is complex and challenging.

Increased eeg synchronization in schizophrenia patients by the glutathione precursor, n-acetyl-cysteine

Background: Glutathione (GSH) dysregulation at the gene, protein and functional levels observed in schizophrenia patients, and schizophrenia-like anomalies in GSH deficit experimental models, suggest that genetic glutathione synthesis impairments represent one major risk factor for the disease (Do et al., 2009). In a randomized, double blind, placebo controlled, add-on clinical trial of 140 patients, the GSH precursor N-Acetyl-Cysteine (NAC, 2 g/day, 6 months) significantly improved the negative symptoms and reduced side-effects due to antipsychotics (Berk et al., 2008). In a subset of patients (n=7), NAC (2 g/day, 2 months, cross-over design) also improved auditory evoked potentials, the NMDAdependent mismatch negativity (Lavoie et al, 2008). Methods: To determine whether increased GSH levels would modulate the topography of functional brain connectivity, we applied a multivariate phase synchronization (MPS) estimator (Knyazeva et al, 2008) to dense-array EEGs recorded during rest with eyes closed at the protocol onset, the point of crossover, and at its end. Phase synchronization phenomena are appealing because they can be associated to synchronized phases while the amplitudes stay uncorrelated. MPS measures the degree of interactions among the recorded neuronal oscillators by quantifiying to what extent they behave like a macro-oscillator (i.e. the oscillators are phase synchronous). To assess the whole-head synchronization topography, we computed the MPS sensor-wise over the cluster of locations defined by the sensor itself and he surrounding ones belonging to its second-order neighborhood (Carmeli et al, 2005). Such a cluster spans about 12 cm on average. Abstracts 245 Results: The whole-head imaging revealed a specific synchronization landscape in NAC compared to placebo condition. In particular, NAC increased MPS over frontal and left temporal regions in a frequency-specific manner. Importantly, the topography and direction of MPS changes were similar and robust in all 7 patients. Moreover, these changes correlated with the changes in the Liddle's score of disorganization (Liddle, 1987) thus linking EEG synchronization to the improvement of clinical picture. Discussion: The data suggest an important pathway towards new therapeutic strategies that target GSH dysregulation in schizophrenia. They also show the utility of MPS mapping as a marker of treatment efficacy.

Insuffisance surrénalienne et hypercalcémie: association fortuite [Adrenal insufficiency and hypercalcemia--an unusual presentation]

A 49 y.o. man was admitted for investigation of an intense fatigue associated with nausea, vomiting, weight loss and headache. Examination and work-up reveals a moderate hypercalcaemia and a panhypopituitarism attributed to a craniopharyngioma. Extensive work-up has excluded the most frequent causes of hypercalcaemia and we finally attributed this anomaly to the adrenal failure. In this article, we discuss the diagnostic approach, the etiology and physiopathology of this hypercalcemia and his association with endocrinological anomalies such as adrenal failure.

Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study.

INTRODUCTION: Published prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of Congenital Anomalies (EUROCAT). METHODS: Cases of CDH delivered between 1980 and 2009 notified to 31 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. RESULTS: There were 3373 CDH cases reported among 12 155 491 registered births. Of 3131 singleton cases, 353 (10.4%) were associated with a chromosomal anomaly, genetic syndrome or microdeletion, 784 (28.2%) were associated with other major structural anomalies. The male to female ratio of CDH cases overall was 1:0.69. Total prevalence was 2.3 (95% CI 2.2 to 2.4) per 10 000 births and 1.6 (95% CI 1.6 to 1.7) for isolated CDH cases. There was a small but significant increase (relative risk (per year)=1.01, 95% credible interval 1.00-1.01; p=0.030) in the prevalence of total CDH over time but there was no significant increase for isolated cases (ie, CDH cases that did not occur with any other congenital anomaly). There was significant variation in total and isolated CDH prevalence between registers. The proportion of cases that survived to 1 week was 69.3% (1392 cases) for total CDH cases and 72.7% (1107) for isolated cases. CONCLUSIONS: This large population-based study found an increase in total CDH prevalence over time. CDH prevalence also varied significantly according to geographical location. No significant association was found with maternal age.

Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study.

Constraining 3-D electrical resistance tomography with GPR reflection data forimproved aquifer characterization

Surface-based ground penetrating radar (GPR) and electrical resistance tomography (ERT) are common tools for aquifer characterization, because both methods provide data that are sensitive to hydrogeologically relevant quantities. To retrieve bulk subsurface properties at high resolution, we suggest incorporating structural information derived from GPR reflection data when inverting surface ERT data. This reduces resolution limitations, which might hinder quantitative interpretations. Surface-based GPR reflection and ERT data have been recorded on an exposed gravel bar within a restored section of a previously channelized river in northeastern Switzerland to characterize an underlying gravel aquifer. The GPR reflection data acquired over an area of 240×40 m map the aquifer's thickness and two internal sub-horizontal regions with different depositional patterns. The interface between these two regions and the boundary of the aquifer with then underlying clay are incorporated in an unstructured ERT mesh. Subsequent inversions are performed without applying smoothness constraints across these boundaries. Inversion models obtained by using these structural constraints contain subtle resistivity variations within the aquifer that are hardly visible in standard inversion models as a result of strong vertical smearing in the latter. In the upper aquifer region, with high GPR coherency and horizontal layering, the resistivity is moderately high (N300 Ωm). We suggest that this region consists of sediments that were rearranged during more than a century of channelized flow. In the lower low coherency region, the GPR image reveals fluvial features (e.g., foresets) and generally more heterogeneous deposits. In this region, the resistivity is lower (~200 Ωm), which we attribute to increased amounts of fines in some of the well-sorted fluvial deposits. We also find elongated conductive anomalies that correspond to the location of river embankments that were removed in 2002.

Gabbro, plagiogranite and associated dykes in the supra-subduction zone Evros Ophiolites, NE Greece

The incomplete Evros ophiolites in NE Greece form a NE-SW-oriented discontinuous belt in the Alpine orogen of the north Aegean. Field data, petrology and geochemistry are presented here for the intrusive section and associated mafic dykes of these ophiolites. Bodies of high-level isotropic gabbro and plagiogranite in the ophiolite suite are cross-cut by NE-SW-trending boninitic and tholeiitic-boninitic affinity dykes, respectively. The dykes fill tensile fractures or faults, which implies dyke emplacement in an extensional tectonic regime. The tholeiitic-transitional boninitic gabbro is REE- and HFS-depleted relative to N-MORB, indicating derivation from melting of a refractory mantle peridotite source. Associated boninitic dykes are slightly LREE-enriched, showing mineral and whole-rock geochemistry similar to the gabbro. The plagiogranite is a strongly REE-enriched high-silica trondhjemite, with textures and composition typical for an oceanic crust differentiate. Plagiogranite-hosted tholeiitic and transitional boninitic dykes are variably REE-enriched. Geochemical modelling indicates origin of the plagiogranite by up to 75% fractional crystallization of basaltic magma similar to that producing the associated tholeiitic dykes. All mafic rocks have high LILE/HFSE ratios and negative Ta-Nb-Ti and Ce anomalies, typical for subduction zone-related settings. The mafic rocks show a similar trace-element character to the mafic lavas of an extrusive section in Bulgaria, suggesting they both form genetically related intrusive and extrusive suites of the Evros ophiolites. The field occurrence, the structural context, the petrology and geochemical signature of the studied magmatic assemblage provide evidence for its origin in a proto-arc (fore-arc) tectonic setting, thus tracing the early stages of the tectono-magmatic evolution of Jurassic arc-marginal basin system that has generated the supra-subduction type Evros ophiolites.

Hirschsprung's disease prevalence in Europe: A register based study.

BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age. Birth Defects Research (Part A), 100:695-702, 2014. © 2014 Wiley Periodicals, Inc.

Arthrogryposis multiplexa congenita: an epidemiologic study of nearly 9 million births in 24 EUROCAT registers.

