The influence of aortoseptal angulation on provocable left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

OBJECTIVES: Aortoseptal angulation (AoSA) can predict provocable left ventricular outflow tract obstruction (LVOTO) in patients with symptomatic hypertrophic cardiomyopathy (HCM). Lack of a standardised measurement technique in HCM without the need for complex three-dimensional (3D) imaging limits its usefulness in routine clinical practice. This study aimed to validate a simple measurement of AoSA using 2D echocardiography and cardiac MR (CMR) imaging as a predictor of LVOTO. METHODS: We retrospectively assessed 160 patients with non-obstructive HCM, referred for exercise stress echocardiography. AoSA was measured using resting 2D echocardiography in all patients, and CMR in 29. Twenty-five controls with normal echocardiograms were used for comparison. RESULTS: Patients with HCM had a reduced AoSA compared with controls (113°±12 vs 126°±6), p<0.0001. Sixty (38%) patients had provocable LVOTO, with smaller angles than non-obstructive patients (108°±12 vs 116°±12, p<0.0001). AoSA, degree of mitral valvular regurgitation and incomplete systolic anterior motion (SAM) were associated with peak left ventricular outflow tract gradient (r=0.508, p<0.0001). An angle ≤100° had 27% sensitivity, 91% specificity and 59% positive predictive value for predicting provocable LVOTO. When combined with SAM, specificity was 99% and positive predictive value 88%. Intraclass correlation coefficient of AoSA measured by two observers was 0.901 (p<0.0001). Bland-Altman analysis of echocardiographic AoSA showed good agreement with the CMR-derived angle. CONCLUSIONS: Measurement of AoSA using echocardiography in HCM is easy, reproducible and comparable to CMR. Patients with provocable LVOTO have reduced angles compared with non-obstructive patients. AoSA is highly specific for provocable LVOTO and should prompt further evaluation in symptomatic patients without resting obstruction

La diversidad sexual y sus representaciones en la juventud (Young people’s sexual diversity and its representations)

¿Resumen:  Objetivo: El objetivo del presente estudio fue indagar la percepción de la diversidad sexual a partir de las representaciones que, a través del discurso, los jóvenes expresan. Método: Se trabajó con un diseño no experimental, de corte transversal/transaccional de alcance descriptivo. Como instrumento se utilizó la técnica de Redes Semánticas Modificadas; trabajándose los siguientes indicadores: tamaño de la red, peso semántico, diferencia semántica cuantitativa y núcleo de la red. La muestra se integró por 250 jóvenes de ambos sexos, con edades entre los 19 y los 29 años.  Se empleó un muestreo no probabilístico, cuyos criterios de inclusión fueron: la disponibilidad y el consentimiento informado. Resultados: Los resultados demuestran que los sujetos refieren construcciones cada vez menos rígidas en torno a la diversidad sexual, revelando en algunos casos discursos contradictorios en torno a ésta; por un lado, emociones negativas como el miedo y por otro, mayor apertura a la igualdad y al respeto. Conclusiones: Es necesario considerar que, a pesar de haberse observado una tendencia al cambio en las respuestas de los participantes de este estudio, se debe continuar monitoreando esta tendencia y sus implicaciones en generaciones pasadas y futuras. Abstract Objective: The aim of the present study was to investigate the perception of sexual diversity based on the representations that young people express through discourse. Method: We worked with a non-experimental, cross-sectional / transactional cross-sectional design. As instrument was used the technique of Modified Semantic Networks; Working the following indicators: network size, semantic weight, quantitative semantic difference and network core. The sample was composed of 250 young men and women, aged between 19 and 29 years. A non-probabilistic sampling was used, whose inclusion criteria were: availability and informed consent. Results: The results show that the subjects refer to increasingly rigid constructions around sexual diversity, revealing in some cases contradictory discourses around it; On the one hand, negative emotions such as fear and on the other, greater openness to equality and respect. Conclusions: It is necessary to consider that, despite a tendency to change the responses of the participants of this study, this trend and its implications in past and future generations should be monitored

