Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis.

Introduction: Exome sequencing has a diagnostic yield ranging from 25% to 70% in rare diseases and regularly implicates genes in novel disorders. Retrospective data reanalysis has demonstrated strong efficacy in improving diagnosis, but poses organizational difficulties for clinical laboratories. Patients and methods: We applied a reanalysis strategy based on intensive prospective bibliographic monitoring along with direct application of the GREP command-line tool (to "globally search for a regular expression and print matching lines") in a large ES database. For 18 months, we submitted the same five keywords of interest [(intellectual disability, (neuro)developmental delay, and (neuro)developmental disorder)] to PubMed on a daily basis to identify recently published novel disease-gene associations or new phenotypes in genes already implicated in human pathology. We used the Linux GREP tool and an in-house script to collect all variants of these genes from our 5,459 exome database. Results: After GREP queries and variant filtration, we identified 128 genes of interest and collected 56 candidate variants from 53 individuals. We confirmed causal diagnosis for 19/128 genes (15%) in 21 individuals and identified variants of unknown significance for 19/128 genes (15%) in 23 individuals. Altogether, GREP queries for only 128 genes over a period of 18 months permitted a causal diagnosis to be established in 21/2875 undiagnosed affected probands (0.7%). Conclusion: The GREP query strategy is efficient and less tedious than complete periodic reanalysis. It is an interesting reanalysis strategy to improve diagnosis.

Are people good prognosticators of their own pain? An exploration of the relationship between sex-specific pain beliefs and clinical pain evaluation.

BACKGROUND: Under-explored to date are the interacting influences of patient sex on multi-modal evaluation techniques that tap different domains of the pain experience. OBJECTIVES: The primary aim of Study 1 was to explore the accuracy of sex-specific personal pain beliefs in relation to quantitative pain indicators within sexes, and the secondary objective was to compare the accuracy of sex-specific personal pain beliefs in relation to quantitative pain indicators between sexes. The primary objective of Study 2 was to explore the accuracy of sex-specific personal pain beliefs and self-rated pain severity within sexes, and the secondary objective was to compare sex-specific personal pain beliefs and pain severity ratings between sexes. METHODS: A cross-sectional analysis on two datasets was performed (Study 1, n = 50; Study 2, n = 111). For both studies, independent samples t-tests were used to identify differences in clinical pain evaluations based on sex-specific pain beliefs. Receiver Operating Characteristic (ROC) curves were used to compare the predictive accuracy of males and females clinical pain evaluations based on their ability to handle pain. RESULTS: There were no statistically significant differences in clinical pain evaluations based on self-rated pain beliefs in either study. In Study 2, males were descriptively more accurate predictors of their clinical pain evaluations than were females, though none of the between sex comparisons were statistically significant. CONCLUSION: This work highlights the importance of considering all available clinical pain evaluations as one technique is unlikely to represent the patients pain experience.

Rinderpest experience.

Rinderpest, the most dreaded disease of cattle, originated as far back as the domestication of cattle, occurring in Asia more than 10,000 years ago. It has been the main preoccupation of Veterinary Service activities for many centuries and was the major motivation for establishing the first veterinary school in Lyon, France, in 1761. Gaining control of the disease was the impetus for the founding of many regional and international organisations (including the World Organisation for Animal Health). Outbreaks of rinderpest have led to food shortages and starvation, economic losses and poverty, social unrest, and disrupted transport networks in regions where agriculture was dependent on draught cattle. The rinderpest virus, causative agent of the disease, has also been used as a biological weapon in the past. Many regional rinderpest eradication campaigns have been implemented, including Joint Project 15; the Pan-African Rinderpest Campaign (PARC); the South Asia Rinderpest Eradication Campaign; the West Asia Rinderpest Eradication Campaign; and the Pan African Programme for the Control of Epizootics. All of these campaigns were supported by regional and international organisations, and the disease was finally eradicated in 2011. The benefit of PARC in terms of the value of avoided losses in cattle products due to the decrease in the disease's occurrence was estimated to be between 581,000 and 35,433,000 European currency units. Currently, the world is prepared to prevent the deliberate or accidental release of the remaining infectious rinderpest virus material which exists in research and diagnostic facilities across the world.

