Parámetros sagitales espino-pélvicos en una población asintomática Argentina

PubMed Central

Guiroy, Alfredo; Gagliardi, Martín; Sícoli, Alfredo; Masanés, Nicolás Gonzalez; Ciancio, Alejandro Morales; Jalón, Pablo; Mezzadri, Juan José

2018-01-01

Resumen Introducción: Analizar y describir los parámetros sagitales espinales y pelvianos de una serie de 100 voluntarios argentinos. Métodos: Se realizaron prospectivamente espinogramas digitalizados de perfil a 100 voluntarios (30 hombres y 70 mujeres), con un promedio de edad 34,14 años. Todos los voluntarios eran asintomáticos al momento de realizarse el estudio. Los espinogramas se hicieron en un equipo Kodak Elite CR. Se realizaron las mediciones usando el software Surgimap®, versión 2.2.9.9.2. Se tomaron los siguientes parámetros: C7 SVA, C2-C7 CL, TK, LL, TPA, T1 tilt, PI, PT, SS, ángulo L4-S1, ángulo L1-L4, PI-LL y CTPA. Los datos fueron analizados empleando el paquete estadístico Medcalc 11.2. Se determinaron las estadísticas descriptivas adecuadas para cada variable según su escala de medición y distribución. Se realizó la estimación de intervalos de referencia del 95% y de intervalos de confianza del 95% para todas las variables. Así, el nivel de significación obtenido fue igual a 0.05. Se dividió a los voluntarios según la clasificación morfométrica de Roussouly en cuatro tipos. Resultados: El promedio para cada variable fue CL −10.04, TK 30.14, T1SPi −6.5, L1-L4 −12.45, L4-S1 −46.16, CTPA 2.5, TPA 4.65, PT 11.22, PI 48.04, LL −59.10, PI-LL −11.11, C7 SVA mm −23.68. Los ±2 desvíos estándar para cada variable fueron: CL (−33.26, 13.12); TK (17.15, 43.30); T1SPi (−11.78, −1.25), L1-L4 (−25.55, 0.25), L4-S1 (−64.44, −27.55), CTPA (0.33, 4.80), TPA (−8.64, 18.22), PT (−1.99, 24.75), PI (25.23, 71.44), LL (−78.74, −39.89), PI-LL (−29.10, 7.04), C7 SVA mm (−79.45, 32.08). Conclusión: En esta serie prospectiva de 100 adultos voluntarios se determinaron los valores de normalidad de los parámetros sagitales espinales y pelvianos en una población de Argentina. PMID:29430329

Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases

PubMed Central

Fan, Yun; Xu, Yanjun; Gong, Lei; Fang, luo; Lu, Hongyang; Qin, Jing; Han, Na; Xie, Fajun; Qiu, Guoqin; Huang, Zhiyu

2017-01-01

EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23.9–30.1 months). There was no difference in OS between the RT followed by icotinib group and the icotinib alone group (31.9 vs. 27.9 months, P = 0.237), and similar results were found in the SRS subgroup (35.5 vs. 27.9 months, P = 0.12). Patients with the EGFR Del19 mutation had a longer OS than patients with the exon 21 L858R mutation (32.7 vs. 27.4, P = 0.037). Intracranial progression-free survival (PFS) was improved in the patients who received RT followed by icotinib compared to those receiving icotinib alone (22.4 vs. 13.9 months, P = 0.043). Patients with EGFR-mutant adenocarcinoma and BM treated with icotinib exhibited prolonged survival. A longer duration of intracranial control was observed with brain RT. PMID:28332624

Effects of icotinib with and without radiation therapy on patients with EGFR mutant non-small cell lung cancer and brain metastases.

PubMed

Fan, Yun; Xu, Yanjun; Gong, Lei; Fang, Luo; Lu, Hongyang; Qin, Jing; Han, Na; Xie, Fajun; Qiu, Guoqin; Huang, Zhiyu

2017-03-23

EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23.9-30.1 months). There was no difference in OS between the RT followed by icotinib group and the icotinib alone group (31.9 vs. 27.9 months, P = 0.237), and similar results were found in the SRS subgroup (35.5 vs. 27.9 months, P = 0.12). Patients with the EGFR Del19 mutation had a longer OS than patients with the exon 21 L858R mutation (32.7 vs. 27.4, P = 0.037). Intracranial progression-free survival (PFS) was improved in the patients who received RT followed by icotinib compared to those receiving icotinib alone (22.4 vs. 13.9 months, P = 0.043). Patients with EGFR-mutant adenocarcinoma and BM treated with icotinib exhibited prolonged survival. A longer duration of intracranial control was observed with brain RT.

Relationship of Estuarine Plant Contaminants to Existing Data Bases

DTIC Science & Technology

1988-02-01

shipyards. 3) Mouriscas - located near the old tidal-mill of Quinta das Mouriscas, a few Km west of the Aguas de Moura channel. The fine sediments...globulus) from natural (mean values) and industrialized areas (maximum values) in the Chile coast. (Gonzilez & Bergqvist, 1986). NATURAL HEAVILY...Sector del Secano Costero de Ia V Re- gion. Agricultura Tecnica ( Chile ), 46: 299-306. HARDIMAN, R.T., Banin, A. & Jacoby, B. (1984). The Effect of Soil

Discovery and characterization of a novel irreversible EGFR mutants selective and potent kinase inhibitor CHMFL-EGFR-26 with a distinct binding mode

PubMed Central

Chen, Cheng; Yu, Kailin; Zou, Fengming; Wang, Wenchao; Wang, Wei; Wu, Jiaxin; Liu, Juan; Wang, Beilei; Wang, Li; Ren, Tao; Zhang, Shanchun; Yun, Cai-Hong; Liu, Jing; Liu, Qingsong

2017-01-01

EGFR T790M mutation accounts for about 40-55% drug resistance for the first generation EGFR kinase inhibitors in the NSCLC. Starting from ibrutinib, a highly potent irreversible BTK kinase inhibitor, which was also found to be moderately active to EGFR T790M mutant, we discovered a highly potent irreversible EGFR inhibitor CHMFL-EGFR-26, which is selectively potent against EGFR mutants including L858R, del19, and L858R/T790M. It displayed proper selectivity window between the EGFR mutants and the wide-type. CHMFL-EGFR-26 exhibited good selectivity profile among 468 kinases/mutants tested (S score (1)=0.02). In addition, X-ray crystallography revealed a distinct “DFG-in” and “cHelix-out” inactive binding mode between CHMFL-EGFR-26 and EGFR T790M protein. The compound showed highly potent anti-proliferative efficacy against EGFR mutant but not wide-type NSCLC cell lines through effective inhibition of the EGFR mediated signaling pathway, induction of apoptosis and arresting of cell cycle progression. CHMFL-EGFR-26 bore acceptable pharmacokinetic properties and demonstrated dose-dependent tumor growth suppression in the H1975 (EGFR L858R/T790M) and PC-9 (EGFR del19) inoculated xenograft mouse models. Currently CHMFL-EGFR-26 is undergoing extensive pre-clinical evaluation for the clinical trial purpose. PMID:28407693

Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes

PubMed Central

2012-01-01

Introduction The underlying pathogenic mechanism of a large fraction of DNA variants of disease-causing genes is the disruption of the splicing process. We aimed to investigate the effect on splicing of the BRCA2 variants c.8488-1G > A (exon 20) and c.9026_9030del (exon 23), as well as 41 BRCA2 variants reported in the Breast Cancer Information Core (BIC) mutation database. Methods DNA variants were analyzed with the splicing prediction programs NNSPLICE and Human Splicing Finder. Functional analyses of candidate variants were performed by lymphocyte RT-PCR and/or hybrid minigene assays. Forty-one BIC variants of exons 19, 20, 23 and 24 were bioinformatically selected and generated by PCR-mutagenesis of the wild type minigenes. Results Lymphocyte RT-PCR of c.8488-1G > A showed intron 19 retention and a 12-nucleotide deletion in exon 20, whereas c.9026_9030del did not show any splicing anomaly. Minigene analysis of c.8488-1G > A displayed the aforementioned aberrant isoforms but also exon 20 skipping. We further evaluated the splicing outcomes of 41 variants of four BRCA2 exons by minigene analysis. Eighteen variants presented splicing aberrations. Most variants (78.9%) disrupted the natural splice sites, whereas four altered putative enhancers/silencers and had a weak effect. Fluorescent RT-PCR of minigenes accurately detected 14 RNA isoforms generated by cryptic site usage, exon skipping and intron retention events. Fourteen variants showed total splicing disruptions and were predicted to truncate or eliminate essential domains of BRCA2. Conclusions A relevant proportion of BRCA2 variants are correlated with splicing disruptions, indicating that RNA analysis is a valuable tool to assess the pathogenicity of a particular DNA change. The minigene system is a straightforward and robust approach to detect variants with an impact on splicing and contributes to a better knowledge of this gene expression step. PMID:22632462

Time Delays Between Decimetric Type-Iii Bursts and Associated Hard X-Rays

NASA Astrophysics Data System (ADS)

Sawant, H. S.; Lattari, C. J. B.; Benz, A. O.; Dennis, B. R.

1990-11-01

RESUMEN. En julio de 1987, se efectuaron radio observaciones en 1.6 CHz usando la antena de 13.7-m de Itapetinga con un tiempo de resoluci5n de 3 ms. Las observaciones en rayos-X fueron obtenidas del HXRBS en SMM. Comparaciones de observaciones de 1.6 CHz con espectro dinamico en el intervalo de (1000 - 100) MHz y rayos-X duros muestran los siguientes resultados: I) en 12 casos, identificamos la continuaci6n de brotes de tipo Ill-RD hasta 1.6 GHz. ii) Por primera vez, hemos identificadopicos de rayos-X demorados en comparaci6n con el brote decimetrico tipolll-RD. Estos retardos son mas largos - 1 5 - que lo esperado ( " 100 ms) y han sido interpretados suponiendo que la emisi6n decimetrica es la 2a. ar- m6nica y esta causada por el borde delantero del excitador, mientras que los picos de los rayos-X han sido atribuidos a la entrada completa del excitador dentro de la regi6n que produce los rayos-X. ABSTRACT. In July, 1985 radio observations were made at 1.6 GHz using 13.7 m Itapetinga antenna with time resolution of 3 ms. The hard X-ray observations were obtained from HXRBS on SMM. Comparison of 1.6 GHz observations with dynamic spectra in the frequency range of (1000 - 100) MHz and hard X-rays shows the following results: i) In 12 cases, we identify continuation of type Ill-RD bursts up to 1.6 GHz suggesting presence of type Ill-RD bursts at 1.6 GHz. ii) For the first time, we have idetified hard X-ray peaks delayed in comparison to decimetric type Ill-RD bursts. These dalays are longer - 1 5 - than expected ( 100 ms) and have been interpreted assuming that the decimetric emission is at 2 nd harmonic and caused by the leading edge of the exciter, whereas peaks of X-rays have been attributed to entire entry of the exciter into the X-ray producing region. Keq : SUN BURSTS - SUN-

Virus-like attachment sites as structural landmarks of plants retrotransposons.

PubMed

Ochoa Cruz, Edgar Andres; Cruz, Guilherme Marcello Queiroga; Vieira, Andréia Prata; Van Sluys, Marie-Anne

2016-01-01

The genomic data available nowadays has enabled the study of repetitive sequences and their relationship to viruses. Among them, long terminal repeat retrotransposons (LTR-RTs) are the largest component of most plant genomes, the Gypsy and Copia superfamilies being the most common. Recently it has been found that Del lineage, an LTR-RT of Gypsy superfamily, has putative virus-like attachment (vl-att) sites. This signature, originally described for retroviruses, is recognized by retroviral integrase conferring specificity to the integration process. Here we retrieved 26,092 putative complete LTR-RTs from 10 lineages found in 10 fully sequenced angiosperm genomes and found putative vl-att sites that are a conserved structural landmark across these genomes. Furthermore, we reveal that each plant genome has a distinguishable LTR-RT lineage amplification pattern that could be related to the vl-att sites diversity. We used these patterns to generate a specific quick-response (QR) code for each genome that could be used as a barcode of identification of plants in the future. The universal distribution of vl-att sites represents a new structural feature common to plant LTR-RTs and retroviruses. This is an important finding that expands the information about the structural similarity between LTR-RT and retroviruses. We speculate that the sequence diversity of vl-att sites could be important for the life cycle of retrotransposons, as it was shown for retroviruses. All the structural vl-att site signatures are strong candidates for further functional studies. Moreover, this is the first identification of specific LTR-RT content and their amplification patterns in a large dataset of LTR-RT lineages and angiosperm genomes. These distribution patterns could be used in the future with biotechnological identification purposes.

Sentido de coherencia y mapa de activos para la salud en jóvenes presos de la Comunidad Valenciana en España.

PubMed

Vera-Remartínez, Enrique J; Paredes-Carbonell, Joan J; Aviñó Juan-Ulpiano, Dory; Jiménez-Pérez, Mercedes; Araujo Pérez, Rosa; Agulló-Cantos, José M; Mora Notario, Almudena

2017-09-01

Estudio realizado desde el enfoque de la salutogénesis que pretende determinar el sentido de coherencia (SOC) en jóvenes presos de la Comunidad Valenciana en España y elaborar un mapa de activos para la salud dirigido a promover la salud en esta población. Se utilizó el test "SOC-13" y un cuestionario de preguntas abiertas elaborado ad hoc, el cual autocompletaron los internos de 18 a 22 años de edad, de los tres centros penitenciarios de la región. Participaron 124 jóvenes varones (ya que no había ninguna mujer) y se recogieron variables sociodemográficas y penitenciarias. En el análisis cuantitativo, las variables categóricas se expresaron como frecuencias absolutas y relativas; y las cuantitativas, mediante medias con intervalos de confianza (IC) al 95%. Se realizó un estudio comparativo bivariante, utilizando las siguientes pruebas: Student t-test, análisis de variación (ANOVA), Wilcoxon y Ji-cuadrado. Del cuestionario de preguntas abiertas, se realizó un análisis cualitativo descriptivo temático de los activos identificados, clasificándolos en: internos (recursos personales, en relación con los demás y capacidad para realizar comportamientos saludables) y externos (personas, grupos, instituciones y espacios físicos, situados tanto dentro como fuera de prisión). La edad media fue de 21,1 años (IC 95%: 20,8-21,3); y el SOC de 52,4 (IC 95%: 50,5-54,3), de entre un valor mínimo de 13 y máximo de 91 para la prueba. Los internos del centro penitenciario que ofrecía más actividades escolares y deportivas obtuvieron una puntuación mayor en la dimensión de significatividad del SOC ( p = 0,024), y los internos inmigrantes presentaron un SOC superior ( p = 0,037) a los españoles, en los tres centros. Los jóvenes identificaron los activos internos que cualitativamente se vinculan con las dimensiones de comprensibilidad, manejabilidad y significatividad del SOC; y los activos externos, sobre todo los amigos, familiares y espacios relacionados con la actividad físico-deportiva, tanto dentro como fuera de prisión. Estos activos y sus interrelaciones podrían incorporarse al diseño de futuras intervenciones de promoción de la salud.

The effect of the common c.2299delG mutation in USH2A on RNA splicing.

PubMed

Lenassi, Eva; Saihan, Zubin; Bitner-Glindzicz, Maria; Webster, Andrew R

2014-05-01

Recessive variants in the USH2A gene are an important cause of both Usher syndrome and nonsyndromic retinitis pigmentosa. A single base-pair deletion in exon 13 (c.2299delG, p.Glu767Serfs*21) is considered the most frequent mutation of USH2A. It is predicted to generate a premature termination codon and is presumed to lead to nonsense mediated decay. However the effect of this variant on RNA has not been formally investigated. It is not uncommon for exonic sequence alterations to cause aberrant splicing and the aim of the present report is to evaluate the effect of c.2299delG on USH2A transcripts. Nasal cells represent the simplest available tissue to study splicing defects in USH2A. Nasal brushing, RNA extraction from nasal epithelial cells and reverse transcription PCR were performed in five Usher syndrome patients who were homozygous for c.2299delG, two unaffected c.2299delG heterozygotes and seven control individuals. Primers to amplify between exons 12 and 15 and exons 10 and 14 were utilised. Significant variability was observed between different RT-PCR experiments. Importantly, in controls, PCR product of the expected size were amplified on all occasions (13/13 experiments); for patients this was true in only 4/14 experiments (Fisher exact test p = 0.0002). Bioinformatics tools predict the c.2299delG change to disrupt an exonic splicing enhancer and to create an exonic splicing silencer within exon 13. Here, we report an effect of the common c.2299delG mutation on splicing of exons 12 and 13 of USH2A. Future studies are expected to provide important insights into the contribution of this effect on the phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of a Hybrid Detection and Location Scheme to Volcanic Systems

NASA Astrophysics Data System (ADS)

Thurber, C. H.; Lanza, F.; Roecker, S. W.

2017-12-01

We are using a hybrid method for automated detection and onset estimation, called REST, that combines a modified version of the nearest-neighbor similarity scheme of Rawles and Thurber (2015; RT15) with the regression approach of Kushnir et al. (1990; K90). This approach incorporates some of the windowing ideas proposed by RT15 into the regression techniques described in K90. The K90 and RT15 algorithms both define an onset as that sample where a segment of noise at earlier times is most "unlike" a segment of data at later times; the main difference between the approaches is how one defines "likeness." Hence, it is fairly straightforward to adapt the RT15 ideas to a K90 approach. We also incorporated the running mean normalization scheme of Bensen et al. (2007), used in ambient noise pre-processing, to reduce the effects of coherent signals (such as earthquakes) in defining noise segments. This is especially useful for aftershock sequences, when the persistent high amplitudes due to many earthquakes biases the true noise level. We use the fall-off of the K90 estimation function to assign uncertainties and the asymmetry of the function as a causality constraint. The detection and onset estimation stage is followed by iterative pick association and event location using a grid-search method. Some fine-tuning of some parameters is generally required for optimal results. We present 2 applications of this scheme to data from volcanic systems: Makushin volcano, Alaska, and Laguna del Maule (LdM), Chile. In both cases, there are permanent seismic networks, operated by the Alaska Volcano Observatory (AVO) and Observatorio Volcanológico de Los Andes del Sur (OVDAS), respectively, and temporary seismic arrays were deployed for a year or more. For Makushin, we have analyzed a year of data, from summer 2015 to summer 2016. The AVO catalog has 691 events in our study volume; REST processing yields 1784 more events. After quality control, the event numbers are 151 AVO events and 344 additional REST events. For LdM, we have analyzed 3 months of data from the beginning of 2017. The OVDAS catalog contains only 6 events. In contrast, REST processing yields over 100 events. We will show both the grid search locations and relocations obtained as part of tomographic inversions, and discuss some of the advantages and weaknesses of the REST processing scheme.

Catalogue of Main Characteristics of Pulsations of 173 Semi-Regular Stars

NASA Astrophysics Data System (ADS)

Chinarova, L. L.; Andronov, I. L.

2000-12-01

The characteristics of brightness variations of 173 semi-regular stars are tabulated: the moments and brightness of the extrema; the effective periods, amplitudes and significance obtained by using different methods: a) the periodogram analysis (harmonic least squares t) with prewhitening to determine characteristics and significance of waves with 3 periods; b) the wavelet analysis to determine characteristics of statistically significant waves; ) the "running parabola" scalegram analysis to determine the optimal filter half - width for smoothing. The characteristics may be used for more precise classification of semi-regular variables. Characteristics of the 6509 extrema of 147 stars are listed. The electronic version is available via http://ila.webjump.om. The observations for the analysis have been taken from the AFOEV and VSOLJ databases (with a duration up to 94 years) for the stars: AQ, EH, EK, RS, RU, RV, ST, TV, TY, TZ, UX, VX And; GY, PX, S, V, V844 Aql; V, Z Aqr; T Ari; AG, RS, S, UU, Z Aur; RV, RW, RX, RZ, U, V, WY Boo; T Cae; RR, RS, RY, S, ST, U Cam; RT Cap; PZ, SV, UX, V393, V465, WZ Cas; T, Y Cen; AR, RU, RW, RX, SS, TY, W Cep; T Cet; RS, RT, T, X Cnc; RR, RS, TT CrB; V, Y Cvn; AA, AF, AI, AV, AW, BC, RS, RU, RV, RW, RZ, TT, V460, W Cyg; EU, U Del; RS, RY, S, TX, UX, WZ Dra; SY, Z Eri; IS, NQ, RS, SW, TU, TV, Y Gem; DE, MZ, RR, ST, SX, UU, X Her; FF, RT, U, V, W, Y Hya; RS Lac; RY, SX Leo; RX, S Lep; U, W LMi; Y, EG, R, SZ Lyr; RV, SW, X Mon; V759 Oph; BQ, FX, GT, RT, W Ori; AF, AK, SV, TX Peg; AD, BU, DY, FZ, RS, RU, S, SU, SY, T, UZ, W, XX Per; R Pic; RT, RW, Z Psc; BM Sco; S Sct; FG Ser; X Sge; AB, TT, W, Y Tau; W Tri; RX, RY, RZ, ST,SV, V, Y, Z UMa; R, V UMi; RT, SS, SW Vir; RU Vul.

Calibración del retardo ionosférico en observaciones astrométricas y geodésicas a partir de observaciones GPS

NASA Astrophysics Data System (ADS)

Brunini, C.; Kleusberg, A.; Arias, E. F.; de Biasi, M. S.

Los parámetros astrométricos y geodésicos de precisión se determinan hoy mediante la observación con técnicas espaciales (VLBI, GPS y LSR). Las técnicas VLBI y GPS operan en la banda de microondas y en ella la ionósfera terrestre es dispersiva. Las señales que provienen de las radiofuentes y de los satélites atraviesan la ionósfera, donde el índice de refracción difiere de la unidad en una cantidad que es proporcional a la densidad de electrones libres e inversamente proporcional al cuadrado de la frecuencia de la onda portadora. Actualmente el International GPS Service for Geodynamics (IGS) mantiene operacional una red global integrada por más de 50 estaciones equipadas con receptores GPS de alta performance; las observaciones diarias son accesibles a los usuarios mediante ftp. La posibilidad de utilizar estas observaciones en un monitoreo continuo de la ionósfera fue señalada por diversos autores, razón por la cual en los últimos años se ha invertido un significativo esfuerzo en la producción de mapas ionosféricos regionales y globales. En el presente trabajo se utilizan 28 estaciones cuyas observaciones mapean la mayor parte de la ionósfera global. Los resultados obtenidos demuestran la posibilidad de obtener mapas ionosféricos globales con una resolución de medio día y con una precisión de (1.5 nseg (rms)). Dichos mapas proveen valores medios globales para el intervalo ajustado. Los residuos del ajuste por mínimos cuadrados constituyen una señal a partir de la cual pueden estudiarse mejor las variaciones geográficas de la ionósfera y las componentes estadísticas de su variación temporal.

Nonspherical Radiation Driven Wind Models Applied to Be Stars

NASA Astrophysics Data System (ADS)

Arauxo, F. X.

1990-11-01

ABSTRACT. In this work we present a model for the structure of a radiatively driven wind in the meridional plane of a hot star. Rotation effects and simulation of viscous forces were included in the motion equations. The line radiation force is considered with the inclusion of the finite disk correction in self-consistent computations which also contain gravity darkening as well as distortion of the star by rotation. An application to a typical BlV star leads to mass-flux ratios between equator and pole of the order of 10 and mass loss rates in the range 5.l0 to Mo/yr. Our envelope models are flattened towards the equator and the wind terminal velocities in that region are rather high (1000 Km/s). However, in the region near the star the equatorial velocity field is dominated by rotation. RESUMEN. Se presenta un modelo de la estructura de un viento empujado radiativamente en el plano meridional de una estrella caliente. Se incluyeron en las ecuaciones de movimiento los efectos de rotaci6n y la simulaci6n de fuerzas viscosas. Se consider6 la fuerza de las lineas de radiaci6n incluyendo la correcci6n de disco finito en calculos autoconsistentes los cuales incluyen oscurecimiento gravitacional asi como distorsi6n de la estrella por rotaci6n. La aplicaci6n a una estrella tipica BlV lleva a cocientes de flujo de masa entre el ecuador y el polo del orden de 10 de perdida de masa en el intervalo 5.l0 a 10 Mo/ano. Nuestros modelos de envolvente estan achatados hacia el ecuador y las velocidads terminales del viento en esa regi6n son bastante altas (1000 Km/s). Sin embargo, en la regi6n cercana a la estrella el campo de velocidad ecuatorial esta dominado por la rotaci6n. Key words: STARS-BE -- STARS-WINDS

Influence of correlation between HLA-G polymorphism and Interleukin-6 (IL6) gene expression on the risk of schizophrenia.

PubMed

Shivakumar, Venkataram; Debnath, Monojit; Venugopal, Deepthi; Rajasekaran, Ashwini; Kalmady, Sunil V; Subbanna, Manjula; Narayanaswamy, Janardhanan C; Amaresha, Anekal C; Venkatasubramanian, Ganesan

2018-07-01

Converging evidence suggests important implications of immuno-inflammatory pathway in the risk and progression of schizophrenia. Prenatal infection resulting in maternal immune activation and developmental neuroinflammation reportedly increases the risk of schizophrenia in the offspring by generating pro-inflammatory cytokines including IL-6. However, it is not known how prenatal infection can induce immuno-inflammatory responses despite the presence of immuno-inhibitory Human Leukocyte Antigen-G (HLA-G) molecules. To address this, the present study was aimed at examining the correlation between 14 bp Insertion/Deletion (INDEL) polymorphism of HLA-G and IL-6 gene expression in schizophrenia patients. The 14 bp INDEL polymorphism was studied by PCR amplification/direct sequencing and IL-6 gene expression was quantified by using real-time RT-PCR in 56 schizophrenia patients and 99 healthy controls. We observed significantly low IL6 gene expression in the peripheral mononuclear cells (PBMCs) of schizophrenia patients (t = 3.8, p = .004) compared to the controls. In addition, schizophrenia patients carrying Del/Del genotype of HLA-G 14 bp INDEL exhibited significantly lower IL6 gene expression (t = 3.1; p = .004) than the Del/Ins as well as Ins/Ins carriers. Our findings suggest that presence of "high-expressor" HLA-G 14 bp Del/Del genotype in schizophrenia patients could attenuate IL-6 mediated inflammation in schizophrenia. Based on these findings it can be assumed that HLA-G and cytokine interactions might play an important role in the immunological underpinnings of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fragilidad y su asociación con mortalidad, hospitalizaciones y dependencia funcional en mexicanos de 60 años o más

PubMed Central

de León González, Enrique Díaz; Pérez, Héctor Eloy Tamez; Hermosillo, Hugo Gutiérrez; Rodríguez, Javier Armando Cedillo; Torres, Gabriela

2016-01-01

Fundamento y objetivo Determinar la asociación entre fragilidad y mortalidad, dependencia funcional, caídas y hospitalizaciones en el Estudio Nacional de Salud y Envejecimiento en México (ENASEM). Sujetos y métodos Estudio prospectivo poblacional en México en el que se seleccionaron sujetos de 60 años o más, que fueron evaluados en las variables de fragilidad durante la primera vuelta del estudio en el año 2001 y que incluyó: dificultad para levantarse de una silla después de haber estado sentado(a) durante largo tiempo, pérdida de peso de 5 kilogramos o más en los últimos dos años y falta de energía. Los sujetos fueron catalogados como robustos, prefrágiles y frágiles cuando tenían cero, una o dos de las características anteriores, respectivamente. La mortalidad, hospitalizaciones, caídas y dependencia funcional fueron evaluadas en la segunda vuelta del estudio en el año 2003. Se calculó el riesgo relativo para cada una de las complicaciones, así como análisis multivariado con regresión de Cox para el caso de mortalidad y regresión logística para el resto. Resultados Los estados de prefragilidad y fragilidad se asociaron independientemente con mortalidad, con índices de riesgo ajustados de 1,61 (intervalo de confianza del 95% [IC 95%] 1,01-2,55) y 1,94 (IC 95% 1,20-3,13), respectivamente. Sólo el estado de fragilidad se asoció independientemente con hospitalización y dependencia funcional, con una razón de momios ajustada de 1,53 (IC 95% 1,13-2,07) y 3,07 (IC 95% 1,76-5,34), respectivamente. No hubo asociación entre los estados de prefragilidad y fragilidad con caídas. Conclusión El estado de fragilidad se asocia independientemente con mortalidad, hospitalizaciones y disfuncionalidad en actividades básicas de la vida diaria en los siguientes dos años en población mexicana. PMID:21612803

Modelo analítico del efecto de PRS sobre satélites GPS

NASA Astrophysics Data System (ADS)

Meza, A.; Brunini, C.; Usandivaras, J. C.

El sistema GPS (Global Position System) es, hoy en día, la herramienta de navegación y posicionamiento más potente y lo será sin duda en la próxima década. Gran parte de su valiosa utilidad se debe a la alta precisión que permite lograr y ésta, a su vez, depende, entre otras causas, de la precisión con que se conocen las órbitas de los satélites. La presión de radiación solar (PRS) fija el límite de la precisión con que pueden calcularse en la actualidad las efemérides satelitarias. El objetivo de este trabajo es proponer una mejor resolución de este fenómeno. El modelo analítico aquí presentado, se basa en el análisis del comportamiento de los residuos de un ajuste por mínimos cuadrados en el que se utiliza el modelo de PRS propuesto por Beutler. El mismo consiste en un modelo determinista del fenómeno con dos parámetros libres. Los resultados obtenidos ponen de manifiesto que, aún después de aplicar dichos parámetros, prevalecen en los residuos efectos semidiurnos en las componentes radial,tangencial y normal. Estos resultados obtenidos se comparan con los de un trabajo desarrollado por el Instituto de Berne (Beutler et al., 1994), en el que se utilizaron como pseudo-observaciones las órbitas precisas del IGS (CODE). El intervalo de integración escogido por este centro fueron las semanas 680 y 681. En resumen se tienen arcos de 14 días para todos los satélites, donde las efemérides precisas de los mismos para los 14 días fueron utilizados como pseudo-observaciones. El modelo de fuerza que empleó dicho centro fue básicamente el tradicional en lo que respecta al modelo de las fuerzas gravitacionales, y para la PRS utilizo el modelo standard de Beutler. Los parámetros de este modelo junto con las 6 condiciones iniciales (posición y velocidad) fueron ajustados por el método general de mínimos cuadrados. Los residuos en la componente radial, tangencial y normal, para los satélites con un buen comportamiento, presentan una componente semidiurna. El modelo analítico planteado en este trabajo, predice el comportamiento de los residuos que se observan en las publicaciones más recientes. Esto abre el camino para plantear una estimación distinta de las incógnitas del problema, basado en el método de colocación por mínimos cuadrados. Ello requiere modelar estadísticamente la señal debida a las componentes de la PRS que no son tomadas en cuenta en el modelo determinista.

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax.

PubMed

Anderson, Mary Ann; Tam, Constantine; Lew, Thomas E; Juneja, Surender; Juneja, Manu; Westerman, David; Wall, Meaghan; Lade, Stephen; Gorelik, Alexandra; Huang, David C S; Seymour, John F; Roberts, Andrew W

2017-06-22

The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials. Investigations at progression included positron emission tomography scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and 8 with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) ( P = .003). Among patients who received the recommended phase 2 dose of venetoclax or higher (≥400 mg/d), fludarabine refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 [95% confidence interval 1.7-28.5]; P = .002 and 6.6 [1.5-29.8]; P = .005, respectively), whereas del(17p) and/or TP53 mutation were not ( P = .75). Median postprogression survival was 13 (<1-49.9) months. Bruton tyrosine kinase inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine refractory or who have complex cytogenetics should have occult RT excluded before initiating venetoclax therapy. © 2017 by The American Society of Hematology.

Comparison among the efficacy of interventions for the return rate to receive the pap test report: randomized controlled clinical trial.

PubMed

Vasconcelos, Camila Teixeira Moreira; Pinheiro, Ana Karina Bezerra; Nicolau, Ana Izabel Oliveira; Lima, Thaís Marques; Barbosa, Denise de Fátima Fernandes

2017-03-02

to test the effects of a behavioral, an educative and a comparative intervention on women's adherence to the return appointment to receive the pap test report. randomized controlled clinical trial at a Primary Health Care Service, involving three groups: EG (educative session and test demonstration), BG (recall ribbon) and standard intervention (card containing the return appointment - graphical reminder), called comparative group here (CG). To select the sample, the following was established: having started sexual activity and undergoing the pap smear during the study, resulting in 775 women. among the 775 women, 585 (75.5%) returned to receive the test result within 65 days. The educative group presented the highest return rate (EG=82%/CG=77%/BG=66%), statistically significant only when compared to the behavioral group (p=0.000). The educative group obtained the smallest interval (p<0.05) concerning the mean number of days of return to receive the test result (EG:M=43days/BG:M=47.5days/CG:M=44.8 days). the educative group reached higher return rates and the women returned earlier, but the behavioral intervention showed to be the least effective. Brazilian Clinical Trial Register: RBR-93ykhs. testar los efectos de una intervención comportamental (GCP), educativa (GE) y otra comparativa (GCA) en la adhesión de las mujeres a la consulta de retorno para recibir el laudo de citología vaginal. estudio experimental aleatorizado controlado en una Unidad de Atención Primaria de Salud con tres grupos: GE (sesión educativa y demonstración del examen), GCP (cinta recuerdo) e intervención estándar (tarjeta con la fecha de la consulta de retorno - recuerdo gráfico), llamado de grupo comparativo (GCA). Para seleccionar la muestra, fue establecido: haber iniciado actividad sexual y hacer la citología vaginal durante el estudio, resultando en 775 mujeres. entre las 775 mujeres, 585 (75,5%) regresaron para recibir el resultado del examen con hasta 65 días. El grupo educativo presentó el mayor porcentaje de retorno (GE=82%/GCA=77%/GCP=66%), con significancia estadística sólo cuando comparado al comportamental (p=0,000). El grupo educativo alcanzó menor intervalo (p<0,05) del promedio de días de retorno para recibir el resultado del examen (GE:M=43 días/GCP:M=47,5 días/GCA:M=44,8 días). el grupo educativo alcanzó proporciones mayores de retorno, y las mujeres regresaron más precozmente, pero la intervención comportamental se mostró la menos eficaz. Registro Brasileño de Ensayo Clínico: RBR-93ykhs. testar os efeitos de uma intervenção comportamental (GCP), educativa (GE) e outra de comparação (GCA) na adesão das mulheres à consulta de retorno para receber o laudo do exame colpocitológico. estudo experimental randomizado controlado em uma Unidade de Atenção Primária à Saúde com três grupos: GE (sessão educativa e demonstração do exame), GCP (fita lembrança) e intervenção-padrão (cartão contendo a data da consulta de retorno - lembrete gráfico), aqui denominado de grupo de comparação (GCA). Para a seleção da amostra, estabeleceu-se: ter iniciado atividade sexual e realizar o exame colpocitológico durante o estudo, resultando em 775 mulheres. dentre as 775 mulheres, 585 (75,5%) retornaram para receber, o resultado do exame com até 65 dias. O grupo educativo apresentou o maior percentual de retorno (GE=82%/GCA=77%/GCP=66%), com significância estatística apenas quando comparado ao comportamental (p=0,000). O grupo educativo obteve menor intervalo (p<0,05) da média de dias de retorno para receber o resultado do exame (GE:M=43dias/GCP:M=47,5dias/GCA:M=44,8 dias) . o grupo educativo atingiu proporções maiores de retorno, e as mulheres retornaram mais precocemente, porém a intervenção comportamental mostrou-se a menos eficaz. Registro Brasileiro de Ensaio Clínico: RBR-93ykhs.

Seguridad del paciente en Radioterapia Intraoperatoria: Impacto de los elementos controlados por el Radiofisico

NASA Astrophysics Data System (ADS)

Tarjuelo, Juan Lopez

Introduccion: En la administracion de la radioterapia intervienen profesionales y equipos de tratamiento, por lo que existe el riesgo de error y se precisa que dicho equipamiento funcione conforme a lo esperado. A los radiofisicos les corresponde participar en las actividades de garantia o aseguramiento de la calidad, incluyendo el control de calidad de los equipos, y en la evaluacion de los riesgos asociados. La radioterapia intraoperatoria (RIO) es una tecnica radioterapica de intensificacion de dosis, altamente selectiva, dirigida a volumenes anatomicos restringidos durante el tratamiento quirurgico oncologico, basada en la administracion de una dosis absorbida alta por medio de un haz de electrones tras el examen visual directo del lecho tumoral. Como incorporar los ultimos avances en el refuerzo de la seguridad en radioterapia es una tarea ambiciosa y compleja, resulta mas concreta y de inmediata aplicacion su introduccion en la RIO. El objetivo es analizar los elementos que reducen los riesgos y aumentan la seguridad en la RIO y su dosimetria, y valorar la funcion del radiofisico en esta labor. Material y metodos: Se emplearon el planificador Radiance de GMV y el acelerador lineal de los tratamientos de RIO Elekta Precise, controlado con el verificador diario de haces Daily QA Check 1090 y medido con las camaras de ionizacion PPC 40, FC65-G y FC65-P de PTW-Freiburg, a su vez verificadas con fuentes radiactivas adecuadas de estroncio-90 modelos CDP y CDC de IBA Dosimetry. Se realizo un analisis de modos de fallo y efectos (failure mode and effect analysis, FMEA) con el fin de identificar los elementos que forman la RIO y aplicar las herramientas necesarias para la minimizacion de los riesgos y la mejora de la seguridad en la tecnica. Se estudiaron las verificaciones diarias de dicho acelerador Precise con el control estadistico de procesos (statistical process control, SPC) y se simularon intervenciones para devolverlo al estado llamado en control. El SPC tambien se uso para estudiar la estabilidad de las camaras de ionizacion mencionadas. Se realizo la dosimetria in vivo en 45 pacientes con MOSFET reforzados mobile TN-502RDM-H, pelicula radiocromica Gafchromic MD-55-2, y se elaboro un modelo teorico para explicar los datos. Por ultimo, al precisarse el uso en RIO de la simulacion virtual y del calculo de la dosis absorbida en el paciente virtual, se ha ilustrado este apartado con la aceptacion y el estado de referencia inicial del planificador de tratamientos modulados con calculo de Monte Carlo Elekta Monaco. Para ello se utilizaron la camara de ionizacion TW31016-0104 y la matriz seven29 de PTW-Freiburg, pelicula radiocromica Gafchromic EBT-2, y diferentes maniquies. Resultados: El FMEA identifico 57 modos de fallo y efectos potenciales. No se experimentaron sucesos relativos a una administracion inadecuada de la dosis absorbida. Se identificaron las revisiones dobles y por un par como claves para reducir los riesgos asociados al equipo de profesionales involucrado en la RIO. Se identificaron tambien oportunidades de mejora con el uso de la automatizacion y el enclavamiento. En cuanto al SPC, los indices de capacidad del proceso abarcaron de 1,6 a 9,3 para un nivel de especificaciones del +/-2%. Las intervenciones simuladas alcanzaron del 2% al 34% de las sesiones de medida. Las camaras de ionizacion Farmer derivaron en direcciones opuestas en un periodo de 6 anos; aunque ello no se aprecio en los informes de calibracion del laboratorio acreditado. No derivo la camara PPC-40. En la dosimetria in vivo, las medidas de los MOSFET no se desviaron significativamente de las medidas con pelicula. Los valores centrales de las dosis absorbidas quedaron entre la dosis absorbida prescrita y la maxima, con lo que indicaron un tratamiento correcto del lecho tumoral. Las anchuras de los intervalos de confianza de las dosis absorbidas esperadas segun el modelo teorico al nivel del 95% abarcaron del 8,6% al 14,7%. Las verificaciones de Monaco resultaron satisfactorias excepto en el caso de la transferencia de datos, que obligo a cambiar el flujo de trabajo. Conclusiones: El FMEA es crucial para priorizar las intervenciones reductoras del riesgo. Tipos diferentes de procesos fallidos se pueden eliminar o paliar con tipos diferentes de tales intervenciones. El SPC puede evaluar la variabilidad inherente del procedimiento monitorizador de haces de electrones, indica cuando intervenir para devolver un proceso al estado de control y si un proceso es capaz con respecto a unas especificaciones o requisitos establecidos. Es viable realizar dosimetria in vivo con un acelerador convencional fijo y obtener resultados satisfactorios en cada localizacion estudiada a pesar de su variabilidad. El modelo teorico desarrollado puede describir con exito resultados globales, aunque no puede explicar todos los datos experimentales. Se ha mostrado que un planificador puede funcionar correctamente en condiciones de laboratorio o trabajando solo; pero puede fallar cuando se conecta con otros equipos de radioterapia. Todos estos aspectos presentados y evaluados aqui constituyen competencias actuales o futuras, y deseables, de los radiofisicos, tanto en el campo de la RIO como en la extension a la radioterapia en su conjunto.

DUCHAS VAGINALES Y OTROS RIESGOS DE VAGINOSIS BACTERIANA

PubMed Central

Chávez, Natividad; Molina, Helfer; Sánchez, Jorge; Gelaye, Bizu; Sánchez, Sixto E.

2010-01-01

Vaginosis bacteriana (VB) es una infección caracterizada por el cambio en la microflora de la vagina, asociándose a resultados adversos del embarazo y a la adquisición de infecciones de transmisión sexual (ITS), incluyendo el VIH. En este estudio se buscó la asociación entre el uso de duchas vaginales y otros factores de riesgos con VB. Se usó un diseño observacional descriptivo transversal prospectivo, en 1,252 mujeres que asistieron al servicio de planificación familiar de tres hospitales nacionales (Dos de Mayo, Arzobispo Loayza, San Bartolomé) y el Instituto Materno Perinatal, durante el año 1997. Se utilizó un cuestionario estructurado donde se registraron variables socio demográficas y características del estilo de vida de las participantes. VB fue diagnosticada mediante el puntaje de Nugent. Se empleó análisis de regresión logística para calcular odds ratio (OR) e intervalos de confianza al 95%. La edad promedio de las participantes fue 25.1 ± 4,7 años, el 23.4% tenían más de 11 años de educación. La prevalencía de VB fue 20,1%. Las mujeres que practicaban duchas vaginales tuvieron 2.28 veces (OR = 2.28, IC 95% [1.0–5.0]) mayor probabilidad de tener VB comparado con aquellas que no lo practicaban. Tener dos o más parejas sexuales estuvo asociado con 2.0 veces (OR =2.0, IC 95% [1.2–3.5]) mayor probabilidad de adquirir VB comparado con aquellas que habían tenido solo una pareja sexual. Las participantes que iniciaron una relación sexual a una edad temprana tuvieron 1.4 veces (OR=1.4, IC 95% [1.0 –1.9]) mayor probabilidad de adquirir VB. El uso de duchas vaginales es un factor de riesgo de VB. Los programas destinados a la salud de la mujer deben abordar las repercusiones perjudiciales para la salud asociados con las duchas vaginales. PMID:21132048

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis.

PubMed

de Haas, S; Ghossein-Doha, C; van Kuijk, S M J; van Drongelen, J; Spaanderman, M E A

2017-02-01

To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07-1.19 L), an increase of 45.6% (95% CI, 43.0-48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59-1.02 L), an increase of 32.3% (95% CI, 23.6-41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001). During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptación fisiológica del volumen del plasma materno durante el embarazo: una revisi\\xF3n sistemática y metaanálisis RESUMEN OBJETIVO: Describir el patrón fisiológico de los cambios en el volumen del plasma gestacional en embarazos normales con feto único y compararlo con el patrón en los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal. MÉTODOS: Se realizó un metaanálisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiológicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmático (no embarazada, antes del embarazo o después del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmático a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird. En el metaanálisis se incluyeron treinta estudios con fechas de publicación entre 1934 y 2007. El volumen plasmático aumentó en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuó aumentando en el tercer trimestre con un aumento combinado máximo de 1,13L (IC 95%, 1,7-1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0-48,1%) en embarazos fisiológicas en comparación con el valor de referencia. El aumento del volumen plasmático en los embarazos con hipertensión y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59-1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6-41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiológicos (P <0,0001). Durante el embarazo fisiológico el volumen de plasma aumenta, en promedio, más de 1L, en comparación con el de las no embarazadas. En los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal, el aumento del volumen plasmático en el tercer trimestre es un 13,3% menor que en el embarazo normal. :meta : ,、。 : meta。PubMed(NCBI)EMBASE(Ovid)。(、)。DerSimonianLaird,。 : Meta30,19342007。,。,1.13 L(95% CI,1.07~1.19 L),,45.6%(95% CI,43.0%~48.1%)。0.80 L(95%CI,0.59~1.02 L),32.3%(95% CI,23.6%~41.1%),(P<0.0001)。 : ,,1 L。、,13.3%。. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Overexpression of Multiple Detoxification Genes in Deltamethrin Resistant Laodelphax striatellus (Hemiptera: Delphacidae) in China

PubMed Central

Xu, Lu; Wu, Min; Han, Zhaojun

2013-01-01

Background The small brown planthopper (SBPH), Laodelphax striatellus (Fallén), is one of the major rice pests in Asia and has developed resistance to multiple classes of insecticides. Understanding resistance mechanisms is essential to the management of this pest. Biochemical and molecular assays were performed in this study to systematically characterize deltamethrin resistance mechanisms with laboratory-selected resistant and susceptible strains of SBPH. Methodology/Principal Findings Deltamethrin resistant strains of SBPH (JH-del) were derived from a field population by continuously selections (up to 30 generations) in the laboratory, while a susceptible strain (JHS) was obtained from the same population by removing insecticide pressure for 30 generations. The role of detoxification enzymes in the resistance was investigated using synergism and enzyme activity assays with strains of different resistant levels. Furthermore, 71 cytochrome P450, 93 esterases and 12 glutathione-S-transferases cDNAs were cloned based on transcriptome data of a field collected population. Semi-quantitative RT-PCR screening analysis of 176 identified detoxification genes demonstrated that multiple P450 and esterase genes were overexpressed (>2-fold) in JH-del strains (G4 and G30) when compared to that in JHS, and the results of quantitative PCR coincided with the semi-quantitative RT-PCR results. Target mutation at IIS3–IIS6 regions encoded by the voltage-gated sodium channel gene was ruled out for conferring the observed resistance. Conclusion/Significance As the first attempt to discover genes potentially involved in SBPH pyrethroid resistance, this study putatively identified several candidate genes of detoxification enzymes that were significantly overexpressed in the resistant strain, which matched the synergism and enzyme activity testing. The biochemical and molecular evidences suggest that the high level pyrethroid resistance in L. striatellus could be due to enhanced detoxification rather than target insensitivity. The findings lay a solid ground for further resistance mechanism elucidation studies. PMID:24324548

Morphological, ultrastructural and functional imaging of frozen/thawed and vitrified/warmed human ovarian tissue retrieved from oncological patients.

PubMed

Fabbri, R; Vicenti, R; Macciocca, M; Martino, N A; Dell'Aquila, M E; Pasquinelli, G; Morselli-Labate, A M; Seracchioli, R; Paradisi, R

2016-08-01

Which is the best method for human ovarian tissue cryopreservation: slow freezing/rapid thawing (SF/RT) or vitrification/warming (V/W)? The conventional SF/RT protocol used in this study seems to better preserve the morpho-functional status of human cryopreserved ovarian tissue than the used open carrier V/W protocol. Cryopreservation of human ovarian tissue is generally performed using the SF/RT method. However, reduction in the follicular pool and stroma damage are often observed. An emerging alternative procedure is represented by V/W which seems to allow the maintenance of the morphological integrity of the stroma. This is a retrospective cohort study including six patients affected by oncological diseases and enrolled from January to December 2014. Ovarian tissue was laparoscopically harvested from the right and left ovaries and was cryopreserved using a routinary SF/RT protocol or a V/W method, involving tissue incubation in two solutions (containing propylene glycol, ethylene glycol and sucrose at different concentrations) and vitrification in an open system. For each patient, three pieces from each ovary were collected at the time of laparoscopy (fresh tissue) and after storage (SF/RT or V/W) and processed for light microscopy (LM) and transmission electron microscopy (TEM), to assess the morphological and ultrastructural features of follicles and stroma, and for laser scanning confocal microscopy (LSCM), to determine the functional energetic/redox stroma status. The preservation status of SF/RT and V/W ovarian tissues was compared with that of fresh ones, as well as between them. By LM and TEM, SF/RT and V/W samples showed cryodamage of small entity. Interstitial oedema and increased stromal cell vacuolization and chromatin clumping were observed in SF/RT samples; in contrast, V/W samples showed oocyte nuclei with slightly thickened chromatin and irregular shapes. The functional imaging analysis by LSCM revealed that the mitochondrial activity and intracellular reactive oxygen species levels were reduced both in SF/RT and in V/W samples compared with fresh samples. The study also showed progressive dysfunction of the mitochondrial activity going from the outer to the inner serial section of the ovarian cortex. The reduction of mitochondrial activity of V/W samples compared with fresh samples was significantly higher in the inner section than in the outer section. The results report the bioenergetic and oxidative status assessment of fresh and cryopreserved human ovarian tissue by LSCM, a technique recently applied to tissue samples. The use of LSCM on human ovarian tissues after SF/RT or V/W is a new application that requires validation. The procedures for mitochondrial staining with functional probes and fixing are not yet standardized. Xenografting of the cryopreserved ovarian tissue in severe combined immunodeficient mice and in vitro culture have not yet been performed. The identification of a cryopreservation method able to maintain the morpho-functional integrity of the ovarian tissue and a number of follicles comparable with those observed in fresh tissue might optimize results in clinical practice, in terms of recovery, duration of ovarian function and increased delivery outcomes after replanting. The SF/RT protocol allowed better morpho-functional tissue integrity than the V/W procedure. Funding was provided by Fondazione del Monte di Bologna e Ravenna, Italy. Dr N.A.M. was granted by the project ONEV MIUR PONa3 00134-n.254/R&C 18 5 2011 and the project GR-2011-02351396 (Ministry of Health, Young Researchers Grant 2011/2012). There are no competing interests. Clinical trial 74/2001/0 (approved:13 2 2002): 'Pilot study on cryopreservation of human ovarian tissue: morphological and immunohistochemical analysis before and after cryopreservation'. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of a new LAMP assay for the detection of CSFV strains from Cuba: a proof-of-concept study.

PubMed

Postel, Alexander; Pérez, Lester J; Perera, Carmen L; Schmeiser, Stefanie; Meyer, Denise; Meindl-Boehmer, Alexandra; Rios, Liliam; Austermann-Busch, Sophia; Frias-Lepoureau, Maria T; Becher, Paul

2015-06-01

Classical swine fever (CSF) is a devastating animal disease of great economic impact worldwide. In many countries, CSF has been endemic for decades, and vaccination of domestic pigs is one of the measures to control the disease. Consequently, differentiating infected from vaccinated animals by antibody ELISA screening is not applicable. In some countries, such as Cuba, lack of molecular techniques for sensitive, rapid and reliable detection of virus genomes is a critical point. To overcome this problem, an easy-to-use one-tube assay based on the loop-mediated isothermal amplification (LAMP) principle has been developed for detection of the genome of CSF virus (CSFV) of endemic Cuban genotype 1.4 isolates. The assay reliably detected recent isolates from three different regions of Cuba with an analytical sensitivity 10-100 times lower than that of quantitative reverse transcription RT-qPCR. Diagnostic test sensitivity was examined using reference sera from two groups of pigs experimentally infected with Cuban virulent strain CSF0705 "Margarita" and the recent field isolate CSF1058 "Pinar del Rio". Differences in pathogenicity of the two viruses were reflected in the clinical course of disease as well as in virus loads of blood samples. Low viral RNA loads in samples from pigs infected with the field isolate caused serious detection problems in RT-LAMP as well as in RT-qPCR. Thus, it will be necessary in future research to focus on targeted sampling of diseased animals and to restrict diagnosis to the herd level in order to establish LAMP as an efficient tool for diagnosing CSF under field conditions.