Evolution of Robustness to Noise and Mutation in Gene Expression Dynamics

Phenotype of biological systems needs to be robust against mutation in order to sustain themselves between generations. On the other hand, phenotype of an individual also needs to be robust against fluctuations of both internal and external origins that are encountered during growth and development. Is there a relationship between these two types of robustness, one during a single generation and the other during evolution? Could stochasticity in gene expression have any relevance to the evolution of these robustness? Robustness can be defined by the sharpness of the distribution of phenotype; the variance of phenotype distribution due to genetic variation gives a measure of `genetic robustness' while that of isogenic individuals gives a measure of `developmental robustness'. Through simulations of a simple stochastic gene expression network that undergoes mutation and selection, we show that in order for the network to acquire both types of robustness, the phenotypic variance induced by mutations must be smaller than that observed in an isogenic population. As the latter originates from noise in gene expression, this signifies that the genetic robustness evolves only when the noise strength in gene expression is larger than some threshold. In such a case, the two variances decrease throughout the evolutionary time course, indicating increase in robustness. The results reveal how noise that cells encounter during growth and development shapes networks' robustness to stochasticity in gene expression, which in turn shapes networks' robustness to mutation. The condition for evolution of robustness as well as relationship between genetic and developmental robustness is derived through the variance of phenotypic fluctuations, which are measurable experimentally.Comment: 25 page

Congestion-aware routing and rebalancing of autonomous mobility-on-demand systems in mixed traffic

This paper studies congestion-aware route-planning policies for Autonomous Mobility-on-Demand (AMoD) systems, whereby a fleet of autonomous vehicles provides on demand mobility under mixed traffic conditions. Specifically, we first devise a network flow model to optimize the AMoD routing and rebalancing strategies in a congestion-aware fashion by accounting for the endogenous impact of AMoD flows on travel time. Second, we capture reactive exogenous traffic consisting of private vehicles selfishly adapting to the AMoD flows in a user centric fashion by leveraging an iterative approach. Finally, we showcase the effectiveness of our framework with a case-study considering the transportation sub-network in New York City. Our results suggest that for high levels of demand, pure AMoD travel can be detrimental due to the additional traffic stemming from its rebalancing flows, whilst the combination of AMoD with walking or micro mobility options can significantly improve the overall system performance.Accepted manuscrip

First GPS Baseline Results from the North Andes

The CASA UNO GPS (Global Positioning System) experiment (January-February 1988) has provided the first epoch baseline measurements for the study of plate motions and crustal deformation in and around the North Andes. Two dimensional horizontal baseline repeatabilities are as good as 5 parts in 108 for short baselines (100-1000km), and better than3 parts in 108 for long baselines (\u3e1000km). Vertical repeatabilities are typically 4 -6 cm, with a weak dependence on baseline length. The expected rate of plate convergence across the Colombia Trench is 6-8 cm/yr, which should be detectable by the repeat experiment planned for 1991. Expected deformation rates within the North Andes are of the order of 1 cm/yr, which may be detectable with the 1991 experiment

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P&lt;0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P&lt;0.001), and elevated mGPS and NLR (both P&lt;0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas

BACKGROUND: Intraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established. METHODS: During the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12–15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location. RESULTS: In the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group. CONCLUSIONS: IORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone

Plan de negocio para implementar una plataforma virtual que facilite la ejecuci?n de clases acad?micas complementarias en los distritos de Trujillo y V?ctor Larco Herrera, en la provincia de Trujillo, en el departamento de La Libertad

La presente tesis tiene como objetivo, evaluar la viabilidad econ?mica de un modelo de negocio multilateral entre los demandantes y ofertantes de clases acad?micas complementarias de reforzamiento. El plan de negocio busca implementar la plataforma virtual T-ense?o que facilite la ejecuci?n de clases acad?micas complementarias a estudiantes de primaria y secundaria que pertenecen a los NSE A, B y C de los distritos de Trujillo y V?ctor Larco Herrera, en la Provincia de Trujillo, Departamento de La Libertad. Dentro de su propuesta de valor, contribuye con los tutores que son los padres o representantes de los estudiantes (tutorados), a encontrar asesores acad?micos calificados para el reforzamiento de las clases, buscando mejorar su nivel educativo; y, por el otro, contribuye con los asesores acad?micos a contactar a los tutores antes indicados y obtener ingresos adicionales. Los atributos m?s importantes de la propuesta de valor para los tutores son: el acceso a profesionales calificados, brindando un pool de asesores acad?micos, la seguridad por el buen historial civil de ?stos; y, el logro de mejores calificaciones de los tutorados. Y, para los asesores acad?micos son: generar ingresos extras, desarrollo de sus competencias t?cnicas y digitales, y, luego de un uso recurrente, obtendr?n incentivos

UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection