Premier épisode thymique: cas particulier de l'intervention dans la phase précoce des troubles bipolaires [First episode of mood disorders: an opportunity for early intervention in bipolar disorders].

While early intervention strategies have been developed for psychotic disorders, affective psychoses and bipolar disorders have been neglected by this movement. However, when considering that outcome of bipolar disorders is often not as favorable as previously thought and that delay between illness onset and introduction of an adequate treatment is often very long, such developments seem clearly justified. In this paper we briefly review arguments supporting early intervention in bipolar disorders, the practical and theoretical obstacles that still need to be overcome, the strategies that may already now contribute to decrease treatment delay, and we describe current state of research regarding identification of the prodromal phase of bipolar disorders.

First description of Candida nivariensis in Brazil: antifungal susceptibility profile and potential virulence attributes

This study evaluated the antifungal susceptibility profile and the production of potential virulence attributes in a clinical strain of Candida nivariensis for the first time in Brazil, as identified by sequencing the internal transcribed spacer (ITS)1-5.8S-ITS2 region and D1/D2 domains of the 28S of the rDNA. For comparative purposes, tests were also performed with reference strains. All strains presented low planktonic minimal inhibitory concentrations (PMICs) to amphotericin B (AMB), caspofungin (CAS), and voriconazole. However, our strain showed elevated planktonic MICs to posaconazole (POS) and itraconazole, in addition to fluconazole resistance. Adherence to inert surfaces was conducted onto glass and polystyrene. The biofilm formation and antifungal susceptibility on biofilm-growing cells were evaluated by crystal violet staining and a XTT reduction assay. All fungal strains were able to bind both tested surfaces and form biofilm, with a binding preference to polystyrene (p < 0.001). AMB promoted significant reductions (≈50%) in biofilm production by our C. nivariensis strain using both methodologies. This reduction was also observed for CAS and POS, but only in the XTT assay. All strains were excellent protease producers and moderate phytase producers, but lipases were not detected. This study reinforces the pathogenic potential of C. nivariensis and its possible resistance profile to the azolic drugs generally used for candidiasis management.

New clinical practice guideline on enteral feeding in very low birth weight infants; first part.

The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see whether our nutrition policy was involved, we undertook a systematic review and drew up clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. After conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of well-proven measurements reduces the variation in clinical practice and improves results.

A Formal Framework for Specifying, Reusing and Implementing Learning Processes. First level

This file contains the ontology of patterns of educational settings, as part of the formal framework for specifying, reusing and implementing educational settings. Furthermore, it includes the set of rules that extend the ontology of educational scenarios as well as a brief description of the level of patters of such ontological framework.

First insights into the transcriptome and development of new genomic tools of a widespread circum-Mediterranean tree species, Pinus halepensis Mill.

Aleppo pine (Pinus halepensis Mill.) is a relevant conifer species for studying adaptive responses to drought and fire regimes in the Mediterranean region. In this study, we performed Illumina next-generation sequencing of two phenotypically divergent Aleppo pine accessions with the aims of (i) characterizing the transcriptome through Illumina RNA-Seq on trees phenotypically divergent for adaptive traits linked to fire adaptation and drought, (ii) performing a functional annotation of the assembled transcriptome, (iii) identifying genes with accelerated evolutionary rates, (iv) studying the expression levels of the annotated genes and (v) developing gene-based markers for population genomic and association genetic studies. The assembled transcriptome consisted of 48,629 contigs and covered about 54.6 Mbp. The comparison of Aleppo pine transcripts to Picea sitchensis protein-coding sequences resulted in the detection of 34,014 SNPs across species, with a Ka /Ks average value of 0.216, suggesting that the majority of the assembled genes are under negative selection. Several genes were differentially expressed across the two pine accessions with contrasted phenotypes, including a glutathione-s-transferase, a cellulose synthase and a cobra-like protein. A large number of new markers (3334 amplifiable SSRs and 28,236 SNPs) have been identified which should facilitate future population genomics and association genetics in this species. A 384-SNP Oligo Pool Assay for genotyping with the Illumina VeraCode technology has been designed which showed an high overall SNP conversion rate (76.6%). Our results showed that Illumina next-generation sequencing is a valuable technology to obtain an extensive overview on whole transcriptomes of nonmodel species with large genomes.

Cost-effectiveness analysis of the first-line therapies for nicotine dependence.

BACKGROUND: Nicotine dependence is the major obstacle for smokers who want to quit. Guidelines have identified five effective first-line therapies, four nicotine replacement therapies (NRTs)--gum, patch, nasal spray and inhaler--and bupropion. Studying the extent to which these various treatments are cost-effective requires additional research. OBJECTIVES: To determine cost-effectiveness (CE) ratios of pharmacotherapies for nicotine dependence provided by general practitioners (GPs) during routine visits as an adjunct to cessation counselling. METHODS: We used a Markov model to generate two cohorts of one-pack-a-day smokers: (1) the reference cohort received only cessation counselling from a GP during routine office visits; (2) the second cohort received the same counselling plus an offer to use a pharmacological treatment to help them quit smoking. The effectiveness of adjunctive therapy was expressed in terms of the resultant differential in mortality rate between the two cohorts. Data on the effectiveness of therapies came from meta-analyses, and we used odds ratio for quitting as the measure of effectiveness. The costs of pharmacotherapies were based on the cost of the additional time spent by GPs offering, prescribing and following-up treatment, and on the retail prices of the therapies. We used the third-party-payer perspective. Results are expressed as the incremental cost per life-year saved. RESULTS: The cost per life-year saved for only counselling ranged from Euro 385 to Euro 622 for men and from Euro 468 to Euro 796 for women. The CE ratios for the five pharmacological treatments varied from Euro 1768 to Euro 6879 for men, and from Euro 2146 to Euro 8799 for women. Significant variations in CE ratios among the five treatments were primarily due to differences in retail prices. The most cost-effective treatments were bupropion and the patch, and, then, in descending order, the spray, the inhaler and, lastly, gum. Differences in CE between men and women across treatments were due to the shape of their respective mortality curve. The lowest CE ratio in men was for the 45- to 49-year-old group and for women in the 50- to 54-year-old group. Sensitivity analysis showed that changes in treatment efficacy produced effects only for less-well proven treatments (spray, inhaler, and bupropion) and revealed a strong influence of the discount rate and natural quit rate on the CE of pharmacological treatments. CONCLUSION: The CE of first-line treatments for nicotine dependence varied widely with age and sex and was sensitive to the assumption for the natural quit rate. Bupropion and the nicotine patch were the two most cost-effective treatments.

Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

PURPOSE: Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. MATERIALS AND METHODS: RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). RESULTS: Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). CONCLUSION: Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue.

The Swiss Willensnation at Risk: Teachers in the Cultural Gap during the First World War

As a neutral and multilingual country, Switzerland struggled with major domestic political conflicts during the First World War due to the two cultures of the French-speaking and German-speaking parts of the country. The divided cultural loyalties ('fossé moral', 'Röstigraben'), consisting of Swiss-Germans supporting Germany and Swiss-French supporting France, were discussed intensively in both of the main teachers' journals in Switzerland. Teachers felt the need to react and to promote unity from the beginning of the war. Despite the fact that the cantons are responsible for public education and, therefore, for the education of their students, teachers considered themselves called to educate their students to be national citizens rather than to be members of a language group. This threefold citizenship - communal, cantonal and national - was not scrutinised, but national unity became crucial due to the critical political circumstances. How did teachers promote and constitute citizenship for themselves and for their students in a nation united by free will during the First World War, a time of severe internal political conflicts?

Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation.

Using quantitative fluorescence in situ hybridization and flow cytometry, the telomere length of telomere repeat sequences after stem cell transplantation (SCT) were measured. The study included the telomeres of peripheral blood monocytes that should reflect the length of telomeres in stem cells and the telomeres of T lymphocytes that could shorten as a result of peripheral expansion. The loss of telomeres in monocytes and in memory T cells, although accelerated initially, became comparable to the loss of telomeres in healthy controls from the second year after transplantation. In addition, the telomere length in the naive T cells that were produced by the thymus was comparable to the telomere length in the naive T cells of the donor. Compared to the total length of telomeres available, the loss of telomere repeats in leukocytes after SCT resembles the accelerated shortening seen in early childhood and remains, therefore, relatively insignificant.

The joint R&D project: The case of the first Brazilian microcontroller chip

ABSTRACT The interorganizational cooperation, through joint efforts with various actors, allows the high-tech companies to complement resources, especially in R&D projects. Collaborative projects have been identified in many studies as an important strategy to produce complex products and services in uncertain and competitive environments. Thus, this research aims at deepening the understanding of how the development dynamics of a collaborative R&D project in an industry of high technology occur. In order to achieve the proposed objective, the R&D project of the first microcontroller in the Brazilian semiconductor industry was defined as the object of analysis. The empirical choice is justified by the uniqueness of the case, besides bringing a diversity of actors and a level of complementarity of resources that were significant to the success of the project. Given the motivation to know who the actors were and what the main forms of interorganizational coordination were used in this project, interviews were carried out and a questionnaire was also made, besides other documents related to the project. The results presented show a network of nine actors and their roles in the interorganizational collaboration process, as well as the forms of social and temporal overlapping, used in the coordination of collective efforts. Focusing on the mechanisms of temporal and social integration highlighted throughout the study, the inclusion of R&D projects in the typology for interorganizational projects is proposed in this paper, which was also proposed by Jones and Lichtenstein (2008).

Anxiety and Psychological Stress Before Prenatal Screening in First-Time Mothers Who Conceived Through IVF/ICSI or Spontaneously.

Mothers' general anxiety, anxiety about the well-being of the child and psychological stress before prenatal testing was studied by comparing women who conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with women who conceived naturally. Before the first trimester screening test for Down's syndrome, a group of 51 women who conceived through IVF/ICSI and a group of 54 women who conceived spontaneously completed the State Scale of the State-Trait Anxiety Inventory (S-Anxiety; Spielberger, 1983), the Fear of Bearing a Physically or Mentally Handicapped Child Subscale of the Pregnancy-related Anxiety Questionnaire (PRAQ-R; Huizink et al., 2004), the Psychological Stress Measure (PSM; Lemyre & Tessier, 1988), and the Prenatal Psychosocial Profile (PPP; Curry, Campbell, & Christian, 1994). Women who conceived through IVF/ICSI had more elevated levels of general anxiety and psychological stress than the women who conceived naturally; however, no difference was observed between the two groups for anxiety specifically related to the health of the child. These results underline the need to monitor women's emotional state after conception via IVF/ICSI-when counseling usually ends-and around the time of the first trimester screening. Counseling might thus be extended.

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C.

Background & Aims: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-alpha/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.Methods: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naive Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-alpha 2a (180 mu g weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.Results: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted p <0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p <0.001). In univariate analyses, Trs12979860 was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, Trs12979860 was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline.Conclusions: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-alpha/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

L'état de santé des Lausannois: premiers résultats de l'étude CoLaus. [Health examination survey of the Lausanne population: first results of the CoLaus study].

Cardiovascular diseases (CVD) remain the main cause of morbidity and mortality in our society. CoLaus is a population-based health examination survey started in 2003 in Lausanne in order to assess: 1. Prevalence of cardiovascular risk factors, 2. New genetic determinants of cardiovascular risk factors such as hypertension, 3. Association of mood disorders with incidence of cardiovascular events and 4. Trends in prevalence of cardiovascular risk factors. In order to do so, over 6000 subjects (ages 35-75 years) provided data on CVD risk factors. Herein we provide preliminary results of this study, in particular on classical risk factors such as hypertension, obesity and diabetes. Implications and perspectives of this population based-study for public health and genetic studies are also discussed.

Functional significance of first metatarso-phalangeal joint arthrodesis : FM101

Introduction: Indications for arthrodesis of the first metatarsophalangeal joint (MTP1) are commonly arthrosis (hallux rigidus), rheumatoid arthritis, failed hallux valgus surgery, severe hallux valgus, infectious arthritis, fractures and neuroarthropathies. Many reports focus on technical and radiological issues but few studies emphasize the functional outcome considering daily activities, sports and expectation of the patient. Method: We retrospectively reviewed the patients who underwent MTP1-arthrodesis from 2002 to 2005 in our institution. Clinical and radiological results were assessed but we specially focussed on the functional outcome. Scoring systems used were the SF-12, EQ-5D, PASI, FFI and AOFAS (10 points given to MTP1 mobility) scales. Results: 61 of 64 consecutive patients were evaluated. Female to male ratio was 49:15, mean age at surgery was 67 years, the average follow up was 29 month. Even if radiological consolidation was incomplete in 18 patients, all patients had a clinically stable and rigid arthrodesis. Mean AOFAS score was 87 (24-100) points at follow up. The FFI was 5.91% (0-66%). Patient satisfaction was excellent in 37 patients (60%), good in 18 (30%), fair in 5(8%) and poor in1 (2%). EQ- 5D was 0.7 (0.4-1).40 patients (66%) estimated their cosmetic result as excellent, 15 (25%) as good, 4(6%) as fair and 2 (3%)as poor. 10 patients (16%) had no shoe wear limitation , 48 (79%) had to wear comfortable shoes and 3 (5%) needed orthopaedic wearing. Professionally 34 patients (56%) had better performances, 18 (26%) had no change and 9 (18%) had aggravation of their capacities but this was due to other health reasons. In sports, 16 patients (26%) had better performances, 35 patients (57%) no change and 10 (17%) were worse as consequence of other health problems for 7. Finally, 56 patients (92%) would recommend the operation and 5 (8%) would not. Conclusion: Experience of clinical practice suggests that the idea of fusing the first MTP joint is initially frequently disregarded by the patients because they fear to be limited by a rigid forefoot. Our results show, in fact, that this procedure can be proposed for numerous pathological situations with the perspective of good to excellent outcome in terms of function and quality of life in the majority of cases.