Ice clouds optical properties in the Far Infrared from the ECOWAR-COBRA Experiment

NASA Astrophysics Data System (ADS)

Rizzi, Rolando; Tosi, Ennio

ECOWAR-COBRA (Earth COoling by WAter vapouR emission -Campagna di Osservazioni della Banda Rotazionale del vapor d'Acqua) field campaign took place in Italy from 3 to 17 March 2007 with the main goal of studying the scarcely sensed atmospheric emission occurring beyond 17 microns. Instrumentation involved in the campaign included two different Fourier Transforms Spectrometers (FTS) : REFIR-PAD (at Testa Grigia Station, 3500 m a.s.l.) and FTIR-ABB (at Cervinia Station, 1990 m a.s.l.). In this work cloudy sky data have been ana-lyzed. A cloud properties retrieval methodology (RT-RET), based on high spectral resolution measurements in the atmospheric window (800-1000 cm-1), is applied to both FTS sensors. Cloud properties determined from the infrared retrievals are compared with those obtained from Raman lidar taken by the BASIL Lidar system that was operating at Cervinia station. Cloud microphysical and optical properties retrieved by RT-RET are used to perform forward simulations over the entire FTSs measurements spectral interval. Results are compared to FTS data to test the ability of single scattering ice crystals models to reproduce cloudy sky radiances in the Far Infra-Red (FIR) part of the spectrum. New methods to retrieve cloud optical and microphysical properties exploiting high spectral resolution FIR measurements are also investigated.

Hydrogeology of a fractured shale (Opalinus Clay): Implications for deep geological disposal of radioactive wastes

NASA Astrophysics Data System (ADS)

Gautschi, Andreas

2001-01-01

As part of the Swiss programme for high-level radioactive-waste disposal, a Jurassic shale (Opalinus Clay) is being investigated as a potential host rock. Observations in clay pits and the results of a German research programme focusing on hazardous waste disposal have demonstrated that, at depths of 10-30 m, the permeability of the Opalinus Clay decreases by several orders of magnitude. Hydraulic tests in deeper boreholes (test intervals below 300 m) yielded hydraulic conductivities <10-12 m/s, even though joints and faults were included in some of the test intervals. These measurements are consistent with hydrogeological data from Opalinus Clay sections in ten tunnels in the Folded Jura of northern Switzerland. Despite extensive faulting, only a few indications of minor water inflow were encountered in more than 6,600 m of tunnel. All inflows were in tunnel sections where the overburden is less than 200 m. The hydraulic data are consistent with clay pore-water hydrochemical and isotopic data. The extensive hydrogeological data base - part of which derives from particularly unfavourable geological environments - provides arguments that advective transport through faults and joints is not a critical issue for the suitability of Opalinus Clay as a host rock for deep geological waste disposal. Résumé. Dans le cadre du programme suisse de stockage de déchets hautement radioactifs, une formation argileuse du Jurassique, l'argile à Opalinus, a été étudiée en tant que roche hôte potentielle. Des observations dans des cavités dans l'argile et les résultats du programme de recherche allemand consacré au stockage de déchets à risques ont démontré que, à des profondeur de 10 à 30 m, la perméabilité des argiles à Opalinus décroît de plusieurs ordres de grandeur. Des essais hydrauliques dans des forages plus profonds (intervalles de test á une profondeur de plus de 300 m) ont donné des conductivités hydrauliques inférieures à 10-12 m/s, même lorsque des fractures et des failles existaient dans certains des intervalles d'essais. Ces mesures sont conformes aux données hydrogéologiques tirées du recoupement des argiles à Opalinus par dix tunnels du Jura plissé du nord de la Suisse. Malgré une tectonique intense, peu de manifestations de faibles venues d'eau ont été rencontrées dans plus de 6600 m de tunnel. Toutes les venues d'eau se sont produites dans des sections de tunnel où le recouvrement est inférieur à 200 m. Les données hydrauliques sont en bon accord avec les données hydrochimiques et isotopiques de l'eau porale des argiles. En se basant sur le grand nombre de données hydrogéologiques, qui portent en partie sur les environnements géologiques particulièrement peu propices, on peut avancer que le transport advectif le long des failles et des fractures n'est pas un facteur susceptible de remettre en question le choix de l'argile à Opalinus comme roche hôte pour le stockage de déchets radioactifs en formation géologique profonde. Resúmen. Dentro del programa suizo de eliminación de residuos radiactivos de alta actividad, se está investigando la posibilidad de utilizar unos esquistos Jurásicos (Arcilla Opalina) como depósito geológico. Las observaciones efectuadas en pozos en arcilla y los resultados de un programa de estudio alemán sobre eliminación de residuos peligrosos han demostrado que, a profundidades de entre 10 y 30 m, la permeabilidad de la Arcilla Opalina decrece en varios órdenes de magnitud. Los ensayos hidráulicos realizados en sondeos más profundos (en intervalos situados a más de 300 m) proporcionaron conductividades hidráulicas inferiores a 10-12 m/s, pese a que algunos de los intervalos interceptaban juntas y fallas. Estas medidas son coherentes con los datos hidrogeológicos de las secciones de Arcilla Opalina existentes en 10 túneles del Jurásico Plegado, al norte de Suiza. A pesar de las fallas extensivas, apenas se hallaron indicios de entrada de agua en los más de 6.600 m de túnel. Todos los flujos tenían lugar en secciones del túnel que soportan sobrecargas inferiores a 200 m. Los datos hidráulicos son coherentes con los datos hidroquímicos e isotópicos del agua intersticial de las arcillas. Los abundantes datos hidrogeológicos -parte de los cuales proceden de medios particularmente desfavorables desde el punto de vista geológico- proporcionan argumentos de que el transporte advectivo a través de fallas y juntas no es un aspecto crítico en lo que respecta a la idoneidad de la Arcilla Opalina como almacenamiento geológico profundo de residuos.

Accuracy of a pediatric early warning score in the recognition of clinical deterioration.

PubMed

Miranda, Juliana de Oliveira Freitas; Camargo, Climene Laura de; Nascimento, Carlito Lopes; Portela, Daniel Sales; Monaghan, Alan

2017-07-10

to evaluate the accuracy of the version of the Brighton Pediatric Early Warning Score translated and adapted for the Brazilian context, in the recognition of clinical deterioration. a diagnostic test study to measure the accuracy of the Brighton Pediatric Early Warning Score for the Brazilian context, in relation to a reference standard. The sample consisted of 271 children, aged 0 to 10 years, blindly evaluated by a nurse and a physician, specialists in pediatrics, with interval of 5 to 10 minutes between the evaluations, for the application of the Brighton Pediatric Early Warning Score for the Brazilian context and of the reference standard. The data were processed and analyzed using the Statistical Package for the Social Sciences and VassarStats.net programs. The performance of the Brighton Pediatric Early Warning Score for the Brazilian context was evaluated through the indicators of sensitivity, specificity, predictive values, area under the ROC curve, likelihood ratios and post-test probability. the Brighton Pediatric Early Warning Score for the Brazilian context showed sensitivity of 73.9%, specificity of 95.5%, positive predictive value of 73.3%, negative predictive value of 94.7%, area under Receiver Operating Characteristic Curve of 91.9% and the positive post-test probability was 80%. the Brighton Pediatric Early Warning Score for the Brazilian context, presented good performance, considered valid for the recognition of clinical deterioration warning signs of the children studied. avaliar a acurácia da versão traduzida e adaptada do Brighton Paediatric Early Warning Score para o contexto brasileiro, no reconhecimento da deterioração clínica. estudo de teste diagnóstico para medir a acurácia do Brighton Paediatric Early Warning Score, para o contexto brasileiro, em relação a um padrão de referência. A amostra foi composta por 271 crianças de 0 a 10 anos, avaliadas de forma cega por uma enfermeira e um médico, especialistas em pediatria, com intervalo de 5 a 10 minutos entre as avaliações, para aplicação do Brighton Paediatric Early Warning Score, para o contexto brasileiro e do padrão de referência. Os dados foram processados e analisados nos programas Statistical Package for the Social Sciences e VassarStats.net. O desempenho do Brighton Paediatric Early Warning Score para o contexto brasileiro foi avaliado por meio dos indicadores de sensibilidade, especificidade, valores preditivos, área sob a curva ROC, razões de probabilidades e probabilidade pós-teste. o Brighton Paediatric Early Warning Score para o contexto brasileiro apresentou sensibilidade de 73,9%, especificidade de 95,5%, valor preditivo positivo de 73,3%, valor preditivo negativo de 94,7%, área sob a Receiver Operating Characteristic Curve de 91,9% e a probabilidade pós-teste positivo foi de 80%. o Brighton Paediatric Early Warning Score, para o contexto brasileiro, apresentou bom desempenho, considerado válido para o reconhecimento de sinais de alerta de deterioração clínica das crianças estudadas. evaluar la precisión de la versión traducida y adaptada del Brighton Paediatric Early Warning Score para el contexto brasileño, en el reconocimiento de la deterioración clínica. estudio de test diagnóstico para medir la precisión del Brighton Paediatric Early Warning Score para el contexto brasileño, en relación a un estándar de referencia. La muestra estuvo compuesta por 271 niños de 0 a 10 años, evaluadas de forma ciega por especialistas en pediatría, una enfermera y un médico, con intervalo de 5 a 10 minutos entre las evaluaciones, para aplicación del Brighton Paediatric Early Warning Score para el contexto brasileño. Los datos fueron procesados y analizados en los programas Statistical Package for the Social Sciences y VassarStats.net. El desempeño del Brighton Paediatric Early Warning Score para el contexto brasileño fue evaluado por medio de los indicadores de sensibilidad, especificidad, valores predictivos, área debajo de la curva ROC, razones de probabilidades y probabilidad postest. el Brighton Paediatric Early Warning Score para el contexto brasileño presentó sensibilidad de 73,9%, especificidad de 95,5%, valor predictivo positivo de 73,3%, valor predictivo negativo de 94,7%, área bajo la Receiver Operating Characteristic Curve de 91,9% y la probabilidad postest positivo fue de 80%. el Brighton Paediatric Early Warning Score para el contexto brasileño, presentó buen desempeño, considerado válido para el reconocimiento de señales de alerta de deterioración clínica de los niños estudiados.

Razonamiento de Estudiantes Universitarios sobre Variabilidad e Intervalos de Confianza en un Contexto Inferencial Informal = University Students' Reasoning on Variability and Confidence Intervals in Inferential Informal Context

ERIC Educational Resources Information Center

Inzunsa Cazares, Santiago

2016-01-01

This article presents the results of a qualitative research with a group of 15 university students of social sciences on informal inferential reasoning developed in a computer environment on concepts involved in the confidence intervals. The results indicate that students developed a correct reasoning about sampling variability and visualized…

Evolución de estrellas enanas blancas de Helio de masa baja e intermedia

NASA Astrophysics Data System (ADS)

Althaus, L. G.; Benvenuto, O. G.

Numerosas observaciones realizadas particularmente en los últimos dos años parecen confirmar que las enanas blancas (EB) de helio de masa baja e intermedia son el resultado de la evolución de sistemas binarios cercanos. Con el objeto de realizar una adecuada interpretación de estos objetos son necesarios modelos de EBs de helio lo más detallado posibles. En este estudio presentamos cálculos detallados de la evolución de EBs de helio con masas entre M=0.1Msolar y M=0.5Msolar a intervalos de 0.05Msolar . Para ello, hemos tenido en cuenta los efectos de temperatura finita mediante un código de evolución estelar lo más actualizado posible. En particular, el transporte de energía es descripto en el marco del nuevo modelo para la convección turbulenta desarrollado por Canuto - Mazzitelli. Además hemos considerado la nueva ecuación de estado para plasmas de helio de Saumon et al. y nuevas opacidades radiativas OPAL. Las pérdidas por neutrinos fueron asimismo tenidas en cuenta. Excepto para las EBs más masivas, nuestros modelos iniciales están ubicados en las cercanías de la correspondiente línea de Hayashi para configuraciones de helio. Nuestros resultados muestran que existe una región prohibida en el diagrama observacional HR donde ninguna EB de helio puede encontrarse. Dicha región es para log{(L/Lsolar )}>= -0.25 and log{Teff} >= 4.45. Hemos encontrado también que los tracks evolutivos en el diagrama HR en el dominio de alta luminosidad (pre - EB) son fuertemente afectados por la eficiencia convectiva y que las pérdidas por neutrinos son importantes en los modelos más masivos. Finalmente hemos analizado la estructura de la zona convectiva externa encontrando que la teoría de Canuto - Mazzitelli conduce a un perfil convectivo muy diferente del dado por cualquier versión de la popular teoría de la mixing length. Si bién este comportamiento es decisivo en el contexto de las inestabilides pulsacionales, los radios y gravedades superficiales de los modelos no son afectados al incluir la nueva teoría de convección.

Associations between frailty syndrome and sociodemographic characteristics in long-lived individuals of a community.

PubMed

Grden, Clóris Regina Blanski; Lenardt, Maria Helena; Sousa, Jacy Aurelia Vieira de; Kusomota, Luciana; Dellaroza, Mara Solange Gomes; Betiolli, Susanne Elero

2017-06-05

investigating the association between frailty syndrome and sociodemographic characteristics in long-lived individuals of a community. a cross-sectional study with a proportional stratified sample consisting of 243 long-lived individuals. A structured instrument, scales and tests that comprise evaluating frailty were applied for data collection. Univariate and multivariate analyzes were performed by logistic regression (p<0.05) by Statistica 10(r) software and Odds Ratio (95% Confidence Interval) were calculated for the predictive models. of the 243 long-lived individuals evaluated, 36 (14.8%) were frail, 55 (63.8%) were pre-frail and 52 (21.4%) were not frail. A predominance of females (n=161; 66.3%), widows/widowers (n=158; 65%), who lived with family members (n=144; 59.3%) and in a self-reported satisfactory financial situation (n=108; 44.5%) was observed. A significant association was found between the demographic variable of age (p=0.043) and frailty syndrome. The best predictor model for the syndrome included the variables: gender, age and household companion. the variable of age contributed most to the fragilization process of long-lived individuals residing in the community. It is essential that gerontological nursing care contemplates early detection of this syndrome, considering age as being indicative of care needs. investigar a associação entre a síndrome da fragilidade física e as características sociodemográficas de idosos longevos da comunidade. estudo transversal, com amostra estratificada proporcional constituída por 243 longevos. Para a coleta de dados aplicaram-se instrumento estruturado, escalas e testes que compõem a avaliação da fragilidade física. Realizaram-se análises univariada e multivariada por regressão logística (p<0,05) pelo software Statistica 10(r) e para os modelos preditores foram calculadas Odds Ratio (Intervalo de Confiança de 95%). dos 243 longevos avaliados, 36 (14,8%) eram frágeis, 155 (63,8%) pré-frágeis e 52 (21,4%) não frágeis. Houve predomínio do sexo feminino (n=161; 66,3%), viúvos (n=158; 65%), que residiam com familiares (n=144; 59,3%) e com situação financeira autorrelatada satisfatória (n=108; 44,5%). Identificou-se associação significativa entre a variável demográfica idade (p=0,043) e a síndrome da fragilidade física. O melhor modelo preditor da síndrome compreendeu as variáveis: sexo, idade e com quem mora. a variável idade foi a que mais contribuiu para o processo de fragilização dos longevos que residem na comunidade. É essencial que o cuidado de enfermagem gerontológico contemple o rastreamento precoce da síndrome e considere a idade como um indicativo de necessidades de cuidados. investigar la asociación entre el síndrome de la fragilidad física y las características sociodemográficas de ancianos con edad más avanzada de la comunidad. estudio transversal, con muestra estratificada proporcional constituida por 243 longevos. Para la recolección de datos se aplicó: instrumento estructurado, escalas y pruebas que componen la evaluación de la fragilidad física. Se realizaron análisis univariado y multivariado por regresión logística (p<0,05) con el programa Statistica 10(r) y para los modelos de predicción fueron calculados los Odds Ratio (Intervalo de Confianza de 95%). de los 243 longevos evaluados, 36 (14,8%) eran frágiles, 155 (63,8%) pre-frágiles y 52 (21,4%) no frágiles. Hubo predominio del sexo femenino (n=161; 66,3%), viudos (n=158; 65%), residían con familiares (n=144; 59,3%) y con situación financiera autorrelatada satisfactoria (n=108; 44,5%). Se identificó asociación significativa entre la variable demográfica edad (p=0,043) y el síndrome de la fragilidad física. El mejor modelo predictor del síndrome contuvo las variables: sexo, edad y con quien reside. la variable edad fue la que más contribuyó para el proceso de fragilización de los longevos que residen en la comunidad. Es esencial que el cuidado de enfermería gerontológico contemple el rastreo precoz del síndrome y considere la edad como un indicativo de necesidades de cuidados.

Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and requirement of the carboxyl-terminus for its effect.

PubMed

Fujita, H; Okada, F; Hamada , J; Hosokawa, M; Moriuchi, T; Koya, R C; Kuzumaki, N

2001-09-01

Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell motility. In addition, we have reported that cellular levels of gelsolin are decreased in various tumor cells, and overexpression of gelsolin by gene transfer suppresses tumorigenicity. We sought to assess the effects of gelsolin overexpression on metastasis and to determine the importance of a carboxyl-terminus that confers Ca(2+) dependency on gelsolin for effects of its overexpression. Expression vectors with cDNA encoding either full-length wild-type or His321 mutant form, isolated from a flat revertant of Ras-transformed cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We characterized phenotypes of transfectants, such as growth rate, colony formation in soft agar, cell motility and metastasis formation in vivo. Transfectants expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced growth ability in soft agar. Although expression of integrin beta1 or alpha4 on the cell surface of transfectants was not changed, wild-type and His321 mutant gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading, reduced chemotatic migration to fibronectin and suppressed lung colonization in spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as well as a tumor suppressor gene. The carboxyl-terminus of gelsolin is important for retardation of cell spreading, reduced chemotasis and metastasis suppression. Copyright 2001 Wiley-Liss, Inc.

Analysis of the discrepancies identified during medication reconciliation on patient admission in cardiology units: a descriptive study.

PubMed

Lombardi, Natália Fracaro; Mendes, Antonio Eduardo Matoso; Lucchetta, Rosa Camila; Reis, Wálleri Christini Torelli; Fávero, Maria Luiza Drechsel; Correr, Cassyano Januário

2016-08-15

this observational study aimed to describe the discrepancies identified during medication reconciliation on patient admission to cardiology units in a large hospital. the medication history of patients was collected within 48 hours after admission, and intentional and unintentional discrepancies were classified as omission, duplication, dose, frequency, timing, and route of drug administration. most of the patients evaluated were women (58.0%) with a mean age of 59 years, and 75.5% of the patients had a Charlson comorbidity index score between 1 and 3. Of the 117 discrepancies found, 50.4% were unintentional. Of these, 61.0% involved omission, 18.6% involved dosage, 18.6% involved timing, and 1.7% involved the route of drug administration. this study revealed a high prevalence of discrepancies, most of which were related to omissions, and 50% were unintentional. These results reveal the number of drugs that are not reincorporated into the treatment of patients, which can have important clinical consequences. este estudo observacional teve como objetivo descrever discrepâncias encontradas na realização de conciliação medicamentosa de pacientes admitidos em unidades de cardiologia de um hospital de grande porte. a história de medicação dos pacientes foi coletada dentro de 48h após a admissão, e as discrepâncias, identificadas como intencionais ou não intencionais, foram classificadas como de: omissão, duplicidade, dose, frequência, intervalo e via. a maioria dos pacientes incluídos pertençia ao sexo feminino (58,0%), com idade média de 59 anos, e com índice de comorbidades de Charlson entre 1 e 3 (75,5% dos casos). Das 117 discrepâncias encontradas, 50,4% foram não intencionais. Dessas, 61,0% foram de omissão, 18,6% de dose, 18,6% de intervalo e 1,7% de via de administração. o estudo mostra a alta prevalência de discrepâncias, principalmente de omissão, sendo quase metade não intencionais. Esse dado remete ao número de medicamentos que não são reincorporados ao tratamento dos pacientes, podendo repercutir em consequências clínicas importantes. este estudio observacional tuvo como objetivo describir discrepancias encontradas en la realización de la conciliación medicamentosa de pacientes admitidos en unidades de cardiología de un hospital de gran porte. la historia de medicación de los pacientes fue recolectada dentro de 48h después de la admisión, y las discrepancias, identificadas como intencionales o no intencionales, fueron clasificadas como: omisión, duplicidad, dosis, frecuencia, intervalo y vía. la mayoría de los pacientes incluidos pertenecía al sexo femenino (58,0%), con edad promedio de 59 años, y con índice de comorbilidad de Charlson entre 1 y 3 (75,5% de los casos). De las 117 discrepancias encontradas, 50,4% fueron no intencionales. De estas, 61,0% fueron de omisión, 18,6% de dosis, 18,6% de intervalo y 1,7% de vía de administración. el estudio muestra la alta prevalencia de discrepancias, principalmente de omisión, siendo casi mitad de ellas no intencionales. Ese dato nos indica el número de medicamentos que no son reincorporados al tratamiento de los pacientes, lo que puede repercutir en consecuencias clínicas importantes.

Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients.

PubMed

Liu, Bao-Ming; Li, Tong; Xu, Jie; Li, Xiao-Guang; Dong, Jian-Ping; Yan, Ping; Yang, Jing-Xian; Yan, Ling; Gao, Zhi-Yong; Li, Wen-Peng; Sun, Xie-Wen; Wang, Yu-Hua; Jiao, Xiu-Juan; Hou, Chun-Sheng; Zhuang, Hui

2010-03-01

Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naïve Chinese patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously reported potential NA resistance (NAr) mutation positions in RT region were analyzed. Patients were found with either B-genotype (28.65%) or C-genotype (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were identified as B- and C-genotype-dependent polymorphic AA positions. AA substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173, rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected. However, potential NAr mutations were found in 30.73% (59/192) isolates, which involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including sG145R mutation. One-third of mutation positions were located in functional RT domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a' determinant and showing most concomitant immune-associated mutations) and non-A-B interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed several preferred positions to mutate. These results might provide insights into understanding the evolution and selection basis of NAr HBV strains under antiviral therapy.

Identification of a Cryptic Insertion ins(11;X)(q23;q28q12) Resulting in a KMT2A-FLNA Fusion in a 13-Month-Old Child with Acute Myelomonocytic Leukemia.

PubMed

Lentes, Jana; Thomay, Kathrin; Schneider, Dominik T; Bernbeck, Benedikt; Reinhardt, Dirk; Marschalek, Rolf; Meyer, Claus; Schlegelberger, Brigitte; Göhring, Gudrun

2016-01-01

In pediatric acute myeloid leukemia (AML), chromosomal abnormalities leading to a disruption of the lysine methyltransferase 2A (KMT2A) gene in 11q23 are the most frequent rearrangements. Here, we report on the identification of a novel cryptic insertion, ins(11;X)(q23;q28q12), resulting in a translocation of the KMT2A gene in 11q23, leading to a KMT2A-FLNA fusion in a 13-month-old boy with de novo acute myelomonocytic leukemia, who died 38 days after diagnosis. The patient presented a complex karyotype 48∼49,Y,del(X)(q12),+del(X)(q12),+8,ins(11;X)(q23; q28q12),+19. The identified fusion gene was predicted to be out-of-frame (fusion of portions of KMT2A exon 11 with FLNA exon 11). However, RT-PCR experiments demonstrated that a potentially functional transcript was generated by alternative splicing where KMT2A exon 10 was spliced in-frame to the truncated FLNA exon 11. This case report helps to better understand the rare but potentially severe impact of KMT2A- FLNA fusions in infants with AML to improve prognostic stratification of therapy and clinical management. © 2017 S. Karger AG, Basel.

Assessing the residual CFTR gene expression in human nasal epithelium cells bearing CFTR splicing mutations causing cystic fibrosis

PubMed Central

Masvidal, Laia; Igreja, Susana; Ramos, Maria D; Alvarez, Antoni; de Gracia, Javier; Ramalho, Anabela; Amaral, Margarida D; Larriba, Sara; Casals, Teresa

2014-01-01

The major purpose of the present study was to quantify correctly spliced CFTR transcripts in human nasal epithelial cells from cystic fibrosis (CF) patients carrying the splicing mutations c.580-1G>T (712-1G>T) and c.2657+5G>A (2789+5G>A) and to assess the applicability of this model in CFTR therapeutic approaches. We performed the relative quantification of CFTR mRNA by reverse transcription quantitative PCR (RT-qPCR) of these splicing mutations in four groups (wild type, CF-F508del controls, CF patients and CF carriers) of individuals. In addition, in vitro assays using minigene constructs were performed to evaluate the effect of a new CF complex allele c.[2657+5G>A; 2562T>G]. Ex vivo qPCR data show that the primary consequence of both mutations at the RNA level is the skipping of their neighboring exon (6 and 16, respectively). The CFTR minigenes results mimicked the ex vivo data, as exon 16 skipping is the main aberrant transcript, and the correctly spliced transcript level was observed in a similar proportion when the c.2657+5G>A mutation is present. In summary, we provide evidence that ex vivo quantitative transcripts analysis using RT/qPCR is a robust technology that could be useful for measuring the efficacy of therapeutic approaches that attempt to achieve an increase in CFTR gene expression. PMID:24129438

Investigating the role of feedback and motivation in clinical reaction time assessment.

PubMed

Eckner, James T; Chandran, Srikrishna; Richardson, James K

2011-12-01

To investigate the influence of performance feedback and motivation during 2 tests of simple visuomotor reaction time (RT). Cross-sectional, observational study. Outpatient academic physiatry clinic. Thirty-one healthy adults (mean [SD], 54 ± 15 years). Participants completed a clinical test of RT (RT(clin)) and a computerized test of RT with and without performance feedback (RT(compFB) and RT(compNoFB), respectively) in randomly assigned order. They then ranked their degree of motivation during each test. RT(clin) measured the time required to catch a suspended vertical shaft by hand closure after release of the shaft by the examiner. RT(compFB) and RT(compNoFB) both measured the time required to press a computer key in response to a visual cue displayed on a computer monitor. Performance feedback (visual display of the previous trial and summary results) was provided for RT(compFB), but not for RT(compNoFB). Means and standard deviations of RT(clin), RT(compFB), and RT(compNoFB) and participants' self-reported motivation on a 5-point Likert scale for each test. There were significant differences in both the means and standard deviations of RT(clin), RT(compFB), and RT(compNoFB) (F(2,60) = 81.66, P < .0001; F(2,60) = 32.46, P < .0001, respectively), with RT(clin) being both the fastest and least variable of the RT measurements. RT(clin) was more strongly correlated with RT(compFB) (r = 0.449, P = .0011) than with RT(compNoFB) (r = 0.314, P = .086). The participants reported similar levels of motivation between RT(clin) and RT(compFB), both of which were reported to be more motivating than RT(compNoFB). The stronger correlation between RT(clin) and RT(compFB) as well as the higher reported motivation during RT(clin) and RT(compFB) testing suggest that performance feedback is a positive motivating factor that is inherent to RT(clin) testing. RT(clin) is a simple, inexpensive technique for measuring RT and appears to be an intrinsically motivating task. This motivation may promote faster, more consistent RT performance compared with currently available computerized programs, which do not typically provide performance feedback. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

PREVALENCE OF HELICOBACTER PYLORI TEN YEARS AGO COMPARED TO THE CURRENT PREVALENCE IN PATIENTS UNDERGOING UPPER ENDOSCOPY.

PubMed

Frugis, Sandra; Czeczko, Nicolau Gregori; Malafaia, Osvaldo; Parada, Artur Adolfo; Poletti, Paula Bechara; Secchi, Thiago Festa; Degiovani, Matheus; Rampanazzo-Neto, Alécio; D Agostino, Mariza D

2016-01-01

Helicobacter pylori has been extensively studied since 1982 it is estimated that 50% of the world population is affected. The literature lacks studies that show the change of its prevalence in the same population over time. To compare the prevalence of H. pylori in 10 years interval in a population that was submitted to upper endoscopy in the same endoscopy service. Observational, retrospective and cross-sectional study comparing the prevalence of H. pylori in two samples with 10 years apart (2004 and 2014) who underwent endoscopy with biopsy and urease. Patients were studied in three consecutive months of 2004, compared to three consecutive months of 2014. The total number of patients was 2536, and 1406 in 2004 and 1130 in 2014. There were positive for H. pylori in 17 % of the sample as a whole. There was a significant decrease in the prevalence from 19.3% in 2004 to 14.1% in 2014 (p<0.005). There was a 5.2% reduction in the prevalence of H. pylori comparing two periods of three consecutive months with 10 years apart in two equivalent population samples. Helicobacter pylori vem sendo amplamente estudado desde 1982 estimando-se que 50% da população mundial esteja afetada. A literatura carece de estudos que mostrem a mudança de sua prevalência em uma mesma população ao longo do tempo. Comparar a prevalência do H.pylori no intervalo de 10 anos em população que realizou endoscopia digestiva alta no mesmo serviço de endoscopia. Estudo observacional, retrospectivo e transversal, comparando a prevalência de H. pylori em duas amostras com intervalo de 10 anos (2004 e 2014) que realizaram endoscopia digestiva alta com biópsias e teste da urease para a pesquisa de H. pylori. Foram estudados pacientes em três meses consecutivos de 2004, comparados aos de três meses consecutivos de 2014. O número total de pacientes avaliados foi 2536, sendo 1406 em 2004 e 1130 em 2014. Constatou-se resultado positivo para H.pylori em 17% da amostra como um todo. Houve queda significativa da prevalência de H.pylori de 19,3% em 2004 para 14,1% em 2014 (p<0.005). Houve redução de 5,2% da prevalência de H. pylori comparando-se dois períodos de três meses consecutivos com intervalo de 10 anos em duas amostras populacionais equivalentes.

Evolución Dinámica de Cúmulos Estelares Abiertos

NASA Astrophysics Data System (ADS)

de La Fuente Marcos, R.

Las estrellas que observamos no se formaron aisladamente, sino que lo hicieron en grupos o cúmulos. Estos sistemas estelares recibenel nombre de cúmulos estelares abiertos o galácticos cuando están constituidos por estrellas de la Población I. Los cúmulos abiertos se localizan preferentemente en el plano galáctico, y en muchos de ellos está teniendo lugar aún una activa formación estelar. El propósito principal de esta tesis doctoral es el estudio de la evolución dinámica de estos sistemas estelares por medio de simulaciones numéricas y de la comparación de sus resultados con datos observacionales. Con este fin se analizan los efectos que, sobre la dinámica de los cúmulos, ejercen varios fenómenos de interés astrofísico tales como el campo gravitatorio galáctico, la pérdida de masa causada por la evolución estelar y la presencia de binarias primordiales. En este trabajo se presentan los resultados de más de un centenar de modelos de cúmulos, con poblaciones comprendidas en el intervalo [100, 10.000] estrellas, calculados con NBODY5, un programa estándar en el campo de la Dinámica Estelar Experimental. De los mismos se deduce que el mecanismo principal que rige la dinámica de los cúmulos abiertos es la evolución estelar de su distribución de masas, encontrándose un comportamiento diferencial fuertemente dependiente de la población inicial del cúmulo. Los mecanismos responsables de la desintegración de los cúmulos abiertos son analizados en detalle, proponiéndose un modelo analítico que ajusta razonablemente los resultados de las simulaciones. Además, y con el fin de explicar el elevado número de sistemas múltiples observados en cúmulos abiertos, se estudian los efectos que, sobre los mismos, ejerce la presencia de una cierta fracción de binarias primordiales. El papel de las binarias tambiín depende de la riqueza del cúmulo y sus efectos se interrelacionan con aquellos debidos a la evolución estelar. Por último, se aborda la posibilidad de construir diagramas de Hertzsprung-Russell teóricos a partir de las simulaciones y compararlos con datos procedentes de cúmulos abiertos reales.

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. There was no significant difference in all groups (P > 0.05). IC + RT + AC group had heavier acute toxicity effects than other groups, but it did not affect the treatment process, all patients could be tolerated. This retrospective study has demonstrated that alternating Chemo-radiotherapy and early radiotherapy not only can improve the survival rate for locally Advanced Nasopharyngeal Carcinoma, but also have slight toxicities and side reaction, all patients may tolerated.

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94

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

Fietkau, Rainer; Roedel, Claus; Hohenberger, Werner

2007-03-15

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, andmore » delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.« less

The DICOM-based radiation therapy information system

NASA Astrophysics Data System (ADS)

Law, Maria Y. Y.; Chan, Lawrence W. C.; Zhang, Xiaoyan; Zhang, Jianguo

2004-04-01

Similar to DICOM for PACS (Picture Archiving and Communication System), standards for radiotherapy (RT) information have been ratified with seven DICOM-RT objects and their IODs (Information Object Definitions), which are more than just images. This presentation describes how a DICOM-based RT Information System Server can be built based on the PACS technology and its data model for a web-based distribution. Methods: The RT information System consists of a Modality Simulator, a data format translator, a RT Gateway, the DICOM RT Server, and the Web-based Application Server. The DICOM RT Server was designed based on a PACS data model and was connected to a Web application Server for distribution of the RT information including therapeutic plans, structures, dose distribution, images and records. Various DICOM RT objects of the patient transmitted to the RT Server were routed to the Web Application Server where the contents of the DICOM RT objects were decoded and mapped to the corresponding location of the RT data model for display in the specially-designed Graphic User Interface. The non-DICOM objects were first rendered to DICOM RT Objects in the translator before they were sent to the RT Server. Results: Ten clinical cases have been collected from different hopsitals for evaluation of the DICOM-based RT Information System. They were successfully routed through the data flow and displayed in the client workstation of the RT information System. Conclusion: Using the DICOM-RT standards, integration of RT data from different vendors is possible.

Comparison of electron microscopy, ELISA, real time RT-PCR and insulated isothermal RT-PCR for the detection of Rotavirus group A (RVA) in feces of different animal species.

PubMed

Soltan, Mohamed A; Tsai, Yun-Long; Lee, Pei-Yu A; Tsai, Chuan-Fu; Chang, Hsiao-Fen G; Wang, Hwa-Tang T; Wilkes, Rebecca P

2016-09-01

There is no gold standard for detection of Rotavirus Group A (RVA), one of the main causes of diarrhea in neonatal animals. Sensitive and specific real-time RT-PCR (rtRT-PCR) assays are available for RVA but require submission of the clinical samples to diagnostic laboratories. Patient-side immunoassays for RVA protein detection have shown variable results, particularly with samples from unintended species. A sensitive and specific test for detection of RVA on the farm would facilitate rapid management decisions. The insulated isothermal RT-PCR (RT-iiPCR) assay works in a portable machine to allow sensitive and specific on-site testing. The aim of this investigation was to evaluate a commercially available RT-iiPCR assay for RVA detection in feces from different animal species. This assay was compared to an in-house rtRT-PCR assay and a commercially available rtRT-PCR kit, as well as an ELISA and EM for RVA detection. All three PCR assays targeted the well-conserved NSP5 gene. Clinical fecal samples from 108 diarrheic animals (mainly cattle and horses) were tested. The percentage of positive samples by ELISA, EM, in-house rtRT-PCR, commercial rtRT-PCR, and RT-iiPCR was 29.4%, 31%, 36.7%, 51.4%, 56.9%, respectively. The agreement between different assays was high (81.3-100%) in samples containing high viral loads. The sensitivity of the RT-iiPCR assay appeared to be higher than the commercially available rtRT-PCR assay, with a limit of detection (95% confidence index) of 3-4 copies of in vitro transcribed dsRNA. In conclusion, the user-friendly, field-deployable RT-iiPCR system holds substantial promise for on-site detection of RVA. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

PubMed

Wild, Aaron T; Gandhi, Nishant; Chettiar, Sivarajan T; Aziz, Khaled; Gajula, Rajendra P; Williams, Russell D; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F; Cosgrove, David; Pawlik, Timothy M; Maitra, Anirban; Wong, John; Hales, Russell K; Torbenson, Michael S; Herman, Joseph M; Tran, Phuoc T

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

PubMed Central

Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

Arterial Perfusion Imaging–Defined Subvolume of Intrahepatic Cancer

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Farjam, Reza; Feng, Mary

2014-05-01

Purpose: To assess whether an increase in a subvolume of intrahepatic tumor with elevated arterial perfusion during radiation therapy (RT) predicts tumor progression after RT. Methods and Materials: Twenty patients with unresectable intrahepatic cancers undergoing RT were enrolled in a prospective, institutional review board–approved study. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed before RT (pre-RT), after delivering ∼60% of the planned dose (mid-RT) and 1 month after completion of RT to quantify hepatic arterial perfusion. The arterial perfusions of the tumors at pre-RT were clustered into low-normal and elevated perfusion by a fuzzy clustering-based method, and the tumor subvolumesmore » with elevated arterial perfusion were extracted from the hepatic arterial perfusion images. The percentage changes in the tumor subvolumes and means of arterial perfusion over the tumors from pre-RT to mid-RT were evaluated for predicting tumor progression post-RT. Results: Of the 24 tumors, 6 tumors in 5 patients progressed 5 to 21 months after RT completion. Neither tumor volumes nor means of tumor arterial perfusion at pre-RT were predictive of treatment outcome. The mean arterial perfusion over the tumors increased significantly at mid-RT in progressive tumors compared with the responsive tumors (P=.006). From pre-RT to mid-RT, the responsive tumors had a decrease in the tumor subvolumes with elevated arterial perfusion (median, −14%; range, −75% to 65%), whereas the progressive tumors had an increase of the subvolumes (median, 57%; range, −7% to 165%) (P=.003). Receiver operating characteristic analysis of the percentage change in the subvolume for predicting tumor progression post-RT had an area under the curve of 0.90. Conclusion: The increase in the subvolume of the intrahepatic tumor with elevated arterial perfusion during RT has the potential to be a predictor for tumor progression post-RT. The tumor subvolume could be a radiation boost candidate for response-driven adaptive RT.« less

Comparison of four molecular assays for the detection of Tembusu virus.

PubMed

Tang, Yi; Yeh, Yin-Ting; Chen, Hao; Yu, Chunmei; Gao, Xuhui; Diao, Youxiang

2015-10-01

Tembusu virus (TMUV) belongs to the genus Flavivirus that may cause severe egg drop in ducks. In order to evaluate the most efficient TMUV detection method, the performances of a conventional RT-PCR (C-RT-PCR), a semi-nested PCR (SN-RT-PCR), a reverse-transcriptase real-time quantitative PCR (Q-RT-PCR), and a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) targeting the TMUV virus-specific NS5 gene were examined. In order to compare the sensitivity of these four techniques, two templates were used: (1) plasmid DNA that contained a partial region of the NS5 gene and (2) genomic RNA from TMUV-positive cell culture supernatants. The sensitivities using plasmid DNA detection by C-RT-PCR, SN-RT-PCR, Q-RT-PCR, and RT-LAMP were 2 × 10(4) copies/μL, 20 copies/μL, 2 copies/μL, and 20 copies/μL, respectively. The sensitivities using genomic RNA for the C-RT-PCR, SN-RT-PCR, Q-RT-PCR, and RT-LAMP were 100 pg/tube, 100, 10, and 100 fg/tube, respectively. All evaluated assays were specific for TMUV detection. The TMUV-specific RNA was detected in cloacal swabs from experimentally infected ducks using these four methods with different rates (52-92%), but not in the control (non-inoculated) samples. The sensitivities of RT-PCR, SN-RT-PCR, Q-RT-PCR, and RT-LAMP performed with cloacal swabs collected from suspected TMUV infected ducks within 2 weeks of severe egg-drop were 38/69 (55.1%), 52/69 (75.4%), 57/69 (82.6%), and 55/69 (79.7%), respectively. In conclusion, both RT-LAMP and Q-RT-PCR can provide a rapid diagnosis of TMUV infection, but RT-LAMP is more useful in TMUV field situations or poorly equipped laboratories.

New quality assurance program integrating "modern radiotherapy" within the German Hodgkin Study Group.

PubMed

Kriz, J; Baues, C; Engenhart-Cabillic, R; Haverkamp, U; Herfarth, K; Lukas, P; Schmidberger, H; Marnitz-Schulze, S; Fuchs, M; Engert, A; Eich, H T

2017-02-01

Field design changed substantially from extended-field RT (EF-RT) to involved-field RT (IF-RT) and now to involved-node RT (IN-RT) and involved-site RT (IS-RT) as well as treatment techniques in radiotherapy (RT) of Hodgkin's lymphoma (HL). The purpose of this article is to demonstrate the establishment of a quality assurance program (QAP) including modern RT techniques and field designs within the German Hodgkin Study Group (GHSG). In the era of modern conformal RT, this QAP had to be fundamentally adapted and a new evaluation process has been intensively discussed by the radiotherapeutic expert panel of the GHSG. The expert panel developed guidelines and criteria to analyse "modern" field designs and treatment techniques. This work is based on a dataset of 11 patients treated within the sixth study generation (HD16-17). To develop a QAP of "modern RT", the expert panel defined criteria for analysing current RT procedures. The consensus of a modified QAP in ongoing and future trials is presented. With this schedule, the QAP of the GHSG could serve as a model for other study groups.

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

Mackillop, William J., E-mail: william.mackillop@krcc.on.ca; Kong, Weidong; Brundage, Michael

Purpose: Estimates of the appropriate rate of use of radiation therapy (RT) are required for planning and monitoring access to RT. Our objective was to compare estimates of the appropriate rate of use of RT derived from mathematical models, with the rate observed in a population of patients with optimal access to RT. Methods and Materials: The rate of use of RT within 1 year of diagnosis (RT{sub 1Y}) was measured in the 134,541 cases diagnosed in Ontario between November 2009 and October 2011. The lifetime rate of use of RT (RT{sub LIFETIME}) was estimated by the multicohort utilization tablemore » method. Poisson regression was used to evaluate potential barriers to access to RT and to identify a benchmark subpopulation with unimpeded access to RT. Rates of use of RT were measured in the benchmark subpopulation and compared with published evidence-based estimates of the appropriate rates. Results: The benchmark rate for RT{sub 1Y}, observed under conditions of optimal access, was 33.6% (95% confidence interval [CI], 33.0%-34.1%), and the benchmark for RT{sub LIFETIME} was 41.5% (95% CI, 41.2%-42.0%). Benchmarks for RT{sub LIFETIME} for 4 of 5 selected sites and for all cancers combined were significantly lower than the corresponding evidence-based estimates. Australian and Canadian evidence-based estimates of RT{sub LIFETIME} for 5 selected sites differed widely. RT{sub LIFETIME} in the overall population of Ontario was just 7.9% short of the benchmark but 20.9% short of the Australian evidence-based estimate of the appropriate rate. Conclusions: Evidence-based estimates of the appropriate lifetime rate of use of RT may overestimate the need for RT in Ontario.« less

What is access to radiation therapy? A conceptual framework and review of influencing factors.

PubMed

Sundaresan, Puma; Stockler, Martin R; Milross, Christopher G

2016-02-01

Optimal radiation therapy (RT) utilisation rates (RURs) have been defined for various cancer indications through extensive work in Australia and overseas. These benchmarks remain unrealised. The gap between optimal RUR and actual RUR has been attributed to inadequacies in 'RT access'. We aimed to develop a conceptual framework for the consideration of 'RT access' by examining the literature for existing constructs and translating it to the context of RT services. We further aimed to use this framework to identify and examine factors influencing 'RT access'. Existing models of health care access were reviewed and used to develop a multi-dimensional conceptual framework for 'RT access'. A review of the literature was then conducted to identify factors reported to affect RT access and utilisation. The electronic databases searched, the host platform and date range of the databases searched were Ovid MEDLINE, 1946 to October 2014 and PsycINFO via OvidSP,1806 to October 2014. The framework developed demonstrates that 'RT access' encompasses opportunity for RT as well as the translation of this opportunity to RT utilisation. Opportunity for RT includes availability, affordability, adequacy (quality) and acceptability of RT services. Several factors at the consumer, referrer and RT service levels affect the translation of this opportunity for RT to actual RT utilisation. 'Access' is a term that is widely used in the context of health service related research, planning and political discussions. It is a multi-faceted concept with many descriptions. We propose a conceptual framework for the consideration of 'RT access' so that factors affecting RT access and utilisation may be identified and examined. Understanding these factors, and quantifying them where possible, will allow objective evaluation of their impact on RT utilisation and guide implementation of strategies to modify their effects.

Locally targeted delivery of a micron-size radiation therapy source using temperature-sensitive hydrogel.

PubMed

Kim, Yusung; Seol, Dong Rim; Mohapatra, Sucheta; Sunderland, John J; Schultz, Michael K; Domann, Frederick E; Lim, Tae-Hong

2014-04-01

To propose a novel radiation therapy (RT) delivery modality: locally targeted delivery of micron-size RT sources by using temperature-sensitive hydrogel (RT-GEL) as an injectable vehicle. Hydrogel is a water-like liquid at room temperature but gels at body temperature. Two US Food and Drug Administration-approved polymers were synthesized. Indium-111 (In-111) was used as the radioactive RT-GEL source. The release characteristics of In-111 from polymerized RT-GEL were evaluated. The injectability and efficacy of RT-GEL delivery to human breast tumor were tested using animal models with control datasets of RT-saline injection. As proof-of-concept studies, a total of 6 nude mice were tested by injecting 4 million tumor cells into their upper backs after a week of acclimatization. Three mice were injected with RT-GEL and 3 with RT-saline. Single-photon emission computed tomography (SPECT) and CT scans were performed on each mouse at 0, 24, and 48 h after injection. The efficacy of RT-GEL was determined by comparison with that of the control datasets by measuring kidney In-111 accumulation (mean nCi/cc), representing the distant diffusion of In-111. RT-GEL was successfully injected into the tumor by using a 30-gauge needle. No difficulties due to polymerization of hydrogel during injection and intratumoral pressure were observed during RT-GEL injection. No back flow occurred for either RT-GEL or RT-saline. The residual tumor activities of In-111 were 49% at 24 h (44% at 48 h, respectively) for RT-GEL and 29% (22%, respectively) for RT-saline. Fused SPECT-CT images of RT-saline showed considerable kidney accumulation of In-111 (2886%, 261%, and 262% of RT-GEL at 0, 24, and 48 h, respectively). RT-GEL was successfully injected and showed much higher residual tumor activity: 170% (200%, respectively), than that of RT-saline at 24 h (48 h, respectively) after injection with a minimal accumulation of In-111 to the kidneys. Preliminary data of RT-GEL as a delivery modality of a radiation source to a local tumor are promising. Published by Elsevier Inc.

UV-LIGA Microfabrication of 220 GHz Sheet Beam Amplifier Gratings with SU-8 Photoresists

DTIC Science & Technology

2010-01-01

4 4 4a Diethyl ether 3d, RT 0 Tetrahydrofuran (THF) 3d, RT 1 2 4 3 3 Py + pyridinium (Pym) HBr crystals 2d, RT 1 2 3 2 Py + Pym HCl crystals 2d, RT 1...1 1 Acetone + Pym HBr crystals 2d, RT 1 0 Pym dichromate in Py 2d, RT 1 2 1 Pym chlorochromate in Py 2d, RT 4 1 2 1a Propylamine (PA) 2d, RT 1 2 3 2

A Novel High-Throughput Method for Molecular Detection of Human Pathogenic Viruses Using a Nanofluidic Real-Time PCR System

PubMed Central

Coudray-Meunier, Coralie; Fraisse, Audrey; Martin-Latil, Sandra; Delannoy, Sabine; Fach, Patrick; Perelle, Sylvie

2016-01-01

Human enteric viruses are recognized as the main causes of food- and waterborne diseases worldwide. Sensitive and quantitative detection of human enteric viruses is typically achieved through quantitative RT-PCR (RT-qPCR). A nanofluidic real-time PCR system was used to develop novel high-throughput methods for qualitative molecular detection (RT-qPCR array) and quantification of human pathogenic viruses by digital RT-PCR (RT-dPCR). The performance of high-throughput PCR methods was investigated for detecting 19 human pathogenic viruses and two main process controls used in food virology. The conventional real-time PCR system was compared to the RT-dPCR and RT-qPCR array. Based on the number of genome copies calculated by spectrophotometry, sensitivity was found to be slightly better with RT-qPCR than with RT-dPCR for 14 viruses by a factor range of from 0.3 to 1.6 log10. Conversely, sensitivity was better with RT-dPCR than with RT-qPCR for seven viruses by a factor range of from 0.10 to 1.40 log10. Interestingly, the number of genome copies determined by RT-dPCR was always from 1 to 2 log10 lower than the expected copy number calculated by RT-qPCR standard curve. The sensitivity of the RT-qPCR and RT-qPCR array assays was found to be similar for two viruses, and better with RT-qPCR than with RT-qPCR array for eighteen viruses by a factor range of from 0.7 to 3.0 log10. Conversely, sensitivity was only 0.30 log10 better with the RT-qPCR array than with conventional RT-qPCR assays for norovirus GIV detection. Finally, the RT-qPCR array and RT-dPCR assays were successfully used together to screen clinical samples and quantify pathogenic viruses. Additionally, this method made it possible to identify co-infection in clinical samples. In conclusion, given the rapidity and potential for large numbers of viral targets, this nanofluidic RT-qPCR assay should have a major impact on human pathogenic virus surveillance and outbreak investigations and is likely to be of benefit to public health. PMID:26824897

PubMed

Domínguez, Vanihamín; Aguiñiga, Itzen; Moreno, Leticia; Torres, Beatriz; Santiago-Osorio, Edelmiro

2017-12-01

Introducción. El caseinato de sodio, una sal de la caseína utilizada como agente proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e incrementar la producción de citocinas esenciales en dicho evento.Objetivo. Evaluar si el caseinato de sodio es capaz de inducir un efecto biológico en células de origen linfoide y la producción de citocinas involucradas con este linaje.Materiales y métodos: Se utilizaron ratones hembra BALB/c de 8 a 12 semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48 horas, por vía intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v). La población de linfocitos B y la incorporación de bromodesoxiuridina (BrdU) se analizaron mediante citometría de flujo. La detección de la interleucina 7 se evaluó mediante la técnica de ELISA.Resultados. Tras la inyección por vía intraperitoneal, el número de linfocitos B 220+ provenientes del bazo de ratones tratados con caseinato de sodio aumentó comparados con los que solo recibieron el vehículo como tratamiento (89,01±1,03 Vs. 75,66±2,08), así como la incorporación de BrdU en células B220+ (38,59±4,48 Vs. 11,82±1,04). Se evidenció, asimismo, el incremento en la concentración de la interleucina 7 (IL-7) en el suero de los ratones tratados con caseinato de sodio, comparados con los que solo recibieron el vehículo (62,1±17,5 Vs. 26,9±4,4 pg/ml).Conclusión. El caseinato de sodio fue capaz de aumentar el número de linfocitos B en bazo de ratones, así como inducir la producción de IL-7, citocina clave para la linfopoyesis B.

A Quantitative Analysis of the Relationship Between Radiation Therapy Use and Travel Time.

PubMed

Liu, Emma; Santibáñez, Pablo; Puterman, Martin L; Weber, Leah; Ma, Xiang; Sauré, Antoine; Olivotto, Ivo A; Halperin, Ross; French, John; Tyldesley, Scott

2015-11-01

To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services. Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time-RT1y curve was represented by generalized additive and segmented regression models. Analyses were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined. After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time-RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter. Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

A Quantitative Analysis of the Relationship Between Radiation Therapy Use and Travel Time

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

Liu, Emma; Santibáñez, Pablo; Puterman, Martin L.

Purpose: To model and quantify the relationship between radiation therapy (RT) use and travel time to RT services. Methods and Materials: Population-based registries and databases were used to identify both incident cancer patient and patients receiving RT within 1 year of diagnosis (RT1y) in British Columbia, Canada, between 1992 and 2011. The effects of age, gender, diagnosis year, income, prevailing wait time, and travel duration for RT on RT1y were assessed. Significant factors from univariate analyses were included in a multivariable logistic regression model. The shape of the travel time–RT1y curve was represented by generalized additive and segmented regression models. Analysesmore » were conducted for breast, lung, and genitourinary cancer separately and for all cancer sites combined. Results: After adjustment for age, gender, diagnosis year, income, and prevailing wait times, increasing travel time to the closest RT facility had a negative impact RT1y. The shape of the travel time–RT1y curve varied with cancer type. For breast cancer, the odds of RT1y were constant for the first 2 driving hours and decreased at 17% per hour thereafter. For lung cancer, the odds of RT1y decreased by 16% after 20 minutes and then decreased at 6% per hour. Genitourinary cancer RT1y was relatively independent of travel time. For all cancer sites combined, the odds of RT1y were constant within the first 2 driving hours and decreased at 7% per hour thereafter. Conclusions: Travel time to receive RT has a different impact on RT1y for different tumor sites. The results provide evidence-based insights for the configuration of catchment areas for new and existing cancer centers providing RT.« less

Effect of micro mist sauna bathing on thermoregulatory and circulatory functions and thermal sensation in humans

NASA Astrophysics Data System (ADS)

Iwase, Satoshi; Kawahara, Yuko; Nishimura, Naoki; Sugenoya, Junichi

2016-05-01

To examine the effects of micro mist sauna bathing, produced by water crushing method, we exposed ten male subjects to five cases of micro mist sauna, namely (1) room temperature (RT) 38 °C with 100 % (actually 91 %) relative humidity (RH), (2) RT 41.5 °C with 80 % (actually 81 %) RH, (3) RT 41.5 °C with 100 % (actually 96 %) RH, (4) RT 45.0 °C with 64 % (actually 61 %) RH, and (5) RT 45.0 °C with 100 % (actually 86 %) RH, and measured tympanic temperature, mean skin temperature, heart rate (HR), and cheek moisture content, as well as ratings of thermal and sweating sensation tympanic temperatures at RT 45 °C were significantly higher at 86 % RH than those at 61 % RH; however, those at RT 45 °C with 61 % RH were higher than those with 86 % RH during recovery. There were no significant differences at RT 41.5 °C between with 81 % RH and with 96 % RH. Mean skin temperature was the highest at RT 45 °C 86 % RH case, followed by at RT 41.5 °C 96 % RH, RT 45 °C 61 % RH, RT 41.5 °C 81 % RH, and finally at RT 38 °C 91 % RH. HR change showed the same order as for mean skin temperature. A significant difference in cheek moisture content was observed between RT 41.5 °C with 81 % RH and RT 45 °C with 86 % RH 10 min after the micro mist bathing. There were no significant differences between ratings of thermal sensation at RT 41.5 °C with 81 % RH and at RT 45 °C with 61 % RH and RT 45 °C with 61 % RH and RT 45 °C with 86 % RH. Between RT 45 °C with 86 % RH and RT 41.5 °C with 81 % RH, there was a tendency for interaction (0.05 < p < 0.1). Other cases showed significant higher ratings of thermal sensation at higher room temperature or higher relative humidity. The ratings of sweating sensation 10 min after the mist sauna bathing were significantly higher at higher RT and RH except between RT 41.5 °C 96 % RH and RT 45 °C 86 % RH which exhibited no significant difference. We concluded that the micro mist sauna produced by water crushing method induced more moderate and effective thermal effect during micro mist sauna bathing than the conventional mist sauna bathing. In addition, micro mist sauna is as effective for heating the human subjects as bathtub bathing as well as more moderate thermal and sweating sensations.

A novel and highly sensitive real-time nested RT-PCR assay in a single closed tube for detection of enterovirus.

PubMed

Shen, Xin-Xin; Qiu, Fang-Zhou; Zhao, Huai-Long; Yang, Meng-Jie; Hong, Liu; Xu, Song-Tao; Zhou, Shuai-Feng; Li, Gui-Xia; Feng, Zhi-Shan; Ma, Xue-Jun

2018-03-01

The sensitivity of qRT-PCR assay is not adequate for the detection of the samples with lower viral load, particularly in the cerebrospinal fluid (CSF) of patients. Here, we present the development of a highly sensitive real-time nested RT-PCR (RTN RT-PCR) assay in a single closed tube for detection of human enterovirus (HEV). The clinical performance of both RTN RT-PCR and qRT-PCR was also tested and compared using 140 CSF and fecal specimens. The sensitivities of RTN RT-PCR assay for EV71, Coxsackievirus A (CVA)16, CVA6 and CVA10 achieved 10 -8 dilution with a corresponding Ct value of 38.20, 36.45, 36.75, and 36.45, respectively, which is equal to traditional two-step nested RT-PCR assay and approximately 2-10-fold lower than that of qRT-PCR assay. The specificity of RTN RT-PCR assay was extensively analyzed insilico and subsequently verified using the reference isolates and clinical samples. Sixteen qRT-PCR-negative samples were detected by RTN RT-PCR and a variety of enterovirus serotypes was identified by sequencing of inner PCR products. We conclude RTN RT-PCR is more sensitive than qRT-PCR for the detection of HEV in clinical samples. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement and evaluation of national family planning programs.

PubMed

Mauldin, W P

1967-03-01

RESUMEN: En los últimos quince años diez paises han inaugurado programas nacionales de planeamiento familiar: India, Pakistán, Corea del Sur, Taiwan, Turquía, Malasia, Ceilán, Túez, la República Arabe Unida, y Marruecos. Otros paises, incluyendo Tailandia, Hong Kong, Singapur, Kenya, Barbados, Trinidad y los Estados Unidos, apoyan y/o estimulan actividades de planeamiento familiar. En la mayor parte de los casos la razón fundamental del programa ha sido que si la tasa de crecimiento poblacional disminuyera, aumentaría la tasa de crecimiento económico.Las metas de largo alcance, expresadas típicamente en términos de reducir las tasa.de de natalidad o de crecimiento, tienen su ejemplo en el propósito de Pakistán de reducir su tasa de crecimiento a 26 para 1970; el de Corea de reducir su tasa de natalidad a 20 para 1971; y el de India de reducir su tasa de natalidad a 25 para 1973.Los objectivos intermedios, que cubren diversos aspectos del pro grama, incluyen metas específicas para un determinado mes a año, considerando personal, la adquisición de anticonceptivos, y el número de usarios por método. Las metas específicas anuales de aceptantes de dispositivos intrauterinos (IUD), para Taiwán, Corea, Túnez, Pakistán e India, son comunes, tanto por la naturaleza del artefacto, como por la facilidad de medición de los que continúan utilizándolos. El programa de evaluación en Taiwán, que trata de medir por diversos medios los efectos inmediatos, mediatos y de largo plazo del programa de planeamiento familiar sirve de modelo. El propósito de la evaiuación de un programa de planeamiento familiar es contribuir a la efectividad y eficiencia del programa, midiendo y analizando su progreso. Las áreas a medir pueden ser clasificadas como- (1) conocimiento acerca de; (2) actitudes hacia; (3) práctica de control de natalidad; y (4) nivel de fecundidad.Un buen sistema de evaluación debería incluir: A. Un buen conjunto de estadísticas de servicio presentadas en formularios estandarizados, en las siguienies formas: 1. Informes nensuales por áreas administrativas, sobre los actuales servicios de planeamiento familiar proporcionados en la actualidad, de carácter permanente o de larga duración (al presente, esterilización y IUD de acuerdo a las siguientes características del receptor: residencia, edad, paridad (número de hijos vivos por sexo), y donde se enteró del programa, si es posible "clase";(probablemente educación de la madre, pero posiblemente ocupación del esposo, ingreso, o equivalente); prácticas anticonceptivas anteriores; intervalo; y deseo de tener más hijos. En un programa grande estos datos pueden obtenerse en base a una muestra. 2. Informes mensuales sobre la distribución de suministros anticonceptivos (condones, píldoras, sustancias efervescentes, etc.), los primeros suministros deben ir acompañados de un registro de las características del recipiente, como anteriormente; los suministros subsecuentes se regietrarán sólo en volumen bruto. Esto también se aplicará al ritmo, donde éste método se enseñe a un número considerable de mujeres. 3. Informes regulares sobre las actividades de planeamiento familiar de médicos privados, como una estimación del efecto catalítico del programa del gobierno sobre ci sector privado. 4. Datos generates mensuales, ppr áreas admirtistrativas importantes, sabre: visitas domiciliarias, reuniones, cuñas radiates y televisadas, avisos en los periódicos y personal que trabaja. 5. Para propósitos de seguimiento una entrevi eta de campo cada 6 a 12 meses a cada N mujer de las listas para (1) y (2) arriba, en un total de 300 o 400, para conocer las tasas de continuación y las razones de abandono (ej: desea otro hijo, insatisfecha can ci método, otras). Las mue.stras podrían ser de 300 cada una, con una supuesta experiencia de 6, 12, 18 y 24 meses. B. Un buen conjunto de datos sobre costa (datos sobre cotos actulaes atribuíbles directamente al programa de planeamiento familiar) fraccionados par áreas principales y cinco a seis categorías de costos importantes tales coma: adminietración, personal de campo, publicidad, suministros, etc. C. Un buen conjunto de dates globales sobre la distribución de los suministros comerciales que puedan llegar tan cerca como sea posible del último consumidor, to cual significa probablemente obtener información de los mayoristas. D. Una encuesta de conocimientos, actitudes y prácticas (KAP) para una evaluación general cada dos años. Las preguntas básicas (además de las antes mencionadas y estatus marital y étnico cuando sea pertinente) son: actitud hacia e interés por la anticoncepción, número de niños por sexo, deseo de tener más hijos, prácticas anticonceptivas, experiencia sobre abortos, tal vez historia de embarazo (especialmente si esta producirá una tasa de fecundidad válida), aprobación del programa gubernamental (para uso politico), y si está actualmente embarazada (la única y mejor pregunta cuya respuesta habla del efecto sobre la tasa de natalidad). Administrativamente, la responsabilidad por la evalucion debe estar cerca al director, se debe tomar provisiones para obtener informes regulares (meneulaes) y especiales dirigidos a preguntar sobre política. El corolario es que el jefe de evaluación debe tener la confianza del director y debe estar al día en cuanto a las decisiones sabre la politics a seguir. Su trabajo consiste en extractar los aspectos principales que funcionan bien y los no operantes. En cuanto a costos, la evaluación debe hacerse sobre no más del 10 par ciento del costa del programa en paises pequeños (de menos de 30 milliones) y sabre no más del 5 per ciento en paises más grandes.Para medir en que forma el programa satisface el criterio final-la magnitud en que cambia la fecundidad-se debe realizar un trabajo más elaborado en el centro (Universidades, Consejos de población, etc.) para desarrollar una forma (a formas) segura de traducir las estadísticas de servicio en práticas y tal vez aún datos sobre suministro comercial en datos sabre tasas de natalidad. Esto incluye, par ejemplo, los esfuerzos para consolidar observaciones coma "cinco años-mujer de usa de IUD, a 400 condones equivalen a la prevención de un nacimiento," y esfuerzos como los de Pakistán de calcular tasas coma "años de protección de una pareja contra el embarazo."In the belief that a decrease in the rate of population growth will increase economic development, more than ten countries have inaugurated family planning programs in the past fifteen years. To provide a model for measuring the immediate, intermediate, and long-term effects of any such program, the authors use the Taiwan evaluation.The model suggests that a good system of evaluation should include monthly statistics on (1) participants, who are grouped by characteristics; (2) the distribution of supplies, reported at first by the characteristics of recipients, but after by gross volume only; (3) family planning activities of private physicians to measure the catalytic effect on the private sector; (4) new contacts and amount of advertising in mass media; (5) costs broken down by areas and by cost categories; and (6) distribution of commercial supplies. In addition, the program should conduct 300-400 interviews every 6-12 months to learn the rates of continuation and the rates and reasons for discontinuation. Finally, a KAP survey should be conducted every two years.The administration of the evaluation should be close to the director for policy decisions and for the ultimate work of evaluation-the finding of new ways to measure the main goal of change in fertility by the translation of statistics on Services provided and commercial supplies into birth rate data.

SU-F-J-219: Predicting Ventilation Change Due to Radiation Therapy: Dependency On Pre-RT Ventilation and Effort Correction

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

Patton, T; Du, K; Bayouth, J

Purpose: Ventilation change caused by radiation therapy (RT) can be predicted using four-dimensional computed tomography (4DCT) and image registration. This study tested the dependency of predicted post-RT ventilation on effort correction and pre-RT lung function. Methods: Pre-RT and 3 month post-RT 4DCT images were obtained for 13 patients. The 4DCT images were used to create ventilation maps using a deformable image registration based Jacobian expansion calculation. The post-RT ventilation maps were predicted in four different ways using the dose delivered, pre-RT ventilation, and effort correction. The pre-RT ventilation and effort correction were toggled to determine dependency. The four different predictedmore » ventilation maps were compared to the post-RT ventilation map calculated from image registration to establish the best prediction method. Gamma pass rates were used to compare the different maps with the criteria of 2mm distance-to-agreement and 6% ventilation difference. Paired t-tests of gamma pass rates were used to determine significant differences between the maps. Additional gamma pass rates were calculated using only voxels receiving over 20 Gy. Results: The predicted post-RT ventilation maps were in agreement with the actual post-RT maps in the following percentage of voxels averaged over all subjects: 71% with pre-RT ventilation and effort correction, 69% with no pre-RT ventilation and effort correction, 60% with pre-RT ventilation and no effort correction, and 58% with no pre-RT ventilation and no effort correction. When analyzing only voxels receiving over 20 Gy, the gamma pass rates were respectively 74%, 69%, 65%, and 55%. The prediction including both pre- RT ventilation and effort correction was the only prediction with significant improvement over using no prediction (p<0.02). Conclusion: Post-RT ventilation is best predicted using both pre-RT ventilation and effort correction. This is the only prediction that provided a significant improvement on agreement. Research support from NIH grants CA166119 and CA166703, a gift from Roger Koch, and a Pilot Grant from University of Iowa Carver College of Medicine.« less

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

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

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita

2007-09-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites.

PubMed

Gewandter, Jennifer S; Walker, Joanna; Heckler, Charles E; Morrow, Gary R; Ryan, Julie L

2013-12-01

Skin reactions and pain are commonly reported side effects of radiation therapy (RT). To characterize RT-induced symptoms according to treatment site subgroups and identify skin symptoms that correlate with pain. A self-report survey-adapted from the MD Anderson Symptom Inventory and the McGill Pain Questionnaire--assessed RT-induced skin problems, pain, and specific skin symptoms. Wilcoxon Sign Ranked tests compared mean severity or pre- and post-RT pain and skin problems within each RT-site subgroup. Multiple linear regression (MLR) investigated associations between skin symptoms and pain. Survey respondents (N = 106) were 58% female and on average 64 years old. RT sites included lung, breast, lower abdomen, head/neck/brain, and upper abdomen. Only patients receiving breast RT reported significant increases in treatment site pain and skin problems (P < or = .007). Patients receiving head/neck/brain RT reported increased skin problems (P < .0009). MLR showed that post-RT skin tenderness and tightness were most strongly associated with post-RT pain (P = .066 and P = .122, respectively). Small sample size, exploratory analyses, and nonvalidated measure. Only patients receiving breast RT reported significant increases in pain and skin problems at the RT site while patients receiving head/neck/brain RT had increased skin problems but not pain. These findings suggest that the severity of skin problems is not the only factor that contributes to pain and that interventions should be tailored to specifically target pain at the RT site, possibly by targeting tenderness and tightness. These findings should be confirmed in a larger sampling of RT patients.

Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

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

Jang, Joanne W.; Hwang, Wei-Ting; Guzzo, Thomas J.

2012-08-01

Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Securitymore » Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.« less

Maladaptive repetitive thought as a transdiagnostic phenomenon and treatment target: An integrative review.

PubMed

Kaplan, Deanna M; Palitsky, Roman; Carey, Angela L; Crane, Tracy E; Havens, Cody M; Medrano, Michael R; Reznik, Samantha J; Sbarra, David A; O'Connor, Mary-Frances

2018-07-01

Maladaptive repetitive thought (RT), the frequent and repetitive revisiting of thoughts or internal experiences, is associated with a range of psychopathological processes and disorders. We present a synthesis of prior research on maladaptive RT and develop a framework for elucidating and distinguishing between five forms of maladaptive RT. In addition to the previously studied maladaptive RT (worry, rumination, and obsession), this framework is used to identify two additional forms of maladaptive RT (yearning and interoceptive RT). We then present a review of extant psychotherapy intervention research targeting maladaptive RT, focusing both on specific empirically based treatment strategies, and also constructs within treatments that impact maladaptive RT. The paper concludes with recommendations for future basic and intervention research on maladaptive RT and related psychopathologies. © 2018 Wiley Periodicals, Inc.

Combined Effects of Lignosus rhinocerotis Supplementation and Resistance Training on Isokinetic Muscular Strength and Power, Anaerobic and Aerobic Fitness Level, and Immune Parameters in Young Males.

PubMed

Chen, Chee Keong; Hamdan, Nor Faeiza; Ooi, Foong Kiew; Wan Abd Hamid, Wan Zuraida

2016-01-01

This study investigated the effects of Lignosus rhinocerotis (LRS) supplementation and resistance training (RT) on isokinetic muscular strength and power, anaerobic and aerobic fitness, and immune parameters in young males. Participants were randomly assigned to four groups: Control (C), LRS, RT, and combined RT-LRS (RT-LRS). Participants in the LRS and RT-LRS groups consumed 500 mg of LRS daily for 8 weeks. RT was conducted 3 times/week for 8 weeks for participants in the RT and RT-LRS groups. The following parameters were measured before and after the intervention period: Anthropometric data, isokinetic muscular strength and power, and anaerobic and aerobic fitness. Blood samples were also collected to determine immune parameters. Isokinetic muscular strength and power were increased ( P < 0.05) in participants of both RT and RT-LRS groups. RT-LRS group had shown increases ( P < 0.05) in shoulder extension peak torque, shoulder flexion and extension average power, knee flexion peak torque, and knee flexion and extension average power. There were also increases ( P < 0.05) in anaerobic power and capacity and aerobic fitness in this group. Similarly, RT group had increases ( P < 0.05) in shoulder flexion average power, knee flexion and extension peak torque, and knee flexion and extension average power. In addition, increases ( P < 0.05) in anaerobic power and capacity, aerobic fitness, T lymphocytes (CD3 and CD4), and B lymphocytes (CD19) counts were observed in the RT group. RT elicited increased isokinetic muscular strength and power, anaerobic and aerobic fitness, and immune parameters among young males. However, supplementation with LRS during RT did not provide additive benefits.

Combined Effects of Lignosus rhinocerotis Supplementation and Resistance Training on Isokinetic Muscular Strength and Power, Anaerobic and Aerobic Fitness Level, and Immune Parameters in Young Males

PubMed Central

Chen, Chee Keong; Hamdan, Nor Faeiza; Ooi, Foong Kiew; Wan Abd Hamid, Wan Zuraida

2016-01-01

Background: This study investigated the effects of Lignosus rhinocerotis (LRS) supplementation and resistance training (RT) on isokinetic muscular strength and power, anaerobic and aerobic fitness, and immune parameters in young males. Methods: Participants were randomly assigned to four groups: Control (C), LRS, RT, and combined RT-LRS (RT-LRS). Participants in the LRS and RT-LRS groups consumed 500 mg of LRS daily for 8 weeks. RT was conducted 3 times/week for 8 weeks for participants in the RT and RT-LRS groups. The following parameters were measured before and after the intervention period: Anthropometric data, isokinetic muscular strength and power, and anaerobic and aerobic fitness. Blood samples were also collected to determine immune parameters. Results: Isokinetic muscular strength and power were increased (P < 0.05) in participants of both RT and RT-LRS groups. RT-LRS group had shown increases (P < 0.05) in shoulder extension peak torque, shoulder flexion and extension average power, knee flexion peak torque, and knee flexion and extension average power. There were also increases (P < 0.05) in anaerobic power and capacity and aerobic fitness in this group. Similarly, RT group had increases (P < 0.05) in shoulder flexion average power, knee flexion and extension peak torque, and knee flexion and extension average power. In addition, increases (P < 0.05) in anaerobic power and capacity, aerobic fitness, T lymphocytes (CD3 and CD4), and B lymphocytes (CD19) counts were observed in the RT group. Conclusions: RT elicited increased isokinetic muscular strength and power, anaerobic and aerobic fitness, and immune parameters among young males. However, supplementation with LRS during RT did not provide additive benefits. PMID:27833721

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites

PubMed Central

Gewandter, Jennifer S.; Walker, Joanna; Heckler, Charles E.; Morrow, Gary R.; Ryan, Julie L.

2015-01-01

Background Skin reactions and pain are commonly reported side effects of radiation therapy (RT). Objective To characterize RT-induced symptoms according to treatment site subgroups and identify skin symptoms that correlate with pain. Methods A self-report survey, adapted from the MD Anderson Symptom Inventory and the McGill Pain Questionnaire, assessed RT-induced skin problems, pain, and specific skin symptoms. Wilcoxon Sign Ranked tests compared mean severity of pre- and post-RT pain and skin problems within each RT-site subgroup. Multiple linear regression (MLR) investigated associations between skin symptoms and pain. Results Survey respondents (n=106) were 58% female and on average 64 years old. RT sites included lung, breast, lower abdomen, head/neck/brain, and upper abdomen. Only patients receiving breast RT reported significant increases in treatment site pain and skin problems (p≤0.007). Patients receiving head/neck/brain RT reported increased skin problems (p<0.0009). MLR showed that post-RT skin tenderness and tightness were most strongly associated with post-RT pain (p=0.066 and p=0.122, respectively). Limitations Small sample size, exploratory analyses, and non-validated measure. Conclusions Only patients receiving breast RT reported significant increases in pain and skin problems at the RT site, while patients receiving head/neck/brain RT had increased skin problems, but not pain. These findings suggest that the severity of skin problems is not the only factor that contributes to pain, and interventions should be tailored to specifically target pain at the RT site, possibly by targeting tenderness and tightness. These findings should be confirmed in a larger sampling of RT patients. PMID:24645338

Murine Leukemia Virus Reverse Transcriptase: Structural Comparison with HIV-1 Reverse Transcriptase

PubMed Central

Coté, Marie L.; Roth, Monica J.

2008-01-01

Recent X-ray crystal structure determinations of Moloney murine leukemia virus reverse transcriptase (MoMLV RT) have allowed for more accurate structure/function comparisons to HIV-1 RT than were formerly possible. Previous biochemical studies of MoMLV RT in conjunction with knowledge of sequence homologies to HIV-1 RT and overall fold similarities to RTs in general, provided a foundation upon which to build. In addition, numerous crystal structures of the MoMLV RT fingers/palm subdomain had also shed light on one of the critical functions of the enzyme, specifically polymerization. Now in the advent of new structural information, more intricate examination of MoMLV RT in its entirety can be realized, and thus the comparisons with HIV-1 RT may be more critically elucidated. Here, we will review the similarities and differences between MoMLV RT and HIV-1 RT via structural analysis, and propose working models for the MoMLV RT based upon that information. PMID:18294720

Anxiety at the first radiotherapy session for non-metastatic breast cancer: key communication and communication-related predictors.

PubMed

Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Van Houtte, Paul; Coucke, Philippe; Salamon, Emile; Razavi, Darius

2015-01-01

Patients may experience clinically relevant anxiety at their first radiotherapy (RT) sessions. To date, studies have not investigated during/around the RT simulation the key communication and communication-related predictors of this clinically relevant anxiety. Breast cancer patients (n=227) completed visual analog scale (VAS) assessments of anxiety before and after their first RT sessions. Clinically relevant anxiety was defined as having pre- and post-first RT session VAS scores ⩾4 cm. Communication during RT simulation was assessed with content analysis software (LaComm), and communication-related variables around the RT simulation were assessed with questionnaires. Clinically relevant anxiety at the first RT session was predicted by lower self-efficacy to communicate with the RT team (OR=0.65; p=0.020), the perception of lower support received from the RT team (OR=0.70; p=0.020), lower knowledge of RT-associated side effects (OR=0.95; p=0.057), and higher use of emotion-focused coping (OR=1.09; p=0.013). This study provides RT team members with information about potential communication strategies, which may be used to reduce patient anxiety at the first RT session. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of the flexibility training performed immediately before resistance training on muscle hypertrophy, maximum strength and flexibility.

PubMed

Junior, Roberto Moriggi; Berton, Ricardo; de Souza, Thiago Mattos Frota; Chacon-Mikahil, Mara Patrícia Traina; Cavaglieri, Cláudia Regina

2017-04-01

It has been suggested that flexibility training may reduce the total volume of training during resistance trainings. The purpose of this study was to compare the effect of flexibility training immediately before resistance training (FLEX-RT) versus resistance training without flexibility training (RT) on maximum strength and the vastus lateralis muscle cross-sectional area (CSA). Participants had each leg assigned to RT or FLEX-RT. Both groups performed four sets of leg extensions to voluntary failure of 80% of one repetition maximum (1RM); however, FLEX-RT performed two sets of 25 s of static stretching before resistance training. Number of repetitions and total volume were calculated during weeks 1-5 and 6-10. Vastus lateralis muscle CSA, 1RM, and flexibility were assessed at baseline and after 10 weeks. The number of repetitions and total training volume were greater for RT than FLEX-RT for weeks 1-5 and 6-10. Regarding the vastus lateralis muscle CSA, a main time effect was observed, however, greater change was observed for RT than FLEX-RT (12.7 and 7.4%, respectively). A main time effect for 1RM was also observed with similar changes for RT and FLEX-RT (12.7 and 12.9%, respectively). Flexibility was increased pre- to post-training for FLEX-RT with greater change for FLEX-RT (10.1%) than RT (2.1%). These results show that performing flexibility training immediately before resistance training can contribute to a lower number of repetitions, total volume, and muscle hypertrophy.

Structure and expression of MHC class Ib genes of the central M region in rat and mouse: M4, M5, and M6.

PubMed

Lambracht-Washington, Doris; Moore, Yuki F; Wonigeit, Kurt; Lindahl, Kirsten Fischer

2008-04-01

The M region at the telomeric end of the murine major histocompatibility complex (MHC) contains class I genes that are highly conserved in rat and mouse. We have sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones. For the coding parts of the genes few differences were found between the two RT1 haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames; whereas in BN all three genes were intact. In line with the findings in BN, transcription was found for all three rat genes in several tissues from strain Sprague Dawley. Protein expression in transfectants could be demonstrated for RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered, which maps next to RT1.M6-1 outside of the region covered by the cosmid. In addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading frame. Other important differences between the corresponding parts of the M region of the two species are insertion of long LINE repeats, duplication of RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial evolutionary dynamics in this region despite conservation of the class I gene sequences themselves.

Identification of Variables Determining Intrahemispheric Interference between Processing Demands

DTIC Science & Technology

1989-04-01

Abstract Concrete Nonword Visual Field + LVF RVF LVF RVF LVF RVF Measure + RT %Err RT %Err RT %Err RT %Err RT %Err RT %Err Hand + I Left (N-6) 1205 39 1070...LUME I 113. SAND 50 6.89 NADS 114. TENT 50 6.92 ENTT 115. MILK 99 6.92 KLIM 116. FLAG 50 6.92 GLAF 117. TIRE 99 6.92 RETE 118. GIRL 99 6.95 LIRG 119

HIV-1 reverse transcriptase and antiviral drug resistance. Part 2.

PubMed

Das, Kalyan; Arnold, Eddy

2013-04-01

Structures of RT and its complexes combined with biochemical and clinical data help in illuminating the molecular mechanisms of different drug-resistance mutations. The NRTI drugs that are used in combinations have different primary mutation sites. RT mutations that confer resistance to one drug can be hypersensitive to another RT drug. Structure of an RT-DNA-nevirapine complex revealed how NNRTI binding forbids RT from forming a polymerase competent complex. Collective knowledge about various mechanisms of drug resistance by RT has broader implications for understanding and targeting drug resistance in general. In Part 1, we discussed the role of RT in developing HIV-1 drug resistance, structural and functional states of RT, and the nucleoside/nucleotide analog (NRTI) and non-nucleoside (NNRTI) drugs used in treating HIV-1 infections. In this part, we discuss structural understanding of various mechanisms by which RT confers antiviral drug resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke.

PubMed

Nathaniel, Thomas I; Cochran, Thomas; Chaves, Jose; Fulmer, Eric; Sosa, Crystal; Yi, Sara; Fredwall, Megan; Sternberg, Shannon; Blackhurst, Dawn; Nelson, Alfred; Leacock, Rodney

2016-01-01

The objective of this study was to characterize the comorbidities in a population of patients with an acute ischaemic stroke, comparing patients that received recombinant tissue plasminogen activator (rt-PA) to those that did not receive rt-PA. In a retrospective sample of 663 patients admitted for acute ischaemic stroke, this study analysed the effects of co-morbid conditions in the use of rt-PA. It determined non-cerebrovascular risk factors (comorbidities) that differentiate patients who received rt-PA from those who did not receive rt-PA. Patients with a history of carotid stenosis, CHF and previous strokes are significantly (p < 0.05) associated with high risk of not receiving rt-PA. A significant number of patients with a history of hypertension and smoking received rt-PA (p < 0.05). The findings indicate that certain risk factors including carotid stenosis, CHF and previous stroke history impact the treatment of patients with acute ischaemic stroke, specifically the decision to administer rt-PA. Treatment with rt-PA is dependent on stroke severity and onset to treatment time, but the findings suggest that rt-PA use may also depend on patient comorbidities.

Patterns of Care for Locally Advanced Pancreatic Adenocarcinoma Using the National Cancer Database.

PubMed

Amini, Arya; Jones, Bernard L; Stumpf, Priscilla; Leong, Stephen; Lieu, Christopher H; Weekes, Colin; Davis, S Lindsey; Messersmith, Wells A; Purcell, William T; Ghosh, Debashis; Schefter, Tracey; Goodman, Karyn A

2017-08-01

The role of radiotherapy (RT) in locally advanced pancreatic cancer (LAPC) is uncertain. This study examines patterns of care and survival outcomes of LAPC undergoing chemotherapy alone versus chemotherapy plus RT (C + RT). The National Cancer Database was queried for nonmetastatic LAPC patients who received chemotherapy alone or C + RT. Of the 13,695 patients included, 5306 underwent chemotherapy alone and 4971, C + RT. Use of C + RT declined from 2003 to 2011 (73%-53%), whereas chemotherapy alone increased. Of those receiving RT, rates of intensity-modulated radiotherapy (IMRT) increased (27%-72%), whereas 3-dimensional (3D) RT decreased (73%-28%). Unadjusted 1-year overall survival (OS) was longer for versus chemotherapy (45.6% vs 38.7%), as was 2-year OS (12.9% vs 11.9%) (hazard ratio, 0.88; 0.85-0.91; P < 0.001). Under multivariate analysis, C + RT was associated with improved OS (hazard ratio, 0.84; 0.81-0.87; P < 0.001). On subgroup analysis comparing C + IMRT, C + 3D RT, and chemotherapy alone, 1-year OS was 49.1%, 45.1%, and 38.7%, and 2-year OS was 13.1%, 11.6%, and 11.9% accordingly. Utilization of RT in LAPC is decreasing, whereas chemotherapy alone is increasing. Of patients undergoing RT, rates of IMRT are increasing. Whereas C + IMRT appeared to be associated with improved OS compared with chemotherapy alone, 3D RT was not.

Endurance Training Intensity Does Not Mediate Interference to Maximal Lower-Body Strength Gain during Short-Term Concurrent Training

PubMed Central

Fyfe, Jackson J.; Bartlett, Jonathan D.; Hanson, Erik D.; Stepto, Nigel K.; Bishop, David J.

2016-01-01

We determined the effect of concurrent training incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT) on maximal strength, counter-movement jump (CMJ) performance, and body composition adaptations, compared with single-mode resistance training (RT). Twenty-three recreationally-active males (mean ± SD: age, 29.6 ± 5.5 y; V˙O2peak, 44 ± 11 mL kg−1·min−1) underwent 8 weeks (3 sessions·wk−1) of either: (1) HIT combined with RT (HIT+RT group, n = 8), (2) work-matched MICT combined with RT (MICT+RT group, n = 7), or (3) RT performed alone (RT group, n = 8). Measures of aerobic capacity, maximal (1-RM) strength, CMJ performance and body composition (DXA) were obtained before (PRE), mid-way (MID), and after (POST) training. Maximal (one-repetition maximum [1-RM]) leg press strength was improved from PRE to POST for RT (mean change ± 90% confidence interval; 38.5 ± 8.5%; effect size [ES] ± 90% confidence interval; 1.26 ± 0.24; P < 0.001), HIT+RT (28.7 ± 5.3%; ES, 1.17 ± 0.19; P < 0.001), and MICT+RT (27.5 ± 4.6%, ES, 0.81 ± 0.12; P < 0.001); however, the magnitude of this change was greater for RT vs. both HIT+RT (7.4 ± 8.7%; ES, 0.40 ± 0.40) and MICT+RT (8.2 ± 9.9%; ES, 0.60 ± 0.45). There were no substantial between-group differences in 1-RM bench press strength gain. RT induced greater changes in peak CMJ force vs. HIT+RT (6.8 ± 4.5%; ES, 0.41 ± 0.28) and MICT+RT (9.9 ± 11.2%; ES, 0.54 ± 0.65), and greater improvements in maximal CMJ rate of force development (RFD) vs. HIT+RT (24.1 ± 26.1%; ES, 0.72 ± 0.88). Lower-body lean mass was similarly increased for RT (4.1 ± 2.0%; ES; 0.33 ± 0.16; P = 0.023) and MICT+RT (3.6 ± 2.4%; ES; 0.45 ± 0.30; P = 0.052); however, this change was attenuated for HIT+RT (1.8 ± 1.6%; ES; 0.13 ± 0.12; P = 0.069). We conclude that concurrent training incorporating either HIT or work-matched MICT similarly attenuates improvements in maximal lower-body strength and indices of CMJ performance compared with RT performed alone. This suggests endurance training intensity is not a critical mediator of interference to maximal strength gain during short-term concurrent training. PMID:27857692

Endurance Training Intensity Does Not Mediate Interference to Maximal Lower-Body Strength Gain during Short-Term Concurrent Training.

PubMed

Fyfe, Jackson J; Bartlett, Jonathan D; Hanson, Erik D; Stepto, Nigel K; Bishop, David J

2016-01-01

We determined the effect of concurrent training incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT) on maximal strength, counter-movement jump (CMJ) performance, and body composition adaptations, compared with single-mode resistance training (RT). Twenty-three recreationally-active males (mean ± SD: age, 29.6 ± 5.5 y; [Formula: see text], 44 ± 11 mL kg -1 ·min -1 ) underwent 8 weeks (3 sessions·wk -1 ) of either: (1) HIT combined with RT (HIT+RT group, n = 8), (2) work-matched MICT combined with RT (MICT+RT group, n = 7), or (3) RT performed alone (RT group, n = 8). Measures of aerobic capacity, maximal (1-RM) strength, CMJ performance and body composition (DXA) were obtained before (PRE), mid-way (MID), and after (POST) training. Maximal (one-repetition maximum [1-RM]) leg press strength was improved from PRE to POST for RT (mean change ± 90% confidence interval; 38.5 ± 8.5%; effect size [ES] ± 90% confidence interval; 1.26 ± 0.24; P < 0.001), HIT+RT (28.7 ± 5.3%; ES, 1.17 ± 0.19; P < 0.001), and MICT+RT (27.5 ± 4.6%, ES, 0.81 ± 0.12; P < 0.001); however, the magnitude of this change was greater for RT vs. both HIT+RT (7.4 ± 8.7%; ES, 0.40 ± 0.40) and MICT+RT (8.2 ± 9.9%; ES, 0.60 ± 0.45). There were no substantial between-group differences in 1-RM bench press strength gain. RT induced greater changes in peak CMJ force vs. HIT+RT (6.8 ± 4.5%; ES, 0.41 ± 0.28) and MICT+RT (9.9 ± 11.2%; ES, 0.54 ± 0.65), and greater improvements in maximal CMJ rate of force development (RFD) vs. HIT+RT (24.1 ± 26.1%; ES, 0.72 ± 0.88). Lower-body lean mass was similarly increased for RT (4.1 ± 2.0%; ES; 0.33 ± 0.16; P = 0.023) and MICT+RT (3.6 ± 2.4%; ES; 0.45 ± 0.30; P = 0.052); however, this change was attenuated for HIT+RT (1.8 ± 1.6%; ES; 0.13 ± 0.12; P = 0.069). We conclude that concurrent training incorporating either HIT or work-matched MICT similarly attenuates improvements in maximal lower-body strength and indices of CMJ performance compared with RT performed alone. This suggests endurance training intensity is not a critical mediator of interference to maximal strength gain during short-term concurrent training.

Evaluation of a simple test of reaction time for baseline concussion testing in a population of high school athletes.

PubMed

MacDonald, James; Wilson, Julie; Young, Julie; Duerson, Drew; Swisher, Gail; Collins, Christy L; Meehan, William P

2015-01-01

A common sequela of concussions is impaired reaction time. Computerized neurocognitive tests commonly measure reaction time. A simple clinical test for reaction time has been studied previously in college athletes; whether this test is valid and reliable when assessing younger athletes remains unknown. Our study examines the reliability and validity of this test in a population of high school athletes. Cross-sectional study. Two American High Schools. High school athletes (N = 448) participating in American football or soccer during the academic years 2011 to 2012 and 2012 to 2013. All study participants completed a computerized baseline neurocognitive assessment that included a measure of reaction time (RT comp), in addition to a clinical measure of reaction time that assessed how far a standard measuring device would fall prior to the athlete catching it (RT clin). Validity was assessed by determining the correlation between RT clin and RT comp. Reliability was assessed by measuring the intraclass correlation coefficients (ICCs) between the repeated measures of RT clin and RT comp taken 1 year apart. In the first year of study, RT clin and RT comp were positively but weakly correlated (rs = 0.229, P < 0.001). In the second year, there was no significant correlation between RT clin and RT comp (rs = 0.084, P = 0.084). Both RT clin [ICC = 0.608; 95% confidence interval (CI), 0.434-0.728] and RT comp (ICC = 0.691; 95% CI, 0.554-0.786) had marginal reliability. In a population of high school athletes, RT clin had poor validity when compared with RT comp as a standard. Both RT clin and RT comp had marginal test-retest reliability. Before considering the clinical use of RT clin in the assessment of sport-related concussions sustained by high school athletes, the factors affecting reliability and validity should be investigated further. Reaction time impairment commonly results from concussion and is among the most clinically important measures of the condition. The device evaluated in this study has previously been investigated as a reaction time measure in college athletes. This study investigates the clinical generalizability of the device in a younger population. A video abstract showing how the RT clin device is used in practice is available as Supplemental Digital Content 1, http://links.lww.com/JSM/A43.

Effect of low frequency ultrasound on combined rt-PA and eptifibatide thrombolysis in human clots.

PubMed

Meunier, Jason M; Holland, Christy K; Pancioli, Arthur M; Lindsell, Christopher J; Shaw, George J

2009-01-01

Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 microL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA + Epf), with (+US) or without (-US) ultrasound for 30 minutes at 37 degrees C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. LR values for (- US) treated clots were 0.8+/-0.1(control), 1.8+/-0.3 (Epf), 1.5+/-0.2 (rt-PA), and 1.3+/-0.4 (rt-PA + Epf) (% clot width/minute) respectively. In comparison, the (+ US) group exhibited LR values of 1.6+/-0.2 (control), 4.3+/-0.4 (Epf), 6.3+/-0.4 (rt-PA), and 4.6+/-0.6 (rt-PA + Epf). For (- US) treated clots, FCL was 6.0+/-0.8 (control), 9.2+/-2.5 (Epf), 15.6+/-1.7 (rt-PA), and 28.0+/-2.2% (rt-PA + Epf) respectively. FCL for (+ US) clots was 13.5+/-2.4 (control), 20.7+/-6.4 (Epf), 44.4+/-3.6 (rt-PA) and 30.3+/-3.6% (rt-PA + Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined ultrasound, rt-PA and eptifibatide exposure.

Effect of Low Frequency Ultrasound on Combined rt-PA and Eptifibatide Thrombolysis in Human Clots

PubMed Central

Meunier, Jason M.; Holland, Christy K.; Pancioli, Arthur M.; Lindsell, Christopher J.; Shaw, George J.

2009-01-01

Introduction Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment. However, little is known of the efficacy of combined GP IIb-IIIa inhibitor, fibrinolytic and ultrasound treatment. We measure the lytic efficacy of rt-PA, eptifibatide (Epf) and 120 kHz ultrasound treatment in an in-vitro human clot model. Materials and Methods Blood was drawn from 15 subjects after IRB approval. Clots were made in 20 μL pipettes, and placed in a water tank for microscopic visualization during lytic treatment. Clots were exposed to control, rt-PA (rt-PA), eptifibatide (Epf), or rt-PA+eptifibatide (rt-PA+Epf), with or without ultrasound for 30 minutes at 37°C in human plasma. Clot lysis was measured over time, using a microscopic imaging technique. The fractional clot loss (FCL) and initial lytic rate (LR) were used to quantify lytic efficacy. Results and Conclusions LR values for (−US) treated clots were 0.8±0.1(control), 1.8±0.3 (Epf), 1.5±0.2 (rt-PA), and 1.3±0.4 (rt-PA+Epf) (% clot width/minute) respectively. In comparison, the (+US) group exhibited LR values of 1.6±0.2 (control), 4.3±0.4 (Epf), 6.3±0.4 (rt-PA), and 4.6±0.6 (rt-PA+Epf). For (−US) treated clots, FCL was 6.0±0.8 (control), 9.2±2.5 (Epf), 15.6±1.7 (rt-PA), and 28.0±2.2% (rt-PA+Epf) respectively. FCL for (+US) clots was 13.5±2.4 (control), 20.7±6.4 (Epf), 44.4±3.6 (rt-PA) and 30.3±3.6% (rt-PA+Epf) respectively. Although the addition of eptifibatide enhances the in-vitro lytic efficacy of rt-PA in the absence of ultrasound, the efficacy of ultrasound and rt-PA is greater than that of combined ultrasound, rt-PA and eptifibatide exposure. PMID:18619651

Early Detection of Dengue Virus by Use of Reverse Transcription-Recombinase Polymerase Amplification

PubMed Central

Teoh, Boon-Teong; Sam, Sing-Sin; Tan, Kim-Kee; Danlami, Mohammed Bashar; Shu, Meng-Hooi; Johari, Jefree; Hooi, Poh-Sim; Brooks, David; Piepenburg, Olaf; Nentwich, Oliver; Wilder-Smith, Annelies; Franco, Leticia; Tenorio, Antonio

2015-01-01

A method for the rapid diagnosis of early dengue virus (DENV) infection is highly needed. Here, a prototype reverse transcription-recombinase polymerase amplification (RT-RPA) assay was developed. The assay detected DENV RNA in <20 min without the need for thermocycling amplification. The assay enabled the detection of as few as 10 copies of DENV RNA. The designed RT-RPA primers and exo probe detected the DENV genome of at least 12 genotypes of DENV circulating globally without cross-reacting with other arboviruses. We assessed the diagnostic performance of the RT-RPA assay for the detection of DENV RNA in 203 serum samples of patients with clinically suspected dengue. The sera were simultaneously tested for DENV using a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay, quantitative RT-PCR (qRT-PCR), and IgM- and IgG-capture enzyme-linked immunosorbent assays (ELISA). Acute DENV infection was confirmed in 130 samples and 61 of the samples (46.9%) were classified as viremic with qRT-PCR. The RT-RPA assay showed good concordance (κ of ≥0.723) with the RT-LAMP and qRT-PCR assays in detecting the dengue viremic samples. When used in combination with ELISA, both the RT-RPA and RT-LAMP assays increased the detection of acute DENV infection to ≥95.7% (≥45/47) in samples obtained within 5 days of illness. The results from the study suggest that the RT-RPA assay is the most rapid molecular diagnostic tool available for the detection of DENV. Hence, it is possible to use the RT-RPA assay in a laboratory to complement routine serology testing for dengue. PMID:25568438

One-Year Longitudinal Study of Fatigue, Cognitive Functions, and Quality of Life After Adjuvant Radiotherapy for Breast Cancer

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

Noal, Sabine; Clinical Research Department, Centre Francois Baclesse, Caen; Levy, Christelle

Purpose: Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life. Methods and Materials: Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules. Results: At baseline, 60% of the CT-RT patientsmore » expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment. Conclusions: Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.« less

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

Kotti, Angeliki, E-mail: angkotti@yahoo.gr; Holmqvist, Annica; Albertsson, Maria

Purpose: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT. Methods and Materials: The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosamore » (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry. Results: Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569). Conclusions: SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.« less

Breast-Conserving Treatment in the Elderly: Long-Term Results of Adjuvant Hypofractionated and Normofractionated Radiotherapy

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

Kirova, Youlia M.; Campana, Francois; Savignoni, Alexia

2009-09-01

Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). Methods and Materials: Between 1995 and 1999, 367 women aged {>=}70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed bymore » a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.« less

1H-MR spectroscopy and diffusion tensor imaging of normal-appearing temporal white matter in patients with nasopharyngeal carcinoma after irradiation: initial experience.

PubMed

Xiong, Wei Feng; Qiu, Shi Jun; Wang, Hong Zhuo; Lv, Xiao Fei

2013-01-01

To detect radiation-induced changes of temporal lobe normal-appearing white mater (NAWM) following radiation therapy (RT) for nasopharyngeal carcinoma (NPC). Seventy-five H(1)-MR spectroscopy and diffusion-tensor imaging (DTI) examinations were performed in 55 patients before and after receiving fractionated radiation therapy (total dose; 66-75GY). We divided the dataset into six groups, a pre-RT control group and five other groups based on time after completion of RT. N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr, mean diffusibility (MD), functional anisotropy (FA), radial diffusibility (λ(⊥)), and axial diffusibility (λ(||)) were calculated. NAA/Cho and NAA/Cr decreased and λ(⊥) increased significantly within 1 year after RT compared with pre-RT. After 1 year, NAA/Cho, NAA/Cr, and λ(⊥) were not significantly different from pre-RT. In all post-RT groups, FA decreased significantly. λ(||) decreased within 9 months after RT compared with pre-RT, but was not significantly different from pre-RT more than 9 months after RT. DTI and H(1)-MR spectroscopy can be used to detect early radiation-induced changes of temporal lobe NAWM following radiation therapy for NPC. Metabolic alterations and water diffusion characteristics of temporal lobe NAWM in patients with NPC after RT were dynamic and transient. Copyright © 2012 Wiley Periodicals, Inc.

Decoupling of reaction time-related default mode network activity with cognitive demand.

PubMed

Barber, Anita D; Caffo, Brian S; Pekar, James J; Mostofsky, Stewart H

2017-06-01

Reaction Time (RT) is associated with increased amplitude of the Blood Oxygen-Level Dependent (BOLD) response in task positive regions. Few studies have focused on whether opposing RT-related suppression of task activity also occurs. The current study used two Go/No-go tasks with different cognitive demands to examine regions that showed greater BOLD suppression for longer RT trials. These RT-related suppression effects occurred within the DMN and were task-specific, localizing to separate regions for the two tasks. In the task requiring working memory, RT-related de-coupling of the DMN occurred. This was reflected by opposing RT-BOLD effects for different DMN regions, as well as by reduced positive RT-related Psycho-Physiological Interaction (PPI) connectivity within the DMN and a lack of negative RT-related PPI connectivity between DMN and task positive regions. The results suggest that RT-related DMN suppression is task-specific. RT-related de-coupling of the DMN with more complex task demands may contribute to lapses of attention and performance decrements that occur during cognitively-demanding tasks.

Evaluation of two singleplex reverse transcription-Insulated isothermal PCR tests and a duplex real-time RT-PCR test for the detection of porcine epidemic diarrhea virus and porcine deltacoronavirus.

PubMed

Zhang, Jianqiang; Tsai, Yun-Long; Lee, Pei-Yu Alison; Chen, Qi; Zhang, Yan; Chiang, Cheng-Jen; Shen, Yu-Han; Li, Fu-Chun; Chang, Hsiao-Fen Grace; Gauger, Phillip C; Harmon, Karen M; Wang, Hwa-Tang Thomas

2016-08-01

Recent outbreaks of porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) in multiple countries have caused significant economic losses and remain a serious challenge to the swine industry. Rapid diagnosis is critical for the implementation of efficient control strategies before and during PEDV and PDCoV outbreaks. Insulated isothermal PCR (iiPCR) on the portable POCKIT™ device is user friendly for on-site pathogen detection. In the present study, a singleplex PEDV RT-iiPCR, a singleplex PDCoV RT-iiPCR, and a duplex PEDV/PDCoV real-time RT-PCR (rRT-PCR) commercial reagents targeting the M gene were compared to an N gene-based PEDV rRT-PCR and an M gene-based PDCoV rRT-PCR that were previously published and used as reference PCRs. All PCR assays were highly specific and did not cross react with other porcine enteric pathogens. Analytical sensitivities of the PEDV RT-iiPCR, PDCoV RT-iiPCR and duplex PEDV/PDCoV rRT-PCR were determined using in vitro transcribed RNA as well as viral RNA extracted from ten-fold serial dilutions of PEDV and PDCoV cell culture isolates. Performance of each PCR assay was further evaluated using 170 clinical samples (86 fecal swabs, 24 feces, 19 intestines, and 41 oral fluids). Compared to the reference PEDV rRT-PCR, the sensitivity, specificity and accuracy of the PEDV RT-iiPCR were 97.73%, 98.78%, and 98.24%, respectively, and those of the duplex PEDV/PDCoV rRT-PCR were 98.86%, 96.34%, and 97.65%, respectively. Compared to the reference PDCoV rRT-PCR, the sensitivity, specificity and accuracy of the PDCoV RT-iiPCR were 100%, 100%, and 100%, respectively, and those of the PEDV/PDCoV duplex rRT-PCR were 96.34%, 100%, and 98.24%, respectively. Overall, all three new PCR assays were comparable to the reference rRT-PCRs for detection of PEDV and/or PDCoV. The PEDV and PDCoV RT-iiPCRs are potentially useful tools for on-site detection and the duplex PEDV/PDCoV rRT-PCR provides a convenient method to simultaneously detect the two viruses and differentiate PEDV from PDCoV. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of the interferon genes in homozygous rainbow trout reveals two novel genes, alternate splicing and differential regulation of duplicated genes

USGS Publications Warehouse

Purcell, M.K.; Laing, K.J.; Woodson, J.C.; Thorgaard, G.H.; Hansen, J.D.

2009-01-01

The genes encoding the type I and type II interferons (IFNs) have previously been identified in rainbow trout and their proteins partially characterized. These previous studies reported a single type II IFN (rtIFN-??) and three rainbow trout type I IFN genes that are classified into either group I (rtIFN1, rtIFN2) or group II (rtIFN3). In this present study, we report the identification of a novel IFN-?? gene (rtIFN-??2) and a novel type I group II IFN (rtIFN4) in homozygous rainbow trout and predict that additional IFN genes or pseudogenes exist in the rainbow trout genome. Additionally, we provide evidence that short and long forms of rtIFN1 are actively and differentially transcribed in homozygous trout, and likely arose due to alternate splicing of the first exon. Quantitative reverse transcriptase PCR (qRT-PCR) assays were developed to systematically profile all of the rainbow trout IFN transcripts, with high specificity at an individual gene level, in na??ve fish and after stimulation with virus or viral-related molecules. Cloned PCR products were used to ensure the specificity of the qRT-PCR assays and as absolute standards to assess transcript abundance of each gene. All IFN genes were modulated in response to Infectious hematopoietic necrosis virus (IHNV), a DNA vaccine based on the IHNV glycoprotein, and poly I:C. The most inducible of the type I IFN genes, by all stimuli tested, were rtIFN3 and the short transcript form of rtIFN1. Gene expression of rtIFN-??1 and rtIFN-??2 was highly up-regulated by IHNV infection and DNA vaccination but rtIFN-??2 was induced to a greater magnitude. The specificity of the qRT-PCR assays reported here will be useful for future studies aimed at identifying which cells produce IFNs at early time points after infection. ?? 2008 Elsevier Ltd.

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PubMed

Peters, W A; Liu, P Y; Barrett, R J; Stock, R J; Monk, B J; Berek, J S; Souhami, L; Grigsby, P; Gordon, W; Alberts, D S

2000-04-01

To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

Development of recombinase polymerase amplification assays for the rapid detection of peste des petits ruminants virus.

PubMed

Zhang, Yongning; Wang, Jianchang; Zhang, Zhou; Mei, Lin; Wang, Jinfeng; Wu, Shaoqiang; Lin, Xiangmei

2018-04-01

Peste des petits ruminants (PPR) is a severe infectious disease of small ruminants caused by PPR virus (PPRV). Rapid and sensitive detection of PPRV is critical for controlling PPR. This report describes the development and evaluation of a conventional reverse transcription recombinase polymerase amplification (RT-RPA) assay and a real-time RT-RPA assay, targeting the PPRV N gene. Sensitivity analysis revealed that the conventional RT-RPA assay could detect 852 copies of standard PPRV RNA per reaction at 95% probability within 20 min at 41 °C, and the real-time RT-RPA assay could detect 103 copies of RNA molecules per reaction at 95% probability. Specificity analysis showed that both assays have no cross-reactivity with nucleic acid templates prepared from other selected viruses or common pathogens. Clinical evaluation using 162 ovine and hircine serum and nasal swab samples showed that the performance of both the real-time RT-RPA assay and the conventional RT-RPA assay were comparable to that of real-time RT-PCR. The overall agreements between real-time RT-PCR and real-time RT-RPA, and conventional RT-RPA were 99.4% (161/162) and 98.8% (160/162), respectively. The R 2 value of real-time RT-RPA and real-time RT-PCR was 0.900 by linear regression analysis. Our results suggest that both RT-RPA assays have a potential application in the rapid, sensitive and specific detection of PPRV. Copyright © 2018 Elsevier B.V. All rights reserved.

Association of thymidylate synthase gene 3'-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC.

PubMed

Wang, Xia; Wang, Yadi; Wang, Yue; Cheng, Jian; Wang, Yanyun; Ha, Minwen

2013-01-25

Thymidylate synthase (TS) is a key enzyme responsible for DNA synthesis and repair. Altered expression of TS protein or TS gene polymorphisms has been associated with cancer progression and treatment response. This study investigated the expressions of TS and its gene SNPs in non-small cell lung cancer (NSCLC), and then its association with sensitivity to pemetrexed treatment. Immunohistochemistry and qRT-PCR were performed on 160 resected NSCLC specimens and corresponding normal tissues to assess the expressions of TS protein and TS mRNA, and for associations with clinicopathological data. Blood samples of 106 lung adenocarcinoma patients were examined for polymorphisms of the TS gene 3'-UTR 1494del 6 bp, which was then investigated for associations with responses of the patients to pemetrexed treatment and survival. Expression of both TS protein and its mRNA was elevated in NSCLC tissues compared with matched normal tissues, and significantly higher in lung squamous cell carcinoma than in lung adenocarcinoma. TS expression was associated with poor tumor differentiation. Furthermore, the genotyping data showed that 56% of lung adenocarcinoma patients had the TS gene 3'-UTR 1494 bp (-6 bp/-6 bp) genotype and the rest had TS gene 3'-UTR 1494 bp (-6 bp/+6 bp). There was no TS 3'-UTR 1494 bp (+6 bp/+6 bp) genotype in any patients. Statistical analysis revealed that gender, tumor stage, and TS 3'-UTR 1494del 6 bp polymorphism were significant prognostic factors after short-term pemetrexed treatment. Log-rank analysis revealed that patients with the (-6 bp/-6 bp) genotype had significantly better progression-free and overall survival than patients with (-6 bp/+6 bp). This study showed that TS protein is highly expressed in NSCLC and that polymorphisms of TS 3'-UTR 1494del 6 bp are associated with sensitivity of lung adenocarcinoma patients to pemetrexed treatment. This suggests that TS gene polymorphisms should be further evaluated as prognostic markers for personalized therapy in lung adenocarcinoma.

Interference of 1:1 and 2:1 layered phyllosilicates as excipients with ranitidine.

PubMed

Li, Zhaohui; Fitzgerald, Nicole M; Albert, Zachary; Jiang, Wei-Teh

2016-04-01

As natural ingredients and excipients, kaolinite and talc were frequently studied for their interactions with drugs in pharmaceutical formulations. In this study, the uptake of ranitidine (RT) on these two minerals was studied under different physic-chemical conditions and the mechanism of RT uptake on these two minerals contrasted. Although the thermodynamic and kinetic RT uptake on these two minerals was similar and the RT uptake on both minerals were limited to the external surfaces only, drastic difference in RT uptake was found under different equilibrium solution pH and ionic strength conditions. As cation exchange process was strongly affected by solution pH and ionic strength, the RT uptake on kaolinite was dominated by cation exchange and electrostatic interactions, while the RT uptake on talc was more controlled by inter- and intra- molecular hydrogen bonding interactions. For kaolinite, the limiting factor for RT uptake was the specific surface area due to monolayer RT adsorption. In contract, multilayer RT uptake was found on talc surfaces. No matter which mechanism dominated RT uptake on these minerals, the interaction should not be neglected in pharmaceutical formulations should these minerals be used as additives and/or excipients. Copyright © 2015 Elsevier B.V. All rights reserved.

Predictive Models for Regional Hepatic Function Based on 99mTc-IDA SPECT and Local Radiation Dose for Physiologic Adaptive Radiation Therapy

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

Wang, Hesheng, E-mail: hesheng@umich.edu; Feng, Mary; Frey, Kirk A.

2013-08-01

Purpose: High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Methods and Materials: Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF)more » images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose–response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. Results: The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=−0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). Conclusions: 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage.« less

Predictive models for regional hepatic function based on 99mTc-IDA SPECT and local radiation dose for physiologic adaptive radiation therapy.

PubMed

Wang, Hesheng; Feng, Mary; Frey, Kirk A; Ten Haken, Randall K; Lawrence, Theodore S; Cao, Yue

2013-08-01

High-dose radiation therapy (RT) for intrahepatic cancer is limited by the development of liver injury. This study investigated whether regional hepatic function assessed before and during the course of RT using 99mTc-labeled iminodiacetic acid (IDA) single photon emission computed tomography (SPECT) could predict regional liver function reserve after RT. Fourteen patients treated with RT for intrahepatic cancers underwent dynamic 99mTc-IDA SPECT scans before RT, during, and 1 month after completion of RT. Indocyanine green (ICG) tests, a measure of overall liver function, were performed within 1 day of each scan. Three-dimensional volumetric hepatic extraction fraction (HEF) images of the liver were estimated by deconvolution analysis. After coregistration of the CT/SPECT and the treatment planning CT, HEF dose-response functions during and after RT were generated. The volumetric mean of the HEFs in the whole liver was correlated with ICG clearance time. Three models, dose, priori, and adaptive models, were developed using multivariate linear regression to assess whether the regional HEFs measured before and during RT helped predict regional hepatic function after RT. The mean of the volumetric liver HEFs was significantly correlated with ICG clearance half-life time (r=-0.80, P<.0001), for all time points. Linear correlations between local doses and regional HEFs 1 month after RT were significant in 12 patients. In the priori model, regional HEF after RT was predicted by the planned dose and regional HEF assessed before RT (R=0.71, P<.0001). In the adaptive model, regional HEF after RT was predicted by regional HEF reassessed during RT and the remaining planned local dose (R=0.83, P<.0001). 99mTc-IDA SPECT obtained during RT could be used to assess regional hepatic function and helped predict post-RT regional liver function reserve. This could support individualized adaptive radiation treatment strategies to maximize tumor control and minimize the risk of liver damage. Published by Elsevier Inc.

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

Castle, Katherine O., E-mail: kocastle@mdanderson.org; Hoffman, Karen E.; Levy, Lawrence B.

Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis basedmore » on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.« less

Using iRT, a normalized retention time for more targeted measurement of peptides

PubMed Central

Escher, Claudia; Reiter, Lukas; MacLean, Brendan; Ossola, Reto; Herzog, Franz; Chilton, John; MacCoss, Michael J.; Rinner, Oliver

2014-01-01

Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known. Here we present iRT, an empirically derived dimensionless peptide-specific value that allows for highly accurate RT prediction. The iRT of a peptide is a fixed number relative to a standard set of reference iRT-peptides that can be transferred across laboratories and chromatographic systems. We show that iRT facilitates the setup of multiplexed experiments with acquisition windows more than 4 times smaller compared to in silico RT predictions resulting in improved quantification accuracy. iRTs can be determined by any laboratory and shared transparently. The iRT concept has been implemented in Skyline, the most widely used software for MRM experiments. PMID:22577012

Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes?

PubMed

King, Christopher R; Presti, Joseph C; Gill, Harcharan; Brooks, James; Hancock, Steven L

2004-06-01

The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy. Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS. The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively). Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.

Comparison of academic and practice outcomes of rural and traditional track graduates of a family medicine residency program.

PubMed

Petrany, Stephen M; Gress, Todd

2013-06-01

The Marshall University Family Medicine Residency (MUFMR) implemented its rural track (RT) in 1994 to help achieve its mission of producing primary care physicians for practice in rural areas and West Virginia. This study examined the impact of the RT on the program's training outcomes and assessed the academic equivalence of the RT and traditional track (TT) curricula. The authors analyzed academic outcomes (in-training examination [ITE] scores, board certification rates) and practice outcomes (location and type following graduation) for the 174 MUFMR graduates who entered the program from 1984 through 2006. They compared RT and TT graduates who entered after RT implementation (1994-2006) with each other and with graduates who entered during the decade before implementation (1984-1993). There were differences between the 12 RT and 94 TT graduates in rural practice upon graduation (RT: 83% versus TT: 40%; P<.01) and practice in West Virginia (RT 83% versus TT 68%; P=.34). RT and TT graduates had similar mean increases in ITE scores and board certification rates. The 106 post-implementation graduates had a significantly higher rate of West Virginia practice than did the 68 pre-implementation graduates (70% versus 52%; P=.02). RT development was associated with a substantial increase in MUFMR graduates practicing in West Virginia. RT graduates were more likely than TT graduates to practice in rural areas and in the state upon graduation. RT graduates seem to advance academically as well as their TT counterparts.

The structure and health correlates of trait repetitive thought in older adults.

PubMed

Segerstrom, Suzanne C; Roach, Abbey R; Evans, Daniel R; Schipper, Lindsey J; Darville, Audrey K

2010-09-01

Repetitive thought (RT) involves frequent or prolonged thoughts about oneself and one's world, encompassing discrete forms such as trait worry, rumination, processing, and reminiscing. These forms of RT can be described using 3 basic, underlying qualities: total propensity for RT of all types, valence (positive vs. negative content), and purpose (searching or uncertainty vs. solving or certainty). The adaptiveness of discrete forms with regard to health is likely to be related to these qualities, particularly valence and total propensity. The present study confirmed the model and identified the relationship of these qualities of RT to subjective psychological, physical, and cognitive health in older adults aged 60-94 (N = 179). As predicted, more negatively valenced trait RT was associated with worse psychological, physical, and cognitive health. More total propensity for RT was associated only with worse psychological health. Searching purpose was associated only with worse cognitive health. In turn, negatively valenced RT was predicted by poorer executive functions, suggesting that such functions may be important for directing this quality of RT. The valence of older adults' RT is important insofar as it may contribute to their sense of good or ill health. However, the propensity for all kinds of RT to associate with poorer psychological health may reflect the co-occurrence of negative and positive RT, such as rumination and emotional processing. Although RT has not been extensively investigated in older adults, it appears to play an important role in their subjective health. (c) 2010 APA, all rights reserved.

DaRT: A CALL System to Help Students Practice and Develop Reasoning Skills in Choosing English Articles.

ERIC Educational Resources Information Center

Yoshii, Rika; Milne, Alastair

1998-01-01

Describes DaRT, a computer assisted language-learning system for helping English-as-a-Second-Language students master English articles. DaRT uses a diagrammatic reasoning tool to present communicative contexts for exercises in choosing appropriate articles. This paper describes the development of DaRT and DaRT's system components and concludes…

The role of repetitive thought in determining posttraumatic growth and distress following interpersonal trauma.

PubMed

Allbaugh, Lucy Jane; Wright, Margaret O'Dougherty; Folger, Susan F

2016-01-01

Repetitive thought (RT) strategies have been linked to a range of negative outcomes following traumatic interpersonal events but are proposed to serve an adaptive function under particular circumstances. This study examined outcomes following RT within a transdiagnostic framework, and explored the potentially adaptive nature of trait-like and event-related RT. The centrality of a traumatic event to one's identity was explored as a context under which the adaptive nature of RT might change. Young adults with interpersonal violence experiences (N = 163) reported use of trait-like and event-related RT, centrality of the event, depressive, anxious, and posttraumatic stress symptoms (PTSS), posttraumatic depreciation and posttraumatic growth. Hierarchical multiple regression analyses were used to examine main and moderating effects of four types of RT and event centrality on outcome variables. Centrality positively predicted depressive symptoms and PTSS, depreciation, and growth. Brooding RT positively predicted all negative outcomes. Reflecting RT positively predicted anxious symptoms and PTSS and depreciation. Only deliberate RT positively predicted growth. Centrality did not moderate any examined relationships. Findings highlight the importance of addressing specific types of RT in interventions with survivors and of considering centrality as a robust contributor to outcomes following interpersonal violence.

Smart Radiation Therapy Biomaterials.

PubMed

Ngwa, Wilfred; Boateng, Francis; Kumar, Rajiv; Irvine, Darrell J; Formenti, Silvia; Ngoma, Twalib; Herskind, Carsten; Veldwijk, Marlon R; Hildenbrand, Georg Lars; Hausmann, Michael; Wenz, Frederik; Hesser, Juergen

2017-03-01

Radiation therapy (RT) is a crucial component of cancer care, used in the treatment of over 50% of cancer patients. Patients undergoing image guided RT or brachytherapy routinely have inert RT biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to "smart" RT biomaterials, designed to do more than 1 function. Such smart biomaterials include next-generation fiducial markers, brachytherapy spacers, and balloon applicators, designed to respond to stimuli and perform additional desirable functions like controlled delivery of therapy-enhancing payloads directly into the tumor subvolume while minimizing normal tissue toxicities. More broadly, smart RT biomaterials may include functionalized nanoparticles that can be activated to boost RT efficacy. This work reviews the rationale for smart RT biomaterials, the state of the art in this emerging cross-disciplinary research area, challenges and opportunities for further research and development, and a purview of potential clinical applications. Applications covered include using smart RT biomaterials for boosting cancer therapy with minimal side effects, combining RT with immunotherapy or chemotherapy, reducing treatment time or health care costs, and other incipient applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

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

Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan

Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon ofmore » 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.« less

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

Huang Meijuan; Jiang Yu; State Key Laboratory of Biotherapy, West China Hospital, Medical School, Sichuan University, Chengdu

Purpose: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Methods and Materials: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT.more » Results: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving {>=}54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Conclusion: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.« less

Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

PubMed

Specht, Lena

2016-01-01

Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

Monitoring and improving the sensitivity of dengue nested RT-PCR used in longitudinal surveillance in Thailand.

PubMed

Klungthong, Chonticha; Manasatienkij, Wudtichai; Phonpakobsin, Thipwipha; Chinnawirotpisan, Piyawan; Rodpradit, Prinyada; Hussem, Kittinun; Thaisomboonsuk, Butsaya; Ong-ajchaowlerd, Prapapun; Nisalak, Ananda; Kalayanarooj, Siripen; Buddhari, Darunee; Gibbons, Robert V; Jarman, Richard G; Yoon, In-Kyu; Fernandez, Stefan

2015-02-01

AFRIMS longitudinal dengue surveillance in Thailand depends on the nested RT-PCR and the dengue IgM/IgG ELISA. To examine and improve the sensitivity of the nested RT-PCR using a panel of archived samples collected during dengue surveillance. A retrospective analysis of 16,454 dengue IgM/IgG ELISA positive cases collected between 2000 and 2013 was done to investigate the sensitivity of the nested RT-PCR. From these cases, 318 acute serum specimens or extracted RNA, previously found to be negative by the nested RT-PCR, were tested using TaqMan real-time RT-PCR (TaqMan rRT-PCR). To improve the sensitivity of nested RT-PCR, we designed a new primer based on nucleotide sequences from contemporary strains found to be positive by the TaqMan rRT-PCR. Sensitivity of the new nested PCR was calculated using a panel of 87 samples collected during 2011-2013. The percentage of dengue IgM/IgG ELISA positive cases that were negative by the nested RT-PCR varied from 17% to 42% for all serotypes depending on the year. Using TaqMan rRT-PCR, dengue RNA was detected in 194 (61%) of the 318 acute sera or extracted RNA previously found to be negative by the nested RT-PCR. The newly designed DENV-1 specific primer increased the sensitivity of DENV-1 detection by the nested RT-PCR from 48% to 88%, and of all 4 serotypes from 73% to 87%. These findings demonstrate the impact of genetic diversity and signal erosion on the sensitivity of PCR-based methods. Published by Elsevier B.V.

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

Tyldesley, Scott, E-mail: styldesl@bccancer.bc.c; Delaney, Geoff; Foroudi, Farshad

Purpose: Estimates of the need for radiotherapy (RT) using different methods (criterion based benchmarking [CBB]and the Canadian [C-EBEST]and Australian [A-EBEST]epidemiologically based estimates) exist for various cancer sites. We compared these model estimates to actual RT rates for lung, breast, and prostate cancers in British Columbia (BC). Methods and Materials: All cases of lung, breast, and prostate cancers in BC from 1997 to 2004 and all patients receiving RT within 1 year (RT{sub 1Y}) and within 5 years (RT{sub 5Y}) of diagnosis were identified. The RT{sub 1Y} and RT{sub 5Y} proportions in health regions with a cancer center for the mostmore » recent year were then calculated. RT rates were compared with CBB and EBEST estimates of RT needs. Variation was assessed by time and region. Results: The RT{sub 1Y} in regions with a cancer center for lung, breast, and prostate cancers were 51%, 58%, and 33% compared with 45%, 57%, and 32% for C-EBEST and 41%, 61%, and 37% for CBB models. The RT{sub 5Y} rates in regions with a cancer center for lung, breast, and prostate cancers were 59%, 61%, and 40% compared with 61%, 66%, and 61% for C-EBEST and 75%, 83%, and 60% for A-EBEST models. The RT{sub 1Y} rates increased for breast and prostate cancers. Conclusions: C-EBEST and CBB model estimates are closer to the actual RT rates than the A-EBEST estimates. Application of these model estimates by health care decision makers should be undertaken with an understanding of the methods used and the assumptions on which they were based.« less

Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series.

PubMed

Fossati, Nicola; Karnes, R Jeffrey; Boorjian, Stephen A; Moschini, Marco; Morlacco, Alessandro; Bossi, Alberto; Seisen, Thomas; Cozzarini, Cesare; Fiorino, Claudio; Noris Chiorda, Barbara; Gandaglia, Giorgio; Dell'Oglio, Paolo; Joniau, Steven; Tosco, Lorenzo; Shariat, Shahrokh; Goldner, Gregor; Hinkelbein, Wolfgang; Bartkowiak, Detlef; Haustermans, Karin; Tombal, Bertrand; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

2017-06-01

Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT). To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT. Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml. We compared aRT versus observation followed by esRT. The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis). Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population. At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

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

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Uno, Hajime; Krishnan, Monica

2015-10-01

Purpose: Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. Methods and Materials: At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomaticmore » vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. Results: The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. Conclusion: In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥11 and SF RT were associated with a higher rate of SAEs.« less

Patient views and correlates of radiotherapy omission in a population-based sample of older women with favorable-prognosis breast cancer.

PubMed

Shumway, Dean A; Griffith, Kent A; Hawley, Sarah T; Wallner, Lauren P; Ward, Kevin C; Hamilton, Ann S; Morrow, Monica; Katz, Steven J; Jagsi, Reshma

2018-04-18

The omission of radiotherapy (RT) after lumpectomy is a reasonable option for many older women with favorable-prognosis breast cancer. In the current study, we sought to evaluate patient perspectives regarding decision making about RT. Women aged 65 to 79 years with AJCC 7th edition stage I and II breast cancer who were reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results registries were surveyed (response rate, 70%) regarding RT decisions, the rationale for omitting RT, decision-making values, and understanding of disease recurrence risk. We also surveyed their corresponding surgeons (response rate, 77%). Patient characteristics associated with the omission of RT were evaluated using multilevel, multivariable logistic regression, accounting for patient clustering within surgeons. Of 999 patients, 135 omitted RT (14%). Older age, lower tumor grade, and having estrogen receptor-positive disease each were found to be strongly associated with omission of RT in multivariable analyses, whereas the number of comorbidities was not. Non-English speakers were more likely to omit RT (adjusted odds ratio, 5.9; 95% confidence interval, 1.4-24.5). The most commonly reported reasons for RT omission were that a physician advised the patient that it was not needed (54% of patients who omitted RT) and patient choice (41%). Risk of local disease recurrence was overestimated by all patients: by approximately 2-fold among those who omitted RT and by approximately 8-fold among those who received RT. The risk of distant disease recurrence was overestimated by approximately 3-fold on average. To some extent, decisions regarding RT omission are appropriately influenced by patient age, tumor grade, and estrogen receptor status, but do not appear to be optimally tailored according to competing comorbidities. Many women who are candidates for RT omission overestimate their risk of disease recurrence. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Combination therapy of intravenously injected microglia and radiotherapy prolongs survival in a rat model of spontaneous malignant glioma.

PubMed

Okonogi, Noriyuki; Suzuki, Yoshiyuki; Sato, Hiro; Oike, Takahiro; Yoshimoto, Yuya; Mimura, Kousaku; Noda, Shin-Ei; Okamoto, Masahiko; Tamaki, Tomoaki; Morokoshi, Yukie; Hasegawa, Sumitaka; Ohgaki, Hiroko; Yokoo, Hideaki; Nakano, Takashi

2018-06-18

The aim of this study was to investigate the efficacy of combination therapy with intravenously injected microglia (MI) and radiotherapy (RT) for rat malignant glioma. Transgenic rats expressing v-erbB and spontaneously developing malignant glioma were used. The rats were divided into four groups: control (n = 19), RT alone (n = 10), MI alone (n = 9), and combination of MI and RT (MI+RT) (n = 10). Cranial X-ray irradiation (8 Gy per fraction; once per week) was performed at 50 and 51 weeks of age. Cultured rat microglial cells (5 × 10 6 cells/rat) were intravenously injected via the tail vein within 30 minutes after RT. No evidence of side effects including thrombosis or graft-versus-host disease was noted. Rats treated with RT alone, MI alone, MI+RT, and control survived 60.9, 56.3, 66.0, and 56.1 weeks, respectively. The survival period of MI+RT was significantly longer than that of control (p = 0.014), MI alone (p = 0.027), and RT alone (p = 0.049). Immunohistochemical analysis showed significantly higher number of tumor-infiltrated microglia in the RT alone (p = 0.041) and MI+RT groups (p = 0.014) compared with the control. Significantly more CD8-positive lymphocytes were observed in the MI+RT group (p = 0.049) compared with the control. A positive correlation was found between the number of microglia and CD8-positive lymphocytes (R 2 = 0.556). A positive correlation was also found between CD8-positive lymphocytes and survival periods (R 2 = 0.460). MI+RT increased infiltrated microglia and CD8-positive T cells and prolonged the survival in transgenic rats spontaneously developing malignant glioma. Combined immunocellular therapy and RT may provide a novel treatment strategy for malignant glioma. Copyright © 2018. Published by Elsevier Inc.

A comparative study of digital RT-PCR and RT-qPCR for quantification of Hepatitis A virus and Norovirus in lettuce and water samples.

PubMed

Coudray-Meunier, Coralie; Fraisse, Audrey; Martin-Latil, Sandra; Guillier, Laurent; Delannoy, Sabine; Fach, Patrick; Perelle, Sylvie

2015-05-18

Sensitive and quantitative detection of foodborne enteric viruses is classically achieved by quantitative RT-PCR (RT-qPCR). Recently, digital PCR (dPCR) was described as a novel approach to genome quantification without need for a standard curve. The performance of microfluidic digital RT-PCR (RT-dPCR) was compared to RT-qPCR for detecting the main viruses responsible for foodborne outbreaks (human Noroviruses (NoV) and Hepatitis A virus (HAV)) in spiked lettuce and bottled water. Two process controls (Mengovirus and Murine Norovirus) were used and external amplification controls (EAC) were added to examine inhibition of RT-qPCR and RT-dPCR. For detecting viral RNA and cDNA, the sensitivity of the RT-dPCR assays was either comparable to that of RT-qPCR (RNA of HAV, NoV GI, Mengovirus) or slightly (around 1 log10) decreased (NoV GII and MNV-1 RNA and of HAV, NoV GI, NoV GII cDNA). The number of genomic copies determined by dPCR was always from 0.4 to 1.7 log10 lower than the expected numbers of copies calculated by using the standard qPCR curve. Viral recoveries calculated by RT-dPCR were found to be significantly higher than by RT-qPCR for NoV GI, HAV and Mengovirus in water, and for NoV GII and HAV in lettuce samples. The RT-dPCR assay proved to be more tolerant to inhibitory substances present in lettuce samples. This absolute quantitation approach may be useful to standardize quantification of enteric viruses in bottled water and lettuce samples and may be extended to quantifying other human pathogens in food samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiocurability by Targeting Tumor Necrosis Factor-{alpha} Using a Bispecific Antibody in Carcinoembryonic Antigen Transgenic Mice

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

Larbouret, Christel; Robert, Bruno; Linard, Christine

2007-11-15

Purpose: Tumor necrosis factor-{alpha} (TNF-{alpha}) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-{alpha} to target this cytokine in a CEA-expressing colon carcinoma. We report the evaluation of this strategy in immunocompetent CEA-transgenic mice. Methods and Materials: The murine CEA-transfected colon carcinoma MC-38 was used for all experiments. In vitro, clonogenic assays were performed after RT alone, TNF-{alpha} alone, and RT plus TNF-{alpha}. In vivo, the mice were randomly assigned to treatment groups: control, TNF-{alpha}, BsAb, BsAb plus TNF-{alpha},more » RT, RT plus TNF-{alpha}, and RT plus BsAb plus TNF-{alpha}. Measurements of endogenous TNF-{alpha} mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. Results: In vitro, combined RT plus TNF-{alpha} resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p < 0.00001). In vivo, we observed a complete response in 5 (50%) of 10, 2 (20%) of 10, 2 (18.2%) of 11, and 0 (0%) of 12 treated mice in the RT plus BsAb plus TNF-{alpha}, RT plus TNF-{alpha}, RT alone, and control groups, respectively. This difference was statistically significant when TNF-{alpha} was targeted with the BsAb (p = 0.03). The addition of exogenous TNF-{alpha} to RT significantly increased the endogenous TNF-{alpha} mRNA level, particularly when TNF-{alpha} was targeted with BsAb (p < 0.01). The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-{alpha} group. Conclusion: These results suggest that targeting TNF-{alpha} with the BsAb provokes RT curability in a CEA-expressing digestive tumor syngenic model and could be considered as a solid rationale for clinical trials.« less

Comparison of reverse transcriptase PCR, reverse transcriptase loop-mediated isothermal amplification, and culture-based assays for Salmonella detection from pork processing environments.

PubMed

Techathuvanan, Chayapa; Draughon, Frances Ann; D'Souza, Doris Helen

2011-02-01

Novel rapid Salmonella detection assays without the need for sophisticated equipment or labor remain in high demand. Real-time reverse transcriptase PCR (RT-PCR) assays, though rapid and sensitive, require expensive thermocyclers, while a novel RT loop-mediated isothermal amplification (RT-LAMP) method requires only a simple water bath. Our objective was to compare the detection sensitivity of Salmonella Typhimurium from the pork processing environment by RT-LAMP, RT-PCR, and culture-based assays. Carcass and surface swabs and carcass rinses were obtained from a local processing plant. Autoclaved carcass rinses (500 ml) were spiked with Salmonella Typhimurium and filtered. Filters were placed in stomacher bags containing tetrathionate broth (TTB) and analyzed with or without 10-h enrichment at 37 °C. Natural swabs were stomached with buffered peptone water, and natural carcass rinses were filtered, preenriched, and further enriched in TTB. Serially-diluted enriched samples were enumerated by spread plating on xylose lysine Tergitol 4 agar. RNA was extracted from 5 ml of enriched TTB with TRIzol. RT-LAMP assay using previously described invA primers was conducted at 62 °C for 90 min in a water bath with visual detection and by gel electrophoresis. SYBR Green I-based-real-time RT-PCR was carried out with invA primers followed by melt temperature analysis. The results of RT-LAMP detection for spiked carcass rinses were comparable to those of RT-PCR and cultural plating, with detection limits of 1 log CFU/ml, although they were obtained significantly faster, within 24 h including preenrichment and enrichment. RT-LAMP showed 4 of 12 rinse samples positive, while RT-PCR showed 1 of 12 rinse samples positive. For swabs, 6 of 27 samples positive by RT-LAMP and 5 of 27 by RT-PCR were obtained. This 1-day RT-LAMP assay shows promise for routine Salmonella screening by the pork industry. Copyright ©, International Association for Food Protection

The Influence of Radiation Modality and Lymph Node Dissection on Survival in Early-Stage Endometrial Cancer

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

Chino, Junzo P., E-mail: junzo.chino@duke.edu; Jones, Ellen; Berchuck, Andrew

2012-04-01

Background: The appropriate uses of lymph node dissection (LND) and adjuvant radiation therapy (RT) for Stage I endometrial cancer are controversial. We explored the impact of specific RT modalities (whole pelvic RT [WPRT], vaginal brachytherapy [VB]) and LND status on survival. Materials and Methods: The Surveillance Epidemiology and End Results dataset was queried for all surgically treated International Federation of Gynecology and Obstetrics (FIGO) Stage I endometrial cancers; subjects were stratified into low, intermediate and high risk cohorts using modifications of Gynecologic Oncology Group (GOG) protocol 99 and PORTEC (Postoperative Radiation Therapy in Endometrial Cancer) trial criteria. Five-year overall survivalmore » was estimated, and comparisons were performed via the log-rank test. Results: A total of 56,360 patients were identified: 70.4% low, 26.2% intermediate, and 3.4% high risk. A total of 41.6% underwent LND and 17.6% adjuvant RT. In low-risk disease, LND was associated with higher survival (93.7 LND vs. 92.7% no LND, p < 0.001), whereas RT was not (91.6% RT vs. 92.9% no RT, p = 0.23). In intermediate-risk disease, LND (82.1% LND vs. 76.5% no LND, p < 0.001) and RT (80.6% RT vs. 74.9% no RT, p < 0.001) were associated with higher survival without differences between RT modalities. In high-risk disease, LND (68.8% LND vs. 54.1% no LND, p < 0.001) and RT (66.9% RT vs. 57.2% no RT, p < 0.001) were associated with increased survival; if LND was not performed, VB alone was inferior to WPRT (p = 0.01). Conclusion: Both WPRT and VB alone are associated with increased survival in the intermediate-risk group. In the high-risk group, in the absence of LND, only WPRT is associated with increased survival. LND was also associated with increased survival.« less

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

Eich, Hans Theodor; Gossmann, Axel; Engert, Andreas

Purpose: The role of radiotherapy (RT) after intensive chemotherapy in patients with advanced stage Hodgkin's lymphoma (HL) is still unclear. The German Hodgkin Study Group (GHSG) randomized HD12 trial was designed to test whether consolidative RT in the region of initial bulky disease and of residual disease is necessary after effective chemotherapy. A quality control program based on a multidisciplinary panel of radiation oncologists, radiologists, and medical oncologists who reviewed all patients' staging and restaging imaging was initiated. Methods and Materials: A total of 1661 patients aged 16 to 65 years with HL in Stage IIB (large mediastinal mass and/ormore » E-lesions) or Stage III to IV were randomized from January 1999 to January 2003 according to a factorial design between: 8 esc.BEACOPP + RT (arm A), 8 esc.BEACOPP non-RT (arm B), 4+4BEACOPP + RT (arm C), 4+4BEACOPP non-RT (arm D). Results: In the fifth interim analysis, 1449 patients were eligible for the arm comparison with regard to RT. After a median observation time of 48 months the FFTF rate was 86% and the OS 92%. The FFTF was 95% in the RT arms A+C and 88% in the non-RT arms B+D: no sequential significant difference. One thousand and eighty four patients were evaluated by the panel. The panel defined initial bulky disease in 800 patients and residual disease in 600 patients. The panel recommended continuation of therapy according to the randomization for 934 of 1084 patients and additive RT independently from the randomization arm for 145 of 1084 patients. Conclusions: The study showed that RT can be reduced substantially after effective chemotherapy. However, because of the irradiation of 10% of patients in the non-RT arms, equivalent effectiveness of a non-RT strategy cannot be proved. A substantial limitation of consolidative RT according to expert panel recommendations appears to be possible without reducing effectiveness.« less

Need for Resourcefulness Training for Women Caregivers of Elders with Dementia.

PubMed

Zauszniewski, Jaclene A; Lekhak, Nirmala; Yolpant, Wichiya; Morris, Diana L

2015-01-01

Nearly ten million American women are caregivers of elders with dementia and may experience overwhelming stress that adversely affects their mental health. Interventions to teach them resourcefulness skills for managing stress can promote optimal mental health and facilitate continued caregiving. However, effectiveness of resourcefulness training (RT) cannot be examined until its need is established. This pilot trial with 138 women caregivers of someone with dementia examined the need for RT using subjective and objective data. Data were collected before and after RT. Data analysis focused on baseline resourcefulness scores (higher scores = lower need); scores in relation to attrition; correlations among resourcefulness, stress, and depressive symptoms; and post-RT evaluation of the need for RT. Baseline resourcefulness scores were normally distributed and showed that 74% of the caregivers had a moderate to high need for RT. Reasons for attrition were unrelated to the need for RT; however, caregivers who dropped out had resourcefulness scores that averaged two points higher than those who remained in the study. Lower resourcefulness was associated greater stress (r = -.37, p < .001) and depressive symptoms (r = -.52, p < .001). Of the 63 caregivers who received RT, 82% (n = 52) reported a felt need for RT and 94% (n = 59) believed that other caregivers need RT. The results suggest a substantial need for resourcefulness training in women dementia caregivers and support moving forward to test RT's effectiveness for reducing caregiver stress and depressive symptoms.

Modeling Real-Time Applications with Reusable Design Patterns

NASA Astrophysics Data System (ADS)

Rekhis, Saoussen; Bouassida, Nadia; Bouaziz, Rafik

Real-Time (RT) applications, which manipulate important volumes of data, need to be managed with RT databases that deal with time-constrained data and time-constrained transactions. In spite of their numerous advantages, RT databases development remains a complex task, since developers must study many design issues related to the RT domain. In this paper, we tackle this problem by proposing RT design patterns that allow the modeling of structural and behavioral aspects of RT databases. We show how RT design patterns can provide design assistance through architecture reuse of reoccurring design problems. In addition, we present an UML profile that represents patterns and facilitates further their reuse. This profile proposes, on one hand, UML extensions allowing to model the variability of patterns in the RT context and, on another hand, extensions inspired from the MARTE (Modeling and Analysis of Real-Time Embedded systems) profile.

HIV-1 RT Inhibitors with a Novel Mechanism of Action: NNRTIs that Compete with the Nucleotide Substrate

PubMed Central

Maga, Giovanni; Radi, Marco; Gerard, Marie-Aline; Botta, Maurizio; Ennifar, Eric

2010-01-01

HIV-1 reverse transcriptase (RT) inhibitors currently used in antiretroviral therapy can be divided into two classes: (i) nucleoside analog RT inhibitors (NRTIs), which compete with natural nucleoside substrates and act as terminators of proviral DNA synthesis, and (ii) non-nucleoside RT inhibitors (NNRTIs), which bind to a hydrophobic pocket close to the RT active site. In spite of the efficiency of NRTIs and NNRTIs, the rapid emergence of multidrug-resistant mutations requires the development of new RT inhibitors with an alternative mechanism of action. Recently, several studies reported the discovery of novel non-nucleoside inhibitors with a distinct mechanism of action. Unlike classical NNRTIs, they compete with the nucleotide substrate, thus forming a new class of RT inhibitors: nucleotide-competing RT inhibitors (NcRTIs). In this review, we discuss current progress in the understanding of the peculiar behavior of these compounds. PMID:21994659

Evaluation of dog owners' perceptions concerning radiation therapy

PubMed Central

Denneberg, Nanna Åkerlund; Egenvall, Agneta

2009-01-01

Background External radiation therapy (RT) has been available for small animals in Sweden since 2006. This study was designed to obtain information on owner experiences and perceptions related to RT of cancer in their dogs. Another survey was used to determine the attitudes about use of RT in a group of Swedish veterinarians. Their responses were analyzed and compared to their level of knowledge of oncology and RT. Methods Owners of all dogs (n = 23) who had undergone RT for malignancy at Jönköping Small Animal Hospital between March 2006 to September 2007 were interviewed. A questionnaire was given to a selected group of veterinarians. Results All 23 owners responded. All owners thought that their dog did well during RT and most that their dog was also fine during the following phase when acute RT-related skin reactions occur and heal. Three owners stated that their dog had pain that negatively impacted quality of life because of radiation dermatitis. Five owners reported that RT positively impacted quality of life of the dog during the first weeks after RT because palliation was achieved. The owners were not disturbed by the efforts required of them. All but one owner (22 of 23) stated that they would make the same decision about RT again if a similar situation occurred. The most important factor for this decision was the chance to delay occurrence of tumour-related discomfort. The chance for cure was of less importance but still essential, followed by expected side effects. Time commitments, travel, number of treatments required and financial cost; all had low impact. The veterinarian survey showed that less background knowledge of small animal oncology/RT was associated with more negative expectations of RT for small animals. Conclusion The results show that for these owners, RT was a worthwhile treatment modality and that the discomfort for the dog was manageable and acceptable relative to the benefits. Improved continuing education about small animal RT in Sweden will likely result in increased evidence-based and positive treatment recommendations concerning RT by veterinarians. PMID:19402904

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

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

Sher, David J., E-mail: david_sher@rush.edu; Fidler, Mary Jo; Seder, Christopher W.

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gymore » (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to achieve additional benefit with dose escalation.« less

Does adjuvant radiotherapy suppress liver regeneration after partial hepatectomy?

PubMed

Choi, Jin-Hwa; Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W

2009-05-01

To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 +/- 38.3cm(3) and 81.5 +/- 75.6cm(3), respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

Bacterial screening of apheresis platelets with a rapid test: a 113-month single center experience.

PubMed

Ruby, Kristen N; Thomasson, Reggie R; Szczepiorkowski, Zbigniew M; Dunbar, Nancy M

2018-04-17

The 2016 Food and Drug Administration draft guidance describes the use of a rapid test (RT) to enhance platelet transfusion safety and availability. This study reports a 113-month experience of screening of apheresis platelets (APs) by RT. From July 2008 to October 2015, all APs underwent an RT on Day 4. Day 6 and 7 units were transfused with transfusion medicine physician approval. Any units remaining on Day 8 had a second RT performed. From November 2015 to November 2017, APs underwent an RT on Day 5 with a repeat RT on Days 6 and 7. During both periods, positive RTs underwent confirmatory testing with culture when repeat testing was positive. A total of 9009 APs underwent an RT on Day 4 or 5. Of these, 45 (0.5%) were RT positive, with no true positives. A total of 754 underwent a second RT on Day 8, with no positives. Since November 2015, 1152 platelets have undergone a second RT on Day 6; 391 have undergone a third RT on Day 7. Of these, five (0.4%) were RT positive on Day 6, with no true positives. There were no septic transfusion reactions identified by passive surveillance at our institution during either study period. To date, we have not detected any true positives after performing 11,306 tests on 9009 APs. A total of 1906 underwent testing twice, and 391 underwent testing three times. We did not identify any conversions from negative to positive on repeat testing. © 2018 AABB.

Comparison of Treatment Tolerance and Outcomes in Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy in a Prospective Randomized Trial or With Standard Treatment

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

Torres, Mylin A.; Jhingran, Anuja; Thames, Howard D.

Purpose: To compare the treatment and outcomes of cervical cancer patients treated with concurrent chemoradiotherapy (CT-RT) in a multi-institutional trial or as standard care. Patients and Methods: We reviewed the records of 302 patients treated with CT-RT for locoregionally confined, intact cervical cancer between 1990 and 2005. Of the 302 patients, 76 were treated using cisplatin and 5-fluorouracil (C/F) on Radiation Therapy Oncology Group protocol 90-01 (CT-RT{sub 90-01}); 226 underwent CT-RT as standard care with either C/F [CT-RT{sub SC(C/F)}; n = 115] or weekly cisplatin [CT-RT{sub SC(WC)}; n = 111). Results: The CT-RT{sub 90-01} patients more often had tumors {>=}6more » cm and were less often diabetic than were the CT-RT{sub SC} patients. The CT-RT{sub SC(WC)} patients were more likely than the CT-RT{sub SC(C/F)} patients to be {>=}60 years old or to have Stage III-IV disease. During treatment, CT-RT{sub SC(C/F)} patients experienced more Grade 2-3 neutropenia and were, therefore, less likely to receive 200 mg/m{sup 2} cisplatin than were either CT-RT{sub SC(WC)} or CT-RT{sub 90-01} patients (52% vs. 77% vs. 85%, respectively; p <0.001). At 5 years, the disease-specific survival rates were greater for patients treated with C/F [CT-RT{sub SC(C/F)}, 75%; CT-RT{sub 90-01}, 79%] than for those treated with CT-RT{sub SC(WC)} (58%; p = 0.02). On multivariate analysis, C/F chemotherapy, cisplatin dose {>=}200 mg/m{sup 2}, Stage I-II disease, and negative pelvic lymph nodes were independent predictors of improved disease-specific survival. Conclusions: Even within a large comprehensive cancer center, the high rates of chemotherapy completion achieved on a multi-institutional trial can be difficult to reproduce in standard practice. Although C/F toxicity was greater in the standard care patients, their outcomes were similar to those of patients treated with C/F on Radiation Therapy Oncology Group protocol 90-01.« less

Using iRT, a normalized retention time for more targeted measurement of peptides.

PubMed

Escher, Claudia; Reiter, Lukas; MacLean, Brendan; Ossola, Reto; Herzog, Franz; Chilton, John; MacCoss, Michael J; Rinner, Oliver

2012-04-01

Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known. Here we present iRT, an empirically derived dimensionless peptide-specific value that allows for highly accurate RT prediction. The iRT of a peptide is a fixed number relative to a standard set of reference iRT-peptides that can be transferred across laboratories and chromatographic systems. We show that iRT facilitates the setup of multiplexed experiments with acquisition windows more than four times smaller compared to in silico RT predictions resulting in improved quantification accuracy. iRTs can be determined by any laboratory and shared transparently. The iRT concept has been implemented in Skyline, the most widely used software for MRM experiments. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Reverse Transcription Thermostable Helicase-Dependent DNA Amplification for the Detection of Tomato Spotted Wilt Virus.

PubMed

Wu, Xinghai; Chen, Chanfa; Xiao, Xizhi; Deng, Ming Jun

2016-11-01

A protocol for the reverse transcription-helicase-dependent amplification (RT-HDA) of isothermal DNA was developed for the detection of tomato spotted wilt virus (TSWV). Specific primers, which were based on the highly conserved region of the N gene sequence in TSWV, were used for the amplification of virus's RNA. The LOD of RT-HDA, reverse transcriptase-loop-mediated isothermal amplification (RT-LAMP), and reverse transcriptase-polymerase chain reaction (RT-PCR) assays were conducted using 10-fold serial dilution of RNA eluates. TSWV sensitivity in RT-HDA and RT-LAMP was 4 pg RNA compared with 40 pg RNA in RT-PCR. The specificity of RT-HDA for TSWV was high, showing no cross-reactivity with other tomato and Tospovirus viruses including cucumber mosaic virus (CMV), tomato black ring virus (TBRV), tomato mosaic virus (ToMV), or impatiens necrotic spot virus (INSV). The RT-HDA method is effective for the detection of TSWV in plant samples and is a potential tool for early and rapid detection of TSWV.

Archaeological Testing of the Bauman Site (23STG158) Ste. Genevieve County, Missouri.

DTIC Science & Technology

1985-05-01

represented--Odocoileus (deer) spp., Cervis canadensis (elk), and Procyon lotor (raccoon)-- and only two taxa of fish-- Amia calva (bowfin) and...t. complete (153) Amia calve maxilla rt. complete (153) Asnia calva ectopterygoid it. complete (153) Amia calve hymandibular rt. complete (153) Asia...calve articular rt. complete (154) Amia calva dorsal postorbital It. complete (155) Asnia calve ceratohyal rt. complete (156) Aia calve parital rt

β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men.

PubMed

Stout, Jeffrey R; Fukuda, David H; Kendall, Kristina L; Smith-Ryan, Abbie E; Moon, Jordan R; Hoffman, Jay R

2015-04-01

The effects of 12-weeks of HMB ingestion and resistance training (RT) on abdominal adiposity were examined in 48 men (66-78 yrs). All participants were randomly assigned to 1 of 4 groups: no-training placebo (NT-PL), HMB only (NT-HMB), RT with PL (RT-PL), or HMB with RT (RT-HMB). DXA was used to estimate abdominal fat mass (AFM) by placing the region of interest over the L1-L4 region of the spine. Outcomes were assessed by ANCOVA, with Bonferroni-corrected pairwise comparisons. Baseline AFM values were used as the covariate. The ANCOVA indicated a significant difference (p = 0.013) between group means for the adjusted posttest AFM values (mean (kg) ± SE: NT-PL = 2.59 ± 0.06; NT-HMB = 2.59 ± 0.61; RT-PL = 2.59 ± 0.62; RT-HMB = 2.34 ± 0.61). The pairwise comparisons indicated that AFM following the intervention period in the RT-HMB group was significantly less than NT-PL (p = 0.013), NT-HMB (p = 0.011), and RT-PL (p = 0.010). These data suggested that HMB in combination with 12 weeks of RT decreased AFM in elderly men. Copyright © 2015. Published by Elsevier Inc.

Evaluation of a duplex reverse-transcription real-time PCR assay for the detection of encephalomyocarditis virus.

PubMed

Qin, Shaomin; Underwood, Darren; Driver, Luke; Kistler, Carol; Diallo, Ibrahim; Kirkland, Peter D

2018-06-01

We evaluated a fluorogenic probe-based assay for the detection of encephalomyocarditis virus (EMCV) by comparing a set of published primers and probe to a new set of primers and probe. The published reagents failed to amplify a range of Australian isolates and an Italian reference strain of EMCV. In contrast, an assay based on 2 new sets of primers and probes that were run in a duplex reverse-transcription real-time PCR (RT-rtPCR) worked well, with high amplification efficiency. The analytical sensitivity was ~100-fold higher than virus isolation in cell culture. The intra-assay variation was 0.21-4.90%. No cross-reactivity was observed with a range of other porcine viruses. One hundred and twenty-two clinical specimens were tested simultaneously by RT-rtPCR and virus isolation in cell culture; 72 specimens gave positive results by RT-rtPCR, and 63 of these were also positive by virus isolation. Of 245 archived cell culture isolates of EMCV that were tested in the RT-rtPCR, 242 samples were positive. The new duplex RT-rtPCR assay is a reliable tool for the detection of EMCV in clinical specimens and for use in epidemiologic investigations.

Effect of Combined Sensorimotor-Resistance Training on Strength, Balance, and Jumping Performance of Soccer Players.

PubMed

Manolopoulos, Konstantinos; Gissis, Ioannis; Galazoulas, Christos; Manolopoulos, Evaggelos; Patikas, Dimitrios; Gollhofer, Albert; Kotzamanidis, Christos

2016-01-01

The purpose of the study was to investigate the effects of resistance training (RT) and sensorimotor training combined with RT (SM-RT) on balance, 1 repetition maximum (RM), rate of force development (RFD), and squat jump (SJ) height. Twenty amateur soccer players were equally divided into 2 groups assigned as SM-RT group (age: 22 ± 1.7 years, body mass: 79.9 ± 6.3 kg, body height: 1.81 ± 0.06 m) and RT group (age: 21.3 ± 1.3 years, body mass: 77.4 ± 9.3 kg, body height: 1.78 ± 0.04 m). Both groups were trained over a 6-week period with 2 session units per week. SM-RT group performed sensorimotor training (balance on balance board) followed by a high-intensity RT at 8-5RM leg press. The RT group performed the resistance program only. Both groups showed significantly increased 1RM leg press strength, RFD, SJ height, and balance abilities (p ≤ 0.05), whereas no significant between-group differences were observed in any of the outcome variables (p > 0.05). It was concluded that SM-RT was not superior compared with RT for both balance and strength enhancement. These findings have implications in time management during training for soccer players.

Both structural and non-structural forms of the readthrough protein of cucurbit aphid-borne yellows virus are essential for efficient systemic infection of plants.

PubMed

Boissinot, Sylvaine; Erdinger, Monique; Monsion, Baptiste; Ziegler-Graff, Véronique; Brault, Véronique

2014-01-01

Cucurbit aphid-borne yellows virus (CABYV) is a polerovirus (Luteoviridae family) with a capsid composed of the major coat protein and a minor component referred to as the readthrough protein (RT). Two forms of the RT were reported: a full-length protein of 74 kDa detected in infected plants and a truncated form of 55 kDa (RT*) incorporated into virions. Both forms were detected in CABYV-infected plants. To clarify the specific roles of each protein in the viral cycle, we generated by deletion a polerovirus mutant able to synthesize only the RT* which is incorporated into the particle. This mutant was unable to move systemically from inoculated leaves inferring that the C-terminal half of the RT is required for efficient long-distance transport of CABYV. Among a collection of CABYV mutants bearing point mutations in the central domain of the RT, we obtained a mutant impaired in the correct processing of the RT which does not produce the RT*. This mutant accumulated very poorly in upper non-inoculated leaves, suggesting that the RT* has a functional role in long-distance movement of CABYV. Taken together, these results infer that both RT proteins are required for an efficient CABYV movement.

Both Structural and Non-Structural Forms of the Readthrough Protein of Cucurbit aphid-borne yellows virus Are Essential for Efficient Systemic Infection of Plants

PubMed Central

Boissinot, Sylvaine; Erdinger, Monique; Monsion, Baptiste; Ziegler-Graff, Véronique; Brault, Véronique

2014-01-01

Cucurbit aphid-borne yellows virus (CABYV) is a polerovirus (Luteoviridae family) with a capsid composed of the major coat protein and a minor component referred to as the readthrough protein (RT). Two forms of the RT were reported: a full-length protein of 74 kDa detected in infected plants and a truncated form of 55 kDa (RT*) incorporated into virions. Both forms were detected in CABYV-infected plants. To clarify the specific roles of each protein in the viral cycle, we generated by deletion a polerovirus mutant able to synthesize only the RT* which is incorporated into the particle. This mutant was unable to move systemically from inoculated leaves inferring that the C-terminal half of the RT is required for efficient long-distance transport of CABYV. Among a collection of CABYV mutants bearing point mutations in the central domain of the RT, we obtained a mutant impaired in the correct processing of the RT which does not produce the RT*. This mutant accumulated very poorly in upper non-inoculated leaves, suggesting that the RT* has a functional role in long-distance movement of CABYV. Taken together, these results infer that both RT proteins are required for an efficient CABYV movement. PMID:24691251

Development of a reverse transcription loop-mediated isothermal amplification method for the rapid detection of avian influenza virus subtype H7.

PubMed

Bao, Hongmei; Wang, Xiurong; Zhao, Yuhui; Sun, Xiaodong; Li, Yanbing; Xiong, Yongzhong; Chen, Hualan

2012-01-01

A rapid and sensitive reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of the H7 avian influenza virus (H7 AIV) isotype was developed. The minimum detection limit of the RT-LAMP assay was 0.1-0.01 PFU per reaction for H7 AIV RNA, making this assay 100-fold more sensitive than the conventional RT-PCR method. This RT-LAMP assay also has the capacity to detect both high- and low-pathogenic H7 AIV strains. Using a pool of RNAs extracted from influenza viruses corresponding to all 15 HA subtypes (in addition to other avian pathogenic viruses), the RT-LAMP system was confirmed to amplify only H7 AIV RNA. Furthermore, specific pathogen free (SPF) chickens were infected artificially with H7 AIV, throat and cloacal swabs were collected, and viral shedding was examined using viral isolation, RT-PCR and RT-LAMP. Shedding was detected following viral isolation and RT-LAMP one day after infection, whereas viral detection using RT-PCR was effective only on day 3 post-infection. These results indicate that the RT-LAMP method could facilitate epidemiological surveillance and the rapid diagnosis of the avian influenza subtype H7. Copyright © 2011 Elsevier B.V. All rights reserved.

Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology tips the scales.

PubMed

Federmann, Birgit; Mueller, Martin R; Steinhilber, Julia; Horger, Marius S; Fend, Falko

2018-06-12

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2-5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer.

PubMed

Valle, Thaína Dalla; Turrini, Ruth Natalia Teresa; Poveda, Vanessa de Brito

2017-05-15

to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008) and the implementation of preventive follow-up (p<0.001) were associated with shorter periods between the search for care and the beginning of treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated with faster demand for care. the longer interval between the search for medical care and the diagnosis was possibly due to the non-association between the presented symptoms and the disease. identificar o tempo entre os sintomas, a busca por assistência e o início do tratamento em pacientes com câncer de estômago e colorretal e os fatores que interferem nesses processos. estudo descritivo correlacional, incluindo 101 pacientes com diagnóstico de câncer de estômago ou colorretal, atendidos por um hospital especializado em oncologia. dos 101 pacientes investigados, houve predomínio do sexo masculino, média de idade de 61,7 anos. A busca por assistência médica ocorreu em até 30 dias após o início dos sintomas, na maioria dos casos. O tempo médio total entre o aparecimento dos sintomas e o início do tratamento foi de 15,16 meses, sendo que, o tempo médio entre a busca por assistência médica e o diagnóstico foi de 4,78 meses. O histórico familiar de câncer (p=0,008) e a realização de acompanhamento preventivo (p<0,001) estiveram associados a menores períodos entre a busca por assistência e início do tratamento. Naúsea, vômito, hematoquesia, perda ponderal e dor foram associados à procura mais ágil por assistência. o maior intervalo entre a busca por assistência médica e o diagnóstico ocorreu, possivelmente, pela não associação entre os sintomas apresentados e a doença. identificar el tiempo entre los síntomas, la búsqueda de asistencia y el inicio del tratamiento en pacientes con cáncer gástrico y colorrectal y los factores que interfieren en estos procesos. estudio descriptivo correlacional, incluyendo 101 pacientes con diagnostico de cáncer gástrico o colorrectal, atendidos en un hospital especializado en oncología. de 101 pacientes investigados la mayoria eran hombres, con edad media de 61,7 años. La búsqueda de la atención médica se produjo dentro de los 30 días después de la aparición de los síntomas, en la mayoría de los casos. El promedio de tiempo total entre el inicio de los síntomas y el inicio del tratamiento fue de 15,16 meses y el tiempo medio entre la búsqueda de la atención médica y el diagnóstico fue de 4,78 meses. La historia familiar de cáncer (p=0,008) y la realización de seguimiento preventivo (p<0,001) se asociaron con períodos más cortos entre la búsqueda de la atención y el tratamiento temprano. Náuseas, vómitos, hematoquecia, pérdida de peso y dolor se asociaron con la búsqueda más rápida de la asistencia. el intervalo más largo entre la búsqueda de la atención médica y el diagnóstico se produjo posiblemente por asociación negativa entre los síntomas que se presentan y las enfermedades.

Outcomes of WHO Grade I Meningiomas Receiving Definitive or Postoperative Radiotherapy

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

Tanzler, Emily; Morris, Christopher G.; Kirwan, Jessica M.

2011-02-01

Purpose: We analyzed long-term local control and complications in patients with either pathologically confirmed or clinical World Health Organization Grade I meningiomas treated with definitive or postoperative radiotherapy (RT) at the University of Florida. Methods: Between 1984 and 2006, 146 patients were treated with definitive (n = 88) or postoperative RT after subtotal resection (n = 57) or gross total resection (n = 1). Patients were treated with conventional (n = 41), stereotactic (n = 103), or intensity-modulated RT (n = 2) to a median dose of 52.7 Gy and followed for a median of 7.3 years (range, 0.6-22.0 years)more » Results: The local control rates at 5 and 10 years were as follows: definitive RT, 99% and 99%; postoperative RT, 96% and 93%; and overall, 97% and 96%, respectively. The 5- and 10-year cause-specific survival rates were as follows: definitive RT 94% and 94%, postoperative RT, 100% and 96%; and overall, 96% and 95%, respectively. The 5- and 10-year overall survival rates were as follows: definitive RT, 81% and 75%; postoperative RT, 96% and 85%; and overall, 87% and 79%, respectively. Severe RT complications occurred in 6.8% of patients; severe surgery-related complications occurred in 10 (17%) of 58 patients treated surgically. Conclusions: The likelihood of cure after definitive RT or following subtotal resection is excellent. However, a small population of patients experience severe complications, even at the moderate dose used for this disease.« less

Constructive and Unconstructive Repetitive Thought

PubMed Central

Watkins, Edward R.

2008-01-01

The author reviews research showing that repetitive thought (RT) can have constructive or unconstructive consequences. The main unconstructive consequences of RT are (a) depression, (b) anxiety, and (c) difficulties in physical health. The main constructive consequences of RT are (a) recovery from upsetting and traumatic events, (b) adaptive preparation and anticipatory planning, (c) recovery from depression, and (d) uptake of health-promoting behaviors. Several potential principles accounting for these distinct consequences of RT are identified within this review: (a) the valence of thought content, (b) the intrapersonal and situational context in which RT occurs, and (c) the level of construal (abstract vs. concrete processing) adopted during RT. Of the existing models of RT, it is proposed that an elaborated version of the control theory account provides the best theoretical framework to account for its distinct consequences. PMID:18298268

Evaluation of the preventive effect of dexpanthenol in radiation injury by lung perfusion scintigraphy: a preclinical experimental model of radiation injury.

PubMed

Koç, Zehra P; İn, Erdal; Karslioğlu, İhsan; Üçer, Özlem; Canpolat, Sinan

2015-12-01

The aim of this study was to show the preventative effects of dexpanthenol in radiation injuries caused by radiotherapy (RT) through the use of lung perfusion scintigraphy in the pre-RT and post-RT periods. Six male New Zealand rabbits (5-6 months of age and ∼2.5-3 kg in weight) were the used in this study. The animals were subjected to Tc-macroaggregated albumin lung perfusion scintigraphy in the pre-RT and post-RT (i.e. 2 weeks after treatment) periods. The scintigraphies were performed with the same dose by the same staff and the methodology used the same acquisition parameters. The rabbits were divided into two groups: group I (administered RT only) and group II (also administered intramuscular 500 mg dexpanthenol injections for 14 consecutive days after RT). Quantification was performed to compare the groups and the quantification variables were compared using a paired samples t-test, with P value less than 0.05 considered to be statistically significant. Histopathological analysis was also carried out. The post-RT scintigraphies indicated a decrease in the counts in both lungs, suggesting early post-RT injury. The difference between the counts obtained from both lungs in groups I and II was significantly different and favoured group II. Histopathological results confirmed the scintigraphy results. It is possible to estimate post-RT changes in the early period (in contrast to previous data) by lung perfusion scintigraphy. Dexpanthenol may also reduce the effects of RT to a degree. Although this is the first study to report the preventive effects of dexpanthenol on RT injuries, further studies are warranted in this area.

Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth disease virus and look-alike disease viruses

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

Hindson, B J; Reid, S M; Baker, B R

2007-07-26

A high-throughput multiplexed assay was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspect cases of foot-and-mouthmore » disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRT-PCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

Effects of resistance training on the inflammatory response

PubMed Central

Calle, Mariana C

2010-01-01

Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases. PMID:20827340

Evaluating the 4-hour and 30-minute rules: effects of room temperature exposure on red blood cell quality and bacterial growth.

PubMed

Ramirez-Arcos, Sandra; Mastronardi, Cherie; Perkins, Heather; Kou, Yuntong; Turner, Tracey; Mastronardi, Emily; Hansen, Adele; Yi, Qi-Long; McLaughlin, Natasha; Kahwash, Eiad; Lin, Yulia; Acker, Jason

2013-04-01

A 30-minute rule was established to limit red blood cell (RBC) exposure to uncontrolled temperatures during storage and transportation. Also, RBC units issued for transfusion should not remain at room temperature (RT) for more than 4 hours (4-hour rule). This study was aimed at determining if single or multiple RT exposures affect RBC quality and/or promote bacterial growth. Growth and RT exposure experiments were performed in RBCs inoculated with Serratia liquefaciens and Serratia marcescens. RBCs were exposed once to RT for 5 hours (S. liquefaciens) or five times to RT for 30 minutes (S. marcescens) with periodic sampling for bacterial counts. Noncontaminated units were exposed to RT once (5 hr) or five times (30 min each) and sampled to measure in vitro quality variables. RBC core temperature was monitored using mock units with temperature loggers. Growth and RT exposure experiments were repeated three and at least six times, respectively. Statistical analysis was done using mixed-model analysis. RBC core temperature ranged from 7.3 to 11.6°C during 30-minute RT exposures and the time to reach 10°C varied from 22 to 55 minutes during 5-hour RT exposures. RBC quality was preserved after single or multiple RT exposures. Increased growth of S. liquefaciens was only observed after 2 hours of continuous RT exposure. S. marcescens concentration increased significantly in multiple-exposed units compared to the controls but did not reach clinically important levels. Single or multiple RT exposures did not affect RBC quality but slightly promoted bacterial growth in contaminated units. The clinical significance of these results remains unclear and needs further investigation. © 2012 American Association of Blood Banks.

Influence of Noncompliance With Radiation Therapy Protocol Guidelines and Operative Bed Recurrences for Children With Rhabdomyosarcoma and Microscopic Residual Disease: A Report From the Children's Oncology Group

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

Million, Lynn, E-mail: lynn.million@hci.utah.ed; Anderson, James; Breneman, John

2011-06-01

Purpose: Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control. Methods and Materials: All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumormore » excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation. Results: Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children. Conclusion: Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.« less

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

PubMed

AbouAssi, Hiba; Slentz, Cris A; Mikus, Catherine R; Tanner, Charles J; Bateman, Lori A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Penry, Lorrie E; Kraus, Erik A; Huffman, Kim M; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2015-06-15

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Resistance training attenuates fat mass regain after weight loss in ovariectomized rats.

PubMed

Pighon, Abdolnaser; Paquette, Amélie; Barsalani, Razieh; Chapados, Natalie Ann; Rabasa-Lhoret, Rémi; Yasari, Siham; Prud'homme, Denis; Lavoie, Jean-Marc

2009-09-20

The aim of the present study was to investigate the effects of maintaining only one of the two components of a food restriction (FR)+resistance training (RT) regimen on the regain of body weight and fat mass (liver and adipocytes) in ovariectomized (Ovx) rats. Five week Ovx rats were submitted to a weight loss program consisting of a 26% FR combined with RT (OvxFR+RT) for 8 weeks. RT consisted of climbing a 1.5m vertical grid with a load attached to the tail, 20-40 times with progressively increasing loads 4 times/week. Following this weight loss intervention, OvxFR+RT rats were sub-divided into 3 groups for an additional 5 weeks: 2 groups went back to a normal ad libitum feeding with or without RT and the other group kept only FR. Combined FR+RT program in Ovx rats led to lower body mass gain, liver triacylglycerol (TAG) levels, and fat mass gain compared to sedentary normally fed Ovx rats (P<0.01). Stopping both FR and RT over a 5 week period resulted in the regain of body weight, intra-abdominal fat pad weight and liver TAG (P<0.01). When only FR was maintained, the regain of body and fat pad weight as well as liver and plasma TAG concentrations was completely prevented. However, when only RT was maintained, regain in the aforementioned parameters was attenuated but not prevented (P<0.05). It is concluded that following a FR+RT weight loss program, continuation of only RT constitutes an asset to attenuate body weight and fat mass regain in Ovx rats; although the impact is less than the maintaining FR alone. These results suggest that, in post-menopausal women, RT is a positive strategy to reduce body weight and fat mass relapse.

Short rest interval lengths between sets optimally enhance body composition and performance with 8 weeks of strength resistance training in older men.

PubMed

Villanueva, Matthew G; Lane, Christianne Joy; Schroeder, E Todd

2015-02-01

To determine if 8 weeks of periodized strength resistance training (RT) utilizing relatively short rest interval lengths (RI) in between sets (SS) would induce greater improvements in body composition and muscular performance, compared to the same RT program utilizing extended RI (SL). 22 male volunteers (SS: n = 11, 65.6 ± 3.4 years; SL: n = 11, 70.3 ± 4.9 years) were assigned to one of two strength RT groups, following 4 weeks of periodized hypertrophic RT (PHRT): strength RT with 60-s RI (SS) or strength RT with 4-min RI (SL). Prior to randomization, all 22 study participants trained 3 days/week, for 4 weeks, targeting hypertrophy; from week 4 to week 12, SS and SL followed the same periodized strength RT program for 8 weeks, with RI the only difference in their RT prescription. Following PHRT, all study participants experienced increases in lean body mass (LBM) (p < 0.01), upper and lower body strength (p < 0.001), and dynamic power (p < 0.001), as well as decreases in percentage body fat (p < 0.05). Across the 8-week strength RT phase, SS experienced significantly greater increases in LBM (p = 0.001), flat machine bench press 1-RM (p < 0.001), bilateral leg press 1-RM (p < 0.001), narrow/neutral grip lat pulldown (p < 0.01), and Margaria stair-climbing power (p < 0.001), compared to SL. This study suggests 8 weeks of periodized high-intensity strength RT with shortened RI induces significantly greater enhancements in body composition, muscular performance, and functional performance, compared to the same RT prescription with extended RI, in older men. Applied professionals may optimize certain RT-induced adaptations, by incorporating shortened RI.

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).

PubMed

Bateman, Lori A; Slentz, Cris A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2011-09-15

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (∼120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health. Published by Elsevier Inc.

Molecular dynamics study of HIV-1 RT-DNA-nevirapine complexes explains NNRTI inhibition and resistance by connection mutations.

PubMed

Vijayan, R S K; Arnold, Eddy; Das, Kalyan

2014-05-01

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that is targeted by nucleoside analogs (NRTIs) and non-nucleoside RT inhibitors (NNRTIs). NNRTIs are allosteric inhibitors of RT, and constitute an integral part of several highly active antiretroviral therapy regimens. Under selective pressure, HIV-1 acquires resistance against NNRTIs primarily by selecting mutations around the NNRTI pocket. Complete RT sequencing of clinical isolates revealed that spatially distal mutations arising in connection and the RNase H domain also confer NNRTI resistance and contribute to NRTI resistance. However, the precise structural mechanism by which the connection domain mutations confer NNRTI resistance is poorly understood. We performed 50-ns molecular dynamics (MD) simulations, followed by essential dynamics, free-energy landscape analyses, and network analyses of RT-DNA, RT-DNA-nevirapine (NVP), and N348I/T369I mutant RT-DNA-NVP complexes. MD simulation studies revealed altered global motions and restricted conformational landscape of RT upon NVP binding. Analysis of protein structure network parameters demonstrated a dissortative hub pattern in the RT-DNA complex and an assortative hub pattern in the RT-DNA-NVP complex suggesting enhanced rigidity of RT upon NVP binding. The connection subdomain mutations N348I/T369I did not induce any significant structural change; rather, these mutations modulate the conformational dynamics and alter the long-range allosteric communication network between the connection subdomain and NNRTI pocket. Insights from the present study provide a structural basis for the biochemical and clinical findings on drug resistance caused by the connection and RNase H mutations. Copyright © 2013 Wiley Periodicals, Inc.

Structural MRI research in patients with nasopharyngeal carcinoma following radiotherapy: A DTI and VBM study.

PubMed

Leng, Xi; Fang, Peng; Lin, Huan; An, Jie; Tan, Xin; Zhang, Chi; Wu, Donglin; Shen, Wen; Qiu, Shijun

2017-11-01

The aim of the present study was to investigate the microstructural characteristics of the brain lobes following radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC) at distinct times. Diffusion tensor imaging (DTI) and 3D-T1-weighted imaging was performed in 70 age- and sex-matched subjects, 24 of whom were pre-treatment patients. The patients were divided into three groups, according to the time following completion of RT. Fractional anisotropy (FA) and gray matter (GM) volume were determined. The DTI data were analyzed using tract-based spatial statistics and the GM volume was analyzed using voxel-based morphometry (VBM). Compared with the pre-RT group, the mean FA values in the left parietal lobe white matter (WM) and right cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05). In addition, the mean FA values in the right parietal lobe WM decreased significantly in the post-RT 6-12 month group (P<0.05), compared with the pre-RT group. The FA level in the right temporal lobe remained significantly decreased, compared with that in the pre-RT group (P<0.05) for 1 year after RT. Furthermore, compared with pre-RT group, the GM volume in the bilateral frontal lobe, right occipital lobe, left parietal lobe, right temporal lobe and left cerebellum decreased significantly in the post-RT 0-6 month group (P<0.05), and in the bilateral temporal lobe, parietal lobe, right frontal lobe and left cerebellum, the GM volume decreased significantly in the post-RT 6-12 month group (P<0.05). The GM volume in the right temporal lobe, bilateral frontal lobe and bilateral cerebellum remained significantly decreased compared with that in the pre-RT group (P<0.05) for 1 year after RT. A combination of DTI and VBM may be used to determine radiation-induced brain injury in patients treated for NPC.

Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

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

Pasquier, David; Ballereau, Charles

2008-11-15

Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE.more » Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion: Prospective randomized trials are needed to compare immediate postoperative RT with salvage RT and to assess the value of androgen deprivation therapy in this setting.« less

Phase Measurement of Cognitive Impairment Specific to Radiotherapy

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

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Department of Pediatrics, Division of Neuro-Oncology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania; Shera, David M.

Purpose: Memory impairment is an early-delayed effect of radiotherapy (RT). The prospective longitudinal measurement of the cognitive phase effects from RT was conducted on treated and untreated brain tumor patients. The study design investigated semantic vs. perceptual and visual vs. verbal memory to determine the most disease-specific measure of RT-related changes and understanding of the neurotoxicity from RT to the brain. Methods and Materials: Tests of memory that had previously shown RT-related phasic changes were compared with experimental tests of memory to test hypotheses about cognition targeted to the neural toxicity of RT. The results from 41 irradiated and 29more » nonirradiated patients with low-grade, supratentorial tumors were analyzed. The methods controlled for comorbid white matter risk, recurrence, interval after treatment, and age (18-69 years). The effects were examined before RT and at three points after RT to 1 year using a mixed effects model that included interval, group, surgical status, medication use, practice, and individual random effects. Four new tests of memory and other candidate cognitive tests were investigated, and a post hoc analysis of a comprehensive battery of tests was performed to identify the cognitive processes most specific to RT. Results: The RT effects on memory were identified in the treated group only; among the new tests of memory and the complete neurocognitive battery, the RT effects were significant only for delayed recall (p < 0.009) and interval to recognize (p < 0.002). Tumor location was not related to the treatment effect. Memory decline was specific to retrieval of semantic memories; a double dissociation of semantic from perceptual visual memory was demonstrated in the RT group. Conclusions: These results implicate memory dependent on the semantic cortex and the hippocampal memory system. A cognitive measurement that is brief but specific to neural mechanisms is effective and feasible for studies of RT damage.« less

Breath-holding times in various phases of respiration and effect of respiratory training in lung cancer patients.

PubMed

Tibdewal, Anil; Munshi, Anusheel; Pathak, Rima; Misra, Shagun; Daptardar, Anuradha; Singh, Vincent; Agarwal, Jai Prakash

2015-08-01

Breath-holding (BH) technique is used for reducing the intrafraction-tumour motion in mobile lung tumours treated with radiotherapy (RT). There is paucity of literature evaluating differences in BH times in various phases of respiration in patients with lung cancer. One hundred consecutive patients with lung cancer planned for radical RT/chemoradiation were accrued in the study. Eighty-seven patients were eligible for analysis at RT conclusion. Baseline pulmonary function test (PFT) were performed in all patients, and respiratory training was given from the day of RT planning. Deep inspiration breath hold (DIBH), deep expiration breath hold (DEBH) and mid-ventilation breath hold (MVBH) were recorded manually with a stopwatch for each patient at four time points (RT planning/baseline, RT starting, during RT and RT conclusion). Median DIBH times at RT planning, RT starting, during RT and RT conclusion were 21.2, 20.6, 20.1 and 21.1 s, respectively. The corresponding median DEBH and MVBH times were 16.3, 18.2, 18.3, 18.5 s and 19.9, 20.5, 21.3, 22.1 s, respectively. Respiratory training increased MVBH time at RT conclusion compared to baseline, which was statistically significant (19.9-22.1 s, P = 0.002). DIBH or DEBH times were stable at various time points with neither a significant improvement nor decline. Among various patient and tumour factors Forced Vital Capacity pre-bronchodilation (FVCpre ) was the only factor that consistently predicted DIBH, DEBH and MVBH at all four time points with P value <0.05. BH was well tolerated by most lung cancer patients with minimum median BH time of at least 16 s in any of the three phases of respiration. Respiratory training improved MVBH time while consistently maintaining DIBH and DEBH times throughout the course of radiotherapy. © 2015 The Royal Australian and New Zealand College of Radiologists.

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy.

PubMed

Ferris, Matthew J; Zhong, Jim; Switchenko, Jeffrey M; Higgins, Kristin A; Cassidy, Richard J; McDonald, Mark W; Eaton, Bree R; Patel, Kirtesh R; Steuer, Conor E; Baddour, H Michael; Miller, Andrew H; Bruner, Deborah W; Xiao, Canhua; Beitler, Jonathan J

2018-01-01

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients. At pre-RT (baseline), 6th week of RT, and 1-month post-RT time points, Multidimensional Fatigue Inventory (MFI-20) scores were prospectively obtained from 124 patients undergoing definitive treatment for HNC. Medulla, pons, midbrain, total brainstem, cerebellum, posterior fossa, and pituitary dosimetry were evaluated using summary statistics and dose-volume histograms, and associations with MFI-20 scores were analyzed. Maximum dose (Dmax) to the brainstem and medulla was significantly associated with MFI-20 scores at 6th week of RT and 1-month post-RT time points, after controlling for baseline scores (p<0.05). Each 1Gy increase in medulla Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.026), and 0.25 (p=0.037), at the 6th week of RT and 1-month post-RT, respectively. Each 1Gy increase in brainstem Dmax resulted in an increase in total MFI-20 score over baseline of 0.30 (p=0.027), and 0.25 (p=0.037) at the 6th week of RT, 1-month post-RT, respectively. Statistically significant associations were not found between dosimetry for the other CNS structures and MFI-20 scores. In this analysis of PRO fatigue scores from a population of patients undergoing definitive RT for HNC, maximum dose to the brainstem and medulla was associated with a significantly increased risk of acute patient fatigue. Copyright © 2017 Elsevier B.V. All rights reserved.

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

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

Muecke, Ralph; Schomburg, Lutz; Glatzel, Michael

Purpose: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. Methods and Materials: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84{mu}g/L were randomized before RT either to receive 500 {mu}g of selenium (in the form of sodium selenite [selenase (registered) , biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouthmore » on the days of RT and 300 {mu}g of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. Results: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. Conclusions: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.« less

The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

PubMed

Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

2014-06-01

The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p < 0.05) (RT: 64 ± 14 to 80 ± 17 kg; RT+DP: 72 ± 23 to 91 ± 20 kg) and lower (p < 0.05) (RT: 69 ± 20 to 87 ± 28 kg; RT+DP: 78 ± 19 to 100 ± 21 kg) body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05) (4.55 ± 1.57 to 4.04 ± 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 ± 2.75 to 4.27 ± 2.03 U/L). Changes in BAP and CRP were not observed. RT was effective for improving biochemical markers of bone turnover and muscular strength in BCS. A longer and higher intensity intervention may be needed to reveal the true effects of RT and DP on body composition and biochemical markers of inflammation.

The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast Reconstruction using Temporary Tissue Expanders and Permanent Implants.

PubMed

Anker, Christopher J; Hymas, Richard V; Ahluwalia, Ravinder; Kokeny, Kristine E; Avizonis, Vilija; Boucher, Kenneth M; Neumayer, Leigh A; Agarwal, Jayant P

2015-01-01

The optimal method of reconstruction following mastectomy for breast cancer patients receiving radiation therapy (RT) is controversial. This study evaluated patient satisfaction and complication rates among patients who received implant-based breast reconstruction. The specific treatment algorithm analyzed included patients receiving mastectomy and immediate temporary tissue expander (TE), followed by placement of a permanent breast implant (PI). If indicated, RT was delivered to the fully expanded TE. Records of 218 consecutive patients with 222 invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of 10 Gy. Kaplan-Meier analyses were performed to evaluate the cumulative incidence of surgical complications, including permanent PI removal. Risk factors associated with surgical events were analyzed. To evaluate cosmetic results and patient satisfaction, an anonymous survey was administered. Mean follow-up was 44 months (range 6-144). Actuarial 5-year PI removal rates for non-RT and RT patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only factor associated with PI removal was RT (p = 0.009). Surveys were returned describing the outcomes of 149 breasts. For the non-RT and RT groups, those who rated their breast appearance as good or better were 63% versus 62%, respectively. Under 1/3 of each group was dissatisfied with their reconstruction. RT did not significantly affect patient satisfaction scores, but on MVA RT was the only factor associated with increased PI removal. This reconstruction technique may be considered an acceptable option even if RT is needed, but the increased complication risk with RT must be recognized. © 2015 Wiley Periodicals, Inc.

Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

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

Livi, Lorenzo; Saieva, Calogero; Borghesi, Simona

2008-07-01

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m{sup 2}, methotrexate 40 mg/m{sup 2}, and 5-fluorouracil 600 mg/m{sup 2}) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at themore » discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.« less

ScriptingRT: A Software Library for Collecting Response Latencies in Online Studies of Cognition

PubMed Central

Schubert, Thomas W.; Murteira, Carla; Collins, Elizabeth C.; Lopes, Diniz

2013-01-01

ScriptingRT is a new open source tool to collect response latencies in online studies of human cognition. ScriptingRT studies run as Flash applets in enabled browsers. ScriptingRT provides the building blocks of response latency studies, which are then combined with generic Apache Flex programming. Six studies evaluate the performance of ScriptingRT empirically. Studies 1–3 use specialized hardware to measure variance of response time measurement and stimulus presentation timing. Studies 4–6 implement a Stroop paradigm and run it both online and in the laboratory, comparing ScriptingRT to other response latency software. Altogether, the studies show that Flash programs developed in ScriptingRT show a small lag and an increased variance in response latencies. However, this did not significantly influence measured effects: The Stroop effect was reliably replicated in all studies, and the found effects did not depend on the software used. We conclude that ScriptingRT can be used to test response latency effects online. PMID:23805326

Towards integration of PET/MR hybrid imaging into radiation therapy treatment planning

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

Paulus, Daniel H., E-mail: daniel.paulus@imp.uni-erlangen.de; Thorwath, Daniela; Schmidt, Holger

2014-07-15

Purpose: Multimodality imaging has become an important adjunct of state-of-the-art radiation therapy (RT) treatment planning. Recently, simultaneous PET/MR hybrid imaging has become clinically available and may also contribute to target volume delineation and biological individualization in RT planning. For integration of PET/MR hybrid imaging into RT treatment planning, compatible dedicated RT devices are required for accurate patient positioning. In this study, prototype RT positioning devices intended for PET/MR hybrid imaging are introduced and tested toward PET/MR compatibility and image quality. Methods: A prototype flat RT table overlay and two radiofrequency (RF) coil holders that each fix one flexible body matrixmore » RF coil for RT head/neck imaging have been evaluated within this study. MR image quality with the RT head setup was compared to the actual PET/MR setup with a dedicated head RF coil. PET photon attenuation and CT-based attenuation correction (AC) of the hardware components has been quantitatively evaluated by phantom scans. Clinical application of the new RT setup in PET/MR imaging was evaluated in anin vivo study. Results: The RT table overlay and RF coil holders are fully PET/MR compatible. MR phantom and volunteer imaging with the RT head setup revealed high image quality, comparable to images acquired with the dedicated PET/MR head RF coil, albeit with 25% reduced SNR. Repositioning accuracy of the RF coil holders was below 1 mm. PET photon attenuation of the RT table overlay was calculated to be 3.8% and 13.8% for the RF coil holders. With CT-based AC of the devices, the underestimation error was reduced to 0.6% and 0.8%, respectively. Comparable results were found within the patient study. Conclusions: The newly designed RT devices for hybrid PET/MR imaging are PET and MR compatible. The mechanically rigid design and the reproducible positioning allow for straightforward CT-based AC. The systematic evaluation within this study provides the technical basis for the clinical integration of PET/MR hybrid imaging into RT treatment planning.« less

SU-G-JeP3-02: Comparison of Magnitude and Frequency of Patient Positioning Errors in Breast Irradiation Using AlignRT 3D Optical Surface Imaging and Skin Mark Techniques

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

Yao, R; Chisela, W; Dorbu, G

2016-06-15

Purpose: To evaluate clinical usefulness of AlignRT (Vision RT Ltd., London, UK) in reducing patient positioning errors in breast irradiation. Methods: 60 patients undergoing whole breast irradiation were selected for this study. Patients were treated to the left or right breast lying on Qfix Access breast board (Qfix, Avondale, PA) in supine position for 28 fractions using tangential fields. 30 patients were aligned using AlignRT by aligning a breast surface region of interest (ROI) to the same area from a reference surface image extracted from planning CT. When the patient’s surface image deviated from the reference by more than 3mmmore » on one or more translational and rotational directions, a new reference was acquired using AlignRT in-room cameras. The other 30 patients were aligned to the skin marks with room lasers. On-Board MV portal images of medial field were taken daily and matched to the DRRs. The magnitude and frequency of positioning errors were determined from measured translational shifts. Kolmogorov-Smirnov test was used to evaluate statistical differences of positional accuracy and precision between AlignRT and non-AlignRT patients. Results: The percentage of port images with no shift required was 46.5% and 27.0% in vertical, 49.8% and 25.8% in longitudinal, 47.6% and 28.5% in lateral for AlignRT and non-AlignRT patients, respectively. The percentage of port images requiring more than 3mm shifts was 18.1% and 35.1% in vertical, 28.6% and 50.8% in longitudinal, 11.3% and 24.2% in lateral for AlignRT and non-AlignRT patients, respectively. Kolmogorov-Smirnov test showed that there were significant differences between the frequency distributions of AlignRT and non-AlignRT in vertical, longitudinal, and lateral shifts. Conclusion: As confirmed by port images, AlignRT-assisted patient positioning can significantly reduce the frequency and magnitude of patient setup errors in breast irradiation compared to the use of lasers and skin marks.« less

Development of an in vitro chemo-radiation response assay for cervical carcinoma.

PubMed

Monk, Bradley J; Burger, Robert A; Parker, Ricardo; Radany, Eric H; Redpath, Leslie; Fruehauf, John P

2002-11-01

To determine if synergistic effects of radiation (RT) and chemotherapy (chemo) on human cervical carcinoma cell lines and fresh tumor explants could be determined using an in vitro assay. In vitro radiation response was determined for 4 cell lines and 26 fresh tumor explants in an agar-based assay. Cells were exposed to increasing doses of RT with or without cisplatin (CDDP), carmustine (BCNU), buthionine sulfoximine (BSO), or paclitaxel (Tax). Cell suspensions were cultured for 5 days, with [(3)H]thymidine added on day 3 and proliferation was measured. Results were reported as the fraction of proliferation compared to control (FC). For each combination of irradiation and drug, synergy was tested using the Chou analysis, where a combination index (CI) <1 indicated synergistic interaction. In simple correlation analysis, an R value of >0.7 indicated cross-resistance. RT dose-dependent proliferation inhibition was observed for 2 of the 4 cell lines, and for all but 1 of the fresh specimens. Significant heterogeneity of tumor response to RT was seen. Four specimens that were 1 standard deviation below the median FC response after exposure to 300 cGy were classified as extremely radiation resistant. Twenty-one tumors were evaluated for synergistic response using the combination of chemo and RT with a median FC of 0.27 (+/-0.27) for 6.0 Gy of RT alone, 0.22 (+/-0.21) for CDDP alone, and 0.05 (+/-0.08) for the combination. A CI of 0.35 and an R value of 0.09 demonstrated synergy between chemo and RT without cross-resistance. Similar synergy without cross-resistance was found for RT in combination with BCNU, BSO, and TAX. Heterogeneous RT dose-response relationships in the in vitro assay were demonstrated. Explants were more sensitive to RT than cell lines. Unlike cell lines, fresh tumor cells consistently displayed synergy with RT and chemo. The synergy between RT and BSO suggests that glutathione depletion may enhance the effect of RT. The assay was feasible for examining fresh tumors and may be an important tool for studying RT or drug resistance. Clinical trials to evaluate this assay are indicated.

Adoption of Preoperative Radiation Therapy for Rectal Cancer From 2000 to 2006: A Surveillance, Epidemiology, and End Results Patterns-of-Care Study

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

Mak, Raymond H.; McCarthy, Ellen P.; Das, Prajnan

2011-07-15

Purpose: The German rectal study determined that preoperative radiation therapy (RT) as a component of combined-modality therapy decreased local tumor recurrence, increased sphincter preservation, and decreased treatment toxicity compared with postoperative RT for rectal cancer. We evaluated the use of preoperative RT after the presentation of the landmark German rectal study results and examined the impact of tumor and sociodemographic factors on receiving preoperative RT. Methods and Materials: In total, 20,982 patients who underwent surgical resection for T3-T4 and/or node-positive rectal adenocarcinoma diagnosed from 2000 through 2006 were identified from the Surveillance, Epidemiology, and End Results tumor registries. We analyzedmore » trends in preoperative RT use before and after publication of the findings from the German rectal study. We also performed multivariate logistic regression to identify factors associated with receiving preoperative RT. Results: Among those treated with RT, the proportion of patients treated with preoperative RT increased from 33.3% in 2000 to 63.8% in 2006. After adjustment for age; gender; race/ethnicity; marital status; Surveillance, Epidemiology, and End Results registry; county-level education; T stage; N stage; tumor size; and tumor grade, there was a significant association between later year of diagnosis and an increase in preoperative RT use (adjusted odds ratio, 1.26/y increase; 95% confidence interval, 1.23-1.29). When we compared the years before and after publication of the German rectal study (2000-2003 vs. 2004-2006), patients were more likely to receive preoperative RT than postoperative RT in 2004-2006 (adjusted odds ratio, 2.35; 95% confidence interval, 2.13-2.59). On multivariate analysis, patients who were older, who were female, and who resided in counties with lower educational levels had significantly decreased odds of receiving preoperative RT. Conclusions: After the publication of the landmark German rectal study, there was widespread, rapid adoption of preoperative RT for locally advanced rectal cancer. However, preoperative RT may be underused in certain sociodemographic groups.« less

Fluorodeoxyglucose Uptake on Positron Emission Tomography Is a Useful Predictor of Long-Term Pain Control After Palliative Radiation Therapy in Patients With Painful Bone Metastases: Results of a Single-Institute Prospective Study

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

Tahara, Takatoshi, E-mail: taka.t-may7@med.Tottori-u.ac.jp; Fujii, Shinya; Ogawa, Toshihide

Purpose: To determine whether fluorodeoxyglucose positron emission tomography (FDG-PET) before and after palliative radiation therapy (RT) can predict long-term pain control in patients with painful bone metastases. Methods and Materials: Thirty-one patients with bone metastases who received RT were prospectively included. Forty painful metastatic treatment fields were evaluated. All patients had undergone pre-RT and post-RT PET/CT scanning. We evaluated the relationships between the pre-RT, post-RT, and changes in maximum standardized uptake value (SUV{sub max}) and the pain response, and between SUV{sub max} and pain relapse of the bone metastases in the treatment field. In addition, we compared the SUV{sub max}more » according to the length of time from the completion of RT to pain relapse of the bone metastases. Results: Regarding the pain response at 4 weeks after the completion of RT, there were 36 lesions of 27 patients in the responder group and 4 lesions of 4 patients in the nonresponder group. Changes in the SUV{sub max} differed significantly between the responder and nonresponder groups in both the early and delayed phases (P=.0292 and P=.0139, respectively), but no relationship was observed between the pre-RT and post-RT SUV{sub max} relative to the pain response. The responder group was evaluated for the rate of relapse. Thirty-five lesions of 26 patients in the responder group were evaluated, because 1 patient died of acute renal failure at 2 months after RT. Twelve lesions (34%) showed pain relapse, and 23 lesions (66%) did not. There were significant differences between the relapse and nonrelapse patients in terms of the pre-RT (early/delayed phases: P<.0001/P<.0001), post-RT (P=.0199/P=.0261), and changes in SUV{sub max} (P=.0004/P=.004). Conclusions: FDG-PET may help predict the outcome of pain control in the treatment field after palliative RT for painful bone metastases.« less

Antagonizing SET augments the effects of radiotherapy in hepatocellular carcinoma through reactivating PP2A-mediated AKT downregulation.

PubMed

Huang, Chao-Yuan; Hung, Man-Hsin; Shih, Chi-Ting; Hsieh, Feng-Shu; Kuo, Chiung-Wen; Tsai, Ming-Hsien; Chang, Shih-Shin; Hsiao, Yung-Jen; Chen, Li-Ju; Chao, Tzu-I; Chen, Kuen-Feng

2018-06-18

Increasing evidence suggests that SET functions as an oncoprotein and promotes cancer survival and therapeutic resistance. However, whether SET affects radiotherapy (RT)-mediated anti-cancer effects has not yet been explored. Here, we investigated the impact of SET on RT sensitivity in hepatocellular carcinoma (HCC). Using colony and hepatosphere formation assay, we found that RT-induced proliferative inhibition was critically associated with SET expression. Next, we tested a novel SET antagonist, EMQA, in combination with RT. We showed that additive use of EMQA significantly enhanced the effects of RT against HCC in vitro and in vivo. Notably, compared to mice receiving either RT or EMQA alone, the growth of PLC5 xenografted tumor in mice receiving RT plus EMQA was significantly reduced without compromising treatment tolerability. Furthermore, we proved that antagonizing SET to restore PP2A-mediated p-AKT downregulation was responsible for the synergism between EMQA and RT. Our data demonstrate a new oncogenic property of SET, and provide preclinical evidence that combining a SET antagonist and RT may be effective for treatment of HCC. Further investigation is warranted to validate the clinical relevance of this approach. The American Society for Pharmacology and Experimental Therapeutics.

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer

PubMed Central

Dignam, James J.; Amin, Mahul B.; Bruner, Deborah W.; Low, Daniel; Swanson, Gregory P.; Shah, Amit B.; D’Souza, David P.; Michalski, Jeff M.; Dayes, Ian S.; Seaward, Samantha A.; Hall, William A.; Nguyen, Paul L.; Pisansky, Thomas M.; Faria, Sergio L.; Chen, Yuhchyau; Koontz, Bridget F.; Paulus, Rebecca; Sandler, Howard M.

2016-01-01

Purpose Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation—fewer treatments but at a higher dose per treatment—may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. Patients and Methods A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). Results A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. Conclusion In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. PMID:27044935

Subclinical Cardiotoxicity Detected by Strain Rate Imaging up to 14 months After Breast Radiation Therapy

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

Erven, Katrien, E-mail: katrien.erven@uzleuven.be; Iridium Cancer Network, Antwerp; Florian, Anca

Purpose: Strain rate imaging (SRI) is a new echocardiographic modality that enables accurate measurement of regional myocardial function. We investigated the role of SRI and troponin I (TnI) in the detection of subclinical radiation therapy (RT)-induced cardiotoxicity in breast cancer patients. Methods and Materials: This study prospectively included 75 women (51 left-sided and 24 right-sided) receiving adjuvant RT to the breast/chest wall and regional lymph nodes. Sequential echocardiographs with SRI were obtained before RT, immediately after RT, and 8 and 14 months after RT. TnI levels were measured on the first and last day of RT. Results: Mean heart andmore » left ventricle (LV) doses were both 9 ± 4 Gy for the left-sided patients and 4 ± 4 Gy and 1 ± 0.4 Gy, respectively, for the right-sided patients. A decrease in strain was observed at all post-RT time points for left-sided patients (−17.5% ± 1.9% immediately after RT, −16.6% ± 1.4% at 8 months, and −17.7% ± 1.9% at 14 months vs −19.4% ± 2.4% before RT, P<.01) but not for right-sided patients. When we considered left-sided patients only, the highest mean dose was given to the anterior left ventricular (LV) wall (25 ± 14 Gy) and the lowest to the inferior LV wall (3 ± 3 Gy). Strain of the anterior wall was reduced after RT (−16.6% ± 2.3% immediately after RT, −16% ± 2.6% at 8 months, and −16.8% ± 3% at 14 months vs −19% ± 3.5% before RT, P<.05), whereas strain of the inferior wall showed no significant change. No changes were observed with conventional echocardiography. Furthermore, mean TnI levels for the left-sided patients were significantly elevated after RT compared with before RT, whereas TnI levels of the right-sided patients remained unaffected. Conclusions: In contrast to conventional echocardiography, SRI detected a regional, subclinical decline in cardiac function up to 14 months after breast RT. It remains to be determined whether these changes are related to clinical outcome. In the meantime, we encourage the use of radiation techniques that minimize the exposure of the anterior LV wall in left-sided patients.« less

Characterization of efficacy and toxicity after high-dose pelvic reirradiation with palliative intent for genitourinary second malignant neoplasms or local recurrences after full-dose radiation therapy in the pelvis: A high-volume cancer center experience.

PubMed

Kamran, Sophia C; Harshman, Lauren C; Bhagwat, Mandar S; Muralidhar, Vinayak; Nguyen, Paul L; Martin, Neil E; La Follette, Stephanie; Faso, Sarah; Viswanathan, Akila N; Efstathiou, Jason A; Beard, Clair J

2017-01-01

The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses focused on toxicities and symptom control, and responses were evaluated by 2 independent observers. Twenty-seven male patients (96%) were included. Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer. Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm). Given the severity of the symptoms and the bulk of the disease at the time of re-RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received <60 Gy, hypofractionation of 250 cGy was used. The median cumulative dose was 113.9 Gy (range, 81.5-132.8 Gy). Re-RT was well tolerated with no Radiation Therapy Oncology Group grade 3-4 toxicities. Twenty-four patients (92%) had complete resolution of symptoms, and relief was durable in 67% of patients. The median overall survival was 5.8 months (range, 0.3-38.9 months). Of those patients who are still alive, 100% remain free of initial symptoms. This small series suggests that aggressive re-RT of inoperable and symptomatic GU malignancies that is undertaken with meticulous treatment planning is well tolerated and provides excellent, durable relief without undue short-term toxicity. Validation in a larger prospective cohort is required.

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

LoPresti, J.S.; Gray, D.; Nicoloff, J.T.

To determine the influence of prolonged fasting and refeeding on rT3 metabolism in man, five euthyroid obese subjects underwent a 13-day fast, followed by a refeeding period. Each patient received an iv dose of 25 muCi (125I)rT3 during the fed control period, on days 7 and 13 of the fast, and on the fourth day after refeeding with a regular diet. Serial blood and urine samples were obtained to determine serum rT3 clearance and production rates and the urinary tracer rT3 deiodination fraction. Significant increases in serum rT3 values were noted by day 7 and remained elevated for the durationmore » of the fast (P less than 0.01). Normalization of rT3 levels occurred after 4 days of refeeding. Both 7 and 13 days of fasting decreased rT3 clearance (132.6 +/- 8.3 L/day (P less than 0.001) and 132.2 +/- 9.5 L/day (P less than 0.001), respectively) without changing rT3 production (36.8 +/- 5.3 and 33.0 +/- 3.7 nmol/D, respectively) compared to control values (207.0 +/- 10.9 L/day and 31.8 +/- 3.8 nmol/day, respectively). Refeeding did not restore rT3 clearance (151.2 +/- 6.9 L/day; P less than 0.002), but significantly reduced blood rT3 production (18.4 +/- 3.8 nmol/day; P less than 0.003). The fractional deiodination of rT3 was significantly reduced on day 7 (42.5 +/- 4.6%; P less than 0.01) and day 13 (41.9 +/- 3.7%; P less than 0.01) of fasting compared to the control value (69.2 +/- 2.8%), while refeeding only partially restored deiodination to baseline (48.4 +/- 5.1%; P less than 0.04). The clearance of rT3 was highly dependent on the fractional deiodination rate (r = 0.83; P less than 0.001). Although rT3 production remained constant during fasting, reduced rT3 production was seen on the fourth day of refeeding. This unique observation explained the fall in serum rT3 to prefasting levels after 4 days of refeeding when rT3 clearance was still inhibited.« less

Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

PubMed

Lee, W Robert; Dignam, James J; Amin, Mahul B; Bruner, Deborah W; Low, Daniel; Swanson, Gregory P; Shah, Amit B; D'Souza, David P; Michalski, Jeff M; Dayes, Ian S; Seaward, Samantha A; Hall, William A; Nguyen, Paul L; Pisansky, Thomas M; Faria, Sergio L; Chen, Yuhchyau; Koontz, Bridget F; Paulus, Rebecca; Sandler, Howard M

2016-07-10

Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from > 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer. A total of 1,115 men with low-risk prostate cancer were randomly assigned 1:1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an α of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52). A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P < .001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT. In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. © 2016 by American Society of Clinical Oncology.

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.

PubMed

Eisbruch, A; Kim, H M; Terrell, J E; Marsh, L H; Dawson, L A; Ship, J A

2001-07-01

To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ("oral cavity") were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be independently associated with the xerostomia scores were the pre-RT baseline scores, the time since RT, and the mean doses to the major salivary glands (notably to the submandibular glands) and to the oral cavity. An improvement over time in xerostomia, occurring in tandem with rising salivary production from the spared major salivary glands, suggests a long-term clinical benefit from their sparing. The oral cavity mean dose, representing RT effect on the minor salivary glands, was found to be a significant, independent predictor of xerostomia. Thus, in addition to the major salivary glands, sparing the uninvolved oral cavity should be considered as a planning objective to further reduce xerostomia.

Relationship between daily rumination time and estrus of dairy cows.

PubMed

Reith, S; Hoy, S

2012-11-01

The aim of the study was to investigate whether rumination time (RT) was related to estrus in dairy cattle. On 4 farms, cows were equipped with a microphone-based sensor system that allowed continuous recording (in blocks of 2 h) of RT. The analyzed data set consisted of 265 verified estrus cycles of 224 animals with artificial insemination leading to conception. The day of estrus (d 0) was defined as the day when estrus was identified either by measurement of physical activity or by visual observation. In estrous cows, RT was significantly reduced. With a duration of 355 min/d, the minimum RT was found on the day of estrus compared with the base level of 429 min/d during the reference period (the mean of 3 d before and 3 d after estrus). The average decrease in RT was 17% (74 min), ranging between -71 and +16% among animals. Herd and parity affected the RT decrease during estrus. Among the 4 analyzed herds, the RT decrease of cows in estrus ranged between 14% (60 min/d) and 24% (94 min/d). The decrease in RT was more pronounced in primiparous than in mature cows. In conclusion, RT is reduced on the day of estrus on average. The RT decrease during estrus was characterized by high variation among cows. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial.

PubMed

Miller, Todd; Mull, Stephanie; Aragon, Alan Albert; Krieger, James; Schoenfeld, Brad Jon

2018-01-01

The purpose of this study was to determine the effects of resistance training only (RT; n = 10), dietary intervention only (DIET; n = 10), resistance training plus diet (RT+DIET; n = 10), and control (CON; n = 10) on body composition and resting metabolic rate (RMR) in a cohort of 40 premenopausal female volunteers. Subjects in DIET and RT+DIET were provided with daily macronutrient and calorie goals based on DXA and RMR tests, with protein maintained at 3.1 g/kg/day. Subjects in the RT and RT+DIET groups performed a supervised progressive RT program consisting of exercises for all the major muscle groups of the body. Results showed a significant month-by-group interaction for change in fat mass with no significant linear trend for control. The three treatment groups all showed significant linear decreases in fat mass, but the slope of the decrease became progressively steeper from the RT, to DIET, to RT+DIET. A significant linear increase for lean mass was seen for resistance training only. There was a nonsignificant increase in RMR in all groups from Month 0 to Month 4 but no significant month by group interaction. In conclusion, significant reductions in fat mass were achieved by all experimental groups, but results were maximized by RT+DIET. Only the RT group showed significant increases in lean mass.

A Portable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of Foot-and-Mouth Disease Virus

PubMed Central

Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A.; Hufert, Frank T.; Weidmann, Manfred

2013-01-01

Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4–10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection. PMID:23977101

A portable reverse transcription recombinase polymerase amplification assay for rapid detection of foot-and-mouth disease virus.

PubMed

Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A; Hufert, Frank T; Weidmann, Manfred

2013-01-01

Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4-10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection.

On the Origin of Reverse Transcriptase-Using CRISPR-Cas Systems and Their Hyperdiverse, Enigmatic Spacer Repertoires.

PubMed

Silas, Sukrit; Makarova, Kira S; Shmakov, Sergey; Páez-Espino, David; Mohr, Georg; Liu, Yi; Davison, Michelle; Roux, Simon; Krishnamurthy, Siddharth R; Fu, Becky Xu Hua; Hansen, Loren L; Wang, David; Sullivan, Matthew B; Millard, Andrew; Clokie, Martha R; Bhaya, Devaki; Lambowitz, Alan M; Kyrpides, Nikos C; Koonin, Eugene V; Fire, Andrew Z

2017-07-11

Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains. Nearly all such RTs are present within type III CRISPR-Cas loci, but their phylogeny does not parallel the CRISPR-Cas type classification, indicating that RT-Cas1 is an autonomous functional module that is disseminated by horizontal gene transfer and can function with diverse type III systems. To compare the sequence pools sampled by RT-Cas1-associated and RT-lacking CRISPR-Cas systems, we obtained samples of a commercially grown cyanobacterium- Arthrospira platensis Sequencing of the CRISPR arrays uncovered a highly diverse population of spacers. Spacer diversity was particularly striking for the RT-Cas1-containing type III-B system, where no saturation was evident even with millions of sequences analyzed. In contrast, analysis of the RT-lacking type III-D system yielded a highly diverse pool but reached a point where fewer novel spacers were recovered as sequencing depth was increased. Matches could be identified for a small fraction of the non-RT-Cas1-associated spacers, and for only a single RT-Cas1-associated spacer. Thus, the principal source(s) of the spacers, particularly the hypervariable spacer repertoire of the RT-associated arrays, remains unknown. IMPORTANCE While the majority of CRISPR-Cas immune systems adapt to foreign genetic elements by capturing segments of invasive DNA, some systems carry reverse transcriptases (RTs) that enable adaptation to RNA molecules. From analysis of available bacterial sequence data, we find evidence that RT-based RNA adaptation machinery has been able to join with CRISPR-Cas immune systems in many, diverse bacterial species. To investigate whether the abilities to adapt to DNA and RNA molecules are utilized for defense against distinct classes of invaders in nature, we sequenced CRISPR arrays from samples of commercial-scale open-air cultures of Arthrospira platensis , a cyanobacterium that contains both RT-lacking and RT-containing CRISPR-Cas systems. We uncovered a diverse pool of naturally occurring immune memories, with the RT-lacking locus acquiring a number of segments matching known viral or bacterial genes, while the RT-containing locus has acquired spacers from a distinct sequence pool for which the source remains enigmatic. Copyright © 2017 Silas et al.

Preparation, Mechanical and Thermal Properties of Cement Board with Expanded Perlite Based Composite Phase Change Material for Improving Buildings Thermal Behavior

PubMed Central

Ye, Rongda; Fang, Xiaoming; Zhang, Zhengguo; Gao, Xuenong

2015-01-01

Here we demonstrate the mechanical properties, thermal conductivity, and thermal energy storage performance of construction elements made of cement and form-stable PCM-Rubitherm® RT 28 HC (RT28)/expanded perlite (EP) composite phase change materials (PCMs). The composite PCMs were prepared by adsorbing RT28 into the pores of EP, in which the mass fraction of RT28 should be limited to be no more than 40 wt %. The adsorbed RT28 is observed to be uniformly confined into the pores of EP. The phase change temperatures of the RT28/EP composite PCMs are very close to that of the pure RT28. The apparent density and compression strength of the composite cubes increase linearly with the mass fraction of RT28. Compared with the thermal conductivity of the boards composed of cement and EP, the thermal conductivities of the composite boards containing RT28 increase by 15%–35% with the mass fraction increasing of RT28. The cubic test rooms that consist of six boards were built to evaluate the thermal energy storage performance, it is found that the maximum temperature different between the outside surface of the top board with the indoor temperature using the composite boards is 13.3 °C higher than that of the boards containing no RT28. The thermal mass increase of the built environment due to the application of composite boards can contribute to improving the indoor thermal comfort and reducing the energy consumption in the buildings. PMID:28793671

MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

PubMed

Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2017-03-01

The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

Patterns of care in palliative radiotherapy: a population-based study.

