Health-related quality of life and the burden of prolonged seizures in noninstitutionalized children with epilepsy

OBJECTIVE: This study aimed to provide information on the burden of illness and health-related quality of life (HRQoL) in children with epilepsy who experience prolonged acute convulsive seizures (PACS) in the community setting, and to investigate factors that may predict poor HRQoL in this population. METHODS: Noninstitutionalized children (aged 3–16 years) who had experienced at least one PACS within the past year and had currently prescribed PACS rescue medication were enrolled in a cross-sectional study in Germany, Italy, Spain, and the United Kingdom (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3 [PERFECT-3]). Clinicians, parents/guardians, and patients completed web-based questionnaires regarding clinical characteristics, PACS frequency, and day-to-day impairment. Patients' HRQoL was rated by clinicians, parents/guardians, and patients themselves using the 5-dimension EuroQol questionnaire (EQ-5D) and summarized as a utility score. Potential predictors of poor HRQoL were tested in individual univariate generalized linear models and a global multivariable model. RESULTS: Enrolled children (N = 286) had experienced 1–400 PACS (median: 4) in the past year. Clinicians reported that 216/281 patients (76.9%) had learning disabilities of varying severity. Mean EQ-5D utility scores rated by clinicians (n = 279), parents (n = 277), and patients (n = 85) were 0.52 (standard deviation: 0.41), 0.51 (0.39), and 0.74 (0.29), respectively. Increasing PACS frequency, increasing severity of learning disability, and specialist school attendance were significantly associated with decreasing EQ-5D utility score. In the multivariable model, having learning disabilities was the best predictor of poor HRQoL. SIGNIFICANCE: Health-related quality of life was very poor in many children with epilepsy whose PACS were managed with rescue medication in the community, with learning disability being the most powerful predictor of patients' HRQoL. Mean EQ-5D utility scores were lower (worse) than published values for many other chronic disorders, indicating that optimal treatment should involve helping children and their families to manage learning disabilities and day-to-day impairments, in addition to preventing seizures

Quantum systems in weak gravitational fields

Fully covariant wave equations predict the existence of a class of inertial-gravitational effects that can be tested experimentally. In these equations inertia and gravity appear as external classical fields, but, by conforming to general relativity, provide very valuable information on how Einstein's views carry through in the world of the quantum.Comment: 22 pages. To be published in Proceedings of the 17th Course of the International School of Cosmology and Gravitation "Advances in the interplay between quantum and gravity physics" edited by V. De Sabbata and A. Zheltukhin, Kluwer Academic Publishers, Dordrech

Feynman diagrams versus Fermi-gas Feynman emulator

Precise understanding of strongly interacting fermions, from electrons in modern materials to nuclear matter, presents a major goal in modern physics. However, the theoretical description of interacting Fermi systems is usually plagued by the intricate quantum statistics at play. Here we present a cross-validation between a new theoretical approach, Bold Diagrammatic Monte Carlo (BDMC), and precision experiments on ultra-cold atoms. Specifically, we compute and measure with unprecedented accuracy the normal-state equation of state of the unitary gas, a prototypical example of a strongly correlated fermionic system. Excellent agreement demonstrates that a series of Feynman diagrams can be controllably resummed in a non-perturbative regime using BDMC. This opens the door to the solution of some of the most challenging problems across many areas of physics

Shape - but Not Size - Codivergence between Male and Female Copulatory Structures in Onthophagus Beetles

Genitalia are among the fastest evolving morphological traits in arthropods. Among the many hypotheses aimed at explaining this observation, some explicitly or implicitly predict concomitant male and female changes of genital traits that interact during copulation (i.e., lock and key, sexual conflict, cryptic female choice and pleiotropy). Testing these hypotheses requires insights into whether male and female copulatory structures that physically interact during mating also affect each other's evolution and patterns of diversification. Here we compare and contrast size and shape evolution of male and female structures that are known to interact tightly during copulation using two model systems: (a) the sister species O. taurus (1 native, 3 recently established populations) and O. illyricus, and (b) the species-complex O. fracticornis-similis-opacicollis. Partial Least Squares analyses indicated very little to no correlation between size and shape of copulatory structures, both in males and females. Accordingly, comparing shape and size diversification patterns of genitalia within each sex showed that the two components diversify readily - though largely independently of each other - within and between species. Similarly, comparing patterns of divergence across sexes showed that relative sizes of male and female copulatory organs diversify largely independent of each other. However, performing this analysis for genital shape revealed a signature of parallel divergence. Our results therefore suggest that male and female copulatory structures that are linked mechanically during copulation may diverge in concert with respect to their shapes. Furthermore, our results suggest that genital divergence in general, and co-divergence of male and female genital shape in particular, can evolve over an extraordinarily short time frame. Results are discussed in the framework of the hypotheses that assume or predict concomitant evolutionary changes in male and female copulatory organs