La peste bovine, la plus redoutable des maladies bovines, existe depuis l'époque reculée de la domestication des bovins, puisqu'elle est apparue en Asie il y a plus de dix mille ans. Au fil des siècles, cette maladie a été une préoccupation centrale des services en charge de la santé animale et a été le motif principal de la création de la première école vétérinaire, à Lyon (France) en 1761. L'ambition de maîtriser la peste bovine a participé de l'élan qui a vu naître nombre d'organisations régionales et internationales (dont l'Organisation mondiale de la santé animale). Les épidémies de peste bovine ont entraîné des pénuries alimentaires et des famines, des pertes économiques et une pauvreté accrue, une instabilité sociale et l'effondrement des réseaux de transport dans les régions où l'agriculture dépendait des bovidés de trait. Le virus responsable de la peste bovine a également été utilisé en tant qu'arme biologique dans le passé. De nombreuses campagnes d'éradication de la peste bovine ont été mises en œuvre à l'échelle régionale, parmi lesquelles le Projet conjoint 15, la Campagne panafricaine de lutte contre la peste bovine (PARC), la Campagne d'éradication de la peste bovine en Asie du Sud, la Campagne d'éradication de la peste bovine en Asie occidentale et le Programme panafricain de contrôle des épizooties. Ces campagnes ont toutes reçu le soutien d'organisations régionales et internationales et la maladie a finalement été éradiquée en 2011. Les bénéfices du programme PARC en termes de pertes de production évitées dans le secteur bovin grâce au déclin de l'incidence de la maladie ont été estimés entre 581 000 et 35 433 000 ECU (unité de compte européenne). Aujourd'hui, le monde est prêt à prévenir toute libération délibérée ou accidentelle des stocks restants de produits contenant le virus de la peste bovine détenus dans différents établissements de recherche et de diagnostic répartis dans le monde.

Los orígenes de la peste bovina, que es la más temida de las enfermedades del ganado vacuno, se remontan a la domesticación de los bovinos, que se dio en Asia hace más de 10 000 años. Durante muchos siglos ha sido una de las grandes preocupaciones que han guiado el trabajo de los Servicios Veterinarios, y fue uno de los principales factores que motivaron la fundación de la primera escuela de veterinaria en Lyon (Francia) en 1761. El objetivo de llegar a controlar la enfermedad fue el acicate que llevó a la creación de numerosas organizaciones de ámbito regional e internacional (entre ellas la Organización Mundial de Sanidad Animal). Los brotes de peste bovina han causado episodios de escasez de alimentos y hambruna, pérdidas económicas, pobreza y disturbios sociales, sin olvidar la desorganización de las redes de transporte en regiones donde la agricultura dependía del ganado de tiro. En el pasado el virus de la peste bovina, agente causal de la enfermedad, también ha sido utilizado como arma biológica. Numerosas campañas regionales de erradicación de la peste bovina han visto la luz, entre ellas el llamado Proyecto Conjunto 15, la Campaña panafricana contra la peste bovina (PARC), la Campaña de Erradicación de la Peste Bovina en Asia Meridional, la Campaña de Erradicación de la Peste Bovina en Asia Occidental y el Programa Panafricano de Control de Epizootias. Gracias a todas estas iniciativas, respaldadas por organizaciones regionales e internacionales, en 2011 la enfermedad quedó por fin erradicada. Según las estimaciones, basadas en el valor económico de las pérdidas de productos ganaderos evitadas gracias a la reducción de los casos de enfermedad, la PARC deparó entre 581 000 y 35 433 000 Ecus (unidades de cuenta europeas) de beneficios. En la actualidad el mundo está preparado para evitar toda liberación accidental o deliberada de las muestras infecciosas de virus de la peste bovina que aún se conservan en centros de investigación y diagnóstico de todo el planeta.