Validation of a wrist monitor for accurate estimation of RR intervals during sleep.

While the incidence of sleep disorders is continuously increasing in western societies, there is a clear demand for technologies to asses sleep-related parameters in ambulatory scenarios. The present study introduces a novel concept of accurate sensor to measure RR intervals via the analysis of photo-plethysmographic signals recorded at the wrist. In a cohort of 26 subjects undergoing full night polysomnography, the wrist device provided RR interval estimates in agreement with RR intervals as measured from standard electrocardiographic time series. The study showed an overall agreement between both approaches of 0.05 ± 18 ms. The novel wrist sensor opens the door towards a new generation of comfortable and easy-to-use sleep monitors.

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.

Etude de mentions manuscrites apposées dans des conditions non conventionnelles (dans le cadre des articles 322-1 à 322-4 du nouveau code pénal français)

Résumé Les experts forensiques en documents peuvent être confrontés à des écritures réalisées en conditions non conventionnelles. Ces circonstances atypiques pourraient être à l'origine d'une plus grande variabilité de la forme de l'écriture, en particulier lorsque des positions à priori inhabituelles du corps et / ou du support sont impliquées. En effet, en dépit de son aspect stéréotypé /standardisé évident, résultat d'un apprentissage par un modèle, notre écriture est caractérisée par une variabilité intrinsèque de la forme, qui évolue au cours du temps et qui, dans sa dimension qualitative, confère à l'écriture son caractère individuel. En d'autres termes, nous n'écrivons jamais deux fois de la même façon. Cette variabilité intraindividuelle (ou intra-variabilité) observée en condition conventionnelle, c'est-à-dire assis devant un support horizontal, pourrait augmenter en conditions non conventionnelles, par exemple dans une position inconfortable. Cela pourrait rendre plus difficile l'identification d'écrits apposés dans une condition non conventionnelle ou inconnue. Ne pas connaître les circonstances d'apposition d'une mention manuscrite ou ne pas s'interroger sur ces dernières, pourrait conduire l'expert à faire des erreurs d'appréciation. Et le simple fait d'étudier une trace sur laquelle le corps peut exercer une influence fait de l'expertise en écriture une spécialité qui se distingue des autres disciplines forensiques. En cela, la trace écrite diffère des autres types de traces "inanimées" (physiques, chimiques, bigchimiques) considérées comme invariables (mais potentiellement sensibles à d'autres phénomènes tels que la température, la pression atmosphérique...). En effet, le mouvement d'écriture étant commandé et contrôlé par le cerveau, cela lui confère une certaine variabilité. Il est donc assez logique de penser que la connaissance des mécanismes neuroscientifiques à l'origine de ce mouvement facilitera la compréhension des phénomènes observés d'un point de vue forensique. Deux expériences ont été menées afin de comparer les performances de sujets écrivant dans différentes conditions (conventionnelle vs. non conventionnelles). Les résultats ont montré que cinq des sept conditions non conventionnelles n'avaient pas d'impact significatif sur la variabilité d'écriture. L'ensemble des résultats fournit aux experts forensiques des pistes leur permettant de mieux appréhender les écritures rédigées dans des conditions inhabituelles.

Validation of a Low-Cost Human Papillomavirus Genotyping Assay Based on PGMY PCR and Reverse Blotting Hybridization with Reusable Membranes.

The genotyping of human papillomaviruses (HPV) is essential for the surveillance of HPV vaccines. We describe and validate a low-cost PGMY-based PCR assay (PGMY-CHUV) for the genotyping of 31 HPV by reverse blotting hybridization (RBH). Genotype-specific detection limits were 50 to 500 genome equivalents per reaction. RBH was 100% specific and 98.61% sensitive using DNA sequencing as the gold standard (n = 1,024 samples). PGMY-CHUV was compared to the validated and commercially available linear array (Roche) on 200 samples. Both assays identified the same positive (n = 182) and negative samples (n = 18). Seventy-six percent of the positives were fully concordant after restricting the comparison to the 28 genotypes shared by both assays. At the genotypic level, agreement was 83% (285/344 genotype-sample combinations; κ of 0.987 for single infections and 0.853 for multiple infections). Fifty-seven of the 59 discordant cases were associated with multiple infections and with the weakest genotypes within each sample (P < 0.0001). PGMY-CHUV was significantly more sensitive for HPV56 (P = 0.0026) and could unambiguously identify HPV52 in mixed infections. PGMY-CHUV was reproducible on repeat testing (n = 275 samples; 392 genotype-sample combinations; κ of 0.933) involving different reagents lots and different technicians. Discordant results (n = 47) were significantly associated with the weakest genotypes in samples with multiple infections (P < 0.0001). Successful participation in proficiency testing also supported the robustness of this assay. The PGMY-CHUV reagent costs were estimated at $2.40 per sample using the least expensive yet proficient genotyping algorithm that also included quality control. This assay may be used in low-resource laboratories that have sufficient manpower and PCR expertise.

Identification and validation of copy number variants using SNP genotyping arrays from a large clinical cohort.

BACKGROUND: Genotypes obtained with commercial SNP arrays have been extensively used in many large case-control or population-based cohorts for SNP-based genome-wide association studies for a multitude of traits. Yet, these genotypes capture only a small fraction of the variance of the studied traits. Genomic structural variants (GSV) such as Copy Number Variation (CNV) may account for part of the missing heritability, but their comprehensive detection requires either next-generation arrays or sequencing. Sophisticated algorithms that infer CNVs by combining the intensities from SNP-probes for the two alleles can already be used to extract a partial view of such GSV from existing data sets. RESULTS: Here we present several advances to facilitate the latter approach. First, we introduce a novel CNV detection method based on a Gaussian Mixture Model. Second, we propose a new algorithm, PCA merge, for combining copy-number profiles from many individuals into consensus regions. We applied both our new methods as well as existing ones to data from 5612 individuals from the CoLaus study who were genotyped on Affymetrix 500K arrays. We developed a number of procedures in order to evaluate the performance of the different methods. This includes comparison with previously published CNVs as well as using a replication sample of 239 individuals, genotyped with Illumina 550K arrays. We also established a new evaluation procedure that employs the fact that related individuals are expected to share their CNVs more frequently than randomly selected individuals. The ability to detect both rare and common CNVs provides a valuable resource that will facilitate association studies exploring potential phenotypic associations with CNVs. CONCLUSION: Our new methodologies for CNV detection and their evaluation will help in extracting additional information from the large amount of SNP-genotyping data on various cohorts and use this to explore structural variants and their impact on complex traits.

The systematic profiling of false identity documents: method validation and performance evaluation using seizures known to originate from common and different sources

False identity documents constitute a potential powerful source of forensic intelligence because they are essential elements of transnational crime and provide cover for organized crime. In previous work, a systematic profiling method using false documents' visual features has been built within a forensic intelligence model. In the current study, the comparison process and metrics lying at the heart of this profiling method are described and evaluated. This evaluation takes advantage of 347 false identity documents of four different types seized in two countries whose sources were known to be common or different (following police investigations and dismantling of counterfeit factories). Intra-source and inter-sources variations were evaluated through the computation of more than 7500 similarity scores. The profiling method could thus be validated and its performance assessed using two complementary approaches to measuring type I and type II error rates: a binary classification and the computation of likelihood ratios. Very low error rates were measured across the four document types, demonstrating the validity and robustness of the method to link documents to a common source or to differentiate them. These results pave the way for an operational implementation of a systematic profiling process integrated in a developed forensic intelligence model.

Jaundice-Should "yellow" be a red code?

Objective: Jaundice is the clinical manifestation, of hyperbilirubinemia. It is considered as a sign of either a liver disease or, less often, of a hemolytic disorder. It can be divided into obstructive and non obstructive type, involving increase of indirect (non-conjugated) bilirubin or increase of direct (conjugated) bilirubin, respectively, but it can be also manifested as mixed type. Methods: This article updates the current knoweledge concerning the jaundice's etiology, pathophysiological mechanisms, and complications ant treatment by reviewing of the latest medical literature. It also presents an approach of jaundice's treatment and pathogenesis, in special populations as in neonates and pregnant women. Results: The treatment is consistent in the management of the subjective diseases responsible for the jaundice and its complications.The clinical prognosis of the jaundice depends on the etiology. Surgical treatment of jaundiced patients is associated with high mortality and morbidity rates. Studies have shown that the severity of jaundice and the presence of malignant disease are importan risk factors for post-operative mortality. Conclusions: Early detection of jaundice is of vital importance because of its involvement in malignancy or in other benign conditions requiring immediate treatment in order to avoid further complications.

Photopolymerizable hydrogels for implants: Monte-Carlo modeling and experimental in vitro validation.

Photopolymerization is commonly used in a broad range of bioapplications, such as drug delivery, tissue engineering, and surgical implants, where liquid materials are injected and then hardened by means of illumination to create a solid polymer network. However, photopolymerization using a probe, e.g., needle guiding both the liquid and the curing illumination, has not been thoroughly investigated. We present a Monte Carlo model that takes into account the dynamic absorption and scattering parameters as well as solid-liquid boundaries of the photopolymer to yield the shape and volume of minimally invasively injected, photopolymerized hydrogels. In the first part of the article, our model is validated using a set of well-known poly(ethylene glycol) dimethacrylate hydrogels showing an excellent agreement between simulated and experimental volume-growth-rates. In the second part, in situ experimental results and simulations for photopolymerization in tissue cavities are presented. It was found that a cavity with a volume of 152  mm3 can be photopolymerized from the output of a 0.28-mm2 fiber by adding scattering lipid particles while only a volume of 38  mm3 (25%) was achieved without particles. The proposed model provides a simple and robust method to solve complex photopolymerization problems, where the dimension of the light source is much smaller than the volume of the photopolymerizable hydrogel.

Validation de la mesure de l'oedème postopératoire par bioimpédance chez les patients opérés d'une prothèse totale du genou : une expérience de collaboration entre physiothérapeutes et ingénieurs

Fondements : La recherche sur l'oedème postopératoire consécutif à la chirurgie prothétique du genou est peu développée, notamment en raison de l'absence d'une méthode de mesure adaptée. Une collaboration entre physiothérapeutes et ingénieurs a permis de développer et valider une méthode de mesure innovante et facilement applicable. Les physiothérapeutes ont identifié un besoin clinique, les ingénieurs ont apporté leur savoir technologique, et l'équipe a conjointement élaboré le protocole de mesure et effectué l'étude de validation. Introduction : La bioimpédance est fréquemment utilisée pour évaluer l'oedème par l'analyse d'un signal électrique passant au travers du corps, en extrapolant la résistance théorique à une fréquence égale à zéro (R0). La mesure s'avère fiable et rapide, mais n'a jamais été appliquée et validée pour l'évaluation de l'oedème en chirurgie orthopédique. Objectif : L'objectif de l'étude est de valider la mesure de l'oedème du membre inférieur par bioimpédance, chez des patients ayant bénéficié d'une prothèse totale de genou (PTG). Questionnement : Après nous être assurés de l'absence d'influence de l'implant métallique de la PTG sur la mesure, nous nous questionnions sur la validité et la fiabilité des mesures de bioimpédance dans ce contexte. Méthodes : Deux évaluateurs ont mesuré à tour de rôle et à deux reprises successives l'oedème chez 24 patients opérés d'une PTG, à trois temps différents (préopératoire, J+2, J+8). L'oedème a été évalué par bioimpédance (R0) et par conversion en volume de mesures centimétriques du membre inférieur (MI). Nous avons calculé le ratio moyen des MI pour chaque méthode. Nous avons évalué la reproductibilité intra- et inter-observateurs de la bioimpédance (coefficient de corrélation intraclasse, CCI) et la corrélation entre méthodes (Spearman). Résultats : Le ratio moyen opéré/sain du volume des MI est de 1.04 (SD ± 0.06) en préopératoire, 1.18 (SD ± 0.09) à J+2 et 1.17 (SD ± 0.10) à J+8. Le ratio sain/opéré des MI de R0 est de 1.04 (SD ± 0.07) en préopératoire, 1.51 (SD ± 0.22) à J+2 et 1.65 (SD ± 0.21) à J+8. En préopératoire, à J+2 et J+8, les CCI tous supérieurs à 0.95 pour la reproductibilité intra- et inter-observateurs de la bioimpédance. La corrélation entre méthodes est de 0.71 en préopératoire, 0.61 à J2 et 0.33 à J8. Analyse et conclusion : La variation du ratio des MI entre les temps préopératoire, J+2 et J+8 est plus marquée pour R0. La mesure de bioimpédance bénéficie d'une excellente reproductibilité intra- et inter-observateurs. L'évolution dans le temps de la corrélation entre méthodes peut être expliquée par l'influence potentielle de facteurs confondants sur R0 (modification de la composition liquidienne) et par l'influence de l'atrophie musculaire postopératoire sur la mesure de volume. La collaboration physiothérapeutes-ingénieurs a permis le développement et l'évaluation d'une nouvelle méthode de mesure.

A Monte Carlo-based procedure for independent monitor unit calculation in IMRT treatment plans.

Intensity-modulated radiotherapy (IMRT) treatment plan verification by comparison with measured data requires having access to the linear accelerator and is time consuming. In this paper, we propose a method for monitor unit (MU) calculation and plan comparison for step and shoot IMRT based on the Monte Carlo code EGSnrc/BEAMnrc. The beamlets of an IMRT treatment plan are individually simulated using Monte Carlo and converted into absorbed dose to water per MU. The dose of the whole treatment can be expressed through a linear matrix equation of the MU and dose per MU of every beamlet. Due to the positivity of the absorbed dose and MU values, this equation is solved for the MU values using a non-negative least-squares fit optimization algorithm (NNLS). The Monte Carlo plan is formed by multiplying the Monte Carlo absorbed dose to water per MU with the Monte Carlo/NNLS MU. Several treatment plan localizations calculated with a commercial treatment planning system (TPS) are compared with the proposed method for validation. The Monte Carlo/NNLS MUs are close to the ones calculated by the TPS and lead to a treatment dose distribution which is clinically equivalent to the one calculated by the TPS. This procedure can be used as an IMRT QA and further development could allow this technique to be used for other radiotherapy techniques like tomotherapy or volumetric modulated arc therapy.

A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR.

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray.

Ruling out coronary heart disease in primary care: external validation of a clinical prediction rule.

BACKGROUND: The Marburg Heart Score (MHS) aims to assist GPs in safely ruling out coronary heart disease (CHD) in patients presenting with chest pain, and to guide management decisions. AIM: To investigate the diagnostic accuracy of the MHS in an independent sample and to evaluate the generalisability to new patients. DESIGN AND SETTING: Cross-sectional diagnostic study with delayed-type reference standard in general practice in Hesse, Germany. METHOD: Fifty-six German GPs recruited 844 males and females aged ≥ 35 years, presenting between July 2009 and February 2010 with chest pain. Baseline data included the items of the MHS. Data on the subsequent course of chest pain, investigations, hospitalisations, and medication were collected over 6 months and were reviewed by an independent expert panel. CHD was the reference condition. Measures of diagnostic accuracy included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, likelihood ratios, and predictive values. RESULTS: The AUC was 0.84 (95% confidence interval [CI] = 0.80 to 0.88). For a cut-off value of 3, the MHS showed a sensitivity of 89.1% (95% CI = 81.1% to 94.0%), a specificity of 63.5% (95% CI = 60.0% to 66.9%), a positive predictive value of 23.3% (95% CI = 19.2% to 28.0%), and a negative predictive value of 97.9% (95% CI = 96.2% to 98.9%). CONCLUSION: Considering the diagnostic accuracy of the MHS, its generalisability, and ease of application, its use in clinical practice is recommended.