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

Team 2: Situation Awareness of an Infantry Unit in a Chemical Environment

from Scythe : Proceedings and Bulletin of the International Data Farming Community, Issue 2 Workshop 14The German Federal Office of Defense Technology and Procurement has been analyzing the influence of networked sensors and effectors on military capabilities. The background of our overall scenario is peace support operations (PSO) in an urban environment. The background for the actual technical evaluations of sensors, effectors and the connecting network is the following scenario vignette: Convoy Protection

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

Profiling of Phenolic Compounds and Antioxidant Activity of Dry Extracts from the Selected Sorbus Species

The antioxidant efficiency of dry extracts from inflorescences and/or leaves of seven Sorbus species was studied using four in vitro tests of SET (single electron transfer) and HAT-type (hydrogen atom transfer) mechanisms. The 70% methanol extracts and its diethyl ether, ethyl acetate, n-butanol and water fractions were tested in parallel with the phenolic standards, e.g., caffeic acid, quercetin, BHA, BHT, and TroloxÒ. The SET-type activity of the extracts depended primarily on the extraction solvent. The most valuable extracts were n-butanol and ethyl acetate ones, which activity was high in the DPPH (EC50 = 3.2–5.2 μg/mL), TEAC (2.8–4.0 mmol Trolox®/g), and FRAP (9.8–13.7 mmol Fe2+/g) tests, and strongly correlated with the total phenolic levels (39.6–58.2% of gallic acid equivalents). The HPLC-PDA analysis of the extracts led to the identification of chlorogenic acid, isoquercitrin, hyperoside, rutin, quercetin 3-O-sophoroside, and sexangularetin 3-O-b-D-glucopyranoside as the main components. Apart from flavonoids and hydroxycinnamic acids, proanthocyanidins have also a significant impact on the SET-type activity. The HAT-reactivity of the extracts in the linoleic acid peroxidation test (IC50 = 36.9–228.3 μg/mL) depended more strongly on the plant tissue than on the extraction solvent, and its correlation with the phenolic content was weak. Both SET and HAT-type activity of the most potent Sorbus extracts was comparable with the activity of the standards, indicating their great potential as effective sources for health products

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

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

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