OBJECTIVE: To examine the occurrence of arthrogryposis multiplex congenita (AMC) in Europe and to identify possible risk factors. STUDY DESIGN: Retrospective population-based epidemiological study using EUROCAT congenital anomaly registries. The study population included all cases of AMC (based on WHO ICD-9 or ICD-10 codes) that were livebirths (LB), fetal deaths (FD) from 20 weeks gestation and underwent termination of pregnancy for fetal anomaly (TOPFA), 1980-2006. RESULTS: Among 8.9 million births covered by 24 EUROCAT congenital anomaly registries, 757 AMC cases were reported. This gives a prevalence of 8.5 per 100,000. Five hundred and four (67%) AMC cases were LB, 199 (26%) cases were TOPFA, and FD occurred in 54 (7%) cases. First week survival status was known for 381 of the 504 LB (76%), of whom 87 (23%) died within the first week of life. Perinatal mortality associated with AMC was 32%. Two hundred and eighty-two (37%) cases had isolated AMC, 90 (12%) had additional syndrome or chromosomal anomalies and 385 (51%) had other major malformations. The same or similar anomaly was reported in 13% of siblings and in 12% of the mother's own family background. Information on prenatal testing was available for 521 cases of which 360 tested positive for a congenital anomaly, representing a sensitivity of 69%. Information on maternal illness before and during pregnancy and medication use in the first trimester was available for approximately a third of the mothers, of whom the vast majority reported no maternal illness or medication use. CONCLUSION: AMC is a rare occurrence, with a reported prevalence of 1:12,000. In this study, while information on potential risk factors such as maternal disease or maternal use of drugs was limited, they did not appear to be associated with the occurrence of AMC. AMC was lethal in a third of cases, either in utero or during the first week of life, although this may not be solely attributed to AMC as most cases had additional malformations.

Petrology, geochemistry and geodynamic implications of Jurassic island arc magmatism as revealed by mafic volcanic rocks in the Mesozoic low-grade sequence, eastern Rhodope, Bulgaria

In the eastern Bulgarian Rhodope, mafic extrusive rocks and underlying greenschists are found in the Mesozoic low-grade unit, which represents the northern extension of similar sequences including the Evros ophiolites in Thrace (Greece). Both rock types define a suite of low-Ti tholeiitic basalts to transitional boninitic basaltic andesites and andesites and associated metapyroclastites (greenschists), intruded at its base by diorite dikes of a boninitic affinity. Mafic lavas and greenschists display large ion lithophile element (LILE) enrichment relative to high-field strength elements (HFSE), flat REE patterns of a slight light REE depletion, a strong island arc tholeiite (IAT) and weak MORB-like signature. All these rocks are characterized by negative Nb anomalies ascribed to arc lavas. They have positive epsilon Nd(i) values in the range of +4.87 to +6.09, approaching the lower limit of MORB-like source, and relatively high ((207)Pb/(204)Pb)(i) (15.57-15.663) at low ((206)Pb/(204)Pb)(i) (18.13-18.54) ratios. The Nd isotopic compositions coupled with trace element data imply a dominantly depleted MORB-like mantle source and a contribution of subduction modified LILE-enriched component derived from the mantle wedge. The diorite dike has a low eNdi value of -2.61 and is slightly more Pb radiogenic ((207)Pb/(204)Pb)(i) (15.64) and ((206)Pb/(204)Pb)(i) (18.56), respectively, reflecting crustal contamination. Petrologic and geochemical data indicate that the greenschists and mafic extrusive rocks represent a magmatic assemblage formed in an island arc setting. The magmatic suite is interpreted as representing an island arc-accretionary complex related to the southward subduction of the Meliata-Maliac ocean under the supra-subduction back-arc Vardar ocean/island arc system. Magmatic activity appears to have initiated in the north during the inception of the island arc system by the Early-Middle Jurassic time in the eastern Rhodope that most likely graded to back-arc spreading southwards as represented by the Late Jurassic MORB-type Samothraki Island ophiolites. This tectonic scenario is further constrained by paleotectonic reconstructions. The arc-trench system collided with the Rhodope in the Late Jurassic times. (c) 2007 Elsevier B.V. All rights reserved.