PubMed

Murphy, James D; Nelson, Lorene M; Chang, Daniel T; Mell, Loren K; Le, Quynh-Thu

2013-09-01

Approximately one half of the radiotherapy (RT) prescribed in the United States is delivered with palliative intent. The purpose of this study was to investigate the patterns of delivery of palliative RT across the United States. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, 51,610 patients were identified with incident stage IV breast, prostate, lung, or colorectal cancer diagnosed between 2000 and 2007 and observed through 2009. Multivariate logistic regression determined predictors of palliative RT. Forty-one percent of the study population received palliative RT, including 53% of patients with lung cancer, followed by those with breast (42%), prostate (40%), and colorectal cancers (12%). Multivariate analysis revealed that older patients (P<.001) and those with higher Charlson comorbidity scores (P<.001) were less likely to receive palliative RT. Black patients with prostate cancer were 20% less likely (P<.001), and black patients with colorectal cancer were 28% less likely (P<.001), than white patients to receive palliative RT. Among those treated with RT, 23% of patients with lung cancer died within 2 weeks of completing treatment, followed by those with colorectal (12%), breast (11%), and prostate cancers (8%). In addition to tumor site, significant predictors (P<.05) of death within 2 weeks of receiving RT included increased age, increased comorbidity, and male sex. Inequality in the receipt of palliative RT exists among the elderly and patients with comorbid conditions and varies with race. In addition, a significant number of patients die shortly after receiving RT. Understanding these patterns of care, along with further research into the underlying causes, will improve access and quality of palliative RT.

Molecular Dynamics Study of HIV-1 RT-DNA-Nevirapine Complexes Explains NNRTI Inhibition, and Resistance by Connection Mutations

PubMed Central

Vijayan, R.S.K.; Arnold, Eddy; Das, Kalyan

2015-01-01

HIV-1 reverse transcriptase (RT) is a multifunctional enzyme that is targeted by nucleoside analogs (NRTIs) and nonnucleoside inhibitors (NNRTIs). NNRTIs are allosteric inhibitors of RT, and constitute an integral part of the highly active antiretroviral therapy (HAART) regimen. Under selective pressure, HIV-1 acquires resistance against NNRTIs primarily by selecting mutations around the NNRTI pocket. Complete RT sequencing of clinical isolates revealed that spatially distal mutations arising in connection and the RNase H domain also confer NNRTI resistance and contribute to NRTI resistance. However, the precise structural mechanism by which the connection domain mutations confer NNRTI resistance is poorly understood. We performed 50-ns MD simulations, followed by essential dynamics, free-energy landscape analyses and network analyses of RT-DNA, RT-DNA-nevirapine, and N348I/T369I mutant RT-DNA-nevirapine complexes. MD simulation studies revealed altered global motions and restricted conformational landscape of RT upon nevirapine binding. Analysis of protein structure network parameters demonstrated a dissortative hub pattern in the RT-DNA complex and an assortative hub pattern in the RT-DNA-nevirapine complex suggesting enhanced rigidity of RT upon nevirapine binding. The connection subdomain mutations N348I/T369I did not induce any significant structural change; rather, these mutations modulate the conformational dynamics and alter the long-range allosteric communication network between the connection subdomain and NNRTI pocket. Insights from the present study provide a structural basis for the biochemical and clinical findings on drug resistance caused by the connection and RNase H mutations. PMID:24174331

Analytical validation of a reverse transcriptase droplet digital PCR (RT-ddPCR) for quantitative detection of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Jia, Peng; Purcell, Maureen; Pan, Guang; Wang, Jinjin; Kan, Shifu; Liu, Yin; Zheng, Xiaocong; SHi, Xiujie; He, Junqiang; Yu, Li; Hua, Qunyi; Lu, Tikang; Lan, Wensheng; Winton, James; Jin, Ningyi; Liu, Hong

2017-01-01

Infectious hematopoietic necrosis virus (IHNV) is an important pathogen of salmonid fishes. A validated universal reverse transcriptase quantitative PCR (RT-qPCR) assay that can quantify levels of IHNV in fish tissues has been previously reported. In the present study, we adapted the published set of IHNV primers and probe for use in a reverse-transcriptase droplet digital PCR (RT-ddPCR) assay for quantification of the virus in fish tissue samples. The RT-ddPCR and RT-qPCR assays detected 13 phylogenetically diverse IHNV strains, but neither assay produced detectable amplification when RNA from other fish viruses was used. The RT-ddPCR assay had a limit of detection (LOD) equating to 2.2 plaque forming units (PFU)/μl while the LOD for the RT-qPCR was 0.2 PFU/μl. Good agreement (69.4–100%) between assays was observed when used to detect IHNV RNA in cell culture supernatant and tissues from IHNV infected rainbow trout (Oncorhynchus mykiss) and arctic char (Salvelinus alpinus). Estimates of RNA copy number produced by the two assays were significantly correlated but the RT-qPCR consistently produced higher estimates than the RT-ddPCR. The analytical properties of the N gene RT-ddPCR test indicated that this method may be useful to assess IHNV RNA copy number for research and diagnostic purposes. Future work is needed to establish the within and between laboratory diagnostic performance of the RT-ddPCR assay.

Dose-response relationship of robot-assisted stroke motor rehabilitation: the impact of initial motor status.

PubMed

Hsieh, Yu-wei; Wu, Ching-yi; Lin, Keh-chung; Yao, Grace; Wu, Kuen-yuh; Chang, Ya-ju

2012-10-01

The increasing availability of robot-assisted therapy (RT), which provides quantifiable, reproducible, interactive, and intensive practice, holds promise for stroke rehabilitation, but data on its dose-response relation are scanty. This study used 2 different intensities of RT to examine the treatment effects of RT and the effect on outcomes of the severity of initial motor deficits. Fifty-four patients with stroke were randomized to a 4-week intervention of higher-intensity RT, lower-intensity RT, or control treatment. The primary outcome, the Fugl-Meyer Assessment, was administered at baseline, midterm, and posttreatment. Secondary outcomes included the Medical Research Council scale, the Motor Activity Log, and the physical domains of the Stroke Impact Scale. The higher-intensity RT group showed significantly greater improvements on the Fugl-Meyer Assessment than the lower-intensity RT and control treatment groups at midterm (P=0.003 and P=0.02) and at posttreatment (P=0.04 and P=0.02). Within-group gains on the secondary outcomes were significant, but the differences among the 3 groups did not reach significance. Recovery rates of the higher-intensity RT group were higher than those of the lower-intensity RT group, particularly on the Fugl-Meyer Assessment. Scatterplots with curve fitting showed that patients with moderate motor deficits gained more improvements than those with severe or mild deficits after the higher-intensity RT. This study demonstrated the higher treatment intensity provided by RT was associated with better motor outcome for patients with stroke, which may shape further stroke rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00917605.

A Qualitative Analysis of Real-Time Continuous Glucose Monitoring Data Sharing with Care Partners: To Share or Not to Share?

PubMed

Litchman, Michelle L; Allen, Nancy A; Colicchio, Vanessa D; Wawrzynski, Sarah E; Sparling, Kerri M; Hendricks, Krissa L; Berg, Cynthia A

2018-01-01

Little research exists regarding how real-time continuous glucose monitoring (RT-CGM) data sharing plays a role in the relationship between patients and their care partners. To (1) identify the benefits and challenges related to RT-CGM data sharing from the patient and care partner perspective and (2) to explore the number and type of individuals who share and follow RT-CGM data. This qualitative content analysis was conducted by examining publicly available blogs focused on RT-CGM and data sharing. A thematic analysis of blogs and associated comments was conducted. A systematic appraisal of personal blogs examined 39 blogs with 206 corresponding comments. The results of the study provided insight about the benefits and challenges related to individuals with diabetes sharing their RT-CGM data with a care partner(s). The analysis resulted in three themes: (1) RT-CGM data sharing enhances feelings of safety, (2) the need to communicate boundaries to avoid judgment, and (3) choice about sharing and following RT-CGM data. RT-CGM data sharing occurred within dyads (n = 46), triads (n = 15), and tetrads (n = 2). Adults and children with type 1 diabetes and their care partners are empowered by the ability to share and follow RT-CGM data. Our findings suggest that RT-CGM data sharing between an individual with diabetes and their care partner can complicate relationships. Healthcare providers need to engage patients and care partners in discussions about best practices related to RT-CGM sharing and following to avoid frustrations within the relationship.

Preparation, Mechanical and Thermal Properties of Cement Board with Expanded Perlite Based Composite Phase Change Material for Improving Buildings Thermal Behavior.

PubMed

Ye, Rongda; Fang, Xiaoming; Zhang, Zhengguo; Gao, Xuenong

2015-11-13

Here we demonstrate the mechanical properties, thermal conductivity, and thermal energy storage performance of construction elements made of cement and form-stable PCM-Rubitherm® RT 28 HC (RT28)/expanded perlite (EP) composite phase change materials (PCMs). The composite PCMs were prepared by adsorbing RT28 into the pores of EP, in which the mass fraction of RT28 should be limited to be no more than 40 wt %. The adsorbed RT28 is observed to be uniformly confined into the pores of EP. The phase change temperatures of the RT28/EP composite PCMs are very close to that of the pure RT28. The apparent density and compression strength of the composite cubes increase linearly with the mass fraction of RT28. Compared with the thermal conductivity of the boards composed of cement and EP, the thermal conductivities of the composite boards containing RT28 increase by 15%-35% with the mass fraction increasing of RT28. The cubic test rooms that consist of six boards were built to evaluate the thermal energy storage performance, it is found that the maximum temperature different between the outside surface of the top board with the indoor temperature using the composite boards is 13.3 °C higher than that of the boards containing no RT28. The thermal mass increase of the built environment due to the application of composite boards can contribute to improving the indoor thermal comfort and reducing the energy consumption in the buildings.

Transportation and platforms perspective

NASA Technical Reports Server (NTRS)

Bennett, Gary L.

1992-01-01

The topics covered are presented in viewgraph form and include the following: Office of Aeronautics and Space Technology; space research and technology (R&T); space R&T mission statement; Space R&T program development; R&T strategy; Office of Space Science and Applications (OSSA) technology needs; transportation technology; and space platforms technology.

Advances in Radiotherapy Management of Esophageal Cancer.

PubMed

Verma, Vivek; Moreno, Amy C; Lin, Steven H

2016-10-21

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC.

Advances in Radiotherapy Management of Esophageal Cancer

PubMed Central

Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

2016-01-01

Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

Targeted radiotherapy with gold nanoparticles: current status and future perspectives

PubMed Central

Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A; Berbeco, Ross; Makrigiorgos, G Mike

2014-01-01

Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed. PMID:24978464

Planning for RtI

ERIC Educational Resources Information Center

Robins, Jennifer; Antrim, Patricia

2013-01-01

In 2004 the Individuals with Disabilities Education Act authorized funding for Response to Intervention (RtI) instruction in the United States. By 2011, 71 percent of school districts had adopted RtI (Institute of Education Sciences 2011). The goal of RtI is to provide personalized, just-in-time intervention in reading and math for students who…

Avian influenza virus detection and quantitation by real-time RT-PCR

USDA-ARS?s Scientific Manuscript database

Real-time RT-PCR (rRT-PCR) has been used for avian influenza virus (AIV) detection since the early 2000’s for routine surveillance, during outbreaks and for research. Some of the advantages of rRT-PCR are: high sensitivity, high specificity, rapid time-to-result, scalability, cost, and its inherentl...

Real-time continuous glucose monitoring systems in the classroom/school environment.

PubMed

Benassi, Kari; Drobny, Jessica; Aye, Tandy

2013-05-01

Children with type 1 diabetes (T1D) spend 4-7 h/day in school with very little supervision of their diabetes management. Therefore, families have become more dependent on technology, such as use of real-time continuous glucose monitoring (RT-CGM), to provide increased supervision of their diabetes management. We sought to assess the impact of RT-CGM use in the classroom/school environment. Children with T1D using RT-CGM, their parents, and teachers completed a questionnaire about RT-CGM in the classroom/school environment. The RT-CGM was tolerated well in the classroom/school environment. Seventy percent of parents, 75% of students, and 51% of teachers found RT-CGM useful in the classroom/school environment. The students found the device to be more disruptive than did their parents and teachers. However, all three groups agreed that RT-CGM increased their comfort with diabetes management at school. Our study suggests that RT-CGM is useful and not disruptive in the classroom/school environment. The development of education materials for teachers could further increase its acceptance in the classroom/school environment.

Real-time RT-PCR, a necessary tool to support the diagnosis and surveillance of rotavirus in Mexico.

PubMed

De La Cruz Hernández, Sergio Isaac; Anaya Molina, Yazmin; Gómez Santiago, Fabián; Terán Vega, Heidi Lizbeth; Monroy Leyva, Elda; Méndez Pérez, Héctor; García Lozano, Herlinda

2018-04-01

Rotavirus produces diarrhea in children under 5 years old. Most of those conventional methods such as polyacrylamide gel electrophoresis (PAGE) and reverse transcription-polymerase chain reaction (RT-PCR) have been used for rotavirus detection. However, these techniques need a multi-step process to get the results. In comparison with conventional methods, the real-time RT-PCR is a highly sensitive method, which allows getting the results in only one day. In this study a real-time RT-PCR assay was tested using a panel of 440 samples from patients with acute gastroenteritis, and characterized by PAGE and RT-PCR. The results show that the real-time RT-PCR detected rotavirus from 73% of rotavirus-negative samples analyzed by PAGE and RT-PCR; thus, the percentage of rotavirus-positive samples increased to 81%. The results indicate that this real-time RT-PCR should be part of a routine analysis, and as a support of the diagnosis of rotavirus in Mexico. Copyright © 2017 Elsevier Inc. All rights reserved.

Daily Tracking of Glioblastoma Resection Cavity, Cerebral Edema, and Tumor Volume with MRI-Guided Radiation Therapy.

PubMed

Mehta, Shahil; Gajjar, Shefali R; Padgett, Kyle R; Asher, David; Stoyanova, Radka; Ford, John C; Mellon, Eric A

2018-03-19

Radiation therapy (RT) plays a critical role in the treatment of glioblastoma. Studies of brain imaging during RT for glioblastoma have demonstrated changes in the brain during RT. However, frequent or daily utilization of standalone magnetic resonance imaging (MRI) scans during RT have limited feasibility. The recent release of the tri-cobalt-60 MRI-guided RT (MR-IGRT) device (ViewRay MRIdian, Cleveland, OH) allows for daily brain MRI for the RT setup. Daily MRI of three postoperative patients undergoing RT and temozolomide for glioblastoma over a six-week course allowed for the identification of changes to the cavity, edema, and visible tumor on a daily basis. The volumes and dimensions of the resection cavities, edema, and T2-hyperintense tumor were measured. A general trend of daily decreases in cavity measurements was observed in all patients. For the one patient with edema, a trend of daily increases followed by a trend of daily decreases were observed. These results suggest that daily MRI could be used for onboard resimulation and adaptive RT for future fluctuations in the sizes of brain tumors, cavities, or cystic components. This could improve tumor targeting and reduce RT of healthy brain tissue.

Daily Tracking of Glioblastoma Resection Cavity, Cerebral Edema, and Tumor Volume with MRI-Guided Radiation Therapy

PubMed Central

Mehta, Shahil; Gajjar, Shefali R; Padgett, Kyle R; Asher, David; Stoyanova, Radka; Ford, John C

2018-01-01

Radiation therapy (RT) plays a critical role in the treatment of glioblastoma. Studies of brain imaging during RT for glioblastoma have demonstrated changes in the brain during RT. However, frequent or daily utilization of standalone magnetic resonance imaging (MRI) scans during RT have limited feasibility. The recent release of the tri-cobalt-60 MRI-guided RT (MR-IGRT) device (ViewRay MRIdian, Cleveland, OH) allows for daily brain MRI for the RT setup. Daily MRI of three postoperative patients undergoing RT and temozolomide for glioblastoma over a six-week course allowed for the identification of changes to the cavity, edema, and visible tumor on a daily basis. The volumes and dimensions of the resection cavities, edema, and T2-hyperintense tumor were measured. A general trend of daily decreases in cavity measurements was observed in all patients. For the one patient with edema, a trend of daily increases followed by a trend of daily decreases were observed. These results suggest that daily MRI could be used for onboard resimulation and adaptive RT for future fluctuations in the sizes of brain tumors, cavities, or cystic components. This could improve tumor targeting and reduce RT of healthy brain tissue. PMID:29796358

Modern Radiation Therapy for Nodal Non-Hodgkin Lymphoma—Target Definition and Dose Guidelines From the International Lymphoma Radiation Oncology Group

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

Illidge, Tim, E-mail: Tim.Illidge@ics.manchester.ac.uk; Specht, Lena; Yahalom, Joachim

2014-05-01

Radiation therapy (RT) is the most effective single modality for local control of non-Hodgkin lymphoma (NHL) and is an important component of therapy for many patients. Many of the historic concepts of dose and volume have recently been challenged by the advent of modern imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the ILROG steering committee on the use of RT in NHL in the modern era. The roles of reduced volume and reduced doses aremore » addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. In the modern era, in which combined-modality treatment with systemic therapy is appropriate, the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. A new concept, involved-site RT, defines the clinical target volume. For indolent NHL, often treated with RT alone, larger fields should be considered. Newer treatment techniques, including intensity modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should be implemented, and their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control.« less

Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

PubMed

Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

2018-04-01

Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

Neoadjuvant Radiation Is Associated With Improved Survival in Patients With Resectable Pancreatic Cancer: An Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry

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

Stessin, Alexander M.; Weill Medical College of Cornell University, New York, NY; Meyer, Joshua E.

2008-11-15

Purpose: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of themore » study was overall survival. Results: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). Conclusions: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.« less

Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters.

PubMed

Isobe, Koichi; Uno, Takashi; Tamaru, Jun-ichi; Kawakami, Hiroyuki; Ueno, Naoyuki; Wakita, Hisashi; Okada, Jun-ichi; Itami, Jun; Ito, Hisao

2006-02-01

The objective of this study was to investigate the correlation between local recurrence and radiotherapeutic parameters, including dose and RT radiotherapy (RT) field. The current study included 35 patients who were diagnosed with immunohistochemically confirmed nasal natural killer (NK)/T-cell lymphoma between 1976 and 2004. There were 21 males and 14 females, and they ranged in age from 18 years to 76 years (median, 51 yrs). The primary tumor originated in the nasal cavity in 28 patients, and 32 patients had Stage I disease. Seventeen patients received treatment solely with RT, and the remaining 18 patients received a combination of chemotherapy and RT. The median tumor dose was 50 grays (Gy) (range, 22-60 Gy). Twenty-seven patients received RT to include all macroscopic lesions, all paranasal sinuses, the palate, and the nasopharynx. Eight patients received RT to all macroscopic lesions with generous margins. A complete remission (CR) or a CR/unconfirmed was achieved in 28 patients (80%). The 5-year overall survival (OAS) rate, disease-free survival (DFS) rate, and local control probability (LCP) were 47.3%, 42.9%, and 65.2%, respectively. Patients who received RT only to macroscopic lesions fared less well in terms of LCP (LCP 5 years, 71.9% vs. 41.7%; P=0.007). The difference in RT field also affected both the OAS rate and the DFS rate. Patients who received RT doses>or=50 Gy tended to achieve favorable local control. In the management of nasal NK/T-cell lymphoma, the RT field affected treatment outcomes. RT doses>or=50 Gy resulted in favorable local control. Copyright (c) 2005 American Cancer Society.

Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth and look-alike disease viruses

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

Hindson, B J; Baker, B R; Bentley Tammero, L F

2007-09-18

A high-throughput multiplexed assay (Multiplex Version 1.0) was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspectmore » cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRTPCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

Patterns of Recurrence Analysis in newly diagnosed GBM following 3D Conformal Radiation Therapy with respect to Pre-RT MR Spectroscopic Findings

PubMed Central

Park, Ilwoo; Tamai, Gregory; Lee, Michael C.; Chuang, Cynthia F.; Chang, Susan M.; Berger, Mitchel S.; Nelson, Sarah J.; Pirzkall, Andrea

2008-01-01

Purpose To determine whether the combined MRI and MR spectroscopy imaging (MRSI) prior to radiation therapy (RT) is valuable for RT target definition, and to evaluate the feasibility of replacing the current definition of uniform margins by custom shaped margins based on the information from MRI and MRSI. Methods and Materials Twenty three GBM patients underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT and at two month follow-up (FU) intervals thereafter. MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a measure of spectroscopic abnormality. A combined anatomic and metabolic ROI (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity and CNI2 based on the pre-RT imaging was compared to CNI2 extent and RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared to the extent of CE at each FU. Results Nine patients showed new or increased CE during FU, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in six patients and within the CNI2 that was not entirely covered by 60 Gy in three patients. New or increased CE resided within the pre-RT MRI/S lesion in 89 % (8/9) of the patients with new or increased CE. Conclusion These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting. PMID:17513061

Utility of Deep Inspiration Breath Hold for Left-Sided Breast Radiation Therapy in Preventing Early Cardiac Perfusion Defects: A Prospective Study

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

Zagar, Timothy M., E-mail: zagar@med.unc.edu; Kaidar-Person, Orit; Tang, Xiaoli

Purpose: To evaluate early cardiac single photon computed tomography (SPECT) findings after left breast/chest wall postoperative radiation therapy (RT) in the setting of deep inspiration breath hold (DIBH). Methods and Materials: We performed a prospective single-institution single-arm study of patients who were planned for tangential RT with DIBH to the left breast/chest wall (± internal mammary nodes). The DIBH was done by use of a controlled surface monitoring technique (AlignRT, Vision RT Ltd, London, UK). The RT was given with tangential fields and a heart block. Radiation-induced cardiac perfusion and wall motion changes were assessed by pre-RT and 6-month post-RTmore » SPECT scans. A cumulative SPECT summed-rest score was used to quantify perfusion in predefined left ventricle segments. The incidence of wall motion abnormalities was assessed in each of these same segments. Results: A total of 20 patients with normal pre-RT scans were studied; their median age was 56 years (range, 39-72 years). Seven (35%) patients also received irradiation to the left internal mammary chain, and 5 (25%) received an additional RT field to supraclavicular nodes. The median heart dose was 94 cGy (range, 56-200 cGy), and the median V25{sub Gy} was zero (range, 0-0.1). None of the patients had post-RT perfusion or wall motion abnormalities. Conclusions: Our results suggest that DIBH and conformal cardiac blocking for patients receiving tangential RT for left-sided breast cancer is an effective means to avoid early RT-associated cardiac perfusion defects.« less

Image storage in radiation oncology: What did we learn from diagnostic radiology?

NASA Astrophysics Data System (ADS)

Blodgett, Kurt; Luick, Marc; Colonias, Athanasios; Gayou, Olivier; Karlovits, Stephen; Werts, E. Day

2009-02-01

The Digital Imaging and Communications in Medicine (DICOM) standard was developed by the National Electrical Manufacturers Association (NEMA) and the American College of Radiology (ACR) for medical image archiving and retrieval. An extension to this implemented a standard named DICOM-RT for use in Radiation Oncology. There are currently seven radiotherapy-specific DICOM objects which include: RT Structure Set, RT Plan, RT Dose, RT Image, RT Beams Treatment Record, RT Brachy Treatment Record, and RT Treatment Summary Record. The type of data associated with DICOM-RT includes (1) Radiation treatment planning datasets (CT, MRI, PET) with radiation treatment plans showing beam arrangements, isodose distributions, and dose volume histograms of targets/normal tissues and (2) Image-guided radiation modalities such as Siemens MVision mega-voltage cone beam CT (MV-CBCT). With the advent of such advancing technologies, there has been an exponential increase in image data collected for each patient, and the need for reliable and accessible image storage has become critical. A potential solution is a Radiation Oncology specific picture archiving and communication systems (PACS) that would allow data storage from multiple vendor devices and support the storage and retrieval needs not only of a single site but of a large, multi-facility network of radiation oncology clinics. This PACS system must be reliable, expandable, and cost-effective to operate while protecting sensitive patient image information in a Health Insurance Portability and Accountability Act (HIPAA) compliant environment. This paper emphasizes the expanding DICOM-RT storage requirements across our network of 8 radiation oncology clinics and the initiatives we undertook to address the increased volume of data by using the ImageGrid (CANDELiS Inc, Irvine CA) server and the IGViewer license (CANDELiS Inc, Irvine CA) to create a DICOM-RT compatible PACS system.

Neurofilament tail phosphorylation: identity of the RT-97 phosphoepitope and regulation in neurons by cross-talk among proline-directed kinases.

PubMed

Veeranna; Lee, Ju-Hyun; Pareek, Tej K; Jaffee, Howard; Boland, Barry; Vinod, K Yaragudri; Amin, Niranjana; Kulkarni, Ashok B; Pant, Harish C; Nixon, Ralph A

2008-10-01

As axons myelinate, establish a stable neurofilament network, and expand in caliber, neurofilament proteins are extensively phosphorylated along their C-terminal tails, which is recognized by the monoclonal antibody, RT-97. Here, we demonstrate in vivo that RT-97 immunoreactivity (IR) is generated by phosphorylation at KSPXK or KSPXXXK motifs and requires flanking lysines at specific positions. extracellular signal regulated kinase 1,2 (ERK1,2) and pERK1,2 levels increase in parallel with phosphorylation at the RT-97 epitope during early postnatal brain development. Purified ERK1,2 generated RT-97 on both KSP motifs on recombinant NF-H tail domain proteins, while cdk5 phosphorylated only KSPXK motifs. RT-97 epitope generation in primary hippocampal neurons was regulated by extensive cross-talk among ERK1,2, c-Jun N-terminal kinase 1,2 (JNK1,2) and cdk5. Inhibition of both ERK1,2 and JNK1,2 completely blocked RT-97 generation. Cdk5 influenced RT-97 generation indirectly by modulating JNK activation. In mice, cdk5 gene deletion did not significantly alter RT-97 IR or ERK1,2 and JNK activation. In mice lacking the cdk5 activator P35, the partial suppression of cdk5 activity increased RT-97 IR by activating ERK1,2. Thus, cdk5 influences RT-97 epitope generation partly by modulating ERKs and JNKs, which are the two principal kinases regulating neurofilament phosphorylation. The regulation of a single target by multiple protein kinases underscores the importance of monitoring other relevant kinases when the activity of a particular one is blocked.

Current role of radiation therapy for multiple myeloma.

PubMed

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K S; Pandey, Manoj K; Malysz, Jozef; Creer, Michael H; Zhu, Junjia; Mir, Muhammad A; Varlotto, John M

2015-01-01

Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

Current Role of Radiation Therapy for Multiple Myeloma

PubMed Central

Talamo, Giampaolo; Dimaio, Christopher; Abbi, Kamal K. S.; Pandey, Manoj K.; Malysz, Jozef; Creer, Michael H.; Zhu, Junjia; Mir, Muhammad A.; Varlotto, John M.

2015-01-01

Background: Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. Methods: We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010–2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. Results: Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. Conclusion: Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT. PMID:25741475

Pattern of radiotherapy care in Bulgaria

PubMed Central

Hadjieva, Tatiana

2015-01-01

The paper reveals the changing pattern of Bulgarian Radiotherapy (RT) care after the successful implementation of 15 projects for 100 million euro under the European Regional Development Fund in Operational Programme for Regional Development 2007–2013. The project enables a total one-step modernization of 14 Bulgarian RT Centres and creation of a new one. At the end of the Programme (mid 2015), 16 new Linacs and 2 modern cobalt machines will be available together with 11 virtual CT simulators, 5 CT simulators, 1 MRI and 1 PET CT for RT planning and all dosimetry facilities needed. Such a modernization has moved Bulgarian RT forward, with 2.7 MV units per one million of population (MV/mln.inh) in comparison with 0.9 MV/mln.inh in 2012. Guild of Bulgarian Radiotherapists includes 70 doctors, 46 physicists and 10 engineers, together with 118 RTTs and 114 nurses and they all have treated 16,447 patients in 2013. Major problems are inadequate reimbursement from the monopolistic Health Insurance Fund (900 euro for 3D conformal RT and 1500 euro for IMRT); fragmentation of RT care with 1–2 MV units per Centre; no payment for patient travel expenses; need for quick and profound education of 26% of doctors and 46% of physicists without RT license, along with continuous education for all others; and resource for 5000–9000 more patients to be treated yearly by RT in order to reach 45–50% from current service of 32%. After 15 years of struggle of RT experts, finally the pattern of Bulgarian RT care at 2014–2015 is approaching the level of modern European RT. PMID:26549991

Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men.

PubMed

Damas, Felipe; Libardi, Cleiton A; Ugrinowitsch, Carlos; Vechin, Felipe C; Lixandrão, Manoel E; Snijders, Tim; Nederveen, Joshua P; Bacurau, Aline V; Brum, Patricia; Tricoli, Valmor; Roschel, Hamilton; Parise, Gianni; Phillips, Stuart M

2018-01-01

Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased 48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns], ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]). Increased SC content was not coupled with changes in myonuclear number. SC have a more pronounced role in muscle repair during the initial phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases.

Criteria for and Appropriateness of Renal Transplantation in Elderly Patients With End-Stage Renal Disease: A Literature Review and Position Statement on Behalf of the European Renal Association-European Dialysis and Transplant Association Descartes Working Group and European Renal Best Practice.

PubMed

Segall, Liviu; Nistor, Ionuţ; Pascual, Julio; Mucsi, Istvan; Guirado, Lluis; Higgins, Robert; Van Laecke, Steven; Oberbauer, Rainer; Van Biesen, Wim; Abramowicz, Daniel; Gavrilovici, Cristina; Farrington, Ken; Covic, Adrian

2016-10-01

During the last 20 years, waiting lists for renal transplantation (RT) have grown significantly older. However, elderly patients (ie ≥65 years of age) are still more rarely referred or accepted to waiting lists and, if enlisted, have less chances of actually receiving a kidney allograft, than younger counterparts. In this review, we looked at evidence for the benefits and risks of RT in the elderly trying to answer the following questions: Should RT be advocated for elderly patients? What should be the criteria to accept elderly patients on the waiting list for RT? What strategies might be used to increase the rate of RT in waitlisted elderly candidates? For selected elderly patients, RT was shown to be superior to dialysis in terms of patient survival. Virtually all guidelines recommend that patients should not be deemed ineligible for RT based on age alone, although a short life expectancy generally might preclude RT. Concerning the assessment of comorbidities in the elderly, special attention should be paid to cardiac evaluation and screening for malignancy. Comorbidity scores and frailty assessment scales might help the decision making on eligibility. Psychosocial issues should also be evaluated. To overcome the scarcity of organ donors, elderly RT candidates should be encouraged to consider expanded criteria donors and living donors, as alternatives to deceased standard criteria donors. It has been demonstrated that expanded criteria donor RT in patients 60 years or older is associated with higher survival rates than remaining on dialysis, whereas living donor RT is superior to all other options.

Development of a highly sensitive real-time nested RT-PCR assay in a single closed tube for detection of enterovirus 71 in hand, foot, and mouth disease.

PubMed

Niu, Peihua; Qi, Shunxiang; Yu, Benzhang; Zhang, Chen; Wang, Ji; Li, Qi; Ma, Xuejun

2016-11-01

Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease (HFMD). A commercial TaqMan probe-based real-time PCR assay has been widely used for the differential detection of EV71 despite its relatively high cost and failure to detect samples with a low viral load (Ct value > 35). In this study, a highly sensitive real-time nested RT-PCR (RTN RT-PCR) assay in a single closed tube for detection of EV71 in HFMD was developed. The sensitivity and specificity of this assay were evaluated using a reference EV71 stock and a panel of controls consisting of coxsackievirus A16 (CVA16) and common respiratory viruses, respectively. The clinical performance of this assay was evaluated and compared with those of a commercial TaqMan probe-based real-time PCR (qRT-PCR) assay and a traditional two-step nested RT-PCR assay. The limit of detection for the RTN RT-PCR assay was 0.01 TCID50/ml, with a Ct value of 38.3, which was the same as that of the traditional two-step nested RT-PCR assay and approximately tenfold lower than that of the qRT-PCR assay. When testing the reference strain EV71, this assay showed favorable detection reproducibility and no obvious cross-reactivity. The testing results of 100 clinical throat swabs from HFMD-suspected patients revealed that 41 samples were positive for EV71 by both RTN RT-PCR and traditional two-step nested RT-PCR assays, whereas only 29 were EV71 positive by qRT-PCR assay.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

PubMed

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Recombinant tissue plasminogen activator enhances microparticle release from mouse brain-derived endothelial cells through plasmin.

PubMed

Garraud, Marie; Khacef, Kahina; Vion, Anne-Clémence; Leconte, Claire; Yin, Min; Renard, Jean-Marie; Marchand-Leroux, Catherine; Boulanger, Chantal M; Margaill, Isabelle; Beray-Berthat, Virginie

2016-11-15

Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved pharmacological strategy for acute ischemic stroke. However, rt-PA exhibits vascular toxicity mainly due to endothelial damage. To investigate the mechanisms underlying rt-PA-induced endothelial alterations, we assessed the role of rt-PA in the generation of endothelial microparticles (EMPs), emerging biological markers and effectors of endothelial dysfunction. The mouse brain-derived endothelial cell line bEnd.3 was used. Cells were treated with rt-PA at 20, 40 or 80μg/ml for 15 or 24h, and EMPs were quantified in the culture media using Annexin-V staining coupled with flow cytometry. Rt-PA enhanced EMP release from bEnd.3 cells with a maximal increase at the 40μg/ml dose for 24h (+78% compared to controls). Using tranexamic acid and aprotinin we demonstrated that plasmin is responsible for rt-PA-induced EMP release. The p38 MAPK inhibitor SB203580 and the poly(ADP-ribose)polymerase (PARP) inhibitor PJ34 also reduced rt-PA-induced EMP production, suggesting that p38 MAPK and PARP are downstream intracellular effectors of rt-PA/plasmin. Rt-PA also altered through plasmin the morphology and the confluence of bEnd.3 cells. By contrast, these changes did not implicate p38 MAPK and PARP. This study demonstrates that rt-PA induces the production of microparticles by cerebral endothelial cells, through plasmin, p38 MAPK and PARP pathways. Determining the phenotype of these EMPs to clarify their role on the endothelium in ischemic conditions could thus be of particular interest. Copyright © 2016 Elsevier B.V. All rights reserved.

A prospective study of cerebral, frontal lobe, and temporal lobe volumes and neuropsychological performance in children with primary brain tumors treated with cranial radiation.

PubMed

Agbahiwe, Harold; Rashid, Arif; Horska, Alena; Mahone, E Mark; Lin, Doris; McNutt, Todd; Cohen, Kenneth; Redmond, Kristin; Wharam, Moody; Terezakis, Stephanie

2017-01-01

Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning. Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated. Quantitative magnetic resonance imaging and neuropsychological assessments (language, memory, auditory and visual processing, and vocabulary) were performed at the baseline and 6, 15, and 27 months after RT. The effects of age, the time since RT, and the cerebral RT dose on brain volumes and neuropsychological performance were analyzed with linear mixed effects model analyses. Cerebral volume increased significantly with age in both groups (P = .01); this increase in volume was more pronounced in younger children. Vocabulary performance was found to be significantly associated with a greater cerebral volume (P = .05) and a lower RT dose (P = .003). No relation was observed between the RT dose and the cerebral volume. There was no difference in the corresponding neuropsychological tests between the 2 groups. This prospective study found significant relations among the RT dose, cerebral volumes, and rate of vocabulary development among children receiving RT. The results of this study provide further support for clinical trials aimed at reducing cranial RT doses in the pediatric population. Cancer 2017;161-168. © 2016 American Cancer Society. © 2016 American Cancer Society.

The combined use of surgery and radiotherapy to treat patients with epidural cord compression due to metastatic disease: a cost-utility analysis

PubMed Central

Furlan, Julio C.; Chan, Kelvin K.-W.; Sandoval, Guillermo A.; Lam, Kenneth C. K.; Klinger, Christopher A.; Patchell, Roy A.; Laporte, Audrey; Fehlings, Michael G.

2012-01-01

Neoplastic metastatic epidural spinal cord compression is a common complication of cancer that causes pain and progressive neurologic impairment. The previous standard treatment for this condition involved corticosteroids and radiotherapy (RT). Direct decompressive surgery with postoperative radiotherapy (S + RT) is now increasingly being chosen by clinicians to significantly improve patients’ ability to walk and reduce their need for opioid analgesics and corticosteroids. A cost-utility analysis was conducted to compare S + RT with RT alone based on the landmark randomized clinical trial by Patchell et al. (2005). It was performed from the perspective of the Ontario Ministry of Health and Long-Term Care. Ontario-based costs were adjusted to 2010 US dollars. S + RT is more costly but also more effective than corticosteroids and RT alone, with an incremental cost-effectiveness ratio of US$250 307 per quality-adjusted life year (QALY) gained. First order probabilistic sensitivity analysis revealed that the probability of S + RT being cost-effective is 18.11%. The cost-effectiveness acceptability curve showed that there is a 91.11% probability of S + RT being cost-effective over RT alone at a willingness-to-pay of US$1 683 000 per QALY. In practice, the results of our study indicate that, by adopting the S + RT strategy, there would still be a chance of 18.11% of not paying extra at a willingness-to-pay of US$50 000 per QALY. Those results are sensitive to the costs of hospice palliative care. Our results suggest that adopting a standard S + RT approach for patients with MSCC is likely to increase health care costs but would result in improved outcomes. PMID:22505658

Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma.

PubMed

Choi, Jinhyun; Kim, Se-Heon; Koh, Yoon Woo; Choi, Eun Chang; Lee, Chang Geol; Keum, Ki Chang

2017-01-01

The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear.

Patterns of care and treatment outcomes of patients with Craniopharyngioma in the national cancer database.

PubMed

Rao, Yuan J; Hassanzadeh, Comron; Fischer-Valuck, Benjamin; Chicoine, Michael R; Kim, Albert H; Perkins, Stephanie M; Huang, Jiayi

2017-03-01

To investigate the patterns of care and outcomes in patients with craniopharyngioma in the National Cancer Data Base (NCDB). This study included 697 patients (166 pediatric and 531 adult cases) treated for craniopharyngioma between 2004 and 2012 in the NCDB. Adjuvant radiotherapy (RT) was defined if within 6 months of surgery. Limited surgery (LS) was defined as biopsy or subtotal resection. Proportional-hazards models were used to evaluate associations between covariates and overall survival (OS). A time-dependent analysis of RT was performed to account for early deaths after surgery. Median follow-up was 46 months. Overall, 21% of patients received adjuvant RT. Of patients with known surgical extent (n = 195), 71% had LS. Utilization of adjuvant RT increased from 18% in 2004-2007 to 24% in 2008-2012. Patterns of care regarding adjuvant RT or LS were not significantly different between adult and pediatric patients. Tumor size, low comorbidity, and LS were associated with increased utilization of adjuvant RT. The 5-year OS among patients treated with LS, LS+RT, and gross total resection were 75, 85, and 82% (p = 0.02). On multivariate analysis of the 195 patients with known surgical extent, LS+RT was associated with improved OS compared to LS (HR 0.22, 95% CI 0.05-0.99, p = 0.04), but was not significant when early deaths (<2 months from surgery) were removed to adjust for immortal-time bias. Medical practice regarding surgical approach and adjuvant RT are similar for pediatric and adult craniopharyngiomas. Immortal-time bias may confound assessment of OS for adjuvant RT. Prospective studies comparing adjuvant RT versus observation after LS are warranted.

Real-Time Three-Dimensional Echocardiography: Characterization of Cardiac Anatomy and Function-Current Clinical Applications and Literature Review Update.

PubMed

Velasco, Omar; Beckett, Morgan Q; James, Aaron W; Loehr, Megan N; Lewis, Taylor G; Hassan, Tahmin; Janardhanan, Rajesh

2017-01-01

Our review of real-time three-dimensional echocardiography (RT3DE) discusses the diagnostic utility of RT3DE and provides a comparison with two-dimensional echocardiography (2DE) in clinical cardiology. A Pubmed literature search on RT3DE was performed using the following key words: transthoracic, two-dimensional, three-dimensional, real-time, and left ventricular (LV) function. Articles included perspective clinical studies and meta-analyses in the English language, and focused on the role of RT3DE in human subjects. Application of RT3DE includes analysis of the pericardium, right ventricular (RV) and LV cavities, wall motion, valvular disease, great vessels, congenital anomalies, and traumatic injury, such as myocardial contusion. RT3DE, through a transthoracic echocardiography (TTE), allows for increasingly accurate volume and valve motion assessment, estimated LV ejection fraction, and volume measurements. Chamber motion and LV mass approximation have been more accurately evaluated by RT3DE by improved inclusion of the third dimension and quantification of volumetric movement. Moreover, RT3DE was shown to have no statistical significance when comparing the ejection fractions of RT3DE to cardiac magnetic resonance (CMR). Analysis of RT3DE data sets of the LV endocardial exterior allows for the volume to be directly quantified for specific phases of the cardiac cycle, ranging from end systole to end diastole, eliminating error from wall motion abnormalities and asymmetrical left ventricles. RT3DE through TTE measures cardiac function with superior diagnostic accuracy in predicting LV mass, systolic function, along with LV and RV volume when compared with 2DE with comparable results to CMR.

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer

PubMed Central

Greenup, Rachel A.; Blitzblau, Rachel C.; Houck, Kevin L.; Sosa, Julie Ann; Horton, Janet; Peppercorn, Jeffrey M.; Taghian, Alphonse G.; Smith, Barbara L.; Hwang, E. Shelley

2018-01-01

Introduction Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. Patients and Methods Using the National Cancer Database, we identified women with T1–T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. Results Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. Conclusion Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures. PMID:28291382

Radiation costing methods: a systematic review

PubMed Central

Rahman, F.; Seung, S.J.; Cheng, S.Y.; Saherawala, H.; Earle, C.C.; Mittmann, N.

2016-01-01

Objective Costs for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used. Methods A systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as “radiation,” “radiotherapy,” “neoplasm,” “cost,” “ cost analysis,” and “cost benefit analysis” to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars. Results Most of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%). Conclusions Costing methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed. PMID:27536189

Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.

PubMed

Troyano-Rodriguez, Eva; Lladó-Pelfort, Laia; Santana, Noemi; Teruel-Martí, Vicent; Celada, Pau; Artigas, Francesc

2014-12-15

The neurobiological basis of action of noncompetitive N-methyl-D-aspartate acid receptor (NMDA-R) antagonists is poorly understood. Electrophysiological studies indicate that phencyclidine (PCP) markedly disrupts neuronal activity with an overall excitatory effect and reduces the power of low-frequency oscillations (LFO; <4 Hz) in thalamocortical networks. Because the reticular nucleus of the thalamus (RtN) provides tonic feed-forward inhibition to the rest of the thalamic nuclei, we examined the effect of PCP on RtN activity, under the working hypothesis that NMDA-R blockade in RtN would disinhibit thalamocortical networks. Drug effects (PCP followed by clozapine) on the activity of RtN (single unit and local field potential recordings) and prefrontal cortex (PFC; electrocorticogram) in anesthetized rats were assessed. PCP (.25-.5 mg/kg, intravenous) reduced the discharge rate of 19 of 21 RtN neurons to 37% of baseline (p < .000001) and the power of LFO in RtN and PFC to ~20% of baseline (p < .001). PCP also reduced the coherence between PFC and RtN in the LFO range. A low clozapine dose (1 mg/kg intravenous) significantly countered the effect of PCP on LFO in PFC but not in RtN and further reduced the discharge rate of RtN neurons. However, clozapine administration partly antagonized the fall in coherence and phase-locking values produced by PCP. PCP activates thalamocortical circuits in a bottom-up manner by reducing the activity of RtN neurons, which tonically inhibit thalamic relay neurons. However, clozapine reversal of PCP effects is not driven by restoring RtN activity and may involve a cortical action. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The impact of radiation therapy sequencing on survival and cardiopulmonary mortality in the combined modality treatment of patients with esophageal cancer.

PubMed

Wojcieszynski, Andrzej P; Berman, Abigail T; Wan, Fei; Plastaras, John P; Metz, James M; Mitra, Nandita; Apisarnthanarax, Smith

2013-06-01

The addition of chemoradiation (CRT) to surgery has been shown to improve survival in patients with esophageal cancer. In the current study, the authors determined whether the sequencing of CRT has an effect on survival and cardiopulmonary mortality in patients with esophageal cancer. Patients with the following inclusion criteria were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988 through 2007: adenocarcinoma or squamous cell carcinoma of the esophagus and having undergone esophagectomy. Patients who died within 90 days of surgery were excluded. Demographic, tumor, and survival data were compared between patients receiving preoperative and postoperative RT. Cox proportional hazards regression models were calculated to identify parameters associated with cause-specific survival and overall survival. A competing risk analysis was performed to account for death due to esophageal cancer in the calculation of cardiopulmonary mortality. Of 5512 patients, 1881 received preoperative RT, 901 received postoperative RT, and 2730 did not receive RT. Patients receiving preoperative RT had improved 5-year cause-specific survival (41% vs 31%; P < .0001) and overall survival (33% vs 23%; P < .0001) compared with those receiving postoperative RT. No differences in adjusted cardiopulmonary mortality were found between patients who received RT versus those who did not (8% vs 10% at 10 years; hazards ratio [HR], 0.84 [95% confidence interval (95% CI), 0.64-1.12] [P = .24]) or between those treated with preoperative RT versus those treated with postoperative RT (HR, 0.70; 95% CI, 0.46-1.08 [P = .11]). These population-based data support the use of preoperative RT in patients with locally advanced esophageal cancer. RT should not be withheld out of concern for cardiopulmonary mortality. Copyright © 2013 American Cancer Society.

The timing of surgery after neoadjuvant radiotherapy influences tumor dissemination in a preclinical model

PubMed Central

Leroi, Natacha; Sounni, Nor Eddine; Van Overmeire, Eva; Blacher, Silvia; Marée, Raphael; Van Ginderachter, Jo; Lallemand, François; Lenaerts, Eric; Coucke, Philippe; Noel, Agnès; Martinive, Philippe

2015-01-01

Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving local tumor control and patient overall survival. The neoRT schedule and the timing of the surgical treatment (ST) are empirically based and influenced by the clinician's experience. The current study examines how the sequencing of neoRT and ST affects metastatic dissemination. In a breast carcinoma model, tumors were exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day 4 or 11 post-RT. The impact on the tumor microenvironment and lung metastases was evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy, early ST (at day 4 post-RT) led to increased size and number of lung metastases as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST protected the mice against lung metastases. This intriguing relationship between tumor aggressiveness and ST timing could not be explained by differences in classical parameters studied such as hypoxia, vessel density and matrix remodeling. The study of tumor-related inflammation and immunity reveals an increased circulating NK cell percentage following neoRT as compared to non irradiated mice. Then, radiation treatment and surgery were applied to tumor-bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung metastatic dissemination as compared to non irradiated tumor-bearing mice. Altogether our data demonstrate that the neoRT schedule and the ST timing affect metastasis formation in a pre-clinical model and points out the potential role of NK cells. These findings highlight the importance to cautiously tailor the optimal window for ST following RT. PMID:26440148

Development and evaluation of a simple and effective RT-qPCR inhibitory assay for detection of the efficacy of compounds towards HIV reverse transcriptase.

PubMed

Marino-Merlo, Francesca; Frezza, Caterina; Papaianni, Emanuela; Valletta, Elena; Mastino, Antonio; Macchi, Beatrice

2017-11-01

Assessing the actual efficacy of compounds to directly inhibit HIV reverse transcriptase (RT) activity is a main goal in preclinical antiretroviral studies. Our previous studies demonstrated that the effects of inhibitor compounds towards HIV-RT could be efficiently assessed through a simple cell-free assay based on conventional reverse transcription PCR. In the present study, we describe a modified variant of our assay, termed RT real-time quantitative PCR inhibitory assay (RT-qPCR-IA), in which the ability of compounds to restrict the complementary DNA (cDNA) generation by HIV-RT using a specific RNA template is performed by the real-time technique, in order to improve both accuracy and sensitivity of the method. As specific RNA template, RNA extracted from stable transfectants ectopically expressing the herpes simplex virus 1 glycoprotein D gene was utilized. HIV-RT, of both commercial or house-made viral lysate origin, was employed for the assay. To assess the reliability of RT-qPCR-IA, we performed a comparative, quantitative analysis of the dose-dependent effect exerted by known nucleotide and non-nucleotide reverse-transcriptase inhibitors, using the SYBR Green dye chemistry as detection system. The results obtained with RT-qPCR-IA were compared to that obtained using a one-step PicoGreen technology-based commercial kit. The outcome of our study indicates that the development of the novel RT-qPCR-IA will provide rapid and accurate evaluation of the inhibitory efficacy of compounds towards HIV-RT activity. This evaluation could be very useful for large-scale screening of potential new anti-HIV drugs.

Prospective Study of Psychosocial Distress Among Patients Undergoing Radiotherapy for Head and Neck Cancer

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

Chen, Allen M.; Jennelle, Richard; Grady, Victoria

Purpose: To determine the prevalence of psychosocial distress among patients undergoing radiotherapy (RT) for head and neck cancer and to examine the association between depression and anxiety and demographic and medical variables. Methods and Materials: A total of 40 patients (25 men and 15 women) with nonmetastatic head and neck cancer were enrolled in this prospective study and underwent RT administered with definitive (24 patients) or postoperative (16 patients) intent. Twenty patients (50%) received concurrent chemotherapy. All patients completed the Hospital Anxiety and Depression Scale and Beck Depression Inventory-II instrument before RT, on the last day of RT, and atmore » the first follow-up visit. The effect of patient-, tumor-, and treatment-related factors on psychosocial distress was analyzed. Results: The prevalence of mild to severe pre-RT depression was 58% and 45% using the Hospital Anxiety and Depression Scale-D and Beck Depression Inventory-II scale, respectively. The prevalence of severe pre-RT anxiety was 7%. The depression levels, as determined by the Hospital Anxiety and Depression Scale and Beck Depression Inventory-II instrument increased significantly during RT and remained elevated at the first follow-up visit (p < 0.001 for both). The variables that were significantly associated with post-RT depression included a greater pre-RT depression level, employment status (working at enrollment), younger age (<55 years), single marital status, and living alone (p < 0.05, for all). Conclusion: The results of our study have shown that an alarming number of patients undergoing RT for head and neck cancer have symptoms suggestive of psychosocial distress even before beginning treatment. This proportion increases significantly during RT. Studies investigating the role of antidepressants and/or psychiatric counseling might be warranted in the future.« less

Efficacy of Sunitinib and Radiotherapy in Genetically Engineered Mouse Model of Soft-Tissue Sarcoma

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

Yoon, Sam S.; Stangenberg, Lars; Lee, Yoon-Jin

Purpose: Sunitinib (SU) is a multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors. The present study examined SU and radiotherapy (RT) in a genetically engineered mouse model of soft tissue sarcoma (STS). Methods and Materials: Primary extremity STSs were generated in genetically engineered mice. The mice were randomized to treatment with SU, RT (10 Gy x 2), or both (SU+RT). Changes in the tumor vasculature before and after treatment were assessed in vivo using fluorescence-mediated tomography. The control and treated tumors were harvested and extensively analyzed. Results: The mean fluorescence in themore » tumors was not decreased by RT but decreased 38-44% in tumors treated with SU or SU+RT. The control tumors grew to a mean of 1378 mm{sup 3} after 12 days. SU alone or RT alone delayed tumor growth by 56% and 41%, respectively, but maximal growth inhibition (71%) was observed with the combination therapy. SU target effects were confirmed by loss of target receptor phosphorylation and alterations in SU-related gene expression. Cancer cell proliferation was decreased and apoptosis increased in the SU and RT groups, with a synergistic effect on apoptosis observed in the SU+RT group. RT had a minimal effect on the tumor microvessel density and endothelial cell-specific apoptosis, but SU alone or SU+RT decreased the microvessel density by >66% and induced significant endothelial cell apoptosis. Conclusion: SU inhibited STS growth by effects on both cancer cells and tumor vasculature. SU also augmented the efficacy of RT, suggesting that this combination strategy could improve local control of STS.« less

Rapid and sensitive detection of canine distemper virus by real-time reverse transcription recombinase polymerase amplification.