Effect of rescue medication on seizure duration in non-institutionalized children with epilepsy

OBJECTIVES: Characterize the real-world management of and outcomes for children with epilepsy receiving rescue medication for prolonged acute convulsive seizures (PACS) in the community. METHODS: PERFECT-3 (Practices in Emergency and Rescue medication For Epilepsy managed with Community-administered Therapy 3) was a European, retrospective observational study. Eligible patients were non-institutionalized children with epilepsy aged 3–16 years who had experienced ≥1 PACS in the past year and had ≥1 currently prescribed PACS rescue medication. Investigators provided clinical assessments and parents/guardians completed questionnaires. Statistical tests were post hoc; p values are descriptive. RESULTS: At enrollment (N = 286), most patients had prescriptions for diazepam (69.2%) and/or midazolam (55.9%); some had two (26.6%) or three (2.4%) prescribed rescue medications. Most patients experienced PACS despite regular anti-epilepsy medication. According to parents, the average duration of their child’s seizures without rescue medication was <5 minutes in 35.7% of patients, 5–<20 minutes in 42.6%, and ≥20 minutes in 21.7% (n = 258); with rescue medication seizure duration was <5 minutes in 69.4% of patients, 5–<20 minutes in 25.6%, and ≥20 minutes in 5.0%. Rescue medication use was significantly associated with average seizures lasting <5 minutes (χ2 = 58.8; p < 0.0001). At the time of their most recent PACS, 58.5–67.8% of children reportedly received rescue medication within 5 minutes of seizure onset, and 85.4–94.1% within 10 minutes. CONCLUSION: This study provides the first real-world data that rescue medications administered in the community reduce the duration of PACS in children with epilepsy. Study limitations including potential recall bias are acknowledged

An ecological method for the sampling of nonverbal signalling behaviours of young children with profound and multiple learning disabilities (PMLD)

- Background: Profound and multiple learning disabilities (PMLD) are a complex range of disabilities that affect the general health and wellbeing of the individual and their capacity to interact and learn. - Method: We developed a new methodology to capture the nonsymbolic signalling behaviours of children with PMLD within the context of a face-to-face interaction with a caregiver to provide analysis at a micro-level of descriptive detail incorporating the use of the ELAN digital video software. - Conclusion: The signalling behaviours of participants in a natural, everyday interaction can be better understood with the use of this innovation in methodology, which is predicated on the ecology of communication. Recognition of the developmental ability of the participants is an integral factor within that ecology. The method presented establishes an advanced account of the modalities through which a child affected by PMLD is able to communicate

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points

Improvisation and Transformation: Yes to the Mess

The field of organizational change has chiefly been studied from a teleological perspective. Most models of change emphasize action that is rational and goal oriented. What often gets overlooked and under theorized is the continuous, iterative nature of organizational life, the unplanned and serendipitous actions by and between people that lead to new discoveries and innovation. Recent research on organizational improvisation seeks to explore this area. In this chapter we will address two questions – what is the experience of improvisation and what are the conditions that support improvisation to flourish in organizations? In the first part of this paper, we look at the phenomenology of improvisation, the actual lived experience of those who improvise in the face of the unknown or in the midst of chaotic conditions. We will explore the strategies that some professional improvisers employ to deliberately create the improvisatory moment. We will then look at the dynamics of organizational life and explore the cultural beliefs, organizational structures, and leadership practices that support improvisation. We will draw primarily upon the model from Barrett (2012) that focuses on the how the nature of jazz improvisation and the factors that support improvisation can be transferred to leadership activities. This falls in the tradition of others who draw upon arts-based metaphors, including jazz music and theatrical improvisation, to suggest insights for leadership and ways of organizing. Since this is a book devoted to individual transformation as well as organizational transformation, we will also touch on the topic of how improvisation is a developmental project and explore the potential for improvisation to lead to personal transformation. We will attempt to move back and forth between both themes – organizational and personal transformation. Ultimately the two topics are not separate. Any significant organizational transformation begins with an improvisation. And any meaningful improvisatory move by a person is potentially a moment of self-discovery and an identity-shaping event

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

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