MIBG scintigraphy for the diagnosis and follow-up of children with neuroblastoma.

Neuroblastoma (NBL) is the commonest extra-cranial solid tumor in children and the leading cause of cancer related deaths in childhood between the age of 1 to 4 years. NBL may behave in very different ways, from the less aggressive stage 4S NBL or congenital forms that may resolve without treatment in up to 90% of the children, to the high-risk disseminated stage 4 disease in older children with a cure rate of 35 to 40%. Initial staging is crucial for effective management and radiolabeled metaiodobenzylguanidine (MIBG) with iodine-123 is a powerful tool with a sensitivity around 90% and a specificity close to 100% for the diagnosis of NBL. MIBG scintigraphy is used routinely and is mandatory in most investigational clinical trials both for the initial staging of the disease, the evaluation of the response to treatment, as well as for the detection of recurrence during follow-up. With respect to outcome of children presenting disseminated stage 4 NBL, the role of post-therapeutic [(123)I]MIBG scan has been investigated by several groups but so far there is no consensus whereas a complete or very good partial response as assessed by MIBG may be of prognostic value. NBL needs a multimodality approach at diagnosis and during follow-up and MIBG scintigraphy keeps its pivotal role, in particular with respect to bone marrow involvement and/or cortical bone metastases.

Reconciliation of metabolites and biochemical reactions for metabolic networks.

Genome-scale metabolic network reconstructions are now routinely used in the study of metabolic pathways, their evolution and design. The development of such reconstructions involves the integration of information on reactions and metabolites from the scientific literature as well as public databases and existing genome-scale metabolic models. The reconciliation of discrepancies between data from these sources generally requires significant manual curation, which constitutes a major obstacle in efforts to develop and apply genome-scale metabolic network reconstructions. In this work, we discuss some of the major difficulties encountered in the mapping and reconciliation of metabolic resources and review three recent initiatives that aim to accelerate this process, namely BKM-react, MetRxn and MNXref (presented in this article). Each of these resources provides a pre-compiled reconciliation of many of the most commonly used metabolic resources. By reducing the time required for manual curation of metabolite and reaction discrepancies, these resources aim to accelerate the development and application of high-quality genome-scale metabolic network reconstructions and models.

Tenofovir use is associated with an increase in serum alkaline phosphatase in the Swiss HIV Cohort Study.

BACKGROUND: Tenofovir (TDF) use has been associated with proximal renal tubulopathy, reduced calculated glomerular filtration rates (cGFR) and losses in bone mineral density. Bone resorption could result in a compensatory osteoblast activation indicated by an increase in serum alkaline phosphatase (sAP). A few small studies have reported a positive correlation between renal phosphate losses, increased bone turnover and sAP. METHODS: We analysed sAP dynamics in patients initiating (n = 657), reinitiating (n = 361) and discontinuing (n = 73) combined antiretroviral therapy with and without TDF and assessed correlations with clinical and epidemiological parameters. RESULTS: TDF use was associated with a significant increase of sAP from a median of 74 U/I (interquartile range 60-98) to a plateau of 99 U/I (82-123) after 6 months (P < 0.0001), with a prompt return to baseline upon TDF discontinuation. No change occurred in TDF-sparing regimes. Univariable and multivariable linear regression analyses revealed a positive correlation between sAP and TDF use (P < or = 0.003), but no correlation with baseline cGFR, TDF-related cGFR reduction, changes in serum alanine aminotransferase (sALT) or active hepatitis C. CONCLUSIONS: We document a highly significant association between TDF use and increased sAP in a large observational cohort. The lack of correlation between TDF use and sALT suggests that the increase in sAP is because of the bone isoenzyme and indicates stimulated bone turnover. This finding, together with published data on TDF-related renal phosphate losses, this finding raises concerns that TDF use could result in osteomalacia with a loss in bone mineral density at least in a subset of patients. This potentially severe long-term toxicity should be addressed in future studies.

