339 research outputs found
An agglomeration-based massively parallel non-overlapping additive Schwarz preconditioner for high-order discontinuous Galerkin methods on polytopic grids
In this article we design and analyze a class of two-level non-overlapping
additive Schwarz preconditioners for the solution of the linear system of
equations stemming from discontinuous Galerkin discretizations of second-order
elliptic partial differential equations on polytopic meshes. The preconditioner
is based on a coarse space and a non-overlapping partition of the computational
domain where local solvers are applied in parallel. In particular, the coarse
space can potentially be chosen to be non-embedded with respect to the finer
space; indeed it can be obtained from the fine grid by employing agglomeration
and edge coarsening techniques. We investigate the dependence of the condition
number of the preconditioned system with respect to the diffusion coefficient
and the discretization parameters, i.e., the mesh size and the polynomial
degree of the fine and coarse spaces. Numerical examples are presented which
confirm the theoretical bounds
A educação dramática na formação inicial de professores e educadores
As atividades de Educação Dramática convocam uma diversidade de possibilidades expressivas. Integradas no currÃculo de formação inicial de professores e educadores, os projetos de criação dramática, orientados para a performance, implicam, no seu processo criativo, um envolvimento grupal que deverá constituir matéria suficiente de análise e de avaliação por parte dos seus intervenientes em relação à sua própria participação e à s relações interpares. O paradigma metodológico orientador do processo dramático-teatral a que nos remetemos assenta num modelo construtivista do processo educacional. Pelo seu caráter explorativo e experimental, a aprendizagem dramático-teatral deverá ser sustentada em estratégias colaborativas entre professor e aluno, implicando, para tal, a possibilidade de tomada de decisões partilhadas, num ambiente de respeito e igualdade.The activities of Drama Education are open to a diversity of expressive possibilities. Integrated in the pre-service training curriculum for teachers and educators, the dramatic creation projects, oriented to performance, imply, in its creative process, a group involvement that should be sufficient matter of analysis and evaluation by those involved in relation to its own participation and relations between peers. The methodological guidance paradigm of the dramatic and theatrical process that guide us is based on a constructivist model of the educational process. Due its exploratory and experimental character, dramatic and theatrical learning should be based on collaborative strategies between teacher and student, implying, to this end, that decision-making possibilities could be shared in an environment of respect and equality.CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT), Portugal. Fundos Nacionais através da FCT (Fundação para a Ciência e a Tecnologia) e cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) através do COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) com a referência POCI-01-0145-FEDER-007562info:eu-repo/semantics/publishedVersio
FlorItaly-the portal to the flora of Italy
Digital data concerning the flora of Italy are largely fragmented among different resources hosted on different platforms, and often with different data standards, which are neither connected by a common access point, nor by web services, thus constituting a relevant obstacle to data access and usage. Taxonomic incongruences add a further complication. This paper describes "FlorItaly", an online information system which allows to access and query updated information on the checklist of the flora of Italy, aiming at becoming an aggregator for Italian botanical resources. "FlorItaly" was developed in a collaborative effort by more than 50 taxonomists, with the support of the Italian Botanical Society, and of Project "Dryades" (University of Trieste), to provide a better and reliable organization of botanical knowledge in Italy, as well as a relevant simplification for data retrieval, and a further stimulus towards a more collaborative approach in botanical research
Overcoming the Challenges to Clinical Development of X-Linked Retinitis Pigmentosa Therapies: Proceedings of an Expert Panel
UNLABELLED: X-linked retinitis pigmentosa (XLRP) is a rare inherited retinal disease manifesting as impaired night vision and peripheral vision loss that progresses to legal blindness. Although several trials of ocular gene therapy for XLRP have been conducted or are in progress, there is currently no approved treatment. In July 2022, the Foundation Fighting Blindness convened an expert panel to examine relevant research and make recommendations for overcoming the challenges and capitalizing on the opportunities in conducting clinical trials of RPGR-targeted therapy for XLRP. Data presented concerned RPGR structure and mutation types known to cause XLRP, RPGR mutation-associated retinal phenotype diversity, patterns in genotype/phenotype relationships, disease onset and progression from natural history studies, and the various functional and structural tests used to monitor disease progression. Panel recommendations include considerations, such as genetic screening and other factors that can impact clinical trial inclusion criteria, the influence of age on defining and stratifying participant cohorts, the importance of conducting natural history studies early in clinical development programs, and the merits and drawbacks of available tests for measuring treatment outcomes. We recognize the need to work with regulators to adopt clinically meaningful end points that would best determine the efficacy of a trial. Given the promise of RPGR-targeted gene therapy for XLRP and the difficulties encountered in phase III clinical trials to date, we hope these recommendations will help speed progress to finding a cure.
TRANSLATIONAL RELEVANCE: Examination of relevant data and recommendations for the successful clinical development of gene therapies for RPGR-associated XLRP
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Perimacular Atrophy Following Voretigene Neparvovec-Rzyl Treatment in the Setting of Previous Contralateral Eye Treatment With a Different Viral Vector
PurposeTo report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.DesignSingle-center, retrospective chart review.MethodsIn this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.ResultsThree out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.ConclusionsWe observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.Translational relevanceCaution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies
Molecular and Clinical Findings in Patients With Knobloch Syndrome
IMPORTANCE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described. OBJECTIVE: To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome. DESIGN, SETTING AND PARTICIPANTS: Twelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015. MAIN OUTCOMES AND MEASURES: Results of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1. RESULTS: Of the 12 patients (6 males; mean age at last review, 16 years [range, 2-38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children. CONCLUSIONS AND RELEVANCE: This report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications
Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children
Aim: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. Methods: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. Results: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. Conclusion: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking
Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye
Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.National Institutes of Health (U.S.) (Grant R01-EY023285)National Institutes of Health (U.S.) (Grant R01-EY024544)National Institutes of Health (U.S.) (Grant DP3 DK104397)National Institutes of Health (U.S.) (Grant R01-EY11289)National Institutes of Health (U.S.) (Grant K08-EY021186)National Institutes of Health (U.S.) (Grant T32-EY23211)National Institutes of Health (U.S.) (Grant P30-EY010572)Clinical and Translational Science Award Grant UL1TR000128Research to Prevent Blindness, Inc. (United States) (Grant and Career Development Award CD-NMT-0914-0659-OHSU)United States. Air Force Office of Scientific Research (Foundation Fighting Blindness Career Development Award FA9550-10-1-0551)German Research Foundation (Grant DFG-HO-1791/11-1)German Research Foundation (Grant DFG-GSC80-SAOT
Notulae to the Italian alien vascular flora: 2
In this contribution, new data concerning the Italian distribution of alien vascular flora are presented. It includes new records, exclusions and confirmations for Italy or for Italian administrative regions for taxa in the genera Ageratum, Aster, Buddleja, Cedrus, Centranthus, Cephalotaxus, Clerodendrum, Cotoneaster, Cyperus, Honorius, Lantana, Ligustrum, Morus, Muscari, Oenothera, Opuntia, Platycladus, Plumbago, Pseudotsuga, Sedum, Sporobolus, Stachys, Ulmus and Yucca. A nomen novum, Stachys talbotii, is proposed as a replacement name for Sideritis purpurea
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