IntroductionKeratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC.MethodsThe PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” and “cornea” were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches.ResultsAn association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed.ConclusionTwenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.

IntroductionKeratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000–1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL.MethodsPubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” “proteins”, “collagen” and “cornea’’ were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL.ResultsA total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control.ConclusionThe pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

Frequencies of the thalassaemias in Cyprus were examined by a survey of hospital inpatients and haematological investigations of adult and newborn population samples. The data indicate that 15% of the Greek and Turkish Cypriots are carriers of beta-thalassaemia genes, while 10% of the population carry alpha-thalassaemia genes. These are the highest frequencies of thalassaemia genes found today in any Caucasian population.

This paper documents the construction of a Virtual Engine, with particular reference to its geometry and conceptual description.. The phrase Virtual Engine denotes a system which allows simulations of whole gas-turbine engines to be undertaken at any desired level of fidelity or physical modeling. In order to be of any practical use, the system must allow the computations to be setup as automatically as possible and needs to contain provisions for the exchange of boundary data between adjacent computational domains — e.g. solid-gas interfaces. The paper illustrates the application of the system to the representation and analysis of a modern commercial turbofan engine.

A new effective method for comprehensive modeling of gas flow effects on vibration of nonlinear vibration of bladed disks has been developed for a case when the effect of the gas flow on the mode shapes is significant. The method separates completely the structural dynamics calculations from the significantly more computationally expensive computational fluid dynamics (CFD) calculations while providing the high accuracy of modeling for aerodynamic effects. A comprehensive analysis of the forced response using the new method has been performed for a realistic turbine bladed disk with root-disk joints, tip, and under-platform dampers. The full chain of aerodynamic and structural calculations are performed: (i) determination of boundary conditions for CFD, (ii) CFD analysis, (iii) calculation of the aerodynamic characteristics required by the new method, and (iv) nonlinear forced response analysis using the modal aerodynamic influence matrix (MAIM). The efficiency of the friction damping devices has been studied and compared for several resonance frequencies and engine orders. Advantages of the method for aerodynamic effect modeling have been demonstrated.