2,971 research outputs found

    Molecular diagnostic challenges for non-retinal developmental eye disorders in the United Kingdom

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    Overall, approximately one-quarter of patients with genetic eye diseases will receive a molecular diagnosis. Patients with developmental eye disorders face a number of diagnostic challenges including phenotypic heterogeneity with significant asymmetry, coexisting ocular and systemic disease, limited understanding of human eye development and the associated genetic repertoire, and lack of access to next generation sequencing as regarded not to impact on patient outcomes/management with cost implications. Herein, we report our real world experience from a pediatric ocular genetics service over a 12 month period with 72 consecutive patients from 62 families, and that from a cohort of 322 patients undergoing whole genome sequencing (WGS) through the Genomics England 100,000 Genomes Project; encompassing microphthalmia, anophthalmia, ocular coloboma (MAC), anterior segment dysgenesis anomalies (ASDA), primary congenital glaucoma, congenital cataract, infantile nystagmus, and albinism. Overall molecular diagnostic rates reached 24.9% for those recruited to the 100,000 Genomes Project (73/293 families were solved), but up to 33.9% in the clinic setting (20/59 families). WGS was able to improve genetic diagnosis for MAC patients (15.7%), but not for ASDA (15.0%) and congenital cataracts (44.7%). Increased sample sizes and accurate human phenotype ontology (HPO) terms are required to improve diagnostic accuracy. The significant mixed complex ocular phenotypes distort these rates and lead to missed variants if the correct gene panel is not applied. Increased molecular diagnoses will help to explain the genotype-phenotype relationships of these developmental eye disorders. In turn, this will lead to improved integrated care pathways, understanding of disease, and future therapeutic development

    Spherical structures on torus knots and links

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    The present paper considers two infinite families of cone-manifolds endowed with spherical metric. The singular strata is either the torus knot t(2n+1,2){\rm t}(2n+1, 2) or the torus link t(2n,2){\rm t}(2n, 2). Domains of existence for a spherical metric are found in terms of cone angles and volume formul{\ae} are presented.Comment: 17 pages, 5 figures; typo

    Rapid interrogation of the physical and chemical characteristics of salbutamol sulphate aerosol from a pressurised metered-dose inhaler (pMDI)

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    Individual micron-sized solid particles from a Salamols pharmaceutical inhaler are stably captured in air using an optical trap for the first time. Raman spectroscopy of the levitated particles allows online interrogation of composition and deliquescent phase change within a high humidity environment that mimics the particle’s travel from inhaler to lun

    An R^4 non-renormalisation theorem in N=4 supergravity

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    We consider the four-graviton amplitudes in CHL constructions providing four-dimensional N=4 models with various numbers of vector multiplets. We show that in these models the two-loop amplitude has a prefactor of d^2R^4. This implies a non-renormalisation theorem for the R^4 term, which forbids the appearance of a three-loop ultraviolet divergence in four dimensions in the four-graviton amplitude. We connect the special nature of the R^4 term to the U(1) anomaly of pure N=4 supergravity.Comment: v2: added comments about one-loop UV divergences. Assorted stylistic corrections. Added references. v3: Eq. III.21 corrected and assorted minor corrections and clarifications. Version to be published. v4: minor corrections. 18 pages. one figur

    Seasonal effects on reconciliation in Macaca Fuscata Yakui

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    Dietary composition may have profound effects on the activity budgets, levelof food competition, and social behavior of a species. Similarly, in seasonally breeding species, the mating season is a period in which competition for mating partners increases, affecting amicable social interactions among group members. We analyzed the importance of the mating season and of seasonal variations in dietary composition and food competition on econciliation in wild female Japanese macaques (Macaca fuscata yakui) on Yakushima Island, Japan. Yakushima macaques are appropriate subjects because they are seasonal breeders and their dietary composition significantly changes among the seasons. Though large differences occurred between the summer months and the winter and early spring months in activity budgets and the consumption of the main food sources, i.e., fruits, seeds, and leaves, the level of food competition and conciliatory tendency remained unaffected. Conversely,conciliatory tendency is significantly lower during the mating season than in the nonmating season. Moreover, conciliatory tendency is lower when 1 or both female opponents is in estrous than when they are not. Thus the mating season has profound effects on reconciliation, whereas seasonal changes in activity budgets and dietary composition do not. The detrimental effects of the mating season on female social relationships and reconciliation may be due to the importance of female competition for access to male partners in multimale, multifemale societies

    Early Deglaciation in the Tropical Andes

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    Analysis of sediment records from lakes located beyond the glacial limit in the Andes has provided, for the first time, an independent assessment of effective moisture ( precipitation minus evaporation) and the timing of the last glaciation (1). Conditions were wet at the LGM and remained so until approximately 15,000 cal yr B.P. (2). However, deglaciation was under way from the LGM between 22,000 and 19,500 cal yr B.P., which reinforces the observation that deglaciation in the tropical Andes was primarily forced by an increase in mean annual temperature during a wet postglacial interval (3, 4)

    Early Deglaciation in the Tropical Andes

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    Analysis of sediment records from lakes located beyond the glacial limit in the Andes has provided, for the first time, an independent assessment of effective moisture ( precipitation minus evaporation) and the timing of the last glaciation (1). Conditions were wet at the LGM and remained so until approximately 15,000 cal yr B.P. (2). However, deglaciation was under way from the LGM between 22,000 and 19,500 cal yr B.P., which reinforces the observation that deglaciation in the tropical Andes was primarily forced by an increase in mean annual temperature during a wet postglacial interval (3, 4)

    Applying a User-centred Approach to Interactive Visualization Design

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    Analysing users in their context of work and finding out how and why they use different information resources is essential to provide interactive visualisation systems that match their goals and needs. Designers should actively involve the intended users throughout the whole process. This chapter presents a user-centered approach for the design of interactive visualisation systems. We describe three phases of the iterative visualisation design process: the early envisioning phase, the global specification hase, and the detailed specification phase. The whole design cycle is repeated until some criterion of success is reached. We discuss different techniques for the analysis of users, their tasks and domain. Subsequently, the design of prototypes and evaluation methods in visualisation practice are presented. Finally, we discuss the practical challenges in design and evaluation of collaborative visualisation environments. Our own case studies and those of others are used throughout the whole chapter to illustrate various approaches

    Spatial interactions in agent-based modeling

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    Agent Based Modeling (ABM) has become a widespread approach to model complex interactions. In this chapter after briefly summarizing some features of ABM the different approaches in modeling spatial interactions are discussed. It is stressed that agents can interact either indirectly through a shared environment and/or directly with each other. In such an approach, higher-order variables such as commodity prices, population dynamics or even institutions, are not exogenously specified but instead are seen as the results of interactions. It is highlighted in the chapter that the understanding of patterns emerging from such spatial interaction between agents is a key problem as much as their description through analytical or simulation means. The chapter reviews different approaches for modeling agents' behavior, taking into account either explicit spatial (lattice based) structures or networks. Some emphasis is placed on recent ABM as applied to the description of the dynamics of the geographical distribution of economic activities, - out of equilibrium. The Eurace@Unibi Model, an agent-based macroeconomic model with spatial structure, is used to illustrate the potential of such an approach for spatial policy analysis.Comment: 26 pages, 5 figures, 105 references; a chapter prepared for the book "Complexity and Geographical Economics - Topics and Tools", P. Commendatore, S.S. Kayam and I. Kubin, Eds. (Springer, in press, 2014
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