CHANGING PARADIGMS IN PREOPERATIVE FASTING: RESULTS OF A JOINT EFFORT IN PEDIATRIC SURGERY.

PubMed

Carvalho, Carlos Augusto Leite de Barros; Carvalho, Augusto Aurélio de; Nogueira, Paulo Luiz Batista; Aguilar-Nascimento, José Eduardo de

2017-01-01

Current researches associate long fasting periods to several adverse consequences. The fasting abbreviation to 2 h to clear liquids associated with the use of drinks containing carbohydrates attenuates endocrinometabolic response to surgical trauma, but often is observed children advised to not intake food from 00:00 h till the scheduled surgical time, regardless of what it is. To evaluate the safety of a protocol of preoperative fasting abbreviation with a beverage containing carbohydrates, and early postoperative feeding in children underwent elective small/mid-size surgical procedures during a national task-force on pediatric surgery. Thirty-six patients were prospectively included, and for several reasons five were excluded. All 31 who remained in the study received a nutritional supplement containing 150 ml of water plus 12.5% maltodextrin 2 h before the procedure. Data of the pre-operative fasting time, anesthetic complications and time of postoperative refeeding, were collected. Twenty-three (74.2%) were males, the median age was 5 y, and the median weight was 20 kg. The median time of pre-operative fasting was 145 min and the time of post-operative refeeding was 135 min. There were no adverse effects on the anesthetic procedures or during surgery. Post-operatively, two children (6.5%) vomited. The abbreviation of pre-operative fasting to 2 h with beverage containing carbohydrate in pediatric surgery is safe. Early refeeding in elective small/mid-size procedures can be prescribed. Trabalhos atuais associam longos períodos de jejum com diversas consequências adversas. A abreviação do jejum de 2 h para líquidos claros associado ao uso de bebidas contendo carboidratos atenua resposta endocrinometabólica ao trauma, porém frequentemente as crianças são orientadas a não ingerir alimentos a partir das 00:00 h do dia anterior à operação, independente do horário do procedimento cirúrgico. Avaliar a segurança de um protocolo de abreviação do jejum pré-operatório, com o uso de bebida contendo carboidratos, e realimentação precoce. Foram avaliados prospectivamente 36 crianças submetidas a procedimentos cirúrgicos eletivos de pequeno e médio porte. Cinco foram posteriormente excluídos do estudo. Todos os 31 remanescentes receberam suplemento nutricional com maltodextrina 12,5% em 150 ml de água aproximadamente 2 h antes do procedimento. Foram coletados dados do tempo de jejum pré-operatório, complicações anestésicas e tempo de realimentação. Vinte e três (74,2%) eram do gênero masculino, com idade mediana de cinco anos e peso mediano de 20 kg. O tempo mediano de jejum pré-operatório foi de 145 min e o tempo mediano para realimentação foi de 135 min. Não houve eventos adversos durante a anestesia ou operação. No período pós-operatório, duas (6,5%) crianças vomitaram. A abreviação de jejum pré-operatório para 2 h com uso de bebida contendo carboidratos, em operações eletivas de crianças, é seguro e não está associado ao maior risco de broncoaspiração pulmonar. Realimentação precoce pode ser prescrita nos procedimentos cirúrgicos analisados.

Asynchronous data acquisition and on-the-fly analysis of dose fractionated cryoEM images by UCSFImage

PubMed Central

Li, Xueming; Zheng, Shawn; Agard, David A.; Cheng, Yifan

2015-01-01

Newly developed direct electron detection cameras have a high image output frame rate that enables recording dose fractionated image stacks of frozen hydrated biological samples by electron cryomicroscopy (cryoEM). Such novel image acquisition schemes provide opportunities to analyze cryoEM data in ways that were previously impossible. The file size of a dose fractionated image stack is 20 ~ 60 times larger than that of a single image. Thus, efficient data acquisition and on-the-fly analysis of a large number of dose-fractionated image stacks become a serious challenge to any cryoEM data acquisition system. We have developed a computer-assisted system, named UCSFImage4, for semi-automated cryo-EM image acquisition that implements an asynchronous data acquisition scheme. This facilitates efficient acquisition, on-the-fly motion correction, and CTF analysis of dose fractionated image stacks with a total time of ~60 seconds/exposure. Here we report the technical details and configuration of this system. PMID:26370395

Continuous Inkjet Printing of Enalapril Maleate onto Orodispersible Film Formulations.

PubMed

Thabet, Yasmin; Lunter, Dominique; Breitkreutz, Joerg

2018-05-10

Piezoelectric inkjet printing onto orodispersible films (ODFs) was proven to be a successful technique applying flexible doses of active pharmaceutical ingredients (APIs) onto edible substrates. The reported API printing and ODF production was conducted in a non-continuous production approach. Within this study, drug-free and hydrochlorothiazide (HCT) containing ODFs should be imprinted in-line with enalapril maleate (EM) ink during continuous ODF production. Macrogol inks based on various solvents and solvent-water mixtures were developed providing dynamic viscosities from 7 to 17 mPa∗s. Water based inks contained 1.25%, methanol based inks up to 10% EM. Both inks could be printed (500-1000 Hz) during continuous ODF production. No EM recrystallization was observed for water-based inks. Mechanical properties were not affected by drug printing using various firing frequencies. ODF imprinted with water-based EM inks contained 0.04 mg EM / 6cm 2 . EM amount can be increased to a paediatric therapeutic dose of 0.5 mg EM utilizing methanol-based inks. These inks were successfully printed onto HCT ODFs resulting in a therapeutically relevant fixed-dose combination. No EM migration into the HCT layer could be observed. In conclusion, it was feasible to print EM doses onto drug-free and HCT ODFs during an in-line continuous manufacturing process. Copyright © 2018 Elsevier B.V. All rights reserved.

Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD.

PubMed

Brown, J T; Abdel-Rahman, S M; van Haandel, L; Gaedigk, A; Lin, Y S; Leeder, J S

2016-06-01

The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 μM*h in EM2s to 5.8 ± 1.7 μM*h, 16.3 ± 2.9 μM*h, and 50.2 ± 7.3 μM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication. © 2015 American Society for Clinical Pharmacology and Therapeutics.

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Assessment of operative times of multiple surgical specialties in a public university hospital.

PubMed

Costa, Altair da Silva

2017-01-01

To evaluate the indicators duration of anesthesia, operative time and time patients stay in the operating rooms of different surgical specialties at a public university hospital. It was done by a descriptive cross-sectional study based on the operating room database. The following stages were measured: duration of anesthesia, procedure time and patient length of stay in the room of the various specialties. We included surgeries carried out in sequence in the same room, between 7:00 a.m. and 5 p.m., either elective or emergency. We calculated the 80th percentile of the stages, where 80% of procedures were below this value. The study measured 8,337 operations of 12 surgical specialties performed within one year. The overall mean duration of anesthesia of all specialties was 178.12±110.46 minutes, and the 80th percentile was 252 minutes. The mean operative time was 130.45±97.23 minutes, and the 80th percentile was 195 minutes. The mean total time of the patient in the operating room was 197.30±113.71 minutes, and the 80th percentile was 285 minutes. Thus, the variation of the overall mean compared to the 80th percentile was 41% for anesthesia, 49% for surgeries and 44% for operating room time. In average, anesthesia took up 88% of the operating room period, and surgery, 61%. This study identified patterns in the duration of surgery stages. The mean values of the specialties can assist with operating room planning and reduce delays. Avaliar os indicadores de tempo da anestesia, da operação e da permanência do paciente em sala de diversas especialidades do centro cirúrgico de um hospital universitário. Foi realizado em estudo descritivo transversal a partir da base de dados do centro cirúrgico e mensuradas as seguintes etapas: duração de anestesia, tempo do procedimento e tempo de permanência do paciente em sala das diversas especialidades. Foram incluídas as operações realizadas em sequência na mesma sala, das 7h às 17h, eletivas ou de urgências. Realizamos o calculo do percentil 80 da duração das etapas, onde 80% dos procedimentos ficaram abaixo deste valor obtido. O estudo incluiu 8.337 operações realizadas no período de 1 ano de 12 especialidades cirúrgicas. A média geral da duração da anestesia de todas as especialidades foi de 178,12±110,46 minutos, e o percentil 80 foi de 252 minutos. A média do tempo operatório foi 130,45±97,23 minutos, e o percentil 80 foi de 195 minutos. A média do tempo total do paciente em sala operatória foi de 197,30±113,71 minutos, e o percentil 80 foi de 285 minutos. A variação da média geral em relação ao percentil 80 foi de 41% na anestesia, 49% nas operações e 44% no tempo de sala. Na média geral, a anestesia ocupou 88% do tempo de sala e a operação, 61%. Este estudo identificou padrões nas durações das etapas das operações. A informação das médias históricas das especialidades pode auxiliar no planejamento do centro cirúrgico e diminuir os atrasos.

Identificabilidade e estabilidade dos parâmetros no método Grade of Membership (GoM): considerações metodológicas e práticas

PubMed Central

Guedes, Gilvan Ramalho; Caetano, André Junqueira; Machado, Carla Jorge; Brondízio, Eduardo Sonewend

2011-01-01

O método Grade of Membership (GoM) tem sido cada vez mais utilizado por demógrafos brasileiros e tem a vantagem de possuir um parâmetro que mensura a heterogeneidade individual, com base nas correlações não-observáveis entre as categorias de resposta das variáveis de interesse, gerando um medida do grau de pertencimento de cada indivíduo a perfis extremos. Alguns autores, contudo, chamam atenção para questões importantes na calibragem dos modelos finais que utilizam o programa GoM versão 3.4, como o problema de identificabilidade – soluções múltiplas para parâmetros estimados. Neste artigo, é sugerido um procedimento capaz de identificar um modelo final com solução única que descreva os tipos puros mais fidedignos à base de dados, em uma tentativa de otimização. Para ilustrar esse processo, utilizou-se uma base de dados correspondente a um levantamento econômico e sociodemográfico de uma população de pequenos agricultores residentes ao longo da Rodovia Transamazônica, no Estado do Pará. Também identificou-se a existência de instabilidade nos parâmetros estimados pelo programa GoM 3.4, sendo proposto um método de estabilização de seus valores. Com esses procedimentos combinados, os usuários do programa GoM 3.4 poderão descrever sua base de dados de forma mais adequada e responder às críticas sobre questões de identificabilidade e estabilidade dos modelos resultantes. Essas soluções empíricas são relevantes por afetarem cálculos de prevalência e de incidência de eventos de interesse, além de trazerem consequências importantes sobre o ponto e o momento corretos para intervenções de políticas públicas ou de planejamento prospectivo em análises de projeção. PMID:21709732

Estimativa de imagens solares soho através de redes neurais artificiais

NASA Astrophysics Data System (ADS)

Andrade, M. C.; Fernandes, F. C. R.; Cecatto, J. R.; Rios Neto, A.; Rosa, R. R.; Sawant, H. S.

2003-08-01

A Rede Neural Artificial (RNA), no âmbito da teoria computacional, constitui uma teoria emergente que, por possuir habilidade em aprender a partir de dados de entrada, encontra diferentes aplicações em diferentes áreas. Um exemplo é a utilização de RNA na caracterização de padrões associados à dinâmica de processos espaço-temporais relacionados a fenômenos físicos não-lineares. Para obter informações sobre o comportamento destes fenômenos físicos utiliza-se, em diversos casos, seqüências de imagens digitalizadas, onde a caracterização de alguns fenômenos espaço-temporais é o procedimento mais viável para descrever a dinâmica das regiões ativas do Sol. Com base em imagens observadas por telescópios a bordo de satélites, estudos de previsão de eventos solares podem ser programados, permitindo prever possíveis efeitos posteriores nas regiões mais próximas da Terra (tempestades geomagnéticas e irregularidades ionosféricas). Neste trabalho avaliamos o desempenho da RNA para estimar padrões espaço-temporais, ou seja, imagens solares em ultravioleta, obtidas através do telescópio a bordo do satélite SOHO. Os resultados mostraram que as RNA conseguem generalizar os padrões de maneira satisfatória sem perder de forma significativa os principais aspectos da configuração global da atmosfera solar, comprovando a eficácia da RNA como ferramenta para esse tipo de aplicação. Portanto, este trabalho comprova a viabilidade de uso desta ferramenta em projetos voltados ao estudo do comportamento solar, em trabalhos do grupo de Física do Meio Interplanetário (FMI) na DAS e em programas desenvolvidos pelo Núcleo de Simulação e Análise de Sistemas Complexos (NUSASC) do Laboratório Associado de Computação e Matemática Aplicada (LAC) do INPE.

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Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.

PubMed

Taylor, Hugh S; Giudice, Linda C; Lessey, Bruce A; Abrao, Mauricio S; Kotarski, Jan; Archer, David F; Diamond, Michael P; Surrey, Eric; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Rowan, Jean P; Duan, W Rachel; Ng, Juki; Schwefel, Brittany; Thomas, James W; Jain, Rita I; Chwalisz, Kristof

2017-07-06

Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).

Embolização arterial superseletiva para tratamento de angiomiolipoma em paciente com rim único

PubMed Central

Góes, Adenauer Marinho de Oliveira; Jeha, Salim Abdon Haber; Salgado, José Rui Couto

2016-01-01

Resumo Os autores relatam o caso de uma paciente jovem previamente submetida a nefrectomia direita por apresentar angiomiolipomas renais (AMLRs) e portadora de dois volumosos angiomiolipomas no rim esquerdo remanescente. A paciente foi encaminhada pelo urologista para tratamento endovascular. Realizou-se embolização superseletiva de um dos tumores, localizado no polo renal inferior e em situação subcapsular; apesar de várias tentativas, não foi obtido um cateterismo seletivo suficiente para embolizar o segundo angiomiolipoma (localizado no polo renal superior) sem que um volume considerável de parênquima renal adjacente sofresse isquemia. O procedimento e a recuperação da paciente transcorreram sem complicações. A paciente recebeu alta no primeiro pós-operatório e vem sendo acompanhada ambulatorialmente há 9 meses sem intercorrências. É feita uma breve revisão sobre indicações, aspectos técnicos e complicações do tratamento endovascular dos AMLRs, além de serem discutidas vantagens dessa técnica quando comparada à ressecção cirúrgica dos tumores. PMID:29930580

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Reduced suppression of CO2-induced ventilatory stimulation by endomorphins relative to morphine.

PubMed

Czapla, Marc A; Zadina, James E

2005-10-19

Opioids are among the most effective analgesics, but a major limitation for their therapeutic usefulness is their induction of respiratory depression. Endomorphin-1 (EM1), in contrast to several other mu opioids, exhibits a threshold for respiratory depression that is well above its threshold for analgesia. Its effect on sensitivity to CO(2), however, remains unknown. Minute ventilation (V(E)) in 2, 4, and 6% CO(2) was measured before and after systemic administration of EM1, endomorphin-2 (EM2), DAMGO, and morphine in the conscious rat. EM1 and EM2 attenuated the hypercapnic ventilatory response (HCVR) only in high doses, while DAMGO and morphine diminished the HCVR in much lower doses. The ventilatory effects of high doses of all 4 agonists were blocked by the mu-opioid antagonist naloxone (0.4 mg/kg i.v.), but not by the peripherally restricted mu-opioid antagonist, methyl-naloxone (0.4 mg/kg i.v.). It was concluded that the endomorphins attenuated the HCVR only in large doses, well beyond the analgesic threshold, and did so through a centrally mediated mu-opioid mechanism.

Otimização de procedimento de manobra para indução de reentrada de um satélite retornável

NASA Astrophysics Data System (ADS)

Schulz, W.; Suarez, M.

2003-08-01

Veículos espaciais que retornam à Terra passam por regimes de velocidade e condições de vôo distintos. Estas diferenças dificultam sua concepção aerodinâmica e o planejamento de seu retorno. A partir de uma proposta de um veículo orbital retornável (satélite SARA, em desenvolvimento no IAE/CTA) para realização de experimentos científicos e tecnológicos em ambiente de baixa gravidade, surge a necessidade de realizarem-se estudos considerando-se os aspectos relativos à sua aerodinâmica. Após o lançamento, o veículo deve permanecer em órbita pelo tempo necessário para a condução de experimentos, sendo depois direcionado à Terra e recuperado em solo. A concepção aerodinâmica é de importância para o vôo em suas diversas fases e deve considerar aspectos relativos à estabilização Aerodinâmica e ao arrasto atmosférico, sendo este último de importância crucial na análise do aquecimento a ser enfrentado. A manobra de retorno inclui considerações sobre as condições atmosféricas e dinâmica de reentrada, devendo ser calculada de forma mais precisa possível. O trabalho proposto avalia estudos da dinâmica de vôo de um satélite recuperável considerando aspectos relativos à determinação orbital com GPS, técnica utilizada com sucesso na CONAE, e seu comportamento aerodinâmico em vôo balístico de retorno, com ênfase em sua fase de reentrada atmosférica. Busca-se otimizar a manobra de reentrada de tal forma que a utilização do sistema GPS garanta minimizar a área de impacto com o solo.

Astronomia cultural e meio ambiente segundo uma abordagem holística

NASA Astrophysics Data System (ADS)

Jafelice, L. C.

2003-08-01

Neste trabalho ampliamos a discussão da abordagem holística para o ensino de astronomia que temos desenvolvido nos últimos anos, analisamos novos resultados e apresentamos exemplos práticos para interessados em experimentá-la. A constatação básica a orientar este enfoque é que cursos introdutórios em astronomia costumam ser excessiva e prematuramente técnicos, além de assumirem uma visão tradicional, muito estreita, do que seja educação científica, herdada da era cartesiana e positivista da ciência. Fundamentamos porque é importante que elementos de astronomia cultural ofereçam o mote e constituam o eixo norteador daqueles cursos e porque é urgente revermos a visão que temos da relação entre astronomia e meio ambiente. Um ponto central nesta abordagem é explorar formas de reativar e atualizar uma relação orgânica com o meio e excitar a consciência de nossa inevitável e profunda interdependência com ele em nível cósmico. Neste trabalho exemplificamos a possibilidade de concretização desta proposta em três diferentes situações: disciplinas de cursos de licenciatura em geografia e em física; escolas de nível fundamental; e, neste caso ainda a ser implementada, comunidades carentes. Estes casos envolvem públicos e espaços diferenciados para educação formal e não-formal. Dos casos já implementados, destacamos os resultados alcançados pelos alunos: enriquecimento cultural, aprendizagem significativa de conteúdos astronômicos tradicionais; mudanças de comportamento, incorporando contato diário com o céu; e freqüentes vivências de sentimentos empáticos que redirecionam a relação com a natureza e a consciência ecológica global. Além disto, para interessados em aplicar esta proposta, também socializamos procedimentos e cuidados para a implementação de ações alternativas consonantes com a mesma. (PPGECNM/UFRN; PRONEX/FINEP; NUPA/USP; Temáticos/FAPESP)

Profilaxia da trombose venosa profunda em cirurgia bariátrica: estudo comparativo com doses diferentes de heparina de baixo peso molecular

PubMed Central

Goslan, Carlos José; Baretta, Giórgio Alfredo Pedroso; de Souza, Hemuara Grasiela Pestana; Orsi, Bruna Zanin; Zanoni, Esdras Camargo A.; Lopes, Marco Antonio Gimenez; Engelhorn, Carlos Alberto

2018-01-01

Resumo Contexto A cirurgia bariátrica é considerada a melhor opção para o tratamento da obesidade, cujos pacientes são considerados de alto risco para fenômenos tromboembólicos. Objetivos Comparar o uso de doses diferentes de heparina de baixo peso molecular (HBPM) na profilaxia da trombose venosa profunda (TVP) em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, alteração na dosagem do fator anti-Xa e sangramento pré ou pós-operatório. Métodos Estudo comparativo transversal em pacientes submetidos à cirurgia bariátrica distribuídos em dois grupos, que receberam doses de HBPM de 40 mg (grupo controle, GC) e 80 mg (grupo de estudo, GE). Foram avaliados por ultrassonografia vascular e dosagem de KPTT, TAP, plaquetas e fator anti-Xa. Resultados Foram avaliados 60 pacientes, sendo 34 no GC e 26 no GE. Foi observada diferença significativa somente no peso (p = 0,003) e índice de massa corporal (p = 0,018) no GE em relação ao GC. Não houve diferença na dosagem de KPTT, TAP, plaquetas e fator anti-Xa entre os grupos. Não foram detectados TVP ou sangramentos significativos em ambos os grupos. Conclusões Não houve diferença estatisticamente significativa na utilização de doses maiores de HBPM na profilaxia da TVP em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, dosagem do fator anti-Xa e sangramento pré ou pós-operatório.

Comparison of the effects of the antiestrogens EM-800 and tamoxifen on the growth of human breast ZR-75-1 cancer xenografts in nude mice.

PubMed

Couillard, S; Gutman, M; Labrie, C; Bélanger, A; Candas, B; Labrie, F

1998-01-01

Although estrone supplementation in ovariectomized (OVX) nude mice bearing ZR-75-1 xenografts caused a 365% increase in average tumor size during the 4-month treatment period, administration of the antiestrogen EM-800 at the daily oral doses of 50, 150, or 400 microg completely prevented estrogen-stimulated tumor growth. At the same doses of tamoxifen, tumor size was inhibited to 189, 117, and 120% above pretreatment values. However, when EM-800 (150 microg/day) was added to the daily 150- and 400-microg doses of tamoxifen, final tumor size was decreased further to 12 and 38% above pretreatment values, respectively. EM-800 (400 microg daily) administered to estrone-supplemented OVX mice caused complete, partial, and stable responses in 11, 22, and 49% of estrone-stimulated tumors, respectively, whereas 19% (7 of 37) progressed. At the same dose of tamoxifen, the corresponding responses were 3% (complete response), 3% (partial response), and 25% (no change), whereas 69% (22 of 32) of tumors progressed. In the absence of estrone supplementation, tamoxifen (400 microg) alone administered to OVX mice stimulated tumor growth to 161% compared with initial size whereas the same dose of EM-800 reduced tumor size by 55%, a value superimposable to that observed in OVX control animals. The agonistic effect of tamoxifen is thus illustrated by the observation that 73% of tumors progressed when tamoxifen was administered alone to OVX animals whereas no tumor progressed with EM-800. The present data strongly suggest that at least part of the initial lack of response and resistance to tamoxifen during tamoxifen treatment in women is due to the estrogenic activity of this compound, whereas the new antiestrogen EM-800 exerts pure antagonistic action.

Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.

PubMed

Tuboly, Gabor; Mecs, Laszlo; Benedek, György; Horvath, Gyöngyi

2009-04-01

1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.

Observações no âmbito dos "additional programs" do satélite COROT

NASA Astrophysics Data System (ADS)

Janot Pacheco, E.

2003-08-01

O satélite Fraco-europeu COROT fará fotometria de altissima precisão (pretende-se atingir uma parte em um milhão), grande campo (3x3 graus) e por longos períodos, de duas regiões pré-determinadas do céu, com 10 graus de raio. Suas finalidades básicas serão estudos em sismologia estelar e a procura de exoplanetas. A comunidade astronômica brasileira participará dessa missão espacial, com direitos iguais aos dos parceiros europeus. Isso se deve a que o satélite utilizará a estação de recepção de dados de Natal (INPE), 5 a 6 brasileiros participarão das equipes de software e cientistas do país atuarão na fase de pré-lançamento. Apresentamos nesta comunicação sugestões para a preparação de propostas de observações com COROT, no âmbito dos Programas Adicionais, que contemplam outros projetos que não de sismologia ou exoplanetas. As últimas definições técnicas e decisões tomadas na 4th Corot Week de junho último serão igualmente apresentadas, em particular quanto às regiões de observação escolhidas e quanto aos procedimentos a seguir para se propor observações.

Flexible and precise dosing of enalapril maleate for all paediatric age groups utilizing orodispersible minitablets.

PubMed

Thabet, Yasmin; Walsh, Jennifer; Breitkreutz, Joerg

2018-04-25

Enalapril is an off-patent angiotensin-converting enzyme inhibitor for which no paediatric age-appropriate formulation is commercially available in Europe, and enalapril maleate (EM) orodispersible minitablets (ODMTs) have previously been formulated within the LENA (labelling enalapril from neonates to adolescents) project. In this study, a dilution method has been developed by dispersing the lowest dose strength ODMTs to enable flexible and precise EM dosing during the dose titration phase of the therapy. Furthermore, the physicochemical stability of the ODMTs has been investigated in child-friendly beverages and the administration of ODMTs via nasogastric tubes (NGT) of different sizes and materials has been evaluated. The results for the ODMT dilution procedure reveal that dispersion within an oral syringe is preferred over dispersion in a separate container, leading to flexible and precise dosing down to 0.025 mg EM. Although ODMTs were stable in the beverages over the investigated time period, dispersion in tap water only is recommended due to prolonged disintegration times within the other beverages. Dispersed ODMTs can be administered through NGTs of CH5. Almost no adsoprtion of EM on silicone, polyurethane or polyvinyl chloride could be observed. The ODMT concept together with the investigated dispersion method enables the safe administration of EM for all paediatric subpopulations from new-borns to adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunogenetic Risk and Protective Factors for Development of L-tryptophan-associated Eosinophilia-Myalgia Syndrome and Associated Symptoms

PubMed Central

Okada, Satoshi; Kamb, Mary L.; Pandey, Janardan P.; Philen, Rossanne M.; Love, Lori A.; Miller, Frederick W.

2009-01-01

Objective To assess L-tryptophan (LT) dose, age, gender and immunogenetic markers as possible risk or protective factors for development of LT-associated eosinophilia myalgia syndrome (EMS) and related clinical findings. Methods HLA DRB1 and DQA1 allele typing and GM/KM phenotyping were performed on a cohort of 94 Caucasian subjects with documented LT ingestion and standardized evaluations. Multivariate analyses compared LT dose, age, gender and alleles among groups of subjects who ingested LT and subsequently developed surveillance criteria for EMS (EMS), or developed EMS or characteristic features of EMS (EMS spectrum disorder), or developed no features of EMS (unaffected). Results Considering all sources of LT, higher LT dose (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.8), age >45 years (OR 3.0, CI 1.03-8.8) and HLA DRB1*03 (OR 3.9, CI 1.2-15.2), DRB1*04 (OR 3.9, CI 1.1-16.4) and DQA1*0601 (OR 13.7, CI 1.3-1874) were risk factors for the development of EMS, while DRB1*07 (OR 0.12, CI 0.02-0.48) and DQA1*0501 (OR 0.23, CI 0.05-0.85) were protective. Similar risk and protective factors were seen for developing EMS following ingestion of implicated LT, except DRB1*03 was not a risk factor and DQA1*0201 was an additional protective factor. EMS spectrum disorder also showed similar findings, but with DRB1*04 being a risk factor and DRB1*07 and DQA1*0201 being protective. There were no differences in gender distribution, GM/KM allotypes or GM/KM phenotypes among any groups. Conclusion In addition to the xenobiotic dose and subject age, polymorphisms in immune response genes may underlie the development of certain xenobiotic-induced immune-mediated disorders and these findings may have implications for future related epidemics. PMID:19790128

Electron Microscopy.

ERIC Educational Resources Information Center

Beer, Michael

1980-01-01

Reviews technical aspects of structure determination in biological electron microscopy (EM). Discusses low dose EM, low temperature microscopy, electron energy loss spectra, determination of mass or molecular weight, and EM of labeled systems. Cites 34 references. (CS)

BIODEGRADABLE BILIARY STENTS: A NEW APPROACH FOR THE MANAGEMENT OF HEPATICOJEJUNOSTOMY STRICTURES FOLLOWING BILE DUCT INJURY. PROSPECTIVE STUDY.

PubMed

Giménez, Mariano E; Palermo, Mariano; Houghton, Eduardo; Acquafresca, Pablo; Finger, Caetano; Verde, Juan M; Cúneo, Jorge Cardoso

2016-01-01

Once a biliary injury has occurred, repair is done by a hepaticojejunostomy. The most common procedure is to perform a dilatation with balloon with a success of 70 %. Success rates range using biodegradable stents is from 85% to 95%. Biodegradable biliary stents should change the treatment of this complication. To investigate the use of biodegradable stents in a group of patients with hepaticojejunonostomy strictures. In a prospective study 16 biodegradable stents were placed in 13 patients with hepaticojejunostomy strictures secondary to bile duct repair of a biliary surgical injury. Average age was 38.7 years (23-67), nine were female and four male. All cases had a percutaneous drainage before at the time of biodegradable stent placement. In one case, temporary haemobilia was present requiring blood transfusion. In another, pain after stent placement required intravenous medication. In the other 11 patients, hospital discharge was the next morning following stent placement. During the patient´s follow-up, none presented symptoms during the first nine months. One patient presented significant alkaline phosphatase elevation and stricture recurrence was confirmed. One case had recurrence of cholangitis 11 months after the stent placement. 84.6% continued asymptomatic with a mean follow-up of 20 months. The placement of biodegradable stents is a safe and feasible technique. Was not observed strictures caused by the stent or its degradation. It could substitute balloon dilation in strictures of hepaticojejunostomy. Uma vez que lesão biliar ocorreu, o reparo é feito por hepaticojejunostomia. O procedimento mais comum é efetuar dilatação com balão com sucesso de 70%. As taxas de sucesso utilizando stents biodegradáveis ​​é de 85% a 95%. Stents biliares biodegradáveis ​​devem mudar o tratamento desta complicação. Investigar o uso de stents biodegradáveis em um grupo de pacientes com estenose hepaticojejunal. Em estudo prospectivo 16 stents biodegradáveis ​​foram colocados em 13 pacientes com estenose de hepaticojejunostomia secundárias usados para reparação do ductos biliares de lesão cirúrgica. A média de idade foi de 38,7 anos (23-67), nove pacientes eram homens e quatro mulheres. Todos os casos tiveram drenagem percutânea antes do momento da colocação de stent biodegradável. Em um caso, haemobilia temporária estava presente com necessidade de transfusão de sangue. Em outro, dor após a colocação do stent necessitou de medicação intravenosa. Nos outros 11 pacientes, alta hospitalar foi na manhã seguinte após o procedimento. Durante o seguimento, nenhum apresentou sintomas durante os primeiros nove meses. Um paciente apresentou significativa elevação da fosfatase alcalina por recidiva da estenose. Um caso teve recorrência de colangite 11 meses após a colocação do stent. Continuaram assintomáticos 84,6% com média de acompanhamento de 20 meses. A colocação de stents biodegradáveis ​​é técnica segura e viável. Não foram observadas restrições causadas pelo stent ou pela sua degradação. Stent pode substituir dilatação com balão na estenose de hepaticojejunostomia.

Baclofen for alcohol dependence: Relationships between baclofen and alcohol dosing and the occurrence of major sedation.

PubMed

Rolland, Benjamin; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Gautier, Sophie; Auffret, Marine; Pignon, Baptiste; Valin, Thomas; Bordet, Régis; Cottencin, Olivier

2015-10-01

High-dose baclofen, i.e., 300 mg/d or more, has recently emerged as a strategy for treating alcohol dependence. The impact that the co-exposure of large amounts of alcohol and baclofen has on sedation is unclear. In a prospective cohort of 253 subjects with alcohol dependence, we collected daily alcohol and baclofen doses across the first year of baclofen treatment and the monthly maximum subjective sedation experienced by each patient (0-10 visual analog scale). For each patient-month, we determined the average weekly alcohol consumption (AWAC; standard-drinks/week) and the maximum daily dose of baclofen (DDB; mg/d). The occurrence of an episode of major sedation (EMS) during a patient-month was defined as a sedation score ≥7. The relationship between the EMS occurrence and the concurrent AWAC and DDB was investigated using a generalized estimating equation model. In total, 1528 patient-months were compiled (70 with an EMS). Univariate analyses demonstrated that the rate of patient-month to EMS increased gradually with AWAC (p<0.001), from 0.9% for AWAC=0 to 9.4% for AWAC >35. There was also a significant gradual risk for EMS associated with DDB (<0.001). Multivariate analysis demonstrated a significant interaction between DDB and AWAC on EMS risk (p=0.047). Each 20mg/d increase in DDB was associated with an OR of EMS in AWAC >35 of 1.22 (95%CI, 1.08-1.38) versus 1.11 (95%CI, 0.96-1.29) in AWAC=1-35, and 0.95 (95%CI, 0.76-1.19) in AWAC=0. The level of sedation observed in patients using baclofen for alcohol dependence appears to directly depend on the immediate doses of both the baclofen and the alcohol. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

PubMed Central

2017-01-01

Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

PubMed

Kim, Da Hee; Seong, Seok Ju; Kim, Mi Kyoung; Bae, Hyo Sook; Kim, Mi La; Yun, Bo Seong; Jung, Yong Wook; Shim, Jeong Yun

2017-01-01

To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

General 4-week toxicity study with EMS in the rat.

PubMed

Pfister, Thomas; Eichinger-Chapelon, Anne

2009-11-12

In this subacute toxicity study, ethyl methanesulfonate (EMS) was administered daily by oral gavage to SPF-bred Wistar rats of both sexes at dose levels of 20, 60 and 180/120 mg/kg body weight (bw)/day for a period of 28 days (for 19 days in the high-dose group). A control group was treated similarly with the vehicle, bidistilled water, only. The groups comprised 10 animals per sex, which were sacrificed after 28 days, respectively 19 days in the high-dose group, of treatment. Additional five rats per sex and group were treated accordingly and then allowed a 14 days treatment-free recovery period. Additional six rats per sex and group (three rats per sex in the control group) were treated accordingly and used for hemoglobin adduct analysis after EMS exposure. All animals survived until their scheduled necropsy. Treatment with EMS had a direct dose-dependent effect on food consumption and consequently on body weight at doses > or =20mg/kgbw/day in male rats and at > or =60 mg/kgbw/day in females rats. Hence, treatment with the high dose of 180 mg/kgbw/day had to be interrupted for 9 days after which, the animals were re-dosed at 120 mg/kgbw/day. This dose was also poorly tolerated over the remaining two treatment weeks causing again a marked reduction in food consumption and body weight. A dose of 60 mg/kgbw/day was moderately tolerated over 4 weeks treatment with mean daily food consumption and body weight distinctly lower than in controls. Primary targets of systemic toxicity were the hematopoietic system, thymolymphatic system and sexual organs. Characteristic changes in hematology parameters were decreased red blood cell counts, hematocrit, and hemoglobin concentration. White blood cell counts were also decreased due to reduced lymphocyte and granulocyte populations of each fraction. The corresponding histopathology findings were fatty atrophy of bone marrow and minimal hypocellularity of the white pulp of the spleen. Similarly, treatment with EMS caused an involution of the thymolymphatic system characterized by decreased organ weight of thymus, lymph nodes, and spleen microscopically associated with atrophy of the thymus and hypocellularity of Peyer's patches, lymph nodes and the white pulp of the spleen. The effects on sexual organs included lower organ weight/reduced size for testes, epididymides, seminal vesicles, prostate, and uterus. Tubular atrophy, single cell necrosis of the germ cells and in epididymides reduced spermatozoa were recorded microscopically. The described findings occurred at doses of 60 and 180/120 mg/kgbw/day and were dose-dependent with regard to incidence and severity. Other target organs were the pancreas (acinar cell vacuolation), thyroid gland (follicular cell hypertrophy), and salivary gland (secretory depletion of convoluted ducts). The systemic exposure to EMS was monitored by hemoglobin ethylvaline adduct measurement. The concentration of hemoglobin ethylvaline adducts was linear with the dose and accumulated 11-26-fold over the treatment period. In summary, decreases in food consumption and body weight were the dose-limiting effects of treatment with EMS. Organ toxicity was characterized by depression of cell proliferation (hematopoiesis and spermatogenesis) and changes suggestive of reduced metabolism and/or physiological imbalances (e.g. thymolymphatic system and thyroid gland) without signs of inflammatory or necrotic lesions. For some findings, especially the effects on the thymolymphatic system and sexual organs, it cannot be excluded that starvation-like condition contributed to the occurrence of such changes. The low dose of 20 mg/kgbw/day was basically free of adverse effects despite of a clear evidence for hemoglobin adducts.

Differential cardiorespiratory effects of endomorphin 1, endomorphin 2, DAMGO, and morphine.

PubMed

Czapla, M A; Gozal, D; Alea, O A; Beckerman, R C; Zadina, J E

2000-09-01

The novel endogenous mu-opioid receptor (MOR) agonists endomorphin 1 (EM1) and 2 (EM2) were tested for their cardiorespiratory effects in conscious, freely behaving rats. After systemic (intravenous) administration of EM1, EM2, or the selective MOR agonist DAMGO, analgesia, minute ventilation (V E), heart rate (HR) and mean arterial blood pressure (BP) were measured. The threshold dose for analgesia was similar for all 3 peptides ( approximately 900 nmol/kg). All 3 compounds elicited biphasic V E responses, with marked, short-lived V E depressions (4-6 s) followed by more sustained V E increases (10-12 min). However, compared with responses elicited by EM2 or DAMGO, EM1 decreased V E only at higher doses, and produced greater V E stimulation. Morphine produced a V E decrease, but no subsequent V E increase. EM2 and DAMGO decreased HR and BP, while EM1 decreased HR, but did not decrease BP in conscious rats at doses up to 9,600 nmol/kg. In anesthetized rats, all 3 peptides decreased HR and BP. The decreases in V E, HR, and BP were blocked by the MOR antagonist, naloxone HCI (NIx). Only the HR and BP responses, however, were blocked by naloxone-methiodide (MeNIx), indicating central mediation of V E responses and peripheral mediation of cardiovascular responses. We conclude that MOR-selective compounds vary in their cardiorespiratory response characteristics which could be linked to differential cellular actions. The results support the concept that the analgesic, respiratory, and cardiovascular effects of MOR agonists can be dissociated and that EM1-like compounds could provide the basis for novel, safer analgesics.

A Dose-Rate Effect in Single-Particle Electron Microscopy

PubMed Central

Chen, James Z.; Sachse, Carsten; Xu, Chen; Mielke, Thorsten; Spahn, Christian M. T.; Grigorieff, Nikolaus

2008-01-01

A low beam-intensity, low electron-dose imaging method has been developed for single-particle electron cryo-microscopy (cryo-EM). Experiments indicate that the new technique can reduce beam-induced specimen movement and secondary radiolytic effects, such as “bubbling”. The improvement in image quality, especially for multiple-exposure data collection, will help single-particle cryo-EM to reach higher resolution. PMID:17977018

A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low-dose tamoxifen.

PubMed

Johansson, Harriet; Gandini, Sara; Serrano, Davide; Gjerde, Jennifer; Lattanzi, Monia; Macis, Debora; Guerrieri-Gonzaga, Aliana; Aristarco, Valentina; Mellgren, Gunnar; Lien, Ernst; DeCensi, Andrea; Bonanni, Bernardo

2016-08-01

Decreased CYP2D6 activity is associated with lower levels of active tamoxifen metabolites. We examined the impact of CYP2D6 genotype on tamoxifen pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low-dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose (1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n = 171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced (IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN) enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles) versus slow metabolizers (PM/IM or PM/PM) were investigated through random effects models, with 'study' as the random factor, and Cox regression models, adjusting for confounders. Rapid metabolizers had higher endoxifen levels than slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8 versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels, demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a median follow-up of 12 years, rapid metabolizers with prior history of breast neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6 genotype may have an impact on tamoxifen efficacy at low doses. Trials investigating tamoxifen dose adjustments based on the woman's hormonal context and CYP2D6 genotype are warranted.

Exposures involving perturbations of the EM field have non-linear effects on radiation response and can alter the expression of radiation induced bystander effects

NASA Astrophysics Data System (ADS)

Mothersill, Carmel; Seymour, Colin

2012-07-01

Our recent data suggest there is a physical component to the bystander signal induced by radiation exposure and that alternative medicine techniques such as Reiki and acupuncture or exposures to weak EM fields alter the response of cells to direct irradiation and either altered bystander signal production or altered the response of cells receiving bystander signals. Our proposed mechanism to explain these findings is that perturbation of electromagnetic (EM) fields is central to the induction of low radiation dose responses especially non-targeted bystander effects. In this presentation we review the alternative medicine data and other data sets from our laboratory which test our hypothesis that perturbation of bio-fields will modulate radiation response in the low dose region. The other data sets include exposure to MRI, shielding using lead and or Faraday cages, the use of physical barriers to bystander signal transmission and the use of membrane channel blockers. The data taken together strongly suggest that EM field perturbation can modulate low dose response and that in fact the EM field rather than the targeted deposition of ionizing energy in the DNA may be the key determinant of dose response in a cell or organism The results also lead us to suspect that at least when chemical transmission is blocked, bystander signals can be transmitted by other means. Our recent experiments suggest light signals and volatiles are not likely. We conclude that alternative medicine and other techniques involving electromagnetic perturbations can modify the response of cells to low doses of ionizing radiation and can induce bystander effects similar to those seen in medium transfer experiments. In addition to the obvious implications for mechanistic studies of low dose effects, this could perhaps provide a novel target to exploit in space radiation protection and in optimizing therapeutic gain during radiotherapy.

Dose-response relationships of rabeprazole 5, 10, 20, and 40 mg once daily on suppression of gastric acid secretion through the night in healthy Japanese individuals with different CYP2C19 genotypes.

PubMed

Hayato, Seiichi; Hasegawa, Setsuo; Hojo, Seiichiro; Okawa, Hiroki; Abe, Hiroaki; Sugisaki, Nobuyuki; Munesue, Masahiro; Horai, Yukio; Ohnishi, Akihiro

2012-05-01

This study was designed to investigate the antisecretory activity of rabeprazole administered once daily in doses of 5, 10, 20, and 40 mg and different cytochrome P450 2C19 (CYP2C19) genotypes on gastric pH in healthy individuals. Additional objectives were delineating the nighttime from the daytime effect and determining the relationships between the pharmacokinetics and pharmacodynamics of rabeprazole. Eight individuals of each of the three genotypes of CYP2C19-homozygous extensive metabolizers (homo-EMs), heterozygous EMs (hetero-EMs), and poor metabolizers (PMs)-were recruited. Twenty-four individuals received a once-daily dose, with dosing interval 24 h of 5, 10, 20, or 40 mg rabeprazole for 5 days in a 4-period crossover fashion. Twenty-four-hour intragastric pH and plasma rabeprazole concentrations were determined on day 5. A dose-dependent increase in median pH and in pH 4 holding time was observed across all CYP2C19 genotypes. When rabeprazole was increased from 20 mg to 40 mg, the differences and 95% confidence intervals (CIs) of nighttime pH 4 holding time between 40 mg and 20 mg in homo-EMs, hetero-EMs, and PMs were 8.0% (-5.0% -21.0%), 28.7% (15.7% -41.6%), and 16.9% (3.9% -29.9%), respectively. The relationship between the area under the plasma concentration-time curve up to the last time point at which rabeprazole was quantifiable (AUC(0-t)) and the pH 4 holding time could be described using a sigmoid maximum effect (E(max)) model. Our data demonstrate that increasing rabeprazole dose up to 40 mg once daily results in an increasing pharmacodynamic effect, which is most apparent for the control of nocturnal gastric acid secretion.

Robust EM Continual Reassessment Method in Oncology Dose Finding

PubMed Central

Yuan, Ying; Yin, Guosheng

2012-01-01

The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To overcome these limitations, we naturally treat the unobserved toxicity outcomes as missing data, and use the expectation-maximization (EM) algorithm to estimate the dose toxicity probabilities based on the incomplete data to direct dose assignment. To enhance the robustness of the design, we propose prespecifying multiple sets of toxicity probabilities, each set corresponding to an individual CRM model. We carry out these multiple CRMs in parallel, across which model selection and model averaging procedures are used to make more robust inference. We evaluate the operating characteristics of the proposed robust EM-CRM designs through simulation studies and show that the proposed methods satisfactorily resolve both limitations of the CRM. Besides improving the MTD selection percentage, the new designs dramatically shorten the duration of the trial, and are robust to the prespecification of the toxicity probabilities. PMID:22375092

Diabetes attenuates the inhibitory effects of endomorphin-2, but not endomorphin-1 on gastrointestinal transit in mice.

PubMed

Wang, Chang-lin; Diao, Yu-xiang; Xiang, Qiong; Ren, Yu-kun; Gu, Ning

2014-09-05

Diabetes affects the entire gastrointestinal tract from the esophagus to the anus. In the present study, the charcoal meal test was undertaken to evaluate and compare the effects of intracerebroventricular (i.c.v.) administration of endomorphins (EMs) on gastrointestinal transit in non-diabetic and diabetic mice. Significantly delayed gastrointestinal transit was found in both 4 and 8 weeks alloxan-induced diabetes compared to non-diabetes. Moreover, i.c.v. EM-1 and EM-2 dose-dependently delayed gastrointestinal transit in non-diabetes and diabetes. The EM-1-induced inhibitory effects of gastrointestinal transit in 4 weeks diabetes were qualitatively similar to those of non-diabetes. However, at higher doses, the EM-1-induced effects in 8 weeks diabetes were largely enhanced. Different to EM-1, the EM-2-induced inhibition of gastrointestinal transit in diabetic mice was significantly attenuated compared to non-diabetic mice. Moreover, these effects were further decreased in 8 weeks diabetes. The delayed gastrointestinal transit effects caused by EM-1 may be primarily mediated by μ2-opioid receptor in both non-diabetes and 4 weeks diabetes. Interestingly, in 8 weeks diabetes, these effects were mediated by μ2- and δ-receptors. However, the inhibitory effects of EM-2 were mediated by μ1-opioid receptor, which exerted a reduced function in diabetes. Also, poor blood glucose control might result in the attenuated effects of EM-2. Our present results demonstrated that diabetes attenuates the inhibitory effects of EM-2, but not EM-1 on gastrointestinal transit in mice. The different effects of EM-1 and EM-2 on gastrointestinal transit in diabetes may be due to changes of opioid receptor subtypes and their functional responses. Copyright © 2014 Elsevier B.V. All rights reserved.

Pediatric vascular trauma in Manaus, Amazon - Brazil.

PubMed

Costa, Cleinaldo DE Almeida; Souza, José Emerson Dos Santos; Araújo, Antônio Oliveira DE; Melo, Flávio Augusto Oliva; Costa, Isabelle Nascimento; Klein, Paulo Henrique

2016-01-01

to assess the incidence of pediatric vascular injuries in patients treated at the Emergency Room of the Eastern Children's Hospital, in Manaus. we conducted a retrospective study of pediatric patients who suffered vascular injuries treated between February 2001 to February 2012. we studied 71 patients, predominantly male (78.87%), with a mean age of 7.63 years. The predominant mechanism of injury was stab wound in 27 patients (38.03%). The average hospital stay was 10.18 days; 16 patients required care in intensive care unit, with average stay of 8.81 days. The main injuries occurred in the extremities, the upper limb being the most affected, with lesions of the ulnar artery in 13 (15.66%) and radial in 10 (12.04%). The mostly applied procedure was vascular exploration 35 (32.4%). Complications occurred in nine patients (12.68%). Mortality was 1.4%, in one patient with a lesion of the common iliac vein and the inferior vena cava due fall from height. pediatric vascular injury occurred predominantly in the extremities. The dimensions of the injured vessels made surgical correction more complex and increased complication rates, particularly amputations. avaliar a incidência de traumatismos vasculares pediátricos em doentes atendidos no Hospital Pronto Socorro da Criança Zona Leste, na cidade de Manaus. estudo retrospectivo de doentes pediátricos vítimas de traumatismos vasculares atendidos no período de fevereiro de 2001 a fevereiro de 2012. foram estudados 71 doentes com predominância do sexo masculino (78,87%) com média de idade de 7,63 anos. O mecanismo de trauma predominante foi o ferimento por arma branca em 27 pacientes (38,03%). A média de internação foi 10,18 dias, com 16 doentes necessitando de cuidados em unidade de tratamento intensivo com permanência média de 8,81 dias. As principais lesões ocorreram em extremidades, com predomínio do membro superior, com lesões das artérias ulnar em 13 (15,66%) e radial em dez (12,04%). O procedimento mais utilizado foi a exploração vascular 35 (32,4%). Em nove doentes (12,68%) ocorreram complicações. A mortalidade foi 1,4%, em um paciente com lesão da veia ilíaca comum e da veia cava inferior, devido à queda de altura. o traumatismo vascular pediátrico ocorreu predominantemente em extremidades. As dimensões dos vasos lesionados tornaram a correção cirúrgica mais complexa e aumentaram os índices de complicações, particularmente, de amputações.

Prehospital Care for the Adult and Pediatric Seizure Patient: Current Evidence-based Recommendations.

PubMed

Silverman, Eric C; Sporer, Karl A; Lemieux, Justin M; Brown, John F; Koenig, Kristi L; Gausche-Hill, Marianne; Rudnick, Eric M; Salvucci, Angelo A; Gilbert, Greg H

2017-04-01

We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of adult and pediatric patients with a seizure and to compare these recommendations against the current protocol used by the 33 emergency medical services (EMS) agencies in California. We performed a review of the evidence in the prehospital treatment of patients with a seizure, and then compared the seizure protocols of each of the 33 EMS agencies for consistency with these recommendations. We analyzed the type and route of medication administered, number of additional rescue doses permitted, and requirements for glucose testing prior to medication. The treatment for eclampsia and seizures in pediatric patients were analyzed separately. Protocols across EMS Agencies in California varied widely. We identified multiple drugs, dosages, routes of administration, re-dosing instructions, and requirement for blood glucose testing prior to medication delivery. Blood glucose testing prior to benzodiazepine administration is required by 61% (20/33) of agencies for adult patients and 76% (25/33) for pediatric patients. All agencies have protocols for giving intramuscular benzodiazepines and 76% (25/33) have protocols for intranasal benzodiazepines. Intramuscular midazolam dosages ranged from 2 to 10 mg per single adult dose, 2 to 8 mg per single pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intranasal midazolam dosages ranged from 2 to 10 mg per single adult or pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intravenous/intrasosseous midazolam dosages ranged from 1 to 6 mg per single adult dose, 1 to 5 mg per single pediatric dose, and 0.05 to 0.1 mg/kg as a weight-based dose. Eclampsia is specifically addressed by 85% (28/33) of agencies. Forty-two percent (14/33) have a protocol for administering magnesium sulfate, with intravenous dosages ranging from 2 to 6 mg, and 58% (19/33) allow benzodiazepines to be administered. Protocols for a patient with a seizure, including eclampsia and febrile seizures, vary widely across California. These recommendations for the prehospital diagnosis and treatment of seizures may be useful for EMS medical directors tasked with creating and revising these protocols.

Evaluation of Cameroonian plants towards experimental bone regeneration.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Siddiqui, Jawed Akhtar; Tewari, Deepshikha; Nagar, Geet K; Tiwari, Satish C; Theophile, Dimo; Maurya, Rakesh; Chattopadhyay, Naibedya

2012-05-07

Elephantopus mollis, Spilanthes africana, Urena lobata, Momordica multiflora, Asystasia gangetica and Brillantaisia ovariensis are used in Cameroonian traditional medicine for the treatment of bone diseases and fracture repair. The aim of this study was to evaluate the effect of ethanolic extracts of six Cameroonian medicinal plants on bone regeneration following bone and marrow injury. Ethanol extract of Cameroonian medicinal plants were administered (each extract at 250, 500 and 750mg/kg doses) orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of fractured bone was performed to evaluate bone regeneration (calcein labeling). Only active plant extracts were used for further experiments. Thus, callus was analyzed by microcomputed tomography. Osteogenic effects of the extracts were evaluated by assessing mineralized nodules formation of bone marrow stromal cells and osteoblast recruitment at drill hole site by immunohistochemistry. Ethanolic extract of the leaves and twigs of Elephantopus mollis (EM) and whole plant of Spilanthes africana (SA) dose-dependently stimulated bone regeneration at the drill hole site. EM at 250 and 750mg/kg doses and SA at 750mg/kg dose significantly increased mineral deposition compared to controls. Both extracts at 500 and 750mg/kg doses improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. EM and SA extracts increased the formation of mineralized nodules from the bone marrow stromal cells. In addition, EM and SA extracts increased osteoblast recruitment at the drill hole site evident from increased Runx-2 positive cells following their treatments compared to control. Ethanolic extracts of EM and SA accelerate fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying their traditional use. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing.

PubMed

Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie L; Boston, Raymond C

2015-12-01

(1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2) To develop an HC phenotype-specific dosing strategy for HC that accounts for HM production using clinical pharmacokinetics integrated with pharmacogenetics for patient safety. In silico clinical trial simulation. Healthy white men and women without comorbidities or history of opioid, or any other drug or nutraceutical use, age 26.3±5.7 years (mean±SD; range, 19 to 36 y) and weight 71.9±16.8 kg (range, 50 to 108 kg). CYP2D6 phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype-specific percentages of HM formed from HC. PMs had lower indices of HC disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and the t1/2 was increased by about 68% compared with EMs. The canonical order for HC clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke, was reduced about 70% in PM. However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects. Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

Perfis de temperatura eletrônica em regiões HII

NASA Astrophysics Data System (ADS)

Copetti, M. V. F.

2003-08-01

As flutuações de temperatura eletrônica em regiões HII, inicialmente propostas para explicar as discrepâncias entre os valores de temperatura obtidos por diferentes métodos, têm sido apontadas como a causa mais provável das enormes diferenças encontradas entre as abundâncias químicas medidas através de linhas excitadas colisionalmente e de linhas de recombinação. Recentemente têm sido reportadas tentativas de detecção e quantificação diretas das flutuações de temperatura eletrônica através de medidas ponto a ponto, obtidas por meio de espectroscopia de fenda longa, das razões de linhas [OIII]l4263/l5007 e [NII]l5755/l6584, principais sensores de temperatura. Neste trabalho, utilizamos o código numérico de fotoionização Cloudy para avaliar a confiabilidade desse procedimento. Concluímos que, para valores de densidade eletrônica e de temperatura efetiva da estrela ionizante típicos das regiões HII, os perfis superficiais de temperatura obtidos via medidas do sensor [OIII]l4263/l5007 são bons traçadores dos gradientes internos de temperatura eletrônica. Já os perfis de temperatura eletrônica medidos por meio da razão [NII]l5755/l6584 não reproduzem os gradientes verdadeiros de temperatura.

ANATOMIC VARIATIONS OF HEPATIC ARTERY: A STUDY IN 479 LIVER TRANSPLANTATIONS.

PubMed

Fonseca-Neto, Olival Cirilo Lucena da; Lima, Heloise Caroline de Souza; Rabelo, Priscylla; Melo, Paulo Sérgio Vieira de; Amorim, Américo Gusmão; Lacerda, Cláudio Moura

2017-01-01

The incidence of anatomic variations of hepatic artery ranges from 20-50% in different series. Variations are especially important in the context of liver orthotopic transplantation, since, besides being an ideal opportunity for surgical anatomical study, their precise identification is crucial to the success of the procedure. To identify the anatomical variations in the hepatic arterial system in hepatic transplantation. 479 medical records of transplanted adult patients in the 13-year period were retrospectively analyzed, and collected data on hepatic arterial anatomy of the deceased donor. It was identified normal hepatic arterial anatomy in 416 donors (86.84%). The other 63 patients (13.15%) showed some variation. According to the Michels classification, the most frequently observed abnormalities were: right hepatic artery branch of superior mesenteric artery (Type III, n=27, 5.63%); left hepatic artery branch of the left gastric artery (Type II, n=13, 2.71%); right hepatic artery arising from the superior mesenteric artery associated with the left hepatic artery arising from the left gastric artery (Type IV, n=4, 0.83%). Similarly, in relation to Hiatt classification, the most prevalent changes were: right hepatic accessory artery or substitute of the superior mesenteric artery (Type III, n=28, 6.05%)), followed by liver ancillary left artery or replacement of gastric artery left (Type II, n=16, 3.34. Fourteen donors (2.92%) showed no anatomical abnormalities defined in classifications, the highest frequency being hepatomesenteric trunk identified in five (01.04%). Detailed knowledge of the variations of hepatic arterial anatomy is of utmost importance to surgeons who perform approaches in this area, particularly in liver transplantation, since their identification and proper management are critical to the success of the procedure. A incidência das variações anatômicas da artéria hepática varia de 20-50% em diferentes casuísticas. Elas são especialmente importantes no contexto do transplante ortotópico hepático, visto que, além de representar oportunidade ideal para seu estudo anatômico cirúrgico, a sua precisa identificação é determinante para o sucesso do procedimento. Identificar as variações anatômicas no sistema arterial hepático em transplantes hepáticos. Foram analisados retrospectivamente, no período de 13 anos, 479 prontuários de pacientes adultos transplantados, sendo coletados dados referentes à anatomia arterial hepática do doador falecido. Identificou-se anatomia arterial hepática normal em 416 doadores (86,84%). Os outros 63 indivíduos (13,15%) apresentaram alguma variação. De acordo com a classificação de Michels, as anomalias mais frequentes foram: artéria hepática direita ramo da artéria mesentérica superior (Tipo III, n=27, 5,63%); artéria hepática esquerda ramo da artéria gástrica esquerda (Tipo II, n=13, 2,71%); artéria hepática direita ramo da artéria mesentérica superior associada à artéria hepática esquerda ramo da artéria gástrica esquerda (Tipo IV, n=4, 0,83%). Do mesmo modo, em relação à Classificação de Hiatt, as variações mais prevalentes foram: artéria hepática direita acessória ou substituta da artéria mesentérica superior (Tipo III, n=28, 6,05%), seguida da artéria hepática esquerda acessória ou substituta da artéria gástrica esquerda (Tipo II, n=16, 3,34%). Quatorze pessoas (2,92%) apresentaram alterações anatômicas sem classificação definida, sendo a de maior frequência o tronco hepatomesentérico, identificado em cinco (1,04%). O conhecimento detalhado das variações da anatomia arterial hepática é de grande importância aos cirurgiões que realizam abordagens nessa região, em especial no transplante hepático, visto que sua identificação e correto manejo são fundamentais para o êxito do procedimento.

IRIS Assessment Plan for Uranium (Scoping and Problem Formulation Materials)

EPA Science Inventory

In January 2018, EPA released the IRIS Assessment Plan for Uranium (Oral Reference Dose) (Scoping and Problem Formulation Materials). An IRIS Assessment Plan (IAP) communicates to the public the plan for assessing each individual chemical and includes summary informatio...

Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19

PubMed Central

Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin; Yang, Byung-Hwan; Shin, Sang-Goo; Yim, Dong-Seok

2002-01-01

Aims The pharmacokinetics of omeprazole and its metabolites in healthy subjects were evaluated to determine if a single dose of moclobemide inhibited CYP2C19 activity. Methods Sixteen volunteers, of whom eight were extensive metabolizers (EM) and eight were poor metabolizers for CYP2C19, participated in two studies. Venous blood samples were collected for 24 h after oral ingestion of 40 mg omeprazole with or without 300 mg moclobemide coadministration. The pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole concentrations were assessed to test for an interaction between omeprazole and moclobemide. Results The coadministration of moclobemide in EMs approximately doubled the mean AUC (from 1834 to 3760 ng ml−1 h) and Cmax (from 987 to 1649 ng ml−1) of omeprazole, and increased the AUC of omeprazole sulphone without changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide coadministration more than doubled the AUC ratio of omeprazole to 5-hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were seen in the results for omeprazole and omeprazole sulphone AUCs. Conclusions A single dose of moclobemide resulted in significant suppression of CYP2C19 activity in EMs. We conclude that physicians prescribing moclobemide should pay attention to its pharmacokinetic interactions even on the first day of coadministration with CYP2C19 substrates. PMID:11966672

Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19.

PubMed

Cho, Joo-Youn; Yu, Kyung-Sang; Jang, In-Jin; Yang, Byung-Hwan; Shin, Sang-Goo; Yim, Dong-Seok

2002-04-01

The pharmacokinetics of omeprazole and its metabolites in healthy subjects were evaluated to determine if a single dose of moclobemide inhibited CYP2C19 activity. Sixteen volunteers, of whom eight were extensive metabolizers (EM) and eight were poor metabolizers for CYP2C19, participated in two studies. Venous blood samples were collected for 24 h after oral ingestion of 40 mg omeprazole with or without 300 mg moclobemide coadministration. The pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole concentrations were assessed to test for an interaction between omeprazole and moclobemide. The coadministration of moclobemide in EMs approximately doubled the mean AUC (from 1834 to 3760 ng ml(-1) h) and C(max) (from 987 to 1649 ng ml(-1)) of omeprazole, and increased the AUC of omeprazole sulphone without changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide coadministration more than doubled the AUC ratio of omeprazole to 5-hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were seen in the results for omeprazole and omeprazole sulphone AUCs. A single dose of moclobemide resulted in significant suppression of CYP2C19 activity in EMs. We conclude that physicians prescribing moclobemide should pay attention to its pharmacokinetic interactions even on the first day of coadministration with CYP2C19 substrates.

The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the rat inflamed joint model.

PubMed

Mecs, Laszlo; Tuboly, Gabor; Nagy, Endre; Benedek, Gyorgy; Horvath, Gyongyi

2009-10-01

Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/20 microL) into the tibiotarsal joint of the right hind leg. The mechanical pain threshold was assessed by von Frey filaments (0.064-110 g). EM1 (30, 100, and 200 microg), KYNA (30, 100, 200, and 400 microg), and their combinations in a fixed-dose ratio (1:1) were injected into the inflamed joint, and the pain threshold was determined repeatedly for 75 min after the drug administrations. Neither EM1 nor KYNA administered to the inflamed joint influenced the pain threshold at the noninflamed side. Both ligands produced dose-dependent antihyperalgesia, and the highest doses caused a prolonged effect. EM1 had higher potency (30% effective dose [ED(30)] and 50% effective dose [ED(50)] values were 112 microg [confidence interval {CI}: 80-146] and 167 microg [CI: 135-220], respectively) compared with KYNA (ED(30) and ED(50) values were 204 microg [CI: 160-251] and 330 microg [CI: 280-407], respectively). The antinociceptive effect of EM1 was prevented by subcutaneous naltrexone pretreatment. The coadministration of EM1 with KYNA caused an enhanced and/or prolonged antinociceptive effect. The ED(30) and ED(50) values of the combination were 141 microg [CI: 83-182] and 231 microg [CI: 190-293], respectively, which did not differ significantly from the theoretically additive values (ED(30) and ED(50) values were 145 microg [CI: 68-237] and 220 microg [CI: 144-230], respectively), thus the interaction between these ligands is additive. None of the treatments caused any sign of side effects. Peripherally administered endogenous opioid agonist and NMDA receptor antagonist ligands might be beneficial in inflammatory pain. Because both drugs barely cross the blood-brain barrier, their local administration causes no central side effects.

Actively triggered 4d cone-beam CT acquisition.

PubMed

Fast, Martin F; Wisotzky, Eric; Oelfke, Uwe; Nill, Simeon

2013-09-01

4d cone-beam computed tomography (CBCT) scans are usually reconstructed by extracting the motion information from the 2d projections or an external surrogate signal, and binning the individual projections into multiple respiratory phases. In this "after-the-fact" binning approach, however, projections are unevenly distributed over respiratory phases resulting in inefficient utilization of imaging dose. To avoid excess dose in certain respiratory phases, and poor image quality due to a lack of projections in others, the authors have developed a novel 4d CBCT acquisition framework which actively triggers 2d projections based on the forward-predicted position of the tumor. The forward-prediction of the tumor position was independently established using either (i) an electromagnetic (EM) tracking system based on implanted EM-transponders which act as a surrogate for the tumor position, or (ii) an external motion sensor measuring the chest-wall displacement and correlating this external motion to the phase-shifted diaphragm motion derived from the acquired images. In order to avoid EM-induced artifacts in the imaging detector, the authors devised a simple but effective "Faraday" shielding cage. The authors demonstrated the feasibility of their acquisition strategy by scanning an anthropomorphic lung phantom moving on 1d or 2d sinusoidal trajectories. With both tumor position devices, the authors were able to acquire 4d CBCTs free of motion blurring. For scans based on the EM tracking system, reconstruction artifacts stemming from the presence of the EM-array and the EM-transponders were greatly reduced using newly developed correction algorithms. By tuning the imaging frequency independently for each respiratory phase prior to acquisition, it was possible to harmonize the number of projections over respiratory phases. Depending on the breathing period (3.5 or 5 s) and the gantry rotation time (4 or 5 min), between ∼90 and 145 projections were acquired per respiratory phase resulting in a dose of ∼1.7-2.6 mGy per respiratory phase. Further dose savings and decreases in the scanning time are possible by acquiring only a subset of all respiratory phases, for example, peak-exhale and peak-inhale only scans. This study is the first experimental demonstration of a new 4d CBCT acquisition paradigm in which imaging dose is efficiently utilized by actively triggering only those projections that are desired for the reconstruction process.

IMPACT OF VITAMIN D AND CALCIUM DEFICIENCY IN THE BONES OF PATIENTS UNDERGOING BARIATRIC SURGERY: A SYSTEMATIC REVIEW.

PubMed

Cabral, Jefry Alberto Vargas; Souza, Gabriela Pereira de; Nascimento, Juliana de Almeida; Simoneti, Luis Fernando; Marchese, Carolina; Sales-Peres, Silvia Helena de Carvalho

Bariatric surgery is considered the most effective tool in the control and treatment of severe obesity, but patients undergoing this procedure are at increased risk of developing nutritional deficiencies by limiting the intake and absorption of many nutrients. To assess the impact of vitamin D deficiency and calcium in bone in patients after gastric bypass in Roux-en-Y, pointing directly at the type of administration, doses and effects after surgery. Was conducted a systematic review with articles related to the topic of the last 10 years searched in PubMed (US National Library of Medicine National Institutes of Health, Medline, Lilacs, Scielo and Cochrane using the headings "bariatric surgery", "bone", "obesity", "vitamin D '', "calcium" AND "absorption". Exclusion criteria to research on animals, smokers, pregnant women and patient treated with bisphosphonates. Five articles were included in this review. All refer that bariatric surgery can lead to nutritional deficiencies and poor absorption of fats and fat-soluble vitamins and other micronutrients such as calcium. Patients submitted to RYGB should make use of multivitamins and minerals especially vitamin D and calcium to prevent bone fractures. Monitoring, treatment and control of risk factors are essential to prevent complications after this operation. A cirurgia bariátrica é considerada o tratamento mais eficaz no controle e tratamento da obesidade severa; porém, indivíduos submetidos a este procedimento apresentam maior risco de desenvolver deficiências nutricionais pela limitação na ingestão e absorção de muitos nutrientes. Avaliar o impacto da deficiência de vitamina D e do cálcio ósseo de pacientes após gastroplastia em Y-de-Roux, relacionando tipo de administração, dose e efeito pós-cirúrgico. Realizou-se revisão sistemática com artigos relacionados ao tema dos últimos 10 anos e pesquisados na PubMed (US National Library of Medicine National Institutes of Health, Medline, Lilacs, Scielo e Cochrane usando os descritores "bariatric surgery", "bone", "obesity", " vitamin D'', "calcium'' AND "absortion". Foram excluídos os estudos em animais, fumantes, grávidas ou gestantes e indivíduos que ingeriram bisfosfonatos. Foram incluídos ao final cinco artigos. Todos referem que a cirurgia bariátrica pode levar à deficiências nutricionais como má absorção de gorduras, vitaminas lipossolúveis, micronutrientes e cálcio. Os pacientes submetidos ao RYGB devem fazer uso de polivitamínicos e minerais principalmente a vitamina D e o cálcio para evitar fraturas ósseas. Monitoramento, tratamento e controle dos fatores de risco são essenciais para prevenir estas complicações após a operação.

Low completion rate of hepatitis B vaccination in female sex workers.

PubMed

Magalhães, Rosilane de Lima Brito; Teles, Sheila Araújo; Reis, Renata Karina; Galvão, Marli Teresinha Gimeniz; Gir, Elucir

2017-01-01

to assess predictive factors for noncompletion of the hepatitis B vaccination schedule in female sex workers in the city of Teresina, Northeastern Brazil. 402 women were interviewed and, for those who did not wish to visit specialized sites, or did not know their hepatitis B vaccination status, the vaccine was offered at their workplaces. Bi- and multivariate analyses were performed to identify potential predictors for noncompletion of the vaccination schedule. of the 284 women eligible for vaccination, 258 (90.8%) received the second dose, 157/258 (60.8%) and 68/258 (26.3%) received the second and third doses, respectively. Working at clubs and consuming illicit drugs were predictors for noncompletion of the vaccination schedule. the high acceptability of the vaccine's first dose, associated with low completion rates of the vaccination schedule in sex workers, shows the need for more persuasive strategies that go beyond offering the vaccine at their workplaces. avaliar fatores preditores de não completude do esquema vacinal contra hepatite B em mulheres que se prostituem em Teresina, Nordeste do Brasil. Um total de 402 mulheres foi entrevistado e, para as que se negaram a irem a lugares especializados, ou desconheciam sua situação vacinal contra hepatite B, a vacina foi oferecida no local do trabalho. Análises bi e multivariadas foram realizadas para identificar potenciais preditores de não completude do esquema vacinal. Das 284 mulheres elegíveis para vacinação, 258 (90,8%) receberam a primeira dose, 157/258 (60,8%) e 68/258 (26,3%) receberam a segunda e terceira doses. Trabalhar em boates e consumir drogas ilícitas foram preditores de não completude do esquema vacinal (p<0,05). A elevada aceitabilidade da primeira dose da vacina, associada à baixa completude do esquema vacinal em profissionais do sexo, evidencia a necessidade de estratégia mais persuasiva que vá além da oferta da vacina no local de trabalho.

New tools for subsurface imaging of 3D seismic Node data in hydrocarbon exploration =

NASA Astrophysics Data System (ADS)

Benazzouz, Omar

A aquisicao de dados sismicos de reflexao multicanal 3D/4D usando Ocean Bottom NODES de 4 componentes constitui atualmente um sector de importancia crescente no mercado da aquisicao de dados reflexao sismica marinha na industria petrolifera. Este tipo de dados permite obter imagens de sub-superficie de alta qualidade, com baixos niveis de ruido, banda larga, boa iluminacao azimutal, offsets longos, elevada resolucao e aquisicao de tanto ondas P como S. A aquisicao de dados e altamente repetitiva e portanto ideal para campanhas 4D. No entanto, existem diferencas significativas na geometria de aquisicao e amostragem do campo de ondas relativamente aos metodos convencionais com streamers rebocados a superficie, pelo que e necessario desenvolver de novas ferramentas para o processamento deste tipo de dados. Esta tese investiga tres aspectos do processamento de dados de OBSs/NODES ainda nao totalmente resolvidos de forma satisfatoria: a deriva aleatoria dos relogios internos, o posicionamento de precisao dos OBSs e a implementacao de algoritmos de migracao prestack 3D em profundidade eficientes para obtencao de imagens precisas de subsuperficie. Foram desenvolvidos novos procedimentos para resolver estas situacoes, que foram aplicados a dados sinteticos e a dados reais. Foi desenvolvido um novo metodo para deteccao e correccao de deriva aleatoria dos relogios internos, usando derivadas de ordem elevada. Foi ainda desenvolvido um novo metodo de posicionamento de precisao de OBSs usando multilateracao e foram criadas ferramentas de interpolacao/extrapolacao dos modelos de velocidades 3D de forma a cobrirem a extensao total area de aquisicao. Foram implementados algoritmos robustos de filtragem para preparar o campo de velocidades para o tracado de raios e minimizar os artefactos na migracao Krichhoff pre-stack 3D em profundidade. Os resultados obtidos mostram um melhoramento significativo em todas as situacoes analisadas. Foi desenvolvido o software necessario para o efeito e criadas solucoes computacionais eficientes. As solucoes computacionais desenvolvidas foram integradas num software standard de processamento de sismica (SPW) utilizado na industria, de forma a criar, conjuntamente com as ferramentas ja existentes, um workflow de processamento integrado para dados de OBS/NODES, desde a aquisicao e controle de qualidade a producao dos volumes sismicos migrados pre-stack em profundidade.

Influência da termoablação com baixa e alta densidade de energia na junção safeno-femoral, utilizando laser endovenoso 1470 nm

PubMed Central

de Araujo, Walter Junior Boim; Erzinger, Fabiano Luiz; Caron, Filipe Carlos; Nejm, Carlos Seme; Timi, Jorge Rufino Ribas

2017-01-01

Resumo Contexto Faz-se importante o conhecimento técnico dos ajustes de potência e de densidade de energia linear endovenosa (linear endovenous energy density, LEED) adequados para atingir o objetivo final da termoablação endovenosa (endovenous laser ablation, EVLA). Objetivos Avaliar a influência de diferentes LEEDs em termos de patência e presença de refluxo, bem como determinar a evolução clínica. Métodos Foram incluídas 60 veias safenas magnas (VSM). Os pacientes foram randomizados em dois grupos: EVLA com baixa potência (7 W e LEED de 20-40 J/cm) e com alta potência (15 W e LEED de 80-100 J/cm). O acompanhamento com eco-Doppler e escore de severidade clínica venoso (VCSS) foi realizado nos intervalos de 3-5 dias, 30 dias, 180 dias e 1 ano após o procedimento. Resultados Dezoito pacientes (29 membros) tratados com 7W de potência e 13 pacientes (23 membros) com 15 W completaram o estudo. Não houve diferença significativa considerando idade, tempo de cirurgia e o uso de analgésicos, lateralidade, gênero e presença de comorbidades. O LEED médio foi de 33,54 J/cm no grupo de 7 W e de 88,66 J/cm no de 15 W. Ambos apresentaram melhora no VCSS, redução significativa dos diâmetros da JSF e ausência de diferença significativa quanto ao aumento do comprimento do coto da VSM e de refluxo após o tratamento. Conclusões A utilização de maior densidade de energia mostrou-se mais efetiva em relação à estabilização do comprimento do coto da VSM e do refluxo em 6 meses. Fazem-se necessários estudos com um período de acompanhamento maior para fundamentar essa hipótese. PMID:29930650

IRIS Assessment Plan for Uranium (Scoping and Problem Formulation Materials)

EPA Science Inventory

In January 2018, EPA released the IRIS Assessment Plan for Uranium (Oral Reference Dose) (Scoping and Problem Formulation Materials). An IRIS Assessment Plan , or IAP communicates to the public the plan for assessing each individual chemical and includes summary informat...

First-in-human study assessing safety, tolerability and pharmacokinetics of BI 409306, a selective phosphodiesterase 9A inhibitor, in healthy males.

PubMed

Moschetti, Viktoria; Boland, Katja; Feifel, Ulrich; Hoch, Anja; Zimdahl-Gelling, Heike; Sand, Michael

2016-11-01

The aim of the present study was to investigate the safety, tolerability, dose proportionality and relative bioavailability of tablet and oral solution formulations of BI 409306 in healthy male subjects, and to compare the safety and pharmacokinetics in subjects who were extensive metabolizers (EMs) or poor metabolizers (PMs) of cytochrome P450 (CYP)-2C19. The present randomized, double-blind, placebo-controlled, single-centre study evaluated single rising doses of BI 409306 (0.5-500 mg) administered as a tablet or oral solution to EMs or PMs. Of 80 enrolled subjects (mean age 36.7 years), 79 (CYP2C19 EMs, 71; CYP2C19 PMs, eight) received treatment and completed the study. Adverse events (AEs) were mild to moderate in intensity. Overall, 17/71 (23.9%) EMs and 6/8 (75.0%) PMs experienced 28 and eight AEs, respectively, of which, 25 and seven AEs, respectively, were considered to be drug related. The most frequently reported AEs were nervous system and eye disorders; all occurred shortly (20-30 min) after administration and mostly resolved within 1-2 h. No serious AEs occurred. BI 409306 systemic absorption and elimination were rapid; peak plasma concentration (C max ) was reached <1 h after drug administration, and the half-life ranged from 0.99 h to 2.71 h. Both the tablet and oral solution resulted in similar exposures. In PMs, at dose levels of 10 mg and 100 mg, C max was 2.2-2.3-fold higher, and the area under the plasma concentration-time curve over the time interval 0 extrapolated to infinity was 4.1-5.0-fold higher compared with EMs. In healthy male subjects, BI 409306 was generally safe and well tolerated, with rapid absorption and elimination. Systemic exposure was higher in CYP2C19 PMs than EMs at the same dose level. © 2016 Boehringer Ingelheim. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Improvement of antioxidant and defense properties of Tomato (var. Pusa Rohini) by application of bioaugmented compost

PubMed Central

Verma, Shikha; Sharma, Anamika; Kumar, Raj; Kaur, Charanjit; Arora, Anju; Shah, Raghubir; Nain, Lata

2014-01-01

Nutrient management practices play a significant role in improving the nutritional quality of tomato. The present study deals with the evaluation of compost prepared using Effective Microorganisms (EM), on antioxidant and defense enzyme activities of Tomato (Lycopersicon esculentum). A field experiment with five treatments (control, chemical fertilizer and EM compost alone and in combination) was conducted in randomized block design. An increment of 31.83% in tomato yield was recorded with the combined use of EM compost and half recommended dose of chemical fertilizers (N50P30K25 + EM compost at the rate of 5 t ha−1). Similarly, fruit quality was improved in terms of lycopene content (35.52%), antioxidant activity (24–63%) and defense enzymes activity (11–54%), in tomatoes in this treatment as compared to the application of recommended dose of fertilizers. Soil microbiological parameters also exhibited an increase of 7–31% in the enzyme activities in this treatment. Significant correlation among fruit quality parameters with soil microbiological activities reveals the positive impact of EM compost which may be adopted as an eco-friendly strategy for production of high quality edible products. PMID:25972746

Novel Treatment Using Low-Dose Naltrexone for Lichen Planopilaris.

PubMed

Strazzulla, Lauren C; Avila, Lorena; Lo Sicco, Kristen; Shapiro, Jerry

2017-11-01

Lichen planopilaris (LPP) is a variant of lichen planus that affects the scalp causing scarring hair loss. Patients also frequently experience symptoms of scalp itch, pain, and burning. To date, there are no long-term remittive nor curative therapies available. Low-dose naltrexone has anti-inflammatory properties and has recently been described in the context of treating autoimmune conditions. This retrospective medical record review describes four LPP patients treated with low-dose (3 milligrams per day) naltrexone. This medication provided benefit in these four patients including reduction in symptoms of pruritus, clinical evidence of inflammation of the scalp, and disease progression. All patients tolerated naltrexone without adverse effects. This is the first case series demonstrating the beneficial effects of low-dose naltrexone for patients with LPP. This medication was well-tolerated by the patients and is cost-effective.

J Drugs Dermatol. 2017;16(11):1140-1142.

Pharmaceutical interventions in medications prescribed for administration via enteral tubes in a teaching hospital.

PubMed

Ferreira, Carolina Justus Buhrer; Plodek, Caroline Koga; Soares, Franciny Kossemba; Andrade, Rayza Assis de; Teleginski, Fernanda; Rocha, Maria Dagmar da

2016-01-01

to analyze the impact of guidelines regarding errors in medications prescribed for administration through enteral tubes. quantitative study, in three phases, undertaken in internal medicine, neurology and an intensive care unit in a general teaching hospital. In Phase 1, the following was undertaken: a protocol for dilution and unit-dose repackaging and administration for 294 medications via enteral tubes; a decision flowchart; operational-standard procedures for dilution and unit-dose repackaging of oral pharmaceutical forms and for administration of medications through enteral tubes. In phase 2, errors in 872 medications prescribed through enteral tubes, in 293 prescriptions for patients receiving inpatient treatment between March and June, were investigated. This was followed by training of the teams in relation to the guidelines established. In Phase 3, pharmaceutical errors and interventions in 945 medications prescribed through enteral tubes, in 292 prescriptions of patients receiving inpatient treatment between August and September, were investigated prospectively. The data collected, in a structured questionnaire, were compiled in the Microsoft Office Excel(r) program, and frequencies were calculated. 786 errors were observed, 63.9% (502) in Phase 2, and 36.1% (284) in Phase 3. In Phase 3, a reduction was ascertained in the frequency of prescription of medications delivered via enteral tubes, medications which were contraindicated, and those for which information was not available. guidelines and pharmaceutical interventions were determined in the prevention of errors involving medications delivered through enteral tubes. analisar o impacto de diretrizes sobre erros em medicamentos prescritos para administração via sondas enterais. estudo quantitativo, em três fases, realizado em clínica médica, neurologia e unidade de terapia intensiva de hospital geral universitário. Na Fase 1 elaborou-se: protocolo de diluição, unitarização - transformação e administração para 294 medicamentos via sondas enterais; fluxograma decisório; procedimentos operacionais-padrão de diluição e unitarização de formas farmacêuticas orais e de administração de medicamentos via sondas enterais. Na Fase 2 investigou-se, retrospectivamente, erros em 872 medicamentos prescritos via sondas enterais, em 293 prescrições de pacientes internados de março a junho. Seguiu-se capacitação das equipes sobre diretrizes estabelecidas. Na Fase 3 investigou-se, prospectivamente, erros e intervenções farmacêuticas em 945 medicamentos prescritos via sondas enterais, em 292 prescrições de pacientes internados de agosto a setembro. Dados coletados, em formulário estruturado, foram compilados no programa Microsoft Office Excel(r) e calculadas as frequências. foram observados 786 erros, 63,9% (502) na Fase 2 e 36,1% (284) na Fase 3. Na Fase 3 verificou-se redução na frequência de prescrição de medicamentos, via sondas enterais, contraindicados e sem informações disponíveis. diretrizes e intervenções farmacêuticas foram determinantes na prevenção dos erros de medicamentos via sondas enterais. analizar el impacto de directrices sobre errores en medicamentos prescritos para administración vía sondas enterales. estudio cuantitativo, en tres fases, realizado en una clínica médica-neurología y en unidad de terapia intensiva de un hospital general universitario. En la Fase 1 se elaboró: protocolo de dilución, reenvasado - transformación y administración para 294 medicamentos vía sondas enterales; diagrama de flujo de decisión; procedimientos operacionales estándar de dilución y reenvasado - transformación de formas farmacéuticas orales y de administración de medicamentos vía sondas enterales. En la Fase 2 se investigó, retrospectivamente, errores en 872 medicamentos prescritos vía sondas enterales, en 293 prescripciones de pacientes internados de marzo a junio. La continuación, capacitación de los equipos sobre directrices establecidas. En la Fase 3 se investigó, prospectivamente, errores e intervenciones farmacéuticas en 945 medicamentos prescritos vía sondas enterales, en 292 prescripciones de pacientes internados de agosto a septiembre. Datos fueron colectados en un formulario estructurado, compilados en el programa Microsoft Office Excel(r) y se calcularon las frecuencias. se observaron 786 errores, 63,9% (502) en la Fase 2 y 36,1% (284) en la Fase 3. En la Fase 3 se verificó una reducción en la frecuencia de prescripción de medicamentos, vía sondas enterales, contraindicados y sin informaciones disponibles. las directrices e intervenciones farmacéuticas fueron determinantes en la prevención de los errores de medicamentos vía sondas enterales.

IRIS Toxicological Review of 1,4-Dioxane (with Inhalation Update) (Final Report)

EPA Science Inventory

The final IRIS Toxicological Review of 1,4-dioxane (with inhalation update) provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to 1,4-dioxane. Human health risk concerns for 1,4-dioxane are primarily relat...

Extension of PENELOPE to protons: simulation of nuclear reactions and benchmark with Geant4.

PubMed

Sterpin, E; Sorriaux, J; Vynckier, S

2013-11-01

Describing the implementation of nuclear reactions in the extension of the Monte Carlo code (MC) PENELOPE to protons (PENH) and benchmarking with Geant4. PENH is based on mixed-simulation mechanics for both elastic and inelastic electromagnetic collisions (EM). The adopted differential cross sections for EM elastic collisions are calculated using the eikonal approximation with the Dirac-Hartree-Fock-Slater atomic potential. Cross sections for EM inelastic collisions are computed within the relativistic Born approximation, using the Sternheimer-Liljequist model of the generalized oscillator strength. Nuclear elastic and inelastic collisions were simulated using explicitly the scattering analysis interactive dialin database for (1)H and ICRU 63 data for (12)C, (14)N, (16)O, (31)P, and (40)Ca. Secondary protons, alphas, and deuterons were all simulated as protons, with the energy adapted to ensure consistent range. Prompt gamma emission can also be simulated upon user request. Simulations were performed in a water phantom with nuclear interactions switched off or on and integral depth-dose distributions were compared. Binary-cascade and precompound models were used for Geant4. Initial energies of 100 and 250 MeV were considered. For cases with no nuclear interactions simulated, additional simulations in a water phantom with tight resolution (1 mm in all directions) were performed with FLUKA. Finally, integral depth-dose distributions for a 250 MeV energy were computed with Geant4 and PENH in a homogeneous phantom with, first, ICRU striated muscle and, second, ICRU compact bone. For simulations with EM collisions only, integral depth-dose distributions were within 1%/1 mm for doses higher than 10% of the Bragg-peak dose. For central-axis depth-dose and lateral profiles in a phantom with tight resolution, there are significant deviations between Geant4 and PENH (up to 60%/1 cm for depth-dose distributions). The agreement is much better with FLUKA, with deviations within 3%/3 mm. When nuclear interactions were turned on, agreement (within 6% before the Bragg-peak) between PENH and Geant4 was consistent with uncertainties on nuclear models and cross sections, whatever the material simulated (water, muscle, or bone). A detailed and flexible description of nuclear reactions has been implemented in the PENH extension of PENELOPE to protons, which utilizes a mixed-simulation scheme for both elastic and inelastic EM collisions, analogous to the well-established algorithm for electrons/positrons. PENH is compatible with all current main programs that use PENELOPE as the MC engine. The nuclear model of PENH is realistic enough to give dose distributions in fair agreement with those computed by Geant4.

Extension of PENELOPE to protons: Simulation of nuclear reactions and benchmark with Geant4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sterpin, E.; Sorriaux, J.; Vynckier, S.

2013-11-15

Purpose: Describing the implementation of nuclear reactions in the extension of the Monte Carlo code (MC) PENELOPE to protons (PENH) and benchmarking with Geant4.Methods: PENH is based on mixed-simulation mechanics for both elastic and inelastic electromagnetic collisions (EM). The adopted differential cross sections for EM elastic collisions are calculated using the eikonal approximation with the Dirac–Hartree–Fock–Slater atomic potential. Cross sections for EM inelastic collisions are computed within the relativistic Born approximation, using the Sternheimer–Liljequist model of the generalized oscillator strength. Nuclear elastic and inelastic collisions were simulated using explicitly the scattering analysis interactive dialin database for {sup 1}H and ICRUmore » 63 data for {sup 12}C, {sup 14}N, {sup 16}O, {sup 31}P, and {sup 40}Ca. Secondary protons, alphas, and deuterons were all simulated as protons, with the energy adapted to ensure consistent range. Prompt gamma emission can also be simulated upon user request. Simulations were performed in a water phantom with nuclear interactions switched off or on and integral depth–dose distributions were compared. Binary-cascade and precompound models were used for Geant4. Initial energies of 100 and 250 MeV were considered. For cases with no nuclear interactions simulated, additional simulations in a water phantom with tight resolution (1 mm in all directions) were performed with FLUKA. Finally, integral depth–dose distributions for a 250 MeV energy were computed with Geant4 and PENH in a homogeneous phantom with, first, ICRU striated muscle and, second, ICRU compact bone.Results: For simulations with EM collisions only, integral depth–dose distributions were within 1%/1 mm for doses higher than 10% of the Bragg-peak dose. For central-axis depth–dose and lateral profiles in a phantom with tight resolution, there are significant deviations between Geant4 and PENH (up to 60%/1 cm for depth–dose distributions). The agreement is much better with FLUKA, with deviations within 3%/3 mm. When nuclear interactions were turned on, agreement (within 6% before the Bragg-peak) between PENH and Geant4 was consistent with uncertainties on nuclear models and cross sections, whatever the material simulated (water, muscle, or bone).Conclusions: A detailed and flexible description of nuclear reactions has been implemented in the PENH extension of PENELOPE to protons, which utilizes a mixed-simulation scheme for both elastic and inelastic EM collisions, analogous to the well-established algorithm for electrons/positrons. PENH is compatible with all current main programs that use PENELOPE as the MC engine. The nuclear model of PENH is realistic enough to give dose distributions in fair agreement with those computed by Geant4.« less

Kinetic characterization of glucose aerodehydrogenase from Aspergillus niger EMS-150-F after optimizing the dose of mutagen for enhanced production of enzyme

PubMed Central

Umbreen, Huma; Zia, Muhammad Anjum; Rasul, Samreen

2013-01-01

In the present study enhanced production of glucose aerodehydrogenase from Aspergillus niger has been achieved after optimizing the dose of chemical mutagen ethyl methane sulfonate (EMS) that has not been reported earlier. Different doses of mutagen were applied and a strain was developed basing upon the best production. The selected strain Aspergillus niger EMS-150-F was optimized for nutrient requirements in order to produce enzyme through fermentation and the results showed the best yield at 2% corn steep liquor (CSL), 36 hours fermentation time, pH 5, 30°C temperature, 0.3% KH2PO4, 0.3% urea and 0.06% CaCO3. The enzyme was then purified and resulted in 57.88 fold purification with 52.12% recovery. On kinetic characterization, the enzyme showed optimum activity at pH 6 and temperature 30°C. The Michaelis-Menton constants (Km, Vmax, Kcat and Kcat/Km) were 20 mM, 45.87 U mL−1, 1118.81 s−1 and 55.94 s−1 mM−1, respectively. The enzyme was found to be thermaly stable and the enthalpy and free energy showed an increase with increase in temperature and ΔS* was highly negative proving the enzyme from A. niger EMS-150-F resistant to temperature and showing a very little disorderliness. PMID:24688499

Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Victoria; Kishan, Amar U.; Cao, Minsong

2014-03-15

Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Basedmore » on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.« less

Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy male volunteers.

PubMed

Ruan, Can-Jun; Liu, Dong-Yang; Jiang, Ji; Hu, Pei

2012-12-01

Icotinib hydrochloride {4-[(3-ethynylphenyl)amino]-6,7-benzo-12-crown-4-quinazoline hydrochloride}, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), was designed for the treatment of non-small cell lung cancer (NSCLC). In the present study, we investigated the influence of the CYP2C19*2 and CYP2C19*3 alleles on the pharmacokinetics of icotinib in healthy Chinese volunteers. In a single-dose pharmacokinetic study, 12 healthy Chinese volunteers received an oral dose of 600 mg of icotinib. Plasma was sampled for up to 72 h post-dose, followed by quantification of icotinib by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS). Five subjects genotyped as homozygous extensive metabolizers (CYP2C19*1/*1), 6 subjects genotyped as heterozygous extensive metabolizers (CYP2C19*1/*2 or CYP2C19*1/*3), and 1 subject genotyped as a poor metabolizer (CYP2C19*2/*3) and was withdrawn from the research because of urticaria. The mean icotinib AUC(0-∞) and C(max) (14.56 ±5.31 h mg/L and 2.32 ± 0.49 μg/mL) in homozygous EMs was 1.56 and 1.41-fold lower than that in heterozygous EMs (22.7 ± 6.11 and 3.28 ± 0.48, P = 0.046 and 0.047). The mean CL/F (44.18 ± 12.17 L/h) in homozygous EMs was 1.55-fold higher than that in heterozygous EMs (28.42 ± 9.23 L/h, P = 0.013). The data showed that the pharmacokinetics of icotinib differ significantly between homozygous EMs and heterozygous EMs in CYP2C19.

TOTAL COST OF HOSPITALIZATION OF PATIENTS UNDERGOING ELECTIVE LAPAROSCOPIC CHOLECYSTECTOMY RELATED TO NUTRITIONAL STATUS.

PubMed

Menezes, Francisco Julimar Correia de; Menezes, Lara Gadelha Luna de; Silva, Guilherme Pinheiro Ferreira da; Melo-Filho, Antônio Aldo; Melo, Daniel Hardy; Silva, Carlos Antonio Bruno da

2016-01-01

In the Western world, the population developed an overweight profile. The morbidly obese generate higher cost to the health system. However, there is a gap in this approach with regard to individuals above the eutrofic pattern, who are not considered as morbidly obese. To correlate nutritional status according to BMI with the costs of laparoscopic cholecystectomy in a public hospital. Data were collected from medical records about: nutritional risk assessment, nutricional state and hospital cost in patients undergoing elective laparoscopic cholecystectomy. Were enrolled 814 procedures. Average age was 39.15 (±12.16) years; 47 subjects (78.3%) were women. The cost was on average R$ 6,167.32 (±1830.85) to 4.06 (±2.76) days of hospitalization; 41 (68.4%) presented some degree of overweight; mean BMI was 28.07 (±5.41) kg/m²; six (10%) individuals presented nutritional risk ≥3. There was a weak correlation (r=0.2) and not significant (p <0.08) between the cost of hospitalization of the sample and length of stay; however, in individuals with normal BMI, the correlation was strong (r=0,57) and significant (p<0.01). Overweight showed no correlation between cost and length of stay. However, overweight individuals had higher cost of hospitalization than those who had no complications, but with no correlation with nutritional status. Compared to those with normal BMI, there was a strong and statistically significant correlation with the cost of hospital stay, stressing that there is normal distribution involving adequate nutritional status and success of the surgical procedure with the consequent impact on the cost of hospitalization. No mundo ocidental, a população desenvolveu um perfil de excesso de peso corporal. Os obesos mórbidos geram custo mais alto para o sistema de saúde. Entretanto, observa-se um hiato no tocante aos indivíduos acima do eutrofismo, mas não considerados obesos mórbidos. Correlacionar estado nutricional, segundo o IMC, com custo de internação de colecistectomias videolaparoscópicas. Coleta de dados dos prontuários sobre: avaliação de risco nutricional, estado nutricional e custo de internação de pacientes submetidos à colecistectomia videolaparoscópica eletiva no período de janeiro de 2012 a dezembro de 2014. Foram analisados 814 procedimentos. A idade média foi de 39,15 (±12,16) anos; 47 (78,3%) eram mulheres. O custo de internação foi, em média, de R$ 6.167,32 (±1.830,85) para 4,06 (±2,76) dias de internação. Quarenta e um (68,4%) pacientes apresentavam algum grau de sobrepeso; o IMC médio foi 28,07 (±5,41) kg/m²; seis (10%) indivíduos apresentavam risco nutricional ≥3. Houve correlação fraca (r=0,2) e não significativa (p<0,08) entre o custo de hospitalização e o tempo de permanência. No entanto, em indivíduos com IMC normal, a correlação foi forte (r=0,57) e significante (p<0,01). Sobrepeso não demonstrou correlação entre custo e tempo de internação. Entretanto, os indivíduos com sobrepeso apresentaram custo maior de internação em relação aos que não tiveram intercorrência, mas sem correlação com o estado nutricional. Em relação aos com IMC normal, houve correlação forte e estatisticamente significante com o custo para tempo de internação, reforçando que há provável distribuição normal envolvendo estado nutricional adequado e sucesso do procedimento cirúrgico com consequente impacto no custo de internação.

Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

PubMed

Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

2016-08-01

Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects.

PubMed

Wang, Chang-Lin; Qiu, Ting-Ting; Yang, Dai-Jun; Yuan, Bi-Yu; Han, Feng-Tong; Li, Li; Gu, Ning

2017-04-01

C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity. Moreover, analogs 1-3 displayed potent antinociceptive activities after intracerebroventricular (i.c.v.) administration. Analogs 1 and 3 exhibited about 2-fold higher antinociception than EM-2, and differential opioid mechanisms were involved. In addition, EM-2 at 50 μmol/kg failed to produce any significant antinociceptive activity after subcutaneous (s.c.) administration, whereas equimolar dose of analogs 1-3 produced significant analgesic effects. Analog 3 showed the highest antinociceptive activity after systemic administration, which was consistent with its in vitro stability and lipophilicity. We further evaluated the antinociceptive tolerance of analogs 1-3. In acute tolerance test, analogs 1-3 shifted the dose-response curves rightward by only 1.4-3.2 fold as determined by tolerance ratio, whereas EM-2 by 5.6-fold, demonstrating reduced antinociceptive tolerance. Also, analogs 1 and 2 decreased chronic antinociceptive tolerance by central and peripheral administration of drugs. In particular, analogs 3 displayed insignificant chronic antinociceptive tolerance. Furthermore, analogs 1-3 were less prone to induce gastrointestinal side effects at analgesic doses. The present investigation gave the evidence that C-terminal esterified modifications of EM-2 will facilitate the development of novel opioid analgesics with reduced side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative assessment of the dose-response of alkylating agents in DNA repair proficient and deficient ames tester strains.

PubMed

Tang, Leilei; Guérard, Melanie; Zeller, Andreas

2014-01-01

Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.

Cost of nursing most frequent procedures performed on severely burned patients.

PubMed

Melo, Talita de Oliveira; Lima, Antônio Fernandes Costa

2017-01-01

to identify the mean direct cost (MDC) of the most frequent procedures performed by nursing professionals on severely burned patients in an Intensive Care Unit. exploratory-descriptive quantitative single-case study. The MDC was calculated by multiplying time (timed) spent by nursing professionals in the performance of the procedures by the unit cost of direct labor, and adding the costs of material and medicine/solutions. a MDC of US$ 0.65 (SD=0.36) was obtained for "vital signs monitoring"; US$ 10.00 (SD=24.23) for "intravenous drug administration"; US$ 5.90 (SD=2.75) for "measurement of diuresis"; US$ 0.93 (SD=0.42) for "capillary blood glucose monitoring"; and US$ 99.75 (SD=129.55) for "bandaging". the knowledge developed can support managerial decision-making, contribute to the efficiency distribution of the resources involved and, when possible, provide cost-containment or cost-minimization strategies without impairing the quality of nursing care. identificar o custo direto médio (CDM) dos procedimentos realizados, com maior frequência, por profissionais de enfermagem, em uma Unidade de Terapia Intensiva, aos pacientes grandes queimados. pesquisa quantitativa, exploratório-descritiva, do tipo estudo de caso único. O CDM foi calculado multiplicando-se o tempo (cronometrado) despendido por profissionais de enfermagem na execução dos procedimentos, objeto de estudo, pelo custo unitário da mão de obra direta, somando-se ao custo dos materiais e soluções/medicamentos. obteve-se o CDM de US$ 0.65 (SD=0.36) para "controle dos sinais vitais"; US$ 10.00 (SD=24.23) para "administração de medicamentos via intravenosa"; US$ 5.90 (SD=2.75) para "mensuração de diurese"; US$ 0.93 (SD=0.42) para "verificação de glicemia capilar"; e US$ 99.75 (SD=129.55) para "curativo". o conhecimento desenvolvido pode fundamentar as tomadas de decisão gerenciais subsidiando a eficiência alocativa dos recursos envolvidos e, quando possível, indicar estratégias de contenção/minimização de custos sem prejuízos à qualidade da assistência de enfermagem.

Compilação de dados atômicos e moleculares do UV ao IV próximo para uso em síntese espectral

NASA Astrophysics Data System (ADS)

Coelho, P.; Barbuy, B.; Melendez, J.; Allen, D. M.; Castilho, B.

2003-08-01

Espectros sintéticos são utéis em uma grande variedade de aplicações, desde análise de abundâncias em espectros estelares de alta resolução ao estudo de populações estelares em espectros integrados. A confiabilidade de um espectro sintético depende do modelo de atmosfera adotado, do código de formação de linhas e da qualidade dos dados atômicos e moleculares que são determinantes no cálculo das opacidades da fotosfera. O nosso grupo no departamento de Astronomia no IAG tem utilizado espectros sintéticos há mais de 15 anos, em aplicações voltadas principalmente para a análise de abundâncias de estrelas G, K e M e populações estelares velhas. Ao longo desse tempo, as listas de linhas vieram sendo construídas e atualizadas continuamente, e alguns acréscimos recentes podem ser citados: Castilho (1999, átomos e moléculas no UV), Schiavon (1998, bandas moleculares de TiO) e Melendez (2001, átomos e moléculas no IV próximo). Com o intuito de calcular uma grade de espectros do UV ao IV próximo para uso no estudo de populações estelares velhas, se fazia necessário compilar e homogeneizar as diversas listas em apenas uma lista atômica e uma molecular. Nesse processo, a nova lista compilada foi correlacionada com outras bases de dados (NIST, Kurucz Database, O' Brian et al. 1991) para atualização dos parâmetros que caracterizam a transição atômica (comprimento de onda, log gf e potencial de excitação). Adicionalmente as constantes de interação C6 foram calculadas segundo a teoria de Anstee & O'Mara (1995) e artigos posteriores. As bandas moleculares de CH e CN foram recalculadas com o programa LIFBASE (Luque & Crosley 1999). Nesse poster estão detalhados os procedimentos citados acima, as comparações entre espectros calculados com as novas listas e espectros observados em alta resolução do Sol e de Arcturus, e uma análise do impacto decorrente da utilização de diferentes modelos de atmosfera no espectro sintético. Ao final, temos uma lista de linhas atômicas com mais de 24.000 linhas e uma lista molecular com as moléculas CN, CH, OH, NH, MgH, C2, TiO Gama, CO, FeH, adequadas ao estudo de estrelas G, K e M e populações estelares velhas.

Tendências de teses e dissertações sobre ensino de astronomia no Brasil

NASA Astrophysics Data System (ADS)

Bretones, P. S.; Megid Neto, J.

2003-08-01

Neste trabalho são apresentados os resultados de uma pesquisa do tipo estado da arte sobre teses e dissertações defendidas no Brasil e relativas ao ensino de Astronomia. Teve por objetivo identificar essa produção e conhecer as principais tendências da pesquisa nesse campo. O procedimento inicial consistiu de um levantamento bibliográfico junto ao Centro de Documentação em Ensino de Ciências (CEDOC) da Faculdade de Educação da UNICAMP e ao Banco de Teses da CAPES disponível na Internet. Foram localizadas 13 dissertações de mestrado e 3 teses de doutorado, as quais foram estudadas em função dos seguintes aspectos: instituição, ano de defesa, nível escolar abrangido no estudo, foco temático do estudo e gênero de trabalho acadêmico. Deste conjunto de pesquisas, 13 (81,3%) delas foram defendidas a partir da segunda metade dos anos 90, indicando uma preocupação mais recente com temas relativos ao ensino de Astronomia no conjunto da produção acadêmica em programas de pós-graduação no Brasil. Verificou-se que 43,7% dos trabalhos foram produzidas na USP e 18,8% na UNICAMP. Quanto ao nível escolar abrangido nos estudos, predominaram os estudos direcionados ao Ensino Fundamental de 5a a 8a séries (62,5%). No que diz respeito ao foco temático das pesquisas, as principais tendências voltaram-se: 56,3% para Conteúdo e Método; 43,8% para Concepções do Professor; 37,5% para Currículo e Programas; 37,5% para Recursos Didáticos. Quanto ao gênero de trabalho acadêmico, verificou-se que 43,8% são de Pesquisa Experimental e 31,3% de Pesquisa de Análise de Conteúdo. Estudos de revisão bibliográfica como este visam colaborar com a divulgação ampla da produção acadêmica em determinada área, traçando algumas de suas tendências. Ao mesmo tempo possibilita, a partir de investigações decorrentes, apontar as suas contribuições para o ensino e sinalizar com necessidades a serem supridas por futuras pesquisas.

Incorporando a variabilidade no processo de identificação do modelo de máximo global no Grade of Membership (GoM): considerações metodológicas

PubMed Central

Guedes, Gilvan Ramalho; Siviero, Pamila Cristina Lima; Caetano, André Junqueira; Machado, Carla Jorge; Brondízio, Eduardo

2012-01-01

A disponibilidade de bases de dados cada vez mais complexas e multidimensionais é um dos principais motivadores para o aumento do número de estudos que utilizam análises multivariadas baseadas em lógica de conjuntos nebulosos. Apesar da disseminação do método Grade of Membership nos trabalhos empíricos brasileiros da área de ciências sociais e saúde, questões relativas à identificabilidade e estabilidade dos parâmetros finais estimados pelo programa GoM 3.4 não foram suficientemente aprofundadas. Dada a relevância de se obterem parâmetros únicos e estáveis, Guedes et al. (2010) propuseram um procedimento empírico para localizar um modelo de máximo global (MG) com parâmetros estáveis. Entretanto, seu localizador de MG não incorpora qualquer medida de variabilidade. Neste artigo, tal limitação é contornada por meio da utilização de uma estatística de ponderação – Máximo Global Ponderado (MGP) – semelhante ao coeficiente de variação. Esse indicador busca não penalizar de forma desproporcional situações nas quais os desvios médios, apesar de diferentes de zero, são muito pequenos. Apresentam-se evidências de que o localizador MGP reduz a distância do modelo identificado à real estrutura latente dos dados em análise, quando comparados ao modelo identificado pelo localizador não ponderado, MG. PMID:23293402

An observational study of Venlafaxine and CYP2D6 in clinical practice.

PubMed

Rolla, R; Gramaglia, Carla; Dalò, Valentina; Ressico, Francesca; Prosperini, Pierluigi; Vidali, Matteo; Meola, Silvia; Pollarolo, Paola; Bellomo, Giorgio; Torre, Eugenio; Zeppegno, Patrizia

2014-01-01

Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.

SU-F-J-152: Accuracy of Charge Particle Transport in Magnetic Fields Using EGSnrc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mainegra-Hing, E; Bouchard, H; Tessier, F

Purpose: Determine accuracy of the current implementation of electron transport under magnetic fields in EGSnrc by means of single scattering (SS) and Fano convergence tests, and establish quantitatively the electron step size restriction required to achieve a desired level of accuracy for ionization chamber dosimetry. Methods: Condensed history (CH) dose calculations are compared to SS results for a PTW30013 ionization chamber irradiated in air by a 60Co photon beam. CH dose results for this chamber irradiated in a water phantom by a source of mono-energetic electrons are compared to the prediction of Fano’s theorem for step size restrictions EM ESTEPEmore » from 0.01 to 0.1 and strengths of 0.5 T, 1.0 T, and 1.5 T. Results: CH calculations in air for 60Co photons using an EM ESTEPE of 0.25 overestimate SS values by 6% for a 1.5 T field and by 1.5% for a 0.5 T field. Agreement improves with decreasing EM ESTEPE reducing this difference at 0.02 to 0.13% and 0.04% for 1.5 T and 0.5 T respectively. CH results converge with decreasing EM ESTEPE reaching an agreement of 0.2% at a value of EM ESTEPE of 0.01 for 100 keV electrons. SS results at 100 keV for 1.5 T show the same EM ESTEPE dependency as the CH results. Conclusion: Accurate transport of charged particles in magnetic fields is only possible if the step size is significantly restricted. An EM ESTEPE value of 0.02 is required to reproduce SS results at the 0.1% level for a calculation in air. The EM ESTEPE dependency of the SS results suggests SS is bypassed when simulating the transport of charged particles in magnetic fields. Fano test results for in water calculation suggest that only a 0.2% accuracy can be achieved with the current implementation.« less

Modified technique for preparation of venous circulation resin casts in the cirrhotic liver.

PubMed

Vasconcelos, José Olímpio Maia DE; Batista, Laécio Leitão; Pitta, Guilherme Benjamin Brandão; Lacerda, Cláudio Moura

2016-01-01

This study describes two major adaptations for the preparation of resin casts in human cirrhotic liver, harvested at the time of transplantation. The first is the way of fixing the catheter in the ostia of the hepatic and portal veins through a cerclage, so as to prevent displacement of the catheter and / or leakage of the resin during its injection. The second is the extension of corrosion time in the NaOH solution, averaging 6.8 days, with daily replacement the solution until complete removal of parenchymal tissue. We applied the method in 14 cirrhotic livers, with good filling and coloring of the portal and hepatic vein territories, using different colors. This allows an anatomical study of these vessels, able to complement the knowledge of the histopathology in research work, and the planning of therapeutic procedures, such as the Trans-Jugular Intrahepatic Port-Systemic Shunt (TIPS). RESUMO Este estudo descreve duas importantes adaptações para o preparo de moldes de resina em fígado humano cirrótico, captado no momento do transplante: a primeira, é a maneira de fixação dos cateteres nos "óstios" das veias hepáticas e porta, através de uma "cerclagem" dos mesmos, de modo a evitar o deslocamento do cateter e/ou extravasamento da resina durante sua injeção, e a segunda, é o prolongamento do tempo de corrosão na solução de NaOH, atingindo a média de 6,8 dias, com a substituição diária da solução, até a remoção completa do tecido parenquimatoso. O método foi empregado em 14 fígados cirróticos com bom preenchimento e coloração dos territórios das veias porta e hepáticas, utilizando cores distintas. Isto permite um estudo anatômico desses vasos, capaz de complementar os conhecimentos da histopatologia em trabalhos de pesquisa, e planejar procedimentos terapêuticos como a derivação porto-sistêmica intra-hepática transjugular (TIPS - Transjugular Intrahepatic Postosystemic Shunt).

Effectiveness of egg immersion in aqueous solutions of thiamine and thiamine analogs for reducing early mortality syndrome

USGS Publications Warehouse

Brown, S.B.; Brown, L.R.; Brown, M.; Moore, K.; Villella, M.; Fitzsimons, J.D.; Williston, B.; Honeyfield, D.C.; Hinterkopf, J.P.; Tillitt, D.E.; Zajicek, J.L.; Wolgamood, M.

2005-01-01

Protocols used for therapeutic thiamine treatments in salmonine early mortality syndrome (EMS) were investigated in lake trout Salvelinus namaycush and coho salmon Oncorhynchus kisutch to assess their efficacy. At least 500 mg of thiamine HCl/L added to egg baths was required to produce a sustained elevation of thiamine content in lake trout eggs. Thiamine uptake from egg baths was not influenced by a pH ranging from 5.5 to 7.5 or by a water hardness between 2 and 200 mg CaCO3/L. There was poorer thiamine uptake when initial thiamine levels were low, suggesting that current treatment regimes may not be as effective when thiamine levels are severely depressed and that higher treatment doses are necessary. Exposure of eggs to the more lipid-soluble thiamine analog allithiamine (1,000 mg/L) during water hardening increased egg thiamine levels by 1.5-2.5 nmol/g and was completely effective at reversing EMS. Another more lipid-soluble thiamine analog, benfotiamine (100 mg/L), reduced EMS but did not produce detectable increases in egg thiamine content. Although benfotiamine may be more effective than thiamine at mitigating EMS, it is more expensive than thiamine HCl or allithiamine. In addition, there still needs to be a more thorough examination of dose-response relationships. We conclude that allithiamine is an alternative to the use of thiamine in egg baths as a therapeutic treatment for salmonid EMS. ?? Copyright by the American Fisheries Society 2005.

Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia

PubMed Central

Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

2014-01-01

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP. PMID:24586889

Pion and electromagnetic contribution to dose: Comparisons of HZETRN to Monte Carlo results and ISS data

NASA Astrophysics Data System (ADS)

Slaba, Tony C.; Blattnig, Steve R.; Reddell, Brandon; Bahadori, Amir; Norman, Ryan B.; Badavi, Francis F.

2013-07-01

Recent work has indicated that pion production and the associated electromagnetic (EM) cascade may be an important contribution to the total astronaut exposure in space. Recent extensions to the deterministic space radiation transport code, HZETRN, allow the production and transport of pions, muons, electrons, positrons, and photons. In this paper, the extended code is compared to the Monte Carlo codes, Geant4, PHITS, and FLUKA, in slab geometries exposed to galactic cosmic ray (GCR) boundary conditions. While improvements in the HZETRN transport formalism for the new particles are needed, it is shown that reasonable agreement on dose is found at larger shielding thicknesses commonly found on the International Space Station (ISS). Finally, the extended code is compared to ISS data on a minute-by-minute basis over a seven day period in 2001. The impact of pion/EM production on exposure estimates and validation results is clearly shown. The Badhwar-O'Neill (BO) 2004 and 2010 models are used to generate the GCR boundary condition at each time-step allowing the impact of environmental model improvements on validation results to be quantified as well. It is found that the updated BO2010 model noticeably reduces overall exposure estimates from the BO2004 model, and the additional production mechanisms in HZETRN provide some compensation. It is shown that the overestimates provided by the BO2004 GCR model in previous validation studies led to deflated uncertainty estimates for environmental, physics, and transport models, and allowed an important physical interaction (π/EM) to be overlooked in model development. Despite the additional π/EM production mechanisms in HZETRN, a systematic under-prediction of total dose is observed in comparison to Monte Carlo results and measured data.

Tritium contamination at EG&G/EM in North Las Vegas, Nevada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sowell, C.V.; Arent, L.J.

1996-06-01

The tritium contamination discovered at the EG&G Energy Measurements (EG&G/EM) facility in North Las Vegas, Nevada, on 20 April 1995, could have been averted by good health physics practices and/or adequate management oversight. Scandium tritide (ScT{sub 3}) targets were installed for use in sealed tube neutron generators at EG&G/EM. In addition, EG&G/EM was also storing zirconium tritide (ZrT{sub 3}) and titanium tritide (TiT{sub 3}) foils. Since the targets were classified as sealed sources, the appropriate administrative and engineering control measures such as relocating targets/sources, air monitoring, bioassay, waste stream management, labeling/posting and training were not implemented. In all there weremore » six unreported incidents of tritium contamination from March 1994 to July 1995. Swipe surveys revealed areas exceeding the action level of 10,000 dpm/100 cm{sup 2} by up to three orders of magnitude. After reclassifying the targets as unsealed sources, a bioassay program was instituted, and the results were higher than expected for three employees. The doses assigned to the three individuals working in the contaminated area were 35, 58, and 61 mrem committed effective dose equivalent. Though the doses were low, the decontamination costs were in excess of $350,000.00. An investigation, was initiated by the U.S. Department of Energy Nevada Operations Office to analyze the events that led to the tritium contamination and recommend actions to prevent recurrence. Event and causal factor charting, Project Evaluation Tree (PET) analysis techniques, and root cause analysis, were used to evaluate management systems, causal sequences, and systems factors contributing to the tritium release.« less

Long-Term Follow-Up of Patients after Percutaneous Coronary Intervention with Everolimus-Eluting Bioresorbable Vascular Scaffold.

PubMed

Meneguz-Moreno, Rafael Alexandre; Costa, José de Ribamar; Moscoso, Freddy Antônio Britto; Staico, Rodolfo; Tanajura, Luiz Fernando Leite; Centemero, Marinella Patrizia; Chaves, Auréa Jacob; Abizaid, Andrea Claudia Leão de Sousa; Sousa, Amanda Guerra de Moraes Rego E; Abizaid, Alexandre Antonio Cunha

2017-02-01

Bioresorbable vascular scaffolds (BVS) were developed to improve the long-term results of percutaneous coronary intervention, restoring vasomotion. To report very late follow-up of everolimus-eluting Absorb BVS (Abbott Vascular, Santa Clara, USA) in our center. Observational retrospective study, in a single Brazilian center, from August 2011 to October 2013, including 49 patients submitted to Absorb BVS implantation. Safety and efficacy outcomes were analyzed in the in-hospital and very late follow-up phases (> 2 years). All 49 patients underwent a minimum follow-up of 2.5 years and a maximum of 4.6 years. Mean age was 56.8 ± 7.6 years, 71.4% of the patients were men, and 26.5% were diabetic. Regarding clinical presentation, the majority (94%) had stable angina or silent ischemia. Device success was achieved in 100% of cases with 96% overall procedure success rate. Major adverse cardiovascular events rate was 4% at 30 days, 8.2% at 1 year, and 12.2% at 2 years, and there were no more events until 4.6 years. There were 2 cases of thrombosis (1 subacute and 1 late). In this preliminary analysis, Absorb BVS showed to be a safe and effective device in the very late follow-up. Establishing the efficacy and safety profiles of these devices in more complex scenarios is necessary. Os suportes vasculares bioabsorvíveis (SVB) foram desenvolvidos com o intuito de melhorar os resultados da intervenção coronária percutânea a longo prazo, restabelecendo-se a vasomotricidade. Reportar o seguimento muito tardio do implante do SVB eluidor de everolimus Absorb® (Abbot Vascular, Santa Clara, EUA) em nosso centro. Estudo observacional, retrospectivo, em um único centro brasileiro, que incluiu 49 pacientes submetidos ao implante do SVB Absorb® entre agosto/2011 e outubro/2013. Foram analisados os desfechos de segurança e eficácia na fase hospitalar e bastante tardia (> 2 anos). Todos os 49 pacientes completaram um seguimento mínimo de 2,5 anos, sendo o máximo de 4,6 anos. A média de idade foi 56,8 ± 7,6 anos, sendo 71,4% da população estudada do sexo masculino e 26,5% composta por diabéticos. Considerando a apresentação clínica, a grande maioria (94%) tinha angina estável ou isquemia silenciosa. Obteve-se sucesso do dispositivo em 100% dos casos e do procedimento, em 96%. A taxa de eventos cardiovasculares maiores foi de 4% aos 30 dias, de 8,2% em 1 ano, e de 12,2% em 2 anos, sem mais eventos até 4,6 anos. Houve 2 casos de trombose (1 subaguda e 1 tardia) até o último seguimento. Nesta análise preliminar, o uso do SVB Absorb® mostrou-se seguro e eficaz no seguimento bastante tardio. Faz-se necessário estabelecer o perfil de eficácia e segurança destes dispositivos em cenários de maior complexidade.

Publicly Released Prompt Radiation Spectra Suitable for Nuclear Detonation Simulations

DTIC Science & Technology

2017-03-01

emission. During the Hiroshima and Nagasaki bombings , the prompt radiation contributed from 40%-70% of the free-in-air dose depending on distance from...intermediate- and low-yield thermonuclear weapons for initial radiation shielding calculations No Gritzner, et al. 1976 ( EM -1, Low, Henre...DNA 4267F ( EM -1 Fission) Neutron Gritzner, et al. 1976 1.00 x 1023 Glasstone (Thermonuclear) Neutron Glasstone & Dolan 1977 1.445 x 1023 ORNL-TM

Applications for a hybrid operating room in thoracic surgery: from multidisciplinary procedures to --image-guided video-assisted thoracoscopic surgery.

PubMed

Terra, Ricardo Mingarini; Andrade, Juliano Ribeiro; Mariani, Alessandro Wasum; Garcia, Rodrigo Gobbo; Succi, Jose Ernesto; Soares, Andrey; Zimmer, Paulo Marcelo

2016-01-01

The concept of a hybrid operating room represents the union of a high-complexity surgical apparatus with state-of-the-art radiological tools (ultrasound, CT, fluoroscopy, or magnetic resonance imaging), in order to perform highly effective, minimally invasive procedures. Although the use of a hybrid operating room is well established in specialties such as neurosurgery and cardiovascular surgery, it has rarely been explored in thoracic surgery. Our objective was to discuss the possible applications of this technology in thoracic surgery, through the reporting of three cases. RESUMO O conceito de sala híbrida traduz a união de um aparato cirúrgico de alta complexidade com recursos radiológicos de última geração (ultrassom, TC, radioscopia e/ou ressonância magnética), visando a realização de procedimentos minimamente invasivos e altamente eficazes. Apesar de bem estabelecido em outras especialidades, como neurocirurgia e cirurgia cardiovascular, o uso da sala hibrida ainda é pouco explorado na cirurgia torácica. Nosso objetivo foi discutir as aplicações e as possibilidades abertas por essa tecnologia na cirurgia torácica através do relato de três casos.

Equine platelet lysate as an alternative to fetal bovine serum in equine mesenchymal stromal cell culture - too much of a good thing?

PubMed

Russell, K A; Koch, T G

2016-03-01

Multipotent mesenchymal stromal cells (MSC) are often culture-expanded in vitro. Presently, expansion medium (EM) for MSC is supplemented with fetal bovine serum (FBS). However, increasing cost, variable composition and potential risks associated with bovine antigens call for alternatives. Platelet lysate (PL) has shown promise as an alternative supplement. To determine how equine umbilical cord blood (CB) MSC proliferate in EM enriched with PL or FBS at various concentrations. Randomised dose escalation study. Platelet concentrate was generated from 5 equine whole blood samples through a double centrifugation method and standardised to 1 × 10(12) platelets/l prior to a freeze/thaw cycle to produce PL. Pooled PL or pooled FBS was added to EM at concentrations of 5% to 60%. Proliferation of 4 equine CB-MSC cultures was determined after 4 days using a resazurin semiquantitative assay. Cord blood-MSC proliferated with a dose-dependent response with no significant difference found between PL and FBS up to a 30% concentration. Beyond 30%, proliferation fell in the PL-cultured cells, while continued dose-dependent proliferation was noted in the FBS-cultured cells. Despite reduced cell numbers in high PL concentrations, live/dead staining revealed that adherent cells remained viable. Expansion medium enriched with PL can support short-term equine CB-MSC proliferation at conventional culture concentrations. Based on the unexpected suppression of CB-MSC at higher PL concentrations, an in vivo dose study is indicated to investigate if combinational therapies of CB-MSC and platelet-rich plasma are associated with synergistic or antagonistic effect on CB-MSC function. © 2015 EVJ Ltd.

Shielding NSLS-II light source: Importance of geometry for calculating radiation levels from beam losses

NASA Astrophysics Data System (ADS)

Kramer, S. L.; Ghosh, V. J.; Breitfeller, M.; Wahl, W.

2016-11-01

Third generation high brightness light sources are designed to have low emittance and high current beams, which contribute to higher beam loss rates that will be compensated by Top-Off injection. Shielding for these higher loss rates will be critical to protect the projected higher occupancy factors for the users. Top-Off injection requires a full energy injector, which will demand greater consideration of the potential abnormal beam miss-steering and localized losses that could occur. The high energy electron injection beam produces significantly higher neutron component dose to the experimental floor than a lower energy beam injection and ramped operations. Minimizing this dose will require adequate knowledge of where the miss-steered beam can occur and sufficient EM shielding close to the loss point, in order to attenuate the energy of the particles in the EM shower below the neutron production threshold (<10 MeV), which will spread the incident energy on the bulk shield walls and thereby the dose penetrating the shield walls. Designing supplemental shielding near the loss point using the analytic shielding model is shown to be inadequate because of its lack of geometry specification for the EM shower process. To predict the dose rates outside the tunnel requires detailed description of the geometry and materials that the beam losses will encounter inside the tunnel. Modern radiation shielding Monte-Carlo codes, like FLUKA, can handle this geometric description of the radiation transport process in sufficient detail, allowing accurate predictions of the dose rates expected and the ability to show weaknesses in the design before a high radiation incident occurs. The effort required to adequately define the accelerator geometry for these codes has been greatly reduced with the implementation of the graphical interface of FLAIR to FLUKA. This made the effective shielding process for NSLS-II quite accurate and reliable. The principles used to provide supplemental shielding to the NSLS-II accelerators and the lessons learned from this process are presented.

Transection of the hepatic parenchyma associated or not with the contralateral portal vein branch ligature and its effect in liver regeneration.

PubMed

Wiederkehr, Henrique de Aguiar; Wiederkehr, Julio Cesar; Collaço, Luiz Martins; Sousa, Eros Luiz de; Salvalaggio, Paolo; Carvalho, Caroline Aragão de; Wiederkehr, Barbara de Aguiar; Marques, Camila Aparecida Moraes; Rosa, Francielle França da; Nanni, Felipe de Negreiros; Fuchs, Taíse

2017-01-01

To analyze the influence of portal vein ligation in hepatic regeneration by immunohistochemical criteria. Ten pigs divided into two groups of five animals underwent hepatectomy in two stages, and the groups were differentiated by ligation or not of the left portal vein tributary, which is responsible for vascularization of the left lateral and medial lobes of the pig liver. Five days after the procedure, the animals underwent liver biopsies for further analysis of histological and immunohistochemical with marker Ki67. The group submitted to hepatectomy with vascular ligation showed an increase of approximately 4% of hepatocytes in regeneration status, as well as a greater presence of Kupffer and inflammatory cells as compared to control. As a result of positive cell replication observed through the Ki67 marker, we can suspect that the ligation of a tributary of the portal vein associated with liver resection promoted a greater stimulus of liver regeneration when compared to liver resection alone. Analisar a influência da ligadura da tributária da veia porta no estímulo regenerativo hepático por meio de critérios imuno-histoquímicos. Dez suínos, divididos em dois grupos de cinco animais, foram submetidos à hepatectomia em dois estágios, sendo que os grupos foram diferenciados pela ligadura ou não da tributária da veia porta, responsável pela vascularização dos lobos lateral e medial esquerdos do fígado do suíno. Cinco dias após o procedimento, os animais foram reabordados para retirada de amostras hepáticas para posterior análise de histológica e imunoistoquímica com o marcador Ki67. O grupo submetido à hepatectomia com ligadura vascular apresentou incremento de 4% aproximadamente de hepatócitos em processo de regeneração, bem como grande número de células de Kupffer e células inflamatórias, quando comparado ao controle. Em virtude da análise positiva da replicação celular observada por meio do marcador Ki67, pode-se observar que a ligadura de uma tributária da veia porta promoveu um maior estímulo de regeneração hepática, efeito observado com menor intensidade no grupo submetido apenas à ressecção hepática.

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog.

PubMed

Jeunesse, Elisabeth C; Schneider, Marc; Woehrle, Frederique; Faucher, Mathieu; Lefebvre, Herve P; Toutain, Pierre-Louis

2013-12-11

Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin-induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs.For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD).The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 μg/L for creeping speed, 284 μg/L for the lameness score, 161 μg/L for the ground reaction vertical force and 193 μg/L for the body temperature.To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was determined for confirmatory clinical trials.

Pharmacokinetic/pharmacodynamic modeling for the determination of a cimicoxib dosing regimen in the dog

PubMed Central

2013-01-01

Background Cimicoxib is a new coxib anti-inflammatory drug for use in the dog. To determine a preclinical dosage regimen for cimicoxib in dog, a reversible model of kaolin–induced paw inflammation was used. Dosage regimens were established using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach (indirect response model). Results Analgesic, anti-inflammatory and antipyretic endpoints investigated with the inflammation model established the efficacy of cimicoxib at a dose of 2 mg/kg administered orally (single dose) in 12 beagle dogs. For both the oral and IV route of administration two groups of dogs to be identified namely Poor Metabolizers (PM) and Extensive Metabolizers (EM).The terminal half-life after oral administration was 8.0 ± 0.6 h for the PM and 4.6 ± 2.6 h for the EM groups, with the corresponding values after the IV route being 5.6 ± 1.7 h and 2.7 ± 0.9 h (mean ± SD). The main pharmacodynamic parameters (potency, efficacy, and sensitivity) were estimated for four endpoints (body temperature, creeping speed, ground vertical reaction force and clinical lameness score). The plasma concentration corresponding to half the maximum of the indirect effect were 239 μg/L for creeping speed, 284 μg/L for the lameness score, 161 μg/L for the ground reaction vertical force and 193 μg/L for the body temperature. To document possible polymorphism of the cimicoxib disposition in the target dog population, cimicoxib was administered by the intravenous route to 40 dogs (four different sized breeds). The cimicoxib half-lives in these 40 dogs were of same order of the magnitude as those of the EM beagle dogs. Thus pharmacokinetic and pharmacodynamic parameters obtained from the EM beagle dogs were selected to simulate the dose-effect relationship of cimicoxib after an oral administration allowing a dosage regimen to be selected for confirmation by a clinical trial. Conclusions Cimicoxib was an efficacious anti-inflammatory, antipyretic and analgesic drug and a dosage regimen of 2 mg/kg daily was determined for confirmatory clinical trials. PMID:24330630

Ultrasound-guided intrapleural positioning of pleural catheters: influence on immediate lung expansion and pleurodesis in patients with recurrent malignant pleural effusion.

PubMed

Araujo, Pedro Henrique Xavier Nabuco de; Terra, Ricardo Mingarini; Santos, Thiago da Silva; Chate, Rodrigo Caruso; Paiva, Antonio Fernando Lins de; Pêgo-Fernandes, Paulo Manuel

2017-01-01

To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE). This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure. Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35 patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in 10 (12%). No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL; interquartile range: -225 to 257 mL; p = 0.923), and clinical success of pleurodesis (85.8%; p = 0.676). Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE. Avaliar o papel do posicionamento intrapleural do cateter pleural na expansão pulmonar precoce e no sucesso da pleurodese em pacientes com derrame pleural maligno recorrente (DPMR). Trata-se de um estudo retrospectivo aninhado em um estudo prospectivo de coorte maior com pacientes com DPMR recrutados em um hospital-escola universitário terciário entre junho de 2009 e setembro de 2014. Os pacientes foram submetidos a inserção de cateter pleural e, em seguida, pleurodese à beira do leito. A TC de tórax foi realizada duas vezes: imediatamente antes da pleurodese (TCi) e 30 dias após a pleurodese (TC30). Com base na TCi, a posição do cateter foi classificada em posterolateral, anterior, fissural e subpulmonar. Usamos o volume pleural na TCi para estimar a expansão pulmonar precoce e a diferença entre os volumes pleurais na TC30 e na TCi a fim de avaliar o sucesso radiológico da pleurodese. Considerou-se que a pleurodese teve êxito clínico quando não foi necessário realizar nenhum outro procedimento pleural. Dos 131 pacientes elegíveis do estudo original, 85 foram incluídos neste estudo aninhado (64 mulheres; média de idade: 60,74 anos). A posição da ponta do cateter foi subpulmonar em 35 pacientes (41%), anterior em 23 (27%), posterolateral em 17 (20%) e fissural em 10 (12%). Não houve diferenças significativas entre os grupos quanto à expansão pulmonar precoce (mediana da cavidade pleural residual = 377 ml; intervalo interquartil: 171-722 ml; p = 0,645), sucesso radiológico da pleurodese (mediana do volume = 33 ml; intervalo interquartil: -225 a 257 ml; p = 0,923) e sucesso clínico da pleurodese (85,8%; p = 0,676). Nossos resultados sugerem que a posição da ponta do cateter pleural não influencia nem a expansão pulmonar precoce nem o sucesso da pleurodese à beira do leito em pacientes com DPMR.

CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc prolongation.

PubMed

Kumar, Yingying; Kung, Simon; Shinozaki, Gen

2014-12-01

Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome P450 system. We investigate associations between citalopram and escitalopram dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a retrospective chart review of citalopram or escitalopram patients with the inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and QTc interval on ECG. We further identified 42 citalopram users with citalopram serum concentration measurements and ECG. Regression and one-way ANOVA were used to examine the relationship between citalopram dose, citalopram serum concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients, the EM group had significantly shorter QTc intervals than a combined IM+PM group (427.1±23.6 ms vs. 440.1±26.6 ms, one-tailed t-test, p=0.029). In the 80 escitalopram cohort, there was no significant difference in QTc between phenotype groups. There was no statistical correlation between citalopram (p=0.62) or escitalopram (p=0.30) dose and QTc. QTc was not associated with citalopram serum level (p=0.45). In contrast to the FDA warning, this study found no association between citalopram/escitalopram dose and QTc. However, PM of the drug tended to have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in select patients may be helpful to guide medication optimization while limiting harmful effects. © The Author(s) 2014.

Radiation and chemical mutagen induced somaclonal variations through in vitro organogenesis of cotton (Gossypium hirsutum L.).

PubMed

Muthusamy, Annamalai; Jayabalan, Narayanasamy

2014-12-01

The purpose of the investigation was to induce somaclonal variations by gamma rays (GR), ethylmethane sulphonate (EMS) and sodium azide (SA) during in vitro organogenesis of cotton. The shoot tip explants were irradiated with 5-50 Gray (Gy) GR (Cobalt 60), 0.5-5.0 mM EMS and SA separately, and inoculated on Murashige and Skoog (MS) medium fortified with plant growth regulator (PGR) for organogenesis. The plantlets with well-developed root systems were acclimatized and transferred into the experimental field to screen the somaclonal variations during growth and development. The number of somaclonal variations was observed in growth of irradiated/treated shoot tips, multiplication, plantlet regeneration and growth in vitro and ex vitro. The lower doses/concentrations of mutagenic treatments showed significant enhancement in selected agronomical characters and they showed decreased trends with increasing doses/concentrations of mutagenic agents. The results of the present study revealed the influence of lower doses/concentrations of mutagenic treatments on in vitro and ex vitro growth of cotton plantlets and their significant improvement in agronomical characters which needs further imperative stability analysis. The present observations showed the platform to use lower doses/concentrations of mutagenic agents to induce variability for enhanced agronomical characters, resistant and tolerant cotton varieties.

Systematic training model for teaching, development and training of instructors in inguinal hernia treatment using the Lichtenstein technique. Hernia campaign 2014 & 2015.

PubMed

Lazzarini-Mendes, Carlos José; Pacheco, Adhemar Monteiro; Destro, Bárbara Bozzoli; Tamaro, Caroline; Nogueira, Fábio Antonio Del Picchia DE Araújo; Chen, David; Reinpold, Wolfgang; Bruscagin, Vitor; Roll, Sergio; Silva, Rodrigo Altenfelder

2016-01-01

to evaluate the method of training and continuing education of 18 surgeons in 2014, and 28 surgeons in 2015, in the Holy Homes of Ribeirao Preto, Araraquara, Franca and San Carlos of São Paulo, in the performance of Lichtenstein inguinal herniorrhaphy, tutored by the Faculty of Medical Sciences of the São Paulo Holy Home and the organization HERNIA HELP - "Hernia Repair for the Underserved". the training was tutored and systematized through an active methodology of teaching and learning, aiming to offer competence, skills and attitudes, measured by a previously validated Qualification Form, qualifying leaders in trainees' improvement. in 2014 the outcomes were: the difficulty of the case, direction, incision, dissection, mesh preparation, mesh cutting, mesh setting, closing, instruments, respect to tissues, flow, time and motion, and performance, all presented change in the general rating (p=0.000002); there was greater confidence in the execution of the procedure in 80% of trainees, considered "very valuable" in 93.3% of the interventions. In 2015, 28 surgeons were trained by ten surgeons previously qualified in 2014. The nerve identification rate, a relevant time the Lichtenstein technique, was 95.5% for the Iliohypogastric, 98.5% for the ilioinguinal and 89.4% for the genital branch of the genitofemoral nerve. the applied teaching method is possible, reproducible, reliable and valid. The joint efforts offer enormous opportunity of directed education, reaching underserved populations, revealing the great teacher-student social responsibility. avaliar resultados do método de treinamento e educação continuada de 18 cirurgiões, em 2014, e 28 cirurgiões, em 2015, nas Santas Casas de Ribeirão Preto, Araraquara, Franca e São Carlos do Estado de São Paulo, na realização da Herniorrafia Inguinal à Lichtenstein, tutorados pela Faculdade de Ciências Médicas da Santa Casa de São Paulo e pela organização HERNIA HELP - "Hernia Repair for the Underserved". treinamento tutorado e sistematizado, através de metodologia ativa de ensino e aprendizagem, visando a oferecer competência, habilidade e atitudes, auferidas por um Formulário de Qualificação previamente validado, qualificando líderes no aperfeiçoamento de treinandos. em 2014, os desfechos foram: dificuldade do caso, direção, incisão, dissecção, preparo da tela, corte da tela, fixação da tela, fechamento, instrumentos, respeito aos tecidos, fluxo, tempo e movimento e desempenho, apresentaram mudança na Classificação Geral (p=0,000002); houve maior confiança na execução do procedimento em 80% dos treinandos, sendo considerado "Muito Valioso" em 93,3% das participações. Em 2015, os 28 cirurgiões foram treinados por dez cirurgiões previamente qualificados em 2014. A taxa de identificação dos nervos, tempo relevante da técnica de Lichtenstein, foi 95,5 % para o ílio-hipogástrico, 98,5% para o ilioinguinal e 89,4% para o ramo genital do nervo genitofemoral. o método de ensino aplicado é possível, reprodutível, confiável e válido. Os mutirões oferecem a enorme oportunidade do ensino, dirigido, atingindo populações carentes, revelando a grande responsabilidade social docente-discente.

Screening of drugs to treat 8p11 myeloproliferative syndrome using patient-derived induced pluripotent stem cells with fusion gene CEP110-FGFR1.

PubMed

Yamamoto, Shohei; Otsu, Makoto; Matsuzaka, Emiko; Konishi, Chieko; Takagi, Haruna; Hanada, Sachiyo; Mochizuki, Shinji; Nakauchi, Hiromitsu; Imai, Kohzoh; Tsuji, Kohichiro; Ebihara, Yasuhiro

2015-01-01

Induced pluripotent stem (iPS) cells provide powerful tools for studying disease mechanisms and developing therapies for diseases. The 8p11 myeloproliferative syndrome (EMS) is an aggressive chronic myeloproliferative disorder (MPD) that is caused by constitutive activation of fibroblast growth factor receptor 1. EMS is rare and, consequently, effective treatment for this disease has not been established. Here, iPS cells were generated from an EMS patient (EMS-iPS cells) to assist the development of effective therapies for EMS. When iPS cells were co-cultured with murine embryonic stromal cells, EMS-iPS cells produced more hematopoietic progenitor and hematopoietic cells, and CD34+ cells derived from EMS-iPS cells exhibited 3.2-7.2-fold more macrophage and erythroid colony forming units (CFUs) than those derived from control iPS cells. These data indicate that EMS-iPS cells have an increased hematopoietic differentiation capacity, which is characteristic of MPDs. To determine whether a tyrosine kinase inhibitor (TKI) could suppress the increased number of CFUs formed by EMS-iPS-induced CD34+ cells, cells were treated with one of four TKIs (CHIR258, PKC 412, ponatinib, and imatinib). CHIR258, PKC 412, and ponatinib reduced the number of CFUs formed by EMS-iPS-induced CD34+ cells in a dose-dependent manner, whereas imatinib did not. Similar effects were observed on primary peripheral blood cells (more than 90% of which were blasts) isolated from the patient. This study provides evidence that the EMS-iPS cell line is a useful tool for the screening of drugs to treat EMS and to investigate the mechanism underlying this disease.

Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7.

PubMed

Helås, T; Sagafos, D; Kleggetveit, I P; Quiding, H; Jönsson, B; Segerdahl, M; Zhang, Z; Salter, H; Schmelz, M; Jørum, E

2017-09-01

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity. Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose-response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na V 1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia. Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na V 1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance. Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na V 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in Na V 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls. © 2017 European Pain Federation - EFIC®.

Ultrastable gold substrates: Properties of a support for high-resolution electron cryomicroscopy of biological specimens

PubMed Central

Russo, Christopher J.; Passmore, Lori A.

2016-01-01

Electron cryomicroscopy (cryo-EM) allows structure determination of a wide range of biological molecules and specimens. All-gold supports improve cryo-EM images by reducing radiation-induced motion and image blurring. Here we compare the mechanical and electrical properties of all-gold supports to amorphous carbon foils. Gold supports are more conductive, and have suspended foils that are not compressed by differential contraction when cooled to liquid nitrogen temperatures. These measurements show how the choice of support material and geometry can reduce specimen movement by more than an order of magnitude during low-dose imaging. We provide methods for fabrication of all-gold supports and preparation of vitrified specimens. We also analyse illumination geometry for optimal collection of high resolution, low-dose data. Together, the support structures and methods herein can improve the resolution and quality of images from any electron cryomicroscope. PMID:26592474

Melhoramentos no código Wilson-Devinney para binárias eclipsantes

NASA Astrophysics Data System (ADS)

Vieira, L. A.; Vaz, L. P. R.

2003-08-01

A análise de curvas de luz e velocidades radiais de sistemas binários eclipsantes pode ser feita por meio de vários modelos. Um desses é o Modelo Wilson-Devinney (WD). Ao longo dos anos, esse modelo sofreu várias alterações em seus códigos principais, com a finalidade de torná-lo mais consistente tanto fíisica como numericamente. O Modelo WD tem sido melhorado de várias maneiras em seus dois códigos: um para a predição das curvas de luz teórica e de velocidade radiais e outra para as soluções destas curvas. Teoricamente, na física do modelo, nós introduzimos a possibilidade de levar em conta os efeitos do movimento apsidal. Numericamente, nós introduzimos a possibilidade de usar o Método SIMPLEX no procedimento da solução, como uma alternativa para o já implementado Método de Mínimos Quadrados (Least Squares Method). Estas modificações, juntamente com outras já introduzidas pelo nosso grupo anteriormente, tornam o código mais eficiente na solução das curvas de luz e de velocidade radiais de binárias eclipsantes. Como o modelo tem sido usado para analisar sistemas com componentes pré-sequência principal (TY CrA, Casey et al. 1998, Vaz et al. 1998), SM 790, Stassun et al. 2003), este melhoramento beneficiará estes casos também. Apresentamos os resultados obtidos com a modificação do código WD por meio do uso de dados da estrela GL Carinae, comprovando, (1) que os parâmetros orbitais calculados por nós são coerentes com os obtidos anteriormente na literatura (Giménez & Clausen, 1986) e com os obtidos por Faria (1987), e (2) que a implementação do Método SIMPLEX torna o código mais lento mas completamente consistente internamente e evita os problemas gerados pelo uso do Método de Mínimos Quadrados, tais como imprecisão no cálculo das derivadas parciais e convergência para mínimos locais.

Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ji Hyun; Stein, Anthony; Tsai, Nicole

Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph nodemore » chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.« less

Utilization of a quantitative mammalian cell mutation system, CHO/HGPRT, in experimental mutagenesis and genetic toxicology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsie, A. W.; Couch, D. B.; O'Neill, J. P.

1977-01-01

Development of the CHO/HGPRT system is described and a host-mediated CHO/HGPRT assay is discussed. The following topics are discussed: evidence for the genetic origin of mutation induction in the CHO/HGPRT system; dose-response relationship for EMS-mediated mutation induction and cell lethality; apparent dosimetry of EMS-induced mutagenesis; structure-activity relationship of alkylating agents and ICR compounds; mutagenicity and cytotoxicity of congeners of two classes of nitrosi compounds; and preliminary validation of the CHO/HGPRT assay in predicting chemical carcinogenicity. (HLW)

Enantioselectivity of debrisoquine 4-hydroxylation in Brazilian Caucasian hypertensive patients phenotyped as extensive metabolizers.

PubMed

Cerqueira, P M; Mateus, F H; Cesarino, E J; Bonato, P S; Lanchote, V L

2000-12-01

Debrisoquine (D), an antihypertensive drug metabolized to 4-hydroxydebrisoquine (4-OHD) by CYP2D6, is commonly used as an in vivo probe of CYP2D6 activity and can be used to phenotype individuals as either extensive (EMs) or poor metabolizers (PMs) of such drugs as beta-adrenergic blockers, tricyclic antidepressants, and class 1C antiarrhythmics. This report describes reversed-phase HPLC systems by which D and 4-OHD or S-(+) and R-(-)-4-OHD in urine are more selectively quantified without the need for derivatization techniques. We also studied the urinary excretion of R-(-)- and S-(+)-4-hydroxydebrisoquine in EM hypertensive patients in order to determine weather 4-OHD formation exhibits enantioselectivity. Twelve patients with mild to severe essential hypertension were admitted to the study. They received a single tablet of Declinax containing 10 mg debrisoquine sulfate. All the urine excreted during the following 8 h was collected. The debrisoquine metabolic ratio (DMR) was calculated as % of dose excreted as D/% of dose excreted as 4-OHD and the debrisoquine recovery ratio (DRR) was calculated as % of dose excreted as 4-OHD/% of dose excreted as D+4-OHD. Debrisoquine and its metabolite were determined in urine by HPLC using a reversed-phase Select B LiChrospher column, a mobile phase of 0.25 N acetate buffer, pH 5-acetonitrile (9:1, v/v) and a fluorescence detector. The limit of quantitation was determined to be 25.0 ng/ml for D and 18.75 ng/ml for 4-OHD. Intra- and inter-day relative standard deviations (RSDs) were less than 10%. All hypertensive patients studied showed a DMR of less than 12.6 or a DRR higher than 0.12 and were classified as EMs. Direct enantioselective separation on chiral stationary phase involved resolution of S-(+)-4-OHD and R-(-)-4-OHD on a Chiralcel OD-R column with a mobile phase of 0.125 N sodium perchlorate, pH 5-acetonitrile-methanol (85:12:3, v/v/v). The quantitation limit of each enantiomer was 3.75 ng/ml of urine. Intra- and inter-day RSDs were less than 10% for each enantiomer. A high degree of enantioselectivity in the 4-hydroxylation of D favouring the S-(+) enantiomer was observed, resulting in R-(-)-4-OHD not detected in the urine of the EM hypertensive patients studied.

Shielding NSLS-II light source: Importance of geometry for calculating radiation levels from beam losses

DOE PAGES

Kramer, S. L.; Ghosh, V. J.; Breitfeller, M.; ...

2016-08-10

We present that third generation high brightness light sources are designed to have low emittance and high current beams, which contribute to higher beam loss rates that will be compensated by Top-Off injection. Shielding for these higher loss rates will be critical to protect the projected higher occupancy factors for the users. Top-Off injection requires a full energy injector, which will demand greater consideration of the potential abnormal beam miss-steering and localized losses that could occur. The high energy electron injection beam produces significantly higher neutron component dose to the experimental floor than a lower energy beam injection and rampedmore » operations. Minimizing this dose will require adequate knowledge of where the miss-steered beam can occur and sufficient EM shielding close to the loss point, in order to attenuate the energy of the particles in the EM shower below the neutron production threshold (<10 MeV), which will spread the incident energy on the bulk shield walls and thereby the dose penetrating the shield walls. Designing supplemental shielding near the loss point using the analytic shielding model is shown to be inadequate because of its lack of geometry specification for the EM shower process. To predict the dose rates outside the tunnel requires detailed description of the geometry and materials that the beam losses will encounter inside the tunnel. Modern radiation shielding Monte-Carlo codes, like FLUKA, can handle this geometric description of the radiation transport process in sufficient detail, allowing accurate predictions of the dose rates expected and the ability to show weaknesses in the design before a high radiation incident occurs. The effort required to adequately define the accelerator geometry for these codes has been greatly reduced with the implementation of the graphical interface of FLAIR to FLUKA. In conclusion, this made the effective shielding process for NSLS-II quite accurate and reliable. The principles used to provide supplemental shielding to the NSLS-II accelerators and the lessons learned from this process are presented.« less

Evaluation of genotoxic activity of maleic hydrazide, ethyl methane sulfonate, and N-nitroso diethylamine in Tradescantia.

PubMed

Alvarez-Moya, C; Santerre-Lucas, A; Zúñiga-González, G; Torres-Bugarín, O; Padilla-Camberos, E; Feria-Velasco, A

2001-01-01

To assess the genotoxic activity of N-nitroso diethylamine (NDEA), maleic hydrazide (MH), and ethyl methane sulfonate (EMS) using two systems: the comet assay on nuclei from Tradescantia, and the pink mutation test on Tradescantia staminal hairs (clone 4430). Tradescantia cups was obtained from Laboratorio de Citogenética y Mutagénesis del Centro de Ciencias de la Atmósfera de la Universidad Nacional Autónoma de México and treated with: N-nitroso diethylamine (NDEA) at 1, 5, 10 mM, maleic hydrazide (MH) at 1, 5, 10 mM and ethyl methane sulfonate (EMS) at 15, 30 and 45 mM; and used in both pink mutation assay and comet assay using cellular nuclei from Tradescantia staminal hairs. The observation of staminal hair was realized along eight days (6-14) after treatment), flowers produced day 14 after treatment were utilized done according to Underbrink. In previous reports on plants, were comet assay was used, breaking cellular wall and separating by centrifugation gradient are necessary. Here, nuclei from staminal hairs were obtained by squashing the cells (is not necessary to utilize to break special procedure cellular wall), collected using a nylon mesh of 80 Mm and next the comet assay was applied. Student's T test was the statistical test used for analyzing the comet assay data. Both assays showed a great sensitivity to the studied mutagens. A relationship between the dose-pink event and the dose-tail length was evident. Even though the Tradescantia mutation assay is a sensitive test with MH and EMS, low doses of NDEA were not able to induce a significant increase in the pink event frequencies; however, the comet assay was able to detect the mutagenic effect of NDEA at the same dose. Thus, it is clear that the comet assay is highly sensitive to the lowest dose of chemical mutagens. The comet assay on nuclei from Tradescantia staminal hairs is a useful tool to monitor genotoxic agents; it is simple, highly sensitive, and faster than the pink mutation test.

Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele.

PubMed

Cui, Yi M; Teng, Choo H; Pan, Alan X; Yuen, Eunice; Yeo, Kwee P; Zhou, Ying; Zhao, Xia; Long, Amanda J; Bangs, Mark E; Wise, Stephen D

2007-10-01

To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects. Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.

NON-TOXIC MELANOMA THERAPY BY A NOVEL TUBULIN-BINDING AGENT

PubMed Central

Aneja, Ritu; Asress, Seneshaw; Dhiman, Neerupma; Awasthi, Anshumali; Rida, Padmashree C.G.; Arora, Sudarshan K.; Zhou, Jun; Glass, Jonathan D.; Joshi, Harish C.

2009-01-01

(S)-3-((R)-9-bromo-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquino-lin-5-yl)-6,7-dimethoxyisobenzofuran-1(3H)-one (EM011) is a tubulin-binding agent with significant anticancer activity. Here we show that EM011 modulates microtubule dynamics at concentrations that do not alter the total polymer mass of tubulin. In particular, EM011 decreases the transition frequencies between growth and shortening phases and increases the duration microtubules spend in an idle ‘pause’ state. Using B16LS9 murine melanoma cells, we show that EM011 briefly arrests cell-cycle progression at the G2/M phase by formation of multiple aster spindles. An aberrant mitotic exit without cytokinesis then occurs, leading to the accumulation of abnormal multinucleated cells prior to apoptosis. Our pharmacokinetic studies conformed to a linear dose-response relationship upto 150 mg/kg. However, non-linearity was observed at 300 mg/kg. In a syngeneic murine model of subcutaneous melanoma, better antitumor responses were seen at 150 mg/kg compared to 300 mg/kg of EM011. Unlike currently available chemotherapeutics, EM011 is non-toxic to normal tissues and most importantly, does not cause any immunosuppression and neurotoxicity. Our data thus warrant a clinical evaluation of EM011 for melanoma therapy. PMID:19626589

Disparity in Cutaneous Pigmentary Response to LED vs Halogen Incandescent Visible Light: Results from a Single Center, Investigational Clinical Trial Determining a Minimal Pigmentary Visible Light Dose.

PubMed

Soleymani, Teo; Cohen, David E; Folan, Lorcan M; Okereke, Uchenna R; Elbuluk, Nada; Soter, Nicholas A

2017-11-01

Background: While most of the attention regarding skin pigmentation has focused on the effects of ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. The purpose of this study was to investigate the cutaneous pigmentary response to pure visible light irradiation, examine the difference in response to different sources of visible light irradiation, and determine a minimal pigmentary dose of visible light irradiation in melanocompetent subjects with Fitzpatrick skin type III - VI. The study was designed as a single arm, non-blinded, split-side dual intervention study in which subjects underwent visible light irradiation using LED and halogen incandescent light sources delivered at a fluence of 0.14 Watts/cm2 with incremental dose progression from 20 J/cm2 to 320 J/cm2. Pigmentation was assessed by clinical examination, cross-polarized digital photography, and analytic colorimetry. Immediate, dose-responsive pigment darkening was seen with LED light exposure in 80% of subjects, beginning at 60 Joules. No pigmentary changes were seen with halogen incandescent light exposure at any dose in any subject. This study is the first to report a distinct difference in cutaneous pigmentary response to different sources of visible light, and the first to demonstrate cutaneous pigment darkening from visible LED light exposure. Our findings raise the concern that our increasing daily artificial light surroundings may have clandestine effects on skin biology.

J Drugs Dermatol. 2017;16(11):1105-1110.

Vaccine-induced toxic epidermal necrolysis: A case and systematic review.

PubMed

Chahal, Dev; Aleshin, Maria; Turegano, Mamina; Chiu, Melvin; Worswick, Scott

2018-01-15

Erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are cutaneous hypersensitivityreactions that develop in response to specific triggers such as medications and certain infections. Vaccines, which undergo rigorous safety testing prior to use in humans, are a rare cause of SJS/TEN and little is known about the frequency of such events and corresponding pathogenesis. Herein, we discuss a case of suspected TEN in a 19-year-old woman who received the meningococcal B vaccine (the first report of such an association) and conduct a systematic review of the associated literature. We also discuss management of this patient with a single dose of etanercept. Relevant literature was searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. A total of 29 articles reporting EM, SJS, or TEN following vaccination were included from >5 countries. Of the 29, 22 articles reported EM, 6/29 reported SJS, and 4/29 reported TEN (3 articlesreported cases of both EM and SJS/TEN). We suggest consideration of vaccines as an etiology for cases of SJS or TEN that begin with an EM-like presentation, and provide further evidence for the use of etanercept as a viable treatment for TEN.

Test of 3D CT reconstructions by EM + TV algorithm from undersampled data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evseev, Ivan; Ahmann, Francielle; Silva, Hamilton P. da

2013-05-06

Computerized tomography (CT) plays an important role in medical imaging for diagnosis and therapy. However, CT imaging is connected with ionization radiation exposure of patients. Therefore, the dose reduction is an essential issue in CT. In 2011, the Expectation Maximization and Total Variation Based Model for CT Reconstruction (EM+TV) was proposed. This method can reconstruct a better image using less CT projections in comparison with the usual filtered back projection (FBP) technique. Thus, it could significantly reduce the overall dose of radiation in CT. This work reports the results of an independent numerical simulation for cone beam CT geometry withmore » alternative virtual phantoms. As in the original report, the 3D CT images of 128 Multiplication-Sign 128 Multiplication-Sign 128 virtual phantoms were reconstructed. It was not possible to implement phantoms with lager dimensions because of the slowness of code execution even by the CORE i7 CPU.« less

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

PubMed

Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof

2018-06-06

To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. ClinicalTrials.gov, NCT01760954 and NCT02143713.

Investigation of contrast-enhanced subtracted breast CT images with MAP-EM based on projection-based weighting imaging.

PubMed

Zhou, Zhengdong; Guan, Shaolin; Xin, Runchao; Li, Jianbo

2018-06-01

Contrast-enhanced subtracted breast computer tomography (CESBCT) images acquired using energy-resolved photon counting detector can be helpful to enhance the visibility of breast tumors. In such technology, one challenge is the limited number of photons in each energy bin, thereby possibly leading to high noise in separate images from each energy bin, the projection-based weighted image, and the subtracted image. In conventional low-dose CT imaging, iterative image reconstruction provides a superior signal-to-noise compared with the filtered back projection (FBP) algorithm. In this paper, maximum a posteriori expectation maximization (MAP-EM) based on projection-based weighting imaging for reconstruction of CESBCT images acquired using an energy-resolving photon counting detector is proposed, and its performance was investigated in terms of contrast-to-noise ratio (CNR). The simulation study shows that MAP-EM based on projection-based weighting imaging can improve the CNR in CESBCT images by 117.7%-121.2% compared with FBP based on projection-based weighting imaging method. When compared with the energy-integrating imaging that uses the MAP-EM algorithm, projection-based weighting imaging that uses the MAP-EM algorithm can improve the CNR of CESBCT images by 10.5%-13.3%. In conclusion, MAP-EM based on projection-based weighting imaging shows significant improvement the CNR of the CESBCT image compared with FBP based on projection-based weighting imaging, and MAP-EM based on projection-based weighting imaging outperforms MAP-EM based on energy-integrating imaging for CESBCT imaging.

Electromagnetic navigation versus fluoroscopy in aortic endovascular procedures: a phantom study.

PubMed

Tystad Lund, Kjetil; Tangen, Geir Arne; Manstad-Hulaas, Frode

2017-01-01

To explore the possible benefits of electromagnetic (EM) navigation versus conventional fluoroscopy during abdominal aortic endovascular procedures. The study was performed on a phantom representing the abdominal aorta. Intraoperative cone beam computed tomography (CBCT) of the phantom was acquired and merged with a preoperative multidetector CT (MDCT). The CBCT was performed with a reference plate fixed to the phantom that, after merging the CBCT with the MDCT, facilitated registration of the MDCT volume with the EM space. An EM field generator was stationed near the phantom. Navigation software was used to display EM-tracked instruments within the 3D image volume. Fluoroscopy was performed using a C-arm system. Five operators performed a series of renal artery cannulations using modified instruments, alternatingly using fluoroscopy or EM navigation as the sole guidance method. Cannulation durations and associated radiation dosages were noted along with the number of cannulations complicated by loss of guidewire insertion. A total of 120 cannulations were performed. The median cannulation durations were 41.5 and 34.5 s for the fluoroscopy- and EM-guided cannulations, respectively. No significant difference in cannulation duration was found between the two modalities (p = 0.736). Only EM navigation showed a significant reduction in cannulation duration in the latter half of its cannulation series compared with the first half (p = 0.004). The median dose area product for fluoroscopy was 0.0836 [Formula: see text]. EM-guided cannulations required a one-time CBCT dosage of 3.0278 [Formula: see text]. Three EM-guided and zero fluoroscopy-guided cannulations experienced loss of guidewire insertion. Our findings indicate that EM navigation is not inferior to fluoroscopy in terms of the ability to guide endovascular interventions. Its utilization may be of particular interest in complex interventions where adequate visualization or minimal use of contrast agents is critical. In vivo studies featuring an optimized implementation of EM navigation should be conducted.

Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.

PubMed

Clemency, Brian M; Thompson, Jeffrey J; Tundo, Gina N; Lindstrom, Heather A

2013-10-01

High-dose intravenous nitroglycerin is a common in-hospital treatment for respiratory distress due to congestive heart failure (CHF) with hypertension. Intravenous (IV) nitroglycerin administration is impractical in the prehospital setting. In 2011, a new regional Emergency Medical Services (EMS) protocol was introduced allowing advanced providers to treat CHF with high-dose oral nitroglycerin. The protocol calls for patients to be treated with two sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as needed. Hypothesis/Problem To assess the protocol's safety, the incidence of hypotension following prehospital administration of multiple simultaneous nitroglycerin (MSN) tabs by EMS providers was studied. This study was a retrospective cohort study of patients from a single commercial EMS agency over a 6-month period. Records from patients with at least one administration of MSN were reviewed. For each administration, the first documented vital signs pre- and post-administration were compared. Administrations were excluded if pre- or post-administration vital signs were missing. One hundred case-patients had at least one MSN administration by an advanced provider during the study period. Twenty-five case-patients were excluded due to incomplete vital signs. Seventy-five case-patients with 95 individual MSN administrations were included for analysis. There were 65 administrations of two tabs, 29 administrations of three tabs, and one administration of four tabs. The mean change in SBP following MSN was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had documented systolic hypotension in the post-administration vital signs (97/71, 78/50 and 66/47). All three patients were over 65 years old, were administered two tabs, had documented improved respiratory status, and had repeat SBP of at least 100. The incidence of hypotension following MSN administration was 3.2%. Discussion High-dose oral nitroglycerin administration is a practical alternative to IV nitroglycerin in the prehospital setting when administered by advanced providers. The prehospital protocol for high dose oral nitroglycerin was demonstrated to be safe in the cohort of patients studied. Limitations of the study include the relatively small sample size and the inability to identify hypotension that may have occurred following the cessation of data collection in the field. Hypotension was rare and self-limited in prehospital patients receiving MSN.

Effect of esomeprazole and rabeprazole on intragastric pH in healthy Chinese: an open, randomized crossover trial.

PubMed

Li, Zhao-Shen; Zhan, Xian-Bao; Xu, Guo-Ming; Cheng, Neng-Neng; Liao, Zhuan

2007-06-01

Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese. Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM). The percentage of time with intragastric pH >4 was significantly higher (P < 0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (P 4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P < 0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH >4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated. Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.

Intensive rehabilitative approach to eosinophilia myalgia syndrome associated with severe polyneuropathy.

PubMed

Draznin, E; Rosenberg, N L

1993-07-01

We report a case of the eosinophilia myalgia syndrome (EMS) with incapacitating myalgias, weakness secondary to a severe polyneuropathy, and contractures in all four extremities requiring aggressive rehabilitation treatment. A 55-year-old woman was admitted to a rehabilitation hospital 11 months after the onset of EMS. At that time, she had severe weakness secondary to peripheral neuropathy and painful contractures in all extremities and required high doses of narcotics for pain control. A continuous passive range of motion machine was used in order to maintain range of motion obtained during active exercise therapy. The patient showed functional improvement in basic mobility and ADL skills. She was withdrawn from narcotics and successfully learned pain management techniques. An aggressive rehabilitation approach in the treatment of EMS associated with peripheral neuropathy may improve functional outcome even when instituted late in the clinical course.

Effects of artichoke (Cynara scolymus) leaf and bloom head extracts on chemically induced DNA lesions in Drosophila melanogaster

PubMed Central

Jacociunas, Laura Vicedo; Dihl, Rafael Rodrigues; Lehmann, Mauricio; de Barros Falcão Ferraz, Alexandre; Richter, Marc François; da Silva, Juliana; de Andrade, Heloísa Helena Rodrigues

2014-01-01

The genotoxicity of bloom head (BHE) and leaf (LE) extracts from artichoke (Cynara scolymus L.), and their ability to modulate the mutagenicity and recombinogenicity of two alkylating agents (ethyl methanesulfonate – EMS and mitomycin C – MMC) and the intercalating agent bleomycin (BLM), were examined using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Neither the mutagenicity nor the recombinogenicity of BLM or MMC was modified by co- or post-treatment with BHE or LE. In contrast, co-treatment with BHE significantly enhanced the EMS-induced genotoxicity involving mutagenic and/or recombinant events. Co-treatment with LE did not alter the genotoxicity of EMS whereas post-treatment with the highest dose of LE significantly increased this genotoxicity. This enhancement included a synergistic increase restricted to somatic recombination. These results show that artichoke extracts promote homologous recombination in proliferative cells of D. melanogaster. PMID:24688296

Effects of artichoke (Cynara scolymus) leaf and bloom head extracts on chemically induced DNA lesions in Drosophila melanogaster.

PubMed

Jacociunas, Laura Vicedo; Dihl, Rafael Rodrigues; Lehmann, Mauricio; de Barros Falcão Ferraz, Alexandre; Richter, Marc François; da Silva, Juliana; de Andrade, Heloísa Helena Rodrigues

2014-03-01

The genotoxicity of bloom head (BHE) and leaf (LE) extracts from artichoke (Cynara scolymus L.), and their ability to modulate the mutagenicity and recombinogenicity of two alkylating agents (ethyl methanesulfonate - EMS and mitomycin C - MMC) and the intercalating agent bleomycin (BLM), were examined using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Neither the mutagenicity nor the recombinogenicity of BLM or MMC was modified by co- or post-treatment with BHE or LE. In contrast, co-treatment with BHE significantly enhanced the EMS-induced genotoxicity involving mutagenic and/or recombinant events. Co-treatment with LE did not alter the genotoxicity of EMS whereas post-treatment with the highest dose of LE significantly increased this genotoxicity. This enhancement included a synergistic increase restricted to somatic recombination. These results show that artichoke extracts promote homologous recombination in proliferative cells of D. melanogaster.

Fast, automatic, and accurate catheter reconstruction in HDR brachytherapy using an electromagnetic 3D tracking system.

PubMed

Poulin, Eric; Racine, Emmanuel; Binnekamp, Dirk; Beaulieu, Luc

2015-03-01

In high dose rate brachytherapy (HDR-B), current catheter reconstruction protocols are relatively slow and error prone. The purpose of this technical note is to evaluate the accuracy and the robustness of an electromagnetic (EM) tracking system for automated and real-time catheter reconstruction. For this preclinical study, a total of ten catheters were inserted in gelatin phantoms with different trajectories. Catheters were reconstructed using a 18G biopsy needle, used as an EM stylet and equipped with a miniaturized sensor, and the second generation Aurora(®) Planar Field Generator from Northern Digital Inc. The Aurora EM system provides position and orientation value with precisions of 0.7 mm and 0.2°, respectively. Phantoms were also scanned using a μCT (GE Healthcare) and Philips Big Bore clinical computed tomography (CT) system with a spatial resolution of 89 μm and 2 mm, respectively. Reconstructions using the EM stylet were compared to μCT and CT. To assess the robustness of the EM reconstruction, five catheters were reconstructed twice and compared. Reconstruction time for one catheter was 10 s, leading to a total reconstruction time inferior to 3 min for a typical 17-catheter implant. When compared to the μCT, the mean EM tip identification error was 0.69 ± 0.29 mm while the CT error was 1.08 ± 0.67 mm. The mean 3D distance error was found to be 0.66 ± 0.33 mm and 1.08 ± 0.72 mm for the EM and CT, respectively. EM 3D catheter trajectories were found to be more accurate. A maximum difference of less than 0.6 mm was found between successive EM reconstructions. The EM reconstruction was found to be more accurate and precise than the conventional methods used for catheter reconstruction in HDR-B. This approach can be applied to any type of catheters and applicators.

Fast, automatic, and accurate catheter reconstruction in HDR brachytherapy using an electromagnetic 3D tracking system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulin, Eric; Racine, Emmanuel; Beaulieu, Luc, E-mail: Luc.Beaulieu@phy.ulaval.ca

2015-03-15

Purpose: In high dose rate brachytherapy (HDR-B), current catheter reconstruction protocols are relatively slow and error prone. The purpose of this technical note is to evaluate the accuracy and the robustness of an electromagnetic (EM) tracking system for automated and real-time catheter reconstruction. Methods: For this preclinical study, a total of ten catheters were inserted in gelatin phantoms with different trajectories. Catheters were reconstructed using a 18G biopsy needle, used as an EM stylet and equipped with a miniaturized sensor, and the second generation Aurora{sup ®} Planar Field Generator from Northern Digital Inc. The Aurora EM system provides position andmore » orientation value with precisions of 0.7 mm and 0.2°, respectively. Phantoms were also scanned using a μCT (GE Healthcare) and Philips Big Bore clinical computed tomography (CT) system with a spatial resolution of 89 μm and 2 mm, respectively. Reconstructions using the EM stylet were compared to μCT and CT. To assess the robustness of the EM reconstruction, five catheters were reconstructed twice and compared. Results: Reconstruction time for one catheter was 10 s, leading to a total reconstruction time inferior to 3 min for a typical 17-catheter implant. When compared to the μCT, the mean EM tip identification error was 0.69 ± 0.29 mm while the CT error was 1.08 ± 0.67 mm. The mean 3D distance error was found to be 0.66 ± 0.33 mm and 1.08 ± 0.72 mm for the EM and CT, respectively. EM 3D catheter trajectories were found to be more accurate. A maximum difference of less than 0.6 mm was found between successive EM reconstructions. Conclusions: The EM reconstruction was found to be more accurate and precise than the conventional methods used for catheter reconstruction in HDR-B. This approach can be applied to any type of catheters and applicators.« less

Enantioselective disposition of rabeprazole in relation to CYP2C19 genotypes

PubMed Central

Miura, Masatomo; Kagaya, Hideaki; Tada, Hitoshi; Uno, Tsukasa; Yasui-Furukori, Norio; Tateishi, Tomonori; Suzuki, Toshio

2006-01-01

Aim Rabeprazole is metabolized to some extent by CYP2C19. The purpose of this study was to elucidate the pharmacokinetics of each rabeprazole enantiomer in three different CYP2C19 genotype groups. Methods Twenty-four healthy subjects, of whom each each were homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs) and poor metabolizers (PMs) for CYP2C19, participated in our study. After a single oral dose of 20 mg of racemic rabeprazole, the plasma concentrations of the rabeprazole enantiomers were measured over the course of 24 h. Results The area under the plasma concentration–time curves (AUC) of (R)-rabeprazole in homEMs, hetEMs and PMs were 1.8-, 2.2- and 2.4-fold, respectively, greater than those of (S)-rabeprazole; the relative AUC ratios of (R)- and (S)-rabeprazole in homEMs, hetEMs and PMs were 1 : 1.1 : 2.1 and 1 : 0.9 : 1.5, respectively. The mean maximum plasma concentrations (Cmax) of (R)-rabeprazole in homEMs, hetEMs and PMs were 1.7-, 1.9- and 1.8-fold higher, respectively, than those of the corresponding (S)-enantiomer (P < 0.05). There was no difference between homEMs and PMs in the elimination half-life of (S)-rabeprazole, whereas the elimination half-life of (R)-rabeprazole was significantly longer in PMs than in homEMs [1.7 h (1.4, 2.0) (mean (95% confidence interval)]vs. 0.8 h (0.6, 1.0), respectively, P < 0.0001). Conclusions (R)-Rabeprazole disposition was influenced to a greater degree by CYP2C19 genetic polymorphisms than was that of (S)-rabeprazole. The effect of CYP2C19 polymorphisms on the stereoselective disposition of rabeprazole was less than those of lansoprazole and omeprazole. PMID:16487225

NUTRITIONAL ASPECTS AND THE USE OF NUTRITIONAL SUPPLEMENTS BY WOMEN WHO UNDERWENT GASTRIC BYPASS.

PubMed

Trindade, Elisangela Mara; Gebara, Telma Souza E Silva; Cambi, Maria Paula Carlini; Baretta, Giorgio Alfredo Pedroso

2017-01-01

Bariatric surgery is deemed one of the most effective procedures for the treatment of obesity and it aims at the reduction and maintenance of weight loss in long term, as the control of the related comorbidities. Quantify the occurrence of alterations of the gastrointestinal tract, suggestive signs of nutritional deficiencies and the use of supplements in a group of women undergoing bariatric surgery. The sample consisted of women aged 20-65 years submitted to Roux-en-Y gastric bypass with monitoring equal to or higher than 24 months. For the qualitative analysis, the Feeding Frequency Questionnaire was used. In the postoperative period, alopecia was the most reported (79.3%), followed by changes in the texture of the nails, both considered predictive of nutritional deficiencies. Changes in the gastrointestinal tract were described in 86.2%, and episodes of dumping were reported in 65.5%. Qualitative analysis has shown reduced daily consumption of sources of animal and plant proteins. After bariatric surgery can occur flatulence, vomiting and dumping syndrome as the most frequent representative symptoms of digestive functional disorders. Alopecia and nail changes are the most important signs of nutritional deficiency. The use of dietary supplements in the postoperative period is scarce and sporadic. A cirurgia bariátrica é considerada um dos procedimentos mais eficazes para tratamento da obesidade e objetiva a redução e manutenção da perda de peso em longo prazo, assim como, o controle das comorbidades associadas. Quantificar a ocorrência de alterações funcionais do trato gastrointestinal, sinais sugestivos de carências nutricionais e o uso de suplementos em um grupo de mulheres submetidas à cirurgia bariátrica. A amostra foi constituída por mulheres com idades entre 20-65 anos submetidas ao bypass gástrico em Y-de-Roux com seguimento igual ou superior a 24 meses. Para análise qualitativa foi utilizado o Questionário de Frequência Alimentar. No período pós-operatório a alopecia foi a mais relatada (79,3%), seguida de alteração na textura das unhas, ambas consideradas preditivos de carências nutricionais. As alterações do trato gastrointestinal foram descritas por 86,2%, e os episódios de dumping foram relatados em 65,5%. Na análise qualitativa foi observado consumo diário reduzido de fontes de proteínas animal e vegetal. Após a cirurgia bariátrica pode ocorrer flatulência, vômitos e síndrome de dumping como sintomas representativos mais frequentes das alterações funcionais digestivas. Alopecia e alterações ungueais são os sinais mais relevantes de carência nutricional. O uso de suplementos alimentares no pós-operatório é escasso e esporádico.

Classificação geométrica de galáxias bianeladas através do metódo CART (Classification And Regression Trees)

NASA Astrophysics Data System (ADS)

Ormeño, M. I.; Faúndez-Abans, M.; Cavada, G.

2003-08-01

A importância deste trabalho deve-se à seleção de objetos ainda não tratados particularmente como uma família e ao emprego de procedimento estatístico robusto que não precisa de pressupostos ou condições de contorno. Contribui, assim, ao melhor entendimento do cenário das Galáxias Aneladas do diagrama de Hubble via classificação e estudo de subclasses. Selecionaram-se 100 galáxias possuidoras de dois anéis do Catalog of Southern Ringed Galaxies compilado por Ronald Buta, de modo a construir uma amostra completa em termos de conhecimento dos semi-eixos dos anéis interno e externo projetados no plano do céu. Visando uma possível classificação destas galáxias aneladas normais em famílias de acordo com as características geométricas dos anéis, empregou-se primeiramente a Análise de Aglomerados (ferramenta de classificação: medições de semelhança em um espaço bidimensional) para explorar a possível existência de famílias. As variáveis analisadas foram: os diâmetros interiores menores d(I) e maiores D(I), os diâmetros exteriores menores d(E) e maiores D(E), e os ângulos de inclinação dos semi-eixos maiores interiores q(I) e exteriores q(E) dos anéis. Como metodologia de discriminação, empregou-se a construção de Árvores de Classificação. As árvores de classificação constituem um método de discriminação alternativo aos modelos clássicos, tais como a Análise Discriminante e a Regressão Logística, onde uma base de dados é dividida em partições (subgrupos) da árvore por ação de um predictor (variável específica). Os pacotes estatísticos utilizados para o processamento da informação foram: SAS versão 8.0 (Statistical Analisys System) e CART versão 3.6.3. Esta análise estatística sugere a existência de três possíveis famílias de galáxias bianeladas, com base apenas na geometria dos anéis. Como forma exploratória inicial deste resultado, a construção de um diagrama BT (magnitude total) versus o índice de cor (B-R), mostra que os três grupos distribuem-se de forma praticamente contínua, porém discriminadas entre si, ocupando três regiões distintas. A classe 3, por exemplo, é geralmente a mais azul, sendo a Classe 1 a mais avermelhada.

Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis.

PubMed

Zhao, Fujun; Wang, Jing; Yang, Yanmei; Wang, Xiaoyong; Shi, Ruihua; Xu, Zekuan; Huang, Zuhu; Zhang, Guoxin

2008-12-01

CYP2C19 polymorphisms have been inconsistently reported to associate with the efficacy of proton pump inhibitor (PPI)-based triple therapies for eradicating Helicobacter pylori infection. The aim of this meta-analysis was to determine whether CYP2C19 polymorphism affect H. pylori eradication rates obtained with first-line PPI-based triple therapies. A systematic literature search was conducted up to July 2007 using Medline, PubMed, EMBase, Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, CNKI (Chinese), and Wanfang (Chinese) digital database. MeSH terms and keywords included proton pump inhibitor, omeprazole, lansoprazole, rabeprazole, pantoprazole, or esomeprazole, cytochrome P4502C19 or CYP2C19, and Helicobacter pylori or H. pylori. Twenty articles met the inclusion criteria, and were included in the meta-analysis by using Review Manager 4.2.8. Eradication rates were significantly different between poor metabolizers (PM) and heterozygous extensive metabolizers (HetEM) (odds ratio (OR) = 1.73, p = .002) and between PM and homozygous extensive metabolizers (HomEM) (OR = 2.79, p < .0001). Moreover, eradication rates were also significant difference between HetEM and HomEM (OR = 2.00, p < .0001). Triple omeprazole and lansoprazole therapies achieved higher H. pylori eradication rates in PM than in HomEM (OR = 4.28, p = .0005 for omeprazole and OR = 3.06, p = .001 for lansoprazole), and higher in HetEM than those in HomEM (OR = 3.22, p < .0001 for omeprazole and OR = 1.95, p = .040 for lansoprazole). Rabeprazole therapies had no significant effect on H. pylori eradication rates (between PM and HomEM, OR = 1.35, p = .610 and between HetEM and HomEM, OR = 1.57, p = .190). No significant difference in H. pylori eradication rates between PM and HetEM was observed in the three individual PPI therapies. The efficacy of omeprazole- and lansoprazole-based first-line triple therapies at the standard doses is dependent on CYP2C19 genotype status, which appears not to affect the efficacy of the regimens including rabeprazole.

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload.

PubMed

Firstenberg, M S; Greenberg, N L; Main, M L; Drinko, J K; Odabashian, J A; Thomas, J D; Garcia, M J

2001-01-01

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

PubMed

Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

2017-01-01

In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do paciente, apresentações disponíveis e forma de obtenção deste recurso terapêutico em nosso meio.

Mecânica celeste.

NASA Astrophysics Data System (ADS)

de Luca, N.; Ferraz-Mello, S.

Contents: Os princípios da mec@OSC@@CCF@anica celeste. O problema de 2-corpos. O sistema de equações canônicas. A teoria das perturbações. O movimento de um satélite artifical. A teoria lunar e o movimento de outros satélites naturais. A teoria planetária. Procedimentos numéricos.

TRANEXAMIC ACID ACTION ON LIVER REGENERATION AFTER PARTIAL HEPATECTOMY: EXPERIMENTAL MODEL IN RATS.

PubMed

Sobral, Felipe Antonio; Daga, Henrique; Rasera, Henrique Nogueira; Pinheiro, Matheus da Rocha; Cella, Igor Furlan; Morais, Igor Henrique; Marques, Luciana de Oliveira; Collaço, Luiz Martins

2016-01-01

Different lesions may affect the liver resulting in harmful stimuli. Some therapeutic procedures to treat those injuries depend on liver regeneration to increase functional capacity of this organ. Evaluate the effects of tranexamic acid on liver regeneration after partial hepatectomy in rats. 40 rats (Rattus norvegicus albinus, Rodentia mammalia) of Wistar-UP lineage were randomly divided into two groups named control (CT) and tranexamic acid (ATX), with 20 rats in each. Both groups were subdivided, according to liver regeneration time of 32 h or seven days after the rats had been operated. The organ regeneration was evaluated through weight and histology, stained with HE and PCNA. The average animal weight of ATX and CT 7 days groups before surgery were 411.2 g and 432.7 g, and 371.3 g and 392.9 g after the regeneration time, respectively. The average number of mitotic cells stained with HE for the ATX and CT 7 days groups were 33.7 and 32.6 mitosis, and 14.5 and 14.9 for the ATX and CT 32 h groups, respectively. When stained with proliferating cell nuclear antigen, the numbers of mitotic cells counted were 849.7 for the ATX 7 days, 301.8 for the CT 7 days groups, 814.2 for the ATX 32 hand 848.1 for the CT 32 h groups. Tranexamic acid was effective in liver regeneration, but in longer period after partial hepatectomy. Muitas são as injúrias que acometem o fígado e levam a estímulo lesivo. Alguns procedimentos terapêuticos para tratamento dessas lesões dependem da regeneração hepática para aumentar a sua capacidade funcional. Avaliar o efeito do ácido tranexâmico na regeneração hepática após hepatectomia parcial em ratos. Foram utilizados 40 ratos (Rattus norvegicus albinus, Rodentia mammalia) convencionais da linhagem Wistar-UP. Foram divididos aleatoriamente em dois grupos de 20: grupo controle (CT) e grupo ácido tranexâmico (ATX). Cada um deles foi divido em dois subgrupos para avaliar a regeneração hepática no tempo de 32 h e 7 dias do pós-operatório. A regeneração do órgão foi avaliada quanto ao peso e histologia, sendo esta última por hematoxilina-eosina e antígeno nuclear de proliferação celular. A média dos pesos dos animais dos grupos ATX 7 dias e CT 7 dias no pré-operatório foram de 411,2 g e 432,7 g, respectivamente, e após a regeneração foram de 371,3 g e 392,9 g. As médias das taxas de mitose coradas por HE dos dois grupos em 7 dias foram de 33,7 e 32,6 mitoses, respectivamente, e de 14,5 e 14,9 mitoses para os grupos ATX e CT 32 h. A contagem de células por antígeno nuclear de proliferação celular mostrou valores de 849,7 para o grupo ATX 7 dias e 301,8 para o CT 7 dias; 814,2 para o grupo ATX 32 h e 848,1 para o CT 32 h. O ácido tranexâmico mostrou-se efetivo na regeneração hepática somente em período mais longo de observação após hepatectomia parcial.

Pacemaker Implants in Children and Adolescents with Chagas Disease in Brazil: 18-Year Incidence.

PubMed

Mizzaci, Carolina Christianini; Souza, Thiago Gonçalves Schroder E; Targueta, Gabriel Pelegrineti; Tótora, Ana Paula Frederico; Mateos, Juan Carlos Pachón; Mateos, José Carlos Pachon

2017-06-01

Chagas disease continues to be a serious public health problem, and accounts for 25-30% of the indications for cardiac stimulation in Brazil. To assess clinical and epidemiological characteristics of patients with Chagas disease, younger than 18 years, who had undergone pacemaker implantation in Brazil between 1994 and 2011, and its temporal trend. This was a cross-sectional analysis of data from the Brazilian Pacemaker Registry database. The following variables were analyzed: year when pacemaker was implanted, location, age, sex, ethnic group, functional class and the main electrocardiographic findings at baseline. In a total of 183,123 implants performed between 1994 and 2011, 214 implants of cardiac stimulation device in Chagas disease patients aged younger than 18 years were identified. Mean age at implantation was 5.6 ± 6.2 years. Second- and third-degree atrioventricular blocks corresponded to 71% of indications for pacemaker implantation. Fifty-six percent of the procedures were performed in the southeast region. Regarding the total number of pacemaker implants per year, there was a remarkable increase in the implants for all causes. However, time series analysis of the implants in Chagas disease patients younger than 18 years revealed a significant reduction in the annual number of implants. There has been an important reduction in the number of pacemaker implantations among children and adolescents with Chagas disease, suggesting a reduction in the vertical transmission of the parasite. A doença de Chagas mantém-se como sério problema de saúde pública e tem sido responsável por aproximadamente 25% a 30% das indicações de estimulação cardíaca no Brasil. Estudar as características clínicas e epidemiológicas dos pacientes menores de 18 anos portadores de doença de Chagas submetidos a implante de marca-passo no território brasileiro entre 1994 e 2011, e sua tendência temporal. Trata-se de um estudo retrospectivo que utilizou informações coletadas pelo Registro Brasileiro de Marca-passo. As variáveis analisadas foram: ano do implante, localidade, idade, sexo, grupo étnico dos pacientes; classificação funcional e os principais achados eletrocardiográficos de base. Em um total de 183 123 implantes realizados entre 1994 e 2011, foram identificados 214 implantes de dispositivos de estimulação cardíaca em portadores de doença de Chagas com idade inferior a 18 anos. A média de idade no momento do implante foi de 5,6 ± 6,2 anos. Bloqueios atrioventriculares de 2º e 3º graus foram responsáveis por 71% das indicações. Dos procedimentos, 55,6% foram realizados na região sudeste. Em relação ao total de implantes de marca-passo por ano, observamos um aumento importante e significante de implante por todas as causas. Entretanto, quando avaliamos a série temporal de implantes em pacientes com doença de Chagas menores que 18 anos, observamos uma redução expressiva e significativa no número anual de implantes. Observa-se uma redução importante do número de implantes de marca-passo em crianças e adolescente chagásicos, o que sugere uma redução da transmissão vertical do parasita.

Training for Technical Assistants: Technical Assistance Program

DTIC Science & Technology

1986-09-01

a portable neutron spectrometer to measure neutron radiation being emitted during high - energy dose applications from linear accelerators . Thus far... received from the Secretary or on therebasis of such other informatin and evidence a h d ems appropri- ate, to individuals or companies, wvhidh in his...laboratory to a given application, in a given discipline. or the horizontal transfer of

WE-A-17A-10: Fast, Automatic and Accurate Catheter Reconstruction in HDR Brachytherapy Using An Electromagnetic 3D Tracking System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulin, E; Racine, E; Beaulieu, L

2014-06-15

Purpose: In high dose rate brachytherapy (HDR-B), actual catheter reconstruction protocols are slow and errors prompt. The purpose of this study was to evaluate the accuracy and robustness of an electromagnetic (EM) tracking system for improved catheter reconstruction in HDR-B protocols. Methods: For this proof-of-principle, a total of 10 catheters were inserted in gelatin phantoms with different trajectories. Catheters were reconstructed using a Philips-design 18G biopsy needle (used as an EM stylet) and the second generation Aurora Planar Field Generator from Northern Digital Inc. The Aurora EM system exploits alternating current technology and generates 3D points at 40 Hz. Phantomsmore » were also scanned using a μCT (GE Healthcare) and Philips Big Bore clinical CT system with a resolution of 0.089 mm and 2 mm, respectively. Reconstructions using the EM stylet were compared to μCT and CT. To assess the robustness of the EM reconstruction, 5 catheters were reconstructed twice and compared. Results: Reconstruction time for one catheter was 10 seconds or less. This would imply that for a typical clinical implant of 17 catheters, the total reconstruction time would be less than 3 minutes. When compared to the μCT, the mean EM tip identification error was 0.69 ± 0.29 mm while the CT error was 1.08 ± 0.67 mm. The mean 3D distance error was found to be 0.92 ± 0.37 mm and 1.74 ± 1.39 mm for the EM and CT, respectively. EM 3D catheter trajectories were found to be significantly more accurate (unpaired t-test, p < 0.05). A mean difference of less than 0.5 mm was found between successive EM reconstructions. Conclusion: The EM reconstruction was found to be faster, more accurate and more robust than the conventional methods used for catheter reconstruction in HDR-B. This approach can be applied to any type of catheters and applicators. We would like to disclose that the equipments, used in this study, is coming from a collaboration with Philips Medical.« less

Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.

PubMed

Cheng, Yaofeng; Wang, Lifei; Iacono, Lisa; Zhang, Donglu; Chen, Weiqi; Gong, Jiachang; Humphreys, William Griffith; Gan, Jinping

2018-01-01

BMS-823778 is an inhibitor of 11β-hydroxysteroid dehydrogenase type-1, and thus a potential candidate for Type 2 diabetes treatment. Here, we investigated the metabolism and pharmacokinetics of BMS-823778 to understand its pharmacokinetic variations in early clinical trials. The metabolism of BMS-823778 was characterized in multiple in vitro assays. Pharmacokinetics were evaluated in healthy volunteers, prescreened as CYP2C19 extensive metabolizers (EM) or poor metabolizers (PM), with a single oral dose of [ 14 C]BMS-823778 (10 mg, 80 μCi). Three metabolites (<5%) were identified in human hepatocytes and liver microsomes (HLM) incubations, including two hydroxylated metabolites (M1 and M2) and one glucuronide conjugate (M3). As the most abundant metabolite, M1 was formed mainly through CYP2C19. M1 formation was also correlated with CYP2C19 activities in genotyped HLM. In humans, urinary excretion of dosed radioactivity was significantly higher in EM (68.8%; 95% confidence interval 61.3%, 76.3%) than in PM (47.0%; 43.5%, 50.6%); only small portions (<2%) were present in faeces or bile from both genotypes. In plasma, BMS-823778 exposure in PM was significantly (5.3-fold, P = 0.0097) higher than in EM. Furthermore, total radioactivity exposure was significantly higher (P < 0.01) than BMS-823778 exposure in all groups, indicating the presence of metabolites. M1 was the only metabolite observed in plasma, and much lower in PM. In urine, the amount of M1 and its oxidative metabolite in EM was 7-fold of that in PM, while more glucuronide conjugates of BMS-823778 and M1 were excreted in PM. CYP2C19 polymorphisms significantly impacted systemic exposure and metabolism pathways of BMS-823778 in humans. © 2017 The British Pharmacological Society.

Beam-induced motion correction for sub-megadalton cryo-EM particles.

PubMed

Scheres, Sjors Hw

2014-08-13

In electron cryo-microscopy (cryo-EM), the electron beam that is used for imaging also causes the sample to move. This motion blurs the images and limits the resolution attainable by single-particle analysis. In a previous Research article (Bai et al., 2013) we showed that correcting for this motion by processing movies from fast direct-electron detectors allowed structure determination to near-atomic resolution from 35,000 ribosome particles. In this Research advance article, we show that an improved movie processing algorithm is applicable to a much wider range of specimens. The new algorithm estimates straight movement tracks by considering multiple particles that are close to each other in the field of view, and models the fall-off of high-resolution information content by radiation damage in a dose-dependent manner. Application of the new algorithm to four data sets illustrates its potential for significantly improving cryo-EM structures, even for particles that are smaller than 200 kDa. Copyright © 2014, Scheres.

Protein secondary structure determination by constrained single-particle cryo-electron tomography.

PubMed

Bartesaghi, Alberto; Lecumberry, Federico; Sapiro, Guillermo; Subramaniam, Sriram

2012-12-05

Cryo-electron microscopy (cryo-EM) is a powerful technique for 3D structure determination of protein complexes by averaging information from individual molecular images. The resolutions that can be achieved with single-particle cryo-EM are frequently limited by inaccuracies in assigning molecular orientations based solely on 2D projection images. Tomographic data collection schemes, however, provide powerful constraints that can be used to more accurately determine molecular orientations necessary for 3D reconstruction. Here, we propose "constrained single-particle tomography" as a general strategy for 3D structure determination in cryo-EM. A key component of our approach is the effective use of images recorded in tilt series to extract high-resolution information and correct for the contrast transfer function. By incorporating geometric constraints into the refinement to improve orientational accuracy of images, we reduce model bias and overrefinement artifacts and demonstrate that protein structures can be determined at resolutions of ∼8 Å starting from low-dose tomographic tilt series. Copyright © 2012 Elsevier Ltd. All rights reserved.

Atomic Resolution Cryo-EM Structure of β-Galactosidase.

PubMed

Bartesaghi, Alberto; Aguerrebere, Cecilia; Falconieri, Veronica; Banerjee, Soojay; Earl, Lesley A; Zhu, Xing; Grigorieff, Nikolaus; Milne, Jacqueline L S; Sapiro, Guillermo; Wu, Xiongwu; Subramaniam, Sriram

2018-05-10

The advent of direct electron detectors has enabled the routine use of single-particle cryo-electron microscopy (EM) approaches to determine structures of a variety of protein complexes at near-atomic resolution. Here, we report the development of methods to account for local variations in defocus and beam-induced drift, and the implementation of a data-driven dose compensation scheme that significantly improves the extraction of high-resolution information recorded during exposure of the specimen to the electron beam. These advances enable determination of a cryo-EM density map for β-galactosidase bound to the inhibitor phenylethyl β-D-thiogalactopyranoside where the ordered regions are resolved at a level of detail seen in X-ray maps at ∼ 1.5 Å resolution. Using this density map in conjunction with constrained molecular dynamics simulations provides a measure of the local flexibility of the non-covalently bound inhibitor and offers further opportunities for structure-guided inhibitor design. Published by Elsevier Ltd.

The implementation and evaluation of an evidence-based statewide prehospital pain management protocol developed using the national prehospital evidence-based guideline model process for emergency medical services.

PubMed

Brown, Kathleen M; Hirshon, Jon Mark; Alcorta, Richard; Weik, Tasmeen S; Lawner, Ben; Ho, Shiu; Wright, Joseph L

2014-01-01

In 2008, the National Highway Traffic Safety Administration funded the development of a model process for the development and implementation of evidence-based guidelines (EBGs) for emergency medical services (EMS). We report on the implementation and evaluation of an evidence-based prehospital pain management protocol developed using this model process. An evidence-based protocol for prehospital management of pain resulting from injuries and burns was reviewed by the Protocol Review Committee (PRC) of the Maryland Institute for Emergency Medical Services Systems (MIEMSS). The PRC recommended revisions to the Maryland protocol that reflected recommendations in the EBG: weight-based dosing and repeat dosing of morphine. A training curriculum was developed and implemented using Maryland's online Learning Management System and successfully accessed by 3,941 paramedics and 15,969 BLS providers. Field providers submitted electronic patient care reports to the MIEMSS statewide prehospital database. Inclusion criteria were injured or burned patients transported by Maryland ambulances to Maryland hospitals whose electronic patient care records included data for level of EMS provider training during a 12-month preimplementation period and a 12-month postimplementation period from September 2010 through March 2012. We compared the percentage of patients receiving pain scale assessments and morphine, as well as the dose of morphine administered and the use of naloxone as a rescue medication for opiate use, before and after the protocol change. No differences were seen in the percentage of patients who had a pain score documented or the percent of patients receiving morphine before and after the protocol change, but there was a significant increase in the total dose and dose in mg/kg administered per patient. During the postintervention phase, patients received an 18% higher total morphine dose and a 14.9% greater mg/kg dose. We demonstrated that the implementation of a revised statewide prehospital pain management protocol based on an EBG developed using the National Prehospital Evidence-based Guideline Model Process was associated with an increase in dosing of narcotic pain medication consistent with that recommended by the EBG. No differences were seen in the percentage of patients receiving opiate analgesia or in the documentation of pain scores.

Reactive oxygen species spermine metabolites generated from amine oxidases and radiation represent a therapeutic gain in cancer treatments.

PubMed

Amendola, Roberto; Cervelli, Manuela; Fratini, Emiliano; Sallustio, Davide E; Tempera, Giampiero; Ueshima, Taichi; Mariottini, Paolo; Agostinelli, Enzo

2013-09-01

The most frequent interventions in cancer therapy are currently the destruction of cells by irradiation or administration of drugs both able to induce radical formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this study was to determine the cell viability of cells undergoing a DNA damage threshold accomplished by ROS overproduction via both ectopic expression of murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes. Low dose of X-irradiation delivers a challenging dose of damage as evaluated in proficient Chinese hamster AA8 cell line and both deficient transcription-coupled nucleotide excision repair (NER) UV61 cells and deficient base excision repair (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX delivers an earlier adaptive response to radiation. The enzymatic formation of toxic metabolites has mainly been investigated on wild-type (WT) and multidrug-resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since SMOX in mammals is differentially activated in a tissue-specific manner and cancer cells can differ in terms of DNA repair and MDR capabilities, it could be of interest to simultaneously treat with very low dose of X-rays and/or to alter SMOX metabolism to generate a differential response in healthy and cancer tissues.

Improved accuracy of ultrasound-guided therapies using electromagnetic tracking: in-vivo speed of sound measurements

NASA Astrophysics Data System (ADS)

Samboju, Vishal; Adams, Matthew; Salgaonkar, Vasant; Diederich, Chris J.; Cunha, J. Adam M.

2017-02-01

The speed of sound (SOS) for ultrasound devices used for imaging soft tissue is often calibrated to water, 1540 m/s1 , despite in-vivo soft tissue SOS varying from 1450 to 1613 m/s2 . Images acquired with 1540 m/s and used in conjunction with stereotactic external coordinate systems can thus result in displacement errors of several millimeters. Ultrasound imaging systems are routinely used to guide interventional thermal ablation and cryoablation devices, or radiation sources for brachytherapy3 . Brachytherapy uses small radioactive pellets, inserted interstitially with needles under ultrasound guidance, to eradicate cancerous tissue4 . Since the radiation dose diminishes with distance from the pellet as 1/r2 , imaging uncertainty of a few millimeters can result in significant erroneous dose delivery5,6. Likewise, modeling of power deposition and thermal dose accumulations from ablative sources are also prone to errors due to placement offsets from SOS errors7 . This work presents a method of mitigating needle placement error due to SOS variances without the need of ionizing radiation2,8. We demonstrate the effects of changes in dosimetry in a prostate brachytherapy environment due to patientspecific SOS variances and the ability to mitigate dose delivery uncertainty. Electromagnetic (EM) sensors embedded in the brachytherapy ultrasound system provide information regarding 3D position and orientation of the ultrasound array. Algorithms using data from these two modalities are used to correct bmode images to account for SOS errors. While ultrasound localization resulted in >3 mm displacements, EM resolution was verified to <1 mm precision using custom-built phantoms with various SOS, showing 1% accuracy in SOS measurement.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method.

PubMed

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC.

Low Dose PET Image Reconstruction with Total Variation Using Alternating Direction Method

PubMed Central

Yu, Xingjian; Wang, Chenye; Hu, Hongjie; Liu, Huafeng

2016-01-01

In this paper, a total variation (TV) minimization strategy is proposed to overcome the problem of sparse spatial resolution and large amounts of noise in low dose positron emission tomography (PET) imaging reconstruction. Two types of objective function were established based on two statistical models of measured PET data, least-square (LS) TV for the Gaussian distribution and Poisson-TV for the Poisson distribution. To efficiently obtain high quality reconstructed images, the alternating direction method (ADM) is used to solve these objective functions. As compared with the iterative shrinkage/thresholding (IST) based algorithms, the proposed ADM can make full use of the TV constraint and its convergence rate is faster. The performance of the proposed approach is validated through comparisons with the expectation-maximization (EM) method using synthetic and experimental biological data. In the comparisons, the results of both LS-TV and Poisson-TV are taken into consideration to find which models are more suitable for PET imaging, in particular low-dose PET. To evaluate the results quantitatively, we computed bias, variance, and the contrast recovery coefficient (CRC) and drew profiles of the reconstructed images produced by the different methods. The results show that both Poisson-TV and LS-TV can provide a high visual quality at a low dose level. The bias and variance of the proposed LS-TV and Poisson-TV methods are 20% to 74% less at all counting levels than those of the EM method. Poisson-TV gives the best performance in terms of high-accuracy reconstruction with the lowest bias and variance as compared to the ground truth (14.3% less bias and 21.9% less variance). In contrast, LS-TV gives the best performance in terms of the high contrast of the reconstruction with the highest CRC. PMID:28005929

Single-particle cryo-EM using alignment by classification (ABC): the structure of Lumbricus terrestris haemoglobin.

PubMed

Afanasyev, Pavel; Seer-Linnemayr, Charlotte; Ravelli, Raimond B G; Matadeen, Rishi; De Carlo, Sacha; Alewijnse, Bart; Portugal, Rodrigo V; Pannu, Navraj S; Schatz, Michael; van Heel, Marin

2017-09-01

Single-particle cryogenic electron microscopy (cryo-EM) can now yield near-atomic resolution structures of biological complexes. However, the reference-based alignment algorithms commonly used in cryo-EM suffer from reference bias, limiting their applicability (also known as the 'Einstein from random noise' problem). Low-dose cryo-EM therefore requires robust and objective approaches to reveal the structural information contained in the extremely noisy data, especially when dealing with small structures. A reference-free pipeline is presented for obtaining near-atomic resolution three-dimensional reconstructions from heterogeneous ('four-dimensional') cryo-EM data sets. The methodologies integrated in this pipeline include a posteriori camera correction, movie-based full-data-set contrast transfer function determination, movie-alignment algorithms, (Fourier-space) multivariate statistical data compression and unsupervised classification, 'random-startup' three-dimensional reconstructions, four-dimensional structural refinements and Fourier shell correlation criteria for evaluating anisotropic resolution. The procedures exclusively use information emerging from the data set itself, without external 'starting models'. Euler-angle assignments are performed by angular reconstitution rather than by the inherently slower projection-matching approaches. The comprehensive 'ABC-4D' pipeline is based on the two-dimensional reference-free 'alignment by classification' (ABC) approach, where similar images in similar orientations are grouped by unsupervised classification. Some fundamental differences between X-ray crystallography versus single-particle cryo-EM data collection and data processing are discussed. The structure of the giant haemoglobin from Lumbricus terrestris at a global resolution of ∼3.8 Å is presented as an example of the use of the ABC-4D procedure.

Volta phase plate data collection facilitates image processing and cryo-EM structure determination.

PubMed

von Loeffelholz, Ottilie; Papai, Gabor; Danev, Radostin; Myasnikov, Alexander G; Natchiar, S Kundhavai; Hazemann, Isabelle; Ménétret, Jean-François; Klaholz, Bruno P

2018-06-01

A current bottleneck in structure determination of macromolecular complexes by cryo electron microscopy (cryo-EM) is the large amount of data needed to obtain high-resolution 3D reconstructions, including through sorting into different conformations and compositions with advanced image processing. Additionally, it may be difficult to visualize small ligands that bind in sub-stoichiometric levels. Volta phase plates (VPP) introduce a phase shift in the contrast transfer and drastically increase the contrast of the recorded low-dose cryo-EM images while preserving high frequency information. Here we present a comparative study to address the behavior of different data sets during image processing and quantify important parameters during structure refinement. The automated data collection was done from the same human ribosome sample either as a conventional defocus range dataset or with a Volta phase plate close to focus (cfVPP) or with a small defocus (dfVPP). The analysis of image processing parameters shows that dfVPP data behave more robustly during cryo-EM structure refinement because particle alignments, Euler angle assignments and 2D & 3D classifications behave more stably and converge faster. In particular, less particle images are required to reach the same resolution in the 3D reconstructions. Finally, we find that defocus range data collection is also applicable to VPP. This study shows that data processing and cryo-EM map interpretation, including atomic model refinement, are facilitated significantly by performing VPP cryo-EM, which will have an important impact on structural biology. Copyright © 2018 Elsevier Inc. All rights reserved.

EM-navigated catheter placement for gynecologic brachytherapy: an accuracy study

NASA Astrophysics Data System (ADS)

Mehrtash, Alireza; Damato, Antonio; Pernelle, Guillaume; Barber, Lauren; Farhat, Nabgha; Viswanathan, Akila; Cormack, Robert; Kapur, Tina

2014-03-01

Gynecologic malignancies, including cervical, endometrial, ovarian, vaginal and vulvar cancers, cause significant mortality in women worldwide. The standard care for many primary and recurrent gynecologic cancers consists of chemoradiation followed by brachytherapy. In high dose rate (HDR) brachytherapy, intracavitary applicators and /or interstitial needles are placed directly inside the cancerous tissue so as to provide catheters to deliver high doses of radiation. Although technology for the navigation of catheters and needles is well developed for procedures such as prostate biopsy, brain biopsy, and cardiac ablation, it is notably lacking for gynecologic HDR brachytherapy. Using a benchtop study that closely mimics the clinical interstitial gynecologic brachytherapy procedure, we developed a method for evaluating the accuracy of image-guided catheter placement. Future bedside translation of this technology offers the potential benefit of maximizing tumor coverage during catheter placement while avoiding damage to the adjacent organs, for example bladder, rectum and bowel. In the study, two independent experiments were performed on a phantom model to evaluate the targeting accuracy of an electromagnetic (EM) tracking system. The procedure was carried out using a laptop computer (2.1GHz Intel Core i7 computer, 8GB RAM, Windows 7 64-bit), an EM Aurora tracking system with a 1.3mm diameter 6 DOF sensor, and 6F (2 mm) brachytherapy catheters inserted through a Syed-Neblett applicator. The 3D Slicer and PLUS open source software were used to develop the system. The mean of the targeting error was less than 2.9mm, which is comparable to the targeting errors in commercial clinical navigation systems.

Stopping powers and cross sections due to two-photon processes in relativistic nucleus-nucleus collision

NASA Technical Reports Server (NTRS)

Cheung, Wang K.; Norbury, John W.

1992-01-01

The radiation dose received from high energy galactic cosmic rays (GCR) is a limiting factor in the design of long duration space flights and the building of lunar and martian habitats. It is of vital importance to have an accurate understanding of the interactions of GCR in order to assess the radiation environment that the astronauts will be exposed to. Although previous studies have concentrated on the strong interaction process in GCR, there are also very large effects due to electromagnetic (EM) interactions. In this report we describe our first efforts at understanding these EM production processes due to two-photon collisions. More specifically, we shall consider particle production processes in relativistic heavy ion collisions (RHICs) through two-photon exchange.

Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.

PubMed

Sheng, Yu-Cheng; Wang, Kun; He, Ying-Chun; Yang, Juan; Zheng, Qing-Shan

2010-11-01

To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach. Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition. The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease. The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.

Sweat test and cystic fibrosis: overview of test performance at public and private centers in the state of São Paulo, Brazil.

PubMed

Servidoni, Maria Fátima; Gomez, Carla Cristina Souza; Marson, Fernando Augusto Lima; Toro, Adyléia Aparecida Dalbo Contrera; Ribeiro, Maria Ângela Gonçalves de Oliveira; Ribeiro, José Dirceu; Ribeiro, Antônio Fernando

2017-01-01

The sweat test (ST) measures chloride levels in sweat and is considered the gold standard for the diagnosis of cystic fibrosis (CF). However, the reliability of a ST depends on their being performed by experienced technicians and in accordance with strict guidelines. Our aim was to evaluate how sweat stimulation, sweat collection, and chloride measurement are performed at 14 centers (9 public centers and 5 private centers) that routinely perform STs in the state of São Paulo, which has the highest frequency of CF in Brazil. This was a cross-sectional cohort study, using a standardized questionnaire administered in loco to the staff responsible for conducting STs. No uniformity regarding the procedures was found among the centers. Most centers were noncompliant with the international guidelines, especially regarding the collection of sweat (the samples were insufficient in 10-50% of the subjects tested); availability of stimulation equipment (which was limited at 2 centers); modernity and certification of stimulation equipment (most of the equipment having been used for 3-23 years); and written protocols (which were lacking at 12 centers). Knowledge of ST guidelines was evaluated at only 1 center. Our results show that STs largely deviate from internationally accepted guidelines at the participating centers. Therefore, there is an urgent need for standardization of STs, training of qualified personnel, and acquisition/certification of suitable equipment. These are essential conditions for a reliable diagnosis of CF, especially with the increasing demand due to newborn screening nationwide, and for the assessment of a possible clinical benefit from the use of modulator drugs. O teste do suor (TS) mede os níveis de cloro no suor e é considerado o padrão ouro para o diagnóstico da fibrose cística (FC). Contudo, a confiabilidade do TS depende de sua realização por técnicos experientes e segundo diretrizes rígidas. Nosso objetivo foi avaliar como são realizadas a estimulação e coleta do suor e a dosagem de cloro em 14 centros (9 públicos e 5 privados) que realizam TS rotineiramente no estado de São Paulo, que possui a maior frequência de FC do Brasil. Estudo de coorte transversal utilizando um questionário padronizado aplicado in loco ao pessoal responsável pela realização dos TS. Não houve uniformidade entre os centros quanto aos procedimentos. A maioria dos centros não era aderente às diretrizes internacionais, especialmente quanto à coleta do suor (amostras insuficientes em 10-50% dos indivíduos testados), disponibilidade de equipamentos de estimulação (limitada em 2 centros), modernidade e certificação dos mesmos (a maioria utilizada há 3-23 anos) e protocolos escritos (ausentes em 12 centros). Avaliou-se o conhecimento sobre diretrizes para TS em apenas 1 centro. Nossos resultados mostram que, nos centros participantes, os TS estão muito distantes das diretrizes internacionalmente aceitas. Portanto, há necessidade urgente de padronização dos TS, de treinamento de pessoal qualificado e de aquisição/certificação de equipamentos adequados. Essas são condições essenciais para um diagnóstico confiável de FC, especialmente com a crescente demanda resultante da triagem neonatal em todo o país, e para a avaliação do possível benefício clínico do uso de moduladores.

Vasorelaxant and Hypotensive Effects of an Ethanolic Extract of Eulophia macrobulbon and Its Main Compound 1-(4′-Hydroxybenzyl)-4,8-Dimethoxyphenanthrene-2,7-Diol

PubMed Central

Wisutthathum, Sutthinee; Chootip, Krongkarn; Martin, Hélène; Ingkaninan, Kornkanok; Temkitthawon, Prapapan; Totoson, Perle; Demougeot, Céline

2018-01-01

Background: Ethnopharmacological studies demonstrated the potential for Eulophia species to treat inflammation, cancer, and cardio-metabolic diseases. The aim of the study was to investigate the vasorelaxant effect of ethanolic Eulophia macrobulbon (EM) extract and its main phenanthrene on rat isolated mesenteric artery and to investigate the hypotensive effect of EM. Methods: The vasorelaxant effects of EM extract or phenanthrene and the underlying mechanisms were evaluated on second-order mesenteric arteries from Sprague Dawley rats. In addition, the acute hypotensive effect was evaluated in anesthetized rats infused with cumulative concentrations of the EM extract. Results: Both EM extract (10-4–1 mg/ml) and phenanthrene (10-7–10-4 M) relaxed endothelium-intact arteries, an effect that was partly reduced by endothelium removal (p < 0.001). A significant decrease in the relaxant effect of the extract and the phenanthrene was observed with L-NAME and apamin/charybdotoxin in endothelium-intact vessels, and with iberiotoxin in denuded vessels. SNP (sodium nitroprusside)-induced relaxation was significantly enhanced by EM extract and phenanthrene. By contrast, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one), 4-aminopyridine and glibenclamide (endothelium-denuded vessels) and indomethacin (endothelium-intact vessels) had no effect. In calcium-free solution, both the EM extract and phenanthrene inhibited extracellular Ca2+-induced contraction in high KCl and phenylephrine (PE) pre-contracted rings. They also inhibited the intracellular Ca2+ release sensitive to PE. The acute infusion of EM extract (20 and 70 mg/kg) induced an immediate and transient dose-dependent hypotensive effect. Conclusion: The ethanolic extract of EM tubers and its main active compound, 1-(4′-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (phenanthrene) induced vasorelaxant effects on rat resistance vessels, through pleiotropic effects including endothelium-dependent effects (NOS activation, enhanced EDH production) and endothelium-independent effects (opening of KCa channels, inhibition of Ca2+ channels, inhibition of intracellular Ca2+ release and PDE inhibition). PMID:29872393

Procedures for measuring and verifying gastric tube placement in newborns: an integrative review.

PubMed

Dias, Flávia de Souza Barbosa; Emidio, Suellen Cristina Dias; Lopes, Maria Helena Baena de Moraes; Shimo, Antonieta Keiko Kakuda; Beck, Ana Raquel Medeiros; Carmona, Elenice Valentim

2017-07-10

to investigate evidence in the literature on procedures for measuring gastric tube insertion in newborns and verifying its placement, using alternative procedures to radiological examination. an integrative review of the literature carried out in the Cochrane, LILACS, CINAHL, EMBASE, MEDLINE and Scopus databases using the descriptors "Intubation, gastrointestinal" and "newborns" in original articles. seventeen publications were included and categorized as "measuring method" or "technique for verifying placement". Regarding measuring methods, the measurements of two morphological distances and the application of two formulas, one based on weight and another based on height, were found. Regarding the techniques for assessing placement, the following were found: electromagnetic tracing, diaphragm electrical activity, CO2 detection, indigo carmine solution, epigastrium auscultation, gastric secretion aspiration, color inspection, and evaluation of pH, enzymes and bilirubin. the measuring method using nose to earlobe to a point midway between the xiphoid process and the umbilicus measurement presents the best evidence. Equations based on weight and height need to be experimentally tested. The return of secretion into the tube aspiration, color assessment and secretion pH are reliable indicators to identify gastric tube placement, and are the currently indicated techniques. investigar, na literatura, evidências sobre procedimentos de mensuração da sonda gástrica em recém-nascidos e de verificação do seu posicionamento, procedimentos alternativos ao exame radiológico. revisão integrativa da literatura nas bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE e Scopus, utilizando os descritores "intubação gastrointestinal" e "recém-nascido" em artigos originais. dezessete publicações foram incluídas e categorizadas em "método de mensuração" ou "técnica de verificação do posicionamento". Como métodos de mensuração, foram encontrados os de tomada de duas distâncias morfológicas e os de aplicação de duas fórmulas, uma baseada no peso e outra na altura. Para técnicas de verificação do posicionamento, encontrou-se traçado eletromagnético, atividade elétrica do diafragma, detecção de CO2, solução de índigo carmim, ausculta do epigástrio, aspiração de secreção gástrica, inspeção da cor, avaliação de pH, enzimas e bilirrubina. o método de mensuração que utiliza as medidas do nariz ao lóbulo da orelha ao ponto médio entre apêndice xifoide e cicatriz umbilical apresenta melhores evidências. As equações baseadas em peso e altura necessitam ser testadas experimentalmente. O retorno de secreção na aspiração da sonda, avaliação da cor e do pH da secreção são indicadores confiáveis na identificação do posicionamento da sonda gástrica, e são as técnicas atualmente indicadas. investigar, en la literatura, evidencias sobre procedimientos de medición de la sonda gástrica en recién nacidos y de verificación de su posicionamiento, procedimientos alternativos al examen radiológico. revisión integradora de la literatura en las bases Biblioteca Cochrane, LILACS, CINAHL, EMBASE, MEDLINE y Scopus, utilizando los descriptores "intubación gastrointestinal" y "recién nacido" en artículos originales. diecisiete publicaciones fueron incluidas y categorizadas en "método de medición" o "técnica de verificación del posicionamiento". Como métodos de medición, fueron encontrados los de medida de dos distancias morfológicas y los de aplicación de dos fórmulas (una basada en el peso y otra en la altura). Para las técnicas de verificación del posicionamiento, se encontró: trazado electromagnético, actividad eléctrica del diafragma, detección de CO2, solución de índigo carmín, auscultación del epigastrio, aspiración de secreción gástrica, inspección del color, evaluación de pH, enzimas y bilirrubina. el método de medición que utiliza las medidas de la nariz al lóbulo de la oreja al punto medio entre apéndice xifoideo y cicatriz umbilical, presenta las mejores evidencias. Las ecuaciones basadas en peso y altura necesitan ser comprobadas experimentalmente. El retorno de secreción en la aspiración de la sonda, evaluación del color y del pH de la secreción son indicadores confiables en la identificación del posicionamiento de la sonda gástrica, y son las técnicas actualmente indicadas.

Desenvolvimento de modelo clínico para predição da possibilidade de identificação da artéria de Adamkiewicz por angiotomografia

PubMed Central

Amato, Alexandre Campos Moraes; Parga, José Rodrigues; Stolf, Noedir Antônio Groppo

2018-01-01

Resumo Contexto Diferenças morfológicas da artéria de Adamkiewicz (AKA) entre a população portadora e não portadora de doença aórtica têm importância clínica, influenciando as complicações neuroisquêmicas da medula espinhal em procedimentos operatórios. Ainda não é conhecida a correlação entre parâmetros clínicos e a previsibilidade da identificação dessa artéria pela angiotomografia. Objetivo Desenvolver um modelo matemático que, através de parâmetros clínicos correlacionados com aterosclerose, possa prever a probabilidade de identificação da AKA em pacientes submetidos a angiotomografias. Método Estudo observacional transversal utilizando banco de imagens e dados de pacientes. Foi feita análise estatística multivariada e criado modelo matemático logit de predição para identificação da AKA. Variáveis significativas foram utilizadas na montagem da fórmula para cálculo da probabilidade de identificação. O modelo foi calibrado, e a discriminação foi avaliada pela curva receiver operating characteristic (ROC). A seleção das variáveis explanatórias foi guiada pela maior área na curva ROC (p = 0,041) e pela significância combinada das variáveis. Resultados Foram avaliados 110 casos (54,5% do sexo masculino, com idade média de 60,97 anos e etnia com coeficiente B -2,471, M -1,297, N -0,971), com AKA identificada em 60,9%. Índice de massa corporal: 27,06 ± 0,98 (coef. -0,101); fumantes: 55,5% (coef. -1,614/-1,439); diabéticos: 13,6%; hipertensos: 65,5% (coef. -1,469); dislipidêmicos: 58,2%; aneurisma aórtico: 38,2%; dissecção aórtica: 12,7%; e trombo mural: 24,5%. Constante de 6,262. Fórmula para cálculo da probabilidade de detecção: (e−(Coef. Etnia+(Coef. IMC×IMC)+Coef.fumante+Coef.HAS+Coef.dislip+Constante)+1)−1 . O modelo de predição foi criado e disponibilizado no link https://vascular.pro/aka-model . Conclusão Com as covariáveis etnia, índice de massa corporal, tabagismo, hipertensão arterial e dislipidemia, foi possível criar um modelo matemático de predição de identificação da AKA com significância combinada de nove coeficientes (p = 0,042). PMID:29930677

Evaluation of γ-radiation-induced DNA damage in two species of bivalves and their relative sensitivity using comet assay.

PubMed

Praveen Kumar, M K; Shyama, S K; Sonaye, B S; Naik, U Roshini; Kadam, S B; Bipin, P D; D'costa, A; Chaubey, R C

2014-05-01

Ionizing radiation is known to induce genetic damage in diverse groups of organisms. Under accidental situations, large quantities of radioactive elements get released into the environment and radiation emitted from these radionuclides may adversely affect both the man and the non-human biota. The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz. Paphia malabarica and Meretrix casta to gamma radiation. The comet assays was optimized and validated using different concentrations (18, 32 and 56 mg/L) of ethyl methanesulfonate (EMS), a direct-acting reference genotoxic agent, to which the bivalves were exposed for various times (24, 48 and 72 h). Bivalves were irradiated (single acute exposure) with 5 different doses (viz. 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay. Haemolymph was collected from the adductor muscle at 24, 48 and 72 h of both EMS-exposed and irradiated bivalves and comet assay was carried out using standard protocol. A significant increase in DNA damage was observed as indicated by an increase in % tail DNA damage at different concentrations of EMS and all the doses of gamma radiation as compared to controls in both bivalve species. This showed a dose-dependent increase of genetic damage induced in bivalves by EMS as well as gamma radiation. Further, the highest DNA damage was observed at 24h. The damage gradually decreased with time, i.e. was smaller at 48 and 72 h than at 24h post irradiation in both species of bivalves. This may indicate repair of the damaged DNA and/or loss of heavily damaged cells as the post irradiation time advanced. The present study reveals that gamma radiation induces single strand breaks in DNA as measured by alkaline comet assay in bivalves and comet assay serves as a sensitive and rapid method to detect genotoxicity of gamma radiation. This study further indicates that both M. casta and P. malabarica exhibit almost identical sensitivity to gamma radiation as measured by DNA damage. Copyright © 2014 Elsevier B.V. All rights reserved.

INFLUENCE OF TOBACCO, ALCOHOL AND DIABETES ON THE COLLAGEN OF CREMASTER MUSCLE IN PATIENTS WITH INGUINAL HERNIAS.

PubMed

Módena, Sérgio Ferreira; Caldeira, Eduardo José; Peres, Marco Antonio O; Andreollo, Nelson Adami

2016-01-01

New findings point out that the mechanism of formation of the hernias can be related to the collagenous tissues, under activity of aggressive agents such as the tobacco, alcohol and diabetes. To analyze the collagen present in the cremaster muscle in patients with inguinal hernias, focusing the effect of tobacco, alcohol, and diabetes. Fifteen patients with inguinal hernia divided in three groups were studied: group I (n=5) was control; group II (n=5) were smokers and/or drinkers; and group III (n=5) had diabetes mellitus. All subjects were underwent to surgical repair of the inguinal hernias obeying the same pre, intra and postoperative conditions. During surgery, samples of the cremaster muscle were collected for analysis in polarized light microscopy, collagen morphometry and protein. The area occupied by the connective tissue was higher in groups II and III (p<0.05). The collagen tissue occupied the majority of the samples analyzed in comparison to the area occupied by muscle cells. The content of total protein was higher in groups II and III compared to the control group (p<0.05). The tobacco, alcohol and diabetes cause a remodel the cremaster muscle, leading to a loss of support or structural change in this region, which may enhance the occurrences and damage related to inguinal hernias. Estudos recentes sinalizam que o mecanismo de formação das hérnias pode estar relacionado aos tecidos colagenosos, sob a ação de agentes agressores como o tabaco, o álcool e o diabete. Avaliar o colágeno presente no músculo cremaster em pacientes com hérnias inguinais enfocando o efeito do tabaco, álcool e diabete. Foram estudados 15 pacientes com hérnias inguinais divididos em: grupo I (n=5) controles; grupo II (n=5) indivíduos fumantes e/ou etilistas; e grupo III (n=5) indivíduos que apresentavam diabete melito. Todos foram submetidos à correção cirúrgica das hérnias inguinais obedecendo às mesmas condições pré, intra e pós-operatórias. Durante o procedimento cirúrgico, amostras do músculo cremaster foram coletadas para análises em microscopia de luz polarizada, morfometria do colágeno e de proteínas. A área ocupada por tecido conjuntivo foi maior nos grupos II e III (p<0,05). O tecido colágeno ocupou a maior parte das amostras analisadas, em comparação à área ocupada pelas células musculares. O conteúdo de proteínas totais foi maior nos grupos II e III, quando comparado com o grupo controle (p<0,05). O tabaco, o álcool e o diabete ocasionam remodelação no músculo cremaster, levando à perda de suporte ou alteração estrutural nesta região, podendo intensificar as ocorrências e os danos relacionados às hérnias inguinais.

Single-particle cryo-EM using alignment by classification (ABC): the structure of Lumbricus terrestris haemoglobin

PubMed Central

Seer-Linnemayr, Charlotte; Ravelli, Raimond B. G.; Matadeen, Rishi; De Carlo, Sacha; Alewijnse, Bart; Portugal, Rodrigo V.; Pannu, Navraj S.; Schatz, Michael; van Heel, Marin

2017-01-01

Single-particle cryogenic electron microscopy (cryo-EM) can now yield near-atomic resolution structures of biological complexes. However, the reference-based alignment algorithms commonly used in cryo-EM suffer from reference bias, limiting their applicability (also known as the ‘Einstein from random noise’ problem). Low-dose cryo-EM therefore requires robust and objective approaches to reveal the structural information contained in the extremely noisy data, especially when dealing with small structures. A reference-free pipeline is presented for obtaining near-atomic resolution three-dimensional reconstructions from heterogeneous (‘four-dimensional’) cryo-EM data sets. The methodologies integrated in this pipeline include a posteriori camera correction, movie-based full-data-set contrast transfer function determination, movie-alignment algorithms, (Fourier-space) multivariate statistical data compression and unsupervised classification, ‘random-startup’ three-dimensional reconstructions, four-dimensional structural refinements and Fourier shell correlation criteria for evaluating anisotropic resolution. The procedures exclusively use information emerging from the data set itself, without external ‘starting models’. Euler-angle assignments are performed by angular reconstitution rather than by the inherently slower projection-matching approaches. The comprehensive ‘ABC-4D’ pipeline is based on the two-dimensional reference-free ‘alignment by classification’ (ABC) approach, where similar images in similar orientations are grouped by unsupervised classification. Some fundamental differences between X-ray crystallography versus single-particle cryo-EM data collection and data processing are discussed. The structure of the giant haemoglobin from Lumbricus terrestris at a global resolution of ∼3.8 Å is presented as an example of the use of the ABC-4D procedure. PMID:28989723

Paramedic attitudes regarding prehospital analgesia.

PubMed

Walsh, Brooks; Cone, David C; Meyer, Emily M; Larkin, Gregory L

2013-01-01

Although pain is a major reason why patients summon emergency medical services (EMS), prehospital medical providers administer analgesic agents at inappropriately low rates. One possible reason is the role of EMS provider attitudes. This study was conducted to elicit attitudes that may act as impediments or deterrents to administering analgesia in the prehospital environment. A qualitative methodology was employed. We recruited experienced paramedics, with at least one year of full-time fieldwork, from a variety of agencies in New England. We sought to include a balance of rural and urban as well as both private and hospital-based agencies. Participants at each site were selected through purposive sampling. A semistructured discussion guide was designed to elicit the paramedics' past experiences with administering analgesia, as well as reflections on their role in the care of patients in pain. Both interviews and focus groups were conducted. These sessions were recorded and transcribed verbatim. The transcripts were topic-analyzed and iteratively coded by two independent investigators utilizing the constant comparative method of Glaser and Strauss' Grounded Theory; coding ambiguities were resolved by consensus. Through a series of conceptual mapping and iterative code refinement, themes and domains were generated. Fifteen paramedics from five EMS agencies in three New England states were recruited. Major themes were: 1) a reluctance to administer opioids to patients without significant objective signs (e.g., deformity, hypertension); 2) a preoccupation with potential malingering; 3) ambivalence about the degree of pain control to target or to expect (e.g., aiming to "take the edge off"); 4) a fear of masking diagnostic symptoms; and 5) an aversion to aggressive dosing of opioids (e.g., initial doses of morphine did not exceed 5 mg). A number of potentially modifiable attitudinal barriers to appropriate pain management were revealed.

Are addiction-related memories malleable by working memory competition? Transient effects on memory vividness and nicotine craving in a randomized lab experiment.

PubMed

Markus, Wiebren; de Weert-van Oene, Gerdien H; Woud, Marcella L; Becker, Eni S; DeJong, Cornelis A J

2016-09-01

Experimental research suggests that working memory (WM) taxation reduces craving momentarily. Using a modified Eye Movement Desensitization and Reprocessing (EMDR) procedure, prolonged reductions in craving and relapse rates in alcohol dependence have been demonstrated. Modified EMDR-procedures may also hold promise in smoking cessation attempts. A proof-of-concept study was conducted to narrow the gap between WM-taxation experiments and clinical EMDR studies. To this end the clinical EMDR-procedure was modified for use in a laboratory experiment. Daily smokers (n = 47), abstaining overnight, were allocated (by minimization randomization) to one of two groups using a parallel design. In both cases a modified EMDR-procedure was used. In the experimental group (n = 24) eye movements (EM) were induced while control group participants (n = 23) fixed their gaze (not taxing WM). During 6 min trials, craving-inducing memories were recalled. Craving, vividness of target memories, and smoking behavior were assessed at several variable-specific time-points between baseline (one week pre-intervention) and one week follow-up. The experimental group showed significant immediate reductions of craving and vividness of targeted memories. However, these effects were lost during a one-week follow-up period. A limited dose of WM-taxation, in the form of EM in a modified EMDR-procedure, resulted in transient effects on memory vividness and nicotine craving. EM provide a valuable way of coping with the acute effects of craving during smoking cessation attempts. Other aspects of the EMDR-procedure may provide additional effects. Component and dose-response studies are needed to establish the potential of EMDR-therapy in smoking cessation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cosmetic Use of AbobotulinumtoxinA in Men: Considerations Regarding Anatomical Differences and Product Characteristics.

PubMed

Bloom, Jason D; Green, Jeremy B; Bowe, Whitney; von Grote, Erika; Nogueira, Alessandra

2016-09-01

The proportion of men seeking facial rejuvenation with botulinum neurotoxin type A (BoNTA) products is increasing. The number of male patients treated in the 5-year period between 2009 and 2014 grew by 25%. There is little clinical data supporting gender-specific efficacy with regard to dosing and injection placement in men. To nurture the confidence associated with treatment of male patients, clinicians are in need of more informational materials to develop their evaluation and treatment strategies. Three BoNTA products are currently available in the United States (US) for treatment of the upper face. The varying potency of the different BoNTA formulations is reflected by disparate dose-response characteristics, meaning they are not interchangeable for injection purposes. Clinicians who are familiar with the characteristics of all the BoNTA options will be equipped with the necessary tools to provide their male patients with a desired outcome.
Among the product options available in the US, Dysport^® (abobotulinumtoxinA) (Galderma Laboratories, L.P., Fort Worth, Texas) is unique in that its recommendations for reconstitution provide the clinician with 2 different final product concentrations. The flexibility provided by a variable dose may be a valuable tool for tailoring treatments to male patient-specific needs, which may include a more conservative outcome, maintaining a certain degree of muscle activity and expressivity. Achieving a conservative outcome may be the key to a positive experience for the male patient.

J Drugs Dermatol. 2016;15(9):1056-1062.

Development and validation of an automated system for detection and assessment of scratching in the rodent

PubMed Central

Marino, Marc; Huang, Polly; Malkmus, Shelle; Robertshaw, Erin; Mac, Elaine A.; Shatterman, Yuri; Yaksh, Tony L.

2012-01-01

Pruritus, the sensation of itch, which evokes reflex scratching behavior, has a diverse etiology. Because of its clinical significance, mechanisms of pruriception are an important topic. In the present work we describe and validate a paw motion detector (PMD) system. The system employs a small removable metal band placed on one hind paw that provides a signal indicative of paw movement through perturbation of an electromagnetic (EM) field. C57Bl/6 mice were fitted with a unilateral hind paw band and adapted to testing cylinders equipped with EM signal emission and detection. The following observations were made: 1) in mice, unilateral SQ injection of 48/80 into the dorsolateral aspect of the neck evoked periodic high frequency bursts of scratching at the injected site with the ipsilateral (banded) but not the contralateral (not banded) hind paw. 2) Cross correlation between PMD and human observer counts after SQ 48/80 using the specified computational algorithm revealed a highly significant correlation. 3) SQ histamine and 48/80 over a 1 hour interval produced dose dependent scratching, which diphenhydramine dose dependently reversed. Chloroquine scratching displayed an inverse u-shaped dose response curve, which was insensitive to diphenhydramine. 4) SQ 48/80 at intervals over 28 days showed no change in the scratching response within the same cohort of mice. 5) Power analysis showed 40% changes in scratching activity could be detected at the p<0.05 level with groups of 4 mice. These observations indicate that the system described can efficiently define the actions and pharmacology of pruritogenic agents. PMID:22971351

Immediate reconstruction with autologous fat grafting: influence in breast cancerregional recurrence.

PubMed

Stumpf, Camile Cesa; Biazus, Jorge Villanova; Zucatto, Fernando Schuh Ângela Erguy; Cericatto, Rodrigo; Cavalheiro, José Antônio Crespo; Damin, Andrea Pires Souto; Melo, Márcia Portela

2017-01-01

to evaluate local and systemic recurrence of breast cancer in patients submitted to autologous fat grafting in the immediate reconstruction after conservative surgery for breast cancer. this is a historical cohort study comparing 167 patients submitted to conservative surgery without reconstruction (conservative surgery group) with 27 patients submitted to conservative treatment with immediate graft reconstruction, following the Coleman's technique (lipofilling group). All patients had invasive carcinoma and were operated by a single surgeon from 2004 to 2011. The postoperative follow-up time was 36 months. the overall incidence of local recurrence was 2.4%. No patient in the lipofilling group had local recurrence during the study period. For systemic recurrence, the rates obtained were 3.7% (one patient) for the fat grafting group and 1.8% (three patients) for the conservative surgery group without reconstruction. there was no significant difference for local or systemic recurrence in the groups studied. Immediate autologous fat grafting appears to be a safe procedure. avaliar recorrência local e sistêmica do câncer de mama em pacientes submetidas ao enxerto autólogo de gordura na reconstrução imediata após cirurgia conservadora para o câncer de mama. estudo de coorte histórica em que foram comparadas 167 pacientes submetidas à cirurgia conservadora sem reconstrução com 27 pacientes submetidas ao tratamento conservador com reconstrução imediata do enxerto, seguindo técnica de Coleman. Todas as pacientes eram portadoras de carcinoma invasor e foram operadas por um único cirurgião, no período de 2004 a 2011. O tempo de acompanhamento pós-operatório foi 36 meses. a incidência global de recidiva local foi 2,4%. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (uma paciente) para o grupo lipoenxertia e 1,8% (três pacientes) para grupo da cirurgia conservadora sem reconstrução. não houve diferença significativa para recorrência local ou sistêmica nos grupos estudados. O enxerto autólogo imediato de gordura parece ser um procedimento seguro.

Costs of topical treatment of pressure ulcer patients.

PubMed

Andrade, Cynthia Carolina Duarte; Almeida, Cláudia Fernanda Dos Santos Calixto de; Pereira, Walkíria Euzébio; Alemão, Márcia Mascarenhas; Brandão, Cristina Mariano Ruas; Borges, Eline Lima

2016-04-01

To evaluate the costs of a topical treatment of pressure ulcer (PU) patients in a hospital unit for treatment of chronic patients in 2014. This is an activity-based costing study. This method encompasses the identification, measurement and pricing of physical and human resources consumed for dressings. Procedure costs varied between BRL 16.41 and BRL 260.18. For PUs of the same category, of near areas and with the same type of barrier/adjuvant, the cost varied between 3.5% and 614.6%. For most dressings, the cost increased proportionally to the increase of the area and to the development of PU category. The primary barrier accounted for a high percentage of costs among all items required to the application of dressings (human and material resources). Dressings applied in sacral PUs had longer application times. This study allowed us to understand the costs involved in the treatment of PUs, and it may support decision-makers and other cost-effectiveness studies. Realizar uma avaliação do custo do tratamento tópico de pacientes com úlceras por pressão (UP), em uma unidade hospitalar de atendimento a pacientes crônicos no ano de 2014. Trata-se de um estudo de custos baseado no Sistema de custeio Baseado em Atividades. Este método contempla a identificação, mensuração e precificação dos recursos físicos e humanos consumidos para a realização de curativos. Os custos dos procedimentos variaram de R$16,41 a R$260,18. Para UP de mesma categoria, de áreas aproximadas e mesmo tipo de cobertura/adjuvante, a variação entre os custos foi de 3,5% a 614,6%. Para a maioria dos curativos, o custo aumentou proporcionalmente ao aumento da área e à progressão da categoria das UP. A cobertura primária representou elevado percentual nos custos entre todos os itens necessários para realizar os curativos (recursos humanos e materiais). Os curativos realizados nas UP sacrais foram os que apresentaram maiores tempos para execução. Este estudo permitiu conhecer os custos envolvidos no tratamento das UP e pode fornecer subsídios para os tomadores de decisão, assim como para a realização de estudos de custo-efetividade.

WE-A-17A-03: Catheter Digitization in High-Dose-Rate Brachytherapy with the Assistance of An Electromagnetic (EM) Tracking System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Damato, AL; Bhagwat, MS; Buzurovic, I

Purpose: To investigate the use of a system using EM tracking, postprocessing and error-detection algorithms for measuring brachytherapy catheter locations and for detecting errors and resolving uncertainties in treatment-planning catheter digitization. Methods: An EM tracker was used to localize 13 catheters in a clinical surface applicator (A) and 15 catheters inserted into a phantom (B). Two pairs of catheters in (B) crossed paths at a distance <2 mm, producing an undistinguishable catheter artifact in that location. EM data was post-processed for noise reduction and reformatted to provide the dwell location configuration. CT-based digitization was automatically extracted from the brachytherapy planmore » DICOM files (CT). EM dwell digitization error was characterized in terms of the average and maximum distance between corresponding EM and CT dwells per catheter. The error detection rate (detected errors / all errors) was calculated for 3 types of errors: swap of two catheter numbers; incorrect catheter number identification superior to the closest position between two catheters (mix); and catheter-tip shift. Results: The averages ± 1 standard deviation of the average and maximum registration error per catheter were 1.9±0.7 mm and 3.0±1.1 mm for (A) and 1.6±0.6 mm and 2.7±0.8 mm for (B). The error detection rate was 100% (A and B) for swap errors, mix errors, and shift >4.5 mm (A) and >5.5 mm (B); errors were detected for shifts on average >2.0 mm (A) and >2.4 mm (B). Both mix errors associated with undistinguishable catheter artifacts were detected and at least one of the involved catheters was identified. Conclusion: We demonstrated the use of an EM tracking system for localization of brachytherapy catheters, detection of digitization errors and resolution of undistinguishable catheter artifacts. Automatic digitization may be possible with a registration between the imaging and the EM frame of reference. Research funded by the Kaye Family Award 2012.« less

THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I ANDCLINICALLY UNCONTROLLED TYPE 2 DIABETES.

PubMed

Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

2016-07-07

Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Research was conducted in PubMed, Medline, PubMed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetesmellitus. In addition, representatives of the societiesinvolved, as an expert panel, issued opinions. Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC≤35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2(DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados PubMed, Medline, PubMed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionadosque foram analisados pelos critérios da medicina baseada em evidências.As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?;Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabólico. A cirurgia metabólica tem mecanismos de ação bem definidos tanto em estudos experimentais quanto em seres humanos. As intervenções gastrointestinais em diabéticos com IMC≤35 kg/m2 possuem segurança e eficácia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clínicos e mudanças de estilo de vida, em parte através de mecanismos independentes da perda ponderal. Não há correlação entre o IMC inicial e perda ponderal em longo prazo com os índices de sucesso do tratamento cirúrgico. O tratamento cirúrgico é opção para os pacientes portadores de DMT2 sem adequado controle clínico, com IMC entre 30 e 35, após minuciosa avaliação seguindo os parâmetros dispostos no Escore de Risco Metabólico aqui proposto. DGYR é a técnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicação da gastrectomia vertical para os casos em que exista contraindicação para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicação, preparo e acompanhamento após as operações e acompanhados com monitorização de complicações micro e macrovasculares.

THE ROLE OF METABOLIC SURGERY FOR PATIENTS WITH OBESITY GRADE I AND TYPE 2 DIABETES NOT CONTROLLED CLINICALLY.

PubMed

Campos, Josemberg; Ramos, Almino; Szego, Thomaz; Zilberstein, Bruno; Feitosa, Heládio; Cohen, Ricardo

Even considering the advance of the medical treatment in the last 20 years with new and more effective drugs, the outcomes are still disappointing as the control of obesity and type 2 Diabetes Mellitus (T2DM) with a large number of patients under the medical treatment still not reaching the desired outcomes. To present a Metabolic Risk Score to better guide the surgical indication for T2DM patients with body mass index (BMI) where surgery for obesity is still controversial. Research was conducted in Pubmed, Medline, Pubmed Central, Scielo and Lilacs between 2003-2015 correlating headings: metabolic surgery, obesity and type 2 diabetes mellitus. In addition, representatives of the societies involved, as an expert panel, issued opinions. Forty-five related articles were analyzed by evidence-based medicine criteria. Grouped opinions sought to answer the following questions: Why metabolic and not bariatric surgery?; Mechanisms involved in glycemic control; BMI as a single criterion for surgical indication for uncontrolled T2DM; Results of metabolic surgery studies in BMI<35 kg/m2; Safety of metabolic surgery in patients with BMI<35 kg/m2; Long-term effects of surgery in patients with baseline BMI<35 kg/m2 and Proposal for a Metabolic Risk Score. Metabolic surgery has well-defined mechanisms of action both in experimental and human studies. Gastrointestinal interventions in T2DM patients with IMC≤35 kg/m2 has similar safety and efficacy when compared to groups with greater BMIs, leading to the improvement of diabetes in a superior manner than clinical treatment and lifestyle changes, in part through weight loss independent mechanisms . There is no correlation between baseline BMI and weight loss in the long term with the success rate after any surgical treatment. Gastrointestinal surgery treatment may be an option for patients with T2DM without adequate clinical control, with a BMI between 30 and 35, after thorough evaluation following the parameters detailed in Metabolic Risk Score defined by the surgical societies. Roux-en-Y gastric bypass (RYGB), because of its well known safety and efficacy and longer follow-up studies, is the main surgical technique indicated for patients eligible for surgery through the Metabolic Risk Score. The vertical sleeve gastrectomy may be considered if there is an absolute contraindication for the RYGB. T2DM patients should be evaluated by the multiprofessional team that will assess surgical eligibility, preoperative work up, follow up and long term monitoring for micro and macrovascular complications. Mesmo considerando o avanço do tratamento clínico ocorrido nos últimos 20 anos, com novos e mais eficientes medicamentos, os dados ainda são desanimadores quanto ao controle da obesidade e da diabete melito tipo 2 (DMT2),com grande parcela de doentes em tratamento clínico ficando fora da meta desejada de controle. Apresentar proposta de Escore de Risco Metabólico para melhor orientar a indicação cirúrgica do diabete em pacientes com índice de massa corpórea (IMC) mais baixo nos quais o uso de procedimento cirúrgico para obesidade ainda é controverso. Foi realizada pesquisa nas bases de dados Pubmed, Medline, Pubmed Central, Scielo e Lilacs entre 2003-2015 correlacionando os descritores:cirurgia metabólica, obesidade e diabete melito tipo 2. Adicionalmente, representantes das sociedades envolvidas emitiram opiniões em pontos nos quais não existia na literatura trabalhos com graus de evidência elevados. Foram encontrados 45 artigos relacionados que foram analisados pelos critérios da medicina baseada em evidências. As opiniões agrupadas procuraram responder as seguintes questões: Porque cirurgia metabólica e não bariátrica?; Mecanismos envolvidos no controle glicêmico; IMC como critério isolado de indicação cirúrgica para o DMT2 não controlado; Resultados de estudos de cirurgia metabólica em IMC<35 kg/m2; Segurança da cirurgia metabólica em pacientes com IMC<35 kg/m2; Efeitos em longo prazo da cirurgia em pacientes com IMC inicial <35 kg/m2; Proposta de Escore de Risco Metabólico. A cirurgia metabólica tem mecanismos de ação bem definidos tanto em estudos experimentais quanto em seres humanos. As intervenções gastrointestinais em diabéticos com IMC≤35 kg/m2 possuem segurança e eficácia semelhantes aos grupos com IMCs maiores, levando a melhora do diabete de forma superior aos tratamentos clínicos e mudanças de estilo de vida, em parte através de mecanismos independentes da perda ponderal. Não há correlação entre o IMC inicial e perda ponderal em longo prazo com os índices de sucesso do tratamento cirúrgico. O tratamento cirúrgico é opção para os pacientes portadores de DMT2 sem adequado controle clínico, com IMC entre 30 e 35, após minuciosa avaliação seguindo os parâmetros dispostos no Escore de Risco Metabólico aqui proposto. DGYR é a técnica indicada para os pacientes selecionados no Escore, existindo a possibilidade de indicação da gastrectomia vertical para os casos em que exista contraindicação para ela. O paciente deve ser avaliado por equipe multiprofissional envolvida na indicação, preparo e acompanhamento após as operações e acompanhados com monitorização de complicações micro e macrovasculares.

Camera selection for real-time in vivo radiation treatment verification systems using Cherenkov imaging.

PubMed

Andreozzi, Jacqueline M; Zhang, Rongxiao; Glaser, Adam K; Jarvis, Lesley A; Pogue, Brian W; Gladstone, David J

2015-02-01

To identify achievable camera performance and hardware needs in a clinical Cherenkov imaging system for real-time, in vivo monitoring of the surface beam profile on patients, as novel visual information, documentation, and possible treatment verification for clinicians. Complementary metal-oxide-semiconductor (CMOS), charge-coupled device (CCD), intensified charge-coupled device (ICCD), and electron multiplying-intensified charge coupled device (EM-ICCD) cameras were investigated to determine Cherenkov imaging performance in a clinical radiotherapy setting, with one emphasis on the maximum supportable frame rate. Where possible, the image intensifier was synchronized using a pulse signal from the Linac in order to image with room lighting conditions comparable to patient treatment scenarios. A solid water phantom irradiated with a 6 MV photon beam was imaged by the cameras to evaluate the maximum frame rate for adequate Cherenkov detection. Adequate detection was defined as an average electron count in the background-subtracted Cherenkov image region of interest in excess of 0.5% (327 counts) of the 16-bit maximum electron count value. Additionally, an ICCD and an EM-ICCD were each used clinically to image two patients undergoing whole-breast radiotherapy to compare clinical advantages and limitations of each system. Intensifier-coupled cameras were required for imaging Cherenkov emission on the phantom surface with ambient room lighting; standalone CMOS and CCD cameras were not viable. The EM-ICCD was able to collect images from a single Linac pulse delivering less than 0.05 cGy of dose at 30 frames/s (fps) and pixel resolution of 512 × 512, compared to an ICCD which was limited to 4.7 fps at 1024 × 1024 resolution. An intensifier with higher quantum efficiency at the entrance photocathode in the red wavelengths [30% quantum efficiency (QE) vs previous 19%] promises at least 8.6 fps at a resolution of 1024 × 1024 and lower monetary cost than the EM-ICCD. The ICCD with an intensifier better optimized for red wavelengths was found to provide the best potential for real-time display (at least 8.6 fps) of radiation dose on the skin during treatment at a resolution of 1024 × 1024.

Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients.

PubMed

Clark, Rachael A; Watanabe, Rei; Teague, Jessica E; Schlapbach, Christoph; Tawa, Marianne C; Adams, Natalie; Dorosario, Andrew A; Chaney, Keri S; Cutler, Corey S; Leboeuf, Nicole R; Carter, Joi B; Fisher, David C; Kupper, Thomas S

2012-01-18

Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant T(CM) from skin, but a diverse population of skin resident T(EM) remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident T(EM) can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin.

Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne.

PubMed

Jones, Terry M; Ellman, Herman; deVries, Tina

2017-10-01

To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well-tolerated treatment option for individuals with moderate-to-severe acne.

J Drugs Dermatol. 2017;16(10):1022-1028.

Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance.

PubMed

Wang, Zi-Long; Li, Ning; Wang, Pei; Tang, Hong-Hai; Han, Zheng-Lan; Song, Jing-Jing; Li, Xu-Hui; Yu, Hong-Ping; Zhang, Ting; Zhang, Run; Xu, Biao; Zhang, Meng-Na; Fang, Quan; Wang, Rui

2016-09-01

Mounting evidences indicate the functional interactions between neuropeptide FF (NPFF) and opioids, including the endogenous opioids. In the present work, EN-9, a chimeric peptide containing the functional domains of the endogenous opioid endomorphin-2 (EM-2) and NPFF, was synthesized and pharmacologically characterized. In vitro cAMP assay demonstrated that EN-9 was a multifunctional agonist of κ-opioid, NPFF1 and NPFF2 receptors. In the mouse tail-flick test, intracerebroventricularly (i.c.v.) administration of EN-9 produced significant antinociception with an ED50 value of 13.44 nmol, which lasted longer than that of EM-2. In addition, EN-9 induced potent antinociception after both intravenous (i.v.) and subcutaneous (s.c.) injection. Furthermore, the experiments using the antagonists of opioid and NPFF receptors indicated that the central antinociception of EN-9 was mainly mediated by κ-opioid receptor, independently on NPFF receptors. Notably, the central antinociception of EN-9 was not reduced over a period of 6 days repeated i.c.v. injection. Repeated i.c.v. administration of EN-9 with the NPFF1 and NPFF2 receptors antagonist RF9 resulted in a progressive loss of analgesic potency, consistent with the development of tolerance. Moreover, central administration of EN-9 induced the place conditioning aversion only at a high dose of 60 nmol, but not at low doses. At supraspinal level, only high dose of EN-9 (60 nmol, i.c.v.) inhibited gastrointestinal transit via NPFF receptors. Similarly, systemic administration of EN-9 also inhibited gastrointestinal transit at high doses (10 and 30 mg/kg, i.v.). Taken together, the multifunctional agonist of κ-opioid and NPFF receptors EN-9 produced a potent, non-tolerance forming antinociception with limited side effects. Copyright © 2016. Published by Elsevier Ltd.

On the nuclear halo of a proton pencil beam stopping in water.

PubMed

Gottschalk, Bernard; Cascio, Ethan W; Daartz, Juliane; Wagner, Miles S

2015-07-21

The dose distribution of a proton beam stopping in water has components due to basic physics and may have others from beam contamination. We propose the concise terms core for the primary beam, halo (see Pedroni et al 2005 Phys. Med. Biol. 50 541-61) for the low dose region from charged secondaries, aura for the low dose region from neutrals, and spray for beam contamination. We have measured the dose distribution in a water tank at 177 MeV under conditions where spray, therefore radial asymmetry, is negligible. We used an ADCL calibrated thimble chamber and a Faraday cup calibrated integral beam monitor so as to obtain immediately the absolute dose per proton. We took depth scans at fixed distances from the beam centroid rather than radial scans at fixed depths. That minimizes the signal range for each scan and better reveals the structure of the core and halo. Transitions from core to halo to aura are already discernible in the raw data. The halo has components attributable to coherent and incoherent nuclear reactions. Due to elastic and inelastic scattering by the nuclear force, the Bragg peak persists to radii larger than can be accounted for by Molière single scattering. The radius of the incoherent component, a dose bump around midrange, agrees with the kinematics of knockout reactions. We have fitted the data in two ways. The first is algebraic or model dependent (MD) as far as possible, and has 25 parameters. The second, using 2D cubic spline regression, is model independent. Optimal parameterization for treatment planning will probably be a hybrid of the two, and will of course require measurements at several incident energies. The MD fit to the core term resembles that of the PSI group (Pedroni et al 2005), which has been widely emulated. However, we replace their T(w), a mass stopping power which mixes electromagnetic (EM) and nuclear effects, with one that is purely EM, arguing that protons that do not undergo hard single scatters continue to lose energy according to the Beth-Bloch formula. If that is correct, it is no longer necessary to measure T(w), and the dominant role played by the 'Bragg peak chamber' vanishes. For mathematical and other details we will refer to Gottschalk et al (2014, arXiv: 1409.1938v1), a long technical report of this project.

On the nuclear halo of a proton pencil beam stopping in water

NASA Astrophysics Data System (ADS)

Gottschalk, Bernard; Cascio, Ethan W.; Daartz, Juliane; Wagner, Miles S.

2015-07-01

The dose distribution of a proton beam stopping in water has components due to basic physics and may have others from beam contamination. We propose the concise terms core for the primary beam, halo (see Pedroni et al 2005 Phys. Med. Biol. 50 541-61) for the low dose region from charged secondaries, aura for the low dose region from neutrals, and spray for beam contamination. We have measured the dose distribution in a water tank at 177 MeV under conditions where spray, therefore radial asymmetry, is negligible. We used an ADCL calibrated thimble chamber and a Faraday cup calibrated integral beam monitor so as to obtain immediately the absolute dose per proton. We took depth scans at fixed distances from the beam centroid rather than radial scans at fixed depths. That minimizes the signal range for each scan and better reveals the structure of the core and halo. Transitions from core to halo to aura are already discernible in the raw data. The halo has components attributable to coherent and incoherent nuclear reactions. Due to elastic and inelastic scattering by the nuclear force, the Bragg peak persists to radii larger than can be accounted for by Molière single scattering. The radius of the incoherent component, a dose bump around midrange, agrees with the kinematics of knockout reactions. We have fitted the data in two ways. The first is algebraic or model dependent (MD) as far as possible, and has 25 parameters. The second, using 2D cubic spline regression, is model independent. Optimal parameterization for treatment planning will probably be a hybrid of the two, and will of course require measurements at several incident energies. The MD fit to the core term resembles that of the PSI group (Pedroni et al 2005), which has been widely emulated. However, we replace their T(w), a mass stopping power which mixes electromagnetic (EM) and nuclear effects, with one that is purely EM, arguing that protons that do not undergo hard single scatters continue to lose energy according to the Beth-Bloch formula. If that is correct, it is no longer necessary to measure T(w), and the dominant role played by the ‘Bragg peak chamber’ vanishes. For mathematical and other details we will refer to Gottschalk et al (2014, arXiv: 1409.1938v1), a long technical report of this project.

Inguinodynia in patients submitted to conventional inguinal hernioplasty.

PubMed

Dias, Bruno Garcia; Santos, Marcelo Protásio Dos; Chaves, Ana Barbara DE Jesus; Willis, Mariana; Gomes, Marcio Couto; Andrade, Fernandes Tavares; Melo, Valdinaldo Aragão DE; Santos, Paulo Vicente Dos

2017-01-01

to evaluate the incidence of chronic pain and its impact on the quality of life of patients submitted to inguinal hernioplasty using the Lichtenstein technique. this was a descriptive, cross-sectional study of patients operated under spinal anesthesia from February 2013 to February 2015 and who had already completed six postoperative months. We questioned patients about the presence of chronic inguinal pain and, if confirmed, invited them to a consultation in which we assessed the pain and its impact on quality of life. out of 158 patients submitted to the procedure, we identified 7.6% as having inguinodynia. Of these, there was an impact on the quality of life in 25%. the incidence of inguinodynia after hernioplasty with repercussion in quality of life was similar to the one of found in the world literature. avaliar a incidência de dor crônica e o seu impacto na qualidade de vida de pacientes submetidos à hernioplastia inguinal pela técnica de Lichtenstein. trata-se de estudo transversal descritivo, de pacientes operados de hérnia inguinal pela técnica de Lichtenstein sob anestesia raquidiana, no período de fevereiro de 2013 a fevereiro de 2015, e que já haviam completado seis meses de pós-operatório. Os pacientes foram questionados sobre a presença de dor inguinal crônica e, caso confirmada, convidados a uma consulta na qual foi feita análise da qualidade da dor e seu impacto na qualidade de vida. do total de 158 pacientes submetidos ao procedimento, 7,6% foram identificados como portadores de inguinodinia. Destes, houve impacto na qualidade de vida em 25%. observou-se incidência de inguinodinia pós-hernioplastia com repercussão na qualidade de vida semelhante à literatura mundial.

Robotic-assisted modified retroauricular cervical approach: initial experience in Latin America.

PubMed

Chulam, Thiago Celestino; Lira, Renan Bezerra; Kowalski, Luiz Paulo

2016-01-01

to evaluate the thickness of the gastric wall at the time of intra gastric balloon (IGB) placement, at the time of its withdrawal and one month after withdrawal. fifteen morbidly obese patients underwent the introduction of IGB under general anesthesia. In all patients, there was infusion of 500ml of distilled water in the balloon for the test. Measurements of the thickness of the gastric wall were made in the antrum, body and proximal body, using a radial echoendoscope with a frequency of 12MHz and maximum zoom, and its own balloon inflated with 5ml of distilled water. the presence of IGB led to increased wall thickness of the gastric body by expanding the muscle layer. These changes were apparently transient, since 30 days after the balloon withdrawal there was a tendency to return of the wall thickness values ​​observed before the balloon insertion. the use of intragastric balloon for the treatment of obesity determines transient increase in the wall thickness of the gastric body caused by expanded muscle layer. A preocupação com a melhoria dos resultados estéticos e funcionais sem comprometimento dos resultados oncológicos na cirurgia de cabeça e pescoço tem aumentado significativamente. Os procedimentos minimamente invasivos e principalmente aqueles que utilizam a tecnologia robótica permitiram o desenvolvimento de novas abordagens, incluindo o acesso retroauricular, que agora é usado rotineiramente, especialmente na Coréia do Sul. A presente nota irá ilustrar a técnica e a experiência inicial na América Latina, demonstrando que esta abordagem é viável, segura e eficaz oncologicamente, podendo ser utilizada em casos selecionados com um benefício estético evidente.

ALTERNATIVE TECHNIQUE FOR CHOLECYSTECTOMY COMPARABLE TO SINGLE PORT.

PubMed

Sabbag, Carlos; Blitzckow, Ana

2017-01-01

With the advancement of laparoscopic surgery, new techniques have been proposed and disseminated in order to reduce the surgical aggression and get better cosmetic results. To present alternative technique for videocholecystectomy comparable to single port technique using conventional material for laparoscopic surgery. Introduction of laparoscopic devices using two incisions; gallbladder traction with thread, exposition of Calot triangle, and ligature of cystic pedicle with polymer clips. Nine operations were carried out with this method, without complications and no increase in operative time, being compared to conventional videocholecistectomy, however vastly superior in aesthetic results. The technique is feasible, reproducible, showing benefits to patient´s safety. Com o avanço da cirurgia laparoscópica, novas técnicas têm sido propostas e difundidas com o objetivo de diminuir a agressão cirúrgica e obter melhores resultados estéticos. Apresentar técnica alternativa para videocolecistectomia similar à técnica de single port, contudo utilizando material convencional para cirurgia laparoscópica. Procedimento de videocolecistectomia com uso de duas incisões, exposição do trígono de Calot por tração da vesícula biliar com fio e ligadura dos elementos do hilo cístico com clipes de polímero. Foram realizadas nove operações com esse método, não se observando complicações e nem aumento do tempo operatório em relação à videocolecistectomia convencional, contudo com resultado estético grandemente superior. A técnica é factível, reprodutível e mostra benefícios e segurança ao paciente.

An accurate model for the computation of the dose of protons in water.

PubMed

Embriaco, A; Bellinzona, V E; Fontana, A; Rotondi, A

2017-06-01

The accurate and fast calculation of the dose in proton radiation therapy is an essential ingredient for successful treatments. We propose a novel approach with a minimal number of parameters. The approach is based on the exact calculation of the electromagnetic part of the interaction, namely the Molière theory of the multiple Coulomb scattering for the transversal 1D projection and the Bethe-Bloch formula for the longitudinal stopping power profile, including a gaussian energy straggling. To this e.m. contribution the nuclear proton-nucleus interaction is added with a simple two-parameter model. Then, the non gaussian lateral profile is used to calculate the radial dose distribution with a method that assumes the cylindrical symmetry of the distribution. The results, obtained with a fast C++ based computational code called MONET (MOdel of ioN dosE for Therapy), are in very good agreement with the FLUKA MC code, within a few percent in the worst case. This study provides a new tool for fast dose calculation or verification, possibly for clinical use. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

EFFECTS OF LONG-TERM ROUX-EN-Y GASTRIC BYPASS ON BODY WEIGHT AND CLINICAL METABOLIC COMORBIDITIES IN BARIATRIC SURGERY SERVICE OF A UNIVERSITY HOSPITAL.

PubMed

Silva, Cátia Ferreira da; Cohen, Larissa; Sarmento, Luciana d'Abreu; Rosa, Felipe Monnerat Marino; Rosado, Eliane Lopes; Carneiro, João Régis Ivar; Souza, Antônio Augusto Peixoto de; Magno, Fernanda Cristina Carvalho Mattos

Due to the high failure rate observed in the clinical treatment of morbid obesity an increase in bariatric surgery indications, as an alternative for the control of obesity and comorbidities, is noticeable. To evaluate the performance of type 2 diabetes mellitus, high blood pressure and dyslipidemia in patients submitted to Roux-en-Y gastric bypass in late follow-up. Retrospective analysis of 59 patients included in the bariatric surgery program. Anthropometric (height and body weight) and laboratory (LDLc, HDLc, VLDLc, triglyceride -TG - and glucose) data were collected on pre- and postoperative stages, through medical records. Among the patients, 86% were female aged 43±11, of whom 52% had attended high school. The average postoperative time was 7±3 years. During the postoperative period, there were decreases of weight and body mass index, respectively (133±06 kg vs 91±04 kg p<0.05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0.05). In comparison to the preoperative stage, lower concentrations of glucose (101.00±26.99 vs 89,11±15.19, p=0.014), total cholesterol rates (179.00±37,95 vs 167.48±28,50, p=0.016), LDLc (104.30±33.12 vs 91.46±24.58, p=0.016), VLDLc (25.40±11,12 vs 15.68±7.40, p<0.01), and TG (143.35±86.35 vs 82.45±37.39, p<0.01) and higher concentrations of HDLc (43.53±8.23 vs 57.90±15.60, p<0.01) were identified in the postoperative stage. 40% of hypertensive patients were still undergoing high blood pressure treatment during the postoperative stage. There was remission of type 2 diabetes mellitus and dyslipidemia on 81% and 94% of the cases, respectively. Roux-en-Y gastric bypass has proven itself to be an effective long term procedure, promoting weight loss, remission of DM2 and dyslipidemia. Em função do alto grau de falência que se observa no tratamento clínico da obesidade mórbida, observa-se um aumento da procura pela cirurgia bariátrica como alternativa para o controle da obesidade e comorbidades. Avaliar a evolução do diabete melito tipo 2, da hipertensão arterial sistêmica e da dislipidemia em pacientes submetidos à gastroplastia redutora em Y-de-Roux no período de pós-operatório tardio. Análise retrospectiva de 59 pacientes inseridos em programa de cirurgia bariátrica. Foram coletados dados antropométricos (altura e peso corporal) e laboratoriais (LDLc, HDLc, VLDLc, triglicerídeo -TG - e glicose) nos períodos pré e pós-operatório por meio de prontuários médicos. Entre os pacientes, 86% eram mulheres com idade de 43±11 anos e 52% tinham cursado o ensino médio. O tempo médio de pós-operatório foi de 7±3 anos. Houve redução no peso e no índice de massa corporal no pós-operatório, respectivamente (133±06 kg vs 91±04 kg p<0,05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0,05). Observou-se concentrações inferiores no pós-operatório, comparado com o pré-operatório, da glicose (101,00±26,99 vs 89,11±15,19, p=0,014), colesterol total (179,00±37,95 vs 167,48±28,50, p=0,016), LDLc (104,30±33,12 vs 91,46±24,58, p=0,016), VLDLc (25,40±11,12 vs 15,68±7,40, p<0,01), e TG (143,35±86,35 vs 82,45±37,39, p<0,01) e maiores de HDLc (43,53±8,23 vs 57,90±15,60, p<0,01 ). No pós-operatório 40% dos pacientes hipertensos ainda estavam em tratamento para hipertensão arterial sistêmica. Houve remissão do diabete melito tipo 2 e da dislipidemia em 81% e 94% dos casos, respectivamente. A gastroplastia redutora em Y-de-Roux mostrou ser procedimento eficaz em longo prazo, com resultados persistentes na perda de peso, remissão do DM2 e da dislipidemia.

Statistical methods for biodosimetry in the presence of both Berkson and classical measurement error

NASA Astrophysics Data System (ADS)

Miller, Austin

In radiation epidemiology, the true dose received by those exposed cannot be assessed directly. Physical dosimetry uses a deterministic function of the source term, distance and shielding to estimate dose. For the atomic bomb survivors, the physical dosimetry system is well established. The classical measurement errors plaguing the location and shielding inputs to the physical dosimetry system are well known. Adjusting for the associated biases requires an estimate for the classical measurement error variance, for which no data-driven estimate exists. In this case, an instrumental variable solution is the most viable option to overcome the classical measurement error indeterminacy. Biological indicators of dose may serve as instrumental variables. Specification of the biodosimeter dose-response model requires identification of the radiosensitivity variables, for which we develop statistical definitions and variables. More recently, researchers have recognized Berkson error in the dose estimates, introduced by averaging assumptions for many components in the physical dosimetry system. We show that Berkson error induces a bias in the instrumental variable estimate of the dose-response coefficient, and then address the estimation problem. This model is specified by developing an instrumental variable mixed measurement error likelihood function, which is then maximized using a Monte Carlo EM Algorithm. These methods produce dose estimates that incorporate information from both physical and biological indicators of dose, as well as the first instrumental variable based data-driven estimate for the classical measurement error variance.

Primary Mitral Valve Regurgitation Outcome in Patients With Severe Aortic Stenosis 1 Year After Transcatheter Aortic Valve Implantation: Echocardiographic Evaluation.

PubMed

Florentino, Thiago Marinho; Bihan, David Le; Abizaid, Alexandre Antonio Cunha; Cedro, Alexandre Vianna; Corrêa, Amably Pessoa; Santos, Alexandre Roginski Mendes Dos; Souza, Alexandre Costa; Bignoto, Tiago Costa; Sousa, José Eduardo Moraes Rego; Sousa, Amanda Guerra de Moraes Rego

2017-07-10

Mitral valve regurgitation (MR), present in up to 74% of the patients with severe aortic stenosis (AS), can be a negative prognostic factor when moderate or severe. The outcome of MR after percutaneous transcatheter aortic valve implantation (TAVI) and predictors associated with that outcome have not been well established in the literature. To assess the outcome of primary MR in patients submitted to TAVI and to identify associated factors. Observational study of patients with symptomatic severe AS submitted to TAVI from January 2009 to April 2015 at two specialized centers. Echocardiographic outcome was assessed with data collected before and 1 year after TAVI. Of the 91 patients with MR submitted to TAVI and followed up for at least 12 months, 67 (73.6%) had minimum/mild MR before the procedure and 24 (26.4%) had moderate/severe MR. Of those with minimum/mild MR, 62 (92.5%) had no change in the MR grade (p < 0.001), while 5 (7.5%) showed worsening. Of those with moderate/severe MR, 8 (33.3%) maintained the same grade and 16 (66.7%) improved it (p = 0.076). Patients with moderate/severe MR who improved MR grade had lower EuroSCORE II (p = 0.023) and STS morbidity (p = 0.027) scores, as compared to those who maintained the MR grade. MR grades change after TAVI. This study suggests a trend towards improvement in moderate/severe MR after TAVI, which was associated with lower preoperative risk scores. A insuficiência valvar mitral (IM), presente em até 74% dos pacientes com estenose aórtica (EA) grave, pode representar um fator prognóstico negativo quando moderada ou importante. A evolução da IM após implante percutâneo de valva aórtica transcateter (TAVI) e preditores associados a essa evolução não estão bem estabelecidos na literatura. Avaliar a evolução da IM primária em pacientes submetidos ao TAVI e identificar fatores associados a essa evolução. Realizou-se um estudo observacional em pacientes com EA grave sintomática, submetidos ao TAVI no período de janeiro de 2009 a abril de 2015 em dois centros especializados. Foram avaliados desfechos ecocardiográficos com dados antes e 1 ano após a intervenção. Dos 91 pacientes com IM que realizaram TAVI e tinham acompanhamento de pelo menos 12 meses, 67 (73,6%) apresentavam IM mínima ou discreta antes da realização do procedimento e 24 (26,4%), IM moderada ou grave. Entre os com IM mínima ou discreta, 62 (92,5%) não apresentaram mudança no grau de refluxo (p < 0,001) e 5 (7,5%) tiveram piora. Entre os com IM moderada ou grave, 8 (33,3%) permaneceram na mesma classe e 16 (66,7%) tiveram melhora (p = 0,076). Pacientes com IM moderada ou grave que melhoraram o grau de insuficiência apresentavam menores valores de EuroSCORE II (p = 0,023) e STS morbidade (p = 0,027), quando comparados aos que continuaram na mesma classe. Observou-se mudança significativa no grau de IM após realização de TAVI. Este estudo sugere uma tendência de melhora da IM moderada ou grave após TAVI, o que se associou a escores de risco pré-operatórios menos elevados.

Improved electromagnetic tracking for catheter path reconstruction with application in high-dose-rate brachytherapy.

PubMed

Lugez, Elodie; Sadjadi, Hossein; Joshi, Chandra P; Akl, Selim G; Fichtinger, Gabor

2017-04-01

Electromagnetic (EM) catheter tracking has recently been introduced in order to enable prompt and uncomplicated reconstruction of catheter paths in various clinical interventions. However, EM tracking is prone to measurement errors which can compromise the outcome of the procedure. Minimizing catheter tracking errors is therefore paramount to improve the path reconstruction accuracy. An extended Kalman filter (EKF) was employed to combine the nonlinear kinematic model of an EM sensor inside the catheter, with both its position and orientation measurements. The formulation of the kinematic model was based on the nonholonomic motion constraints of the EM sensor inside the catheter. Experimental verification was carried out in a clinical HDR suite. Ten catheters were inserted with mean curvatures varying from 0 to [Formula: see text] in a phantom. A miniaturized Ascension (Burlington, Vermont, USA) trakSTAR EM sensor (model 55) was threaded within each catheter at various speeds ranging from 7.4 to [Formula: see text]. The nonholonomic EKF was applied on the tracking data in order to statistically improve the EM tracking accuracy. A sample reconstruction error was defined at each point as the Euclidean distance between the estimated EM measurement and its corresponding ground truth. A path reconstruction accuracy was defined as the root mean square of the sample reconstruction errors, while the path reconstruction precision was defined as the standard deviation of these sample reconstruction errors. The impacts of sensor velocity and path curvature on the nonholonomic EKF method were determined. Finally, the nonholonomic EKF catheter path reconstructions were compared with the reconstructions provided by the manufacturer's filters under default settings, namely the AC wide notch and the DC adaptive filter. With a path reconstruction accuracy of 1.9 mm, the nonholonomic EKF surpassed the performance of the manufacturer's filters (2.4 mm) by 21% and the raw EM measurements (3.5 mm) by 46%. Similarly, with a path reconstruction precision of 0.8 mm, the nonholonomic EKF surpassed the performance of the manufacturer's filters (1.0 mm) by 20% and the raw EM measurements (1.7 mm) by 53%. Path reconstruction accuracies did not follow an apparent trend when varying the path curvature and sensor velocity; instead, reconstruction accuracies were predominantly impacted by the position of the EM field transmitter ([Formula: see text]). The advanced nonholonomic EKF is effective in reducing EM measurement errors when reconstructing catheter paths, is robust to path curvature and sensor speed, and runs in real time. Our approach is promising for a plurality of clinical procedures requiring catheter reconstructions, such as cardiovascular interventions, pulmonary applications (Bender et al. in medical image computing and computer-assisted intervention-MICCAI 99. Springer, Berlin, pp 981-989, 1999), and brachytherapy.

Continuous manufacturing and analytical characterization of fixed-dose, multilayer orodispersible films.

PubMed

Thabet, Yasmin; Lunter, Dominique; Breitkreutz, Joerg

2018-05-30

Various drug therapies require more than one active pharmaceutical ingredient (API) for an effective treatment. There are many advantages, e.g. to improve the compliance or pharmacodynamic response in comparison to a monotherapy or to increase the therapy safety. Until now, there are only a few products available for the paediatric population due to the lack of age appropriate dosage forms or studies proving the efficacy and safety of these products. This study aims to develop orodispersible films (ODFs) in a continuous solvent casting process as child appropriate dosage form containing both enalapril maleate (EM) and hydrochlorothiazide (HCT) separated in different film layers. Furthermore, they should be characterised and the API migration analysed by confocal Raman microscopy (CRM). ODFs were successfully produced in a continuous manufacturing process in form of double- and triple-layer formulations based on hydroxypropylcellulose (HPC) or a combination of HPC and polyvinyl alcohol (PVA). CRM revealed that both APIs migrate within the film layers shortly after manufacturing. PVA inhibits the migration inside the double-layer film, but is not able to prevent the API migration as an interlayer inside a triple-layer ODF. With increasing film layers, the content of residual solvents and the disintegration time increases (mono-layer films: <10 s, triple-layer films: 37 s). In conclusion, it was feasible to produce fixed-dose combinations in therapeutic doses up to 9 mg HCT and 3.5 mg EM for the double-layer film with adequate mechanical properties, which enable coiling up onto jumbo rolls directly after production. The best separation of the two APIs was achieved by casting a double-layer ODF consisting of different film forming polymers, which can be beneficial when processing two incompatible APIs. Copyright © 2018 Elsevier B.V. All rights reserved.

Adaptive radiation therapy for postprostatectomy patients using real-time electromagnetic target motion tracking during external beam radiation therapy.

PubMed

Zhu, Mingyao; Bharat, Shyam; Michalski, Jeff M; Gay, Hiram A; Hou, Wei-Hsien; Parikh, Parag J

2013-03-15

Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow. Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (Dmin) with the planned Dmin to the CTV. Treatments were considered adequate if the delivered CTV Dmin is at least 95% of the planned CTV Dmin. Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: -0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments. Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of extracellular matrix metalloproteinase inducer (EMMPRIN) in the regulation of bovine endometrial cell functions.

PubMed

Mishra, Birendra; Kizaki, Keiichiro; Sato, Takashi; Ito, Akira; Hashizume, Kazuyoshi

2012-06-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell surface glycoprotein that stimulates the production of several matrix metalloproteinases (MMPs) for tissue remodeling. Previously, we detected EMMPRIN in the bovine endometrium, and it is mainly expressed in the luminal and glandular epithelium whereas MMPs are expressed in the underlying stroma. From this expression pattern, we hypothesized that EMMPRIN may regulate stromal MMPs in endometrial cell functions. To test this hypothesis, a coculture of epithelial and stromal cells was performed using a transwell system. In the coculture, epithelial cells were cultured on the insert membrane and stromal cell on the surface of well plates. Expression of stromal MMP-2 and MMP-14 was significantly higher in coculture with epithelial cell. Further, with the addition of anti-EMMPRIN antibody into the epithelial cell compartment, the expression of stromal EMMPRIN and MMP-2 and MMP-14 was decreased. To identify the active site of EMMPRIN for the augmentation of MMPs, EMMPRIN synthetic peptides that correspond to the extracellular loop domain-I (EM1, EM2, EM3, and EM4) were added into the epithelial cell compartment, and only EM2 at a higher dose interfered with EMMPRIN-mediated expression of MMP-14. Next, we examined the effects of progesterone and/or estrogen on the expression of EMMPRIN, MMP-2, and MMP-14. Progesterone (300 nM) significantly stimulated the expression of EMMPRIN but had no effects on any of the MMPs. These results suggest that EMMPRIN derived from epithelial cells regulates MMPs in the endometrium under progesterone-rich conditions and may thereby modulate bovine endometrial cell functions during gestation.

Electromagnetic navigation technology for more precise electrode placement in the foramen ovale: a technical report.

PubMed

Van Buyten, Jean-Pierre; Smet, Iris; Van de Kelft, Erik

2009-07-01

Introduction. Interventional pain management techniques require precise positioning of needles or electrodes, therefore fluoroscopic control is mandatory. This imaging technique does however not visualize soft tissues such as blood vessels. Moreover, patient and physician are exposed to a considerable dose of radiation. Computed tomography (CT)-scans give a better view of soft tissues, but there use requires presence of a radiologist and has proven to be laborious and time consuming. Objectives. This study is to develop a technique using electromagnetic (EM) navigation as a guidance technique for interventional pain management, using CT and/or magnetic resonance (MRI) images uploaded on the navigation station. Methods. One of the best documented interventional procedures for the management of trigeminal neuralgia is percutaneous radiofrequency treatment of the Gasserian ganglion. EM navigation software for intracranial applications already exists. We developed a technique using a stylet with two magnetic coils suitable for EM navigation. The procedure is followed in real time on a computer screen where the patient's multislice CT-scan images and three-dimensional reconstruction of his face are uploaded. Virtual landmarks on the screen are matched with those on the patient's face, calculating the precision of the needle placement. Discussion. The experience with EM navigation acquired with the radiofrequency technique can be transferred to other interventional pain management techniques, for instance, for the placement of a neuromodulation electrode close to the Gasserian ganglion. Currently, research is ongoing to extend the software of the navigation station for spinal application, and to adapt neurostimulation hardware to the EM navigation technology. This technology will allow neuromodulation techniques to be performed without x-ray exposure for the patient and the physician, and this with the precision of CT/MR imaging guidance. © 2009 International Neuromodulation Society.

Mechanical and electromagnetic induction of protection against oxidative stress.

PubMed

Di Carlo, A L; White, N C; Litovitz, T A

2001-01-01

Cells and tissues can be protected against a potentially lethal stress by first exposing them to a brief dose of the same or different stress. This "pre-conditioning" phenomenon has been documented in many models of protection against oxidative stress, including ischemia/reperfusion and ultraviolet (UV) light exposure. Stimuli which induce this protective response include heat, chemicals, brief ischemia, and electromagnetic (EM) field exposures. We report here that constant mechanical vibration pre-conditions chick embryos, protecting them during subsequent stress from hypoxia or UV light exposure. Continuously mechanically vibrated embryos (60 Hz, 1 g (32 ft/s2), 20 min) exhibited nearly double the survival (67.5%, P < 0.001) after subsequent hypoxia as compared to non-vibrated controls (37.6%). As a second set of experiments, embryos were vibrated and then exposed to UV light stress. Those embryos that were vibrated prior to UV had nearly double the survival 3 h after UV exposure (66%, P < 0.001) as compared to controls (35%). The degree of protection, however, was dependent on the constancy of the vibration amplitude. When vibration was turned on and off at 1-s intervals throughout exposure, no increase in hypoxia protection was noted. For 50 s on/off vibration intervals, however, hypoxia protection comparable to continuous vibration was obtained. In contrast, random, inconstant mechanical vibration did not induce protection against subsequent UV exposure. These data suggest that to be an effective pre-conditioning agent, mechanical vibration must have a degree of temporally constancy (on/off intervals of greater than 1 s). Further experiments in both models (hypoxia and UV) indicated an interaction between vibration and EM field-induced protection. Vibration-induced hypoxia protection was inhibited by superposition of a random EM noise field (previously shown to inhibit EM field-induced protection). In addition, EM field-induced UV protection was inhibited by the superposition of random mechanical vibration. Thus, the superposition of either vibrational or EM noise during pre-conditioning virtually eliminated protection against hypoxia and UV. This link between EM field exposures and mechanical vibration is consistent with the hypothesis that cells sense these stimuli via a similar mechanism involving counter ion displacement.

Utility of Ultraportable Echocardiography in the Preoperative Evaluation of Noncardiac Surgery.

PubMed

Costa, Jean Allan; Almeida, Maria Lucia Pereira; Estrada, Tereza Cristina Duque; Werneck, Guilherme Lobosco; Rocha, Alexandre Marins; Rosa, Maria Luiza Garcia; Ribeiro, Mario Luiz; Mesquita, Claudio Tinoco

2016-11-01

The ultraportable echocardiogram machine, with relevant portability and easiness in performing diagnoses, when in experienced hands, may contribute to the reliability of preoperative evaluation in noncardiac surgeries. To assess cardiac function parameters in patients aged older than 60 years, candidates of elective noncardiac surgeries, classified as ASA1 or ASA 2 according to surgical risk. A total of 211 patients referred for elective surgeries, without suspicion of previous heart diseases, were included in the study. Assessment of patients was conducted by conventional echocardiogram using the ultraportable V Scan (GE) device right after the pre-anesthetic clinical evaluation. We assessed the clinical impact of echocardiography results by using a questionnaire addressed to the anesthetist. Mean age of patients was 68.9 ± 7.0 years, 154 were women. The most frequent surgeries were: a) facectomy - cataract - 18; b) inguinal hernia surgery - 18; c) Cholecystectomy - 16. We found 58 normal tests (27.5%), 70 (33.2%) with mild valve reflux, and 83 (39.3%) with relevant abnormality, such as increase in heart chamber size, global and/or segmental contractile dysfunction, significant valve dysfunction or other unspecified. Test results caused delay of surgical procedure for a more detailed cardiac evaluation in 20 (9.5%) patients, and change in anesthetic management in 7 (3.3%). There was a considerable clinical impact with the use of the ultraportable echocardiography, since one out of every ten patients evaluated had their clinical management changed due to the detection of previously unsuspected, significant heart diseases, with the potential for severe complications. O ecocardiógrafo ultraportátil, com importante mobilidade e facilidade diagnóstica em mãos experientes pode contribuir para a segurança na avaliação pré-operatória em cirurgias não cardíacas. Avaliar os parâmetros de função cardíaca nos pacientes com mais de 60 anos de idade, candidatos a cirurgias não-cardíacas eletivas, classificados como ASA 1 ou ASA 2 na classificação de risco cirúrgico. Foram incluídos 211 pacientes direcionados para cirurgias eletivas diversas e sem suspeita prévia de cardiopatia. Os pacientes foram avaliados por técnica ecocardiográfica convencional, usando o aparelho ultraportátil V Scan (GE) logo após a avaliação clínica pré-anestésica. Avaliamos o impacto clínico dos resultados da ecocardiografia por um questionário dirigido ao anestesista. A idade média dos pacientes foi 68,9 ± 7,0 anos, 154 do sexo feminino. As cirurgias mais frequentes foram: a) Facectomia-catarata - 18; b) Herniorrafia inguinal - 18; c) Colecistectomia - 16. No total, foram observados 58 exames normais (27,5%), 70 (33,2%) exames que apresentavam leves refluxos valvares e 83 (39,3%) exames com alguma anormalidade relevante, como aumento de câmara cardíaca, disfunção contrátil global e/ou segmentar, disfunção valvar mais significativa ou outra não especificada. Os resultados determinaram que 20 (9,5%) pacientes tivessem seus procedimentos cirúrgicos adiados até avaliação cardiológica mais detalhada e em 7 (3,3%) houve mudança na conduta anestésica. Houve um impacto clínico considerável com o uso da ecocardiografia ultraportátil, pois um em cada dez pacientes avaliados sofreu modificação na conduta clínica, em função da detecção de cardiopatias significativas, não suspeitadas previamente, e com potencial para complicações graves.

Essential Medicine Utilization and Situation in Selected Ten Developing Countries: A Compendious Audit

PubMed Central

Haque, Mainul

2017-01-01

Medicine improves the quality of life and increases mean age of human beings as it fights against diseases. Accessibility to medicines is the fundamental right of every person. The principle of the essential medicines (EMs) is that a limited number of availability of medicine will promote to a better supply chain and rational prescribing to the rural and remote health centers for any developing countries. Furthermore, it was also expected that this concept will also ensure better procurement policy at lower costs, more in amount, with easier storage. Thereby, EMs will safeguard and improve distribution and dispensing of medicine. Correspondingly, motivational and dedicated training program regarding drug information and adverse drug reactions will boost up access to medicine and health-care. In addition, the selection of medicine from EM is the first step in the direction of the rational use of medicine and progress and ensuring the quality of health care. Thereafter, selection needs to be followed by appropriate use. Everyone should receive the right medicine, in an adequate dose for an adequate duration, with appropriate information and follow-up treatment, and at an affordable cost. The acceptance and implementation of World Health Organization-promoted EM policies in deferent countries have improved quality use of medicine in terms of accessibility and affordability, predominantly in developing countries. The corporations and teamwork among various participants of health care are instantly obligatory to progress equitable access to medicines in low- and middle-income countries. PMID:28852629

The time dependent association of adrenaline administration and survival from out-of-hospital cardiac arrest.

PubMed

Ewy, Gordon A; Bobrow, Bentley J; Chikani, Vatsal; Sanders, Arthur B; Otto, Charles W; Spaite, Daniel W; Kern, Karl B

2015-11-01

Recommended for decades, the therapeutic value of adrenaline (epinephrine) in the resuscitation of patients with out-of-hospital cardiac arrest (OHCA) is controversial. To investigate the possible time-dependent outcomes associated with adrenaline administration by Emergency Medical Services personnel (EMS). A retrospective analysis of prospectively collected data from a near statewide cardiac resuscitation database between 1 January 2005 and 30 November 2013. Multivariable logistic regression was used to analyze the effect of the time interval between EMS dispatch and the initial dose of adrenaline on survival. The primary endpoints were survival to hospital discharge and favourable neurologic outcome. Data from 3469 patients with witnessed OHCA were analyzed. Their mean age was 66.3 years and 69% were male. An initially shockable rhythm was present in 41.8% of patients. Based on a multivariable logistic regression model with initial adrenaline administration time interval (AATI) from EMS dispatch as the covariate, survival was greatest when adrenaline was administered very early but decreased rapidly with increasing (AATI); odds ratio 0.94 (95% Confidence Interval (CI) 0.92-0.97). The AATI had no significant effect on good neurological outcome (OR=0.96, 95% CI=0.90-1.02). In patients with OHCA, survival to hospital discharge was greater in those treated early with adrenaline by EMS especially in the subset of patients with a shockable rhythm. However survival rapidly decreased with increasing adrenaline administration time intervals (AATI). Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Opioid Overdose Outbreak - West Virginia, August 2016.

PubMed

Massey, Joel; Kilkenny, Michael; Batdorf, Samantha; Sanders, Sarah K; Ellison, Debra; Halpin, John; Gladden, R Matthew; Bixler, Danae; Haddy, Loretta; Gupta, Rahul

2017-09-22

On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters. EMS personnel, other first responders, and ED providers administered the opioid antidote naloxone to 16 (80%) patients, six of whom were administered multiple doses, suggesting exposure to a highly potent opioid. No patients received referral for recovery support services. In addition to the public health investigation, a public safety investigation was conducted; comprehensive opioid toxicology testing of clinical specimens identified the synthetic opioid fentanyl* and novel fentanyl analogs, including carfentanil, † which had been used by patients who overdosed in Huntington. Results of these two investigations highlight the importance of collaboration between public health and public safety agencies to provide in-depth surveillance data from opioid overdose outbreaks that involve high-potency fentanyl analogs. These data facilitated a public health response through increased awareness of powerful opioid substances requiring multiple naloxone doses for reversal, and improved patient linkage to recovery support services and a harm reduction program from the ED after opioid overdose.

CT brush and CancerZap!: two video games for computed tomography dose minimization.

PubMed

Alvare, Graham; Gordon, Richard

2015-05-12

X-ray dose from computed tomography (CT) scanners has become a significant public health concern. All CT scanners spray x-ray photons across a patient, including those using compressive sensing algorithms. New technologies make it possible to aim x-ray beams where they are most needed to form a diagnostic or screening image. We have designed a computer game, CT Brush, that takes advantage of this new flexibility. It uses a standard MART algorithm (Multiplicative Algebraic Reconstruction Technique), but with a user defined dynamically selected subset of the rays. The image appears as the player moves the CT brush over an initially blank scene, with dose accumulating with every "mouse down" move. The goal is to find the "tumor" with as few moves (least dose) as possible. We have successfully implemented CT Brush in Java and made it available publicly, requesting crowdsourced feedback on improving the open source code. With this experience, we also outline a "shoot 'em up game" CancerZap! for photon limited CT. We anticipate that human computing games like these, analyzed by methods similar to those used to understand eye tracking, will lead to new object dependent CT algorithms that will require significantly less dose than object independent nonlinear and compressive sensing algorithms that depend on sprayed photons. Preliminary results suggest substantial dose reduction is achievable.

Dextrose 10% in the treatment of out-of-hospital hypoglycemia.

PubMed

Kiefer, Matthew V; Gene Hern, H; Alter, Harrison J; Barger, Joseph B

2014-04-01

Prehospital first responders historically have treated hypoglycemia in the field with an IV bolus of 50 mL of 50% dextrose solution (D50). The California Contra Costa County Emergency Medical Services (EMS) system recently adopted a protocol of IV 10% dextrose solution (D10), due to frequent shortages and relatively high cost of D50. The feasibility, safety, and efficacy of this approach are reported using the experience of this EMS system. Over the course of 18 weeks, paramedics treated 239 hypoglycemic patients with D10 and recorded patient demographics and clinical outcomes. Of these, 203 patients were treated with 100 mL of D10 initially upon EMS arrival, and full data on response to treatment was available on 164 of the 203 patients. The 164 patients' capillary glucose response to initial infusion of 100 mL of D10 was calculated and a linear regression line fit between elapsed time and difference between initial and repeat glucose values. Feasibility, safety, and the need for repeat glucose infusions were examined. The study cohort included 102 men and 62 women with a median age of 68 years. The median initial field blood glucose was 38 mg/dL, with a subsequent blood glucose median of 98 mg/dL. The median time to second glucose testing was eight minutes after beginning the 100 mL D10 infusion. Of 164 patients, 29 (18%) required an additional dose of IV D10 solution due to persistent or recurrent hypoglycemia, and one patient required a third dose. There were no reported adverse events or deaths related to D10 administration. Linear regression analysis of elapsed time and difference between initial and repeat glucose values showed near-zero correlation. In addition to practical reasons of cost and availability, theoretical risks of using 50 mL of D50 in the out-of-hospital setting include extravasation injury, direct toxic effects of hypertonic dextrose, and potential neurotoxic effects of hyperglycemia. The results of one local EMS system over an 18-week period demonstrate the feasibility, safety, and efficacy of using 100 mL of D10 as an alternative. Additionally, the linear regression line of repeat glucose measurements suggests that there may be little or no short-term decay in blood glucose values after D10 administration.

Influence of sex and CYP2D6 genotype on mirtazapine disposition, evaluated in Spanish healthy volunteers.

PubMed

Borobia, Alberto M; Novalbos, Jesús; Guerra-López, Pedro; López-Rodríguez, Rosario; Tabares, Beatriz; Rodríguez, Vanesa; Abad-Santos, Francisco; Carcas, Antonio J

2009-06-01

To evaluate the influence of sex and CYP2D6 genotype on mirtazapine disposition within two bioequivalence studies in healthy volunteers. Seventy-two healthy volunteers were included in two standard 2 x 2 crossover bioequivalence trials. Subjects received a single 30-mg oral dose of each mirtazapine formulation in each study period. Plasma concentrations were measured from 0 to 96 or 120 h by a HPLC with coupled mass spectrometry validated method. CYP2D6 genotyping was available for 68 subjects that were classified into three phenotypic groups depending on the number of active gene copies: extensive/ultrarapid metabolizers (UM-EM), intermediate (IM) and poor metabolizers (PM). To evaluate the influence of sex and genotype on mirtazapine disposition we performed a linear mixed model for repeated measures. Pharmacokinetic data were log-transformed and AUC and C(max) adjusted to the administered dose/weight. Factors included in the model were centre, formulation, period, sequence, sex and genotype as fixed effects, and subject nested sequence x sex x genotype as random one. A second model was also performed adding the interaction sex x genotype to the previous model. Mirtazapine disposition evaluated as AUC(0-infinity) is influenced by sex (p=0.007) and CYP2D6 phenotype group (p=0.01). Attending to the theoretical figures provided by the model, mean (95% CI) dose/weight adjusted AUC(0-infinity) (ng h/ml)/(mg/kg) is 1516.62 (1411.27-1628.22) in EM/UM, 1613.63 (1482.14-1758.55) in IM and 2049.28 (1779.78-2357.24) in PM. In the case of C(max) these figures also show a trend to higher values in PM, but it did not reach statistical significance. Females show a lower dose/weight adjusted AUC(0-infinity): 1594.39 (1477.70-1720.28) vs. 1837.65 (1694.67-1992.70). On the contrary dose/weight adjusted C(max) is higher in females than in males: 38.33 (34.79-42.28) vs. 32.66 (29.44-36.21). Both CYP2D6 genotype group and sex influence the disposition of mirtazapine in healthy volunteers and confirm reported data in the literature obtained by different methods. No sex-by-genotype interaction could be detected.

The influence of nicotine in healing of small bowel anastomoses in rats: angiogenesis and miofibroblasts.

PubMed

Skinovsky, James; Malafaia, Osvaldo; Chibata, Mauricio; Tsumanuma, Fernanda; Panegalli, Flávio; Martins, Marcus Vinícius Dantas de Campos

2016-01-01

to know the effect of nicotine on angiogenesis and myofibroblast formation in anastomoses of the small bowel of rats. we randomly divided 60 Wistar rats into the groups Nicotine (N) and control (C), according to the proposed treatment. Each group was subdivided into three subgroups according to the time interval used for the evaluation (7, 14 or 28 days). The N group with 30 animals received nicotine subcutaneously at a dose of 2mg/kg body weight, diluted in 0.3ml of 0.9% saline, twice daily for 28 days prior to the operation, and for more 7, 14 or 28 days, depending on the subgroup. The C group (also 30 animals) received only saline on the same conditions and time intervals. After 28 days we carried out an end-to-end anastomosis 10cm distal to the duodenojejunal flexure in each rat. After 7, 14 or 28 days after surgery, we euthanized ten animals of each group, sent specimens of the anastomosis areas, 1cm proximal to 1cm distal, to counting of blood vessels and myofibroblasts through immunohistochemical staining by the application of monoclonal anti-factor VIII antibodies and anti-smooth muscle alpha-actin. the administration of nicotine led to the decrease in the number of blood vessels measured on the 28th postoperative day and the number of myofibroblasts measured on the seventh day following completion of the anastomoses. administration of nicotine was deleterious on angiogenesis and myofibroblast formation in rats' small intestine anastomoses. conhecer o efeito da nicotina sobre a angiogênese e formação de miofibroblastos em anastomoses do intestino delgado de ratos. sessenta ratos Wistar foram divididos de maneira aleatória em grupos Nicotina(N) e Controle (C), conforme o tratamento proposto. Cada grupo foi subdividido em três subgrupos, de acordo com o intervalo de tempo utilizado para a avaliação (7, 14 ou 28 dias). O grupo N, com 30 animais, recebeu nicotina por via subcutânea, na dose de 2mg/Kg de peso, diluída em 0,3ml de solução salina a 0,9%, em duas aplicações diárias, durante 28 dias prévios à operação e por mais 7, 14 ou 28 dias, conforme o subgrupo. O grupo C (igualmente com 30 animais) recebeu somente a solução salina nas mesmas condições e intervalos de tempo. Após 28 dias efetuou-se, em cada rato, anastomose término-terminal a 10cm da flexura duodenojejunal. Após 7, 14 ou 28 dias da cirurgia, os dez animais de cada subgrupo foram eutanasiados, sendo que as áreas anastomosadas, 1cm proximal a 1cm distal, foram encaminhadas para contagem de vasos sanguíneos e miofibroblastos, através de coloração imuno-histoquímica por aplicação dos anticorpos monoclonais antifator VIII e anti-alfa-actina muscular lisa. a administração de nicotina levou à diminuição do número de vasos sanguíneos aferidos no 28o dia pós-operatório e do número de miofibroblastos aferidos no sétimo dia após a realização das anastomoses. a administração de nicotina foi deletéria sobre a angiogênese e formação de miofibroblastos em anastomoses do intestino delgado de ratos.

Frequent inoculations with radiation attenuated sporozoite is essential for inducing sterile protection that correlates with a threshold level of Plasmodia liver-stage specific CD8+ T cells.

PubMed

Patel, Hardik; Yadav, Naveen; Parmar, Rajesh; Patel, Satish; Singh, Agam P; Shrivastava, Neeta; Dalai, Sarat K

2017-07-01

Whole sporozoite vaccine (WSV) is shown to induce sterile protection that targets Plasmodium liver-stage infection. There are many underlying issues associated with induction of effective sterile protracted protection. In this study, we have addressed how the alterations in successive vaccine regimen could possibly affect the induction of sterile protection. We have demonstrated that the pattern of vaccination with RAS (radiation attenuated sporozoites) induces varying degrees of protection among B6 mice. Animals receiving four successive doses generated 100% sterile protection. However, three successive doses, though with the same parasite inoculum as four doses, could induce sterile protection in ∼50% mice. Interestingly, mice immunized with the same 3 doses, but with longer gap, could not survive the challenge. We demonstrate that degree of protection correlates with the frequencies of IFN-γ + and multifunctional (IFN-γ + CD107a + ) CD8 + T EM cells present in liver. The failure to achieve protective threshold frequency of these cells in liver might make the host more vulnerable to parasite infection during infectious sporozoite challenge. Copyright © 2017. Published by Elsevier Inc.

Developmental stage-associated differences in the transplacental distribution of 13-cis- and all-trans-retinoic acid as well as their glucuronides in rats and mice.

PubMed

Tzimas, G; Collins, M D; Nau, H

1995-07-01

In mice and rats, 13-cis-retinoic acid (13-cis-RA) has a much lower teratogenic potency than all-trans-retinoic acid (all-trans-RA). Previous studies on Gestational Day (GD) 11 or 12 (in mice or rats, respectively) showed a limited transfer of 13-cis-RA to the embryo, in contrast to the efficient transplacental passage of all-trans-RA. In the present study we examined if the distribution between maternal circulation and embryo of 13-cis- and all-trans-RA as well as their metabolites is different at gestational times when the placenta is developing from a choriovitelline to a chorioallantoic type. In the first experiment, 13-cis-RA was administered orally to pregnant rats (75 mg/kg/day) daily, from either GD 7 to 12 or 11 to 16. In the second experiment, 13-cis-RA or all-trans-RA was given orally to pregnant mice once on either GD 11 or 14, at two dose levels (10 and 100 mg/kg). HPLC analysis of plasma and embryo samples collected at various time points post-treatment showed that 13-cis-RA was predominantly metabolized to its beta-glucuronide (13-cis-RAG) while all-trans-RA was primarily biotransformed to all-trans-4-oxo-RA and to a lesser extent to all-trans-RAG. 13-cis-RA showed a more efficient transplacental passage to the rat embryo on GD 16 than on GD 12, as indicated by higher ratios of embryonic to maternal plasma concentrations (E/M concentration ratio) on GD 16 vs. GD 12 and its E/M ratio of area-under-the-concentration-time-curve values (E/M AUC ratio; twofold higher on GD 16 vs. GD 12). In the mouse, the E/M concentration ratio of 13-cis-RA was significantly higher on GD 14 than on GD 11 only at the low dose. On the other hand, all-trans-RA and all-trans-4-oxo-RA showed an efficient transfer to the mouse embryo at both gestational times. In both species, 13-cis- and all-trans-RAG embryonic concentrations on the later gestational days exceeded significantly the corresponding ones on the earlier gestational days which resulted in far higher E/M concentration and AUC ratios for each of these metabolites on the later vs earlier gestational days. This may result from a more efficient placental transfer of the RAGs during later gestational stages and/or higher capacity of the late embryo or other conceptal tissues to biotransform RAs in situ to their glucuronides.(ABSTRACT TRUNCATED AT 400 WORDS)

Cost-Effectiveness Analysis of Ixekizumab vs Etanercept and Their Manufacturer-Recommended Dosing Regimens in Moderate to Severe Plaque Psoriasis.

PubMed

Udkoff, Jeremy; Eichenfield, Lawrence F

2017-10-01

Biologic therapies have revolutionized the treatment of psoriasis; however, their use is limited by costs. Ixekizumab was more effective than etanercept in the UNCOVER trials, and the Food and Drug Administration (FDA) approved ixekizumab for treating psoriasis. Evaluating the cost-effectiveness of these therapies is crucial for medical decision making and our objective was to determine the cost-effectiveness of various ixekizumab dosing frequencies compared with etanercept. We utilized published data from the UNCOVER comparative efficacy trials, including transitional probabilities and treatment response rates, to create a Markov model simulating the clinical course and cost-effectiveness of three treatment algorithms for patients with moderate to severe plaque psoriasis over 60-weeks: (1) ixekizumab every 2 weeks for 12 weeks then every 4 weeks, (2) ixekizumab every 4 weeks throughout the treatment period, (3) biweekly etanercept for 12 weeks then once weekly. We utilized a standard willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) and Medicaid drug acquisition costs for our calculations. Ixekizumab every 4 weeks was $28,681 (USD) less expensive than biweekly etanercept, and $21,375 less expensive, and 0.006 QALY less effective, than ixekizumab every 2 weeks-- a savings of $28.7 and $21.4 million, respectively, per 1,000 patients. A 95.6% cost reduction to $197.83 per dose is required for ixekizumab every 2 weeks to be more cost-effective than every 4 weeks. Biweekly etanercept requires a 29.5% cost reduction ($743.82 per dose) to be competitive with ixekizumab every 4 weeks. This cost-effectiveness model utilizes strong input data but is a limited approximation of real-life scenarios. Treatment with ixekizumab every 2 weeks is unlikely to be cost-effective compared with ixekizumab every 4 weeks at current U.S. market prices. Yet, the U.S. FDA approval and manufacturer's recommendation are for ixekizumab every 2 weeks. Accordingly, we suggested selecting biologic therapies using cost-effectiveness analyses.

J Drugs Dermatol. 2017;16(10):964-970.

Evolution of soil properties and metals in acid and alkaline mine tailing ponds after amendments and microorganisms application

NASA Astrophysics Data System (ADS)

Acosta, Jose A.; Faz, Ángel; Zornoza, Raúl; Martínez-Martínez, Silvia; Bech, Jaume

2015-04-01

Intense mining activities in the past were carried out in Cartagena-La Unión mining district, SE Spain, and caused excessive accumulation of toxic metals in tailing ponds which poses a high environmental and ecological risk. One of the remediation options gaining considerable interest in recent years is the in situ immobilization of metals. A corresponding reduction in the plant-available metal fraction allows re-vegetation and ecosystem restoration of the heavily contaminated sites. In addition, the use of microorganisms to improve the soil condition is a new tool used to increase spontaneous plant colonization. The aim of this research was to assess the effect of amendments (pig manure, sewage sludge, and lime) and microorganisms on the evolution of soil properties and metals in acid and alkaline tailing ponds and to evaluate the content of metals in Zygophylum fabago one year after amendments application. The study was carried out in two mine ponds (acid and alkaline). Twenty seven square field plots, each one consisting of 4 m2, were located in each pond. Four different doses of microorganism (EM) (0 ml, 20 ml, 100 ml and 200 ml of microorganism solution in each plot) and one dose of pig manure (5 kg per plot), sewage sludge (4 kg per plot) and lime (22 kg per plot) were used. Organic amendment doses were calculated according to European nitrogen legislations, and lime dose was calculated according with the potential acid production through total sulphur oxidation. Three replicates of each treatment (organic amendment + lime + microorganism dose 0, 1, 2, or 3) and control soil (with no amendments) were carried out. Plots were left to the semi-arid climate conditions after the addition of amendments to simulate real potential applications of the results. Soil samples was collected every 4 month from each plot during one year, after this time Zygophylum fabago plants were sampled from each plots. Soil properties including: pH, salinity, total, inorganic and organic carbon, total nitrogen, total phosphorus, potassium, total, bioextractable and soluble metals (Pb, Cu, Zn, As and Cd), basal respiration and microbial biomass carbon; and metals (Pb, Cu, Zn, As and Cd) in roots and shoot from Zygophylum fabago were analyzed. The results showed that the lime increased the concentration of inorganic carbon in both ponds and, therefore, increases the pH until neutral/alkaline values, especially in the acid mine pond, reducing the risk of mobility of As, Pb and Zn to the trophic chain and the risk of leaching and runoff. The application of pig manure increased the salinity in the acid mine pond, as well as the content of OC, TN, K and P in both ponds; also it caused a higher concentration of bioavailable and soluble Cu in both ponds due to the high content of Cu in the manure; finally, an higher concentration of bioavailable and soluble As was observed in the alkaline mine pond due to the formation of organic-metal complexes. The application of sewage sludge increased the content of OC and K in both mine ponds; also it caused an increase in the concentration of bioavailable and water soluble As and a slight increase in the water soluble Cu in the alkaline mine pond likely because of the formation of organic-metal complexes. Both organic amendments increased the microbial biomass carbon (MBC), especially pig manure, indicating that this amendment brings more amount of microorganisms than sewage sludge. Similarly, the application of EM increases MBC, especially in doses 2 and 3, improving soil conditions which favour plant colonization. Furthermore, microbial activity is increased after amendments and EM applications, especially when pig manure was used; indicating that organic matter from pig manure is more easily degradable by microorganisms than organic matter from sewage sludge. Finally, the results indicated that the application of EM promotes the absorption and subsequent translocation to leaves of Cu and As, while prevents the absorption of Cd and Zn in Zygophylum fabago.

Limiting factors in atomic resolution cryo electron microscopy: No simple tricks

PubMed Central

Zhang, Xing; Zhou, Z. Hong

2013-01-01

To bring cryo electron microscopy (cryoEM) of large biological complexes to atomic resolution, several factors – in both cryoEM image acquisition and 3D reconstruction – that may be neglected at low resolution become significantly limiting. Here we present thorough analyses of four limiting factors: (a) electron-beam tilt, (b) inaccurate determination of defocus values, (c) focus gradient through particles, and (d) particularly for large particles, dynamic (multiple) scattering of electrons. We also propose strategies to cope with these factors: (a) the divergence and direction tilt components of electron-beam tilt could be reduced by maintaining parallel illumination and by using a coma-free alignment procedure, respectively. Moreover, the effect of all beam tilt components, including spiral tilt, could be eliminated by use of a spherical aberration corrector. (b) More accurate measurement of defocus value could be obtained by imaging areas adjacent to the target area at high electron dose and by measuring the image shift induced by tilting the electron beam. (c) Each known Fourier coefficient in the Fourier transform of a cryoEM image is the sum of two Fourier coefficients of the 3D structure, one on each of two curved ‘characteristic surfaces’ in 3D Fourier space. We describe a simple model-based iterative method that could recover these two Fourier coefficients on the two characteristic surfaces. (d) The effect of dynamic scattering could be corrected by deconvolution of a transfer function. These analyses and our proposed strategies offer useful guidance for future experimental designs targeting atomic resolution cryoEM reconstruction. PMID:21627992

Utility of RAPD marker for genetic diversity analysis in gamma rays and ethyl methane sulphonate (EMS)-treated Jatropha curcas plants.

PubMed

Dhakshanamoorthy, Dharman; Selvaraj, Radhakrishnan; Chidambaram, Alagappan

2015-02-01

The presence of important chemical and physical properties in Jatropha curcas makes it a valuable raw material for numerous industrial applications, including the production of biofuel. Hence, the researcher's interest is diversified to develop more and better varieties with outstanding agronomic characteristics using conventional breeding. Among these, mutation breeding is one of the best approaches to bring genetic changes in plant species. The aim of this study is to evaluate the diversity and genetic relationship among J. curcas mutants, which were obtained from different doses of gamma rays (control, 5 Kr, 10 Kr, 15 Kr, 20 Kr and 25 Kr) and EMS (1%, 2%, 3% and 4%), using RAPD marker. Among the 21 random primers, 20 produced polymorphic bands. The primers, OPM-14 and OPAW-13, produced a minimum number of bands (3) each across the ten mutants, while the primer OPF-13 produced the maximum number of bands (10), followed by the primers OPU-13, OPAM-06, OPAW-09 and OPD-05, which produced 9 bands each. The number of amplicons varied from 3 to 10, with an average of 7 bands, out of which 4.57 were polymorphic. The percentage of polymorphism ranged from 0.00 to 100 with an average of 57%. In the present study, RAPD markers were found most polymorphic, with an average polymorphism information content (PIC) value of 0.347, effective multiplex ratio (EMR) of 35.14, marker index (MI) of 14.19, resolution power (Rp) of 11.19, effective marker index (EMI) of 8.21 and genotype index (GI) of 0.36, indicating that random primers are useful in studies of genetic characterization in J. curcas mutant plants. In a dendrogram constructed based on Jaccard's similarity coefficients, the mutants were grouped into three main clusters viz., (a) control, 10 Kr, 15 Kr, 20 Kr, 2% EMS, and 3% EMS, (b) 5 Kr and 1% EMS, and (c) 25 Kr and 4% EMS mutants. Based on the attributes of the random primers and polymorphism studied, it is concluded that RAPD analysis offers a useful molecular marker for the identification of the mutants in gamma rays and EMS treated plants. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Treatment of Plaque-Type Psoriasis With Oral CF101: Data from a Phase II/III Multicenter, Randomized, Controlled Trial.

PubMed

David, Michael; Gospodinov, Dimitar Konstantinov; Gheorghe, Nicola; Mateev, Grisha Stefanov; Rusinova, Mariyana Venelinova; Hristakieva, Evgeniya; Solovastru, Laura Gheuca; Patel, Rita V; Giurcaneanu, Calin; Hitova, Mariela Chepileva; Purcaru, Anca Ioana; Horia, Beti; Tsingov, Iliya Iliev; Yankova, Rumyana Kaloferova; Kadurina, Miroslava Ilieva; Ramon, Michal; Rotaru, Maria; Simionescu, Olga; Benea, Vasile; Demerdjieva, Zdravka Velichkova; Cosgarea, Maria Rodica; Morariu, Horia Silviu; Michael, Ziv; Cristodor, Patricia; Nica, Carmen; Silverman, Michael H; Bristol, David R; Harpaz, Zivit; Farbstein, Motti; Cohen, Shira; Fishman, Pnina

2016-08-01

CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.

J Drugs Dermatol. 2016;15(8):931-938.

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Anti-genotoxicity of trans-anethole and eugenol in mice.

PubMed

Abraham, S K

2001-05-01

The naturally occurring flavouring agents trans-anethole and eugenol were evaluated for antigenotoxic effects in mice. The test doses of trans-anethole (40-400 mg/kg body weight) and eugenol (50-500 mg/kg weight) were administered by gavage 2 and 20 h before the genotoxins were injected intraperitoneally. Anti-genotoxic effects were assessed in the mouse bone marrow micronucleus test. Pretreatment with trans-anethole and eugenol led to significant antigenotoxic effects against cyclophosphamide (CPH), procarbazine (PCB), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and urethane (URE). In addition, trans-anethole inhibited the genotoxicity of ethyl methane sulfonate (EMS). Both trans-anethole and eugenol exerted dose-related antigenotoxic effects against PCB and URE. There was no significant increase in genotoxicity when trans-anethole (40-400 mg/kg body weight) and eugenol (50-500 mg/kg body weight) were administered alone.

Exposure setup to study potential adverse effects at GSM 1800 and UMTS frequencies on the auditory systems of rats.

PubMed

Lopresto, V; Pinto, R; De Vita, A; Mancini, S; Galloni, P; Marino, C; Ravazzani, P; Lovisolo, G A

2007-01-01

To investigate possible biological effects of exposure to electromagnetic (EM) fields at the frequencies of global system for mobile communication (GSM) 1800 system and universal mobile telecommunication system (UMTS) on the auditory system of rats, an exposure setup for in vivo experiments is presented. The study was carried out in the framework of two European research projects. The target of the investigation was the cochlea. A dosimetric study was performed, both numerically and through direct measurements, to assess the interaction of the radiated fields and the dose distribution in the biological target. For the local exposure of rats, a loop antenna operating at the frequency bands of interest was designed, realised and characterised through numerical and experimental dosimetric procedures. Moreover, an exposure apparatus was set up, consisting of three arrays of four loop antennas, placed on three levels, thus allowing simultaneous exposure of 12 rats to give statistical power to the experiments. To isolate the exposure arrays, the setup was assembled by a wooden rack with EM field absorbing panels, inserted among the levels and at the four sides of the rack. Isolation was verified by direct measurements. Two exposure arrays were simultaneously supplied, whereas the third one was used for sham exposure. Blind exposure was achieved through a black box, hiding physical connections to the microwave power supply. During exposure sessions, rats were restrained in special plastic jigs for repeatable positioning, thus assuring the fixed level of dose in the target.

Irradiated KHYG-1 retains cytotoxicity: potential for adoptive immunotherapy with a natural killer cell line.

PubMed

Suck, G; Branch, D R; Keating, A

2006-05-01

To evaluate gamma-irradiation on KHYG-1, a highly cytotoxic natural killer (NK) cell line and potential candidate for cancer immunotherapy. The NK cell line KHYG-1 was irradiated at 1 gray (Gy) to 50 Gy with gamma-irradiation, and evaluated for cell proliferation, cell survival, and cytotoxicity against tumor targets. We showed that a dose of at least 10 Gy was sufficient to inhibit proliferation of KHYG-1 within the first day but not its cytolytic activity. While 50 Gy had an apoptotic effect in the first hours after irradiation, the killing of K562 and HL60 targets was not different from non-irradiated cells but was reduced for the Ph + myeloid leukemia lines, EM-2 and EM-3. gamma-irradiation (at least 10 Gy) of KHYG-1 inhibits cell proliferation but does not diminish its enhanced cytolytic activity against several tumor targets. This study suggests that KHYG-1 may be a feasible immunotherapeutic agent in the treatment of cancers.

Evolution of the ablation region after magnetic resonance-guided high-intensity focused ultrasound ablation in a Vx2 tumor model.

PubMed

Wijlemans, Joost W; Deckers, Roel; van den Bosch, Maurice A A J; Seinstra, Beatrijs A; van Stralen, Marijn; van Diest, Paul J; Moonen, Chrit T W; Bartels, Lambertus W

2013-06-01

Volumetric magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) is a completely noninvasive image-guided thermal ablation technique. Recently, there has been growing interest in the use of MR-HIFU for noninvasive ablation of malignant tumors. Of particular interest for noninvasive ablation of malignant tumors is reliable treatment monitoring and evaluation of response. At this point, there is limited evidence on the evolution of the ablation region after MR-HIFU treatment. The purpose of the present study was to comprehensively characterize the evolution of the ablation region after volumetric MR-HIFU ablation in a Vx2 tumor model using MR imaging, MR temperature data, and histological data. Vx2 tumors in the hind limb muscle of New Zealand White rabbits (n = 30) were ablated using a clinical MR-HIFU system. Twenty-four animals were available for analyses. Magnetic resonance imaging was performed before and immediately after ablation; MR temperature mapping was performed during the ablation. The animals were distributed over 7 groups with different follow-up lengths. Depending on the group, animals were reimaged and then killed on day 0, 1, 3, 7, 14, 21, or 28 after ablation. For all time points, the size of nonperfused areas (NPAs) on contrast-enhanced T1-weighted (CE-T1-w) images was compared with lethal thermal dose areas (ie, the tissue area that received a thermal dose of 240 equivalent minutes or greater [EM] at 43°C) and with the necrotic tissue areas on histology sections. The NPA on CE-T1-w imaging showed an increase in median size from 266 ± 148 to 392 ± 178 mm(2) during the first day and to 343 ± 170 mm(2) on day 3, followed by a gradual decrease to 113 ± 103 mm(2) on day 28. Immediately after ablation, the NPA was 1.6 ± 1.4 times larger than the area that received a thermal dose of 240 EM or greater in all animals. The median size of the necrotic area on histology was 1.7 ± 0.4 times larger than the NPA immediately after ablation. After 7 days, the size of the NPA was in agreement with the necrotic tissue area on histology (ratio, 1.0 ± 0.2). During the first 3 days after MR-HIFU ablation, the ablation region increases in size, after which it gradually decreases in size. The NPA on CE-T1-w imaging underestimates the extent of tissue necrosis on histology in the initial few days, but after 1 week, the NPA is reliable in delineating the necrotic tissue area. The 240-EM thermal dose limit underestimates the necrotic tissue area immediately after MR-HIFU ablation. Reliable treatment evaluation techniques are particularly important for noninvasive, image-guided tumor ablation. Our results indicate that CE-T1-w imaging is reliable for MR-HIFU treatment evaluation after 1 week.

COST-EFFECTIVENESS OF PERIOPERATIVE IMMUNONUTRITION IN GASTROINTESTINAL ONCOLOGIC SURGERY: A SYSTEMATIC REVIEW.

PubMed

Reis, Audrey Machado Dos; Kabke, Geórgia Brum; Fruchtenicht, Ana Valéria Gonçalves; Barreiro, Taiane Dias; Moreira, Luis Fernando

2016-01-01

Costs, length of hospital staying and morbidity are frequently and significantly increased as a result of infections and other complications following surgical procedure for gastrointestinal tract cancer. Recently, improving host defence mechanisms have become a target of interest. Immunonutrition aims at improving immunity, most likely providing key nutrients to maintain T-lymphocyte and other host defence. To evaluate the immunonutrition in cancer patients who are operated by digestive diseases and assess the cost-effectiveness of this supplementation. This study consisted of a systematic review of the literature based on reference analyses retrieved from current databases such as PubMed, Lilacs and SciELO. The search strategy was defined by terms related to immunonutrition [immunonutrition, arginine, omega-3 and nucleotides] in combination with [costs, cost-effective and cost-effectiveness] as well as [gastrointestinal cancer surgery, oesophageal, gastric or pancreatic surgery] in English, Portuguese or Spanish language. For cost analyses, currencies used in the manuscripts were all converted to American dollars (US$) in order to uniform and facilitate comparison. Six prospective randomized studies were included in this review. The cost-effectiveness was positive in most of studies, demonstrating that this diet can significantly reduce hospital costs in the North hemisphere. However, similar studies needed to be carried to determine such results among us. Custos, tempo de hospitalização e morbidade estão frequentemente aumentados na presença de infecções e outras complicações decorrentes de procedimentos cirúrgicos para o câncer gastrointestinal. Recentemente, a melhora de mecanismos de defesa do hospedeiro tem se tornado um alvo de interesse. Nutrição adequada está fortemente relacionada com competência imune e redução de infeções. Imunonutrição objetiva a melhora da imunidade, principalmente para manutenção de linfócitos-T e outras defesas. Avaliar a imunonutrição em pacientes oncológicos que são operados por doenças do aparelho digestivo e avaliar a relação custo-eficácia desta suplementação. Revisão sistemática da literatura baseada nas bases de dados PubMed, Lilacs e SciELO. A busca foi realizada com combinação de descritores em inglês e português relacionados ao tema da revisão: [immunonutrition, arginine, omega-3, nucleotides] combinado com [costs, cost-effective, cost-effectiveness] e [gastrointestinal cancer surgery, oesophageal, gastric or pancreatic surgery]. Para análise de custos, moedas usadas nos artigos foram todas convertidas para dólar americano. Seis estudos randomizados prospectivos foram incluídos nesta revisão. O custo-benefício foi positivo na maioria dos estudos, sugerindo que este tipo de dieta reduz significativamente os custos hospitalares nos países do hemisfério norte. Contudo, estudos similares de custo-benefício devem ser realizados para definir o real custo-benefício em nosso meio.

Dose-Dependent Associations between Wine Drinking and Breast Cancer Risk - Meta-Analysis Findings.

PubMed

Chen, Jia-Yan; Zhu, Hong-Cheng; Guo, Qing; Shu, Zheng; Bao, Xu-Hui; Sun, Feng; Qin, Qin; Yang, Xi; Zhang, Chi; Cheng, Hong-Yan; Sun, Xin-Chen

2016-01-01

To investigate any potential association between wine and breast cancer risk. We quantitatively assessed associations by conducting a meta-analysis based on evidence from observational studies. In May 2014, we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify studies examining the effect of wine drinking on breast cancer incidence. The relative risk (RR) or odds ratio (OR) were used to measure any such association. The analysis was further stratified by confounding factors that could influence the results. A total of twenty-six studies (eight case-control and eighteen cohort studies) involving 21,149 cases were included in our meta-analysis. Our study demonstrated that wine drinking was associated with breast cancer risk. A 36% increase in breast cancer risk was observed across overall studies based on the highest versus lowest model, with a combined RR of 1.0059 (95%CI 0.97-1.05) in dose-response analysis. However, 5 g/d ethanol from wine seemed to have protective value from our non-linear model. Our findings indicate that wine drinking is associated with breast cancer risk in a dose-dependent manner. High consumption of wine contributes to breast cancer risk with protection exerted by low doses. Further investigations are needed for clarification.

Development of imidazolinone herbicide tolerant borage (Borago officinalis L.).

PubMed

Song, Dongyan; Wu, Guohai; Vrinten, Patricia; Qiu, Xiao

2017-09-01

Borage (Borago officinalis) is an annual herb that produces a high level of gamma-linolenic acid (GLA) in its seed oil. Due to the recognized health benefits of GLA, borage is now commercially cultivated worldwide. However, an herbicide-tolerant variety for effective weed management has not yet been developed. Here we report the generation and characterization of ethyl methanesulfonate (EMS) induced borage mutant lines tolerant to the herbicide imidazolinone. An EMS-mutagenized borage population was generated by using a series of concentrations of EMS to treat mature borage seeds. Screening of the M2 and M3 borage plants using an herbicide treatment resulted in the identification of two imidazolinone-tolerant lines. Sequence analysis of two acetohydroxyacid synthase (AHAS) genes, AHAS1 and AHAS2, from the mutant (tolerant) and wild type (susceptible) borage plants showed that single nucleotide substitutions which resulted in amino acid changes occurred in AHAS1 and AHAS2, respectively in the two tolerant lines. A KASP marker was then developed to differentiate the homozygous susceptible, homozygous tolerant and heterozygous borage plants. An in vitro assay showed that homozygous tolerant borage carrying the AHAS1 mutation retained significantly higher AHAS activity than susceptible borage across different imazamox concentrations. A herbicide dose response test indicated that the line with the AHAS1 mutation could tolerate four times the normally used field concentration of "Solo" herbicide. Copyright © 2017. Published by Elsevier B.V.

Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes.

PubMed

Nagashima, Zenko; Tsukahara, Kengo; Morita, Satoshi; Endo, Tsutomu; Sugano, Teruyasu; Hibi, Kiyoshi; Himeno, Hideo; Fukui, Kazuki; Umemura, Satoshi; Kimura, Kazuo

2013-09-01

It remains unknown whether the time course of the antiplatelet effects of clopidogrel differs according to cytochrome P450 (CYP) 2C19 phenotype in Japanese patients with acute coronary syndromes (ACS). Platelet reactivity was serially assessed by VerifyNow-P2Y12 assay (Accumetrics, San Diego, CA, USA). Results were expressed as P2Y12-reaction-units (PRU) in 177 patients with ACS who underwent stent implantation and received aspirin plus a 300-mg loading dose of clopidogrel followed by 75 mg/day. High on-clopidogrel treatment platelet reactivity (HTPR) was defined as PRU>235. On the basis of the CYP2C19*2 and *3 alleles, 46 patients (26.0%) were classified as extensive metabolizers (EM), 103 (58.2%) as intermediate metabolizers (IM), and 28 (15.8%) as poor metabolizers (PM). At <7 days, the PRU level (232±102 vs. 279±70, 308±67, p<0.001) and the incidence of HTPR (49% vs. 74%, 86%, p=0.001) was lower in EM than in IM and PM. At 14-28 days the effects of CYP2C19 polymorphisms on PRU levels increased in a stepwise fashion (168±99 vs. 213±77 vs. 278±69, p<0.001), and EM and IM had lower percentages of HTPR than PM (28%, 37% vs. 73%, p<0.001). There was no significant difference in the cumulative frequency of 12-month adverse cardiovascular events among 3 phenotypes (16.5%, 14.1%, 9.2%; p=0.67). About three quarters of Japanese patients with ACS carried CYP2C19 variant alleles. The majority of IM and PM had increased platelet reactivity during the early phase of ACS. Although HTPR was frequently observed even 14-28 days after standard maintenance doses of clopidogrel in PM, the incidence of adverse outcomes did not differ, irrespective of CYP2C19 genotype. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

CORRELATION BETWEEN PRE AND POSTOPERATIVE LEVELS OF GLP-1/GLP-2 AND WEIGHT LOSS AFTER ROUX-EN-Y GASTRIC BYPASS: A PROSPECTIVE STUDY.

PubMed

Cazzo, Everton; Gestic, Martinho Antonio; Utrini, Murillo Pimentel; Pareja, José Carlos; Chaim, Elinton Adami; Geloneze, Bruno; Barreto, Maria Rita Lazzarini; Magro, Daniéla Oliveira

2016-01-01

The role of gut hormones in glucose homeostasis and weight loss achievement and maintenance after bariatric surgery appears to be a key point in the understanding of the beneficial effects observed following these procedures. To determine whether there is a correlation between the pre and postoperative levels of both GLP-1 and GLP-2 and the excess weight loss after Roux-en-Y gastric bypass (RYGB). An exploratory prospective study which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 after standard meal tolerance test (MTT) were determined before and after surgery and then correlated with the percentage of excess loss (%EWL). GLP-2 AUC presented a significant postoperative increase (945.3±449.1 vs.1787.9±602.7; p=0.0037); GLP-1 AUC presented a non-significant trend towards increase after RYGB (709.6±320.4 vs. 1026.5±714.3; p=0.3808). Mean %EWL was 66.7±12.2%. There was not any significant correlation between both the pre and postoperative GLP-1 AUCs and GLP-2 AUCs and the %EWL achieved after one year. There was no significant correlation between the pre and postoperative levels of the areas under the GLP-1 and GLP-2 curves with the percentage of weight loss reached after one year. O papel de hormônios gastrointestinais sobre a homeostase glicêmica e a obtenção e manutenção da perda de peso após a cirurgia bariátrica parece ser elemento fundamental na compreensão dos benefícios observados após estes procedimentos. Determinar se há correlação entre os níveis pré e pós-operatórios de GLP-1 e GLP-2 com a perda do excesso de peso após o bypass gástrico em Y-de-Roux. Estudo prospectivo exploratório que envolveu 11 indivíduos submetidos ao bypass gástrico, acompanhados por 12 meses. Os níveis GLP-1 e GLP-2 após um teste de refeição padrão foram determinados antes e 12 meses após a operação e então foram correlacionados com o percentual de perda do excesso de peso. Houve aumento significativo da área sob a curva do GLP-2 após a operação (945,3±449,1 vs. 1787,9±602,7; p=0,0037); a área sob a curva do GLP-1 apresentou tendência não-significativa à elevação após o procedimento (709,6±320,4 vs. 1026,5±714,3; p=0,3808). O percentual médio de perda de peso foi 66,7±12,2%. Não houve nenhuma correlação significativa entre os níveis pré e pós-operatórios das áreas sob as curvas de GLP-1 e GLP-2 com o percentual de perda de peso atingido após um ano.

Estimated costs of advanced lung cancer care in a public reference hospital.

PubMed

Knust, Renata Erthal; Portela, Margareth Crisóstomo; Pereira, Claudia Cristina de Aguiar; Fortes, Guilherme Bastos

2017-08-17

To estimate the direct medical costs of advanced non-small cell lung cancer care. We assessed a cohort of 277 patients treated in the Brazilian National Cancer Institute in 2011. The costs were estimated from the perspective of the hospital as a service provider of reference for the Brazilian Unified Health System. The materials and procedures used were identified and quantified, per patient, and we assigned to them monetary values, consolidated in phases of the assistance defined. The analyses had a descriptive character with costs in Real (R$). Overall, the cohort represented a cost of R$2,473,559.91, being 71.5% related to outpatient care and 28.5% to hospitalizations. In the outpatient care, costs with radiotherapy (34%) and chemotherapy (22%) predominated. The results pointed to lower costs in the initial phase of treatment (7.2%) and very high costs in the maintenance phase (61.6%). Finally, we identified statistically significant differences of average cost by age groups, education levels, physical performance, and histological type. This study provides a current, useful, and relevant picture of the costs of patients with non-small cell lung cancer treated in a public hospital of reference and it provides information on the magnitude of the problem of cancer in the context of public health. The results confirm the importance of radiation treatment and hospitalizations as the main components of the cost of treatment. Despite some losses of follow-up, we assess that, for approximately 80% of the patients included in the study, the estimates presented herein are satisfactory for the care of the disease, from the perspective of a service provider of reference of the Brazilian Unified Health System, as it provides elements for the management of the service, as well as for studies that result in more rational forms of resource allocation. Estimar os custos médicos diretos da assistência ao câncer de pulmão não pequenas células avançado. Foi avaliada uma coorte de 277 pacientes matriculados no Instituto Nacional do Câncer em 2011. Os custos foram estimados sob a perspectiva do hospital como prestador de serviços de referência para o SUS. Insumos e procedimentos utilizados foram identificados e quantificados, por paciente, sendo a eles atribuídos valores monetários, consolidados por fases da assistência definidas. As análises tiveram caráter descritivo com custos em reais (R$). Em termos globais, a coorte representou um custo de R$2.473.559,91, sendo 71,5% relacionados à atenção ambulatorial e 28,5% as internações. Na atenção ambulatorial, predominaram os custos com radioterapia (34%) e quimioterapia (22%). Os resultados apontaram para custos menores na fase inicial de tratamento (7,2%) e custos muito elevados na fase de manutenção (61,6%). Por fim, identificaram-se diferenças estatisticamente significativas das médias dos custos por faixas etárias, níveis de escolaridade, desempenho físico e tipo histológico. Este estudo fornece um retrato atual, útil e relevante sobre os custos de pacientes com câncer de pulmão não pequenas células assistidos em um hospital público de referência e provê elementos sobre a magnitude do problema do câncer no âmbito da saúde pública. Os resultados ratificam a importância do tratamento radioterápico e das internações como principais componentes de custo do tratamento. Apesar de algumas perdas de seguimento avalia-se que, para cerca de 80% dos pacientes incluídos no estudo, as estimativas aqui apresentadas sejam satisfatoriamente fidedignas ao cuidado da doença, sob a perspectiva de um prestador de referência do SUS, fornecendo elementos para a gestão do serviço, bem como para estudos que redundem em formas mais racionais de alocação de recursos.

ANALYSIS OF BIOMECHANICAL PARAMETERS IN COLONIC ANASTOMOSIS.

PubMed

Iwanaga, Tiago Cavalcanti; Aguiar, José Lamartine de Andrade; Martins-Filho, Euclides Dias; Kreimer, Flávio; Silva-Filho, Fernando Luiz; Albuquerque, Amanda Vasconcelos de

2016-01-01

The use of measures in colonic anastomoses to prevent dehiscences is of great medical interest. Sugarcane molasses, which has adequate tolerability and compatibility in vivo, has not yet been tested for this purpose. To analyze the biomechanical parameters of colonic suture in rats undergoing colectomy, using sugarcane molasses polysaccharide as tape or gel. 45 Wistar rats (Rattus norvegicus albinus) were randomized into three groups of 15 animals: irrigation of enteric sutures with 0.9% saline solution; application of sugarcane molasses polysaccharide as tape; and sugarcane molasses polysaccharide as gel. The rats underwent colon ressection, with subsequent reanastomosis using polypropylene suture; they were treated according to their respective groups. Five rats from each group were evaluated at different times after the procedure: 30, 90 and 180 days postoperatively. The following variables were evaluated: maximum rupture force, modulus of elasticity and specific deformation of maximum force. The biomechanical variables among the scheduled times and treatment groups were statistically calculated. The characteristics of maximum rupture force and modulus of elasticity of the specimens remained identical, regardless of treatment with saline, polysaccharide gel or tape, and treatment time. However, it was found that the specific deformation of maximum force of the intestinal wall was higher after 180 days in the group treated with sugarcane polysaccharide gel (p=0.09). Compared to control, it was detected greater elasticity of the intestinal wall in mice treated with sugarcane polysaccharide gel, without changing other biomechanical characteristics, regardless of type or time of treatment. A aplicação de produtos em anastomoses colônicas que possam prevenir o surgimento de deiscências são de grande interesse médico. O emprego do polissacarídeo de melaço de cana-de-açúcar (Saccharum officinarum), que possui adequada tolerabilidade e compatibilidade in vivo, ainda não foi testado para este fim. Analisar os parâmetros biomecânicos em suturas colônicas de ratos submetidos à colectomia esquerda após aplicação de fita ou gel do polissacarídeo do melaço da cana-de-açúcar no sítio cirúrgico. Quarenta e cinco ratos (Rattus norvegicus albinus da linhagem Wistar) foram sorteados em três grupos de 15 submetidos a: irrigação das suturas entéricas com soro fisiológico a 0,9%; aplicação de fita de polissacarídeo do melaço da cana-de-açúcar; e aplicação do gel do mesmo melaço. Os ratos foram submetidos à colectomia esquerda com anastomose primária, e tratados segundo os respectivos grupos. Cinco ratos de cada grupo foram avaliados em diferentes tempos após o procedimento: 30º, 90º e 180º dias de pós-operatório. Foram avaliadas as variáveis de força máxima de ruptura, módulo de elasticidade e deformação específica da força máxima. As variáveis biomecânicas entre os tempos de coleta da pesquisa e os grupos de tratamento foram analisados estatisticamente. As características biomecânicas de força máxima de ruptura e o módulo de elasticidade do corpo de prova permaneceram idênticas, independente do tratamento com soro, fita ou gel de polissacarídeo, e do tempo de tratamento. No entanto, foi evidenciada maior deformação específica da força máxima da parede intestinal, aos 180 dias nos ratos tratados com gel de polissacarídeo de cana-de-açúcar. (p=0,09). Em relação ao controle, foi detectada maior elasticidade da parede intestinal nos ratos tratados com gel de polissacarídeo de cana-de-açúcar, sem alteração de outras características biomecânicas, independente do tipo ou tempo de tratamento.

Impact of using a local protocol in preoperative testing: blind randomized clinical trial.

PubMed

Santos, Mônica Loureiro; Iglesias, Antônio Carlos

2017-01-01

to evaluate the impact of the use of a local protocol of preoperative test requests in reducing the number of exams requested and in the occurrence of changes in surgical anesthetic management and perioperative complications. we conducted a randomized, blinded clinical trial at the Gaffrée and Guinle University Hospital with 405 patients candidates for elective surgery randomly divided into two groups, according to the practice of requesting preoperative exams: a group with non-selectively requested exams and a protocol group with exams requested according to the study protocol. Studied exams: complete blood count, coagulogram, glycemia, electrolytes, urea and creatinine, ECG and chest X-ray. Primary outcomes: changes in surgical anesthetic management caused by abnormal exams, reduction of the number of exams requested after the use of the protocol and perioperative complications. there was a significant difference (p<0.001) in the number of exams with altered results between the two groups (14.9% vs. 29.1%) and a reduction of 57.3% in the number of exams requested between the two groups (p<0.001), which was more pronounced in patients of lower age groups, ASA I, without associated diseases and submitted to smaller procedures. There was no significant difference in the frequency of conduct changes motivated by the results of exams or complications between the two groups. In the multivariate analysis, complete blood count and coagulogram were the only exams capable of modifying the anesthetic-surgical management. the proposed protocol was effective in eliminating a significant number of complementary exams without clinical indication, without an increase in perioperative morbidity and mortality. avaliar o impacto do uso de um protocolo local de solicitações de exames pré-operatórios na redução do número de exames solicitados e na ocorrência de alterações na conduta anestésico-cirúrgica e de complicações perioperatórias. ensaio clínico randomizado, cego, realizado no Hospital Universitário Gaffrée e Guinle com 405 pacientes candidatos à operação eletiva divididos randomicamente em dois grupos segundo a prática de solicitação de exames pré-operatórios: grupo Rotina com exames solicitados de maneira não seletiva e grupo Protocolo com exames solicitados de acordo com o protocolo em estudo. Exames em estudo: hemograma, coagulograma, glicemia, eletrólitos, ureia e creatinina, ECG e radiografia de tórax. Desfechos primários: alterações na conduta anestésico-cirúrgica motivadas por exames anormais, redução do número de exames solicitados após o uso do protocolo e complicações perioperatórias. foi observada diferença significativa (p<0,001) no número de exames com resultados alterados entre os dois grupos (14,9% x 29,1%) e redução de 57,3% no número de exames pedidos entre os dois grupos (p<0,001), mais acentuada nos pacientes de menor faixa etária, ASA I, sem doenças associadas e submetidos a procedimentos de menor porte. Não houve diferença significativa na frequência de alterações de conduta motivada por resultado de exames, nem de complicações entre os dois grupos. Na análise multivariada hemograma e coagulograma foram os únicos exames capazes de modificar a conduta anestésico-cirúrgica. o protocolo proposto foi efetivo em eliminar um quantitativo significativo de exames complementares sem indicação clínica, sem que houvesse aumento na morbidade e mortalidades perioperatórias.

Impact assessment of leaf pigments in selected landscape plants exposed to roadside dust.

PubMed

Shah, Kamran; Amin, Noor Ul; Ahmad, Imran; Ara, Gulshan

2018-06-02

Continuous addition of undesired effluents to the environment affects foliar surface of leaf, changes their morphology, stomata, photosynthetic pigments, and biochemical constituents which result in massive damage due to persistent nature of the pollutant. In persistent hostile environment, plants fail to grow and develop, and the effects are often extensive. In current study, landscape plants were exposed to different levels of road dust to analyze the effect on various photosynthetic pigments. Dry roadside sediments were collected through a vacuum pump and passed through filters to get fine particles less than 100 μm and sprinkled on Euphorbia milii (EM), Gardenia jasminoides (GJ), and Hibiscus rosa-sinensis (HRs) by using a hand pump, twice daily at T 1 (control), T 2 , T 3 , and T 4 (0, 2, 4, and 6 g/plant, respectively) for a period of 3 months in green house. Road sediment significantly reduces leaf pigments in landscape plants population and the effects were more severe in high level of dust deposition. Individual response of EM, GJ, and HRs to different levels of road dust was variable; however, road sediment significantly reduces leaf pigments at high dose of roadside dust deposition. EM plants exposed to 2 g/plant roadside dust showed higher chlorophyll-a, chlorophyll-b, total chlorophyll, chlorophyllide-b, and polar carotenoid contents as compared to GJ and HRs. Leaf chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, and polar carotenoid contents of EM were higher than GJ and HRs in T 3 and T 4 treatments. However HRs showed significantly higher protochlorophyllide, chlorophyllide-a, and pheophytin-b contents of leaf in T 4 group. EM was found as tolerant landscape plant followed by HRs. GJ was most vulnerable to road dust stress. Present study concludes that the entire biosynthesis of leaf pigments is in chain and interlinked together where effect of road dust on one pigment influences other pigments and their derivatives. Salient features of the present study provide useful evidence to estimate roadside dust as a major risk factor for plant pigments, and plants in green belt along roadside suffer retarded growth and fail to establish and develop.

CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification.

PubMed

Schroth, Werner; Hamann, Ute; Fasching, Peter A; Dauser, Silke; Winter, Stefan; Eichelbaum, Michel; Schwab, Matthias; Brauch, Hiltrud

2010-09-01

This study aimed to validate matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and to investigate the influence of CYP2D6 variant coverage on genotype-phenotype relationships and tamoxifen outcome. Hormone receptor-positive postmenopausal breast cancer patients (n = 492) treated with adjuvant tamoxifen, previously analyzed by MALDI-TOF MS/CNA, were reanalyzed by AmpliChip CYP450 Test and validated by independent methods. Cox proportional hazard ratios (HR) were calculated for recurrence of poor (PM) relative to extensive metabolizer (EM) phenotypes with increasing numbers of CYP2D6 variants. Kaplan-Meier distributions were calculated for different phenotype classifications. Concordance was 99.2% to 99.5% for CNA and 99.8% to 100% per CYP2D6 allele (*3, *4, *5, *9, *10, and *41). The prevalence of predicted phenotypes was 1.2% for ultrarapid metabolizer (UM), 37.2% for EM without variant, 43.5% for heterozygous EM, 9.7% for intermediate metabolizer (IM), and 8.3% for PM. Approximately, one third of patients were misclassified based on a *4 analysis only, but inclusion of all reduced-function alleles increased the PM-associated HR from 1.33 (P = 0.58) to 2.87 (P = 0.006). Kaplan-Meier analyses showed highest and lowest clinical benefit for UM and PM with respect to both the AmpliChip-based and a redefined phenotype assignment. The latter revealed significant allele-dose-dependent associations (P = 0.011) and largest effect size (HR(PM_EM) = 2.77; 95% confidence interval, 1.31-5.89). MALDI-TOF MS/CNA is suitable for accurate CYP2D6 genotyping. For tamoxifen pharmacogenetics, broad CYP2D6 allele coverage is recommended to reduce phenotype misclassification. Classification based on refined EM and reduced-function metabolizers is advisable. AACR.

Seeing tobacco mosaic virus through direct electron detectors

PubMed Central

Fromm, Simon A.; Bharat, Tanmay A.M.; Jakobi, Arjen J.; Hagen, Wim J.H.; Sachse, Carsten

2015-01-01

With the introduction of direct electron detectors (DED) to the field of electron cryo-microscopy, a wave of atomic-resolution structures has become available. As the new detectors still require comparative characterization, we have used tobacco mosaic virus (TMV) as a test specimen to study the quality of 3D image reconstructions from data recorded on the two direct electron detector cameras, K2 Summit and Falcon II. Using DED movie frames, we explored related image-processing aspects and compared the performance of micrograph-based and segment-based motion correction approaches. In addition, we investigated the effect of dose deposition on the atomic-resolution structure of TMV and show that radiation damage affects negative carboxyl chains first in a side-chain specific manner. Finally, using 450,000 asymmetric units and limiting the effects of radiation damage, we determined a high-resolution cryo-EM map at 3.35 Å resolution. Here, we provide a comparative case study of highly ordered TMV recorded on different direct electron detectors to establish recording and processing conditions that enable structure determination up to 3.2 Å in resolution using cryo-EM. PMID:25528571

Climate Prediction Center - Stratosphere: Stratosphere-Troposphere

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The influence of dosing on effect size of exercise therapy for musculoskeletal foot and ankle disorders: a systematic review.

PubMed

Young, Jodi L; Rhon, Daniel I; de Zoete, Rutger M J; Cleland, Joshua A; Snodgrass, Suzanne J

The purpose of this review was to identify doses of exercise therapy associated with greater treatment effect sizes in individuals with common musculoskeletal disorders of the foot and ankle, namely, achilles tendinopathy, ankle sprains and plantar heel pain. AMED, EMBASE and MEDLINE were searched from 2005 to August 2017 for randomized controlled trials related to exercise for these three diagnoses. The Physiotherapy Evidence Database scale was used for methodological quality assessment. Exercise dosing variables and outcome measures related to pain and function were extracted from the studies, and standardized mean differences were calculated for the exercise groups. Fourteen studies met the final inclusion. A majority of the studies showed large effects and two small trends were identified. Patients with plantar heel pain may benefit more from a daily home exercise program than two supervised visits per week (SMD=3.82), but this recommendation is based on weak evidence. In achilles tendinopathy, a relationship was also seen when sets and repetitions of eccentric exercise were performed as tolerated (SMD=1.08 for function, -1.29 for pain). Session duration, frequency, total number of visits, and overall length of care may all be dosing variables with limited value for determining effective exercise prescription. However, the limited number of studies prevents any definitive conclusions. Further investigation is warranted to improve our understanding of the influence exercise dosing has on treatment effect sizes. Future randomized controlled trials comparing specific exercise dose variables should be conducted to clarify the impact of these variables. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. All rights reserved.

Association between Obstructive Sleep Apnea and Myocardial Infarction: A Systematic Review.

PubMed

Porto, Fernanda; Sakamoto, Yuri Saho; Salles, Cristina

2017-04-01

Obstructive sleep apnea (OSA) has been associated to cardiovascular risk factors. However, the association between OSA and cardiovascular disease is still controversial. The objective of the present study was to verify the association between OSA and myocardial infarction (MI). This is a systematic review of the literature performed through electronic data sources MEDLINE/PubMed, PubMed Central, Web of Science and BVS -Biblioteca Virtual em Saúde (Virtual Health Library). The descriptors used were: 'obstructive sleep apnea' AND 'polysomnography' AND 'myocardial infarction' AND 'adults NOT 'treatment.' The present work analysed three prospective studies, selected from 142 articles. The studies followed a total sample of 5,067 OSA patients, mostly composed by male participants. All patients underwent night polysomnography, and all studies found an association between OSA and fatal and non-fatal cardiovascular outcomes. Thus, we were able to observe that 644 (12.7%) of the 5,067 patients suffered MI or stroke, or required a revascularization procedure, and 25.6% of these cardiovascular events were fatal. MI was responsible for 29.5% of all 644 analysed outcomes. There is an association between OSA and MI, in male patients, and apnea and hypopnea index (AHI) are the most reliable markers. Resumo A apneia obstrutiva do sono (AOS) tem sido associada a fatores de risco cardiovascular, porém a relação entre a AOS e doença cardiovascular ainda é controversa. O objetivo do presente estudo foi verificar a associação entre AOS e infarto do miocárdio (IM). Revisão sistemática de literatura por meio das fontes de dados eletrônicas MEDLINE/PubMed, PubMed Central, Web of Science e Biblioteca Virtual em Saúde (BVS). Os descritores utilizados foram: "obstructive sleep apnea" AND "polysomnography" AND "myocardial infarction" AND "adults" NOT "treatment".O presente trabalho analisou três estudos prospectivos, selecionados dentre 142 artigos encontrados. Os estudos acompanharam uma amostra total de 5.067 pacientes diagnosticados com AOS, composta majoritariamente por participantes do sexo masculino. Todos os pacientes realizaram polissonografia noturna, e todas as pesquisas encontraram associação entre AOS e desfechos cardiovasculares fatais e não fatais. Assim, foi possível observar que 644 (12,7%) dos 5.067 pacientes sofreram IM ou acidente vascular cerebral, ou precisaram de procedimento de revascularização, sendo que 25,6% desses eventos cardiovasculares foram fatais. O IM foi responsável por 29,5% do total de 644 desfechos analisados. Existe associação entre AOS e IM, no sexo masculino, sendo o índice de apneia e hipopneia (IAH) um dos marcadores mais fidedignos.

CFSv2 Seasonal Climate Forecasts

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Nino3.4 Nino4 E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) E1 (data) E2 (data) E3 (data) Sea surface height and

Conacyt

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Organismos de Inspección Organismos de Certificación de personas Calidad Acreditación ¿Que es la : Estructuración de la Evaluación de la Conformidad 1.2: Fortalecimiento y articulación de las instituciones Componente 2: Fortalecimiento del Sistema Nacional de Innovación 6: Incorporación de la Innovación en la

Mitogen-activated protein kinase signal transduction and DNA repair network are involved in aluminum-induced DNA damage and adaptive response in root cells of Allium cepa L.

PubMed Central

Panda, Brahma B.; Achary, V. Mohan M.

2014-01-01

In the current study, we studied the role of signal transduction in aluminum (Al3+)-induced DNA damage and adaptive response in root cells of Allium cepa L. The root cells in planta were treated with Al3+ (800 μM) for 3 h without or with 2 h pre-treatment of inhibitors of mitogen-activated protein kinase (MAPK), and protein phosphatase. Also, root cells in planta were conditioned with Al3+ (10 μM) for 2 h and then subjected to genotoxic challenge of ethyl methane sulfonate (EMS; 5 mM) for 3 h without or with the pre-treatment of the aforementioned inhibitors as well as the inhibitors of translation, transcription, DNA replication and repair. At the end of treatments, roots cells were assayed for cell death and/or DNA damage. The results revealed that Al3+ (800 μM)-induced significant DNA damage and cell death. On the other hand, conditioning with low dose of Al3+ induced adaptive response conferring protection of root cells from genotoxic stress caused by EMS-challenge. Pre-treatment of roots cells with the chosen inhibitors prior to Al3+-conditioning prevented or reduced the adaptive response to EMS genotoxicity. The results of this study suggested the involvement of MAPK and DNA repair network underlying Al-induced DNA damage and adaptive response to genotoxic stress in root cells of A. cepa. PMID:24926302

Berkeley Lab - Materials Sciences Division

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2018 [PDF] October 2017 [PDF] July 2017 [PDF] April 2017 [PDF] January 2017 [PDF] October 2016 [PDF ] July 2016 [PDF] April 2016 [PDF] January 2016 [PDF] October 2015 [PDF] March 2015 [PDF] December 2014 [PDF] April 2014 [PDF] February 2014 [PDF] September 2013 [PDF] March 2013 [PDF] October, 2012 [PDF

Anatomic pulmonary resection by video-assisted thoracoscopy: the Brazilian experience (VATS Brazil study).

PubMed

Terra, Ricardo Mingarini; Kazantzis, Thamara; Pinto-Filho, Darcy Ribeiro; Camargo, Spencer Marcantonio; Martins-Neto, Francisco; Guimarães, Anderson Nassar; Araújo, Carlos Alberto; Losso, Luis Carlos; Ghefter, Mario Claudio; Lima, Nuno Ferreira de; Gomes-Neto, Antero; Brito-Filho, Flávio; Haddad, Rui; Saueressig, Maurício Guidi; Lima, Alexandre Marcelo Rodrigues; Siqueira, Rafael Pontes de; Pinho, Astunaldo Júnior de Macedo E; Vannucci, Fernando

2016-01-01

The objective of this study was to describe the results of anatomic pulmonary resections performed by video-assisted thoracoscopy in Brazil. Thoracic surgeons (members of the Brazilian Society of Thoracic Surgery) were invited, via e-mail, to participate in the study. Eighteen surgeons participated in the project by providing us with retrospective databases containing information related to anatomic pulmonary resections performed by video-assisted thoracoscopy. Demographic, surgical, and postoperative data were collected with a standardized instrument, after which they were compiled and analyzed. The surgeons provided data related to a collective total of 786 patients (mean number of resections per surgeon, 43.6). However, 137 patients were excluded because some data were missing. Therefore, the study sample comprised 649 patients. The mean age of the patients was 61.7 years. Of the 649 patients, 295 (45.5%) were male. The majority-521 (89.8%)-had undergone surgery for neoplasia, which was most often classified as stage IA. The median duration of pleural drainage was 3 days, and the median hospital stay was 4 days. Of the 649 procedures evaluated, 598 (91.2%) were lobectomies. Conversion to thoracotomy was necessary in 30 cases (4.6%). Postoperative complications occurred in 124 patients (19.1%), the most common complications being pneumonia, prolonged air leaks, and atelectasis. The 30-day mortality rate was 2.0%, advanced age and diabetes being found to be predictors of mortality. Our analysis of this representative sample of patients undergoing pulmonary resection by video-assisted thoracoscopy in Brazil showed that the procedure is practicable and safe, as well as being comparable to those performed in other countries. O objetivo deste estudo foi descrever os resultados de ressecções pulmonares anatômicas por videotoracoscopia no Brasil. Cirurgiões torácicos (membros da Sociedade Brasileira de Cirurgia Torácica) foram convidados, por correio eletrônico, a participar do estudo. Dezoito cirurgiões participaram do projeto enviando seus bancos de dados retrospectivos referentes a ressecções anatômicas de pulmão por videotoracoscopia. Dados demográficos, cirúrgicos e pós-operatórios foram coletados em um instrumento padronizado e posteriormente compilados e analisados. Dados referentes a 786 pacientes foram encaminhados (média de 43,6 ressecções por cirurgião), sendo 137 excluídos por informações incompletas. Logo, 649 pacientes constituíram nossa população estudada. A média de idade dos pacientes foi de 61,7 anos, 295 eram homens (45,5%), e a maioria - 521 (89,8%) - foi submetida à cirurgia por neoplasia, mais frequentemente classificada como estádio IA. A mediana do tempo de drenagem pleural foi de 3 dias, e a do tempo de internação, 4 dias. Dos 649 procedimentos realizados, 598 (91,2%) foram lobectomias. A taxa de conversão para toracotomia foi de 4,6% (30 casos). Complicações pós-operatórias ocorreram em 124 pacientes (19,1%), sendo pneumonia, escape aéreo prolongado e atelectasia as mais frequentes. A mortalidade em 30 dias foi de 2,0%, tendo como preditores idade avançada e diabetes. A casuística brasileira mostra que as ressecções pulmonares por cirurgia torácica videoassistida são factíveis e seguras, além de comparáveis àquelas de registros internacionais.

Reviving Erathostenes. (Breton Title: Revivendo Eratóstenes.) Reviviendo a Eratóstenes.

NASA Astrophysics Data System (ADS)

Pereira, Paulo Cesar R.

2006-12-01

As part of the commemorations of the International Year of the Physics and having as its main objective to introduce students to the scientific method, the Rio de Janeiro Planetarium Foundation, in partnership with many institutions of Brazil and Europe, coordinated the activity "Reviving Eratosthenes" whose objective was the determination of the Earth's circumference. We used the famous procedure adopted by Eratosthenes more than 2000 years ago, with some adaptations. This work considers and analyzes the method used by us, aiming the application in schools. The use of places in different meridians allows a better understanding of the abstract concepts such as geographic coordinate and time zones. We obtained reasonably precise results, which improve for pairs of distant cities. Finally, one of the most important conclusions achieved by the students involved is the importance of the cooperation (international in this case) to solve problems. Fazendo parte das comemorações do Ano Internacional da Física e tendo como principal objetivo introduzir estudantes do ensino médio ao método científico, a Fundação Planetário da Cidade do Rio de Janeiro, em parceria com diversas instituições do Brasil e da Europa, coordenou a atividade "Revivendo Eratóstenes" cujo objetivo foi a determinação da circunferência da Terra. Para isso, utilizou-se um procedimento semelhante ao empregado pelo sábio Eratóstenes há mais de 2.000 anos, com algumas adaptações. Este trabalho propõe e analisa o método que empregamos, visando a aplicação em escolas. A possibilidade de se trabalhar com locais em diferentes meridianos permite uma melhor compreensão dos conceitos mas abstratos, como coordenadas e fusos horários. A precisão dos resultados é bastante razoável, melhorando para cidades bem afastadas. Finalmente, uma das conclusões mais importantes é a percepção, por parte dos estudantes, da importância da colaboração (neste caso, internacional) para resolver problemas. Como parte de las conmemoraciones del Año Internacional de la Física y con el objetivo principal de introducir a los estudiantes secundarios al método científico, la Fundación Planetario Rio de Janeiro, en conjunto con diversas instituciones de Brasil y de Europa, coordinó la actividad denominada "Reviviendo a Eratóstenes" cuyo objetivo consistió en la determinación de la cincunferencia de la Tierra. Para esto se utilizó un procedimiento semejante al empleado por Eratóstenes hace más de 2.000 años, con algunas adaptaciones. Este trabajo expone y analiza el método empleado, con la intención de aplicarlo en las escuelas. La posibilidad de trabajar en lugares situados en diferentes meridianos permite una mejor comprensión de los conceptos más abstractos, tales como coordenadas y husos horarios. La precisión de los resultados resultó razonable, mejorando para aquellas ciudades mas apartadas. Finalmente, una de las conclusiones más importantes es la de la percepción, por parte de los estudiantes, de la importancia de la colaboración (en este caso internacional) para resolver problemas.

--No Title--

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ACHP | Case Digest - Protecting Historic Properties: Section 106 in Action

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Digest index. Previous issues: Summer 2012 (PDF) Spring 2012 (PDF) Winter 2012 (PDF) Fall 2011 (PDF ) Summer 2011 (PDF) Spring 2011 (PDF) Winter 2011 (PDF) Fall 2010 (PDF) Summer 2010 (PDF) Winter 2010 (PDF ) Fall 2009 (PDF) Summer 2009 (PDF) Spring 2009 (PDF) Winter 2009 (PDF) Fall 2008 (PDF) Summer 2008 (PDF

NOAA Weather Radio

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recepción confiable en algunas localidades debido a bloqueos de las señales y/o distancia excesiva de la mensajes NOTA: Servicio de NWR para un condado depende de recepción confiable la señal, la cual cobertura de NWR, o cobertura parcial, serán indicados. Algunos condados o partes de condados

Periodic Table of Elements: Los Alamos National Laboratory

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, Communication Specialist talks about the Periodic Table of Elements 7/17/17 Back to Elements List Fermium is process, but the identification of Pu-244 raised the possibility that still more neutrons could have been discovery of the new elements, and the new data on neutron capture, was kept secret on the orders of the U.S

Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

PubMed

Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

2018-03-01

There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.

J Drugs Dermatol. 2018;17(3):333-338.

Inducible DNA-repair systems in yeast: competition for lesions.

PubMed

Mitchel, R E; Morrison, D P

1987-03-01

DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate that in this lower eukaryote, mutagen exposure does not necessarily result in a fixed risk of mutation, but that the risk can be markedly influenced by a variety of external stimuli including heat shock or exposure to other mutagens.

Staff - Trystan M. Herriott | Alaska Division of Geological & Geophysical

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sandstone interval in outcrop of the Tonnie Siltstone Member, Chinitna Formation, lower Cook Inlet, south Paveloff Siltstone Member of the Chinitna Formation: Exploring the potential role of facies variations in member of the Upper Jurassic Naknek Formation, northern Chinitna Bay, Alaska, in Wartes, M.A., ed

NOAA Weather Radio

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. -------------------------------------------------------------------------------- La DESCRIPCIÓN DE COLUMNAS EN TABLAS DE ESTADOS Al hacer un clic en un estado o territorio de la la radio. (Todas áreas de ahora en adelante serán llamados condados.) Entonces la radio les mensaje de la emisión, los oyentes oirán un corto estallido estático digital que señala el fin del

Simulation study of the effects of near- and far-field heating during focused ultrasound uterine fibroid ablation using an electronically focused phased array: A theoretical analysis of patient safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellens, Nicholas, E-mail: nicholas.ellens@utoronto.ca; Hynynen, Kullervo

2014-07-15

Purpose: Assess the feasibility of using large-aperture, flat ultrasonic transducer arrays with 6500 small elements operating at 500 kHz without the use of any mechanical components for the thermal coagulation of uterine fibroids. This study examines the benefits and detriments of using a frequency that is significantly lower than that used in clinical systems (1–1.5 MHz). Methods: Ultrasound simulations were performed using the anatomies of five fibroid patients derived from 3D MRI. Using electronic steering solely, the ultrasound focus from a flat, 6500-element phased array was translated around the volume of the fibroids in various patterns to assess the feasibilitymore » of completing full treatments from fixed physical locations. Successive temperature maps were generated by numerically solving the bioheat equation. Using a thermal dose model, the bioeffects of these simulations were quantified and analyzed. Results: The simulations indicate that such an array could be used to perform fibroid treatments to 18 EM{sub 43} at an average rate of 90 ± 20 cm{sup 3}/h without physically moving the transducer array. On average, the maximum near-field thermal dose for each patient was below 4 EM{sub 43}. Fibroid tissue could be treated as close as 40 mm to the spine without reaching temperatures expected to cause pain or damage. Conclusions: Fibroids were successfully targeted and treated from a single transducer position to acceptable extents and without causing damage in the near- or far-field. Compared to clinical systems, treatment rates were good. The proposed treatment paradigm is a promising alternative to existing systems and warrants further investigation.« less

United States Nuclear Data Program (USNDP)

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Report FY 2016 Annual Report FY 2015 Annual Report FY 2014 Annual Report FY 2013 Annual Report FY 2012 Annual Report FY 2011 Annual Report FY 2010 Annual Report FY 2009 Annual Report FY 2008 Annual Report FY 2007 Annual Report FY 2006 Annual Report FY 2005 Annual Report FY 2004 Final Report FY 2003 Final

Staff - Nina T. Harun | Alaska Division of Geological & Geophysical Surveys

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mapping of the Upper Jurassic Naknek Formation in a footwall syncline associated with the Bruin Bay fault Ivishak Formation in the northeastern Brooks Range, Alaska: University of Alaska Fairbanks, M.S. thesis Triassic Ivishak Formation in the Sadlerochit Mountains, northeastern Alaska: Alaska Division of Geological

NOAA Weather Radio

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televisión afuera o dentro de la casa. Todos éstos pueden mejorar recepción a cualquier radio de FM , incluso NWR. Cualquier pregunta específica sobre la recepción (o falta de ella) en su sitio debe Search For Go NWS All NOAA NWR Recepción El área de la recepción nominal para un receptor de Radio

Fermilab Today - Related Content

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Fermilab Today Related Content Subscribe | Contact Fermilab Today | Archive | Classifieds Search Experiment Profiles Current Archive Current Fermilab Today Archive of 2015 Archive of 2014 Archive of 2013 Archive of 2012 Archive of 2011 Archive of 2010 Archive of 2009 Archive of 2008 Archive of 2007 Archive of

Neutron Scattering Reference

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Conversion Factors Periodic Table of the Elements Chart of the Nuclides Map of the Nuclides Computer Index of (Atominstitut der Österreichischen Universitäten) Neutron Activation Table of Elements Neutron Scattering at neutronsources.org. The information contained here in the Neutron Scattering Web has been

Homepage

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Defense.gov Special Report: National Disability Employment Awareness Month

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service at the U.S. Army Corps of Engineers, DeLisa L. Kviz currently works as chief ... Profile photo of of service with the Department of the Navy, including over 11 years ... Profile photo of Ivan E is a technical information specialist in the Analysis and ... Profile photo of Chad A. Molenhour

Owen Barwell - Chief Financial Officer | NREL

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Owen Barwell - Chief Financial Officer Owen Barwell - Chief Financial Officer A photo of Owen , analysis, and management. He previously served as the Acting Chief Financial Officer and Deputy Chief Financial Officer of the U.S. Department of Energy (DOE), where he was directly responsible for DOE's

Smoot Cosmology Group

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. ___________________________________________________________________________________ What do the different colors on the map of the CMB represent? Although the temperature of the CMB is The most conclusive and carefully examined evidence for The Big Bang is the existence of an isotropic radiation bath that permeates the entirety of the universe known as the cosmic microwave

Automotive Research Center

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| photos Web page Web page 2016 PDF | photos Web page Web page 2015 PDF | photos | video Web page Web page 2014 PDF | photos | videos Web page Web page 2013 PDF | photos Web page Web page 2012 PDF | photos Web page Web page 2011 PDF | photos PDF Web page 2010 PDF PDF PDF 2009 PDF PDF PDF 2008 PDF PDF PDF 2007

NOAA Weather Radio - EAS Description

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR

NOAA Weather Radio - Outage Reporting

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR

NOAA Weather Radio

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR SAME

NOAA Weather Radio - Reception Problems

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR

NOAA Weather Radio

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing interés abajo de dentro de la lista entera del archivo nacional Transmisores de NWR en los Estados ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES

AF family shares experience with child's autism > U.S. Air Force >

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Reading List 2017 CSAF Reading List 2016 CSAF Reading List 2015 CSAF Reading List 2014 CSAF Reading List 2013 CSAF Reading List 2012 CSAF Reading List 2011 CSAF Reading List 2010 CSAF Reading List 2009 CSAF Reading List 2008 CSAF Reading List 2007 CSAF Reading List 2006 CSAF Reading List 50 Years of the CMSAF

X-Ray Data Booklet

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X-RAY DATA BOOKLET Center for X-ray Optics and Advanced Light Source Lawrence Berkeley National Laboratory Introduction X-Ray Properties of Elements Electron Binding Energies X-Ray Energy Emission Energies Table of X-Ray Properties Synchrotron Radiation Characteristics of Synchrotron Radiation History of X

Air and Pesticides

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Pesticides and Human Health Pesticide Incidents What Happens to Pesticides Released into the Environment Pesticides and Human Health Pesticide Incidents What Happens to Pesticides Released into the Environment ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife

Smoot Cosmology Group

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all forces show that they are the same basic force, and have frozen out to different forces in the . What do the different colors on the map of the CMB represent? Although the temperature of the CMB is Implications of the COBE DMR Map of the Early Universe What COBE DMR saw: The COBE DMR (Cosmic

What about using pesticides if I am pregnant or have a baby?

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? Related Topics: Pesticides and Human Health Pesticides and Pregnancy Pesticides and Children Understanding @ace.orst.edu. Last updated January 27, 2016 Related Topics: Pesticides and Human Health Pesticides and ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife

Mineral Resources | Alaska Division of Geological & Geophysical Surveys

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and geophysical framework of Alaska as it pertains to the mineral resources of the state. Summary maps and reports illustrate the geology of the state's prospective mineral terranes and provide data on the location, type, and potential of the state's mineral resources. These data aid in the state's management of

Centro Nacional de Información de Pesticidas - Portada

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a.m. a 12:00 p.m. PT, de lunes a viernes A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Índice acuerdo de cooperación entre la Universidad Estatal de Oregón y la Agencia de Protección Ambiental de los Estados Unidos (acuerdo de cooperación # X8-83560101). La información contenida en esta

NOAA Weather Radio - County Coverage by State

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR

NOAA Weather Radio - Deaf and Hard of Hearing

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing ±ol Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR

NOAA Weather Radio

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Emergencia (EAS) de la Comisión Federal de Comunicaciones, Radio NOAA es una red para todo tipo de peligros . De este modo, es la fuente más comprensiva de información del tiempo y emergencias que està químicos o derramamientos de petróleo). Conocida como "La Voz del Servicio Nacional de Meteorología

NOAA Weather Radio - Viewing Outages

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR SAME Programación en Español

Publications - GMC 395 | Alaska Division of Geological & Geophysical

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investigations of the diatom stratigraphy of Borehole TA8, Portage Alaska: Alaska Division of Geological & Visiting Alaska State Employees DGGS State of Alaska search Alaska Division of Geological & Geophysical DGGS GMC 395 Publication Details Title: Preliminary investigations of the diatom stratigraphy of

CXRO - Mi-Young Im, Staff Scientist

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X-Ray Database Zone Plate Education Nanomagnetism X-Ray Microscopy LDJIM EUV Lithography EUV Mask Publications Contact The Center for X-Ray Optics is a multi-disciplined research group within Lawrence Berkeley -Ray Optics X-Ray Database Nanomagnetism X-Ray Microscopy EUV Lithography EUV Mask Imaging

Solar Integration Data Sets | Grid Modernization | NREL

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modeled solar data to study the operational impacts of solar on the electric power grid. Solar Power Data need to estimate power production from hypothetical solar power plants. Solar Integration National Dataset (SIND) Toolkit The next generation of modeled solar data with higher temporal and spatial

CNEA - Centro Atómico Bariloche

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³mica (CNEA), a través de la Sección de... EL RA-6, RENOVADO EN EL AÑO DE SU 35º ANIVERSARIO EL RA-6 DIRIGIDAS A DOCENTES REALIZAN EN EL CAB CAPACITACIONES DIRIGIDAS A... La Comisión Nacional de Energía Atà ... RECONOCIMIENTO PARA LA SECCIÓN DE DIVULGACIÓN CIENTÍFICA Y TECNOLÓGICA DEL CAB RECONOCIMIENTO PARA LA SECCIÃ

NOAA Weather Radio

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para un condado depende de recepción de la seña fiable, que típicamente se extiende en un radio de 40 millas del transmisor, asumiendo terreno plano. Condados sin la cobertura de NWR o cobertura obstáculos de la seña y/o la distancia excesiva del transmisor. Usted puede referirse directamente a

Defense.gov - Special Report - Travels With Gates

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. If you wish to see the latest content, please visit the current version of the site. For persons with look at production of the newest all-terrain vehicles slated for Afghanistan, and praised the modern You have reached a collection of archived material. The content available is no longer being

Publications - PIR 2008-1 | Alaska Division of Geological & Geophysical

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investigations in the Brooks Range Foothills and North Slope, Alaska: Alaska Division of Geological & interpretations of the Nanushuk Formation exposed along the Colville River near the confluences with the Awuna and Surveys Skip to content State of Alaska myAlaska My Government Resident Business in Alaska

Periodic Table of Elements: Los Alamos National Laboratory

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, Communication Specialist talks about the Periodic Table of Elements 7/17/17 Back to Elements List Seaborgium is Phone Periodic Table of Elements: LANL Chemistry Division » Periodic Table of Elements Chemistry the Elements Chemical Properties Elements List Periodic Table Download News LANL Biofuels Work

NIST Digital Archives

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Nederlands Français Search Search Advanced Search Find results with: error div Add another field Search by date Search by date: from after before on from: mm/dd/yyyy to to: mm/dd/yyyy Search Clear All Searching physical science laboratories. Instant Search Search PHOTOS Search Photos Search NIST PUBLICATIONS Search

Department of Navy Chief Information Officer

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(6) Freedom of Information Act (29) IT Investment Management (47) Records Management (37 Management and Knowledge Management programs. DON CIO Information About the DON CIO Website Accessibility this website is to facilitate effective information flow about information management/information

Alternative Fuels Data Center: Recursos en español

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colaboración entre el gobierno y la industria patrocinada por el Programa de Tecnologías de Vehículos del enchufables Recursos en la web Use estas recursos para obtener información sobre: Economía de combustible y huella de carbono de su vehículo Cómo aumentar la economía de combustible Importancia de la economía

NOAA Weather Radio

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¡tico de programación de la Radio del Tiempo de NOAA la capacidad de transmitir en español. Cualquier Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Search For Go NWS All NOAA Las Políticas de Programación en Español Se le añadió al sistema automÃ

Operating the Western Interconnection with 80%-90% Renewables - Text

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different penetration levels. This chart here shows the left column is the actual penetration of the renewables in all of the different scenarios. The higher base load and the higher VG before curtailment are to a lot of results. This next slide shows the generation by the different types of both renewable

Philip A. Parilla | NREL

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atomic layer deposition for applications. He also manages the majority of X-ray characterization equipment at NREL, specifically X-ray diffraction and X-ray fluorescence instrumentation. Additionally, he for EERE's Hydrogen Storage program. He is also an expert in X-ray diffraction and X-ray fluorescence

Energy Analysis Publications | Energy Analysis | NREL

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Systems Impact Analysis We perform impact analysis to evaluate and understand the impact of markets publications. Featured Publications Complex Systems Analysis Complex systems analysis integrates all aspects of , policies, and financing on technology uptake and the impact of new technologies on markets and policy

News

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Professors Senior Mentor Biographies Fact Sheets Commander's Call Topics CCT Archive CSAF Reading List 2017 CSAF Reading List 2016 CSAF Reading List 2015 CSAF Reading List 2014 CSAF Reading List 2013 CSAF Reading List 2012 CSAF Reading List 2011 CSAF Reading List 2010 CSAF Reading List 2009 CSAF Reading List

NREL's Advanced Atomic Layer Deposition Enables Lithium-Ion Battery

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Battery Technology News Release: NREL's Advanced Atomic Layer Deposition Enables Lithium-Ion Battery increasingly demanding needs of any battery application. These lithium-ion batteries feature a hybrid solid further customized lithium-ion battery materials for high performance devices by utilizing our patented

Chunmei Ban | NREL

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degradation in silicon nanowires for lithium ion battery," ACS Nano, 2015, 9(5), pp 5559-5566, DOI molecular layer deposited coating on silicon nanoparticles for lithium ion battery anodes," ACS Nano lithium-ion batteries, lithium-air batteries, organic radical batteries, and magnesium-ion batteries. The

Transportation Research News | Transportation News | Transportation

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Engineering has yielded new insights for lithium-ion (Li-ion) battery electrodes at the microstructural level -Phase Stochastics in Lithium-Ion Battery Electrodes" detailing the research and resulting revolutionizes the way lithium-ion (Li-ion) batteries are evaluated so designs can be improved before batteries

Soft X-ray radiation damage in EM-CCDs used for Resonant Inelastic X-ray Scattering

NASA Astrophysics Data System (ADS)

Gopinath, D.; Soman, M.; Holland, A.; Keelan, J.; Hall, D.; Holland, K.; Colebrook, D.

2018-02-01

Advancement in synchrotron and free electron laser facilities means that X-ray beams with higher intensity than ever before are being created. The high brilliance of the X-ray beam, as well as the ability to use a range of X-ray energies, means that they can be used in a wide range of applications. One such application is Resonant Inelastic X-ray Scattering (RIXS). RIXS uses the intense and tuneable X-ray beams in order to investigate the electronic structure of materials. The photons are focused onto a sample material and the scattered X-ray beam is diffracted off a high resolution grating to disperse the X-ray energies onto a position sensitive detector. Whilst several factors affect the total system energy resolution, the performance of RIXS experiments can be limited by the spatial resolution of the detector used. Electron-Multiplying CCDs (EM-CCDs) at high gain in combination with centroiding of the photon charge cloud across several detector pixels can lead to sub-pixel spatial resolution of 2-3 μm. X-ray radiation can cause damage to CCDs through ionisation damage resulting in increases in dark current and/or a shift in flat band voltage. Understanding the effect of radiation damage on EM-CCDs is important in order to predict lifetime as well as the change in performance over time. Two CCD-97s were taken to PTB at BESSY II and irradiated with large doses of soft X-rays in order to probe the front and back surfaces of the device. The dark current was shown to decay over time with two different exponential components to it. This paper will discuss the use of EM-CCDs for readout of RIXS spectrometers, and limitations on spatial resolution, together with any limitations on instrument use which may arise from X-ray-induced radiation damage.

Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA) and Its Phase I and II Metabolites in Humans.

PubMed

Steuer, Andrea E; Schmidhauser, Corina; Tingelhoff, Eva H; Schmid, Yasmin; Rickli, Anna; Kraemer, Thomas; Liechti, Matthias E

2016-01-01

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs), intermediate metabolizers (IMs), and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs) up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg) dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC24) of R-MDMA (9% and 25%, respectively) and S-MDMA (16% and 38%, respectively). Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide) by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism.

Impact of Cytochrome P450 2D6 Function on the Chiral Blood Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine (MDMA) and Its Phase I and II Metabolites in Humans

PubMed Central

Steuer, Andrea E.; Schmidhauser, Corina; Tingelhoff, Eva H.; Schmid, Yasmin; Rickli, Anna; Kraemer, Thomas; Liechti, Matthias E.

2016-01-01

3,4-methylenedioxymethamphetamine (MDMA; ecstasy) metabolism is known to be stereoselective, with preference for S-stereoisomers. Its major metabolic step involves CYP2D6-catalyzed demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by methylation and conjugation. Alterations in CYP2D6 genotype and/or phenotype have been associated with higher toxicity. Therefore, the impact of CYP2D6 function on the plasma pharmacokinetics of MDMA and its phase I and II metabolites was tested by comparing extensive metabolizers (EMs), intermediate metabolizers (IMs), and EMs that were pretreated with bupropion as a metabolic inhibitor in a controlled MDMA administration study. Blood plasma samples were collected from 16 healthy participants (13 EMs and three IMs) up to 24 h after MDMA administration in a double-blind, placebo-controlled, four-period, cross-over design, with subjects receiving 1 week placebo or bupropion pretreatment followed by a single placebo or MDMA (125 mg) dose. Bupropion pretreatment increased the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC24) of R-MDMA (9% and 25%, respectively) and S-MDMA (16% and 38%, respectively). Bupropion reduced the Cmax and AUC24 of the CYP2D6-dependently formed metabolite stereoisomers of DHMA 3-sulfate, DHMA 4-sulfate, and 4-hydroxy-3-methoxymethamphetamine (HMMA sulfate and HMMA glucuronide) by approximately 40%. The changes that were observed in IMs were generally comparable to bupropion-pretreated EMs. Although changes in stereoselectivity based on CYP2D6 activity were observed, these likely have low clinical relevance. Bupropion and hydroxybupropion stereoisomer pharmacokinetics were unaltered by MDMA co-administration. The present data might aid further interpretations of toxicity based on CYP2D6-dependent MDMA metabolism. PMID:26967321

Should possible recurrence of disease contraindicate liver transplantation in patients with end-stage alveolar echinococcosis? A 20-year follow-up study.

PubMed

Bresson-Hadni, Solange; Blagosklonov, Oleg; Knapp, Jenny; Grenouillet, Frédéric; Sako, Yasuhito; Delabrousse, Eric; Brientini, Marie-Pascale; Richou, Carine; Minello, Anne; Antonino, Anca-Teodora; Gillet, Michel; Ito, Akira; Mantion, Georges André; Vuitton, Dominique Angèle

2011-07-01

Liver transplantation (LT) is currently contraindicated in patients with residual or metastatic alveolar echinococcosis (AE) lesions. We evaluated the long-term course of such patients who underwent LT and were subsequently treated with benzimidazoles. Clinical, imaging, serological, and therapeutic data were collected from 5 patients with residual/recurrent AE lesions who survived for more than 15 years. Since 2004, [(18) F]-2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) images were available, and the levels of serum antibodies (Abs) against Echinococcus multilocularis-recombinant antigens were evaluated. Median survival time after LT was 21 years. These patients were from a prospective cohort of 23 patients with AE who underwent LT: 5 of 8 patients with residual/recurrent AE and 4 of 9 patients without residual/recurrent AE were alive in September 2009. High doses of immunosuppressive drugs, the late introduction of therapy with benzimidazoles, its withdrawal due to side effects, and nonadherence to this therapy adversely affected the prognosis. Anti-Em2(plus) and anti-rEm18 Ab levels and standard FDG-PET enabled the efficacy of therapy on the growth of EA lesions to be assessed. However, meaningful variations in Ab levels were observed below diagnostic cutoff values; and in monitoring AE lesions, images of FDG uptake taken 3 hours after its injection were more sensitive than images obtained 1 hour after its injection. In conclusion, benzimidazoles can control residual/recurrent AE lesions after LT. Using anti-rEm18 or anti-Em2(plus) Ab levels and the delayed acquisition of FDG-PET images can improve the functional assessment of disease activity. The potential recurrence of disease, especially in patients with residual or metastatic AE lesions, should not be regarded as a contraindication to LT when AE is considered to be lethal in the short term. Copyright © 2011 American Association for the Study of Liver Diseases.

DoD ESI

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Information Management, Microsoft Platform Management, Identity & Access Management, Endpoint Systems /2016-24054/category-management). OMB released this IT Success Story for "Information Sharing Management of Common Information Technology: Mobile Devices and Services 7/1/2016 Category Management Policy

Electron Microscopy Lab

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Facilities Science Pillars Research Library Science Briefs Science News Science Highlights Lab Organizations Science Programs Applied Energy Programs Civilian Nuclear Energy Programs Laboratory Directed Research Science Seaborg Institute Fellows Conferences Research Opportunities Center for Integrated

NOAA Weather Radio - Station Search

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR Recepción Explicacion de NWR SAME Programación en Español NOAA

NOAA Weather Radio

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automatizado apoyará la difusión en español. Idioma español de voz sintetizada será proporcionado para algunas oficinas donde el personal permite y los dictados de la población, la radiodifusión española Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing

NOAA Weather Radio - Cobertura de Condado a Condado

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para un condado depende de recepción de la seña fiable, que típicamente se extiende en un radio de 40 millas del transmisor, asumiendo terreno plano. Condados sin la cobertura de NWR o cobertura obstáculos de la seña y/o la distancia excesiva del transmisor. Usted puede referirse directamente a

DIY Solar Market Analysis Webinar Series: PVWatts® | State, Local, and

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, and updates the energy prediction algorithms to be in line with the actual performance of modern the latest update." In this webinar, one of the tool's developers explains how the new version of ® Wednesday, July 9, 2014 As part of a Do-It-Yourself Solar Market Analysis summer series, NREL's Solar

Publications | Argonne National Laboratory

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Carlo, F. De Carlo, Francesco De Graef, Marc de Jalon, Garcia De La Rosa, K. de Leon, P.A. Ignacio- de . Degenkolb, E. DeJongh, M. DeLisi, M. Delmont, T. O. DeLuca, C. Demas, N. Demchenko, Y. Demeshko, I. Demiguel , N. Kyrpides, Nikos La Joie, C. Labarta, J. LaBissoniere, D. Lacinski, L. Lacour, S. Laguna, I. Lai

Solar Requests for Proposals | State, Local, and Tribal Governments | NREL

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who have a lot of experience in this area may handle the process on their own while others may decide greatest number of respondents and give the agency the greatest number of options. Solar RFP Elements As to the selection criteria. Sources Solar Powering Your Community: Key Elements of Solar Requests for

What's New | Galaxy of Images

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] View Images Details ID: SIL32-035-02 Enlarge Image View Images Details ID: SIL32-038-02 Enlarge Image View Images Details ID: SIL-2004_CT_6_1 Enlarge Image View Images Details ID: SIL32-010-01 Enlarge Image View Images Details ID: SIL32-013-05 Enlarge Image View Images Details ID: SIL32-014-02 Enlarge

SMS Two Column Template: Smithsonian Marine Station (SMS) at Fort Pierce

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appreciation of this invaluable natural resource. My image My image My image My image My image Discover: - over difference in IRL water quality Check Out: - the IRL Photo Gallery - the IRL Species Image Collection Downloads: - Species Database - IRL Species Bibliography My image My image My image My image My image EOL

Chief Information Officer > DoDSection508 > Std_Stmt

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Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department of Defense Chief Information Officer Home About DoD CIO Bios Organization DCIO C4&IIC DCIO IE

Chief Information Officer - U.S. Department of Defense

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Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department of Defense Chief Information Officer Home About DoD CIO Bios Organization DCIO C4&IIC DCIO IE

Compcon '95 Paper

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has the ability to view various parts of a frog from many different angles, and with the different here - the Virtual Dissection Kit - has been accessed by 50,000 different sites, in over 50 different form document that is a translation of the user interface into a different language (the Virtual Frog

Welcome - TampaBay.WaterAtlas.org

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An edition of: WaterAtlas.orgPresented By: USF Water Institute Choose a Water Atlas Charlotte Harbor NEP Water Atlas Hillsborough County Water Atlas Lake County Water Atlas Manatee County Water Atlas Orange County Water Atlas Pinellas County Water Atlas Polk County Water Atlas Sarasota County Water Atlas

Publications - GMC 430 | Alaska Division of Geological & Geophysical

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: Formation hardness of Hemlock Formation cores after immersion in water and oil based fracturing fluids; and mechanics: Formation hardness of Hemlock Formation cores after immersion in water and oil based fracturing Surveys Skip to content State of Alaska myAlaska My Government Resident Business in Alaska

NOAA Photo Library

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- nssl0057 Early stage of tornado formation. Photo #1 of a series of classic photographs of this tornado Available Publication of the U.S. Department of Commerce, National Oceanic & Atmospheric Adminstration NOAA Photo Library Banner Takes you to the Top Page Takes you to the About this Site page. Takes

Publications - GMC 303 | Alaska Division of Geological & Geophysical

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DGGS GMC 303 Publication Details Title: The facies of the Ivishak Formation from conventional core , The facies of the Ivishak Formation from conventional core descriptions, electric logs, and Surveys Skip to content State of Alaska myAlaska My Government Resident Business in Alaska

NCEP Operational HWRF Forecasting System

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2010 Basin: North Atlantic Eastern North Pacific Central North Pacific Western North Pacific North ALBERTO01L North Atlantic: (1) active ALBERTO01L Eastern North Pacific: (0) active Central North Pacific: (0 ) active Western North Pacific: (0) active North Indian Ocean: (0) active Southern Hemisphere: (0) active Â

Wind Turbine Control Systems | Wind | NREL

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Turbine Control Systems Wind Turbine Control Systems Advanced wind turbine controls can reduce the loads on wind turbine components while capturing more wind energy and converting it into electricity turbines. A photo of a wind turbine against blue sky with white blades on their sides in the foreground

Wind Energy Modeling and Simulation | Wind | NREL

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Wind Energy Modeling and Simulation Wind Turbine Modeling and Simulation Wind turbines are unique wind turbines. It enables the analysis of a range of wind turbine configurations, including: Two- or (SOWFA) employs computational fluid dynamics to allow users to investigate wind turbine and wind power

Systems Engineering Workshop 2017 | Wind | NREL

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Energy for Wind Systems Today Cost and Value of Wind Power-Implications of Wind Turbine Design, János Aaron Smith, PPI Session II: Uncertainty Impacts on Wind Turbine Design and Performance Mitigation of Wind Turbine Design Load Uncertainties, Anand Natarajan, DTU Wind Energy Uncertainty in the Wind

Science Programs

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Research Library Science Briefs Science News Science Highlights Lab Organizations Science Programs Applied Innovation Research Capabilities Deploying Innovation Technology Opportunities Innovation in New Mexico Los Laboratory Delivering science and technology to protect our nation and promote world stability Science &

Food Safety

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veggies? Federal Pesticide Regulation Pesticides and Human Health Regulating Organic Food Production fruit and veggies? Federal Pesticide Regulation Pesticides and Human Health Regulating Organic Food ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife

--No Title--

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-- OAS Intranet -- Sunday 27 May 2018 Approved Program-Budget 2018 Proposed Program-Budget 2018 Approved Program-Budget 2017 Proposed Program-Budget 2017 Approved Program-Budget 2016 Proposed Program -Budget 2016 Approved Program-Budget 2015 Proposed Program-Budget 2015 Approved Program-Budget 2014

National Centers for Environmental Prediction

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DIFFERENT BETWEEN THE 12-KM NAM PARENT DOMAIN AND THE NAM CONUS NEST? (04 Nov 2011, updated 13 April 2017 . Back to Table of Contents WHY IS THE QPF DIFFERENT BETWEEN THE 12-KM NAM PARENT DOMAIN AND THE NAM different QPF fields between the 12km NAM parent and the NAM nests. 13 April 2017 update: In the 12 August

NOAA Weather Radio - Using NWR SAME

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Transmitter Outages FAQ NWR - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el

NOAA Weather Radio - EAS Event Codes

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Transmitter Outages FAQ NWR - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el

NOAA Weather Radio - Station Listing

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Outages FAQ NWR - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor

NOAA Weather Radio - NWR Voices

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Transmitter Outages FAQ NWR - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el

NOAA Weather Radio - General Information

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista de Emisora y Cobertura Acerca de NWR ESTACIONES NACIONAL Información General Información Para el consumidor receptor NWR

The Sky This Week, 2016 April 26 - May 3 - Naval Oceanography Portal

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the week coursing through the summer Milky Way, skirting the southern reaches of the ecliptic in the morning sky. Last Quarter occurs on the 29th at 11:29 pm Eastern Daylight Time. As Luna wanes through her begins on the 29th and lasts through May 8th. This month's target constellation is Leo, the Lion, which

The Evolving Search for the Nature of Dark Energy | Berkeley Lab

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percent of its contents is ordinary matter, 24 percent is dark matter, and all the rest is dark energy ordinary matter, 24 percent is dark matter, and all the rest is dark energy - unless there's a flaw in our Universe, and it's pushing all the rest - ordinary matter and dark matter - farther apart at an ever

Chief Information Officer > About DoD CIO > Organization > DCIO CS

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Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department of Defense Chief Information Officer Home About DoD CIO Bios Organization DCIO C4&IIC DCIO IE

Defense.gov - Special Report - Progress Report: Department of Defense

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the need to re-shape and re-balance the direction of the Department and an increasingly challenging capabilities, requirements, risks and needs for the purpose of shifting the Department toward a different , the Landing Platform Dock ship and Mobile Landing Platform ship; and Completing production of the C-17

Publications - PIR 2015-5 | Alaska Division of Geological & Geophysical

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superposition of strike-slip and reverse-slip faults in the Bruin Bay fault system, Ursus Head, lower Cook Inlet , Preliminary investigation of fracture populations in Mesozoic strata of the Cook Inlet forearc basin: Iniskin observations: Continued facies analysis of the Lower Jurassic Talkeetna Formation, north Chinitna Bay, Alaska

Publications - GMC 329 | Alaska Division of Geological & Geophysical

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Bee Creek 1976 holes of Chignik C2 Quadrangle (B-1, 265'; B-2, 500'; B-3, 500'; B-4, 300' and B-5, 300 the Bee Creek 1976 holes of Chignik C2 Quadrangle (B-1, 265'; B-2, 500'; B-3, 500'; B-4, 300' and B-5

NOAA Weather Radio

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Search For Go NWS All NOAA NWR Recepción El área de la recepción nominal para un receptor de Radio cosas afectan la recepción de señas de la radio. Por ejemplo, las extensiones grandes de agua de sal de NWR. Siga leyendo si está dentro del área pero tiene dificultad con recepción. Su seña de la

Research | Photovoltaic Research | NREL

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-V cells Hybrid tandems Polycrystalline Thin-Film PV CdTe solar cells CIGS solar cells Perovskites and Organic PV Perovskite solar cells Organic PV solar cells Advanced Materials, Devices, and Science Interfacial and Surface Science Reliability and Engineering Real-Time PV and Solar Resource

Chioke Harris | NREL

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transfer and materials science to the development of high-performance building components. He is member of the Building Energy Science Group, his research focuses on the application of fundamental heat particularly interested in the development of novel opaque insulation and window frame materials using nano

Water Power Research | Water Power | NREL

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Water Power Research Water Power Research NREL conducts water power research; develops design tools Columbia River, Washington. Hydropower Research Hydropower technologies convert the energy of water moving ; and evaluates, validates, and supports the demonstration of innovative water power technologies. Photo

Mengjin Yang | NREL

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on the formation of higher efficiency formamidinium lead triiodide-based solar cells," Chem -0003-2019-4298 Dr. Mengjin Yang received his Ph.D. in Materials Science from the University of Pittsburgh, where he investigated nanomaterials for solar energy conversion under the supervision of Prof

Geothermal Energy | Climate Neutral Research Campuses | NREL

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Geothermal Energy Geothermal Energy Research campuses can take advantage of geothermal resources sections that describe how examining geothermal energy may fit into your climate action plans. Campus Options Considerations Sample Project Related Links Campus Geothermal Energy Options Campuses can use

Battery Control Algorithms | Transportation Research | NREL

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publications. Accounting for Lithium-Ion Battery Degradation in Electric Vehicle Charging Optimization Advanced Reformulation of Lithium-Ion Battery Models for Enabling Electric Transportation Fail-Safe Design for Large Capacity Lithium-Ion Battery Systems Contact Ying Shi Email | 303-275-4240

NREL: News - Winner of Solar Decathlon to be Announced

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Winner of Solar Decathlon to be Announced Friday, October 4, 2002 Washington, D.C.- The winner of National Gallery of Art Note: All houses competing in the Solar Decathlon will be open to the public from 9 the U.S. Department of Energy's first Solar Decathlon will be announced noon, Saturday, October 6 in

Site Description | CTIO

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Preserving the Dark Skies La Oficina de Protección de la Calidad del Cielo del Norte de Chile - OPCC Light view Cerro Pachón CTIO/AURA La Serena Facilities The "El Totoral" Reserve, Cerro Tololo and . back to top Sky Brightness over Cerro Pachón and Cerro Tololo Light pollution from nearby cities (La

AF Week in Photos > U.S. Air Force > Article Display

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Professors Senior Mentor Biographies Fact Sheets Commander's Call Topics CCT Archive CSAF Reading List 2017 CSAF Reading List 2016 CSAF Reading List 2015 CSAF Reading List 2014 CSAF Reading List 2013 CSAF Reading List 2012 CSAF Reading List 2011 CSAF Reading List 2010 CSAF Reading List 2009 CSAF Reading List

National Wind Technology Center | NREL

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. Wind Energy Research Wind turbine blade Wind energy research at the NWTC allows for validation and verification of large and small components and wind turbine systems. Photo by Dennis Schroeder / NREL 40935 Wind energy research at the NWTC has pioneered wind turbine components, systems, and modeling methods

Astronomical Information Center - Naval Oceanography Portal

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section Advanced Search... Sections Home Time Earth Orientation Astronomy Meteorology Oceanography Ice You the Moon Illuminated Time Universal Time and Greenwich Mean Time What is Terrestrial Time? Computing Greenwich Apparent Sidereal Time What are the U.S. Time Zones? World Time Zone Map When Does Daylight Time

Alternative Fuels Data Center: Data Downloads

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Data Downloads to someone by E-mail Share Alternative Fuels Data Center: Data Downloads on Facebook Tweet about Alternative Fuels Data Center: Data Downloads on Twitter Bookmark Alternative Fuels Data Center: Data Downloads on Google Bookmark Alternative Fuels Data Center: Data Downloads on Delicious Rank

Home Page, Alaska Department of Fish and Game

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Orders Media/Press Releases Hot Topics & Issues Board of Fisheries and Game: Actions & Activities Habitat Special Areas Fish Habitat Boards Board of Game Board of Fisheries The Joint Board Commissioner Maps & Area Information File Hunt Report Trapping Boards Board of Fisheries Board of Game

CAEBAT Model Featured on American Chemical Society Journal Tenth

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University's School of Mechanical Engineering has yielded new insights for lithium-ion (Li-ion) battery corresponding article, "Secondary-Phase Stochastics in Lithium-Ion Battery Electrodes" detailing the microstructural modifications can greatly improve overall Li-ion battery performance. The value of this work is

Energy Storage News | Transportation | Transportation Research | NREL

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NREL/Purdue team's corresponding article, "Secondary-Phase Stochastics in Lithium-Ion Battery by NREL and NASA, the Battery ISC Device revolutionizes the way lithium-ion (Li-ion) batteries are collaboration with Purdue University's School of Mechanical Engineering has yielded new insights for lithium-ion

News and Feature Stories | NREL

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insights for lithium-ion (Li-ion) battery electrodes at the microstructural level, that can lead to Lithium-Ion Battery Electrodes" detailing the research and resulting discoveries, is showcased inside 19th annual Middle School Electric Car Competition, where students raced solar and lithium-ion powered

Publications - GMC 73 | Alaska Division of Geological & Geophysical Surveys

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following seven NPRA wells: Fish Creek test well #1; Oumalik test well #1; Peard test well #1; Tunalik #1 ; Umiat test well #11; Wolf Creek test well #3; and Walapka test well #1 Authors: Unknown Publication Date wells: Fish Creek test well #1; Oumalik test well #1; Peard test well #1; Tunalik #1; Umiat test well

Nolan Wilson | NREL

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Nolan Wilson Nolan Wilson Postdoctoral Researcher-Chemical Engineering Nolan.Wilson@nrel.gov | 303 Ph.D., Chemical and Biomolecular Engineering, Clemson University, 2014 M.S., Chemical and Biomolecular Engineering, Clemson University, 2012 B.S., Chemical Engineering, Auburn University, 2007 Professional

GISD

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information on the ecology of the species, its impacts and management, a comprehensive bibliography and a list ) General Impact information Management information Distribution The Distribution page presents the global page collates management information from the profile narrative page plus location-specific management

Staff - Trent D. Hubbard | Alaska Division of Geological & Geophysical

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, R.P., Darrow, M.M., and Hubbard, T.D., 2015, Influence of catchment properties on stability of frozen : Evaluating geologic hazards and the distribution and character of geologic materials on Alaska's North Slope Professor, Department of Biology and Earth Sciences, University of Central Missouri, Warrensburg, MO 2003

Standard Terms and Conditions | NREL

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and Technical Services Subcontracts, Cost-Type (1) Cost Sharing (2) Cost Reimbursement (3) Cost Plus Than Foreign) (1) Cost Sharing (2) Cost Reimbursement (2) Cost Plus Fixed Fee. Appendix B-10 (12/15/16 /15/16) Standard Terms and Conditions for Travel Requirements (1) Cost Sharing (2) Cost Reimbursement

Publications - PIR 2015-5-8 | Alaska Division of Geological & Geophysical

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lower sandstone member of the Upper Jurassic Naknek Formation, northern Chinitna Bay, Alaska, in Wartes member of the Upper Jurassic Naknek Formation, northern Chinitna Bay, Alaska Authors: Wartes, M.A Surveys Skip to content State of Alaska myAlaska My Government Resident Business in Alaska

Publications - PIR 2015-5-4 | Alaska Division of Geological & Geophysical

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facies analysis of the Lower Jurassic Talkeetna Formation, north Chinitna Bay, Alaska, in Wartes, M.A of the Lower Jurassic Talkeetna Formation, north Chinitna Bay, Alaska Authors: Bull, K.F. Publication Surveys Skip to content State of Alaska myAlaska My Government Resident Business in Alaska

Presentations - Herriott, T.M. and others, 2011 | Alaska Division of

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Details Title: Detailed geologic mapping and overview of structural and stratigraphic studies in the east Resident Business in Alaska Visiting Alaska State Employees DGGS State of Alaska search Alaska Division of in the east-central North Slope foothills, Alaska (poster): 3P Arctic, The Polar Petroleum Potential

Idaho Water Resources Research Institute

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Students Parents Alumni Faculty & Staff students walk on University of Idaho campus Visit U of I Learn Visit Students on Campus Title IX Helping to ensure U of I is a safe and engaging place for students to Diversity Athletics Events News Directory A - Z Prospective Students Current Students Parents Alumni Faculty

First International Workshop on Grid Simulator Testing of Wind Turbine

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of Wind Turbine Drivetrains First International Workshop on Grid Simulator Testing of Wind Turbine Wind Turbine Drivetrains June 13-14, 2013, at the National Wind Technology Center near Boulder apparatuses involved in grid compliance testing of utility-scale wind turbine generators. This includes both

Community Solar | State, Local, and Tribal Governments | NREL

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distributed generation owners for the power that their systems contribute to the grid. Community solar generation from an offsite solar system. Some form of VNM must exist for community solar to work properly so Electric Power Association. Community Solar: NREL's Working Group on Community Solar Gardens meeting

NREL Projects Awarded More Than $3 Million to Advance Novel Solar

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in Grid Operations," evaluating a research solution to better integrate solar power generation funding program, which advances state-of-the-art techniques for predicting solar power generation to Office to advance predictive modeling of solar power as part of its Solar Forecasting 2 funding program

Scanning Defect Mapping | Photovoltaic Research | NREL

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SDMS moves the treated wafer across a stationary laser beam and maps the defects for each location on the wafer. The amount of light reflected from an area is proportional to the dislocation density for that area and provides a direct statistical count of the number of dislocations. PV Research Other

Climate Prediction Center - Seasonal Outlook

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ACCOUNT FOR THE LATEST DYNAMICAL AND STATISTICAL GUIDANCE. LONG TERM TRENDS ACCOUNT FOR THE FAMILIAR U Time. Please consult the schedule of 30 & 90-day outlooks for exact release dates. Text Discussions COLLEGE PARK MD 830 AM EDT THU MAY 17 2018 SUMMARY OF THE OUTLOOK FOR NON-TECHNICAL USERS ENSO NEUTRAL

Project Development Model | Integrated Energy Solutions | NREL

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. The five elements of project fundamentals are: Baseline: Analyze the current situation for the site . The two-phase iterative model includes elements in project fundamentals and project development based State and Local Energy Data (SLED) tool, developed by NREL for the U.S. Department of Energy, to get

Rare Earth Elements | Alaska Division of Geological & Geophysical Surveys

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- Mineral Resources main content Rare Earth Elements Rare earth elements and the supply and demand of these deposits containing rare earth elements to meet the perceived future demand. High prices for rare earth earth element occurrences in the DGGS publications catalog. Department of Natural Resources, Division of

John B. Goodenough, Cathode Materials, and Rechargeable Lithium-ion

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cathode materials for the lithium-ion rechargeable battery that is ubiquitous in today’s portable conductors has enabled realization of the rechargeable lithium-ion battery used in cellular telephones and Goodenough, the rechargeable lithium ion battery, and related research is available in electronic documents

La Aventura de las Partículas

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ciertas formas fundamentales. Explore las siguientes rutas que le explicarán la materia del universo! La grande del logo de la Ruta SM) La ruta de las evidencias experimentales : aprenda como los físicos diseà explicación de los "por qué" de las interacciones físicas hay todavía muchos misterios por

NOAA Weather Radio - Información General

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logo La Radio de Canada NWR receiver logo recepción COVERAGE County Coverage Listings State Coverage Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Search For Go NWS All NOAA Información General NWR receiver logo Información de Fondo (incluyendo

Fermilab Today

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Search GO Special Result of the Week Toward a high-intensity muon source Impact of a single pulse of 12 x moment of impact (T=0); b) 9ms after impact; c) 15ms after impact. To solve the mysteries of nature 1012 protons at 14 GeV on a 1cm-wide jet of mercury flowing at 15m/s in a 10T solenoid field: a) at the

Xiaowen Chen | NREL

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Xiaowen Chen Photo of Xiaowen Chen Xiaowen Chen Researcher IV-Chemical Engineering Xiaowen.Chen Education Ph.D., Chemical Engineering, University of Maine, 2009 M.S., Chemical Engineering, University of Maine, 2005 B.S., Chemical Engineering in Polymer Science and Technology, Nanjing University of Science

Sandia National Laboratories: Research: R&D 100 Awards

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high radiation environments such as space. Watch the video. control system for active damping of inter first commercially available, high-voltage, high-frequency, high-current, high-temperature, single-chip Materials Science Nanodevices & Microsystems Radiation Effects & High Energy Density Science

NOAA Photo Library -

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logo and clouds NSSL is one of the National Oceanic and Atmospheric Administration's internationally of tornado Tornadoes picture of vintage doppler radar Instruments picture of clouds Sky Scenes -known Environmental Research Laboratories, leading the way in investigations of all aspects of severe

Batavia Boy Scouts | News

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Financial Officer Finance Section Office of the Chief Operating Officer Facilities Engineering Services Accelerator Division Accelerator Physics Center Office of the Chief Safety Officer Environment, Safety, Health and Quality Section Office of the Chief Project Officer Office of Project Support Services Office of

Tuberculosis Reports - UDOH-EPI

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Tuberculosis Tuberculosis Reports Tuberculosis Reports Tuberculosis Utah Reports Tuberculosis in Utah - Five (IBIS-PH) Tuberculosis 2015 Monthy Reports January February March April May June Tuberculosis National Reports National TB Data and Statistics Tuberculosis Global Reports TB Incidence Map by country TB

Eric O'Shaughnessy | NREL

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of residential solar PV markets. Eric leads the lab's solar data partnerships program. Eric's current green power market research. Research Interests Economic analysis, econometrics, distributed solar PV . Ardani, R. Margolis. 2018. Solar plus: Optimization of distributed solar PV through battery storage and

Photovoltaics | Climate Neutral Research Campuses | NREL

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Photovoltaics Photovoltaics Solar photovoltaics (PV) is a mature, commercially available technology arrays. Campus Solar Energy Options A PV system requires periodic maintenance, but upkeep averages two to undertaking a solar energy assessment or PV installation. Solar Energy Resources Solar energy production

University of Maryland MRSEC - Education: Resources

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. University of Maryland Materials Research Science and Engineering Center Home About Us Leadership Moments in MSE The Materials Science and Engineering Career Resources Center Materials Research Society Central Super Science Fair Projects: Ideas, Topics, & Experiments All Science Fair Projects Science

Pesticide Information for Veterinarians

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; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Home Page Pesticide Health and Safety Information Pesticides and Animal Health Pesticide Information

Pesticide Regulations

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costs and benefits of pesticides to society. They try to identify the potential risks on human health ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure

A to Z Index of Topics

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; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Health and Pesticides Animal Health Care Provider Information Animal Incident Reporting Annual Reports

Council on Tall Buildings and Urban Habitat

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Publications CTBUH Journal Awards Books Technical Guides Research Reports Other Books IJHRB Research Journal TBUH Chinese Journal Virtual Research Journal Conference Publications Posters Awards Global Awards Council on Tall Buildings and Urban Habitat About CTBUH Organization & People Membership

Home | Departamento de Salud de Puerto Rico

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Publicaciones Registros Suicidio Tuberculosis Centro de Aprendizaje Virtual sobre temas de Preparación en Salud Tuberculosis Centro de Aprendizaje Virtual sobre temas de Preparación en Salud Pública Informe de Casos de Departamento de Salud Search... Search It looks like your browser does not have JavaScript enabled

The Evolving Market Structure of the U.S. Residential Solar PV Installation

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Solar PV Installation Industry, 2000-2016 The Evolving Market Structure of the U.S. Residential Solar PV residential solar photovoltaic (PV) system and that the residential PV installation industry has become more concentrated over time. From 2000 to 2016, the U.S. residential solar photovoltaic (PV) installation industry

DefenseLink.mil - Pentagon Memorial Dedication

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Dept. photo by Army Staff Sgt. Michael J. Carden An entry stone at the Pentagon Memorial lists the their lives during the Sept. 11 terrorist attack on the Pentagon. Photo by Staff Sgt. Michael J. Carden Staff Sgt. Michael J. Carden A member of The United States Air Force Band practices before the start of

O, Canada: NREL Partnership Produces New Take on Alternative Fueling

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Fueling Station Locator. The tool, which is part of a significant investment by the Canadian government to to develop a modern, bilingual web tool that makes it easier for drivers of alternative fuel vehicles Locator Tool March 5, 2018 Word of the National Renewable Energy Laboratory's (NREL) deep transportation

Publications - PIR 2015-5-9 | Alaska Division of Geological & Geophysical

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content DGGS PIR 2015-5-9 Publication Details Title: Evidence of a submarine canyon in the Snug Harbor ., Decker, P.L., and Wartes, M.A., 2015, Evidence of a submarine canyon in the Snug Harbor Siltstone and Pomeroy Arkose Members, Naknek Formation, south-central Alaska: Implications for the distribution of

Visualization and Analytics Software Tools for Peregrine System |

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R is a language and environment for statistical computing and graphics. Go to the R web site for System Visualization and Analytics Software Tools for Peregrine System Learn about the available visualization for OpenGL-based applications. For more information, please go to the FastX page. ParaView An open

Inventory of File gfs.t06z.smartguam00.tm00.grib2

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boundary layer WDIR analysis Wind Direction (from which blowing) [degtrue] 013 planetary boundary layer WIND analysis Wind Speed [m/s] 014 planetary boundary layer RH analysis Relative Humidity [%] 015 planetary boundary layer DIST analysis Geometric Height [m] 016 surface 4LFTX analysis Best (4 layer) Lifted

John Lewis | NREL

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Lewis John Lewis John Lewis Researcher IV-Chemical Engineering John.Lewis@nrel.gov | 303-275-3021 Education Ph.D. Chemical Engineering, California Institute of Technology, Pasadena, CA, 1996 M.S. Chemical Engineering, California Institute of Technology, Pasadena, CA, 1993 B.S. Chemical Engineering, Texas A&M

Buy or sell used musical instruments | News

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Financial Officer Finance Section Office of the Chief Operating Officer Facilities Engineering Services Accelerator Division Accelerator Physics Center Office of the Chief Safety Officer Environment, Safety, Health and Quality Section Office of the Chief Project Officer Office of Project Support Services Office of

David Toback re-elected CDF co-spokesperson | News

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Financial Officer Finance Section Office of the Chief Operating Officer Facilities Engineering Services Accelerator Division Accelerator Physics Center Office of the Chief Safety Officer Environment, Safety, Health and Quality Section Office of the Chief Project Officer Office of Project Support Services Office of

MMAB Mission Statement

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services. Marine Modeling and Analysis Branch Logo Click here to go to the EMC/MMAB homepage MMAB Mission Statement The Marine Modeling and Analysis Branch is part of the Environmental Modeling Center, which is Environmental Prediction Environmental Modeling Center Marine Modeling and Analysis Branch 5830 University

Materials and Devices | Photovoltaic Research | NREL

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Polycrystalline Thin-Film PV Cadmium telluride (CdTe) solar cells Copper indium gallium diselenide (CIGS) solar cells Perovskite and Organic PV Perovskite solar cells Perovskite Patent Portfolio Organic PV (OPV ) solar cells Advanced Materials, Devices, and Concepts We explore new PV materials using high-throughput

Silicon Materials and Devices R&D | Photovoltaic Research | NREL

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" and "Si-based Tandem Solar Cells"), Next Generation Photovoltaics (NextGen PV III), and devices, especially for photovoltaic (PV) cell applications. PV Research Other Materials & Devices pages: High-Efficiency Crystalline PV Polycrystalline Thin-Film PV Perovskite and Organic PV Advanced PV

Water Resource Sustainability Conference 2015

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| Honolulu, Hawaii Presented By Water Resources Research Center (WRRC), Hawaii and American Samoa Water and Environmental Research Institute (WERI), Guam Puerto Rico Water Resources and Environmental Research Institute (PRWRERI), Puerto Rico The Virgin Islands Water Resources Research Institute (VI-WRRI), U. S. Virgin

NOAA Photo Library

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reached the mature stage of formation. Image ID: nssl0065, NOAA's National Severe Storms Laboratory (NSSL Available Publication of the U.S. Department of Commerce, National Oceanic & Atmospheric Adminstration NOAA Photo Library Banner Takes you to the Top Page Takes you to the About this Site page. Takes

NOAA Photo Library

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in its early stage of formation. Image ID: nssl0061, NOAA's National Severe Storms Laboratory (NSSL Available Publication of the U.S. Department of Commerce, National Oceanic & Atmospheric Adminstration NOAA Photo Library Banner Takes you to the Top Page Takes you to the About this Site page. Takes

NOAA Photo Library

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in its early stage of formation. Image ID: nssl0062, NOAA's National Severe Storms Laboratory (NSSL Available Publication of the U.S. Department of Commerce, National Oceanic & Atmospheric Adminstration NOAA Photo Library Banner Takes you to the Top Page Takes you to the About this Site page. Takes

NOAA Photo Library

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in its early stage of formation. Image ID: nssl0064, NOAA's National Severe Storms Laboratory (NSSL Available Publication of the U.S. Department of Commerce, National Oceanic & Atmospheric Adminstration NOAA Photo Library Banner Takes you to the Top Page Takes you to the About this Site page. Takes

Wind Maps | Geospatial Data Science | NREL

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Wind Maps Wind Maps Wind Prospector This GIS application supports resource assessment and data exploration for wind development. This collection of wind maps and assessments details the wind resource in Geospatial Data Science Team. National Wind Resource Assessment The national wind resource assessment was

Impacts | Wind | NREL

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in hard hats standing on top of a large wind turbine overlooking several other wind turbines in the Framework Transforms FAST Wind Turbine Modeling Tool NREL Assesses National Design Standards for Offshore Wind Resource NREL Identifies Investments for Wind Turbine Drivetrain Technologies Awards R&D 100

@NWTC Newsletter: Fall 2013 | Wind | NREL

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Assessment of the U.S. Wind Industry in 2012 NREL Identifies Investments for Wind Turbine Drivetrain , medium-speed, medium-voltage wind turbine drivetrain design. Tapping into unparalleled expertise, the The drivetrain of a wind turbine converts the power of the wind into electrical energy. Now

Geothermal Maps | Geospatial Data Science | NREL

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presented in these maps was aggregated from the Geothermal Energy Association 2014 Annual U.S. and Global Geothermal Maps Geothermal Maps Our geothermal map collection covers U.S. geothermal power plants , geothermal resource potential, and geothermal power generation. If you have difficulty accessing these maps

NREL: Renewable Resource Data Center - Geothermal Resource Information

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Energy's Office of Energy Efficiency and Renewable Energy Geothermal Technologies Program. Its collection , and thermal springs. View NREL's Geothermal resource maps as well as maps for other renewable energy Geothermal Resource Information Geothermal Prospector Start exploring U.S. geothermal resources

XHTML Vocabulary

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content of resource. contentinfo contains meta information about the content on the page or the page as a Applications Vocabulary alert A message with important, and usually time-sensitive, information. Also see : true, false, or mixed. columnheader A cell containing header information for a column. combobox A

Federal Pesticide Regulation

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pesticides, the EPA works to protect human health and the environment. The EPA works cooperatively with state ; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure

Before You Control Your Pest

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; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure activities. Public Health Departments Control pests that impact human health and that are a community concern

Alternative Fuels Data Center

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fueled for the fleet to be subject to the regulatory requirements. Under Standard Compliance, the AFVs that may be used toward compliance or banked once the fleet achieves compliance for investments in composition. For more information, visit the EPAct State and Alternative Fuel Provider Fleets website

R&D Nuggets

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Origin of the Chemical Elements and Their Discoveries [added 1/2007] National Laboratories and Other to the content of DOE R&D Accomplishments. Celebrating Einstein - series of articles about Albert Einstein and his work [added 3/2005] Compact Portable Electric Power Sources [added 1/2007] History of the

Fermilab | Science | Historic Results

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quark since the discovery of the bottom quark at Fermilab through fixed-target experiments in 1977. Both cosmic rays. Researchers previously had assumed that cosmic rays approach the Earth uniformly from random impact the Earth generally come from the direction of active galactic nuclei. Many large galaxies

ACHP | Defense Department Compliance with NHPA

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NHPA: Section 202(a)(6) Evaluation Report Defense Department Compliance with the National Historic )(6) Evaluation Report is a preliminary step in helping the Department of Defense marshall its Search skip specific nav links Home arrow Publications arrow Intro: Defense Department Compliance with

SIMES

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image nivo slider image nivo slider image nivo slider image nivo slider image nivo slider image Quick Energy@Stanford&SLAC LINAC Coherent Light Source (LCLS) Stanford Synchrotron Radiation Lightsource 29 30 31 1 2 3 Events (List View) No events See all events ©2012- Stanford University. All rights

Navy.mil The Official Website of the United States Navy: Home Page

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of the Navy Chief Of Naval Operations Master Chief Petty Officer Of The Navy Chief Of Naval Personnel Pentagon Hall of Heroes On May 25, Medal of Honor recipient retired Master Chief Petty Officer (SEAL Of Naval Operations Master Chief Petty Officer Of The Navy Chief Of Naval Personnel Biographies SES

ACHP | News | President Bush Issues Executive Order on Preserve America

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requirements of subsections 3(a)-(c) of this order. To assist agencies, the Council, in consultation with the Preservation Officer in accordance with section 110(c) of the NHPA. The senior official shall ensure that the public benefit from, and access to, Federally owned historic properties. (c) The Council is directed to

Publications - GMC 9 | Alaska Division of Geological & Geophysical Surveys

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; Texaco West Kavik #1; Canning River B-1; ARCO Kavik #1; Forest Kemik #1; BP Kemik #2; Canning River A-1 ; Toolik Federal #1 Authors: Curiale, J.A. Publication Date: 1982 Publisher: Alaska Division of Geological eight North Slope wells: Mobil West Staines #2; Texaco West Kavik #1; Canning River B-1; ARCO Kavik #1

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Energy-Water Nexus and Energy Systems Integration | Energy Systems

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on a new area of research geared at finding ways to balance our water use for power systems. Photo of a body of water NREL's research explores the relationship between how much water is evaporated to spectrum. Learn more about NREL's energy-water nexus research. Team with us on water-energy nexus research

NREL to Lead Novel Field Demonstration of Wind Turbine Control at the Wind

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Power Plant Level | News | NREL to Lead Novel Field Demonstration of Wind Turbine Control at the Wind Power Plant Level NREL to Lead Novel Field Demonstration of Wind Turbine Control at the Wind to test wind turbine technology controls at the overall wind power plant level. This is a significant

Alternative Fuels Data Center: Maps and Data

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2014 2015 2016 Acura 1 2 1 Audi 6 6 7 7 Bentley Motors 3 3 4 4 3 BMW 1 3 1 3 6 6 5 Buick 1 1 1 3 4 5 1 3 2 Cadillac 2 2 4 4 6 4 2 1 Chevrolet 1 2 3 1 4 4 6 5 7 7 8 7 8 9 11 10 11 14 20 26 24 30 27 Chrysler 2 2 3 2 4 1 1 1 3 3 4 2 3 3 3 3 5 5 Coda Automotive 1 1 0 Dodge 2 2 3 7 5 1 4 4 6 6 6 2 4 5 5 5 6

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

PubMed

Campos, Debora Ribeiro; Celotto, Andrea Carla; Albuquerque, Agnes Afrodite S; Ferreira, Luciana Garros; Monteiro, Ariadne Santana E Neves; Coelho, Eduardo Barbosa; Evora, Paulo Roberto Barbosa

2017-06-29

The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce. This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats. The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The effect of sclareol on blood pressure was performed by using three dose (10, 20 and 40 mg/kg). Cumulative dose-response curves for Sclareol were determined for endothelium-intact and endothelium-denuded aortic rings in presence or absence of L-NAME and ODQ. The NOx levels were measure in the plasma sample. The Sclareol administration in vivo caused a significant reduction in blood pressure in both groups. In vitro the sclareol promoted relaxation in aorta, with endothelium, pre-contracted to Phe. The inhibitors of the nitric oxide synthase and soluble guanylate cyclase were as efficient as the removal of endothelium, in inhibiting the Sclareol-induced relaxation. Otherwise, it was no change of NOx. Also, for unknown reasons, the Sclareol is not selective for hypertensive animals. The diterpene Sclareol showed in vivo hypotensive and in-vitro vasodilator effects; The chemiluminescence plasmatic NO analysis showed no significant difference between groups and The Sclareol exhibit better effect on normotensive than hypertensive animals to reduce blood pressure. It is concluded that the diterpenes metabolites would be a promising source prototype for the development of new agents in the cardiovascular therapy. O diterpeno Esclareol tem ação antimicrobiana, efeitos citotóxicos e citostáticos e atividades antitumorais. No entanto, pesquisas sobre o sistema cardiovascular são escassas. Este estudo foi desenvolvido para investigar os mecanismos envolvidos no efeito cardiovascular de Esclareol em ratos normotensos e hipertensos. A hipertensão arterial foi promovida utilizando modelo de 2 clones de 1-clipe em ratos. O efeito do esclareol sobre a pressão arterial foi realizado utilizando três doses (10, 20 e 40 mg/kg). As curvas dose-resposta cumulativas para Esclareol foram determinadas para anéis aórticos endotélio-intactos e desprovidos de endotélio na presença ou ausência de L-NAME e ODQ. Os níveis de NOx foram medidos na amostra de plasma. A administração de Esclareol in vivo causou uma redução significativa na pressão sanguínea em ambos os grupos. In vitro o esclareol promoveu relaxamento na aorta, com endotélio, pré-contraído a Phe. Os inibidores da óxido nítrico sintase e da guanilato ciclase solúvel foram tão eficientes quanto a remoção do endotélio, na inibição do relaxamento induzido por Esclareol. Por outra parte, não houve mudança de NOx. Além disso, por razões desconhecidas, o Sclareol não é seletivo para animais hipertensos. O diterpeno Esclareol apresentou efeitos hipotensores in vivo e vasodilatadores in vitro; A análise de NO plasmático por quimioluminescência não mostrou diferença significativa entre os grupos e O Esclareol exibe melhor efeito sobre os animais normotensos do que hipertensos para reduzir a pressão arterial. Conclui-se que os metabólitos de diterpenos seriam um protótipo de fonte promissora para o desenvolvimento de novos agentes na terapia cardiovascular.

Recycling

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Programación Español Listado de estación Explicacion de SAME Coverage Station Listing County Listing Search For Go NWS All NOAA Lista de Emisora y Cobertura Seleccione aquí para radiofrecuencias (La lista Transmitter Outages FAQ NWR - Special Needs ESPAÑOL Español Condado de cobertura Listado de estación Lista

Concentrating Solar Power Projects - Morón | Concentrating Solar Power |

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, 2018 Project Overview Project Name: Morón Country: Spain Location: Morón de la Frontera (Seville ? Background Technology: Parabolic trough Status: Operational Country: Spain City: Morón de la Frontera Region NREL Morón This page provides information on Morón, a concentrating solar power (CSP) project

Index of /data/nccf/com/gens/prod

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From Nigel Lockyer: Five things you should know | News

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Financial Officer Finance Section Office of the Chief Operating Officer Facilities Engineering Services Accelerator Division Accelerator Physics Center Office of the Chief Safety Officer Environment, Safety, Health and Quality Section Office of the Chief Project Officer Office of Project Support Services Office of

MicroBooNE project team recognized by Department of Energy | News

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DGIC Interconnection Insights | Distributed Generation Interconnection

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Power Association (SEPA), produced a webinar Utility Participation in the Roof Top Solar PV Market with ). These leaders are pioneering utility-owned rooftop solar programs to broaden the reach of solar PV utility hired solar PV developers who, representing CPS Energy, will install, own, and maintain solar

Solar Plus: A Holistic Approach to Distributed Solar PV | Solar Research |

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NREL Plus: A Holistic Approach to Distributed Solar PV Solar Plus: A Holistic Approach to Distributed Solar PV A new NREL report analyzes "solar plus," an emerging approach to distributed solar photovoltaic (PV) deployment that uses energy storage and controllable devices to optimize

2015 PV Solar Resource Workshop | Photovoltaic Research | NREL

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PV Solar Resource Workshop 2015 PV Solar Resource Workshop Friday, February 27, 2015 Chairs understand the solar resource available to PV plants and opportunities for the community to improve over the as Adobe Acrobat PDFs. Solar Resource Needs for Prediction and Monitoring of PV Performance

The New Jersey Water Resources Research Institute at Rutgers NJAES

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Rutgers New Jersey Agricultural Experiment Station [The New Jersey Water Resources Research wetland Program Areas The New Jersey Water Resources Research Institute (NJWRRI) is a federally-funded water in the state. Its mission is to: sponsor research on all aspects of water quality, water quantity

Energy Systems Integration Facility Insight Center | Energy Systems

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simulation data. Photo of researchers studying data on a 3-D power system profile depicting the interaction of renewable energy resources on the grid. Capabilities The Insight Center offers the following Integration Facility Insight Center Located adjacent to the Energy System Integration Facility's High

NREL Leads Wind Farm Modeling Research - Continuum Magazine | NREL

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ten 2-MW Bonus wind turbines. Photo provided by HC Sorensen, Middelgrunden Wind Turbine Cooperative ) has created complex computer modeling tools to improve wind turbine design and overall wind farm activity surrounding a multi-megawatt wind turbine. In addition to its work with Doppler LIDAR, the

@NWTC Newsletter: Summer 2014 | Wind | NREL

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, Developmental Role in Major Wind Journal Boosting Wind Plant Power Output by 4%-5% through Coordinated Turbine . Part 2: Wind Farm Wake Models New Framework Transforms FAST Wind Turbine Modeling Tool (Fact Sheet ) Sensitivity Analysis of Wind Plant Performance to Key Turbine Design Parameters: A Systems Engineering

Geothermal Energy Basics | NREL

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Geothermal Energy Basics Geothermal Energy Basics Many technologies have been developed to take advantage of geothermal energy-the heat from the earth. This heat can be drawn from several sources: hot hot spring. The Earth's heat-called geothermal energy-escapes as steam at a hot springs in Nevada

Nuclear and Particle Physics, Astrophysics and Cosmology : T-2 : LANL

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linked in Search T-2, Nuclear and Particle Physics, Astrophysics and Cosmology T-2 Home T Division Focus Areas Nuclear Information Service Nuclear Physics Particle Physics Astrophysics Cosmology CONTACTS Group energy security, heavy ion physics, nuclear astrophysics, physics beyond the standard model, neutrino

99aa/99ac data sets

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-redshifted), Observed Flux, Statistical Error (Based on the optimal extraction algorithm of the IRAF packages were acquired using different instrumental settings for the blue and red parts of the spectrum to avoid extracted for systematics checks of the wavelength calibration. Wavelength and flux calibration were applied

PEER Annual Meeting | Events

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window. 2018 PEER Annual Meeting, Jan 18-19, 2018 in Berkeley, CA 2016 PEER Annual Meeting, Jan 28-29 home about peer news events research products laboratories publications nisee b.i.p. members education FAQs links Events Calendar of PEER and Other Events PEER Events Archive PEER Annual Meeting 2009

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Nicholas Brunhart-Lupo | NREL

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. Education Ph.D., Computer Science, Colorado School of Mines M.S., Computer Science, University of Queensland B.S., Computer Science, Colorado School of Mines Brunhart-Lupo Nicholas Brunhart-Lupo Computational Science Nicholas.Brunhart-Lupo@nrel.gov

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Smithsonian Marine Station at Fort Pierce Website Search Box Search Field: SMS Website Search Search Submit: Submit Advanced Search IRLSI Home Search the Inventory The IRL Stewardship IRL Photo Institution Privacy SMS Home Contact Us Search NMNH Home DCSIMG

Index of /data/nccf/com/nam/prod

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WPC Maximum Heat Index Forecasts

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Forecasts for Western US CLICK ON MAPS FOR MAXIMUM HEAT INDEX AND PROBABILITY FORECASTS FROM SUN MAY 27 2018 02 CLICK to view SAT JUN 02 forecast SUN JUN 03 CLICK to view SUN JUN 03 forecast SUN JUN 03 CLICK to view SUN JUN 03 forecast SUN JUN 03 CLICK to view SUN JUN 03 forecast SUN JUN 03 CLICK to view SUN JUN

River Flow Advisory Commission: Snow Survey

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Survey River Watch Home → Snow Survey RFAC Information About Us Reports Maine Cooperative Snow Survey About the Snow Survey Snow Survey Map Compare Snow Survey Data Snow Survey Graphs River Watch MEMA Home USGS (Maine) Home Maine Cooperative Snow Survey This information is provided by a partnership with

Bobi A. Garrett - Deputy Laboratory Director and Chief Operating Officer

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| NREL Bobi A. Garrett - Deputy Laboratory Director and Chief Operating Officer Bobi A. Garrett - Deputy Laboratory Director and Chief Operating Officer A photo of Bobi A. Garrett, Deputy Laboratory Director and Chief Operating Officer In her role as deputy laboratory director/chief operating officer (COO

Sistema de Vigilancia de Influenza de Puerto Rico |

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Rico VIH Publicaciones sobre la Salud Otras Publicaciones Registros Suicidio Tuberculosis Centro de Suicidio Tuberculosis Recent Ávisos Públicos Reglamentación Informe de Casos del Síndrome de Guillain Departamento de Salud de Puerto Rico Departamento de Salud Search... Search It looks like your

ACHP | News

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§ 800.10(c) provides further direction for the ACHP to consider requesting the preparation of a Reports Background. Section 213 of the National Historic Preservation Act (NHPA) [16 U.S.C. § 470u ] directs the Secretary of the Interior (Secretary), if requested by the Chairman of the Advisory Council on

Supercell and tornado roles

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where C is the storm motion vector, and k is the unit vector in the vertical (Davies-Jones et al. 1990 mutually interacting perspectives, each addressing different aspects of the supercell storms most directly marked by low clouds, extending to the left. Photograph © 2005 C. Doswell 4. Developing a conceptual

Exploring Renewable Energy Integration in California - Text Version |

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look at different penetrations of solar and understand how the duck chart shape change and how much analyses and different scenario analyses to understand the key drivers behind these challenges. Today, we each of our different scenarios. We have three different renewable portfolios that we looked at. On the

Presentations - Herriott, T.M. and others, 2015 | Alaska Division of

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Details Title: Sequence stratigraphic framework of the Upper Jurassic Naknek Formation, Cook Inlet forearc Resident Business in Alaska Visiting Alaska State Employees DGGS State of Alaska search Alaska Division of ., Wartes, M.A., and Decker, P.L., 2015, Sequence stratigraphic framework of the Upper Jurassic Naknek

Defenselink Special: Remembering September 11, 2001 - Six Years Later ...

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Sept. 11 Memorial observance, honoring the 184 people who perished when American Airline 77 crashed observance today honoring the 184 people who perished when American Airlines Flight 77 crashed into the , Irwin gets emotional quickly when talking about the day that 184 people died here. One-hundred twenty

Wind Data | Geospatial Data Science | NREL

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Class 3 or greater are suitable for most utility-scale wind turbine applications, whereas class 2 areas ) with adequate wind resource for wind turbine applications may exist in some Class 1 areas. The degree Wind Data Wind Data These datasets detail the wind resource available in the United States. 50-m

Publications | Wind | NREL

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-specific analysis can be used to assess the risk induced by loss of a wind turbine blade. The study used for different wind turbine configurations. The authors used assumptions specific to the National Wind ., failure rate for wind turbine rotors) are based on a 13-year-old report on wind turbines installed in

NREL: Renewable Resource Data Center - Wind Resource Information

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and Actual Wind Turbine Sites (September 1982) and a Wind Energy Resource Atlas of the United States Wind Resource Information Photo of five wind turbines at the Nine Canyon Wind Project. The Nine Canyon Wind Project in Benton County, Washington, includes 37 wind turbines and 48 MW of capacity

NREL Research Determines Integration of Plug-in Electric Vehicles Should

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transportation and energy systems engineer at NREL and author of the new Nature Energy paper, "Impact of Muratori, author of the new Nature Energy paper "Impact of Uncoordinated Plug-in Electric Vehicle Integration of Plug-in Electric Vehicles Should Play a Big Role in Future Electric System Planning News

Publications - SR 65 | Alaska Division of Geological & Geophysical Surveys

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; Geophysical Surveys Comments: Your help is crucial in the compilation of future Alaska Minerals Reports. The quality and completeness of the information in these annual reports is dependent on input from all members of the mineral industry. Please take time to fill out the current mining and mineral activity

Publications - SR 52 | Alaska Division of Geological & Geophysical Surveys

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; Geophysical Surveys Comments: Your help is crucial in the compilation of future Alaska Minerals Reports. The quality and completeness of the information in these annual reports is dependent on input from all members of the mineral industry. Please take time to fill out the current mining and mineral activity

SuperCDMS - Home

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radiation and therefore it cannot be seen, which has earned it the title Dark Matter. Dark matter rest (approximately three quarters) of all the matter and energy in the universe is referred to as dark energy. Dark matter is most commonly hypothesized to be made up of exotic particles such as WIMPS (Weakly

Press Release | News | Page 2

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: Attend a Dark Matter Day event October 23, 2017 The world will soon be celebrating the hunt for the universe's most elusive matter in a series of Dark Matter Day events planned in over a dozen countries reveals most accurate measurement of dark matter structure in the universe August 3, 2017 Dark Energy

Press Release | News | Page 3

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, technology, engineering and math fields. New world-leading limit on dark matter search from PICO experiment February 27, 2017 The PICO-60 dark matter bubble chamber experiment has produced a new dark matter limit . Construction of world's most sensitive dark matter detector moves forward September 26, 2016 LUX-ZEPLIN (LZ), a

New Jersey | Midmarket Solar Policies in the United States | Solar Research

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| NRELA> Jersey New Jersey An arrow graphic shows that New Jersey's renewable portfolio standard property by a renewable system is exempt from property tax. Utility Incentive Programs The Board of Public incentive programs. Renewable Portfolio Standard New Jersey Board of Public Utilities: RPS Background New

Joint Center for Energy Storage Research

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singly charged lithium ions in the lithium-ion battery by new doubly or triple charged ions. Learn More Cells that Run on Air Scientists at UIC and Argonne Produce New Design of a True Lithium-air Battery phones from cumbersome bricks to sleek, powerful devices was possible because of the lithium-ion

SLAC Phone Directory: Search Form

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Facilities LCLS Hard X-Ray LCLS IT & Networking LCLS IT Photon Systems LCLS Instrumentation Dev LCLS Delivery Dept LCLS Science Research & DevDiv LCLS Soft X-Ray LCLS Technical Support LCLS User Beam Line Ops Sup SSRL MSD Hard X-rays SSRL MSD Soft X-rays SSRL MSDBeam Line Elec SSRL MSDBeam Line

Inventory of File nam.t00z.smartconus00.tm00.grib2

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(Eta model reduction) [Pa] 014 planetary boundary layer WDIR analysis Wind Direction (from which blowing) [degtrue] 015 planetary boundary layer WIND analysis Wind Speed [m/s] 016 planetary boundary layer RH analysis Relative Humidity [%] 017 planetary boundary layer DIST analysis Geometric Height [m

Richard T. (Rick) Elander | NREL

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T. (Rick) Elander Photo of Rick Elander Richard Elander Researcher VI-Chemical Engineering Chemicals and AIChE Annual Meeting, multiple years Education M.S., Chemical Engineering (Biochemical Engineering), Colorado State University B.S., Chemical Engineering, University of Pennsylvania Professional

Photovoltaic Lifetime Project | Photovoltaic Research | NREL

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PV & Solar Resource Testing Accelerated Testing & Analysis Systems Engineering Project Sandia National Laboratories' PV Performance Modeling Collaborative website. Jinko Solar. PV systems mounted on the ground. Jinko Solar PV Lifetime installation at NREL. need-alt Light-induced degradation

Solar Photovoltaic Technology Basics | NREL

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For more information about solar photovoltaic energy, visit the following resources: Solar PV Photovoltaic Technology Basics Solar Photovoltaic Technology Basics Solar cells, also called photovoltaic (PV) cells by scientists, convert sunlight directly into electricity. PV gets its name from the

Alaska Department of Natural Resources

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Information Information Resource Management Information Resource Management (IRM) maintains the department's DNR's site DNR State of Alaska Toggle main menu visibility Home Contact Us Information Resource Management Recorder's Office/UCC Recorder's Office Recorder's Office Search Uniform Commercial Code (UCC) UCC

Publications | Geothermal Technologies | NREL

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Publications Publications NREL publishes a variety of publications related to geothermal energy geothermal energy research. Featured Publications Mexico's Geothermal Market Assessment Report NREL Technical investment in the country's geothermal energy sector. Since 2013, Mexico has enacted comprehensive reforms to

Pesticide Ingredients

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; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Fact Sheets Types of Pesticides Pest Control Information Pesticide Health and Safety Information

International Pesticide Regulations

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; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure - World Health Organization (WHO) International Agencies: International Websites on Pesticides - OECD

Ella Zhou | NREL

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. 2015. Methods for Analyzing the Economic Value of Concentrating Solar Power with Thermal Energy in the United States, Potential Lessons for ChinaPDF. Golden, CO: National Renewable Energy . Renewable Electricity: Insights for the Coming DecadePDF. Golden, CO: National Renewable Energy Laboratory

Ramin Faramarzi | NREL

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Ramin Faramarzi Photo of Ramin Faramarzi Ramin Faramarzi Researcher V-Mechanical Engineering Engineering, California State University B.S. Mechanical Engineering, North Carolina State University articles and is a registered mechanical engineer in the state of California. Education M.S. Mechanical

Environmental Stewardship

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. Protecting the present through resource management The Laboratory actively manages and protects resources on shared land. Through biological monitoring, the Laboratory strives to minimize operational impacts to plants and animals. Through collaboration with its stakeholders and local tribal governments, the

Home Energy Saver Pro

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welcome your suggestions and feedback. Environmental Protection Agency logo PIER logo Touchstome Energy Cooperatives logo California Air Resouces Board logo Infosys logo Berkeley Lab logo Created for the US the HES API for your projects Department of Energy logo

RadWorks Project. ISS REM - to - BIRD - to - HERA: The Evolution of a Technology

NASA Technical Reports Server (NTRS)

McLeod, Catherine D.

2015-01-01

The advancement of particle detectors based on technologies developed for use in high-energy physics applications has enabled the development of a completely new generation of compact low-power active dosimeters and area monitors for use in space radiation environments. One such device, the TimePix, is being developed at CERN, and is providing the technology basis for the most recent line of radiation detection devices being developed by the NASA AES RadWorks project. The most fundamental of these devices, an ISS-Radiation Environment Monitor (REM), is installed as a USB device on ISS where it is monitoring the radiation environment on a perpetual basis. The second generation of this TimePix technology, the BIRD (Battery-operated Independent Radiation Detector), was flown on the NASA EFT-1 flight in December 2014. Data collected by BIRD was the first data made available from the Trapped Belt region of the Earth's atmosphere in over 40 years. The 3rdgeneration of this technology, the HERA (Hybrid Electronic Radiation Assessor), is planned to be integrated into the Orion EM-1, and EM-2 vehicles where it will monitor the radiation environment. For the EM-2 flight, HERA will provide Caution and Warning notification for SPEs as well as real time dose measurements for crew members. The development of this line of radiation detectors provide much greater information and characterization of charged particles in the space radiation environment than has been collected in the past, and in the process provide greater information to inform crew members of radiation related risks, while being very power and mass efficient.

2004 Environmental Mutagen Society Annual Meeting - Genes, Mutations and Disease: The Environmental Connection

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Samson, Leona D.

2004-08-23

The Meeting consisted of 9 Symposia, 4 Keynote Lectures, 3 Platform Sessions and 4 Poster Sessions. In addition there were Breakfast Meetings for Special Interest Groups designed to inform attendees about the latest advances in environmental mutagenesis research. Several of the topics to be covered at this broad meeting will be of interest to the Department of Energy, Office of Science. The relevance of this meeting to the DOE derives from the fact that low dose radiation may represent one of the most significant sources of human mutations that are attributable to the environment. The EMS membership, and those whomore » attended the EMS Annual Meeting were interested in both chemical and radiation induced biological effects, such as cell death, mutation, teratogenesis, carcinogenesis and aging. These topics thate were presented at the 2004 EMS Annual meeting that were of clear interest to DOE include: human variation in cancer susceptibility, unusual mechanisms of mutation, germ and stem cell mutagenesis, recombination and the maintenance of genomic stability, multiple roles for DNA mismatch repair, DNA helicases, mutation, cancer and aging, Genome-wide transcriptional responses to environmental change, Telomeres and genomic stability: when ends don?t meet, systems biology approach to cell phenotypic decision processes, and the surprising biology of short RNAs. Poster and platform sessions addressed topics related to environmental mutagen exposure, DNA repair, mechanisms of mutagenesis, epidemiology, genomic and proteomics and bioinformatics. These sessions were designed to give student, postdocs and more junior scientists a chance to present their work.« less

Christopher Kinchin | NREL

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Kinchin Photo of Christopher Kinchin Christopher Kinchin Researcher III-Chemical Engineering . Education B.S., Chemical Engineering, Texas Tech University M.S., Chemical Engineering, University of North

Golden Rays - July 2017 | Solar Research | Solar Research | NREL

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Operator, First Solar, and NREL tested a 300-MW PV plant to demonstrate that, with proper controls, PV can technique to measure charge-carrier transport in PV materials. Solar Plus: A Holistic Approach to Distribution Solar PV By optimizing how PV interacts with other electricity loads at the household- and grid

EMC: Mesoscale Branch FAQ

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THE QPF DIFFERENT BETWEEN THE 12-KM NAM PARENT DOMAIN AND THE 4-KM NAM CONUS NEST? (04 Nov 2011) WHAT 28 MAR 2000? Eta Post Processor WHY IS THE SLP DIFFERENT BETWEEN AWIPS AND AFOS? (updated 6 Nov 98 IN THE BUFR OUTPUT DIFFERENT FROM WHAT IS OBSERVED? Eta Data Assimilation System (EDAS) COMMENTS ON

Western Wind Data Set | Grid Modernization | NREL

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replicates the stochastic nature of wind power plant output. NREL modeled hysteresis around wind turbine cut where wind speeds are often near wind turbine cut-out (~25 m/s), SCORE output does not replicate the Vestas V90). The hysteresis-corrected SCORE is an attempt to put the wind turbine hysteresis at cut-out

Wind Energy | Climate Neutral Research Campuses | NREL

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turbine or wind farm is one of the few technologies that supplies renewable energy at the scale required . Before determining whether a site is suitable for a wind turbine, read the Wind Energy Siting Handbook Community College has installed a wind turbine on site and now offers an Associate Degree in wind energy and

Glossary | Efficient Windows Collaborative

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double-hung windows as a means of counterbalancing the weight of the sash during opening and closing. Bay a fixed sash or a double-hung window. Also referred to as bead stop. Blackbody. The ideal, perfect member of the lower sash which meet at the middle of a double-hung window. Clerestory. A window in the

Publications - PDF 97-29I | Alaska Division of Geological & Geophysical

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igneous rocks of the Tanana B-1 Quadrangle and vicinity Authors: Newberry, R.J., and Haug, S.A , and Sr isotopic data for igneous rocks of the Tanana B-1 Quadrangle and vicinity: Alaska Division of ; Isotopes; Plutonic; STATEMAP Project; Trace Elements; Volcanic Top of Page Department of Natural Resources