How critical is timing for the diagnosis of influenza in general practice?

QUESTIONS UNDER STUDY: The diagnostic significance of clinical symptoms/signs of influenza has mainly been assessed in the context of controlled studies with stringent inclusion criteria. There was a need to extend the evaluation of these predictors not only in the context of general practice but also according to the duration of symptoms and to the dynamics of the epidemic. PRINCIPLES: A prospective study conducted in the Medical Outpatient Clinic in the winter season 1999-2000. Patients with influenza-like syndrome were included, as long as the primary care physician envisaged the diagnosis of influenza. The physician administered a questionnaire, a throat swab was performed and a culture acquired to document the diagnosis of influenza. RESULTS: 201 patients were included in the study. 52% were culture positive for influenza. By univariate analysis, temperature >37.8 degrees C (OR 4.2; 95% CI 2.3-7.7), duration of symptoms <48 hours (OR 3.2; 1.8-5.7), cough (OR 3.2; 1-10.4) and myalgia (OR 2.8; 1.0-7.5) were associated with a diagnosis of influenza. In a multivariable logistic analysis, the best model predicting influenza was the association of a duration of symptom <48 hours, medical attendance at the beginning of the epidemic (weeks 49-50), fever >37.8 and cough, with a sensitivity of 79%, specificity of 69%, positive predictive value of 67%, negative predictive value of 73% and an area under the ROC curve of 0.74. CONCLUSIONS: Besides relevant symptoms and signs, the physician should also consider the duration of symptoms and the epidemiological context (start, peak or end of the epidemic) in his appraisal, since both parameters considerably modify the value of the clinical predictors when assessing the probability of a patient having influenza.

Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint.

BACKGROUND: Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom. METHOD: The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up. RESULTS: From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors. CONCLUSION: This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.

Expression of MYC, IgM, As Well As Non-Germinal Centre B-Cell Like Immunophenotype and Positive Immunofish Index Predict a Worse Progression Free Survival and Overall Survival in a Series of 670 De Novo Diffuse Large B-Cell Lymphomas Included in Clinical Trials: A GELA Study of the 2003 Program

Introduction: Diffuse large B-cell lymphomas (DLBCL) represent a heterogeneous disease with variable clinical outcome. Identifying phenotypic biomarkers of tumor cells on paraffin sections that predict different clinical outcome remain an important goal that may also help to better understand the biology of this lymphoma. Differentiating non-germinal centre B-cell-like (non-GCB) from Germinal Centre B-cell-like (GCB) DLBCL according to Hans algorithm has been considered as an important immunohistochemical biomarker with prognostic value among patients treated with R-CHOP although not reproducibly found by all groups. Gene expression studies have also shown that IgM expression might be used as a surrogate for the GCB and ABC subtypes with a strong preferential expression of IgM in ABC DLBCL subtype. ImmunoFISH index based on the differential expression of MUM-1, FOXP1 by immunohistochemistry and on the BCL6 rearrangement by FISH has been previously reported (C Copie-Bergman, J Clin Oncol. 2009;27:5573-9) as prognostic in an homogeneous series of DLBCL treated with R-CHOP. In addition, oncogenic MYC protein overexpression by immunohistochemistry may represent an easy tool to identify the consequences of MYC deregulation in DLBCL. Our aim was to analyse by immunohistochemistry the prognostic relevance of MYC, IgM, GCB/nonGCB subtype and ImmunoFISH index in a large series of de novo DLBCL treated with Rituximab (R)-chemotherapy (anthracyclin based) included in the 2003 program of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. Methods: The 2003 program included patients with de novo CD20+ DLBCL enrolled in 6 different LNH-03 GELA trials (LNH-03-1B, -B, -3B, 39B, -6B, 7B) stratifying patients according to age and age-adjusted IPI. Tumor samples were analyzed by immunohistochemistry using CD10, BCL6, MUM1, FOXP1 (according to Barrans threshold), MYC, IgM antibodies on tissue microarrays and by FISH using BCL6 split signal DNA probes. Considering evaluable Hans score, 670 patients were included in the study with 237 (35.4%) receiving intensive R-ACVBP regimen and 433 (64.6%) R-CHOP/R-mini-CHOP. Results: 304 (45.4%) DLBCL were classified as GCB and 366 (54.6%) as non-GCB according to Hans algorithm. 337/567 cases (59.4%) were positive for the ImmunoFISH index (i.e. two out of the three markers positive: MUM1 protein positive, FOXP1 protein Variable or Strong, BCL6 rearrangement). Immunofish index was preferentially positive in the non-GCB subtype (81.3%) compared to the GCB subtype (31.2%), (p<0.001). IgM was recorded as positive in tumor cells in 351/637 (52.4%) DLBCL cases with a preferential expression in non-GCB 195 (53.3%) vs GCB subtype 100(32.9%), p<0.001). MYC was positive in 170/577 (29.5%) cases with a 40% cut-off and in 44/577 (14.2%) cases with a cut-off of 70%. There was no preferential expression of MYC among GCB or non-GCB subtype (p>0.4) for both cut-offs. Progression-free Survival (PFS) was significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p<0.0001), MYC positive tumor with a 40% threshold (p<0.001), ImmunoFISH positive index (p<0.002), non-GCB DLBCL subtype (p<0.0001). Overall Survival (OS) was also significantly worse among patients with high IPI score (p<0.0001), IgM positive tumor (p=0.02), MYC positive tumor with a 40% threshold (p<0.01), ImmunoFISH positive index (p=0.02), non-GCB DLBCL subtype (p<0.0001). All significant parameters were included in a multivariate analysis using Cox Model and in addition to IPI, only the GCB/non-GCB subtype according to Hans algorithm predicted significantly a worse PFS among non-GCB subgroup (HR 1.9 [1.3-2.8] p=0.002) as well as a worse OS (HR 2.0 [1.3-3.2], p=0.003). This strong prognostic value of non-GCB subtyping was confirmed considering only patients treated with R- CHOP for PFS (HR 2.1 [1.4-3.3], p=0.001) and for OS (HR 2.3 [1.3-3.8], p=0.002). Conclusion: Our study on a large series of patients included in trials confirmed the relevance of immunohistochemistry as a useful tool to identify significant prognostic biomarkers for clinical use. We show here that IgM and MYC might be useful prognostic biomarkers. In addition, we confirmed in this series the prognostic value of the ImmunoFISH index. Above all, we fully validated the strong and independent prognostic value of the Hans algorithm, daily used by the pathologists to subtype DLBCL.

Development of a Sensitive Resource Use Questionnaire

Alcoholism is a chronic disease and the evaluation of its burden usually focuses on long-term co-morbidity and mortality. Clinical Trials evaluating new interventions for alcohol-dependent patients rarely last more than 12 to 24 months. OBJECTIVES: Develop a questionnaire capable of capturing principal resource use yet sensitive enough to show short-term economic benefit of drugs developed to reduce consump¬tion in alcohol-dependent patients. METHODS: Comprehensive Medline literature search using keywords: Alcohol-related-disorders, economics, cost of illness. Further, experts panel discussions provided additional data. RESULTS: Two key cost drivers, hospitalisation and sick leaves were identified by the literature review. Expert findings related to costs of social consequences were incorporated. These three important resources were included in the questionnaire in addition to standard medical resource use consumption input. Finally, the following items were included: consultation visits, hospitalisations, sick leaves and working situation, living situation, social environ¬ment, accidents, arrests and domestic violence. The recall period is 3 months. DISCUSSION: A great deal of information is collected in this questionnaire in order to capture all relevant resources. Tests to validate the questionnaire in a real-life setting will be conducted (face validity, concurrent validity, and test-retest) in a cohort of dependent patients initiated at Lausanne University hospital ( Switzerland). Items not sensitive enough to capture short-term costs and consequences will be removed. Translation into other major languages and adaptation to different settings after cultural validation is planned. CONCLUSIONS: Publication of this tool should facilitate additional knowledge about resource utilisation at the patient level and enable evaluation of short-term economic impact of pharmacological and non-pharmacological interventions.

