Relación entre el valor del ratio elastográfico y la clasificación citológica de Bethesda en la patología tiroidea

ResumenObjetivoPresentar nuestra experiencia en la categorización de la patología tiroidea, a través de la utilización de parámetros ecográficos de malignidad y elastografía con medición del ratio de la deformación tisular, y la correlación de los hallazgos obtenidos con la clasificación citológica de Bethesda.Materiales y métodosSe llevó a cabo un estudio prospectivo y observacional, entre septiembre de 2012 y abril de 2013, que incluyó 137 nódulos tiroideos. Se excluyeron 10 casos Bethesda III-IV. Se realizó ecografía, power Doppler, visualización de micropartículas (Micropure) y elastografía con medición del ratio elastográfico, así como también punción aspirativa con aguja fina guiada por ecografía (con el citólogo presente), utilizando la clasificación Bethesda. Los estudios fueron hechos por el mismo operador con un ecógrafo Toshiba Aplio 400 y los datos estadísticos se evaluaron con el programa IBM SPSS Statistics 20.ResultadosSe estudiaron 127 nódulos en pacientes con una edad promedio de 59±16 años. El 82% de los casos ocurrió en mujeres. Ciento veinte nódulos (94%) fueron clasificados como Bethesda II. La media elastográfica para Bethesda I-II fue de 1,94±2,12 vs. 7,07±5,46 para V-VI (p: 0,048). El punto de corte elastográfico ≤ 2 (87 de 127) presentó una sensibilidad del 85,7% y una especificidad del 81,7% para predecir Bethesda asociada a patología benigna, con un valor predictivo negativo (VPN) del 99% y un valor predictivo positivo del 15%.ConclusionesEl ratio elastográfico permitió descartar la patología tiroidea maligna con valores ≤ 2 y un VPN del 99%, mejorando la selección de los pacientes a punzar. El incremento del ratio elastográfico se asoció a una mayor probabilidad de patología maligna, aunque no se pudo establecer un valor de corte debido al bajo número de casos con Bethesda V-VI.AbstractObjectivesWe present our experience in the categorization of thyroid pathology using the sonographic parameters of malignancy and elastography with measurement elastography strain ratio, to evaluate the relationship between the results found and the Bethesda classification.Materials and methodsProspective observational study, included 137 thyroid nodules studied between September 2012- April 2013. We excluded 10 cases with Bethesda categories III-IV. Ultrasonography, Doppler, Micropure, elastogrphy strain ratio between the lesion and the normal tissue, fine needle aspiration cytology (FNAC),were the diagnosis methods used. The pathologist was always present and the cytological classi fication of Bethesda was used. All study was made by the same physician used Toshiba Aplio 400 ultrasound unit. Results were analyzed with IBM SPSS Statistics 20.ResultsWe studied 127 nodules in patients 59±16 years old, 82% were female; 120 were Bethesda II (94%). The average strain ratio for nodules Bethesda I-II was 1.94±2.12 vs. 7.07±5.46 for those nodules Bethesda V-VI (p:0,048). This means that an elastography strain ratio ≤ 2 (87 of 127 nodules) has a sensibility of 85.7% and a specificity of 81.7% of predicting Bethesda associated with benign pathology with a negative predictive value (NPV) of 99% and a positive predictive value of 15%.ConclusionThe elastography strain ratio allowed to discard malignant nodules with strain ratio ≤ 2 with a NPV of 99% improves the selection of patients for FNAC. The increment in the elastography strain ratio was associated to a higher possibility of malignant thyroid pathology, being unable to determine a limit value due to the low amount of cases with nodules Bethesda V-VI

Company ‘Emigration’ and EC Freedom of Establishment: Daily Mail Revisited

Following the ECJ’s recent case law on EC freedom of establishment (the Centros, Überseering and Inspire Art cases), regulatory competition for corporate law within the European Union takes place at an early stage of the incorporation of new companies. In contrast, as regards the ‘moving out’ of companies from the country of incorporation, the ECJ once considered a tax law restriction against the transfer abroad of a company’s administrative seat as compatible with EC freedom of establishment (the Daily Mail case). For years, this decision has been regarded as applicable to all restrictions imposed by countries of incorporation, even the forced liquidation of the ‘emigrating’ company. This paper addresses the question whether EC freedom of establishment really allows Member States to place any limit on the ‘emigration’ of nationally registered companies. It argues that EC freedom of establishment covers the transfer of the administrative seat as well as the transfer of the registered office and, therefore, that the country of incorporation cannot liquidate ‘emigrating’ companies. In addition, it addresses the question whether a new Directive is needed to allow the transfer of a com- pany’s registered office and the identity-preserving company law changes. It argues that such a Directive is necessary to avoid legal uncertainty and to protect the interests of employees, creditors and minority shareholders, among others, who could be detrimentally affected by the ‘emigration’ of national companies

Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing

MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure–function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer–small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine

Intronic determinants coordinate charme lncRNA nuclear activity through the interaction with MATR3 and PTBP1

Chromatin architect of muscle expression (Charme) is a muscle-restricted long noncoding RNA (lncRNA) that plays an important role in myogenesis. Earlier evidence indicates that the nuclear Charme isoform, named pCharme, acts on the chromatin by assisting the formation of chromatin domains where myogenic transcription occurs. By combining RNA antisense purification (RAP) with mass spectrometry and loss-of-function analyses, we have now identified the proteins that assist these chromatin activities. These proteins—which include a sub-set of splicing regulators, principally PTBP1 and the multifunctional RNA/DNA binding protein MATR3—bind to sequences located within the alternatively spliced intron-1 to form nuclear aggregates. Consistent with the functional importance of pCharme interactome in vivo, a targeted deletion of the intron-1 by a CRISPR-Cas9 approach in mouse causes the release of pCharme from the chromatin and results in cardiac defects similar to what was observed upon knockout of the full-length transcript

Second-Generation Coil Design of the Nb3Sn low-β Quadrupole for the High Luminosity LHC

As part of the Large Hadron Collider (LHC) Luminosity upgrade program, the U.S.-LHC Accelerator Research Program collaboration and CERN are working together to design and build a 150-mm aperture Nb3Sn quadrupole for the LHC interaction regions. A first series of 1.5-m-long coils was fabricated and assembled in a first short model. A detailed visual inspection of the coils was carried out to investigate cable dimensional changes during heat treatment and the position of the windings in the coil straight section and in the end region. The analyses allow identifying a set of design changes which, combined with a fine tune of the cable geometry and a field quality optimization, were implemented in a new second-generation coil design. In this paper, we review the main characteristics of the first generation coils, describe the modification in coil layout and discuss their impact on parts design and magnet analysis

Development of HTS Current Leads for the ITER Project

The HTS current leads for the ITER project will be the largest ever operated, with unprecedented currents, up to 68 kA and voltages, up to 14 kV. According to the ITER agreement they will be provided in-kind by China. After an extensive development program at the Hefei Institute of Plasma Physics (ASIPP), the ITER current leads were designed and qualified. The following discusses the main highlights of this development, with particular emphasis on the description of the design of the different types of ITER current leads and their final qualification in dedicated cold tests in nominal conditions

Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

MicroRNA (miRNA) play a major role in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with co-transcriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. While most miRNA are located within introns of protein coding genes, a substantial minority of miRNA originate from long non coding (lnc) RNA where transcript processing is largely uncharacterized. Here, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis, we show that most lnc-pri-miRNA do not use the canonical cleavage and polyadenylation (CPA) pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a novel RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells