The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models.

Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

Validation transculturelle de l'Oswestry disability index en français [Cross-cultural validation of the Oswestry disability index in French]

AIM: The aim of this study was to interpret and validate a French version of the Oswestry disability index (ODI), using a cross-cultural validation method. The validity and reliability of the questionnaire was assessed in order to ensure the psychometric characteristics. METHOD: The cross-cultural validation was carried out according to Beaton's methodology. The study was conducted with 41 patients suffering from low back pain. The correlation between the ODI and the Roland-Morris disability questionnaire (RMDQ), the medical outcome survey short form-36 (MOS SF-36) and a pain visual analogical scale (VAS) was assessed. RESULTS: The validity of the Oswestry questionnaire was studied using the Cronbach Alpha coefficient calculation: 0.87 (n=36). The significant correlation between the ODI and RMDQ was 0.8 (P<0.001, n=41) and 0.71 (P<0.001, n=36) for the pain VAS. The correlation between the ODI and certain subscales (physical functioning 0.7 (P<0.001, n=41), physical role 0.49 et bodily pain 0.73 (P<0.001, n=41)) of the MOS SF-36 were equally significant. The reproducibility of the ODI was calculated using the Wilcoxon matched pairs test: there was no significant difference for eight out of ten sections or for the final score. CONCLUSION: This French translation of the ODI should be considered as valid and reliable. It should be used for any future clinical studies carried out using French language patients. Complimentary studies must be completed in order to assess its sensitivity to change in the event of any modifications in the patients functional capacity.

La prise en compte des valeurs dans la validation scientifique des méthodes thérapeutiques

L'article met en évidence la nécessité de prendre en compte le registre des valeurs, engagées dans nos croyances, lorsque nous cherchons à évaluer les méthodes psychothérapeutiques et à les valider scientifiquement. Après avoir montré l'apport de l'anthropologie clinique pour une telle démarche et précisé le lien réunissant science et croyance, il propose une double clarification qui apparaît indispensable à opérer en vue de valider une méthode psychothérapeutique, à savoir une clarification d'ordre épistémologique et scientifique.

Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide.

We have previously shown that a 28-amino acid peptide derived from the BRC4 motif of BRCA2 tumor suppressor inhibits selectively human RAD51 recombinase (HsRad51). With the aim of designing better inhibitors for cancer treatment, we combined an in silico docking approach with in vitro biochemical testing to construct a highly efficient chimera peptide from eight existing human BRC motifs. We built a molecular model of all BRC motifs complexed with HsRad51 based on the crystal structure of the BRC4 motif-HsRad51 complex, computed the interaction energy of each residue in each BRC motif, and selected the best amino acid residue at each binding position. This analysis enabled us to propose four amino acid substitutions in the BRC4 motif. Three of these increased the inhibitory effect in vitro, and this effect was found to be additive. We thus obtained a peptide that is about 10 times more efficient in inhibiting HsRad51-ssDNA complex formation than the original peptide.

Development and validation of the Transition to Retirement Questionnaire

The aim of this study was to present the initial validation of a new questionnaire, the Transition to Retirement Questionnaire (TRQ) and to study its relationship with resistance to change and personality dimensions. Based on Schlossberg's typology of the retired, the TRQ is designed to assess five dimensions related to personal perceptions of transition to retirement, retirement, and personal plans and activities. The sample consisted of 1,054 professionally active or retired adults from the Swiss French-speaking Canton of Vaud. Exploratory principal components and confirmatory factor analyses highlighted a five-factor solution that fit coherently with Schlossberg's typology. Moreover, TRQ dimensions were related to resistance to change tendencies and personality dimensions. The TRQ seems to be an interesting tool for use in research but also for interventions with young retirees or people preparing for retirement.

Genetic dissection of azole resistance mechanisms in Candida albicans and their validation in a mouse model of disseminated infection.

Principal mechanisms of resistance to azole antifungals include the upregulation of multidrug transporters and the modification of the target enzyme, a cytochrome P450 (Erg11) involved in the 14alpha-demethylation of ergosterol. These mechanisms are often combined in azole-resistant Candida albicans isolates recovered from patients. However, the precise contributions of individual mechanisms to C. albicans resistance to specific azoles have been difficult to establish because of the technical difficulties in the genetic manipulation of this diploid species. Recent advances have made genetic manipulations easier, and we therefore undertook the genetic dissection of resistance mechanisms in an azole-resistant clinical isolate. This isolate (DSY296) upregulates the multidrug transporter genes CDR1 and CDR2 and has acquired a G464S substitution in both ERG11 alleles. In DSY296, inactivation of TAC1, a transcription factor containing a gain-of-function mutation, followed by sequential replacement of ERG11 mutant alleles with wild-type alleles, restored azole susceptibility to the levels measured for a parent azole-susceptible isolate (DSY294). These sequential genetic manipulations not only demonstrated that these two resistance mechanisms were those responsible for the development of resistance in DSY296 but also indicated that the quantitative level of resistance as measured in vitro by MIC determinations was a function of the number of genetic resistance mechanisms operating in any strain. The engineered strains were also tested for their responses to fluconazole treatment in a novel 3-day model of invasive C. albicans infection of mice. Fifty percent effective doses (ED(50)s) of fluconazole were highest for DSY296 and decreased proportionally with the sequential removal of each resistance mechanism. However, while the fold differences in ED(50) were proportional to the fold differences in MICs, their magnitude was lower than that measured in vitro and depended on the specific resistance mechanism operating.

Answer : African net survey - we respond !

Between the end of August and December 2013, an internet based survey named ANSWER will collect data about sexual health, sexual behavior and risk taking among Sub-Saharan African migrants (SSAm) living in Switzerland. This research is carried out by the Institut de médecine sociale et préventive (IUMSP, Lausanne) on a mandate from the Federal Offi ce of Public Health (FOPH), in cooperation with the Swiss Aids Federation (AHS) and other institutions addressing the prevention and information needs of the African population living in Switzerland.

Validation of the antenatal perceived stress inventory

This article presents the Antenatal Perceived Stress Inventory. The originality of this scale is to assess the impact of events experienced during pregnancy on the stress perceived by mothers. Scale validation was performed using data from 150 French-speaking nulliparous mothers and collected between 36 and 39 weeks of gestation (T1), and between 2 days (T2) and 6 weeks postpartum (T3). Factor analysis revealed a hierarchical three-factor structure that closely fit the data, including medical and obstetric risks/fetal health (F1), psychosocial changes (F2), and the prospect of childbirth (F3). The Antenatal Perceived Stress Inventory is a valid French prenatal stress scale with good psychometric properties.

Development and validation of a self-report version of the Spinal Cord Independence Measure (SCIM III).

Study design:Cross-sectional validation study.Objectives:To develop and validate a self-report version of the Spinal Cord Independence Measure (SCIM III).Setting:Two SCI rehabilitation facilities in Switzerland.Methods:SCIM III comprises 19 questions on daily tasks with a total score between 0 and 100 and subscales for 'self-care', 'respiration & sphincter management' and 'mobility'. A self-report version (SCIM-SR) was developed by expert discussions and pretests in individuals with spinal cord injury (SCI) using a German translation. A convenience sample of 99 inpatients with SCI was recruited. SCIM-SR data were analyzed together with SCIM III data obtained from attending health professionals.Results:High correlations between SCIM III and SCIM-SR were observed. Pearson's r for the total score was 0.87 (95% confidence interval (CI) 0.82-0.91), for the subscales self-care 0.87 (0.81-0.91); respiration & sphincter management 0.81 (0.73-0.87); and mobility 0.87 (0.82-0.91). Intraclass correlations were: total score 0.90 (95% CI 0.85-0.93); self-care 0.86 (0.79-0.90); respiration & sphincter management 0.80 (0.71-0.86); and mobility 0.83 (0.76-0.89). Bland-Altman plots showed that patients rated their functioning higher than professionals, in particular for mobility. The mean difference between SCIM-SR and SCIM III for the total score was 5.14 (point estimate 95% CI 2.95-7.34), self-care 0.89 (0.19-1.59), respiration & sphincter management 1.05 (0.18-2.28 ) and mobility 3.49 (2.44-4.54). Particularly patients readmitted because of pressure sores rated their independence higher than attending professionals.Conclusion:Our results support the criterion validity of SCIM-SR. The self-report version may facilitate long-term evaluations of independence in persons with SCI in their home situation.

Validation study of the French version of the observer-rater scales measuring coping and cognitive errors (CE-CAP) on a non-clinical population

This study examined the validity and reliability of the French version of two observer-rated measures developed to assess cognitive errors (cognitive errors rating system [CERS]) [6] and coping action patterns (coping action patterns rating system [CAPRS]) [22,24]. The CE measures 14 cognitive errors, broken down according to their valence positive or negative (see the definitions by A.T. Beck), and the CAP measures 12 coping categories, based on an comprehensive review literature, each broken down into three levels of action (affective, behavioural, cognitive). Thirty (N = 30) subjects recruited in a community sample participated in the study. They were interviewed according to a standardized clinical protocol: these interviews were transcribed and analysed with both observer-rated systems. Results showed that the inter-rater reliability of the two measures is good and that their internal validity is satisfactory, due to a non-significant canonical correlation between CAP and CE. With regard to discriminant validity, we found a non-significant canonical correlation between CAPRS and CISS, one of most widely used self-report questionnaire measuring coping. The same can be said for the correlation with a self-report questionnaire measuring symptoms (SCL-90-R). These results confirm the absence of confounds in the assessment of cognitive errors and of coping as assessed by these observer-rated scales and add an argument in favour of the French validation of the CE-CAP rating scales. (C) 2010 Elsevier Masson SAS. All rights reserved.

Quality of life after pulmonary embolism: validation of the French version of the PEmb-QoL questionnaire.

Background The PEmb-QoL is a validated 40-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It covers six health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in Dutch and English, we sought to prospectively validate the psychometric properties of a French version of the PEmb-QoL.MethodsWe performed a forward and backward translation of the English version of the PEmb-QoL into French. French-speaking consecutive adult patients with an acute, objectively confirmed PE admitted to the emergency department of a Swiss university hospital between 08/2009 and 09/2011 were recruited telephonically. We used standard psychometric tests and criteria to evaluate the acceptability, reliability, and validity of the French version of the PEmb-QoL. We also performed an exploratory factor analysis.ResultsOverall, 102 patients were enrolled in the study. The French version of the PEmb-QoL showed good reliability (internal consistency, item¿total and inter-item correlations), reproducibility (test-retest reliability), and validity (convergent, discriminant) in French-speaking patients with PE. The exploratory factor analysis suggested three underlying dimensions: limitations in daily activity (items 4b-m, 5a-d), symptoms (items 1a-h and 7), and emotional complaints (items 9a-f and j).ConclusionWe successfully validated the French version of the PEmb-QoL questionnaire in patients with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French-speaking patients.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.