[Voyage en Italie : 1824-1830]. , [à gauche] Plan d'un Edifice dont les ruines existent à peu de distance d'un lieu nommé Roma Vecchia [...] ; [au centre] Maison Antique découverte dans la villa Negroni [...]. [à droite] Maison [de marchand] à Pompeia : [trois petits plans, une coupe longitudinale] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 394

bHLH class transcription factors take centre stage in phytochrome signalling.

The phytochrome family of photoreceptors (there are five phytochromes in Arabidopsis, named phyA to phyE) maximally absorbs red and far-red light and plays important functions throughout the life cycle of plants. Several recent studies have shown that multiple related bHLH (basic helix-loop-helix) class transcription factors play key roles in phytochrome signal transduction. Somewhat surprisingly these transcription factors primarily act as negative regulators of phytochrome signalling. Moreover, in some cases, the phytochromes inhibit those negative regulators.

Prevalence, predictors, and consequences of long-term refusal of antipsychotic treatment in first-episode psychosis.

OBJECTIVE: Studies investigating medication adherence in psychosis are limited by the need of a certain degree of medication adherence and the inclusion of mostly multiple-episode patients. By contrast, noninformed consent, epidemiological studies in first-episode psychosis (FEP) allow the assessment of an important subgroup of patients who persistently refuse antipsychotic medication and thereby never receive an adequate antipsychotic trial. The present study aims to assess the prevalence and predictors of such a "medication refusal" subgroup and its association with illness outcome. METHODS: The present file audit study assessed medication adherence in an epidemiological cohort of 605 FEP patients who were treated within the Early Psychosis Prevention and Intervention Centre for up to 18 months. Medication adherence was categorized into full adherence, nonadherence, and persistent medication refusal. Predictors were analyzed using logistic regression models. RESULTS: During the 18-month treatment period, 204 patients (33.7%) were fully adherent, 287 (47.4%) displayed at least 1 phase of nonadherence, and 114 patients (18.8%) were persistent medication refusers. Poor premorbid functioning, comorbid substance use, and poor insight predicted both medication refusal and nonadherence; a forensic history and no previous contact to psychiatric care were specifically predictive of medication refusal. With respect to illness outcome, nonadherent patients were worse off when compared with fully adherent patients, and medication refusers were even worse off compared with nonadherent patients. CONCLUSIONS: Within a nonselected epidemiological FEP cohort, almost 20% of patients are persistent medication refusers. The found predictors may help to identify the individual risk of persistent medication refusal and may enable an early (preventive) treatment adaptation.

Expérience de dix ans de réanimation chirurgicale d'un centre hospitalier universitaire. Détermination d'un critère d'identification des patients à risque de décéder de coagulopathie irréversible [10 years experience in surgical resuscitation at a university hospital center. Determination of a criterion for identifying patients at risk for fatal irreversible coagulopathy]

The authors evaluated ten years of surgical reanimation in the University Centre of Lausanne (CHUV). Irreversible coagulopathy (IC) is the predominant cause of death for the polytraumatized patient. Acidosis, hypothermy, and coagulation troubles are crucial elements of this coagulopathy. The authors looked for a criterion allowing the identification of dying of IC. In a retrospective study, laboratory results of pH, TP, PTT, thrombocyte count and the need for blood transfusion units were checked for each major step of the primary evaluation and treatment of the polytraumatized patients. These results were considered as critical according to criteria of the literature (30). The authors conclude that the apparation of a third critical value may be useful to identify the polytraumatized patient at risk of dying of IC status. This criterion may also guide the trauma team in selecting a damage control surgical approach (DCS). This criterion was then introduced into an algorithm involving the Emergency Department, the operating room and the Intensive Care Unit. This criterion is a new tool to address the patient at the crucial moment to the appropriate hospital structure.

AT-RISK ALCOHOL USE IN YOUNG ADULTS - EFFECTIVENESS AND MECHANISMS OF BRIEF MOTIVATIONAL INTERVENTION AS A PRIMARY AND SECONDARY PREVENTION MEASURE

SummaryThe alcohol use of adolescents and young adults is one of the world's most important and costliest health problems. Particularly, binge drinking (i.e. drinking an important amount of alcohol in one occasion) among young people increase the risk of detrimental consequences such as blackouts, injuries, at-risk sexual behaviors, involvement in violent acts, academic failure, and suicide attempts. In countries with mandatory conscription mechanisms, such as Switzerland, the army provides a unique opportunity to reach a large portion of this high risk population. We used this sample to evaluate the prevalence of binge drinking among young men, to test the efficacy of brief motivational interventions (BMI) as a primary and secondary preventive measure, and to examine the mechanisms underlying BMI in this age group.We showed that binge drinking among young French-speaking Swiss men is less of an exception than it is the norm. Of those using alcohol, 75.5% had a binge drinking episode at least monthly, and 69.3% of all consumption reported in a one-week diary was due to binge drinking days.We used two different inclusion modes to evaluate the success of alcohol BMI. In the first randomized controlled trial, inclusion relied on a random selection of conscripts. BMI efficacy was evaluated in a sample of conscripts who visited the army recruitment centre that is potentially generalizable to the entire population. In the second randomized controlled trial, we included subjects voluntarily participating in BMI. This venue might be more realistic for young adults; it is more akin to the MI spirit, in which it is crucial for individuals to control their own decisions.Regarding BMI efficacy as a secondary prevention measure (i.e. to help decrease alcohol use among at-risk drinkers, defined here as those having a binge drinking episode at least monthly), it was effective among randomly selected at-risk drinkers, whereas it was not effective among at-risk drinkers who voluntarily showed up. Individuals who showed interest in BMI had more severe patterns of alcohol use, which may have made change more difficult and calls for treatment that is more intensive. BMI demonstrated a 20% reduction in weekly alcohol use among randomly selected participants, indicating potential interest in BMI implementation within similar community settings.Regarding BMI efficacy as a primary prevention measure (i.e. to help maintain low levels of use among low-risk drinkers), it had significant protective effects among low-risk drinkers voluntarily showing up whereas it was not effective among low-risk drinkers randomly selected. This suggests that BMI might help young individuals keep their drinking at low levels, especially when they are interested in discussing their alcohol use. Therefore, BMI has potentially promising uses in primary prevention efforts. The content of these interventions for low-risk drinkers who do not seek BMI on their own should be further evaluated.BMI mechanisms were addressed since little is known about exactly which elements of it work, or which of the counselor and subject communication behaviors are most effective in triggering behavior changes. The causal chain hypothesis developed in the motivational interviewing (MI) theory was followed, and it was found that counselor behaviors consistent with the MI approach (MICO) were significantly more likely to be followed by participant language in favor of change (change talk, CT), while behaviors inconsistent with MI (MIIN) were significantly less likely to do so. Several CT dimensions measured during BMI (particularly Ability, Desire, and Need to change) were predictive of change in alcohol use. Our findings lend strong support for the use of MICO behaviors and the avoidance of MIIN behaviors in eliciting CT, and point out that particular attention should be paid to the utterances in several sub-dimensions of CT and to the strength of expression, since these are good indicators of potential actual behavior change in future.RésuméLa consommation d'alcool chez les adolescents et les jeunes adultes est un des problèmes de santé les plus importants et les plus coûteux dans le monde. En particulier, les consommations importantes d'alcool en une occasion (binge drinking) parmi les jeunes adultes ont été liées à des conséquences telles que pertes de connaissance, accidents et blessures, comportements sexuels à risque, violences, difficultés scolaires et tentatives de suicide. Les pays qui, comme la Suisse, connaissent un processus de recrutement obligatoire pour l'armée offrent une opportunité unique d'atteindre une large portion de cette population à hauts risques. Nous avons utilisé cet échantillon pour évaluer la prévalence du binge drinking parmi les jeunes hommes, pour tester l'efficacité de l'intervention brève motivationnelle (IBM) comme mesure de prévention primaire et secondaire, et pour examiner les mécanismes sous-tendant ce type d'interventions.La première partie de cette étude montre que le binge drinking est moins une exception que la norme parmi les jeunes hommes suisses francophones. 75.5% des personnes consommant de l'alcool avaient au moins un épisode de binge drinking par mois et 69.3% du total des boissons alcoolisées reportées comme consommation de la semaine précédant le questionnaire avaient été consommées lors d'épisodes de binge drinking.Pour évaluer l'efficacité de l'IBM dans ce cadre, nous avons utilisé deux modes d'inclusion. Dans une première étude randomisée contrôlée, nous avons inclus des personnes sélectionnées au hasard parmi toutes celles se présentant au centre de recrutement, créant ainsi un groupe potentiellement représentatif de l'ensemble du collectif. Dans la deuxième étude randomisée contrôlée, nous avons inclus des sujets se présentant volontairement pour recevoir une IBM, prendre des volontaires pouvant être plus proche de la réalité et plus proche de l'esprit motivationnel dans lequel il est crucial que l'individu contrôle ses décisions.En regardant l'IBM comme mesure de prévention secondaire (c'est-à-dire aider à diminuer la consommation d'alcool chez les consommateurs à risque, définis ici comme au moins un épisode de binge drinking par mois), l'IBM était efficace lorsque les participants étaient inclus au hasard et inefficace lorsqu'ils étaient volontaires. Les jeunes hommes volontaires pour un IBM avaient un mode de consommation particulièrement sévère qui pourrait être plus difficile à changer et nécessiter un traitement plus intensif. Parmi les personnes sélectionnées au hasard, l'IBM permettait une diminution de 20% de la consommation hebdomadaire d'alcool, montrant l'intérêt potentiel d'une implémentation de ce type de mesures dans des contextes communautaires similaires.En ce qui concerne l'IBM comme mesure de prévention primaire (c'est-à-dire aider à maintenir une consommation à bas risque chez les consommateurs à bas risque), l'IBM avaient un effet protectif significatif parmi les jeunes hommes volontaires pour une IBM, mais pas d'effet chez ceux sélectionnés au hasard. Ces résultats suggèrent que l'IBM pourrait aider de jeunes personnes à maintenir un niveau de consommation à bas risque si celles-ci s'intéressent à discuter cette consommation et aurait ainsi un potentiel intéressant comme mesure de prévention primaire. Le contenu de l'IBM pour des consommateurs à bas risque non-volontaires pour une IBM devra encore être évalué.Nous avons ensuite examiné les mécanismes de l'IBM car son fonctionnement est encore peu expliqué et les comportements de l'intervenant et du sujet les plus à même de provoquer le changement ne sont pas bien définis. En suivant l'hypothèse d'une chaine causale développée dans la littérature de l'entretien motivationnel (EM), nous avons pu montrer qu'un discours en faveur du changement chez le sujet était plus probable après des comportements de l'intervenant recommandés dans l'EM et moins probable après des comportements à éviter dans l'EM ; et que plusieurs dimensions de ce discours en faveur du changement (notamment la capacité, le désir et le besoin de changer) prédisaient un changement effectif dans la consommation d'alcool. Ces résultats encouragent donc à utiliser des comportements recommandés dans l'EM pour favoriser un discours en faveur du changement. Ils montrent aussi qu'une attention particulière doit être portée à la fréquence et à la force avec laquelle sont exprimées certaines dimensions de ce discours car ceux-ci indiquent un potentiel changement effectif de comportement.Résumé vulgariséLa consommation d'alcool chez les adolescents et les jeunes adultes est un des problèmes de santé les plus importants et les plus coûteux dans le monde. En particulier, les