PubMed

Wang, Jianchang; Wang, Jinfeng; Li, Ruiwen; Liu, Libing; Yuan, Wanzhe

2017-08-15

Canine distemper, caused by Canine distemper virus (CDV), is a highly contagious and fatal systemic disease in free-living and captive carnivores worldwide. Recombinase polymerase amplification (RPA), as an isothermal gene amplification technique, has been explored for the molecular detection of diverse pathogens. A real-time reverse transcription RPA (RT-RPA) assay for the detection of canine distemper virus (CDV) using primers and exo probe targeting the CDV nucleocapsid protein gene was developed. A series of other viruses were tested by the RT-RPA.Thirty-two field samples were further tested by RT-RPA, and the resuts were compared with those obtained by the real-time RT-PCR. The RT-RPA assay was performed successfully at 40 °C, and the results were obtained within 3 min-12 min. The assay could detect CDV, but did not show cross-detection of canine parvovirus-2 (CPV-2), canine coronavirus (CCoV), canine parainfluenza virus (CPIV), pseudorabies virus (PRV) or Newcastle disease virus (NDV), demonstrating high specificity. The analytical sensitivity of RT-RPA was 31.8 copies in vitro transcribed CDV RNA, which is 10 times lower than the real-time RT-PCR. The assay performance was validated by testing 32 field samples and compared to real-time RT-PCR. The results indicated an excellent correlation between RT-RPA and a reference real-time RT-PCR method. Both assays provided the same results, and R 2 value of the positive results was 0.947. The results demonstrated that the RT-RPA assay offers an alternative tool for simple, rapid, and reliable detection of CDV both in the laboratory and point-of-care facility, especially in the resource-limited settings.

Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402

PubMed Central

Cairncross, Gregory; Wang, Meihua; Shaw, Edward; Jenkins, Robert; Brachman, David; Buckner, Jan; Fink, Karen; Souhami, Luis; Laperriere, Normand; Curran, Walter; Mehta, Minesh

2013-01-01

Purpose Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. Patients and Methods Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). Conclusion For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis. PMID:23071247

A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

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

Mourad, Waleed F., E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Packianathan, Satyaseelan

2012-03-01

Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patientsmore » were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.« less

Benefits of Resistance Training with Blood Flow Restriction in Knee Osteoarthritis.

PubMed

Ferraz, Rodrigo Branco; Gualano, Bruno; Rodrigues, Reynaldo; Kurimori, Ceci Obara; Fuller, Ricardo; Lima, Fernanda Rodrigues; DE Sá-Pinto, Ana Lúcia; Roschel, Hamilton

2018-05-01

Evaluate the effects of a low-intensity resistance training (LI-RT) program associated with partial blood flow restriction on selected clinical outcomes in patients with knee osteoarthritis (OA). Forty-eight women with knee OA were randomized into one of the three groups: LI-RT (30% one repetition maximum [1-RM]) associated (blood flow restriction training [BFRT]) or not (LI-RT) with partial blood flow restriction, and high-intensity resistance training (HI-RT, 80% 1-RM). Patients underwent a 12-wk supervised training program and were assessed for lower-limb 1-RM, quadriceps cross-sectional area, functionality (timed-stands test and timed-up-and-go test), and disease-specific inventory (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) before (PRE) and after (POST) the protocol. Similar within-group increases were observed in leg press (26% and 33%, all P < 0.0001), knee extension 1-RM (23% and 22%; all P < 0.0001) and cross-sectional area (7% and 8%; all P < 0.0001) in BFRT and HI-RT, respectively, and these were significantly greater (all P < 0.05) than those of LI-RT. The BFRT and HI-RT showed comparable improvements in timed-stands test (7% and 14%, respectively), with the latter showing greater increases than LI-RT. Timed-up-and-go test scores were not significantly changed within or between groups. WOMAC physical function was improved in BFRT and HI-RT (-49% and -42%, respectively; all P < 0.05), and WOMAC pain was improved in BFRT and LI-RT (-45% and -39%, respectively; all P < 0.05). Four patients (of 16) were excluded due to exercise-induced knee pain in HI-RT. Blood flow restriction training and HI-RT were similarly effective in increasing muscle strength, quadriceps muscle mass, and functionality in knee OA patients. Importantly, BFRT was also able to improve pain while inducing less joint stress, emerging as a feasible and effective therapeutic adjuvant in OA management.

On the Impact of Multi-GNSS Observations on Real-Time Precise Point Positioning Zenith Total Delay Estimates

NASA Astrophysics Data System (ADS)

Ding, Wenwu; Teferle, Norman; Kaźmierski, Kamil; Laurichesse, Denis; Yuan, Yunbin

2017-04-01

Observations from multiple Global Navigation Satellite System (GNSS) can improve the performance of real-time (RT) GNSS meteorology, in particular of the Zenith Total Delay (ZTD) estimates. RT ZTD estimates in combination with derived precipitable water vapour estimates can be used for weather now-casting and the tracking of severe weather events. While a number of published literature has already highlighted this positive development, in this study we describe an operational RT system for extracting ZTD using a modified version of the PPP-wizard (with PPP denoting Precise Point Positioning). Multi-GNSS, including GPS, GLONASS and Galileo, observation streams are processed using a RT PPP strategy based on RT satellite orbit and clock products from the Centre National d'Etudes Spatiales (CNES). A continuous experiment for 30 days was conducted, in which the RT observation streams of 20 globally distributed stations were processed. The initialization time and accuracy of the RT troposphere products using single and/or multi-system observations were evaluated. The effect of RT PPP ambiguity resolution was also evaluated. The results revealed that the RT troposphere products based on single system observations can fulfill the requirements of the meteorological application in now-casting systems. We noted that the GPS-only solution is better than the GLONASS-only solution in both initialization and accuracy. While the ZTD performance can be improved by applying RT PPP ambiguity resolution, the inclusion of observations from multiple GNSS has a more profound effect. Specifically, we saw that the ambiguity resolution is more effective in improving the accuracy, whereas the initialization process can be better accelerated by multi-GNSS observations. Combining all systems, RT troposphere products with an average accuracy of about 8 mm in ZTD were achieved after an initialization process of approximately 9 minutes, which supports the application of multi-GNSS observations and ambiguity resolution for RT meteorological applications.

Historical trends in the use of radiation therapy for pediatric cancers: 1973-2008.

PubMed

Jairam, Vikram; Roberts, Kenneth B; Yu, James B

2013-03-01

This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients who received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy

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

Prabhu, Roshan S., E-mail: rprabhu@emory.edu; Kandula, Shravan; Liebman, Lang

2013-03-01

Purpose: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). Methods and Materials: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without anmore » increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). Results: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. Conclusions: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.« less

Quantitation of TGF-beta1 mRNA in porcine mesangial cells by comparative kinetic RT/PCR: comparison with ribonuclease protection assay and in situ hybridization.

PubMed

Ceol, M; Forino, M; Gambaro, G; Sauer, U; Schleicher, E D; D'Angelo, A; Anglani, F

2001-01-01

Gene expression can be examined with different techniques including ribonuclease protection assay (RPA), in situ hybridisation (ISH), and quantitative reverse transcription-polymerase chain reaction (RT/PCR). These methods differ considerably in their sensitivity and precision in detecting and quantifying low abundance mRNA. Although there is evidence that RT/PCR can be performed in a quantitative manner, the quantitative capacity of this method is generally underestimated. To demonstrate that the comparative kinetic RT/PCR strategy-which uses a housekeeping gene as internal standard-is a quantitative method to detect significant differences in mRNA levels between different samples, the inhibitory effect of heparin on phorbol 12-myristate 13-acetate (PMA)-induced-TGF-beta1 mRNA expression was evaluated by RT/PCR and RPA, the standard method of mRNA quantification, and the results were compared. The reproducibility of RT/PCR amplification was calculated by comparing the quantity of G3PDH and TGF-beta1 PCR products, generated during the exponential phases, estimated from two different RT/PCR (G3PDH, r = 0.968, P = 0.0000; TGF-beta1, r = 0.966, P = 0.0000). The quantitative capacity of comparative kinetic RT/PCR was demonstrated by comparing the results obtained from RPA and RT/PCR using linear regression analysis. Starting from the same RNA extraction, but using only 1% of the RNA for the RT/PCR compared to RPA, significant correlation was observed (r = 0.984, P = 0.0004). Moreover the morphometric analysis of ISH signal was applied for the semi-quantitative evaluation of the expression and localisation of TGF-beta1 mRNA in the entire cell population. Our results demonstrate the close similarity of the RT/PCR and RPA methods in giving quantitative information on mRNA expression and indicate the possibility to adopt the comparative kinetic RT/PCR as reliable quantitative method of mRNA analysis. Copyright 2001 Wiley-Liss, Inc.

Long-term quality of life after treatment of laryngeal cancer. The Veterans Affairs Laryngeal Cancer Study Group.

PubMed

Terrell, J E; Fisher, S G; Wolf, G T

1998-09-01

To assess long-term quality of life in surviving patients with advanced laryngeal cancer. A follow-up long-term quality-of-life survey of patients randomized to the Veterans Affairs Laryngeal Cancer Study No. 268 on induction chemotherapy and radiation (CT + RT) vs surgery and RT. Forty-six (71%) of the 65 surviving patients with prior stage III or IV laryngeal cancer who could be contacted completed the survey: 25 from the surgery and RT group and 21 from the CT + RT group. Baseline demographic and clinical characteristics among survey respondents were similar, except that those in the CT + RT group were significantly older (mean, 61.2 years) than those in the surgery and RT group (mean, 55.7 years; P<.05). Patients completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Studies Short-Form 36 (SF-36) general health survey, the Beck Depression Inventory as well as smoking and alcohol consumption surveys. Patients randomized to the CT + RT group had significantly better (P<.05) quality-of-life scores on the SF-36 mental health domain (76.0) than the surgery and RT group (63.0), and also had better HNQOL pain scores (81.3 vs 64.3). Compared with patients who underwent laryngectomy, patients with intact larynges (CT + RT with larynx) had significantly less bodily pain (88.5 vs 56.5), better scores on the SF-36 mental health (79.8 vs 64.7), and better HNQOL emotion (89.7 vs 79.4) scores. More patients in the surgery and RT group (28%) were depressed than in the CT + RT group (15%). Better quality-of-life scores in the CT + RT groups appear to be related to more freedom from pain, better emotional well-being, and lower levels of depression than to preservation of speech function.

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

PubMed

Assouline, Avi; Levy, Antonin; Abdelnour-Mallet, Maya; Gonzalez-Bermejo, Jesus; Lenglet, Timothée; Le Forestier, Nadine; Salachas, François; Bruneteau, Gaelle; Meininger, Vincent; Delanian, Sylvie; Pradat, Pierre-François

2014-03-01

This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Abilities of the mCP Agar Method and CRENAME Alpha Toxin-Specific Real-Time PCR Assay To Detect Clostridium perfringens Spores in Drinking Water

PubMed Central

Maheux, Andrée F.; Bérubé, Ève; Boudreau, Dominique K.; Villéger, Romain; Cantin, Philippe; Boissinot, Maurice; Bissonnette, Luc

2013-01-01

We first determined the analytical specificity and ubiquity (i.e., the ability to detect all or most strains) of a Clostridium perfringens-specific real-time PCR (rtPCR) assay based on the cpa gene (cpa rtPCR) by using a bacterial strain panel composed of C. perfringens and non-C. perfringens Clostridium strains. All non-C. perfringens Clostridium strains tested negative, whereas all C. perfringens strains tested positive with the cpa rtPCR, for an analytical specificity and ubiquity of 100%. The cpa rtPCR assay was then used to confirm the identity of 116 putative C. perfringens isolates recovered after filtration of water samples and culture on mCP agar. Colonies presenting discordant results between the phenotype on mCP agar and cpa rtPCR were identified by sequencing the 16S rRNA and cpa genes. Four mCP−/rtPCR+ colonies were identified as C. perfringens, whereas 3 mCP+/rtPCR− colonies were identified as non-C. perfringens. The cpa rtPCR was negative with all 51 non-C. perfringens strains and positive with 64 of 65 C. perfringens strains. Finally, we compared mCP agar and a CRENAME (concentration and recovery of microbial particles, extraction of nucleic acids, and molecular enrichment) procedure plus cpa rtPCR (CRENAME + cpa rtPCR) for their abilities to detect C. perfringens spores in drinking water. CRENAME + cpa rtPCR detected as few as one C. perfringens CFU per 100 ml of drinking water sample in less than 5 h, whereas mCP agar took at least 25 h to deliver results. CRENAME + cpa rtPCR also allows the simultaneous and sensitive detection of Escherichia coli and C. perfringens from the same potable water sample. In itself, it could be used to assess the public health risk posed by drinking water potentially contaminated with pathogens more resistant to disinfection. PMID:24077714

Historical Trends in the Use of Radiation Therapy for Pediatric Cancers: 1973-2008

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

Jairam, Vikram; Roberts, Kenneth B.; Yale Cancer Center, New Haven, Connecticut

Purpose: This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients whomore » received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. Results: RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. Conclusions: The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT.« less

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

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

Assouline, Avi, E-mail: avi.assouline@ccpsc.fr; Department of Radiation Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris; Levy, Antonin

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scalemore » (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10{sup −6}). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.« less

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

PubMed Central

Lim, Hyeon Woo; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong

2016-01-01

Purpose To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys. PMID:27730803

Enhancement of Glioma Radiotherapy and Chemotherapy Response With Targeted Antibody Therapy Against Death Receptor 5

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

Fiveash, John B.; Gillespie, G. Yancey; Oliver, Patsy G.

2008-06-01

Purpose: TRA-8 is an agonistic mouse monoclonal antibody that binds to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5, which induces apoptosis in cancer cells through a caspase-8-dependent mechanism. We investigated the ability of TRA-8 to augment the radiotherapy (RT) and chemotherapy response of human glioma cells in vitro and in vivo. Methods and Materials: The in vitro cytotoxicity of TRA-8 and temozolomide (Tmz) or RT was examined using adenosine triphosphate-dependent viability and clonogenic survival assays with five glioma cell lines. Death receptor 5 expression was determined by flow cytometry. In vivo studies included subcutaneous and intracranial xenograft modelsmore » testing various combination treatments, including RT, Tmz, and TRA-8. Results: TRA-8, combined with Tmz or RT, produced enhanced cytotoxicity against five glioma cell lines compared with the use of the individual agents alone. Death receptor 5 upregulation occurred in response to RT. Complete tumor regression in the subcutaneous experiments was the most common in animals that received combination therapy with TRA-8/Tmz/RT. TRA-8 enhanced tumor growth delay in combination with RT or Tmz. TRA-8 alone had limited activity against intracranial tumors. In contrast, the median survival of mice treated with TRA-8/Tmz/RT was significantly greater than the control or TRA-8-alone-treated mice. The median survival of the mice treated with TRA-8/Tmz/RT or chemoradiotherapy only was significantly greater than the control or TRA-8-treated mice. A trend toward improved survival was observed between TRA-8/Tmz/RT-treated and Tmz/RT-treated mice. Conclusions: These preliminary findings support the hypothesis that TRA-8 will augment the RT and chemotherapy response in gliomas. A humanized version of TRA-8 is being evaluated in a Phase II clinical trial.« less

Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

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

Cao Yue, E-mail: yuecao@umich.edu; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Wang Hesheng

2013-01-01

Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation betweenmore » mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which could aid in individualizing therapy, particularly for patients at risk for liver injury after RT.« less

Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

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

Li Guanghui; Zhang Yaping; Tang Jinliang

2010-08-01

Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-{alpha}, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT.more » The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-{alpha}, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.« less

Sequencing of Local Therapy Affects the Pattern of Treatment Failure and Survival in Children With Atypical Teratoid Rhabdoid Tumors of the Central Nervous System

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

Pai Panandiker, Atmaram S., E-mail: atmaram.pai-panandiker@stjude.org; Merchant, Thomas E.; Beltran, Chris

Purpose: To assess the pattern of treatment failure associated with current therapeutic paradigms for childhood atypical teratoid rhabdoid tumors (AT/RT). Methods and Materials: Pediatric patients with AT/RT of the central nervous system treated at our institution between 1987 and 2007 were retrospectively evaluated. Overall survival (OS), progression-free survival, and cumulative incidence of local failure were correlated with age, sex, tumor location, extent of disease, and extent of surgical resection. Radiotherapy (RT) sequencing, chemotherapy, dose, timing, and volume administered after resection were also evaluated. Results: Thirty-one patients at a median age of 2.3 years at diagnosis (range, 0.45-16.87 years) were enrolledmore » into protocols that included risk- and age-stratified RT. Craniospinal irradiation with focal tumor bed boost (median dose, 54 Gy) was administered to 18 patients. Gross total resection was achieved in 16. Ten patients presented with metastases at diagnosis. RT was delayed more than 3 months in 20 patients and between 1 and 3 months in 4; 7 patients received immediate postoperative irradiation preceding high-dose alkylator-based chemotherapy. At a median follow-up of 48 months, the cumulative incidence of local treatment failure was 37.5% {+-} 9%; progression-free survival was 33.2% {+-} 10%; and OS was 53.5% {+-} 10%. Children receiving delayed RT ({>=}1 month postoperatively) were more likely to experience local failure (hazard ratio [HR] 1.23, p = 0.007); the development of distant metastases before RT increased the risk of progression (HR 3.49, p = 0.006); and any evidence of disease progressionbefore RT decreased OS (HR 20.78, p = 0.004). Disease progression occurred in 52% (11/21) of children with initially localized tumors who underwent gross total resection, and the progression rate increased proportionally with increasing delay from surgery to RT. Conclusions: Delayed RT is associated with a higher rate of local and metastatic disease progression in children with AT/RT. Current treatment regimens for pediatric patients with AT/RT are distinctly age stratified; novel protocols investigating RT volumes and sequencing are needed.« less

Can Drugs Enhance Hypofractionated Radiotherapy? A Novel Method of Modeling Radiosensitization Using In Vitro Data

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

Ohri, Nitin; Dicker, Adam P.; Lawrence, Yaacov Richard, E-mail: yaacovla@gmail.com

2012-05-01

Purpose: Hypofractionated radiotherapy (hRT) is being explored for a number of malignancies. The potential benefit of giving concurrent chemotherapy with hRT is not known. We sought to predict the effects of combined modality treatments by using mathematical models derived from laboratory data. Methods and Materials: Data from 26 published clonogenic survival assays for cancer cell lines with and without the use of radiosensitizing chemotherapy were collected. The first three data points of the RT arm of each assay were used to derive parameters for the linear quadratic (LQ) model, the multitarget (MT) model, and the generalized linear quadratic (gLQ) model.more » For each assay and model, the difference between the predicted and observed surviving fractions at the highest tested RT dose was calculated. The gLQ model was fitted to all the data from each RT cell survival assay, and the biologically equivalent doses in 2-Gy fractions (EQD2s) of clinically relevant hRT regimens were calculated. The increase in cell kill conferred by the addition of chemotherapy was used to estimate the EQD2 of hRT along with a radiosensitizing agent. For comparison, this was repeated using conventionally fractionated RT regimens. Results: At a mean RT dose of 8.0 Gy, the average errors for the LQ, MT, and gLQ models were 1.63, 0.83, and 0.56 log units, respectively, favoring the gLQ model (p < 0.05). Radiosensitizing chemotherapy increased the EQD2 of hRT schedules by an average of 28% to 82%, depending on disease site. This increase was similar to the gains predicted for the addition of chemotherapy to conventionally fractionated RT. Conclusions: Based on published in vitro assays, the gLQ equation is superior to the LQ and MT models in predicting cell kill at high doses of RT. Modeling exercises demonstrate that significant increases in biologically equivalent dose may be achieved with the addition of radiosensitizing agents to hRT. Clinical study of this approach is warranted.« less

Clinical outcomes of radiotherapy as initial local therapy for Graves' ophthalmopathy and predictors of the need for post-radiotherapy decompressive surgery.

PubMed

Prabhu, Roshan S; Liebman, Lang; Wojno, Ted; Hayek, Brent; Hall, William A; Crocker, Ian

2012-06-19

The optimal initial local treatment for patients with Graves' ophthalmopathy (GO) is not fully characterized. The purpose of this retrospective study is to describe the clinical outcomes of RT as initial local therapy for GO and define predictors of the need for post-RT salvage bony decompressive surgery. 91 patients with active GO and without prior surgery were treated with RT as initial local therapy between 01/1999 and 12/2010, with a median follow-up period of 18.3 months (range 3.7 - 142 months). RT dose was 24 Gy in 12 fractions. 44 patients (48.4%) had prior use of steroids, with 31 (34.1%) being on steroids at the initiation of RT. The most common presenting symptoms were diplopia (79%), proptosis (71%) and soft tissue signs (62%). 84 patients (92.3%) experienced stabilization or improvement of GO symptoms. 58 patients (64%) experienced improvement in their symptoms. 19 patients (20.9%) underwent salvage post-RT bony decompressive surgery. Smoking status and total symptom score at 4 months were independent predictors of post-RT bony decompression with odds ratios of 3.23 (95% CI 1.03 - 10.2) and 1.59 (95% CI 1.06 - 2.4), respectively. Persistent objective vision loss at 4 months post-RT was the most important symptom type in predicting salvage decompression. Chronic dry eye occurred in 9 patients (9.9%) and cataracts developed in 4 patients (4.4%). RT is effective and well tolerated as initial local therapy for active GO, with only 21% of patients requiring decompressive surgery post RT. Most patients experience stabilization or improvement of GO symptoms, but moderate to significant response occurs in the minority of patients. Smoking status and total symptom severity at 4 months, primarily persistent objective vision loss, are the primary determinants of the need for post-RT salvage bony decompression. Patients who smoke or present with predominantly vision loss symptoms should be advised as to their lower likelihood of symptomatic response to RT and their increased likelihood of requiring post-RT decompressive surgery.

Declining Use of Radiotherapy in Stage I and II Hodgkin's Disease and Its Effect on Survival and Secondary Malignancies

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

Koshy, Matthew, E-mail: mkoshy@radonc.uchicago.edu; Department of Radiation Oncology, University of Illinois at Chicago, Chicago, IL; Rich, Shayna E.

2012-02-01

Purpose: Concerns regarding long-term toxicities have led some to withhold radiotherapy (RT) for the treatment of Stage I and II Hodgkin's disease (HD). The present study was undertaken to assess the use of RT for HD and its effect on overall survival and the development of secondary malignancies. Methods and Materials: The present study included data from the Surveillance, Epidemiology, and End Results database from patients aged {>=}20 years who had been diagnosed with Stage I or II HD between 1988 and 2006. Overall survival was estimated using the Kaplan-Meier method, and the Cox multivariate regression model was used tomore » analyze trends. Results: A total of 12,247 patients were selected, and 51.5% had received RT. The median follow-up for the present cohort was 4.9 years, with 21% of the cohort having >10 years of follow-up. Between 1988 and 1991, 62.9% had undergone RT, but between 2004 and 2006, only 43.7% had undergone RT (p < .001). The 5-year overall survival rate was 76% for patients who had not received RT and 87% for those who had (p < .001). The hazard ratio adjusted for other variables in the regression model showed that patients who had not undergone RT (hazard ratio, 1.72; 95% confidence interval, 1.72-2.02) was associated with significantly worse survival compared with patients who had received RT. The actuarial rate of developing a second malignancy was 14.6% vs. 15.0% at 15 years for those who had and had not undergone RT, respectively (p = .089). Conclusions: The present study is one of the largest studies to examine the role of RT for Stage I and II HD. Our results revealed a survival benefit with the addition of RT with no increase in the development of secondary malignancies compared with patients who had not received RT. Furthermore, the present nationwide study revealed a >20% absolute decrease in the use of RT from 1988 to 2006.« less

Technological Advancements and Error Rates in Radiation Therapy Delivery

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

Margalit, Danielle N., E-mail: dmargalit@partners.org; Harvard Cancer Consortium and Brigham and Women's Hospital/Dana Farber Cancer Institute, Boston, MA; Chen, Yu-Hui

2011-11-15

Purpose: Technological advances in radiation therapy (RT) delivery have the potential to reduce errors via increased automation and built-in quality assurance (QA) safeguards, yet may also introduce new types of errors. Intensity-modulated RT (IMRT) is an increasingly used technology that is more technically complex than three-dimensional (3D)-conformal RT and conventional RT. We determined the rate of reported errors in RT delivery among IMRT and 3D/conventional RT treatments and characterized the errors associated with the respective techniques to improve existing QA processes. Methods and Materials: All errors in external beam RT delivery were prospectively recorded via a nonpunitive error-reporting system atmore » Brigham and Women's Hospital/Dana Farber Cancer Institute. Errors are defined as any unplanned deviation from the intended RT treatment and are reviewed during monthly departmental quality improvement meetings. We analyzed all reported errors since the routine use of IMRT in our department, from January 2004 to July 2009. Fisher's exact test was used to determine the association between treatment technique (IMRT vs. 3D/conventional) and specific error types. Effect estimates were computed using logistic regression. Results: There were 155 errors in RT delivery among 241,546 fractions (0.06%), and none were clinically significant. IMRT was commonly associated with errors in machine parameters (nine of 19 errors) and data entry and interpretation (six of 19 errors). IMRT was associated with a lower rate of reported errors compared with 3D/conventional RT (0.03% vs. 0.07%, p = 0.001) and specifically fewer accessory errors (odds ratio, 0.11; 95% confidence interval, 0.01-0.78) and setup errors (odds ratio, 0.24; 95% confidence interval, 0.08-0.79). Conclusions: The rate of errors in RT delivery is low. The types of errors differ significantly between IMRT and 3D/conventional RT, suggesting that QA processes must be uniquely adapted for each technique. There was a lower error rate with IMRT compared with 3D/conventional RT, highlighting the need for sustained vigilance against errors common to more traditional treatment techniques.« less

Small Molecular Inhibitor of Transforming Growth Factor-{beta} Protects Against Development of Radiation-Induced Lung Injury

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

Anscher, Mitchell S.; Thrasher, Bradley; Zgonjanin, Larisa

2008-07-01

Purpose: To determine whether an anti-transforming growth factor-{beta} (TGF-{beta}) type 1 receptor inhibitor (SM16) can prevent radiation-induced lung injury. Methods and Materials: One fraction of 28 Gy or sham radiotherapy (RT) was administered to the right hemithorax of Sprague-Dawley rats. SM16 was administered in the rat chow (0.07 g/kg or 0.15 g/kg) beginning 7 days before RT. The rats were divided into eight groups: group 1, control chow; group 2, SM16, 0.07 g/kg; group 3, SM16, 0.15 g/kg; group 4, RT plus control chow; group 5, RT plus SM16, 0.07 g/kg; group 6, RT plus SM16, 0.15 g/kg; group 7,more » RT plus 3 weeks of SM16 0.07 g/kg followed by control chow; and group 8, RT plus 3 weeks of SM16 0.15 g/kg followed by control chow. The breathing frequencies, presence of inflammation/fibrosis, activation of macrophages, and expression/activation of TGF-{beta} were assessed. Results: The breathing frequencies in the RT plus SM16 0.15 g/kg were significantly lower than the RT plus control chow from Weeks 10-22 (p <0.05). The breathing frequencies in the RT plus SM16 0.07 g/kg group were significantly lower only at Weeks 10, 14, and 20. At 26 weeks after RT, the RT plus SM16 0.15 g/kg group experienced a significant decrease in lung fibrosis (p = 0.016), inflammatory response (p = 0.006), and TGF-{beta}1 activity (p = 0.011). No significant reduction was found in these measures of lung injury in the group that received SM16 0.7g/kg nor for the short-course (3 weeks) SM16 at either dose level. Conclusion: SM16 at a dose of 0.15 g/kg reduced functional lung damage, morphologic changes, inflammatory response, and activation of TGF-{beta} at 26 weeks after RT. The data suggest a dose response and also suggest the superiority of long-term vs. short-term dosing.« less

Highly favorable physiological responses to concurrent resistance and high-intensity interval training during chemotherapy: the OptiTrain breast cancer trial.

PubMed

Mijwel, Sara; Backman, Malin; Bolam, Kate A; Olofsson, Emil; Norrbom, Jessica; Bergh, Jonas; Sundberg, Carl Johan; Wengström, Yvonne; Rundqvist, Helene

2018-05-01

Advanced therapeutic strategies are often accompanied by significant adverse effects, which warrant equally progressive countermeasures. Physical exercise has proven an effective intervention to improve physical function and reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity interval training (HIIT) in this population are not well established although HIIT has proven effective in other clinical populations. The aim of the OptiTrain trial was to examine the effects of concurrent resistance and high-intensity interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high-intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and physiological outcomes in patients with breast cancer during chemotherapy. Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT-HIIT, or UC. cardiorespiratory fitness, muscle strength, body mass, hemoglobin levels, and pressure-pain threshold. Pre- to post-intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs. UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT-HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = - 0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT (trapezius: ES = 0.30). Sixteen weeks of RT-HIIT significantly improved muscle strength and reduced pain sensitivity. Both exercise programs were well tolerated and were equally efficient in preventing increases in body mass and in preventing declines in cardiorespiratory fitness. These results highlight the importance of implementing a combination of resistance and high-intensity interval training during chemotherapy for women with breast cancer.

SlicerRT: radiation therapy research toolkit for 3D Slicer.

PubMed

Pinter, Csaba; Lasso, Andras; Wang, An; Jaffray, David; Fichtinger, Gabor

2012-10-01

Interest in adaptive radiation therapy research is constantly growing, but software tools available for researchers are mostly either expensive, closed proprietary applications, or free open-source packages with limited scope, extensibility, reliability, or user support. To address these limitations, we propose SlicerRT, a customizable, free, and open-source radiation therapy research toolkit. SlicerRT aspires to be an open-source toolkit for RT research, providing fast computations, convenient workflows for researchers, and a general image-guided therapy infrastructure to assist clinical translation of experimental therapeutic approaches. It is a medium into which RT researchers can integrate their methods and algorithms, and conduct comparative testing. SlicerRT was implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. SlicerRT provides functionality specifically designed for radiation therapy research, in addition to the powerful tools that 3D Slicer offers for visualization, registration, segmentation, and data management. The feature set of SlicerRT was defined through consensus discussions with a large pool of RT researchers, including both radiation oncologists and medical physicists. The development processes used were similar to those of 3D Slicer to ensure software quality. Standardized mechanisms of 3D Slicer were applied for documentation, distribution, and user support. The testing and validation environment was configured to automatically launch a regression test upon each software change and to perform comparison with ground truth results provided by other RT applications. Modules have been created for importing and loading DICOM-RT data, computing and displaying dose volume histograms, creating accumulated dose volumes, comparing dose volumes, and visualizing isodose lines and surfaces. The effectiveness of using 3D Slicer with the proposed SlicerRT extension for radiation therapy research was demonstrated on multiple use cases. A new open-source software toolkit has been developed for radiation therapy research. SlicerRT can import treatment plans from various sources into 3D Slicer for visualization, analysis, comparison, and processing. The provided algorithms are extensively tested and they are accessible through a convenient graphical user interface as well as a flexible application programming interface.

Variations in automatically recorded rumination time as explained by variations in intake of dietary fractions and milk production, and between-cow variation.

PubMed

Byskov, M V; Nadeau, E; Johansson, B E O; Nørgaard, P

2015-06-01

Individual recording of rumination time (RT) is now possible in commercial dairy herds, through development of a microphone-based sensor, which is able to record RT by the sound of rumination activity. The objectives of this study were to examine the relationship between daily RT and intakes of different dietary fractions, the relationship between RT in minutes per kilogram of dry matter intake (DMI) and milk production, and to examine the variation in RT within and between mid-lactating dairy cows. Data from 3 production trials were used in which a total of 27 different diets were fed. The data contained 761, 290, and 203 daily recordings of RT, milk yield, milk components, DMI, and intake of dietary fractions recorded on 29, 26, and 24 Holstein and Swedish Red cows from trials 1, 2, and 3, respectively. The dietary fractions included forage neutral detergent fiber (NDF), concentrate NDF, crude protein, sugar, starch, and the remaining fraction represented by organic matter--(forage NDF+concentrate NDF+crude protein+sugar+starch). The relationship between the dietary fractions and RT was analyzed in 2 steps. In step 1, the dietary fractions, which were significantly related to RT, were selected and simultaneously checked for multicollinearity between the dietary components; in step 2, a multivariate model, including the effect of repeated measurements, the main effect of the selected dietary fractions from step 1, random effects of cow(trial) and trial, and information on breed, days in milk, and parity was used to analyze the relationship between RT and the selected dietary fractions. Relationships between RT in minutes per kilogram of DMI and milk yield and milk components were analyzed, using the same multivariate model as in step 2. Approximately 32% of the variation in daily RT could be explained by variations in intakes of the dietary fractions, whereas 48% of the total variation in RT was accounted for by individual variations between cows. Intakes of forage NDF and starch were positively related to daily RT, whereas intakes of sugar and the remaining fraction were negatively related to daily RT. Rumination time in minutes per kilogram of DMI was negatively related to milk yield and protein percentage, but positively related to milk fat percentage. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

PubMed

Rushdan, M N; Tay, E H; Khoo-Tan, H S; Lee, K M; Low, J H; Ho, T H; Yam, K L

2004-07-01

The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

Prospective evaluation of the prevalence and severity of fatigue in patients with prostate cancer undergoing radical external beam radiotherapy and neoadjuvant hormone therapy.

PubMed

Truong, Pauline T; Berthelet, Eric; Lee, Junella C; Petersen, Ross; Lim, Jan T W; Gaul, Catherine A; Pai, Howard; Blood, Paul; Ludgate, Charles M

2006-06-01

To prospectively evaluate the prevalence and severity of fatigue and its impact on quality of life (QOL) during and after radical external beam radiotherapy (RT) for prostate cancer. Twenty-eight men with prostate cancer undergoing RT over 6-8 consecutive weeks were prospectively accrued. The Brief Fatigue Inventory (BFI), a validated fatigue assessment tool, was administered at five time points: baseline (week 1), middle of RT (week 3-4), end of RT (last week of RT), and follow-up (median 6.5 weeks after RT). The BFI contained nine questions, each using 0-10 ratings to quantify fatigue severity and interference with six QOL domains. The prevalence of moderate-severe fatigue was plotted as a function of time. Mean sum and subscale scores at each time point were compared to baseline scores using Wilcoxon tests. Linear regression analyses were performed to assess associations between fatigue scores and age, tumor and treatment characteristics. The median age was 69 years (range 57-84), Gleason score 7 (range 6-10), and presenting PSA 9.0 ng/mL (range 2.5 ng/mL-103.0 ng/mL). Patients were treated once daily to a median dose of 74 Gy (range 60 Gy-78 Gy) over a median of 37 fractions (range 30-39). Hormone therapy was used in all patients (median duration 12.2 months). The prevalence of moderate-severe present fatigue increased from 7% at baseline to 8% at mid-RT and 32% at RT completion. Compared to baseline (mean score 11.5), fatigue increased significantly mid-RT (mean score 14.6, p = 0.03) and peaked at the end of RT (mean score 23.5, p = 0.001). Fatigue significantly interfered with walking ability, normal work, daily chores, and enjoyment of life only at the end of RT. After RT completion, fatigue improved but remained higher compared to baseline at 6.5 weeks of follow-up (mean score 15.0, p = 0.02). On linear regression analysis, age, Gleason score, PSA, T-stage, hormone therapy duration, RT dose and fractions were not significantly associated with mean fatigue scores. Patients undergoing 6-8 weeks of RT experienced significant fatigue adversely affecting QOL persisting after therapy completion. Since walking ability was not affected until the end of RT, a walking exercise intervention to combat fatigue is likely feasible and is being investigated.

Association of Survival With Shorter Time to Radiation Therapy After Surgery for US Patients With Head and Neck Cancer.

PubMed

Harris, Jeremy P; Chen, Michelle M; Orosco, Ryan K; Sirjani, Davud; Divi, Vasu; Hara, Wendy

2018-04-01

Shortening the time from surgery to the start of radiation (TS-RT) is a consideration for physicians and patients. Although the National Comprehensive Cancer Network recommends radiation to start within 6 weeks, a survival benefit with this metric remains controversial. To determine the association of delayed TS-RT with overall survival (OS) using a large cancer registry. In this observational cohort study, 25 216 patients with nonmetastatic stages III to IV head and neck cancer were identified from the National Cancer Database (NCDB). Patients received definitive surgery followed by adjuvant radiation therapy, with an interval duration defined as TS-RT. Overall survival as a function of TS-RT and the effect of clinicopathologic risk factors and accelerated fractionation. We identified 25 216 patients with nonmetastatic squamous cell carcinoma of the head and neck. There were 18 968 (75%) men and 6248 (25%) women and the mean (SD) age of the cohort was 59 (10.9) years. Of the 25 216 patients, 9765 (39%) had a 42-days or less TS-RT and 4735 (19%) had a 43- to 49-day TS-RT. Median OS was 10.5 years (95% CI, 10.0-11.1 years) for patients with a 42-days or less TS-RT, 8.2 years (95% CI, 7.4-8.6 years; absolute difference, -2.4 years, 95% CI, -1.5 to -3.2 years) for patients with a 43- to 49-day TS-RT, and 6.5 years (95% CI, 6.1-6.8 years; absolute difference, -4.1 years, 95% CI, -3.4 to -4.7 years) for those with a 50-days or more TS-RT. Multivariable analysis found that compared with a 42-days or less TS-RT, there was not a significant increase in mortality with a 43- to 49-day TS-RT (HR, 0.98; 95% CI, 0.93-1.04), although there was for a TS-RT of 50 days or more (HR, 1.07; 95% CI, 1.02-1.12). A significant interaction was identified between TS-RT and disease site. Subgroup effect modeling found that a delayed TS-RT of 7 days resulted in significantly worse OS for patients with tonsil tumors (HR, 1.22; 95% CI, 1.05-1.43) though not other tumor subtypes. Accelerated fractionation of 5.2 fractions or more per week was associated with improved survival (HR, 0.93; 95% CI, 0.87-0.99) compared with standard fractionation. Delayed TS-RT of 50 days or more was associated with worse overall survival. The multidisciplinary care team should focus on shortening TS-RT to improve survival. Unavoidable delays may be an indication for accelerated fractionation or other dose intensification strategies.

Clinical utility of RT-PCR in assessing HER 2 gene expression versus traditional IHC and FISH in breast cancer patients.

PubMed

Suryavanshi, Moushumi; Mehta, Anurag; Jaipuria, Jiten; Kumar, Dushyant; Vishwakarma, Gayatri; Panigrahi, Manoj Kumar; Verma, Haristuti; Saifi, Mumtaz; Sharma, Sanjeev; Tandon, Simran; Doval, D C; Das, Bhudev C

2018-02-09

IHC and FISH are used for categorizing HER 2 status in breast cancer at the protein and DNA level, respectively. HER 2 expression at the RNA level is quantitative, cheaper, easier to standardize and free from interobserver variation. 115 consecutive patients were tested by IHC, FISH and RT-PCR (test cohort). Assuming FISH result to be the response variable, ROC curves for RT-PCR ratio were analyzed to label HER 2 negative, equivocal and positive cases as RT-PCR score 1, 2 and 3, respectively. Inter-relationships between RT-PCR, IHC and FISH were defined. 'Clinical benefit' of a test was defined as proportion of patients labeled unequivocally as HER 2 positive or negative. Population for 1 year was simulated constraint to previous reports of HER 2 positivity and IHC category distribution by a meta-analysis of previous studies that evaluated concordance between IHC and FISH to determine HER 2 status (simulation cohort). Four diagnostic pathways in the simulation cohort were defined-(1) initial IHC, followed by FISH (conventional pathway); (2) initial RT-PCR, followed by FISH; (3) initial IHC, followed by RT-PCR and then by FISH; (4) initial RT-PCR, followed by IHC and then by FISH. The clinical benefit of IHC and RT-PCR in the four pathways was analyzed and sensitivity analysis for incremental cost-effectiveness ratio and cost-benefit comapring RT-PCR against IHC, both as first-line tests and among those with IHC score 2 as a reflex second-line test was performed by the Monte Carlo technique. 115 patients comprised the study population. While none with IHC score of 0 or 1 was FISH positive for HER 2, all cases with IHC score of 3 were FISH positive. 43 cases were assigned IHC score of 2. Thus, 72 patients benefited from the initial IHC testing [clinical benefit 62.6%], with the overall concordance between IHC and FISH being 100% for those with IHC score of 0, 1 and 3 (conclusive IHC categories). For RT-PCR with 100% concordance, 15.7% (115-97 = 18) patients would have benefited from RT-PCR testing if it was used as a first-line test. If RT-PCR would have been used as a second-line test among those with IHC score 2 (n = 43), then only 6 patients would have been assigned a conclusive RT-PCR category (category 1 or 3) translating to a clinical benefit of 14% (6/43) as a second-line test. As a second-line test it had 51% probability to prove more cost-effective than the conventional pathway, provided the cost of RT-PCR was 0.4 times the cost of IHC. Also in a three-step pathway, RT-PCR upfront would have 56% probability of higher cost-benefit provided the cost of RT-PCR was 0.1 times the cost of IHC. RT-PCR results were found to be suboptimal to IHC in terms of discriminative ability and clinical benefit; thus, it is unlikely to replace IHC as a first-line test in the near future.

Iowa Department of Education Guidance Document. Response to Intervention

ERIC Educational Resources Information Center

Iowa Department of Education, 2011

2011-01-01

The purpose of this document is to provide an overview of Response to Intervention (RtI), including essential components. Iowa's RtI document is designed to provide the state with common language and understanding of RtI, why RtI is important for improving student results, general timelines for implementation and answers to Frequently Asked…

Administrator Perceptions Regarding Pennsylvania's MTSS/RtII Framework and Gifted Elementary Students

ERIC Educational Resources Information Center

Murin, Tricia M.

2016-01-01

Providing equitable education for all students is the responsibility of administrators, teachers, and parents. Even though the MTSS/RtII Framework has evolved from the RtI and RtII models, the basis is the same: intervening and identifying students' needs and analyzing data and programming instruction to meet all students' needs. Even though in…

Implementing RtI with Gifted Students

ERIC Educational Resources Information Center

Coleman, Mary Ruth, Ed.; Johnsen, Susan K., Ed.

2012-01-01

"Implementing RtI With Gifted Students" shares how RtI can fit within the framework of gifted education programming models. This edited book will serve as a reference guide for those interested in learning more about RtI and how it might be effectively implemented to meet the needs of all gifted students. Chapters contributed by top gifted…

The NASA Short-Term Prediction Research and Transition (SPoRT) Center: Opportunities for Collaboration in the Great Lakes Region

NASA Technical Reports Server (NTRS)

Molthan, Andrew L.

2010-01-01

The presentation slides include: The SPoRT Center, History and Future of SPoRT, Great Lakes Applications, Great Lakes Forecasting Issues, Applications to the WRF-EMS, Precipitation Science, Lake Effect Precipitation, Sensitivity to Microphysics, Exploring New Schemes, Opportunities for Collaboration, and SPoRT Research and Development.

Structure of novel rat major histocompatibility complex class II genes RT1.Ha and Hb

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

Arimura, Yutaka; Tang, Wei Ran; Koda, Toshiaki

1995-03-01

We have cloned the novel rat MHC class II genes, RT1.Ha and Hb, which are homologous to human HLA-DPA and DPB. RT1.Hb is a pseudogene, whereas RT1.Ha is apparently intact and may have transcriptional potential. In addition, with an RT1.Ha probe, we detecteda single Southern hybridization band in the genome of the mouse. This finding may aford an opportunity to analyze the HLA-DPA homologue in the mouse genome. 18 refs., 4 figs., 1 tab.

[Not Available].

PubMed

Peñailillo Escarate, Luis; Mackay Phillips, Karen; Serrano Duarte, Natalia; Canales Espinoza, Pablo; Miranda Herrera, Pamela; Zbinden-Foncea, Hermann

2016-07-19

Introducción: el entrenamiento de intervalos de alta intensidad (HIIT) y el consumo de ácidos grasos omega-3 (O3) ha demostrado cada uno por separado aumentar la capacidad aeróbica, metabolismo oxidativo y función cardiovascular.Objetivo: examinar el efecto combinado de HIIT más suplementación de O3 en el rendimiento físico, presión arterial y composición corporal en jóvenes sedentarios.Método: 28 jóvenes sedentarios con sobrepeso (Edad=22 ± 4 años; IMC=25.8 ± 2.4 kg·m-2) fueron distribuidos aleatoriamente en cuatro grupos: grupo O3/HIIT (n=7) realizó un protocolo de HIIT, tres veces por semana durante seis semanas y consumió 2 g·día-1 de O3; grupo HIIT (n=7) realizó solo el HIIT; grupo O3 (n=7) solo consumió O3; y grupo CONTROL (n=7) que no realizó ninguna intervención. Consumo de oxígeno peak (VO2peak), velocidad máxima (Vmax), presión arterial sistólica y diastólica (PAS y PAD), y porcentaje de grasa fueron medidos antes y después de la intervención.Resultados: el consumo de oxígeno peak aumentó más en el grupo O3/HIIT (+10.9%) en comparación con HIIT, O3 y CONTROL. Velocidad máxima aumentó en O3/HIIT (+7.1%) y HIIT (+11.9%). La presión arterial sistólica disminuyó más en O3 (-6.8%) en comparación con O3/HIIT, HIIT y CONTROL. Por último, O3/HIIT (-19.2%), HIIT (-20.2%), y O3 (-15.2%) presentaron mayores disminuciones del porcentaje de masa grasa en relación al CONTROL.Conclusión: nuestros resultados sugieren un efecto potenciador de la capacidad aeróbica máxima producto de la combinación de HIIT y suplementación de O3. Además, se observó una disminución de masa grasa en todos los grupos intervenidos.

Favorable Prognosis in Patients With High-Grade Glioma With Radiation Necrosis: The University of Colorado Reoperation Series

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

Rusthoven, Kyle E.; Olsen, Christine; Franklin, Wilbur

Purpose: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). Methods and Materials: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if {>=}80% of the specimen was necrotic and as tumor recurrence if {>=}20% was tumor. Predictors of survival were analyzed using log-rank comparisons andmore » Cox proportional hazards regression. Results: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p = 0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. Conclusions: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.« less

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: A retrospective analysis

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

Saibishkumar, Elantholi P.; Patel, Firuza D.; Ghoshal, Sushmita

2005-11-01

Purpose: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. Methods and Materials: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. Results: The median follow-up was 34 months. The gap between surgery and RT was 23-198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-yearmore » overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. Conclusions: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity.« less

Reference data on reaction time and aging using the Nintendo Wii Balance Board: A cross-sectional study of 354 subjects from 20 to 99 years of age.

PubMed

Blomkvist, Andreas W; Eika, Fredrik; Rahbek, Martin T; Eikhof, Karin D; Hansen, Mette D; Søndergaard, Malene; Ryg, Jesper; Andersen, Stig; Jørgensen, Martin G

2017-01-01

Falls among older adults is one of the major public health challenges facing the rapidly changing demography. The valid assessment of reaction time (RT) and other well-documented risk factors for falls are mainly restricted to specialized clinics due to the equipment needed. The Nintendo Wii Balance Board has the potential to be a multi-modal test and intervention instrument for these risk factors, however, reference data are lacking. To provide RT reference data and to characterize the age-related changes in RT measured by the Nintendo Wii Balance Board. Healthy participants were recruited at various locations and their RT in hands and feet were tested by six assessors using the Nintendo Wii Balance Board. Reference data were analysed and presented in age-groups, while the age-related change in RT was tested and characterized with linear regression models. 354 participants between 20 and 99 years of age were tested. For both hands and feet, mean RT and its variation increased with age. There was a statistically significant non-linear increase in RT with age. The averaged difference between male and female was significant, with males being faster than females for both hands and feet. The averaged difference between dominant and non-dominant side was non-significant. This study reported reference data with percentiles for a new promising method for reliably testing RT. The RT data were consistent with previously known effects of age and gender on RT.

Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation

PubMed Central

Deloch, Lisa; Derer, Anja; Hartmann, Josefin; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo S.

2016-01-01

Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID:27379203

Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies.

PubMed

Rückert, Michael; Deloch, Lisa; Fietkau, Rainer; Frey, Benjamin; Hecht, Markus; Gaipl, Udo S

2018-06-01

Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular. We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies. Based on the knowledge of the manifold immune mechanisms that are triggered by RT, thought-provoking impulse for multimodal radioimmunotherapies is provided. It has become obvious that ionizing radiation induces various forms of cell death and associated processes via DNA damage initiation and triggering of cellular stress responses. Immunogenic cell death (ICD) is of special interest since it activates the immune system via release of danger signals and via direct activation of immune cells. While RT with higher single doses in particular induces ICD, RT with a lower dose is mainly responsible for immune cell recruitment and for attenuation of an existing inflammation. The counteracting immunosuppression emanating from tumor cells can be overcome by combining RT with selected immunotherapies such as immune checkpoint inhibition, TGF-β inhibitors, and boosting of immunity with vaccination. In order to exploit the full power of RT and thereby develop efficient radioimmunotherapies, the dose per fraction used in RT protocols, the fractionation, the quality, and the quantity of certain immunotherapies need to be qualitatively and chronologically well-matched to the individual immune status of the patient.

Application of Reverse Transcriptase -PCR (RT-PCR) for rapid detection of viable Escherichia coli in drinking water samples.

PubMed

Molaee, Neda; Abtahi, Hamid; Ghannadzadeh, Mohammad Javad; Karimi, Masoude; Ghaznavi-Rad, Ehsanollah

2015-01-01

Polymerase chain reaction (PCR) is preferred to other methods for detecting Escherichia coli (E. coli) in water in terms of speed, accuracy and efficiency. False positive result is considered as the major disadvantages of PCR. For this reason, reverse transcriptase-polymerase chain reaction (RT-PCR) can be used to solve this problem. The aim of present study was to determine the efficiency of RT-PCR for rapid detection of viable Escherichia coli in drinking water samples and enhance its sensitivity through application of different filter membranes. Specific primers were designed for 16S rRNA and elongation Factor II genes. Different concentrations of bacteria were passed through FHLP and HAWP filters. Then, RT-PCR was performed using 16srRNA and EF -Tu primers. Contamination of 10 wells was determined by RT-PCR in Arak city. To evaluate RT-PCR efficiency, the results were compared with most probable number (MPN) method. RT-PCR is able to detect bacteria in different concentrations. Application of EF II primers reduced false positive results compared to 16S rRNA primers. The FHLP hydrophobic filters have higher ability to absorb bacteria compared with HAWB hydrophilic filters. So the use of hydrophobic filters will increase the sensitivity of RT-PCR. RT-PCR shows a higher sensitivity compared to conventional water contamination detection method. Unlike PCR, RT-PCR does not lead to false positive results. The use of EF-Tu primers can reduce the incidence of false positive results. Furthermore, hydrophobic filters have a higher ability to absorb bacteria compared to hydrophilic filters.

Symptoms of ADHD Affect Intrasubject Variability in Youths with Autism Spectrum Disorder: An Ex-Gaussian Analysis.

PubMed

Hwang-Gu, Shoou-Lian; Lin, Hsiang-Yuan; Chen, Yu-Chi; Tseng, Yu-Han; Hsu, Wen-Yau; Chou, Miao-Chun; Chou, Wen-Jun; Wu, Yu-Yu; Gau, Susan Shur-Fen

2018-05-30

Increased intrasubject variability in reaction times (RT-ISV) is frequently found in individuals with autism spectrum disorder (ASD). However, how dimensional attention deficit/hyperactivity disorder (ADHD) symptoms impact RT-ISV in individuals with ASD remains elusive. We assessed 97 high-functioning youths with co-occurring ASD and ADHD (ASD+ADHD), 124 high-functioning youths with ASD only, 98 youths with ADHD only, and 249 typically developing youths, 8-18 years of age, using the Conners Continuous Performance Test (CCPT). We compared the conventional CCPT parameters (omission errors, commission errors, mean RT and RT standard error (RTSE) as well as the ex-Gaussian parameters of RT (mu, sigma, and tau) across the four groups. We also conducted regression analyses to assess the relationships between RT indices and symptoms of ADHD and ASD in the ASD group (i.e., the ASD+ADHD and ASD-only groups). The ASD+ADHD and ADHD-only groups had higher RT-ISV than the other two groups. RT-ISV, specifically RTSE and tau, was significantly associated with ADHD symptoms rather than autistic traits in the ASD group. Regression models also revealed that sex partly accounted for RT-ISV variance in the ASD group. A post hoc analysis showed girls with ASD had higher tau and RTSE values than their male counterparts. Our results suggest that RT-ISV is primarily associated with co-occurring ADHD symptoms/diagnosis in children and adolescents with ASD. These results do not support the hypothesis of response variability as a transdiagnostic phenotype for ASD and ADHD and warrant further validation at a neural level.

