Rare and Complex Epilepsies from Childhood to Adulthood: Requirements for Separate Management or Scope for a Lifespan Holistic Approach?

Purpose: In this descriptive review, we describe current models of transition in rare and complex epilepsy syndromes and propose alternative approaches for more holistic management based on disease biology. // Recent Findings: Previously published guidance and recommendations on transition strategies in individuals with epilepsy have not been systematically and uniformly applied. There is significant heterogeneity in models of transition/transfer of care across countries and even within the same country. // Summary: We provide examples of the most severe epilepsy and related syndromes and emphasise the limited data on their outcome in adulthood. Rare and complex epilepsy syndromes have unique presentations and require high levels of expertise and multidisciplinary approach. Lifespan clinics, with no transition, but instead continuity of care from childhood to adulthood with highly specialised input from healthcare providers, may represent an alternative effective approach. Effectiveness should be measured by evaluation of quality of life for both patients and their families/caregivers

Effective Image Fingerprint Extraction Based on Random Bubble Sampling

In this paper we propose an algorithm for image fingerprint extraction based on random selection of circular bubbles on the considered image. In more detail, a fingerprint vector is associated to the image, the components of which are the variances of pixel luminance values in randomly selected circular zones of the image. The positions and radius of these bubbles result from a random selection, whose parameters are user-defined. The obtained fingerprint has then been used for content-based image retrieval, using the standard euclidean distance as similarity metric between the extracted features. Experiments based on the detection of various linearly and nonlinearly distorted versions of a test image in a large database show very promising results

Displacement demand for nonlinear static analyses of masonry structures: Critical review and improved formulations

This paper discusses different formulations for calculating earthquake‐induced displacement demands to be associated with nonlinear static analysis procedures for the assessment of masonry structures. Focus is placed on systems with fundamental periods between 0.1 and 0.5 s, for which the inelastic displacement amplification is usually more pronounced. The accuracy of the predictive equations is assessed based on the results from nonlinear time‐history analyses, carried out on single‐degree‐of‐freedom oscillators with hysteretic force–displacement relationships representative of masonry structures. First, the study demonstrates some limitations of two established approaches based on the equivalent linearization concept: the capacity spectrum method of the Dutch guidelines NPR 9998‐18, and its version outlined in FEMA 440, both of which overpredict maximum displacements. Two codified formulations relying on inelastic displacement spectra are also evaluated, namely the N2 method of Eurocode 8 and the displacement coefficient method of ASCE 41‐17: the former proves to be significantly unconservative, while the latter is affected by excessive dispersion. A non‐iterative procedure, using an equivalent linear system with calibrated optimal stiffness and equivalent viscous damping, is then proposed to overcome some of the problems identified earlier. A recently developed modified N2 formulation is shown to improve accuracy while limiting the dispersion of the predictions

Steps to Improve Precision Medicine in Epilepsy

Precision medicine is an old concept, but it is not widely applied across human health conditions as yet. Numerous attempts have been made to apply precision medicine in epilepsy, this has been based on a better understanding of aetiological mechanisms and deconstructing disease into multiple biological subsets. The scope of precision medicine is to provide effective strategies for treating individual patients with specific agent(s) that are likely to work best based on the causal biological make-up. We provide an overview of the main applications of precision medicine in epilepsy, including the current limitations and pitfalls, and propose potential strategies for implementation and to achieve a higher rate of success in patient care. Such strategies include establishing a definition of precision medicine and its outcomes; learning from past experiences, from failures and from other fields (e.g. oncology); using appropriate precision medicine strategies (e.g. drug repurposing versus traditional drug discovery process); and using adequate methods to assess efficacy (e.g. randomised controlled trials versus alternative trial designs). Although the progress of diagnostic techniques now allows comprehensive characterisation of each individual epilepsy condition from a molecular, biological, structural and clinical perspective, there remain challenges in the integration of individual data in clinical practice to achieve effective applications of precision medicine in this domain

Monogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies

A monogenic aetiology can be identified in up to 40% of people with severe epilepsy. To address earlier and more appropriate treatment strategies, clinicians are required to know the implications that specific genetic causes might have on pathophysiology, natural history, comorbidities and treatment choices. In this narrative review, we summarise concepts on the genetic epilepsies based on the underlying pathophysiological mechanisms and present the current knowledge on treatment options based on evidence provided by controlled trials or studies with lower classification of evidence. Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. Most monogenic disorders are very rare and ASM choices for them are still based on inferences drawn from observational studies and early, often anecdotal, experiences with precision therapies. Precision medicine remains applicable to only a narrow number of patients with monogenic epilepsies and may target only part of the actual functional defects. Phenotypic heterogeneity is remarkable, and some genetic mutations activate epileptogenesis through their developmental effects, which may not be reversed postnatally. Other genes seem to have pure functional consequences on excitability, acting through either loss- or gain-of-function effects, and these may have opposite treatment implications. In addition, the functional consequences of missense mutations may be difficult to predict, making precision treatment approaches considerably more complex than estimated by deterministic interpretations. Knowledge of genetic aetiologies can influence the approach to surgical treatment of focal epilepsies. Identification of germline mutations in specific genes contraindicates surgery while mutations in other genes do not. Identification, quantification and functional characterization of specific somatic mutations before surgery using cerebrospinal fluid liquid biopsy or after surgery in brain specimens, will likely be integrated in planning surgical strategies and re-intervention after a first unsuccessful surgery as initial evidence suggests that mutational load may correlate with the epileptogenic zone. Promising future directions include gene manipulation by DNA or mRNA targeting; although most are still far from clinical use, some are in early phase clinical development

Slicings of parallelogram polyominoes: Catalan, schröder, baxter, and other sequences

We provide a new succession rule (i.e. generating tree) associated with Schröder numbers, that interpolates between the known succession rules for Catalan and Baxter numbers. We define Schröder and Baxter generalizations of parallelogram polyominoes, called slicings, which grow according to these succession rules. In passing, we also exhibit Schröder subclasses of Baxter classes, namely a Schröder subset of triples of non-intersecting lattice paths, a new Schröder subset of Baxter permutations, and a new Schröder subset of mosaic floorplans. Finally, we define two families of subclasses of Baxter slicings: the m-skinny slicings and the m-rowrestricted slicings, for m ∈ N. Using functional equations and the kernel method, their generating functions are computed in some special cases, and we conjecture that they are algebraic for any m

The Highly Miniaturised Radiation Monitor

We present the design and preliminary calibration results of a novel highly miniaturised particle radiation monitor (HMRM) for spacecraft use. The HMRM device comprises a telescopic configuration of active pixel sensors enclosed in a titanium shield, with an estimated total mass of 52 g and volume of 15 cm$^3$. The monitor is intended to provide real-time dosimetry and identification of energetic charged particles in fluxes of up to 10$^8$ cm$^{-2}$ s$^{-1}$ (omnidirectional). Achieving this capability with such a small instrument could open new prospects for radiation detection in space.Comment: 17 pages, 15 figure

Making memories: the development of long-term visual knowledge in children with visual agnosia

There are few reports about the effects of perinatal acquired brain lesions on the development of visual perception. These studies demonstrate nonseverely impaired visual-spatial abilities and preserved visual memory. Longitudinal data analyzing the effects of compromised perceptions on long-term visual knowledge in agnosics are limited to lesions having occurred in adulthood. The study of children with focal lesions of the visual pathways provides a unique opportunity to assess the development of visual memory when perceptual input is degraded. We assessed visual recognition and visual memory in three children with lesions to the visual cortex having occurred in early infancy. We then explored the time course of visual memory impairment in two of them at 2 years and 3.7 years from the initial assessment. All children exhibited apperceptive visual agnosia and visual memory impairment. We observed a longitudinal improvement of visual memory modulated by the structural properties of objects. Our findings indicate that processing of degraded perceptions from birth results in impoverished memories. The dynamic interaction between perception and memory during development might modulate the long-term construction of visual representations, resulting in less severe impairment