THE DISTANCE CENTRALITY: MEASURING STRUCTURAL DISRUPTION OF A NETWORK

This research provides an innovative approach to identifying the influence of vertices on the topology of a graph by introducing and exploring the neighbor matrix and distance centrality. The neighbor matrix depicts the “distance profile” of each vertex, identifying the number of vertices at each shortest path length from the given vertex. From the neighbor matrix, we can derive 11 oft-used graph invariants. Distance centrality uses the neighbor matrix to identify how much influence a given vertex has over graph structure by calculating the amount of neighbor matrix change resulting from vertex removal. We explore the distance centrality in the context of three synthetic graphs and three graphs representing actual social networks. Regression analysis enables the determination that the distance centrality contains different information than four current centrality measures (betweenness, closeness, degree, and eigenvector). The distance centrality proved to be more robust against small changes in graphs through analysis of graphs under edge swapping, deletion, and addition paradigms than betweenness and eigenvector centrality, though less so than degree and closeness centralities. We find that the neighbor matrix and the distance centrality reliably enable the identification of vertices that are significant in different and important contexts than current measures.http://archive.org/details/thedistancecentr1094559576Lieutenant Colonel, United States ArmyApproved for public release; distribution is unlimited

Problems or Possibilities? What Do Early Childhood Preservice Teachers Notice About K-1 Writers?

Responding to a writer, a core practice for writing teachers begins when the teacher notices the author of a written product. The purpose of this study was to understand how early childhood (EC) preservice teachers (PSTs) in a literacy methods course noticed the K-1 writers responsible for seven written products. Given the lack of research regarding how PSTs take notice of the writer, this qualitative study adds insight into what EC PSTs identify as significant in young writers’ work. The implications of this study indicate the value in requiring all EC PSTs of writing to complete a teacher preparation course focused on writing. In that course, it would be ideal for PSTs to practice responding to writers. In the absence of writers, teacher educators might use writing samples so that PSTs can approximate responding to writers. As the PSTs come to understand that they are responding to the writer responsible for a writing product, the PSTs might envision ways to nudge forward the writer using encouragement. As a writer’s writing proficiencies are limited [only] by the abilities of teachers to teach [writing] well” (Gallavan & Bowles, 2007, p. 61), continued emphasis on preparing PSTs to attend to the “surplus of possibilities” (Bomer et al., 2019, p. 140) of a writer holds great promise for educating the next generation of writers

PHASER user`s manual version 2.10

PHASER (Probabilistic Hybrid Analytical System Evaluation Routine) is a computer code for solving the top event probability of a system fault tree. It has the capability for easy migration of individual basic event probabilities from a zero-{open_quotes}scale{close_quotes}-factor (completely subjective) state to one in which the analyst has total knowledge (completely stochastic) about each basic event. The code implements a fuzzy algebra solution for subjective data, a probabilistic solution for stochastic data, and a hybrid mathematics solution for data that are partly subjective and partly stochastic. Events that are not completely subjective or completely stochastic are hybrid events and are internally handled as such. The stochastic and fuzzy ranges of uncertainty in the top event probability are also computed for the analyst. These are provided in the form of a fuzzy function for the subjective uncertainty, a probability density function (PDF) for the stochastic variability, and the overall {open_quotes}confidence{close_quotes} factors for the two constituents of uncertainty, giving a complete hybrid result. PHASER interfaces with other Sandia codes (SABLE, LHS and LHSPOST) to assist the user in determining cutsets, and to compute probability density functions

Metabólitos acumulados na acidemia propiônica comprometem a bioenergética mitocondrial e a homeostase do cálcio em coração e rins de ratos

A acidemia propiônica é um erro inato do metabolismo causado pela deficiência na atividade da enzima mitocondrial propionil-CoA-carboxilase (PCC). A doença é bioquimicamente caracterizada por predominante acúmulo de ácido propiônico (PA) no plasma e clinicamente por severa encefalopatia, além de cardiomiopatia e doença renal crônica. Alta excreção urinária dos ácidos 3-hidroxipropiônico (3OHPA), 2-metilcítrico (2MCA) e maleico (MA) também é reportada nos pacientes. Considerando que os mecanismos patogênicos das alterações cardíacas e renais são praticamente desconhecidos nessa doença, a presente tese investigou os efeitos do PA, 3OHPA, MA e 2MCA (0,05 – 5 mM) sobre críticos parâmetros da homeostase mitocondrial bioenergética e do Ca2+ em preparações mitocondriais e homogeneizados obtidos de coração e rim de ratos Wistar jovens (30 dias de vida), bem como em cultura de células cardíacas (H9c2) e renais (HEK-293). Foram determinados os parâmetros respiratórios estado 3 (estimulado por ADP), estado 4 (estimulado por oligomicina), estado desacoplado (estimulado por CCCP) e razão do controle respiratório (RCR), o potencial de membrana (ΔΨm), o conteúdo de NAD(P)H, a capacidade de retenção de Ca2+ e o inchamento mitocondrial. Além disso, foram avaliados a produção de ATP, a atividade de enzimas do ciclo do ácido cítrico e dos complexos da cadeia respiratória. A viabilidade celular também foi investigada após 24 horas de pré-incubação com o PA e MA. Observou-se que o MA inibiu os estados 3, 4 e desacoplado em preparações mitocondriais de coração e rim utilizando principalmente substratos precursores de NADH (glutamato mais malato, piruvato mais malato, glutamato ou α-cetoglutarato) em comparação ao FADH2 (succinato), que foram associados a uma diminuição na produção de ATP. Por outro lado, o PA e o 3OHPA provocaram efeitos inibitórios sobre a respiração mitocondrial mais moderados, enquanto o 2MCA não causou alterações. Os efeitos marcantes causados pelo MA podem estar em parte relacionados à inibição da α-cetoglutarato desidrogenase e glutamato desidrogenase, além de depleção de CoA pois a inibição da respiração mitocondrial causada pelo MA foi parcialmente revertida por suplementação dessa coenzima. Resultados similares foram obtidos em homogeneizados e cultura de células permeabilizadas desses tecidos, corroborando os achados obtidos em mitocôndrias isoladas. Somando-se a isso, o MA, e o PA em menor extensão, reduziram o ΔΨm, o conteúdo de NAD(P)H e a capacidade de retenção de Ca2+, bem como induziram inchamento em preparações mitocondriais de coração e rim na presença de Ca2+. Esses efeitos foram parcial ou totalmente prevenidos por ciclosporina A e ADP, sugerindo que a abertura do poro de transição de permeabilidade (PTP) mitocondrial possa estar envolvido. Finalmente, o MA reduziu a viabilidade e induziu morte em células renais. Analisando em conjunto, os resultados indicam que o MA, além do PA e 3OHPA de forma mais branda, atuam como inibidores metabólicos, bem como o MA e o PA induzem a abertura PTP, em coração e rins, comprometendo dessa forma a homeostase mitocondrial bioenergética e do Ca2+. Portanto, presume-se que uma disfunção mitocondrial causada pelos metabólitos acumulados na acidemia propiônica possa contribuir para a cardiomiopatia e insuficiência renal crônica que se manifestam nos pacientes acometidos por essa doença.Propionic acidemia is an inborn error of metabolism caused by a deficiency in the mitochondrial enzyme propionyl-CoA-carboxylase (PCC) activity. The disease is biochemically characterized by predominant propionic acid (PA) accumulation in plasma and clinically by severe encephalopathy, besides cardiomyopathy and chronic kidney disease. High urinary excretion of 3-hydroxypropionic (3OHPA), 2-methylcitric (2MCA), and maleic (MA) acids is also reported in patients. The pathogenic mechanisms of cardiac and renal alterations are practically unknown in this disease, the present thesis investigated the effects of PA, 3OHPA, MA, and 2MCA (0.05 – 5 mM) on critical parameters of mitochondrial bioenergetics and Ca2+ homeostasis in isolated mitochondria and homogenates obtained from heart and kidney of young Wistar rats (30 days old), as well as from cardiac (H9c2) and renal (HEK-293) cell cultures. The respiratory parameters state 3 (ADP-stimulated), state 4 (oligomycin- stimulated), uncoupled state (CCCP- stimulated) and respiratory control ratio (RCR), membrane potential (ΔΨm), NAD(P)H content, Ca2+ retention capacity, and mitochondrial swelling were determined. In addition, ATP production, citric acid cycle enzymes, and respiratory chain complexes activities were evaluated. Cellular viability was also investigated after 24 hours of pre-incubation with PA and MA. It was observed that MA inhibited states 3, 4 and uncoupled respiration in heart and kidney mitochondria using primarily NADH-linked substrates (glutamate plus malate, pyruvate plus malate, glutamate or α-ketoglutarate) as compared to FADH2 (succinate), which were associated with a decrease in ATP production. PA and 3OHPA caused milder inhibitory effects on mitochondrial respiration, and 2MCA did not cause any changes. The marked effects caused by MA may be related to the inhibition of α-ketoglutarate dehydrogenase and glutamate dehydrogenase, and CoA depletion since the inhibition of mitochondrial respiration caused by MA was partially reversed by supplementation of this coenzyme. Similar results were obtained in tissue homogenates and permeabilized cell cultures, corroborating the findings obtained in isolated mitochondria. In addition, MA, and PA, to a lesser extent, reduced the ΔΨm, NAD(P)H content, Ca2+ retention capacity, and induced swelling in Ca2+-loaded heart and kidney mitochondrial preparations. These effects were partial or totally prevented by cyclosporine A and ADP, suggesting mitochondrial permeability transition (MPT) pore opening may be involved. Finally, MA reduced viability and induced kidney cells death. Taken together, the data indicate that MA, and PA and 3OHPA, to a lesser degree, acts as metabolic inhibitors, as well as MA and PA induce MPT in the heart and kidney, thus compromising mitochondrial energy and Ca2+ homeostasis. Therefore, it is presumed that mitochondrial dysfunction caused by the metabolites accumulated in propionic acidemia may contribute to the cardiomyopathy and chronic renal failure that manifest in patients affected by this disease

Evidence-based commissioning in the English NHS : who uses which sources of evidence? A survey 2010/2011

Objectives: To investigate types of evidence used by healthcare commissioners when making decisions and whether decisions were influenced by commissioners’ experience, personal characteristics or role at work. Design: Cross-sectional survey of 345 National Health Service (NHS) staff members. Setting: The study was conducted across 11 English Primary Care Trusts between 2010 and 2011. Participants: A total of 440 staff involved in commissioning decisions and employed at NHS band 7 or above were invited to participate in the study. Of those, 345 (78%) completed all or a part of the survey. Main outcome measures: Participants were asked to rate how important different sources of evidence (empirical or practical) were in a recent decision that had been made. Backwards stepwise logistic regression analyses were undertaken to assess the contributions of age, gender and professional background, as well as the years of experience in NHS commissioning, pay grade and work role. Results: The extent to which empirical evidence was used for commissioning decisions in the NHS varied according to the professional background. Only 50% of respondents stated that clinical guidelines and cost-effectiveness evidence were important for healthcare decisions. Respondents were more likely to report use of empirical evidence if they worked in Public Health in comparison to other departments (p<0.0005, commissioning and contracts OR 0.32, 95%CI 0.18 to 0.57, finance OR 0.19, 95%CI 0.05 to 0.78, other departments OR 0.35, 95%CI 0.17 to 0.71) or if they were female (OR 1.8 95% CI 1.01 to 3.1) rather than male. Respondents were more likely to report use of practical evidence if they were more senior within the organisation (pay grade 8b or higher OR 2.7, 95%CI 1.4 to 5.3, p=0.004 in comparison to lower pay grades). Conclusions: Those trained in Public Health appeared more likely to use external empirical evidence while those at higher pay scales were more likely to use practical evidence when making commissioning decisions. Clearly, National Institute for Clinical Excellence (NICE) guidance and government publications (eg, National Service Frameworks) are important for decision-making, but practical sources of evidence such as local intelligence, benchmarking data and expert advice are also influential

Emergency first response to a crisis event a multi-agent simulation approach

Homeland Security Presidential Directive #8 led to the establishment of the National Exercise Program and the Top Officials exercise series to test and evaluate first response agency integration and effectiveness. The last TOPOFF exercise cost $16M and involved over 10,000 people, but did not effectively leverage simulation techniques to make efficient use of resources. This research adapts an existing organizational learning process, integrating low- and high resolution simulation to provide decision support. This process led to the development of a multi-agent simulation methodology for emergency first response, specifically applied to analyze a notional vehicle bomb attack during a festival in the Baltimore Inner Harbor. This simulation demonstrates the potential benefits of low resolution simulation, using efficient experimental design and high-performance computing. Combined, these two ideas result in examining a 48-dimensional response surface and using over 156 CPU centuries of computer time. All experiments were completed in less than three weeks. The analysis of this data set provided insight into several areas, including the importance of standing operating procedures in the early moments of a crisis. Analysis showed that effective procedures may even be more important than the effectiveness of communications devices early in a first response operation.http://archive.org/details/emergencyfirstre109452800Outstanding ThesisUS Army (USA) author.Approved for public release; distribution is unlimited.Approved for public release; distribution is unlimited

Implantação da tecnica de detecção de anticorpos antiilhota pancreatica e sua aplicação em pacientes e irmãos de pacientes com diabetes mellitus tipo I

Orientador: Ricardo PasquiniCo-orientador: Luis Fernando Bleggi TorresDissertação (mestrado) - Universidade Federal do Parana, Setor de Ciencias da SaudeResumo: Desde a primeira descrição dos anticorpos citoplasmáticos contra células da ilhota (ICAs) em pacientes com diabetes tipo I, estes marcadores humorais vem sendo progressivamente mais utilizados em investigação clínica. No presente estudo, um método para detecção dos ICAs foi implantado no Hospital de Clínicas da Universidade Federal do Paraná. Os anticorpos foram determinados de acordo com um protocolo padrão, baseado na técnica convencional de imunofluorescência indireta, em cortes de pâncreas humano realizados em criostato. ICAs foram primeiramente pesquisados pesquisando-se 5 pâncreas diferentes e 10 amostras de soro. Através da comparação dos resultados com aqueles obtidos na Universidade de Minnesota, um dos pâncreas foi selecionado para ser usado na segunda parte do estudo. Uma curva padrão foi construída, baseada no título final de diluição obtido neste mesmo pâncreas para diferentes diluições do soro internacional de referência, possibilitando a expressão dos resultados em unidades JDF (Juvenile Diabetes Foundation). A prevalência dos ICAs foi então determinada em cinqüenta crianças e jovens com diabetes tipo I recémdiagnosticado e em 40 irmãos não-afetados de pacientes com diabetes tipo I. A porcentagem encontrada de pacientes com ICAs na instalação do diabetes (66%) se encontra dentro da variação descrita por outros (50-84%). A freqüência relativamente alta de ICAs no grupo de irmãos (5%) exige testes futuros em um número maior de pessoas, com acompanhamento rigoroso.Abstract: Since the first description of cytoplasmic islet cell antibodies (ICA) in type I diabetic patients, these humoral markers have been increasingly applied in clinical investigations. In this study, a method for ICA detection was established at the Hospital de Clínicas of the Universidade Federal do Paraná. These antibodies were determined according to a standard protocol based on the conventional indirect immunofluorescence technique, on cryostat sections of human pancreas. ICA were first determined using 5 different pancreata and 10 serum samples. By comparison of results with those obtained at the University of Minnesota, one of the pancreas was selected to be used in the second part of the study. A standard curve was constructed based on end-point titers obtained on this very pancreas for different dilutions of the international reference serum, making it possible to express the results in JDF (Juvenile Diabetes Foundation) units. The prevalence of ICA was then studied in 50 newly diagnosed children and juveniles with type I diabetes, and in 40 unaffected siblings of type I diabetic patients. The percentage of patients with ICA at the onset of the disease (66%) was within the range reported by others (50-84%). The relatively high frequency of ICA in the group of siblings (5%) demands further testing in a greater number of persons, and close follow-u

Bringing Particle Scale Properties into Descriptions of Powder Behavior through the Enhanced Centrifuge Method

Inconsistent powder behavior introduces problems such as agglomeration, poor flowability, dust hazards, and segregation that decrease efficiency in powder processing environments. Understanding how a powder interacts with a surface at the particle scale provides insight into how to accommodate individual particle properties and avoid process deficiencies. This project uses an enhanced centrifuge technique to evaluate the adhesion between a stainless-steel surface and a powder comprised of fluorescent particles. Particles are deposited onto stainless steel plates which are rotated in a centrifuge. The adhesion properties are monitored by tracking the rotational speed at which particles of a known size are removed from the steel. To model the adhesion, a simulator was produced in MATLAB to map an ideal model to the experimental observations. In reality, the particles and steel are rough, and the particles are nonuniform in shape. The ideal case assumes the particles are smooth spheres and the steel is smooth. A modified van der Waals force model describes the observed forces. Within this model, a Hamaker constant, which usually describes only the effect of composition on the van der Waals force, is tuned to also describe the effects of the non-uniformity of the particles. This creates a distribution of ‘effective Hamaker constants’ that describes particle scale effects on the adhesion between the bulk powder and the stainless steel. This approach will allow industry to account for the effects of surface roughness, particle shape, and particle size when designing powder processing operations