Reference data on reaction time and aging using the Nintendo Wii Balance Board: A cross-sectional study of 354 subjects from 20 to 99 years of age

PubMed Central

Rahbek, Martin T.; Eikhof, Karin D.; Hansen, Mette D.; Søndergaard, Malene; Ryg, Jesper; Andersen, Stig; Jørgensen, Martin G.

2017-01-01

Background Falls among older adults is one of the major public health challenges facing the rapidly changing demography. The valid assessment of reaction time (RT) and other well-documented risk factors for falls are mainly restricted to specialized clinics due to the equipment needed. The Nintendo Wii Balance Board has the potential to be a multi-modal test and intervention instrument for these risk factors, however, reference data are lacking. Objective To provide RT reference data and to characterize the age-related changes in RT measured by the Nintendo Wii Balance Board. Method Healthy participants were recruited at various locations and their RT in hands and feet were tested by six assessors using the Nintendo Wii Balance Board. Reference data were analysed and presented in age-groups, while the age-related change in RT was tested and characterized with linear regression models. Results 354 participants between 20 and 99 years of age were tested. For both hands and feet, mean RT and its variation increased with age. There was a statistically significant non-linear increase in RT with age. The averaged difference between male and female was significant, with males being faster than females for both hands and feet. The averaged difference between dominant and non-dominant side was non-significant. Conclusion This study reported reference data with percentiles for a new promising method for reliably testing RT. The RT data were consistent with previously known effects of age and gender on RT. PMID:29287063

Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

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

Bae, Sun Hyun; Park, Hee Chul, E-mail: rophc@skku.edu; Lim, Do Hoon

2012-03-15

Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that wouldmore » be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.« less

Reverberation time influences musical enjoyment with cochlear implants.

PubMed

Certo, Michael V; Kohlberg, Gavriel D; Chari, Divya A; Mancuso, Dean M; Lalwani, Anil K

2015-02-01

To identify factors that enhance the enjoyment of music in cochlear implant (CI) recipients. Specifically, we assessed the hypothesis that variations in reverberation time (RT60) may be linked to variations in the level of musical enjoyment in CI users. Prospective analysis of music enjoyment in normal-hearing individuals. Single tertiary academic medical center. Normal-hearing adults (N = 20) were asked to rate a novel 20-second melody on three enjoyment modalities: musicality, pleasantness, and naturalness. Subjective rating of music excerpts. Participants listened to seven different instruments play the melody, each with five levels (0.2, 1.6, 3.0, 5.0, 10.0 s) of RT60, both with and without CI simulation processing. Linear regression analysis with analysis of variance was used to assess the impact of RT60 on music enjoyment. Without CI simulation, music samples with RT60 = 3.0 seconds were ranked most pleasant and most musical, whereas those with RT60 = 1.6 seconds and RT60 = 3.0 seconds were ranked equally most natural (all p < 0.05). With CI simulation, music samples with RT60 = 0.2 seconds were ranked most pleasant, most musical, and most natural (all p < 0.05). Samples without CI simulation show a preference for middle-range RT60, whereas samples with CI simulation show a negative linear relationship between RT60 and musical enjoyment, with preference for minimal reverberation. Minimization of RT60 may be a useful strategy for increasing musical enjoyment under CI conditions, both in altering existing music as well as in composition of new music.

Simultaneous detection of papaya ringspot virus, papaya leaf distortion mosaic virus, and papaya mosaic virus by multiplex real-time reverse transcription PCR.

PubMed

Huo, P; Shen, W T; Yan, P; Tuo, D C; Li, X Y; Zhou, P

2015-12-01

Both the single infection of papaya ringspot virus (PRSV), papaya leaf distortion mosaic virus (PLDMV) or papaya mosaic virus (PapMV) and double infection of PRSV and PLDMV or PapMV which cause indistinguishable symptoms, threaten the papaya industry in Hainan Island, China. In this study, a multiplex real-time reverse transcription PCR (RT-PCR) was developed to detect simultaneously the three viruses based on their distinctive melting temperatures (Tms): 81.0±0.8°C for PRSV, 84.7±0.6°C for PLDMV, and 88.7±0.4°C for PapMV. The multiplex real-time RT-PCR method was specific and sensitive in detecting the three viruses, with a detection limit of 1.0×10(1), 1.0×10(2), and 1.0×10(2) copies for PRSV, PLDMV, and PapMV, respectively. Indeed, the reaction was 100 times more sensitive than the multiplex RT-PCR for PRSV, and 10 times more sensitive than multiplex RT-PCR for PLDMV. Field application of the multiplex real-time RT-PCR demonstrated that some non-symptomatic samples were positive for PLDMV by multiplex real-time RT-PCR but negative by multiplex RT-PCR, whereas some samples were positive for both PRSV and PLDMV by multiplex real-time RT-PCR assay but only positive for PLDMV by multiplex RT-PCR. Therefore, this multiplex real-time RT-PCR assay provides a more rapid, sensitive and reliable method for simultaneous detection of PRSV, PLDMV, PapMV and their mixed infections in papaya.

Evidence for higher reaction time variability for children with ADHD on a range of cognitive tasks including reward and event rate manipulations

PubMed Central

Epstein, Jeffery N.; Langberg, Joshua M.; Rosen, Paul J.; Graham, Amanda; Narad, Megan E.; Antonini, Tanya N.; Brinkman, William B.; Froehlich, Tanya; Simon, John O.; Altaye, Mekibib

2012-01-01

Objective The purpose of the research study was to examine the manifestation of variability in reaction times (RT) in children with Attention Deficit Hyperactivity Disorder (ADHD) and to examine whether RT variability presented differently across a variety of neuropsychological tasks, was present across the two most common ADHD subtypes, and whether it was affected by reward and event rate (ER) manipulations. Method Children with ADHD-Combined Type (n=51), ADHD-Predominantly Inattentive Type (n=53) and 47 controls completed five neuropsychological tasks (Choice Discrimination Task, Child Attentional Network Task, Go/No-Go task, Stop Signal Task, and N-back task), each allowing trial-by-trial assessment of reaction times. Multiple indicators of RT variability including RT standard deviation, coefficient of variation and ex-Gaussian tau were used. Results Children with ADHD demonstrated greater RT variability than controls across all five tasks as measured by the ex-Gaussian indicator tau. There were minimal differences in RT variability across the ADHD subtypes. Children with ADHD also had poorer task accuracy than controls across all tasks except the Choice Discrimination task. Although ER and reward manipulations did affect children’s RT variability and task accuracy, these manipulations largely did not differentially affect children with ADHD compared to controls. RT variability and task accuracy were highly correlated across tasks. Removing variance attributable to RT variability from task accuracy did not appreciably affect between-group differences in task accuracy. Conclusions High RT variability is a ubiquitous and robust phenomenon in children with ADHD. PMID:21463041

Massively parallel single-molecule and single-cell emulsion reverse transcription polymerase chain reaction using agarose droplet microfluidics.

PubMed

Zhang, Huifa; Jenkins, Gareth; Zou, Yuan; Zhu, Zhi; Yang, Chaoyong James

2012-04-17

A microfluidic device for performing single copy, emulsion Reverse Transcription Polymerase Chain Reaction (RT-PCR) within agarose droplets is presented. A two-aqueous-inlet emulsion droplet generator was designed and fabricated to produce highly uniform monodisperse picoliter agarose emulsion droplets with RT-PCR reagents in carrier oil. Template RNA or cells were delivered from one inlet with RT-PCR reagents/cell lysis buffer delivered separately from the other. Efficient RNA/cell encapsulation and RT-PCR at the single copy level was achieved in agarose-in-oil droplets, which, after amplification, can be solidified into agarose beads for further analysis. A simple and efficient method to graft primer to the polymer matrix using 5'-acrydite primer was developed to ensure highly efficient trapping of RT-PCR products in agarose. High-throughput single RNA molecule/cell RT-PCR was demonstrated in stochastically diluted solutions. Our results indicate that single-molecule RT-PCR can be efficiently carried out in agarose matrix. Single-cell RT-PCR was successfully performed which showed a clear difference in gene expression level of EpCAM, a cancer biomarker gene, at the single-cell level between different types of cancer cells. This work clearly demonstrates for the first time, single-copy RT-PCR in agarose droplets. We believe this will open up new possibilities for viral RNA detection and single-cell transcription analysis.

Validated reverse transcription droplet digital PCR serves as a higher order method for absolute quantification of Potato virus Y strains.

PubMed

Mehle, Nataša; Dobnik, David; Ravnikar, Maja; Pompe Novak, Maruša

2018-05-03

RNA viruses have a great potential for high genetic variability and rapid evolution that is generated by mutation and recombination under selection pressure. This is also the case of Potato virus Y (PVY), which comprises a high diversity of different recombinant and non-recombinant strains. Consequently, it is hard to develop reverse transcription real-time quantitative PCR (RT-qPCR) with the same amplification efficiencies for all PVY strains which would enable their equilibrate quantification; this is specially needed in mixed infections and other studies of pathogenesis. To achieve this, we initially transferred the PVY universal RT-qPCR assay to a reverse transcription droplet digital PCR (RT-ddPCR) format. RT-ddPCR is an absolute quantification method, where a calibration curve is not needed, and it is less prone to inhibitors. The RT-ddPCR developed and validated in this study achieved a dynamic range of quantification over five orders of magnitude, and in terms of its sensitivity, it was comparable to, or even better than, RT-qPCR. RT-ddPCR showed lower measurement variability. We have shown that RT-ddPCR can be used as a reference tool for the evaluation of different RT-qPCR assays. In addition, it can be used for quantification of RNA based on in-house reference materials that can then be used as calibrators in diagnostic laboratories.

Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: a longitudinal study.

PubMed

Lewis, Florence; Merckaert, Isabelle; Liénard, Aurore; Libert, Yves; Etienne, Anne-Marie; Reynaert, Christine; Slachmuylder, Jean-Louis; Scalliet, Pierre; Paul, Van Houtte; Coucke, Philippe; Salamon, Emile; Razavi, Darius

2014-05-01

To our knowledge, no study has specifically assessed the time course of anxiety during radiotherapy (RT). The objective of this study was to assess anxiety time courses in patients with non-metastatic breast cancer. This multicenter, descriptive longitudinal study included 213 consecutive patients with breast cancer who completed visual analog scales (VASs) assessing state anxiety before and after the RT simulation and the first and last five RT sessions. Pre- and post-session anxiety mean levels were highest at the RT simulation (respectively, 2.9±2.9 and 1.6±2.5) and first RT session (respectively, 3.4±2.9 and 2.0±2.4), then declined rapidly. Clinically relevant mean differences (⩾1cm on the VAS) between pre- and post-simulation/session VAS scores were found only for the RT simulation (-1.3±2.7; p<0.001) and first RT session (-1.4±2.4; p<0.001). Five percent to 16% of patients presented clinically relevant anxiety (pre- and post-simulation/session VAS scores⩾4cm) throughout treatment. To optimize care, RT team members should offer all patients appropriate information about treatment at the simulation, check patients' understanding, and identify patients with clinically relevant anxiety requiring appropriate support throughout RT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

Qin, Rosie; Olson, Adam; Singh, Bhavana

Purpose: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. Methods and Materials: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. Results: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non–immune-related toxicity were notmore » statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non–statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. Conclusions: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.« less

Radiation therapy for mucosal melanoma of the head and neck.

PubMed

Christopherson, Kaitlin; Malyapa, Robert S; Werning, John W; Morris, Christopher G; Kirwan, Jessica; Mendenhall, William M

2015-02-01

The aim of this study was to evaluate the long-term effectiveness and complications of radiotherapy (RT) in the treatment of patients with mucosal melanomas of the head and neck. The medical records of 21 patients treated with definitive or postoperative (RT) between 1974 and 2011 at the University of Florida Department of Radiation Oncology in Gainesville, FL, and the University of Florida Proton Therapy Institute in Jacksonville, FL, were retrospectively reviewed under an Institutional Review Board-approved protocol. Primary sites included nasal cavity, oropharynx, and paranasal sinuses. Sixteen patients (76%) received surgery and postoperative RT and 5 patients (24%) received RT alone. Seventeen patients received photon RT alone, whereas 4 patients received combined photon-based and proton-based RT. Median follow-up for all patients was 1.05 years (range, 0.36 to 12.97 y); median follow-up for survivors was 2.2 years (range 0.9 to 13.0 y). The 5-year outcomes were: local control, 79%; regional control, 85%; local-regional control, 65%; distant metastasis-free survival, 20%; cause-specific survival, 22%; and overall survival, 22%. Three patients (14%) experienced severe complications including bilateral blindness and skin necrosis. Definitive or postoperative RT for mucosal melanoma of the head and neck yields fairly good local-regional control of disease. The prognosis for patients treated with definitive RT is less promising than for those who receive surgery and postoperative RT.

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

Martin, Olga A.; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC

Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and inmore » 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.« less

Rapid detection of duck hepatitis A virus genotype C using reverse transcription loop-mediated isothermal amplification.

PubMed

Li, Chuanfeng; Chen, Zongyan; Meng, Chunchun; Liu, Guangqing

2014-02-01

A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was used and optimized to develop a rapid and sensitive detection system for duck hepatitis A virus genotype C (DHAV-C) RNA. A set of four specific primers was designed against highly conserved sequences located within the 3D gene from DHAV (strain GX1201). Under optimal reaction conditions, the sensitivity of DHAV-C-specific RT-LAMP was 100-fold higher than that of reverse transcriptase-polymerase chain reaction (RT-PCR), with a detection limit of 0.3pg (6.59×10(4) copies) per reaction. No cross-reactivity was observed from the samples of other duck viruses, which is in good accordance with RT-PCR. Furthermore, a positive reaction can be visually inspected by observing turbidity or color change after the addition of SYBR green I dye. The DHAV-C-specific RT-LAMP assay was applied to the samples and compared with RT-PCR. The positive-sample ratios were 26.7% (12 of 45) by RT-LAMP and 20% (9 of 45) by RT-PCR. Therefore, the newly developed RT-LAMP assay is a rapid, specific, sensitive, and cost-effective method of DHAV-C detection. This assay has potential applications in both clinical diagnosis and field surveillance of DHAV-C infection. Copyright © 2013. Published by Elsevier B.V.

Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

NASA Astrophysics Data System (ADS)

Huang, Su-Hua; Yang, Tsuey-Ching; Tsai, Ming-Hong; Tsai, I.-Shou; Lu, Huang-Chih; Chuang, Pei-Hsin; Wan, Lei; Lin, Ying-Ju; Lai, Chih-Ho; Lin, Cheng-Wen

2008-10-01

Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

Classroom acoustics and hearing ability as determinants for perceived social climate and intentions to stay at work.

PubMed

Persson, Roger; Kristiansen, Jesper; Lund, Søren P; Shibuya, Hitomi; Nielsen, Per Møberg

2013-01-01

Background noise and room acoustics may impede social interactions by interfering with oral communication and other cognitive processes. Accordingly, recent research in school environments has showed that social relationships with peers and teachers are described more negatively in rooms with long reverberation times (RT). The purpose of this study was to investigate how RT and hearing ability (i.e., hearing thresholds [HT] and distortion product oto-acoustic emissions) were associated with school teachers' perceptions of the social climate at work and their intentions to stay on the job. School teachers (n = 107) from 10 schools that worked in classrooms classified by acoustical experts as "short RT" (3 schools, mean RT 0.41-0.47 s), "medium RT" (3 schools, mean RT 0.50-0.53 s), and "long RT" (4 schools, mean RT 0.59-0.73 s) were examined. Teachers who worked in classrooms with long RT perceived their social climate to be more competitive, conflict laden, and less relaxed and comfortable. They were more doubtful about staying on the job. Even if the teachers were generally satisfied with their work the results suggest that the comfort at work may have been further improved by acoustical interventions that focus on reducing sound reflections in the classrooms. Yet, due the study design and the novelty of the findings the potential practical significance of our observations remains to be evaluated.

The compatibility of concurrent high intensity interval training and resistance training for muscular strength and hypertrophy: a systematic review and meta-analysis.

PubMed

Sabag, Angelo; Najafi, Abdolrahman; Michael, Scott; Esgin, Tuguy; Halaki, Mark; Hackett, Daniel

2018-04-16

The purpose of this systematic review and meta-analysis is to assess the effect of concurrent high intensity interval training (HIIT) and resistance training (RT) on strength and hypertrophy. Five electronic databases were searched using terms related to HIIT, RT, and concurrent training. Effect size (ES), calculated as standardised differences in the means, were used to examine the effect of concurrent HIIT and RT compared to RT alone on muscle strength and hypertrophy. Sub-analyses were performed to assess region-specific strength and hypertrophy, HIIT modality (cycling versus running), and inter-modal rest responses. Compared to RT alone, concurrent HIIT and RT led to similar changes in muscle hypertrophy and upper body strength. Concurrent HIIT and RT resulted in a lower increase in lower body strength compared to RT alone (ES = -0.248, p = 0.049). Sub analyses showed a trend for lower body strength to be negatively affected by cycling HIIT (ES = -0.377, p = 0.074) and not running (ES = -0.176, p = 0.261). Data suggests concurrent HIIT and RT does not negatively impact hypertrophy or upper body strength, and that any possible negative effect on lower body strength may be ameliorated by incorporating running based HIIT and longer inter-modal rest periods.

Rapid and sensitive detection of canine distemper virus by one-tube reverse transcription-insulated isothermal polymerase chain reaction.

PubMed

Wilkes, Rebecca P; Tsai, Yun-Long; Lee, Pei-Yu; Lee, Fu-Chun; Chang, Hsiao-Fen Grace; Wang, Hwa-Tang Thomas

2014-09-09

Canine distemper virus (CDV) has been associated with outbreaks of canine infectious respiratory disease in shelters and boarding kennel environments. POCKITTM Nucleic Acid Analyzer is a field-deployable device capable of generating automatically interpreted insulated isothermal polymerase chain reaction (iiPCR) results from extracted nucleic acid within one hour. In this study, reverse transcription iiPCR (RT-iiPCR) was developed to facilitate point-of-need diagnosis of CDV infection. Analytical sensitivity (limit of detection 95%) of the established CDV RT-iiPCR was about 11 copies of in vitro transcribed RNA per reaction. CDV RT-iiPCR generated positive signals from CDV, but not Bordetella bronchiseptica, canine parvovirus, canine herpesvirus, canine adenovirus 2, canine influenza virus (subtype H3N8), canine parainfluenza virus, and canine respiratory coronavirus. To evaluate accuracy of the established reaction in canine distemper clinical diagnosis, 110 specimens from dogs, raccoons, and foxes suspected with CDV infection were tested simultaneously by CDV RT-iiPCR and real-time RT-PCR. CDV RT-iiPCR demonstrated excellent sensitivity (100%) and specificity (100%), compared to real-time RT-PCR. The results indicated an excellent correlation between RT-iiPCR and a reference real time RT-PCR method. Working in a lyophilized format, the established method has great potential to be used for point-of-care diagnosis of canine distemper in animals, especially in resource-limited facilities.

Esthesioneuroblastoma of the nasal cavity.

PubMed

Hollen, Tyler R; Morris, Christopher G; Kirwan, Jessica M; Amdur, Robert J; Werning, John W; Vaysberg, Mikhail; Mendenhall, William M

2015-06-01

Esthesioneuroblastoma is an uncommon cancer of the nasal cavity. We describe the outcomes for 26 patients treated with curative intent with photon radiotherapy (RT) at the University of Florida. Between May 1972 and June 2007, 26 patients received RT for previously untreated esthesioneuroblastoma of the nasal cavity. Sixteen patients were males and 10 were females with a median age of 55 years (range, 3 to 82 y). The modified Kadish stage distribution was: B, 7 patients; C, 17 patients; and D, 2 patients. Treatment modalities included the following: definitive RT, 5 patients; preoperative RT, 2 patients; and postoperative RT after resection, 19 patients. Elective neck irradiation (ENI) was performed in 17 (71%) of 24 N0 patients. Rates of local control, cause-specific survival, and absolute overall survival at 5 years were 79%, 72%, and 69%, respectively. Overall survival among patients treated with definitive RT was 20% at 5 years, compared with 81% among those who underwent surgery and adjuvant RT (P=0.01). One (6%) of 17 patients who received ENI developed a recurrence in the neck and was successfully salvaged. Ultimate neck control was 100% at 5 years for patients who received ENI versus 69% among those not receiving ENI (P=0.0173). Resection combined with adjuvant RT is more effective than surgery or RT alone in the treatment of esthesioneuroblastoma. ENI reduces the risk of regional relapse in patients with Kadish stage B and C cancers.

Benefit from the inclusion of radiation therapy in the treatment of patients with stage III classical Hodgkin lymphoma: A propensity matched analysis of the Surveillance, Epidemiology, and End Results database.

PubMed

Bates, James E; Dhakal, Sughosh; Mazloom, Ali; Casulo, Carla; Constine, Louis S

2017-08-01

While stage III and IV classical Hodgkin lymphoma (HL) patients are often combined and defined as "advanced stage," there are significant differences in disease distribution and burden between the two stages. This may obscure advantages of radiotherapy (RT) in a combined modality therapy strategy in stage III disease due to the relative lack of benefit in stage IV patients. We queried the Surveillance, Epidemiology, and End Results (SEER) database, restricting our search to patients with stage III classical HL diagnosed from 2004 to 2012, to examine the difference in overall and cause-specific survival (OS and CSS) between patients who did or did not receive RT. Patients treated with RT had improved OS and CSS relative to those treated without RT (5-year OS 91.6% with RT compared to 71.4% without RT, HR=0.34, p<0.001) and CSS (5-year OS 95.4% with RT compared to 84.7% without RT, HR=0.32, p<0.001). A benefit in OS and/or CSS was seen in all patient subgroups except for older adults (>64years). These data support at least a cautionary approach to omitting RT from treatment strategies for patients with advanced stage HL. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of RT carry-over for congruence sequence effects in masked priming.

PubMed

Huber-Huber, Christoph; Ansorge, Ulrich

2017-05-01

The present study disentangles 2 sources of the congruence sequence effect with masked primes: congruence and response time of the previous trial (reaction time [RT] carry-over). Using arrows as primes and targets and a metacontrast masking procedure we found congruence as well as congruence sequence effects. In addition, congruence sequence effects decreased when RT carry-over was accounted for in a mixed model analysis, suggesting that RT carry-over contributes to congruence sequence effects in masked priming. Crucially, effects of previous trial congruence were not cancelled out completely indicating that RT carry-over and previous trial congruence are 2 sources feeding into the congruence sequence effect. A secondary task requiring response speed judgments demonstrated general awareness of response speed (Experiments 1), but removing this secondary task (Experiment 2) showed that RT carry-over effects were also present in single-task conditions. During (dual-task) prime-awareness test parts of both experiments, however, RT carry-over failed to modulate congruence effects, suggesting that some task sets of the participants can prevent the effect. The basic RT carry-over effects are consistent with the conflict adaptation account, with the adaptation to the statistics of the environment (ASE) model, and possibly with the temporal learning explanation. Additionally considering the task-dependence of RT carry-over, the results are most compatible with the conflict adaptation account. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Simultaneous detection of three lily viruses using Triplex IC-RT-PCR.

PubMed

Zhang, Yubao; Wang, Yajun; Xie, Zhongkui; Yang, Guo; Guo, Zhihong; Wang, Le

2017-11-01

Viruses commonly infecting lily (Lilium spp.) include: Lily symptomless virus (LSV), Cucumber mosaic virus (CMV) and Lily mottle virus (LMoV). These viruses usually co-infect lilies causing severe economic losses in terms of quantity and quality of flower and bulb production around the world. Reliable and precise detection systems need to be developed for virus identification. We describe the development of a triplex immunocapture (IC) reverse transcription (RT) polymerase chain reaction (PCR) assay for the simultaneous detection of LSV, CMV and LMoV. The triplex IC-RT-PCR was compared with a quadruplex RT-PCR assay. Relative to the quadruplex RT-PCR, the specificity of the triplex IC-RT-PCR system for LSV, CMV and LMoV was 100% for field samples. The sensitivity of the triplex IC-RT-PCR system was 99.4%, 81.4% and 98.7% for LSV, CMV and LMoV, respectively. Agreement (κ) between the results obtained from the two tests was 0.968, 0.844 and 0.984 for LSV, CMV and LMoV, respectively. This is the first report of the simultaneous detection of LSV, CMV and LMoV in a triplex IC-RT-PCR assay. In particular we believe this convenient and reliable triplex IC-RT-PCR method could be used routinely for large-scale field surveys or crop health monitoring of lily. Copyright © 2017. Published by Elsevier B.V.

Response to Intervention (RtI) in Secondary Schools: A Comparison of the RtI Service Delivery Model

ERIC Educational Resources Information Center

Epler-Brooks, Pam L.

2011-01-01

This qualitative, collective case study researched how the Response to Intervention (RtI) service delivery model was used within the secondary educational environment in two Ohio schools. Areas researched included the type of professional development used to introduce and sustain RtI, the amount of administrative support, the use of universal…

Inactivation conditions for human Norovirus measured by an in situ capture-qRT-PCR Method

USDA-ARS?s Scientific Manuscript database

Human noroviruses (HuNoVs) are the major cause of epidemic non-bacterial gastroenteritis. Due to the inability to cultivate HuNoVs, it has been a challenge to determine their infectivity. Quantitative real-time RT-PCR (qRT-PCR) is widely used in detecting HuNoVs. However, qRT-PCR only detects the...

RT-CaCCO process: an improved CaCCO process for rice straw by its incorporation with a step of lime pretreatment at room temperature.

PubMed

Shiroma, Riki; Park, Jeung-yil; Al-Haq, Muhammad Imran; Arakane, Mitsuhiro; Ike, Masakazu; Tokuyasu, Ken

2011-02-01

We improved the CaCCO process for rice straw by its incorporation with a step of lime pretreatment at room temperature (RT). We firstly optimized the RT-lime pretreatment for the lignocellulosic part. When the ratio of lime/dry-biomass was 0.2 (w/w), the RT lime-pretreatment for 7-d resulted in an effect on the enzymatic saccharification of cellulose and xylan equivalent to that of the pretreatment at 120°C for 1h. Sucrose, starch and β-1,3-1,4-glucan, which could be often detected in rice straw, were mostly stable under the RT-lime pretreatment condition. Then, the pretreatment condition in the conventional CaCCO process was modified by the adaptation of the optimized RT lime-pretreatment, resulting in significantly better carbohydrate recoveries via enzymatic saccharification than those of the CaCCO process (120°C for 1 h). Thus, the improved CaCCO process (the RT-CaCCO process) could preserve/pretreat the feedstock at RT in a wet form with minimum loss of carbohydrates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Factors associated with participation in resistance training: a systematic review.

PubMed

Rhodes, Ryan E; Lubans, David R; Karunamuni, Nandini; Kennedy, Sarah; Plotnikoff, Ronald

2017-10-01

Regular participation in resistance training (RT) is critical to health and recommended in most international physical activity guidelines. Few people, however, participate in RT. The purpose of this review was to assess the demographic, behavioural, intrapersonal, interpersonal and environmental factors associated with participating in RT. Eligible studies were from English peer-reviewed published articles that examined correlates or determinants of RT in adult samples. Searches were performed from August 2015 to April 2016 in six databases. We identified 51 independent data sets, from nine countries, primarily of moderate to high quality, and 23 factors related to participating in RT. Education, perceived health status, quality of life, affective judgements, self-efficacy, intention, self-regulation behaviours, subjective norm and programme leadership were associated with RT. Low education levels and poor health status were associated with low participation rates in RT. Intrapersonal factors including affective judgements, self-efficacy, and self-regulation behaviours, and interpersonal factors including subjective norms and programme leadership may be important for promoting RT behaviours. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Blind estimation of reverberation time

NASA Astrophysics Data System (ADS)

Ratnam, Rama; Jones, Douglas L.; Wheeler, Bruce C.; O'Brien, William D.; Lansing, Charissa R.; Feng, Albert S.

2003-11-01

The reverberation time (RT) is an important parameter for characterizing the quality of an auditory space. Sounds in reverberant environments are subject to coloration. This affects speech intelligibility and sound localization. Many state-of-the-art audio signal processing algorithms, for example in hearing-aids and telephony, are expected to have the ability to characterize the listening environment, and turn on an appropriate processing strategy accordingly. Thus, a method for characterization of room RT based on passively received microphone signals represents an important enabling technology. Current RT estimators, such as Schroeder's method, depend on a controlled sound source, and thus cannot produce an online, blind RT estimate. Here, a method for estimating RT without prior knowledge of sound sources or room geometry is presented. The diffusive tail of reverberation was modeled as an exponentially damped Gaussian white noise process. The time-constant of the decay, which provided a measure of the RT, was estimated using a maximum-likelihood procedure. The estimates were obtained continuously, and an order-statistics filter was used to extract the most likely RT from the accumulated estimates. The procedure was illustrated for connected speech. Results obtained for simulated and real room data are in good agreement with the real RT values.

Online estimation of room reverberation time

NASA Astrophysics Data System (ADS)

Ratnam, Rama; Jones, Douglas L.; Wheeler, Bruce C.; Feng, Albert S.

2003-04-01

The reverberation time (RT) is an important parameter for characterizing the quality of an auditory space. Sounds in reverberant environments are subject to coloration. This affects speech intelligibility and sound localization. State-of-the-art signal processing algorithms for hearing aids are expected to have the ability to evaluate the characteristics of the listening environment and turn on an appropriate processing strategy accordingly. Thus, a method for the characterization of room RT based on passively received microphone signals represents an important enabling technology. Current RT estimators, such as Schroeder's method or regression, depend on a controlled sound source, and thus cannot produce an online, blind RT estimate. Here, we describe a method for estimating RT without prior knowledge of sound sources or room geometry. The diffusive tail of reverberation was modeled as an exponentially damped Gaussian white noise process. The time constant of the decay, which provided a measure of the RT, was estimated using a maximum-likelihood procedure. The estimates were obtained continuously, and an order-statistics filter was used to extract the most likely RT from the accumulated estimates. The procedure was illustrated for connected speech. Results obtained for simulated and real room data are in good agreement with the real RT values.

Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

PubMed Central

Yang, Hung-Wei; Hua, Mu-Yi; Lin, Kun-Ju; Wey, Shiaw-Pyng; Tsai, Rung-Ywan; Wu, Siao-Yun; Lu, Yi-Ching; Liu, Hao-Li; Wu, Tony; Ma, Yunn-Hwa

2012-01-01

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases. PMID:23055728

Does the patient's inherent rating tendency influence reported satisfaction scores and affect division ranking?

PubMed

Francis, Patricia; Agoritsas, Thomas; Chopard, Pierre; Perneger, Thomas

2016-04-01

To determine the impact of adjusting for rating tendency (RT) on patient satisfaction scores in a large teaching hospital and to assess the impact of adjustment on the ranking of divisions. Cross-sectional survey. Large 2200-bed university teaching hospital. All adult patients hospitalized during a 1-month period in one of 20 medical divisions. None. Patient experience of care measured by the Picker Patient Experience questionnaire and RT scores. Problem scores were weakly but significantly associated with RT. Division ranking was slightly modified in RT adjusted models. Division ranking changed substantially in case-mix adjusted models. Adjusting patient self-reported problem scores for RT did impact ranking of divisions, although marginally. Further studies are needed to determine the impact of RT when comparing different institutions, particularly across inter-cultural settings, where the difference in RT may be more substantial. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

PubMed

Daoud, Alia M; Hudson, Mack; Magnus, Kenneth G; Huang, Fleur; Danielson, Brita L; Venner, Peter; Saluja, Ronak; LeGuerrier, Bronwen; Daly, Helene; Emmenegger, Urban; Fairchild, Alysa

2016-03-06

Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head.

Development of mRNA-specific RT-PCR for the detection of koi herpesvirus (KHV) replication stage.

PubMed

Yuasa, Kei; Kurita, Jun; Kawana, Morihiko; Kiryu, Ikunari; Oseko, Norihisa; Sano, Motohiko

2012-08-13

An mRNA-specific reverse transcription (RT)-PCR primer set spanning the exon junction of a spliced putative terminase gene in the koi herpesvirus (KHV) was developed to detect the replicating stage of the virus. The proposed RT-PCR amplified a target gene from the RNA template, but not from a DNA template extracted from common carp brain (CCB) cells infected with KHV. In addition, the RT-PCR did not amplify the target gene of templates extracted from specific cell lines infected with either CyHV-1 or CyHV-2. RT-PCR detected mRNA from the scales of koi experimentally infected with KHV at 24 h post exposure (hpe). However, unlike conventional PCR, RT-PCR could not detect KHV DNA in fish at 0 hpe. The results indicate that the RT-PCR developed in this study is mRNA-specific and that the assay can detect the replicating stage of KHV from both fish and cultured cells infected with the virus.

The SPoRT-WRF: Evaluating the Impact of NASA Datasets on Convective Forecasts

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Kozlowski, Danielle; Case, Jonathan; Molthan, Andrew

2012-01-01

Short-term Prediction Research and Transition (SPoRT) seeks to improve short-term, regional weather forecasts using unique NASA products and capabilities SPoRT has developed a unique, real-time configuration of the NASA Unified Weather Research and Forecasting (WRF)WRF (ARW) that integrates all SPoRT modeling research data: (1) 2-km SPoRT Sea Surface Temperature (SST) Composite, (2) 3-km LIS with 1-km Greenness Vegetation Fraction (GVFs) (3) 45-km AIRS retrieved profiles. Transitioned this real-time forecast to NOAA's Hazardous Weather Testbed (HWT) as deterministic model at Experimental Forecast Program (EFP). Feedback from forecasters/participants and internal evaluation of SPoRT-WRF shows a cool, dry bias that appears to suppress convection likely related to methodology for assimilation of AIRS profiles Version 2 of the SPoRT-WRF will premier at the 2012 EFP and include NASA physics, cycling data assimilation methodology, better coverage of precipitation forcing, and new GVFs

Roles of quorum sensing molecules from Rhizobium etli RT1 in bacterial motility and biofilm formation.

PubMed

Dixit, Swarnita; Dubey, Ramesh Chand; Maheshwari, Dinesh Kumar; Seth, Prahlad Kishore; Bajpai, Vivek K

Strain RT1 was isolated from root nodules of Lens culinaris (a lentil) and characterized as Rhizobium etli (a Gram-negative soil-borne bacterium) by 16S rDNA sequencing and phylogenetic analysis. The signaling molecules produced by R. etli (RT1) were detected and identified by high-performance liquid chromatography coupled with mass spectrometry. The most abundant and biologically active N-acyl homoserine lactone molecules (3-oxo-C 8 -HSL and 3-OH-C 14 -HSL) were detected in the ethyl acetate extract of RT1. The biological role of 3-oxo-C 8 -HSL was evaluated in RT1. Bacterial motility and biofilm formation were affected or modified on increasing concentrations of 3-oxo-C 8 -HSL. Results confirmed the existence of cell communication in RT1 mediated by 3-oxo-C 8 -HSL, and positive correlations were found among quorum sensing, motility and biofilm formation in RT1. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Pro-community altruism and social status in a Shuar village.

PubMed

Price, Michael E

2003-06-01

Reciprocity theory (RT) and costly signaling theory (CST) provide different explanations for the high status of pro-community altruists: RT proposes that altruists are positively and negatively sanctioned by others, whereas CST proposes that altruists are attractive to others. Only RT, however, is beset by first- and higher-order free rider problems, which must be solved in order for RT to explain status allocations. In this paper, several solutions to RT's free rider problems are proposed, and data about status allocations to Ecuadorian Shuar pro-community altruists are analyzed in light of RT and CST. These data confirm that perceived pro-community altruists are indeed high status and suggest that (1) community residents skillfully monitor the altruism of coresidents, (2) residents who engage in opportunities to broadcast desirable qualities are high status only to the extent that they are considered altruistic, and (3) individuals who sanction coresidents based on coresidents' contributions to the community are themselves relatively high status. To a greater extent than CST, RT straightforwardly predicts all of these results.

Progressive Resistance Training Improves Overall Physical Activity Levels in Patients With Early Osteoarthritis of the Knee: A Randomized Controlled Trial

PubMed Central

Going, Scott B.; McKnight, Patrick E.; Kasle, Shelley; Cussler, Ellen C.; Cornett, Michelle

2010-01-01

Background Prescription of resistance training (RT) exercises is an essential aspect of management for knee osteoarthritis (OA). However, whether patients with knee OA who are randomly assigned to receive RT simply substitute RT for other modes of physical activity remains unclear. Objective The aim of this study was to determine the effect of a structured RT intervention on overall levels of moderate- and vigorous-intensity physical activity (MVPA) in patients with early-onset knee OA. The study compared patients with early-onset OA who participated in an RT program, those who participated in a self-management (SM) program, and those who participated in both RT and SM. Because participants randomly assigned to receive the RT intervention may simply switch activity modes, resulting in little net effect, we assessed total MVPA in addition to tracking changes in strength (force-generating capacity). Design and Intervention This study was a randomized controlled trial comparing the effectiveness of SM alone, RT alone, and combined RT+SM on MVPA in patients with early OA of the knee. Setting The study was conducted on a university campus, with patient recruitment from the local community. Participants The participants in this study were 171 patients (74% women, 26% men) with knee OA. They had a mean age of 55.1 (SD=7.1) years, a mean body mass index of 27.6 (SD=4.2) kg/m2, and radiographic status of grade II OA (and no higher) in at least one knee, as defined by the Kellgren and Lawrence classification. They wore an accelerometer while awake (X̄=14.2 [SD=2.2] hours) for 5 to 7 contiguous days (X̄=6.8 [SD=0.5] days) at baseline and at 3 and 9 months of intervention. Results The participants engaged in MVPA a mean of 26.2 (SD=19.3) minutes per day at baseline. Both groups significantly increased their MVPA from baseline to 3 months (RT group by 18% [effect size (d)=0.26]; SM group by 22% [effect size (d)=0.25]), but only the RT group sustained those changes at 9 months (RT group maintained a 10% increase [effect size (d)=0.15]; SM group maintained a 2% increase [effect size (d)=0.03]). A significant group × time interaction for MVPA indicated that the RT group maintained higher MVPA levels than the SM group. Limitations. Lack of direct measures of energy expenditure and physical function was a limitation of the study. Conclusions Patients with early-onset OA of the knee can engage in an RT program without sacrificing their overall MVPA levels. These results support the value of RT for management of knee OA. PMID:20056719

Re-evaluation of Ipsilateral Radiation for T1-T2N0-N2b Tonsil Carcinoma at the Princess Margaret Hospital in the Human Papillomavirus Era, 25 Years Later

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

Huang, Shao Hui, E-mail: shaohui.huang@rmp.uhn.on.ca; Waldron, John; Department of Otolaryngology—Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario

Purpose: To report the outcome of ipsilateral radiation therapy (RT) in human papillomavirus (HPV)-positive (HPV+) patients and HPV-negative (HPV−) patients with T1-T2N0-N2b tonsillar cancer treated 25 years after our initial historical cohort. Methods and Materials: Patients with T1-T2N0-N2b tonsillar cancer who received ipsilateral RT or bilateral RT between 1999 and 2014 were reviewed. Overall survival (OS), local control (LC), regional control (RC), and grade 3 to 4 late toxicity (LT) were compared between ipsilateral RT and bilateral RT within HPV+ and HPV− patients, separately. Results: HPV status was ascertained in 379/427 (88%) consecutive patients (ipsilateral RT: 62 HPV+, 34 HPV−; bilateralmore » RT: 240 HPV+ 240, 41 HPV−). The proportion of ipsilateral RT by N category for HPV+ and HPV− patients were as follows: N0: 24/37 (65%) versus 28/48 (74%); N1: 21/49 (43%) versus 4/9 (44%); N2a: 10/39 (26%) versus 1/4 (25%); and N2b: 7/177 (4%) versus 1/24 (4%), respectively. Of the patients receiving ipsilateral RT, 94/96 (98%) were treated with RT alone. The median follow-up time was 5.03 years. The respective 5-year rates of OS, LC, RC, and LT were similar between ipsilateral RT and bilateral RT for the HPV+ patients (OS: 89% vs 87%, P=.55; LC: 97% vs 98%, P=.65; RC: 98% vs 97%, P=.27; LT: 17% vs 12%, P=.83) and HPV− patients (OS: 63% vs 48%, P=.27; LC: 90% vs 80%, P=.19; RC: 94% vs 83%, P=.14; LT: 15% vs 22%, P=.36). Of the 96 patients receiving ipsilateral RT, contralateral neck failure (CNF) occurred in 1/52 HPV+ patients and 1/34 HPV− patients. The 5-year CNF rates were 2% (95% CI: 1-9) (HPV+: 2% [0-14]; HPV−: 3% [0-21], P=.66). Five local failures (2 HPV+; 3 HPV−) and no distant failures were seen. The 5-year rates of LC, RC, and LT were 97% versus 90% (P=.24), 98% versus 94% (P=.25), and 18% versus 15% (P=.75) for the HPV+ and HPV− cohorts, respectively. Osteoradionecrosis occurred in 9 patients: 6/47 (13%) treated with conventional RT and 3/49 (6%) with intensity modulated RT (P=.32). Conclusion: Ipsilateral radiation to selected patients with T1-T2N0-N2b tonsillar cancer results in equally excellent outcomes regardless of tumor HPV status.« less

A DICOM-RT based ePR radiation therapy information system for managing brain tumor patients

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Law, Maria; Huang, H. K.; Zee, C. S.; Chan, Lawrence

2005-04-01

The need for comprehensive clinical image data and relevant information in image-guided Radiation Therapy (RT) is becoming steadily apparent. Multiple standalone systems utilizing the most technological advancements in imaging, therapeutic radiation, and computerized treatment planning systems acquire key data during the RT treatment course of a patient. One example are patients treated for brain tumors of greater sizes and irregular shapes that utilize state-of-the-art RT technology to deliver pinpoint accurate radiation doses. One such system, the Cyberknife, is a radiation treatment system that utilizes image-guided information to control a multi-jointed, six degrees of freedom, robotic arm to deliver precise and required radiation dose to the tumor site of a cancer patient. The image-guided system is capable of tracking the lesion orientations with respect to the patient"s position throughout the treatment process. This is done by correlating live radiographic images with pre-operative, CT and MR imaging information to determine relative patient and tumor position repeatedly over the course of the treatment. The disparate and complex data generated by the Cyberknife system along with related data is scattered throughout the RT department compromising an efficient clinical workflow since the data crucial for a clinical decision may be time-consuming to retrieve, temporarily missing, or even lost. To address these shortcomings, the ACR-NEMA Standards Committee extended its DICOM (Digital Imaging & Communications in Medicine) Standard from Radiology to RT by ratifying seven DICOM RT objects starting in 1997. However, they are rarely used by the RT community in daily clinical operations. In the past, the research focus of an RT department has primarily been developing new protocols and devices to improve treatment process and outcomes of cancer patients with minimal effort dedicated to integration of imaging and information systems. Our research, tightly-coupling radiology and RT information systems, represents a new frontier for medical informatics research that has never been previously considered. By combining our past experience in medical imaging informatics, DICOM-RT expertise, and system integration, we propose to test our hypothesis using a brain tumor case model that a DICOM-RT electronic patient record (ePR) system can improve clinical workflow efficiency for treatment and management of patients. This RT ePR system integrated with clinical images and RT data can impact the RT department in a similar fashion as PACS has already successfully done for Radiology. As a first step, the specific treatment case of patients with brain tumors specifically patients treated with the Cyberknife system will be the initial proof of concept for the research design, implementation, evaluation, and clinical relevance.

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-04-01

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m 2 ) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR ( P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These findings were displayed with a similar time investment per week of 114 vs. 108 min, respectively, to HIIT and RT. NEW & NOTEWORTHY The effects and prevalence of nonresponders (NR) to improve glucose control variables have predominately been reported by endurance training. A uniqueness of the present study was to examine the NR prevalence in women with insulin resistance after high-intensity interval (HIIT) and resistance training (RT). This study demonstrates that 12 wk of HIIT and RT have similar effects and NR prevalence to improve glucose control variables. However, significantly different NR prevalence were observed in other anthropometric, cardiovascular, strength, and endurance performance measurements. Copyright © 2017 the American Physiological Society.

Relationship among eye and muzzle temperatures measured using digital infrared thermal imaging and vaginal and rectal temperatures in hair sheep and cattle.

PubMed

George, W D; Godfrey, R W; Ketring, R C; Vinson, M C; Willard, S T

2014-11-01

Digital infrared thermal imaging (DITI) using a thermal camera has potential to be a useful tool for the production animal industry. Thermography has been used in both humans and a wide range of animal species to measure body temperature as a method to detect injury or inflammation. The objective of these experiments was to compare the temperature of the eye (EYE) or muzzle (MUZ) measured using DITI to vaginal (VT) and rectal temperature (RT) as measures of core body temperature in hair sheep and beef cattle. In Exp.1 EYE, VT and RT were measured in lactating, multiparous hair sheep ewes (St. Croix White, n = 10, and Dorper × St. Croix White, n = 10) in a non-febrile state 5 times over a 48-h period. Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.95), EYE and RT (r = 0.76) and EYE and VT (r = 0.77). In Exp. 2 EYE, MUZ, VT and RT were measured in multiparous, lactating ewes (St. Croix White, n = 2, and Barbados Blackbelly, n = 12) at -12, -1, 0, 1, 2, 3, 4, 6, 12, 24, 36, and 48 h after being administered lipopolysaccharide (LPS; n = 7; 0.2 µg/kg BW, i.v.) or saline (n = 7; 0.5 mL, i.v.). Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. When data were combined across treatments (LPS and saline) there was a high correlation (P < 0.001) between VT and RT (r = 0.96), EYE and RT (r = 0.82), MUZ and RT (r = 0.72), and EYE and VT (r = 0.93). In Exp. 3 EYE, MUZ, VT and RT were measured in multiparous, non-lactating, pregnant Senepol cattle (n = 44) between 0900 and 1200 h on a single day. A digital veterinary thermometer was used to measure both VT and RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.78), a moderate correlation (P < 0.001) between VT and EYE (r = 0.52), RT and EYE (r = 0.58) and EYE and MUZ (r = 0.48). There was no correlation (P > 0.10) between RT or VT and MUZ. The findings of these three studies indicate that temperature of the eye, measured using DITI, can be used as an indicator of core body temperature in hair sheep and beef cattle as an alternative to using vaginal or rectal temperature.

Highly Sensitive Assay for Detection of Enterovirus in Clinical Specimens by Reverse Transcription-PCR with an Armored RNA Internal Control

PubMed Central

Beld, Marcel; Minnaar, René; Weel, Jan; Sol, Cees; Damen, Marjolein; van der Avoort, Harry; Wertheim-van Dillen, Pauline; Breda, Alex van; Boom, René

2004-01-01

The objective of the present study was the development of a diagnostic reverse transcription (RT)-PCR for the specific detection of enterovirus (EV) RNA in clinical specimens controlled by an internal control (IC) RNA. The IC RNA contains the same primer binding sites as EV RNA but has a different probe region. The IC RNA was packaged into an MS2 phage core particle (armored) and was added to the clinical sample to allow monitoring of both extraction efficiency and RT-PCR efficiency. Serial dilutions of the IC RNA were made, and the detection limit of the RT-PCR was tested in a background of EV RNA-negative cerebrospinal fluid. The sensitivity and specificity of the RT-PCR assay were tested by using all 64 known EV serotypes, several non-EV serotypes, and two Quality Control for Molecular Diagnostics (QCMD) Program EV proficiency panels from 2001 and 2002. In total, 322 clinical specimens were tested by RT-PCR, and to establish the clinical utility of the RT-PCR, a comparison of the results of viral culture and RT-PCR was done with 87 clinical specimens. The lower limit of sensitivity was reached at about 150 copies of IC RNA/ml. All 64 EV serotypes were positive, while all non-EV serotypes were negative. All culture-positive samples of the 2001 QCMD proficiency panel (according to the 50% tissue culture infective doses per milliliter) were positive by RT-PCR. Invalid results, i.e., negativity for both EV RNA and IC RNA, due to inhibition of RT-PCR were observed for 33.3% of the members of the 2002 QCMD proficiency panel and 3.1% of the clinical specimens. Inhibition of RT-PCR could be relieved by the addition of 400 ng of bovine α-casein per μl to both the RT reaction mixture and the PCR mixture. With this optimized protocol, the results for all samples of the 2002 QCMD proficiency panel and all clinical specimens except one fecal sample (0.3%) were valid. Evaluation of the clinical samples demonstrated that EV infection could be detected in 12 of 87 samples (13.8%) by RT-PCR, while viral culture was negative. Our data show that the RT-PCR with armored IC RNA offers a very reliable and rapid diagnostic tool for the detection of EV in clinical specimens and that the addition of bovine α-casein relieved inhibition of the RT-PCR for 99.7% of clinical specimens. PMID:15243060

Reduced Toxicity With Intensity Modulated Radiation Therapy (IMRT) for Desmoplastic Small Round Cell Tumor (DSRCT): An Update on the Whole Abdominopelvic Radiation Therapy (WAP-RT) Experience

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

Desai, Neil B.; Stein, Nicholas F.; LaQuaglia, Michael P.

2013-01-01

Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximalmore » surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves hematologic toxicity in particular. Although the long-term efficacy of current treatment options remains disappointing, the improved therapeutic index of IMRT may aid in generalizing its use and allowing the addition of novel approaches such as intraperitoneal immunotherapy.« less

TU-G-BRA-03: Predicting Radiation Therapy Induced Ventilation Changes Using 4DCT Jacobian Calculations

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

Patton, T; Du, K; Bayouth, J

2015-06-15

Purpose: Longitudinal changes in lung ventilation following radiation therapy can be mapped using four-dimensional computed tomography(4DCT) and image registration. This study aimed to predict ventilation changes caused by radiation therapy(RT) as a function of pre-RT ventilation and delivered dose. Methods: 4DCT images were acquired before and 3 months after radiation therapy for 13 subjects. Jacobian ventilation maps were calculated from the 4DCT images, warped to a common coordinate system, and a Jacobian ratio map was computed voxel-by-voxel as the ratio of post-RT to pre-RT Jacobian calculations. A leave-one-out method was used to build a response model for each subject: post-RTmore » to pre-RT Jacobian ratio data and dose distributions of 12 subjects were applied to the subject’s pre-RT Jacobian map to predict the post-RT Jacobian. The predicted Jacobian map was compared to the actual post-RT Jacobian map to evaluate efficacy. Within this cohort, 8 subjects had repeat pre-RT scans that were compared as a reference for no ventilation change. Maps were compared using gamma pass rate criteria of 2mm distance-to-agreement and 6% ventilation difference. Gamma pass rates were compared using paired t-tests to determine significant differences. Further analysis masked non-radiation induced changes by excluding voxels below specified dose thresholds. Results: Visual inspection demonstrates the predicted post-RT ventilation map is similar to the actual map in magnitude and distribution. Quantitatively, the percentage of voxels in agreement when excluding voxels receiving below specified doses are: 74%/20Gy, 73%/10Gy, 73%/5Gy, and 71%/0Gy. By comparison, repeat scans produced 73% of voxels within the 6%/2mm criteria. The agreement of the actual post-RT maps with the predicted maps was significantly better than agreement with pre-RT maps (p<0.02). Conclusion: This work validates that significant changes to ventilation post-RT can be predicted. The differences between the predicted and actual outcome are similar to differences between repeat scans with equivalent ventilation. This work was supported by NIH grant CA166703 and a Pilot Grant from University of Iowa Carver College of Medicine.« less

Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small cell lung cancer patients and response to crizotinib.

PubMed

Xu, Chun-Wei; Wang, Wen-Xian; Chen, Yan-Ping; Chen, Yu; Liu, Wei; Zhong, Li-Hua; Chen, Fang-Fang; Zhuang, Wu; Song, