127 research outputs found

    ΠœΠ½ΠΎΠ³ΠΎΡΠ»ΠΎΠΉΠ½Ρ‹Π΅ ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡ†ΠΈΠΎΠ½Π½Ρ‹Π΅ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Π΅ покрытия Π½Π° основС оксидной ΠΊΠ΅Ρ€Π°ΠΌΠΈΠΊΠΈ ΠΈ ΠΌ-ΠΊΡ€ΠΎΠ»Π΅ΠΉ

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    The paper considers the influence of the parameters of the plasma spraying process on the technological characteristics of multilayer coatings based on nickel-chromium, nickel-chromium-aluminum-yttrium materials, oxide ceramics, Β intended for operation at high temperature and additional dynamic loads. The design of plasma coatings during their application (with subsequent high-energy processing) under such conditions requires a comprehensive solution – both the use Β of high-quality powder ingredients and the optimization of technological parameters. The plasma process of applying powder materials has been improved to obtain the maximum values of their utilization factors. The technological characteristics that affect the properties of plasma coatings are optimized, namely: the flow rates of the plasma-forming and materials-transporting gases, the flow rate ofΒ  supplied powder materials, the current and voltage of the electric arc of the plasma torch, the distance from the plasma torch nozzle exit to the substrate. The paper presents the results of studies of the structure Β of coatings, performed using scanning electron microscopy. Their analysis has made it possible to form general regularities obtained by the action of radiation of compression plasma flows on coatings formed by air plasma. The considered structures are created using the processes of melting, compaction and high-speed cooling of plasma coatings. The main optimization indicators are the maximum local compaction and spillage of the obtained compositions with the absence of defects and Β destruction from the impact of compression plasma flows. The main effect during the action of radiation of a compression plasma flow on previously formed coatings is thermal. It contributes heating of the near-surface layer. When the coating Β is exposed to radiation of compression plasma flows, a remelted layer of oxides with a thickness of about 12–15 Β΅m is created, smoothing the relief of the formed surface and creating a network of cracks on the surface, diverging into the depth of the coating. The liquid-phase processes occurring in the molten phase of the near-surface layers after exposure to compression plasma radiation change the structure of the layers and contribute to the modification of their mechanical properties. Β By smoothing the surface, increasing the density of the surface crystallized layer andΒ  minimizing macro-defects – pores Β or macrocracks – the mechanical characteristics of the coatings increase.РассмотрСно влияниС ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€ΠΎΠ² процСсса ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎΠ³ΠΎ напылСния Π½Π° тСхнологичСскиС характСристики многослойных ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ Π½Π° Π±Π°Π·Π΅ ΠΌΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»ΠΎΠ² никСль-Ρ…Ρ€ΠΎΠΌ ΠΈ никСль-Ρ…Ρ€ΠΎΠΌ-алюминий-ΠΈΡ‚Ρ‚Ρ€ΠΈΠΉ, оксидной ΠΊΠ΅Ρ€Π°ΠΌΠΈΠΊΠΈ, ΠΏΡ€Π΅Π΄Π½Π°Π·Π½Π°Ρ‡Π΅Π½Π½Ρ‹Ρ… для эксплуатации ΠΏΡ€ΠΈ высоких Ρ‚Π΅ΠΌΠΏΠ΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹Ρ… ΠΈ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹Ρ… динамичСских Π½Π°Π³Ρ€ΡƒΠ·ΠΊΠ°Ρ…. ΠšΠΎΠ½ΡΡ‚Ρ€ΡƒΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Ρ… ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ ΠΏΡ€ΠΈ ΠΈΡ… нанСсСнии (с ΠΏΠΎΡΠ»Π΅Π΄ΡƒΡŽΡ‰Π΅ΠΉ высокоэнСргСтичСской ΠΎΠ±Ρ€Π°Π±ΠΎΡ‚ΠΊΠΎΠΉ) Π² Ρ‚Π°ΠΊΠΈΡ… условиях Ρ‚Ρ€Π΅Π±ΡƒΠ΅Ρ‚ комплСксного Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ – ΠΊΠ°ΠΊ примСнСния качСствСнных ΠΏΠΎΡ€ΠΎΡˆΠΊΠΎΠ²Ρ‹Ρ… ΠΈΠ½Π³Ρ€Π΅Π΄ΠΈΠ΅Π½Ρ‚ΠΎΠ², Ρ‚Π°ΠΊ ΠΈ ΠΎΠΏΡ‚ΠΈΠΌΠΈΠ·Π°Ρ†ΠΈΠΈ тСхнологичСских ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€ΠΎΠ². Π£ΡΠΎΠ²Π΅Ρ€ΡˆΠ΅Π½ΡΡ‚Π²ΠΎΠ²Π°Π½ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹ΠΉ процСсс нанСсСния ΠΏΠΎΡ€ΠΎΡˆΠΊΠΎΠ²Ρ‹Ρ… ΠΌΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»ΠΎΠ² для получСния ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡŒΠ½Ρ‹Ρ… Π·Π½Π°Ρ‡Π΅Π½ΠΈΠΉ ΠΈΡ… коэффициСнтов использования. ΠžΠΏΡ‚ΠΈΠΌΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Ρ‹ тСхнологичСскиС характСристики, ΠΎΠΊΠ°Π·Ρ‹Π²Π°ΡŽΡ‰ΠΈΠ΅ влияниС Π½Π° свойства ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Ρ… ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: Π²Π΅Π»ΠΈΡ‡ΠΈΠ½Ρ‹ расходов ΠΏΠ»Π°Π·ΠΌΠΎΠΎΠ±Ρ€Π°Π·ΡƒΡŽΡ‰Π΅Π³ΠΎ ΠΈ Ρ‚Ρ€Π°Π½ΡΠΏΠΎΡ€Ρ‚ΠΈΡ€ΡƒΡŽΡ‰Π΅Π³ΠΎ ΠΌΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ Π³Π°Π·ΠΎΠ², расход ΠΏΠΎΠ΄Π°Π²Π°Π΅ΠΌΡ‹Ρ… ΠΏΠΎΡ€ΠΎΡˆΠΊΠΎΠ²Ρ‹Ρ… ΠΌΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»ΠΎΠ², Ρ‚ΠΎΠΊ ΠΈ напряТСниС элСктричСской Π΄ΡƒΠ³ΠΈ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎΠΉ Π³ΠΎΡ€Π΅Π»ΠΊΠΈ, расстояниС Β ΠΎΡ‚ срСза сопла ΠΏΠ»Π°Π·ΠΌΠΎΡ‚Ρ€ΠΎΠ½Π° Π΄ΠΎ ΠΏΠΎΠ΄Π»ΠΎΠΆΠΊΠΈ. Π’ ΡΡ‚Π°Ρ‚ΡŒΠ΅ ΠΏΡ€ΠΈΠ²Π΅Π΄Π΅Π½Ρ‹ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ исслСдований структуры ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ, Π²Ρ‹ΠΏΠΎΠ»Π½Π΅Π½Π½Ρ‹Ρ… с ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ растровой элСктронной микроскопии. Π˜Ρ… Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ» ΡΡ„ΠΎΡ€ΠΌΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΎΠ±Ρ‰ΠΈΠ΅ закономСрности, ΠΏΠΎΠ»ΡƒΡ‡Π°Π΅ΠΌΡ‹Π΅ ΠΏΡ€ΠΈ воздСйствии излучСния компрСссионных ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Ρ… ΠΏΠΎΡ‚ΠΎΠΊΠΎΠ² Π½Π° сформированныС Π²ΠΎΠ·Π΄ΡƒΡˆΠ½ΠΎΠΉ ΠΏΠ»Π°Π·ΠΌΠΎΠΉ покрытия. РассмотрСнныС структуры созданы ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ процСссов плавлСния, уплотнСния ΠΈ высокоскоростного охлаТдСния ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Ρ… ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ. ΠžΡΠ½ΠΎΠ²Π½Ρ‹Π΅ ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ ΠΎΠΏΡ‚ΠΈΠΌΠΈΠ·Π°Ρ†ΠΈΠΈ – максимальноС локальноС ΡƒΠΏΠ»ΠΎΡ‚Π½Π΅Π½ΠΈΠ΅ ΠΈ ΠΏΡ€ΠΎΠΏΠ»Π°Π²Π»Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Ρ… ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡ†ΠΈΠΉ с отсутствиСм Π΄Π΅Ρ„Π΅ΠΊΡ‚ΠΎΠ² ΠΈ Ρ€Π°Π·Ρ€ΡƒΡˆΠ΅Π½ΠΈΠΉ ΠΎΡ‚ воздСйствия ΠΏΠΎΡ‚ΠΎΠΊΠΎΠ² компрСссионной ΠΏΠ»Π°Π·ΠΌΡ‹. Π“Π»Π°Π²Π½Ρ‹ΠΉ эффСкт ΠΏΡ€ΠΈ воздСйствии излучСния компрСссионного ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΡ‚ΠΎΠΊΠ° Π½Π° Ρ€Π°Π½Π΅Π΅ сформированныС покрытия – Ρ‚Π΅ΠΏΠ»ΠΎΠ²ΠΎΠΉ.  Он способствуСт Π½Π°Π³Ρ€Π΅Π²Ρƒ приповСрхностного слоя. ΠŸΡ€ΠΈ дСйствии Π½Π° покрытия излучСния компрСссионных ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½Ρ‹Ρ… ΠΏΠΎΡ‚ΠΎΠΊΠΎΠ² создаСтся ΠΏΠ΅Ρ€Π΅ΠΏΠ»Π°Π²Π»Π΅Π½Π½Ρ‹ΠΉ слой оксидов Ρ‚ΠΎΠ»Ρ‰ΠΈΠ½ΠΎΠΉ порядка 12–15 ΠΌΠΊΠΌ, ΡΠ³Π»Π°ΠΆΠΈΠ²Π°ΡŽΡ‰ΠΈΠΉ Ρ€Π΅Π»ΡŒΠ΅Ρ„ сформированной повСрхности ΠΈ ΡΠΎΠ·Π΄Π°ΡŽΡ‰ΠΈΠΉ Π½Π° повСрхности сСтку Ρ‚Ρ€Π΅Ρ‰ΠΈΠ½, расходящихся Π² Π³Π»ΡƒΠ±ΠΈΠ½Ρƒ покрытия. ΠŸΡ€ΠΎΠΈΡΡ…ΠΎΠ΄ΡΡ‰ΠΈΠ΅ Π² расплавлСнной Ρ„Π°Π·Π΅ приповСрхностных слоСв ΠΆΠΈΠ΄ΠΊΠΎΡ„Π°Π·Π½Ρ‹Π΅ процСссы послС воздСйствия излучСния компрСссионной ΠΏΠ»Π°Π·ΠΌΡ‹ ΠΈΠ·ΠΌΠ΅Π½ΡΡŽΡ‚ структуру слоСв ΠΈ ΡΠΏΠΎΡΠΎΠ±ΡΡ‚Π²ΡƒΡŽΡ‚ ΠΌΠΎΠ΄ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ ΠΈΡ… мСханичСских свойств. Благодаря сглаТиванию повСрхности, ΡƒΠ²Π΅Π»ΠΈΡ‡Π΅Π½ΠΈΡŽ плотности повСрхностного закристаллизованного слоя ΠΈ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΌΠ°ΠΊΡ€ΠΎΠ΄Π΅Ρ„Π΅ΠΊΡ‚ΠΎΠ² – ΠΏΠΎΡ€ ΠΈΠ»ΠΈ ΠΌΠ°ΠΊΡ€ΠΎΡ‚Ρ€Π΅Ρ‰ΠΈΠ½ – ΠΏΠΎΠ²Ρ‹ΡˆΠ°ΡŽΡ‚ΡΡ мСханичСскиС характСристики ΠΏΠΎΠΊΡ€Ρ‹Ρ‚ΠΈΠΉ

    Computer Aided Autism Diagnosis Using Diffusion Tensor Imaging

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    Β© 2013 IEEE. Autism Spectrum Disorder (ASD), commonly known as autism, is a lifelong developmental disorder associated with a broad range of symptoms including difficulties in social interaction, communication skills, and restricted and repetitive behaviors. In autism spectrum disorder, numerous studies suggest abnormal development of neural networks that manifest itself as abnormalities of brain shape, functionality, and/ or connectivity. The aim of this work is to present our automated computer aided diagnostic (CAD) system for accurate identification of autism spectrum disorder based on the connectivity of the white matter (WM) tracts. To achieve this goal, two levels of analysis are provided for local and global scores using diffusion tensor imaging (DTI) data. A local analysis using the Johns Hopkins WM atlas is exploited for DTI atlas-based segmentation. Furthermore, WM integrity is examined by extracting the most notable features representing WM connectivity from DTI. Interactions of WM features between different areas in the brain, demonstrating correlations between WM areas were used, and feature selection among those associations were made. Finally, a leave-one-subject-out classifier is employed to yield a final per-subject decision. The proposed system was tested on a large dataset of 263 subjects from the National Database of Autism Research (NDAR) with their Autism Diagnostic Observation Schedule (ADOS) scores and diagnosis (139 typically developed: 66 males, and 73 females, and 124 autistics: 66 males, and 58 females), with ages ranging from 96 to 215 months, achieving an overall accuracy of 73%. In addition to this achieved global accuracy, diagnostically-important brain areas were identified, allowing for a better understanding of ASD-related brain abnormalities, which is considered as an essential step towards developing early personalized treatment plans for children with autism spectrum disorder

    Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

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    Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder

    Does size matter for horny beetles? A geometric morphometric analysis of interspecific and intersexual size and shape variation in Colophon haughtoni Barnard, 1929, and C. kawaii Mizukami, 1997 (Coleoptera: Lucanidae)

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    Colophon is an understudied, rare and endangered stag beetle genus with all species endemic to isolated mountain peaks in South Africa’s Western Cape. Geometric morphometrics was used to analyse intersexual and interspecific variation of size and shape in the mandibles, heads, pronota and elytra of two sympatric species: Colophon haughtoni and Colophon kawaii. All measured structures showed significant sexual dimorphism, which may result from male-male competition for females. Female mandibles were too small and featureless for analysis, but male Colophon beetles possess large, ornate mandibles for fighting. Males had significantly larger heads and pronota that demonstrated shape changes which may relate to resource diversion to the mandibles and their supporting structures. Females are indistinguishable across species, but males were accurately identified using mandibles, heads and pronota. Male C. kawaii were significantly larger than C. haughtoni for all structures. These results support the species status of C. kawaii, which is currently in doubt due to its hybridisation with C. haughtoni. We also demonstrate the value of geometric morphometrics as a tool which may aid Colophon conservation by providing biological and phylogenetic insights and enabling species identification

    The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26

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    The multifunctional enzyme tissue transglutaminase (TG2) is reported to both mediate and inhibit tumour progression. To elucidate these different roles of TG2, we established a series of stable-transfected mouse colon carcinoma CT26 cells expressing a catalytically active (wild type) and a transamidating-inactive TG2 (Cys277Ser) mutant. Comparison of the TG2-transfected cells with the empty vector control indicated no differences in cell proliferation, apoptosis and susceptibility to doxorubicin, which correlated with no detectable changes in the activation of the transcription factor NF-?B. TG2-transfected cells showed increased expression of integrin ß3, and were more adherent and less migratory on fibronectin than control cells. Direct interaction of TG2 with ß3 integrins was demonstrated by immunoprecipitation, suggesting that TG2 acts as a coreceptor for fibronectin with ß3 integrins. All cells expressed the same level of TGFß receptors I and II, but only cells transfected with active TG2 had increased levels of TGFß1 and matrix-deposited fibronectin, which could be inhibited by TG2 site-directed inhibitors. Moreover, only cells transfected with active TG2 were capable of inhibiting tumour growth when compared to the empty vector controls. We conclude that in this colon carcinoma model increased levels of active TG2 are unfavourable to tumour growth due to their role in activation of TGFß1 and increased matrix deposition, which in turn favours increased cell adhesion and a lowered migratory and invasive behaviour

    The Monofunctional Catalase KatE of Xanthomonas axonopodis pv. citri Is Required for Full Virulence in Citrus Plants

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    BACKGROUND: Xanthomonas axonopodis pv. citri (Xac) is an obligate aerobic phytopathogen constantly exposed to hydrogen peroxide produced by normal aerobic respiration and by the plant defense response during plant-pathogen interactions. Four putative catalase genes have been identified in silico in the Xac genome, designated as katE, catB, srpA (monofunctional catalases) and katG (bifunctional catalase). METHODOLOGY/PRINCIPAL FINDINGS: Xac catalase activity was analyzed using native gel electrophoresis and semi-quantitative RT-PCR. We demonstrated that the catalase activity pattern was regulated in different growth stages displaying the highest levels during the stationary phase. KatE was the most active catalase in this phase of growth. At this stage cells were more resistant to hydrogen peroxide as was determined by the analysis of CFU after the exposition to different H(2)O(2) concentrations. In addition, Xac exhibited an adaptive response to hydrogen peroxide, displaying higher levels of catalase activity and H(2)O(2) resistance after treatment with sub-lethal concentrations of the oxidant. In the plant-like medium XVM2 the expression of KatE was strongly induced and in this medium Xac was more resistant to H(2)O(2). A XackatE mutant strain was constructed by insertional mutagenesis. We observed that catalase induction in stationary phase was lost meanwhile the adaptive response to peroxide was maintained in this mutant. Finally, the XackatE strain was assayed in planta during host plant interaction rendering a less aggressive phenotype with a minor canker formation. CONCLUSIONS: Our results confirmed that in contrast to other Xanthomonas species, Xac catalase-specific activity is induced during the stationary phase of growth in parallel with the bacterial resistance to peroxide challenge. Moreover, Xac catalases expression pattern is modified in response to any stimuli associated with the plant or the microenvironment it provides. The catalase KatE has been shown to have an important function for the colonization and survival of the bacterium in the citrus plant during the pathogenic process. Our work provides the first genetic evidence to support a monofunctional catalase as a virulence factor in Xac

    Clinical oxidative stress during leprosy multidrug therapy:impact of dapsone oxidation

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    This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518Β±0.029 ΞΌg/mL) and paucibacillary (0.662Β±0.123 ΞΌg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software

    Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

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    Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

    A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

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    BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe
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