Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy

BACKGROUND: The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES: This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS: FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS: The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS: FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels

Compilation and study of a database of tests and results on flexural creep behavior of fibre reinforced concrete specimens

This paper examines the effect of fibres on the flexural creep of fibre reinforced concrete (FRC) in the cracked state based on the analysis of experimental results compiled over the last years. These creep tests were carried out on pre-cracked FRC prismatic specimens, reinforced with either steel, glass, or synthetic fibres. Besides the fibre material, the following variables have also been taken into account: fibre contents, concrete compressive strength resulting from different mix designs, and level of load applied during the flexural creep test. All the specimens have been subjected to sustained flexural loads for at least 90 days following the test setup methodology developed by the authors. Several experimental outputs were retained as main parameters of the residual flexural response under sustained loads: creep coefficients referred to both the origin and the beginning of creep stage, and crack opening rates, all of them at 14, 30 and 90 days. The relationships between these parameters and concrete compressive strength, applied flexural load, fibre type and content have been analysed

Effect of residual strength parameters on FRC flexural creep: multivariate analysis

This paper reports the multivariate analysis of experimental results from more than one hundred FRC prismatic specimens tested under sustained flexural loads for at least 90 days, collected from previously published sources. Principal Component Analysis was used to minimise the number of variables in the modelling process while compromising the minimum amount of information. The creep parameters analysed were the creep coefficients at 14, 30, and 90 days and the corresponding crack opening rates. They were related to the following factors: concrete compressive strength, residual load-bearing capacity in flexure, fibre material, and load. Multiple linear regression was used for the modelling of these relationships. Higher levels of flexural toughness were found to significantly reduce the variability of all creep parameters. Differences in fibre material were detected to introduce important differences in interaction with other factors, especially the load ratio, which was attributed to the association between the range of flexural toughness to be expected and the type of fibres used

Lagesicherheit lose verlegter Waermedaemmplatten auf Flachdaechern gegen Abheben durch Windeinwirkung

TIB Hannover: RN 5973(2121) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Anterior pre-tensioned external fixator for pelvic fractures and dislocations. Initial clinical series.

In the treatment of unstable pelvic ring fractures, external fixators have the limitation of not adequately stabilizing the injured posterior elements. This article presents a novel and simple technique of temporary external fixation of the pelvic ring, able to produce compression of both the anterior and posterior pelvic elements. A curved flexible carbon-fiber rod is used, pre-tensioned before attachment to supra-acetabular Schanz screws. Although more extensive clinical experience is required, favorable preliminary results in a series of 13 patients with unstable pelvic fracture were encouraging: the aim of closing the posterior and anterior elements of the pelvic ring was achieved in all cases treated with this technique, and 12 patients survived. Radiological results were excellent in 3 cases and good in 9 cases. No major complications, such as secondary displacement, vertical re-displacement or deep infection, were observed. Mean operative time was 25min, compatible with emergency management

General Procedure of Creep Test

Regardless of the methodology adopted by each laboratory, there is a consensus about the three main stages in the creep testing procedure: the pre-cracking stage, the creep stage and the post-creep stage. Despite this general procedure, four main methodologies were conducted in fibre-reinforced concrete (FRC) specimens in the round-robin test (RRT): flexure creep test on prismatic specimens based on EN 14651, direct tension creep test, flexure creep test on square panels based on EN 14488-5 and flexure creep test on round panels based on ASTM C1550. An overview of these four main methodologies is described in the following subsections. All the procedures defined by each participant were grouped by methodology and compared in terms of configuration, equipment and measurement devices

Prácticas de CAD

Este cuaderno de prácticas de C.A.D. constituye el séptimo y último de una serie elaborada como soporte documental de la asignatura de C.A.D. El material de base lo constituye el conjunto de ejercicios de exámen planteados desde 1989, cuyo servicio es, principalmente, mostrar la tendencia de los ejercicios y, con ello, los objetivos de conocimiento y destreza que se pretende que se adquieran. A su vez también se ha incorporado alguna orientación metodológica sobre los objetivos de destreza y de conocimiento de cada capítulo. El cuaderno está dividido en siete capítulos, que tratan respectivamente: Las entidades; edición; capas, colores, tipos de línea y sombreados; matrices; bloques; atributos de bloque y acotación.CantabriaES

Statements and Conclusions

A round-robin test (RRT) on creep behaviour in cracked section of fibre-reinforced concrete (FRC) was realised with the participation of 19 international laboratories from 22 institutions. The same concrete matrix was used to design two different FRC mixes with steel (SFRC) and macro-synthetic (SyFRC) fibres and to produce 451 FRC specimens. The use of 124 specimens for creep tests for one year following four main methodologies provided a huge database with more than 15,000 data. The main statements and conclusions derived from the RRT database analysis are summarised in this section. Note that the conclusions derived from this RRT are limited to the ranges of parameters, procedures and variables considered here and should not be extrapolated to other cases

Introduction and Background

The absence of a standardised methodology to evaluate creep in the cracked state of fibre-reinforced concrete (FRC) hindered general comparisons and conclusions that could lead to significant advances in this topic. A coordinated effort was required to improve the knowledge on long-term behaviour of cracked FRC sections and assess the different testing methodologies available. The RILEM Technical Committee 261-CCF launched in 2015 the round-robin test (RRT) on creep behaviour in cracked sections of FRC program. This chapter includes the introduction and background to understand the realisation of this RRT. The main objectives as well as the limitations of the scope of the RRT are explained. The structure of the book is presented to provide a first overview of the book content. Finally, information about institutions involved as well as geographic distribution of RRT participants and number of specimens tested in the RRT is provided