Ellis-van Creveld Syndrome in Grey Alpine Cattle: Morphologic, Immunophenotypic, and Molecular Characterization

Ellis-van Creveld (EvC) syndrome is a human autosomal recessive disorder caused by a mutation in either the EVC or EVC2 gene, and presents with short limbs, polydactyly, and ectodermal and heart defects. The aim of this study was to understand the pathologic basis by which deletions in the EVC2 gene lead to chondrodysplastic dwarfism and to describe the morphologic, immunohistochemical, and molecular hallmarks of EvC syndrome in cattle. Five Grey Alpine calves, with a known mutation in the EVC2 gene, were autopsied. Immunohistochemistry was performed on bone using antibodies to collagen II, collagen X, sonic hedgehog, fibroblast growth factor 2, and Ki67. Reverse transcription polymerase chain reaction was performed to analyze EVC1 and EVC2 gene expression. Autopsy revealed long bones that were severely reduced in length, as well as genital and heart defects. Collagen II was detected in control calves in the resting, proliferative, and hypertrophic zones and in the primary and secondary spongiosa, with a loss of labeling in the resting zone of 2 dwarfs. Collagen X was expressed in hypertrophic zone in the controls but was absent in the EvC cases. In affected calves and controls, sonic hedgehog labeled hypertrophic chondrocytes and primary and secondary spongiosa similarly. FGF2 was expressed in chondrocytes of all growth plate zones in the control calves but was lost in most EvC cases. The Ki67 index was lower in cases compared with controls. EVC and EVC2 transcripts were detected. Our data suggest that EvC syndrome of Grey Alpine cattle is a disorder of chondrocyte differentiation, with accelerated differentiation and premature hypertrophy of chondrocytes, and could be a spontaneous model for the equivalent human disease.

SwissScoring--a nationwide survey of SAPS II assessing practices and its accuracy.

OBJECTIVE The first description of the simplified acute physiology score (SAPS) II dates back to 1993, but little is known about its accuracy in daily practice. Our purpose was to evaluate the accuracy of scoring and the factors that affect it in a nationwide survey. METHODS Twenty clinical scenarios, covering a broad range of illness severities, were randomly assigned to a convenience sample of physicians or nurses in Swiss adult intensive care units (ICUs), who were asked to assess the SAPS II score for a single scenario. These data were compared to a reference that was defined by five experienced researchers. The results were cross-matched with demographic characteristics and data on the training and quality control for the scoring, structural and organisational properties of each participating ICU. RESULTS A total of 345 caregivers from 53 adult ICU providers completed the SAPS II evaluation of one clinical scenario. The mean SAPS II scoring was 42.6 ± 23.4, with a bias of +5.74 (95%CI 2.0-9.5) compared to the reference score. There was no evidence of bias variation according to the case severity, ICU size, linguistic area, profession (physician vs. nurse), experience, initial SAPS II training, or presence of a quality control system. CONCLUSION This nationwide survey revealed substantial variability in the SAPS II scoring results. On average, SAPS II scoring was overestimated by more than 13%, irrespective of the profession or experience of the scorer or of the structural characteristics of the ICUs.

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Imperial Eyes. Van Dycks Porträtmalerei als globale Technologie

Zu Beginn des 17. Jahrhunderts hatte sich die Malerei in Antwerpen vor allem durch Rubens als Medium einer zunehmend global verbundenen Welt etabliert. Doch auch zahlreiche von Van Dycks Porträts sind Zeugnisse eines oft hochgradig ambivalenten Kosmopolitismus. Neben Gemälden von international agierenden Antwerpener Händlern und Gelehrten fertigte der Künstler auch in Genua und England Porträts der adligen Elite an, in welchen sich deren globale Erfahrungen und Ambitionen spiegelten. Van Dyck reagierte in der Inszenierung der Marchesa Elena Grimaldi Cattaneo, mit einem schwarzen Sklaven, wie in der des Earl of Denbigh, zwischen einheimischen und exotischen Elementen, auf spezifische Anforderungen an das repräsentative Porträt im Zeitalter des disenclavement. Diese Anforderungen werden besonders deutlich in dem für eine geplante Expedition nach Madagaskar entstandenen Porträt des Earls of Arundel und dessen Frau Alethea Talbot. Das Gemälde verbindet Elemente herrschaftlicher, merkantilistischer und intellektueller Selbststilisierung mit einer Reduktion auf wenige, innovative Elemente. Die majestätische Inszenierung des Paars ist nur in einem globalen Kontext zu erklären, so dass sich die Frage nach der Funktion des in mehreren Werkstattkopien erhaltenen Gemäldes stellt. Hatte Van Dyck in seiner Komposition eine Lösung gefunden, die im Kontext des englischen Hofes, möglicherweise als Teil eines Festes, wie auch für potentielle Investoren, sowie die verarmte Landbevölkerung, die in der Indentur ihre einzige Hoffnung sah, gleichermaßen überzeugend wirkte? Die Hybris in dem überlebensgroßen Porträts des Paares, das mit leuchtend heller Haut, in kostbar glänzende Stoffe gekleidet und mit modernen Messinstrumenten in den Händen dargestellt ist, lässt es als ideales Medium der globalen Ambitionen des Paars erscheinen.