Correction of Pulmonary Arteriovenous Malformation Using Image-Based Surgical Planning

The objectives of this study were to develop an image-based surgical planning framework that 1) allows for in-depth analysis of pre-operative hemodynamics by the use of cardiac magnetic resonance and 2) enables surgeons to determine the optimum surgical scenarios before the operation. This framework is tailored for applications in which post-operative hemodynamics are important. In particular, it is exemplified here for a Fontan patient with severe left pulmonary arteriovenous malformations due to abnormal hepatic flow distribution to the lungs. Patients first undergo cardiac magnetic resonance for 3-dimensional anatomy and flow reconstruction. After analysis of the pre-operative flow fields, the 3-dimensional anatomy is imported into an interactive surgical planning interface for the surgeon to virtually perform multiple surgical scenarios. Associated hemodynamics are predicted by the use of a fully validated computational fluid dynamic solver. Finally, efficiency metrics (e.g., pressure decrease and hepatic flow distribution) are weighted against surgical feasibility to determine the optimal surgical option

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network

Objectives (1) To develop reference values for health-related fitness in European children and adolescents aged 6–18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. Methods This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test–retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. Results A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu). Conclusion This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ(17–40/42)). The presence of N-terminally truncated Aβ(17–40) and Aβ(17–42) in the control brains was confirmed by Western blotting and the identity of Aβ(17–40) was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ(17–42) immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism

Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

<div><h3>Background</h3><p>It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.</p> <h3>Methodology/Principal Findings</h3><p>In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ_17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ_1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques.</p> <h3>Conclusions/Significance</h3><p>The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.</p> </div

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 9th edition

Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the &ldquo;Standards&rdquo; also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) &ndash; Type 2 DM, 6% (256 202) &ndash; Type 1 DM and 2% (89 870) &ndash; other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don&rsquo;t receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the &ldquo;Standards&rdquo;: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Grou

Harvesting Memory, Preserving Home: A Cookbook of the Painted Turtle Farm/Cosechando Memoria, Preservando el Hogar: Un Libro de Cocina de la Granja de la Tortuga Pintada

About this Project In the fall of 2018, 14 of the families and 32 students from two first-year seminars, Crossing Borders: Immigration, Identity, and Development and Immigrant Stories, worked together to create this cookbook. Families submitted their favorite dishes and then invited students to their homes to demonstrate the preparation. As they cooked and ate together, students recorded the steps to make the recipe and listened as connections between food, memory, family, migration, traditions, and religion emerged. Harvesting Memory, Preserving Home: A Cookbook of the Painted Turtle Farm is the product of this undertaking. In it, we offer the collection of recipes as well as a short story from each family, bring meaning to the food we eat, the places life brings us, and the memories we share. Sobre este Projecto En el otoño de 2018, 12 de las familias y 32 estudiantes de dos clases, Cruzando Fronteras: Immigración, Identidad, y Desarrollo y Las Historias Immigrantes trabajaron juntos para cear este libro de cocina. Las familias escogieron platos con una importancia o una memoria especial para preparar en sus casas con los estudiantes. Durante el proceso de concinar y comer juntos, los estudiantes anotaron los pasos para preparar la receta. Ellos escucharon las conexiones entre la comida, la memoria, la familia, la migración, las tradiciones, y la religión. Cosechando Memoria, Preservando el Hogar: Un Libro de Cocina de la Granja de la Tortuga Pintada es el fruto de este proyecto. Ofrecemos la collección de recetas además de una historia breve de cada familia, para dar significado a los alimentos que comemos, los lugares donde la vida nos trae, y las memorias que nos compartimos