Phenotypic analysis of hemochromatosis subtypes reveals variations in severity of iron overload and clinical disease

The clinical progression of HFE-related hereditary hemochromatosis (HH) and its phenotypic variability has been well studied. Less is known about the natural history of non-HFE HH caused by mutations in the , or genes. The purpose of this study was to compare the phenotypic and clinical presentations of hepcidin-deficient forms of HH. A literature review of all published cases of genetically confirmed HJV, HAMP and TFR2 HH was performed. Phenotypic and clinical data from a total of 156 subjects with non-HFE HH was extracted from 53 publications and compared with data from 984 subjects with -p.C282Y homozygous HH from the QIMR Berghofer Hemochromatosis Database. Analyses confirmed that non-HFE forms of HH have an earlier age of onset and a more severe clinical course than HFE HH. HJV and HAMP HH are phenotypically and clinically very similar and have the most severe presentation, with cardiomyopathy and hypogonadism being particularly prevalent findings. TFR2 HH is more intermediate in its age of onset and severity. All clinical outcomes analyzed were more prevalent in the juvenile forms of HH, with the exception of arthritis and arthropathy which were more commonly seen in HFE HH. This is the first comprehensive analysis comparing the different phenotypic and clinical aspects of the genetic forms of HH and the results will be valuable for the differential diagnosis and management of these conditions. Importantly, our analyses indicate that factors other than iron overload may be contributing to joint pathology in subjects with HFE HH

Assessment of recent theories for predicting failure of composite laminates

It has still not been shown that current failure theories can be accurate for all loading configurations, boundary conditions, layups, and thicknesses of composite laminates. A comprehensive discussion is neither available in the most recent bibliographical reviews, nor in the most recent assessments of their accuracy. In this review article, new failure theories, recent improvements to existing theories, and the most relevant contributions to the modeling of failure mechanisms of composites with continuous reinforcement fibers are discussed, together with their recent applications. The most recent physically based practical failure criteria, which use standard engineering quantities, have affordable computational costs and do not require empirical parameters to be examined for a variety of situations. Their predictions are compared to those of generalized failure criteria currently implemented into widespread finite element codes. The objective is to offer designers a guidance of the range of validity of current theories. To enlarge the set of tests for a single theory, the sample test set, i.e., layups, constituent materials, loading configurations, and boundary conditions, and the experimental results used to develop a failure criterion are used for different criteria. The finite element analysis is carried out using three-dimensional (3D), mixed elements capable of very accurately predicting the local stresses. The ply level stresses are computed discretizing the layers by a 3D meshing. The fiber and matrix stresses, which can differ significantly from the ply level stresses, are computed using a local 3D discretization of the constituents. The phase-averaged fiber and matrix stresses and the ply level stresses are used for failure computations. It is seen that generalized failure criteria can be as accurate as physically based failure criteria for some cases, while the opposite occurs for other cases. Likewise, a criterion can be the most accurate for a particular case and inaccurate in other cases. None of the failure criteria considered appeared accurate for all of the cases considered. However, a group of physically based criteria is identified that, collectively, provides quite accurate predictions. These criteria could be used as reciprocal checks. There on 136 references cited in this reivew article