Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Genetics of calcium homeostasis in humans: continuum between monogenic diseases and continuous phenotypes

Extracellular calcium participates in several key physiological functions, such as control of blood coagulation, bone calcification or muscle contraction. Calcium homeostasis in humans is regulated in part by genetic factors, as illustrated by rare monogenic diseases characterized by hypo or hypercalcaemia. Both serum calcium and urinary calcium excretion are heritable continuous traits in humans. Serum calcium levels are tightly regulated by two main hormonal systems, i.e. parathyroid hormone and vitamin D, which are themselves also influenced by genetic factors. Recent technological advances in molecular biology allow for the screening of the human genome at an unprecedented level of detail and using hypothesis-free approaches, such as genome-wide association studies (GWAS). GWAS identified novel loci for calcium-related phenotypes (i.e. serum calcium and 25-OH vitamin D) that shed new light on the biology of calcium in humans. The substantial overlap (i.e. CYP24A1, CASR, GATA3; CYP2R1) between genes involved in rare monogenic diseases and genes located within loci identified in GWAS suggests a genetic and phenotypic continuum between monogenic diseases of calcium homeostasis and slight disturbances of calcium homeostasis in the general population. Future studies using whole-exome and whole-genome sequencing will further advance our understanding of the genetic architecture of calcium homeostasis in humans. These findings will likely provide new insight into the complex mechanisms involved in calcium homeostasis and hopefully lead to novel preventive and therapeutic approaches. Keyword: calcium, monogenic, genome-wide association studies, genetics.

Hilbert space on probability density functions with Aitchison geometry

Compositional data analysis motivated the introduction of a complete Euclidean structure in the simplex of D parts. This was based on the early work of J. Aitchison (1986) and completed recently when Aitchinson distance in the simplex was associated with an inner product and orthonormal bases were identified (Aitchison and others, 2002; Egozcue and others, 2003). A partition of the support of a random variable generates a composition by assigning the probability of each interval to a part of the composition. One can imagine that the partition can be refined and the probability density would represent a kind of continuous composition of probabilities in a simplex of infinitely many parts. This intuitive idea would lead to a Hilbert-space of probability densities by generalizing the Aitchison geometry for compositions in the simplex into the set probability densities

Estimation of age- and stage-specific Catalan breast cancer survival functions using US and Catalan survival data

During the last part of the 1990s the chance of surviving breast cancer increased. Changes in survival functions reflect a mixture of effects. Both, the introduction of adjuvant treatments and early screening with mammography played a role in the decline in mortality. Evaluating the contribution of these interventions using mathematical models requires survival functions before and after their introduction. Furthermore, required survival functions may be different by age groups and are related to disease stage at diagnosis. Sometimes detailed information is not available, as was the case for the region of Catalonia (Spain). Then one may derive the functions using information from other geographical areas. This work presents the methodology used to estimate age- and stage-specific Catalan breast cancer survival functions from scarce Catalan survival data by adapting the age- and stage-specific US functions. Methods: Cubic splines were used to smooth data and obtain continuous hazard rate functions. After, we fitted a Poisson model to derive hazard ratios. The model included time as a covariate. Then the hazard ratios were applied to US survival functions detailed by age and stage to obtain Catalan estimations. Results: We started estimating the hazard ratios for Catalonia versus the USA before and after the introduction of screening. The hazard ratios were then multiplied by the age- and stage-specific breast cancer hazard rates from the USA to obtain the Catalan hazard rates. We also compared breast cancer survival in Catalonia and the USA in two time periods, before cancer control interventions (USA 1975–79, Catalonia 1980–89) and after (USA and Catalonia 1990–2001). Survival in Catalonia in the 1980–89 period was worse than in the USA during 1975–79, but the differences disappeared in 1990–2001. Conclusion: Our results suggest that access to better treatments and quality of care contributed to large improvements in survival in Catalonia. On the other hand, we obtained detailed breast cancer survival functions that will be used for modeling the effect of screening and adjuvant treatments in Catalonia

Museums and quality, from the concept of the museum that carries out functions to the museum that provides services

Quality management Self-evaluation of the organisation Citizens/customers satisfaction Impact on society evaluation Key performance evaluation Good practices comparison (Benchmarking) Continuous improvement In professional environments, when quality assessment of museums is discussed, one immediately thinks of the honourableness of the directors and curators, the erudition and specialisation of knowledge, the diversity of the gathered material and study of the collections, the collections conservation methods and environmental control, the regularity and notoriety of the exhibitions and artists, the building’s architecture and site, the recreation of environments, the museographic equipment design. We admit that the roles and attributes listed above can contribute to the definition of a specificity of museological good practice within a hierarchised functional perspective (the museum functions) and for the classification of museums according to a scale, validated between peers, based on “installed” appreciation criteria, enforced from above downwards, according to the “prestige” of the products and of those who conceive them, but that say nothing about the effective satisfaction of the citizen/customers and the real impact on society. There is a lack of evaluation instruments that would give us a return of all that the museum is and represents in contemporary society, focused on being and on the relation with the other, in detriment of the ostentatious possession and of the doing in order to meet one’s duties. But it is only possible to evaluate something by measurement and comparison, on the basis of well defined criteria, from a common grid, implicating all of the actors in the self-evaluation, in the definition of the aims to fulfil and in the obtaining of results.

Evaluating raw ensembles with the continuous ranked probability score

The continuous ranked probability score (CRPS) is a frequently used scoring rule. In contrast with many other scoring rules, the CRPS evaluates cumulative distribution functions. An ensemble of forecasts can easily be converted into a piecewise constant cumulative distribution function with steps at the ensemble members. This renders the CRPS a convenient scoring rule for the evaluation of ‘raw’ ensembles, obviating the need for sophisticated ensemble model output statistics or dressing methods prior to evaluation. In this article, a relation between the CRPS score and the quantile score is established. The evaluation of ‘raw’ ensembles using the CRPS is discussed in this light. It is shown that latent in this evaluation is an interpretation of the ensemble as quantiles but with non-uniform levels. This needs to be taken into account if the ensemble is evaluated further, for example with rank histograms.

IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD/

Moho map of South America from receiver functions and surface waves

We estimate crustal structure and thickness of South America north of roughly 40 degrees S. To this end, we analyzed receiver functions from 20 relatively new temporary broadband seismic stations deployed across eastern Brazil. In the analysis we include teleseismic and some regional events, particularly for stations that recorded few suitable earthquakes. We first estimate crustal thickness and average Poisson`s ratio using two different stacking methods. We then combine the new crustal constraints with results from previous receiver function studies. To interpolate the crustal thickness between the station locations, we jointly invert these Moho point constraints, Rayleigh wave group velocities, and regional S and Rayleigh waveforms for a continuous map of Moho depth. The new tomographic Moho map suggests that Moho depth and Moho relief vary slightly with age within the Precambrian crust. Whether or not a positive correlation between crustal thickness and geologic age is derived from the pre-interpolation point constraints depends strongly on the selected subset of receiver functions. This implies that using only pre-interpolation point constraints (receiver functions) inadequately samples the spatial variation in geologic age. The new Moho map also reveals an anomalously deep Moho beneath the oldest core of the Amazonian Craton.

Continuous GRASP with a local active-set method for bound-constrained global optimization

Global optimization seeks a minimum or maximum of a multimodal function over a discrete or continuous domain. In this paper, we propose a hybrid heuristic-based on the CGRASP and GENCAN methods-for finding approximate solutions for continuous global optimization problems subject to box constraints. Experimental results illustrate the relative effectiveness of CGRASP-GENCAN on a set of benchmark multimodal test functions.

On E-functions of semisimple Lie groups

We develop and describe continuous and discrete transforms of class functions on a compact semisimple, but not simple, Lie group G as their expansions into series of special functions that are invariant under the action of the even subgroup of the Weyl group of G. We distinguish two cases of even Weyl groups-one is the direct product of even Weyl groups of simple components of G and the second is the full even Weyl group of G. The problem is rather simple in two dimensions. It is much richer in dimensions greater than two-we describe in detail E-transforms of semisimple Lie groups of rank 3.

Interpolation of Lipschitz functions

This paper describes a new computational approach to multivariate scattered data interpolation. It is assumed that the data is generated by a Lipschitz continuous function f. The proposed approach uses the central interpolation scheme, which produces an optimal interpolant in the worst case scenario. It provides best uniform error bounds on f, and thus translates into reliable learning of f. This paper develops a computationally efficient algorithm for evaluating the interpolant in the multivariate case. We compare the proposed method with the radial basis functions and natural neighbor interpolation, provide the details of the algorithm and illustrate it on numerical experiments. The efficiency of this method surpasses alternative interpolation methods for scattered data.

Smoothing Lipschitz functions

This paper describes a new approach to multivariate scattered data smoothing. It is assumed that the data are generated by a Lipschitz continuous function f, and include random noise to be filtered out. The proposed approach uses known, or estimated value of the Lipschitz constant of f, and forces the data to be consistent with the Lipschitz properties of f. Depending on the assumptions about the distribution of the random noise, smoothing is reduced to a standard quadratic or a linear programming problem. We discuss an efficient algorithm which eliminates the redundant inequality constraints. Numerical experiments illustrate applicability and efficiency of the method. This approach provides an efficient new tool of multivariate scattered data approximation.

Thresholds, incidence functions, and species-specific cues : responses of woodland birds to landscape structure in south-eastern Australia

Looking out from a vantage point across a large tract of forest gives a superficial impression of uniformity: the crowns of canopy trees follow the folds and contours of the landscape to provide a continuous cover of wooded vegetation. But this visual appearance belies the truth: forested landscapes are far from uniform. On closer examination, they comprise a complex mosaic of different vegetation types and and stands of different age-classes, differing structural features, and modified to a varying extent by human land-uses. Forests have a critical role in the conservation of biodiversity throughout the world (Peterken 1996; Laurance and Bierregard 1997; Lindenmayer and Franklin 2002) and a key feature contributing to their conservation value is the response of forest biota to the heterogeneity inherent in forested landscapes (Lindenmayer et al. 2006). Consequently, an understanding of the implications of landscape structure for the maintainance of species and ecological processes is an important foundation for forest management and biodiversity conservation.

Electrospinning of continuous nanofiber bundles and twisted nanofiber yarns

Spinning is a prehistoric technology in which endless filaments, shorter fibers or twisted fibers are put together to produce yarns that serve as key element to assemble multifarious structural designs for diverse functions. Electrospinning has been regarded as the most effective and versatile technology to produce nanofibers with controlled fiber morphology, dimension and functional components from various polymeric materials (Dersch et al., 2007, Frenot and Chronakis, 2003, Schreuder-Gibson et al., 2002). However, most electrospun fibers are produced in the form of randomly-oriented nonwoven fiber mats (Doshi and Reneker, 1995, Madhavamoorthi, 2005). The relatively low mechanical strength and difficulty in tailoring the fibrous structure have restricted their applications. With the rapid development in nanoscience and nanotechnology, yarns composed of nanofibers may uncover new opportunities for development of well-defined three dimensional nano fibrous architectures. This chapter focuses on recent research and advancement in electrospinning of nanofiber bundles and nanofiber yarns. The preparation, morphology, mechanical properties and potential applications of these fibrous materials are discussed in details.

Multitasking: multiple, domain-specific cognitive functions in a virtual environment

Multitasking among three or more different tasks is a ubiquitous requirement of everyday cognition, yet rarely is it addressed in research on healthy adults who have had no specific training in multitasking skills. Participants completed a set of diverse subtasks within a simulated shopping mall and office environment, the Edinburgh Virtual Errands Test (EVET). The aim was to investigate how different cognitive functions, such as planning, retrospective and prospective memory, and visuospatial and verbal working memory, contribute to everyday multitasking. Subtasks were chosen to be diverse, and predictions were derived from a statistical model of everyday multitasking impairments associated with frontal-lobe lesions (Burgess, Veitch, de Lacy Costello, & Shallice, 2000b). Multiple regression indicated significant independent contributions from measures of retrospective memory, visuospatial working memory, and online planning, but not from independent measures of prospective memory or verbal working memory. Structural equation modelling showed that the best fit to the data arose from three underlying constructs, with Memory and Planning having a weak link, but with both having a strong directional pathway to an Intent construct that reflected implementation of intentions. Participants who followed their preprepared plan achieved higher scores than those who altered their plan during multitask performance. This was true regardless of whether the plan was efficient or poor. These results substantially develop and extend the Burgess et al. (2000b) model to healthy adults and yield new insight into the poorly understood area of everyday multitasking. The findings also point to the utility of using virtual environments for investigating this form of complex human cognition.