The relation between time of presentation and the sleep disturbing effects of nocturnally occurring jet aircraft flyovers

The research describes the sleep disturbing effects of jet aircraft flyover noise as it occurs at different times during the night. The results indicate that individuals respond statistically more, in terms of greater cortical desynchronization, during the first and last thirds of the night. During the middle third, while there is still a significant amount of cortical desynchronization in response to the jet aircraft noise, this is always less than that which occurs earlier or later in the night. The implications of this data are that it might be possible to reduce the disruptive effects of at least certain extrinsic sonic stimulation by appropriate scheduling

Sampling, Intervention, Prediction, Aggregation: A Generalized Framework for Model-Agnostic Interpretations

Model-agnostic interpretation techniques allow us to explain the behavior of any predictive model. Due to different notations and terminology, it is difficult to see how they are related. A unified view on these methods has been missing. We present the generalized SIPA (sampling, intervention, prediction, aggregation) framework of work stages for model-agnostic interpretations and demonstrate how several prominent methods for feature effects can be embedded into the proposed framework. Furthermore, we extend the framework to feature importance computations by pointing out how variance-based and performance-based importance measures are based on the same work stages. The SIPA framework reduces the diverse set of model-agnostic techniques to a single methodology and establishes a common terminology to discuss them in future work

The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing

OBJECTIVE: The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing. RESEARCH DESIGN AND METHODS: Skin wounds were created in wild-type (WT) and p66Shc(-/-) control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and beta-catenin. Response to hind limb ischemia was also evaluated. RESULTS: Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of beta-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc(-/-) than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and beta-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc(-/-) dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia. CONCLUSIONS: p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication

The competences of young teachers in education of pupils with special educational needs

Introduction. The present article considers the problem of readiness of young teachers to teach children with special educational needs in countries where the introduction of inclusive education began only in the last decade. The authors describe the key concepts of the theory of formation of professional skills and competences of teachers for working in inclusive education, based on which the results of research conducted in theCzechRepublic,Poland andRussia.The aim of this article is to compare the experience of young teachers in teaching children with special educational needs in relation to their skills and competences needed to perform this task.Methodology and research methods. Questionnaires and interviews were used to collect quantitative and qualitative data, which were eventually processed using basic statistics (quantitative survey) and the open-coding method (qualitative content).Results. The results of the study indicate both strong and weak aspects of the skills of young teachers in teaching students with special educational needs. In particular, a qualitative analysis of teachers’ responses revealed some interesting ideas that can be used in the search for improvements in teacher training, as well as in the support provided to teachers working with children with special educational needs directly in the school environment at the beginning of their professional careers. In general, it can be stated that young teachers in all three countries do not feel sufficiently qualified in terms of training to work with these children and are in need of expert support.Scientific novelty. The results of the current research allow for the determination of some priorities in teacher training for the modern development of inclusive education in the countries examined.Practical significance. The presented materials of the research can become the basis for developing a system of expert support for young teachers in the implementation of inclusive education, as well as new programs for preparing future teachers to work with pupils with special educational needs.Введение. В статье рассмотрена проблема готовности молодых педагогов к обучению детей с особыми образовательными потребностями в странах, где внедрение инклюзивного образования началось только в последнее десятилетие. Авторами описаны ключевые положения теории формирования профессиональных навыков и компетенций учителей для работы в условиях инклюзивного образования, на основании которой представлены результаты исследований, проведенных в Чехии, Польше и России.Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Основная цель статьи – сравнить опыт обучения молодыми педагогами детей с особыми образовательными потребностями в отношении навыков и компетенций, необходимых для выполнения этой задачи. Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Анкетирование и интервью применялись для сбора количественных и качественных данных, которые обрабатывались с использованием базовой статистики (количественный обзор) и метода открытого кодирования (качественный контент). Компетенции молодых педагогов в обучении детей с особыми образовательными потребностями. Результаты исследования указывают как на сильные, так и на слабые стороны навыков молодых педагогов по обучению детей с особыми образовательными потребностями. В частности, качественный анализ их ответов позволил выявить некоторые интересные идеи, которые могут быть использованы для совершенствования подготовки педагогов, а также оказания поддержки учителям, работающим с детьми указанной категории, непосредственно в школьной среде в начале их профессиональной карьеры. В целом можно констатировать, что молодые учителя во всех трех странах не чувствуют себя достаточно квалифицированными в области подготовки к работе с такими детьми и нуждаются в экспертной поддержке. Научная новизна. Результаты исследования позволяют определить некоторые приоритеты подготовки учителей для современного развития инклюзивного образования в рассмотренных странах. Практическая значимость. Представленные материалы могут стать основой разработки системы экспертной поддержки молодых учителей в реализации инклюзивного образования, а также новых программ подготовки будущих педагогов к работе с учениками с особыми образовательными потребностями

Cognitive Aging in Zebrafish

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

<p>Abstract</p> <p>Background</p> <p>The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas.</p> <p>Methods</p> <p>Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1^stbolus of Gd-DTPA over the first hour, and then re-imaged with a 2^ndbolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods.</p> <p>Results</p> <p>The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve.</p> <p>Conclusion</p> <p>Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.</p

Variations in Healthcare Access and Utilization Among Mexican Immigrants: The Role of Documentation Status

The objective of this study is to identify differences in healthcare access and utilization among Mexican immigrants by documentation status. Cross-sectional survey data are analyzed to identify differences in healthcare access and utilization across Mexican immigrant categories. Multivariable logistic regression and the Blinder-Oaxaca decomposition are used to parse out differences into observed and unobserved components. Mexican immigrants ages 18 and above who are immigrants of California households and responded to the 2007 California Health Interview Survey (2,600 documented and 1,038 undocumented immigrants). Undocumented immigrants from Mexico are 27% less likely to have a doctor visit in the previous year and 35% less likely to have a usual source of care compared to documented Mexican immigrants after controlling for confounding variables. Approximately 88% of these disparities can be attributed to predisposing, enabling and need determinants in our model. The remaining disparities are attributed to unobserved heterogeneity. This study shows that undocumented immigrants from Mexico are much less likely to have a physician visit in the previous year and a usual source of care compared to documented immigrants from Mexico. The recently approved Patient Protection and Affordable Care Act will not reduce these disparities unless undocumented immigrants are granted some form of legal status