7 research outputs found
A contemporary look at Hermann Hankel's 1861 pioneering work on Lagrangian fluid dynamics
The present paper is a companion to the paper by Villone and Rampf (2017), titled “Hermann Hankel's On the general theory of motion of fluids, an essay including an English translation of the complete Preisschrift from 1861” together with connected documents [Eur. Phys. J. H 42, 557–609 (2017)]. Here we give a critical assessment of Hankel's work, which covers many important aspects of fluid dynamics considered from a Lagrangian-coordinates point of view: variational formulation in the spirit of Hamilton for elastic (barotropic) fluids, transport (we would now say Lie transport) of vorticity, the Lagrangian significance of Clebsch variables, etc. Hankel's work is also put in the perspective of previous and future work. Hence, the action spans about two centuries: from Lagrange's 1760–1761 Turin paper on variational approaches to mechanics and fluid mechanics problems to Arnold's 1966 founding paper on the geometrical/variational formulation of incompressible flow. The 22-year-old Hankel − who was to die 12 years later — emerges as a highly innovative master of mathematical fluid dynamics, fully deserving Riemann's assessment that his Preisschrift contains “all manner of good things.
Movement disorders associated with neuronal antibodies: a data-driven approach
BACKGROUND
Movement disorders can be associated with anti-neuronal antibodies.
METHODS
We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert's clinical feedback.
RESULTS
Three hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu.
CONCLUSION
Selected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts
The odyssey of complex neurogenetic disorders: From undetermined to positive
The genetic and phenotypic heterogeneity of neurogenetic diseases forces patients and their families into a ?diagnostic odyssey.? An increase in the variability of genetic disorders and the corresponding gene-disease associations suggest the need to periodically re-evaluate the significance of variants of undetermined pathogenicity. Here, we report the diagnostic and clinical utility of Targeted Gene Panel Sequencing (TGPS) and Whole Exome Sequencing (WES) in 341 patients with suspected neurogenetic disorders from centers in Buenos Aires and Cincinnati over the last 4 years, focusing on the usefulness of reinterpreting variants previously classified as of uncertain significance. After a mean of ±2years (IC 95:0.73?3.27), approximately 30% of the variants of uncertain significance were reclassified as pathogenic. The use of next generation sequencing methods has facilitated the identification of both germline and mosaic pathogenic variants, expanding the diagnostic yield. These results demonstrate the high clinical impact of periodic reanalysis of undetermined variants in clinical neurology.Fil: Salinas, Valeria Macarena. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral; ArgentinaFil: Vega, Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Marsili, Luca. University of Cincinnati; Estados UnidosFil: Perez Maturo, Josefina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Martínez, Nerina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Zavala, Lucía. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González Morón, Dolores. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Nancy. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Rodríguez Quiroga, Sergio Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Amartino, Hernán. Universidad Austral. Hospital Universitario Austral; ArgentinaFil: Maxit, Clarisa. Hospital Italiano; ArgentinaFil: Sturchio, Andrea. University of Cincinnati; Estados UnidosFil: Grimberg, Barbara. University of Cincinnati; Estados UnidosFil: Duque, Kevin. University of Cincinnati; Estados UnidosFil: Comas, Betiana. Hospital de la Baxada Dra. Teresa Ratto; ArgentinaFil: Silva, Walter. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Consalvo, Damián. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Sfaello, Ignacio. No especifíca;Fil: Espay, Alberto J.. University of Cincinnati; Estados UnidosFil: Kauffman, Marcelo Andres. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin
Serum levels of IGF-1 and IGFBP-3 during adjuvant chemotherapy for primary breast cancer
Noncoding Mutations of HGF Are Associated with Nonsyndromic Hearing Loss, DFNB39
A gene causing autosomal-recessive, nonsyndromic hearing loss, DFNB39, was previously mapped to an 18 Mb interval on chromosome 7q11.22-q21.12. We mapped an additional 40 consanguineous families segregating nonsyndromic hearing loss to the DFNB39 locus and refined the obligate interval to 1.2 Mb. The coding regions of all genes in this interval were sequenced, and no missense, nonsense, or frameshift mutations were found. We sequenced the noncoding sequences of genes, as well as noncoding genes, and found three mutations clustered in intron 4 and exon 5 in the hepatocyte growth factor gene (HGF). Two intron 4 deletions occur in a highly conserved sequence that is part of the 3′ untranslated region of a previously undescribed short isoform of HGF. The third mutation is a silent substitution, and we demonstrate that it affects splicing in vitro. HGF is involved in a wide variety of signaling pathways in many different tissues, yet these putative regulatory mutations cause a surprisingly specific phenotype, which is nonsydromic hearing loss. Two mouse models of Hgf dysregulation, one in which an Hgf transgene is ubiquitously overexpressed and the other a conditional knockout that deletes Hgf from a limited number of tissues, including the cochlea, result in deafness. Overexpression of HGF is associated with progressive degeneration of outer hair cells in the cochlea, whereas cochlear deletion of Hgf is associated with more general dysplasia