Shrews in suburbia: an application of Goodman's extinction model

An equation is applied for calculating the expected persistence time of an unstructured population of the white-toothed shrew Crocidura russula from Preverenges, a suburban area in western Switzerland. Population abundance data from March and November between 1977 and 1988 were fit to the logistic density dependence model to estimate mean population growth rate as a function of population density. The variance in mean growth rate was approximated with two different models. The largest estimated persistence time was less than a few decades, the smallest less than 10 years. The results are sensitive to the magnitude of variance in population growth rate. Deviations from the logistic density dependence model in November are quite well explained by weather variables but those in March are uncorrelated with weather variables. Variability in population growth rates measured in winter months may be better explained by behavioural mechanisms. Environmental variability, dispersal of juveniles and refugia within the range of the population may contribute to its long-term survival.

Is it really worth the effort to renounce to 5 mm trocars?

Objective: Single port laparoscopy andNOTES aim at decreasing the number¦of trocars, at a price of increased technical difficulty and cost, without until now¦any proof of benefit for the patient.Morbidity related to 5 mm trocar sites (TS)¦is claimed to be low, but there are no good quality data on this topic. The aim¦of the present prospective study is to measure the morbidity and overall specific¦impact related to the 5 mm TS and compare them to larger TS.¦Methods:Wecollected prospectively data on 300 consecutive patients operated¦by laparoscopy in our institution between 2009 and 2010. Pain, morbidity,¦cosmetic, and overall patient discomfort were assessed specifically for each¦TS, using standardized questionnaires, at 3 time points: at discharge from¦the hospital, at 1 month and at 6 months after surgery. Results were compared¦between 5 mmand larger TS (10 mm, 12 mmand 15 mm).Trocar sites replaced¦by a minilaparotomy or a stoma were excluded from analysis. In this study we¦present the short-term results.¦Results: Three-hundred patients (mean age 47·5, women 55%) were operated¦with 1074 TS of which 477(44%) were 5 mm TS. Indication to laparoscopy was¦cholecystectomy (31·3%), appendectomy (26·6%), upper GI surgery (16·3%),¦colon resection (13·3%) or other (12·3%). Follow-up at 1 month was completed¦in 90%.¦The 5 mm TS had an infection rate of 0·2%, and a hematoma rate of 1·7%.¦VAS pain scores at the 5mm TS were ≤3 in 91·6% at rest and in 75·9% upon¦effort at discharge, and in 97% at 1 month. Median patient scar assessment¦score (PSAS) of the 5 mm TS at 1 month was 6 (IQR: 2-9) out of 60 (0 =¦best score). Overall discomfort of the 5 mm TS in a VAS scale was 0 in 77%¦and ≤3 in 95% of patients at 1 month. Morbidity, pain assessments, PSAS, and¦overall discomfort scores were all significantly better for 5 mm TS compared to¦larger TS.¦Conclusion: Morbidity, pain, cosmetic impact and overall patient's discomfort¦related to a 5 mm trocar site is extremely low. For this reason, any potential¦advantage related to omitting 5 mm trocars to perform the same type of surgery¦will be difficult to demonstrate.

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes in central Iran: New geological data, relationships and tectonic implications

The Anarak, Jandaq and Posht-e-Badam metamorphic complexes occupy the NW part of the Central-East Iranian Microcontinent and are juxtaposed with the Great Kavir block and Sanandaj-Sirjan zone. Our recent findings redefine the origin of these complexes, so far attributed to the Precambrian-Early Paleozoic orogenic episodes, and now directly related to the tectonic evolution of the Paleo-Tethys Ocean. This tectonic evolution was initiated by Late Ordovician-Early Devonian rifting events and terminated in the Triassic by the Eocimmerian collision event due to the docking of the Cimmerian blocks with the Asiatic Turan block. The ``Variscan accretionary complex'' is a new name we proposed for the most widely distributed metamorphic rocks connected to the Anarak and Jandaq complexes. This accretionary complex exposed from SW of Jandaq to the Anarak and Kabudan areas is a thick and fine grain siliciclastic sequence accompanied by marginal-sea ophiolitic remnants, including gabbro-basalts with a supra-subduction-geochemical signature. New Ar-40/Ar-39 ages are obtained as 333-320 Ma for the metamorphism of this sequence under greenschist to amphibolite facies. Moreover, the limy intercalations in the volcano-sedimentary part of this complex in Godar-e-Siah yielded Upper Devonian-Tournaisian conodonts. The northeastern part of this complex in the Jandaq area was intruded by 215 +/- 15 Ma arc to collisional granite and pegmatites dated by ID-TIMS and its metamorphic rocks are characterized by Some Ar-40/Ar-39 radiometric ages of 163-156 Ma. The ``Variscan'' accretionary complex was northwardly accreted to the Airekan granitic terrane dated at 549 +/- 15 Ma. Later, from the Late Carboniferous to Triassic, huge amounts of oceanic material were accreted to its southern side and penetrated by several seamounts such as the Anarak and Kabudan. This new period of accretion is supported by the 280-230 Ma Ar-40/Ar-39 ages for the Anarak mild high-pressure metamorphic rocks and a 262 Ma U-Pb age for the trondhjemite-rhyolite association of that area. The Triassic Bayazeh flysch filled the foreland basin during the final closure of the Paleo-Tethys Ocean and was partly deposited and/or thrusted onto the Cimmerian Yazd block. The Paleo-Tethys magmatic arc products have been well-preserved in the Late Devonian-Carboniferous Godar-e-Siah intra-arc deposits and the Triassic Nakhlak fore-arc succession. On the passive margin of the Cimmerian block, in the Yazd region, the nearly continuous Upper Paleozoic platform-type deposition was totally interrupted during the Middle to Late Triassic. Local erosion, down to Lower Paleozoic levels, may be related to flexural bulge erosion. The platform was finally unconformably covered by Liassic continental molassic deposits of the Shemshak. One of the extensional periods related to Neo-Tethyan back-arc rifting in Late Cretaceous time finally separated parts of the Eocimmerian collisional domain from the Eurasian Turan domain. The opening and closing of this new ocean, characterized by the Nain and Sabzevar ophiolitic melanges, finally transported the Anarak-Jandaq composite terrane to Central Iran, accompanied by large scale rotation of the Central-East Iranian Microcontinent (CEIM). Due to many similarities between the Posht-e-Badam metamorphic complex and the Anarak-Jandaq composite terrane, the former could be part of the latter, if it was transported further south during Tertiary time. (C) 2007 Elsevier B.V. All rights reserved.

Epidémiologie des fentes labio-maxillo-palatines dans le canton de Vaud [Epidemiology of lip-maxilla-palate clefts in the canton of Vaud]

Epidemiological variables in oral clefts were examined in a cohort of patients with congenital malformations from the canton of Vaud in Switzerland during the years 1990-1999. Among 77'259 newborns or foetuses, 144 cases of oral clefts were identified in the Registre Vaudois des Anomalies Congénitales (RVAC), yielding a total prevalence of 18.6 per 10'000. These clefts consisted of 84 (58%) cases of cleft lip with or without cleft palate (CL/P) and 60 (42%) cases of cleft palate only (CP). Associated anomalies were found in 45% of cases. Our results are compared with previous reports in other parts of Europe.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.

BACKGROUND: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS). METHODS: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011. All HCV-seronegative patients with at least 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET). RESULTS: HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. Over 23 707 person-years (py) for MSM, 733 py for IDU, and 20 752 py for HET, 101 (3%), 41 (33%), and 25 (1%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion. CONCLUSIONS: In the SHCS, HCV infection incidence decreased in IDU, remained stable in HET, and increased 18-fold in MSM in the last 13 years. These observations underscore the need for improved HCV surveillance and prevention among HIV-infected MSM.

Convergences and divergences of diabetic patients' and healthcare professionals' opinions of care : a qualitative study

OBJECTIVES: To investigate opinions' convergences and divergences of diabetic patients and health-care professionals on diabetes care and the development of a regional diabetes programme. BACKGROUND: Development and implementation of a regional diabetes programme. RESEARCH DESIGN: Qualitative study using focus groups to elicit diabetic patients' and health-care professionals' opinions, followed by content analysis. SETTING AND PARTICIPANTS: Eight focus groups: four focus groups with diabetic patients (n = 39) and four focus groups with various health-care professionals (n = 34) residing or practicing in the canton of Vaud, Switzerland, respectively. RESULTS: Perceived quality of diabetes care varied between individuals and types of participants. To improve quality, patients favoured a comprehensive follow-up while professionals suggested considering existing structures and trained professionals. All participants mentioned communication difficulties between professionals and were favouring teamwork. In addition, they described the role that patients should have in care and self-management. Financial difficulties were also mentioned by both groups of participants. Finally, they were in favour of the development of a regional diabetes programme adapted to actors' needs. For patients indeed, such a programme would represent an opportunity to improve information and to have access to comprehensive care. For professionals, it would help the development of local networks and the reinforcement of existing tools and structures. DISCUSSION AND CONCLUSIONS: Acknowledging convergences and divergences of opinions of both diabetic patients and health-care professionals should help the further development of a programme adapted to users' needs, taking all stakeholders interests and priorities into consideration.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Molecular determinants of vesicular storage and release of the gliotransmitter D-serine from cortical astrocytes

Neuron-astrocyte reciprocal communication at synapses has emerged as a novel signalling pathway in brain function. Astrocytes sense the level of synaptic activity and, in turn, influence its efficacy through the regulated release of 'gliotransmitters' such as glutamate, ATP or D-serine. A calcium-dependent exocytosis is proposed to drive the release of gliotransmitters but its existence is still debated. Over the last years, we have been studying the molecular determinants governing D-serine release from glia using different approaches. Using a novel bioassay for D-serine, we have been able to show that D-serine release occurs mainly through a calcium- and SNARE proteindependent mechanism just supporting the idea that this amino acid is released by exocytosis from glia. We next have pursued our exploration by confocal imaging and tracking of the exocytotic routes for Dserine- mediated gliotransmission and have shown that D-serine releasable pools are confined to synaptobrevin2/cellubrevin-bearing vesicles. To shed light onto the mechanisms controlling the storage and the release of gliotransmitters and namely D-serine, we have developed a new method for the immunoisolation of synaptobrevin 2- positive vesicles from rat cortical astrocytes in culture while preserving their content in gliotransmitters. The purified organelles are clear round shape vesicles of excellent purity with homogeneous size (40 nm) as judged by electron microscopy. Immunoblotting analysis revealed that isolated vesicles contain most of the major proteins already described for neuron-derived vesicles like synaptic vesicle protein 2 (SV2) and the proton pump H?-ATPase. In addition, we have analyzed the content for various amino acids of these vesicles by means of chiral capillary electrophoresis coupled to laser-induced fluorescence detection. The purified vesicles contain large amount of D-serine. We also detect peaks corresponding to unidentified compounds that may correspond to others amino acids. Postembedding immunogold labelling of the rat neocortex further revealed the expression of D-serine in astrocytes processes contacting excitatory synapses. Finally, we have examined the uptake properties for Dserine and glutamate inside the isolated glial vesicles. Our results provide significant support for the existence of an uptake system for D-serine in secretory glial vesicles and for the storage of chemical substances like D-serine and glutamate. 11th International Congress on Amino Acids, Peptides and Proteins 763 123

Evaluation d'une anisocorie et exemples de cas cliniques

L'anisocorie est une anomalie pupillaire fréquemment rencontrée en pratique clinique. Elle peut être physiologique, s'inscrire dans le cadre d'une atteinte oculaire, d'une paralysie pharmacologique, ou encore dans le cadre d'une maladie neurologique. Le but de cet article est de fournir au lecteur une approche systématique de ce problème qui lui permettra de déterminer dans la majorité des cas le mécanisme aboutissant à cette anisocorie.

L'assurance de qualité en dépistage organise du cancer du sein [Quality assurance in organized screening of breast cancer]

Quality assurance is an essential process which should be applied for any organised breast cancer screening program since mammography it the only test available for an early diagnosis. It should also assess the quality of diagnostic and treatment processes in order to ascertain that the quality of the screening program would not be altered by the procedures which take place after the screening. Quality assurance must be applied to each component of the screening process: equipment, radiographers (technicians) as well as radiologists. It is a multidisciplinary approach following a well defined protocol, which should be supervised by a coordination unit, the Breast Cancer Screening Foundation in Canton of Vaud. Performances of the Vaud program show clearly at what extend multiple reading method improves the quality of screening. It seems that there is no inconvenient to involve radiologists who wish to participate without any selection to the reading process provided that there is in place a team of 2nd and 3rd readers who benefit of an appropriate training and experience.