consommations importantes d'alcool en une occasion (binge drinking) parmi les jeunes adultes augmentent fortement les risques de conséquences telles que pertes de connaissance, accidents et blessures, comportements sexuels à risque, violences, difficultés scolaires et tentatives de suicide. Les pays qui, comme la Suisse, connaissent un processus de recrutement obligatoire pour l'armée offrent une opportunité unique d'atteindre une large portion de cette population à hauts risques. Nous avons utilisé cet échantillon pour évaluer l'importance du phénomène de binge drinking, pour tester l'efficacité de l'intervention brève motivationnelle (IBM) comme mesure de prévention de la consommation à risque d'alcool, et pour examiner comment fonctionne ce type d'interventions.La première partie de cette étude montre que le binge drinking est moins une exception que la norme parmi les jeunes hommes suisses francophones. Trois quart des personnes consommant de l'alcool avaient au moins un épisode de binge drinking par mois. Presque 70% du total des boissons alcoolisées consommées durant la semaine précédant le questionnaire avaient été consommées lors d'épisodes de binge drinking.Nous avons ensuite mené deux études pour évaluer l'efficacité de l'IBM dans ce cadre. Dans une première étude, nous avons sélectionné des personnes au hasard parmi toutes celles se présentant au centre de recrutement, créant ainsi un groupe potentiellement représentatif de l'ensemble du collectif. Dans la deuxième étude, nous avons inclus toutes les personnes se présentant volontairement pour recevoir une IBM, prendre des volontaires pouvant être plus proche de la réalité et plus proche de l'approche motivationnelle dans laquelle il est crucial que l'individu contrôle ses décisions. Dans les deux études, nous testions l'efficacité de l'IBM comme mesure de prévention primaire et secondaire (voir ci-dessous).En regardant l'IBM comme mesure de prévention secondaire (c'est-à-dire aider à diminuer la consommation d'alcool chez les consommateurs à risque, définis ici comme au moins un épisode de binge drinking par mois), l'IBM était efficace lorsque les participants étaient inclus au hasard et inefficace lorsqu'ils étaient volontaires. Les jeunes hommes volontaires pour un IBM avaient un mode de consommation particulièrement sévère qui pourrait être plus difficile à changer et nécessiter un traitement plus intensif. Parmi les personnes sélectionnées au hasard, l'IBM permettait une diminution de 20% de la consommation hebdomadaire d'alcool, montrant l'intérêt potentiel de la mise en place de ce type de mesures dans des contextes communautaires similaires.En ce qui concerne l'IBM comme mesure de prévention primaire (c'est-à-dire aider à maintenir une consommation à bas risque chez les consommateurs à bas risque), l'IBM avaient un effet protectif parmi les jeunes hommes volontaires pour une IBM, mais pas d'effet chez ceux sélectionnés au hasard. Ces résultats suggèrent que l'IBM pourrait aider de jeunes personnes à maintenir un niveau de consommation à bas risque si celles-ci s'intéressent à discuter de cette consommation. Le contenu de l'IBM pour des consommateurs à bas risque non-volontaires pour une IBM devra encore être évalué.Nous avons ensuite examiné le fonctionnement de l'IBM et cherché quels comportements de l'intervenant et du jeune homme pouvaient être les plus à même d'amener à un changement dans la consommation. Nous avons pu montrer que 1) un discours en faveur du changement chez le jeune homme était plus probable après des comportements de l'intervenant recommandés dans l'approche motivationnelle et moins probable après des comportements non-recommandés ; et 2) plusieurs dimensions de ce discours en faveur du changement (notamment la capacité, le désir et le besoin de changer) prédisaient un changement effectif dans la consommation d'alcool. Ces résultats encouragent donc à utiliser des comportements recommandés dans l'EM pour favoriser un discours en faveur du changement. Ils montrent aussi qu'une attention particulière doit être portée à certaines dimensions de ce discours car celles-ci indiquent un potentiel changement effectif de comportement.

The GENCODE pseudogene resource.

BACKGROUND: Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data. RESULTS: As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection. CONCLUSIONS: At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.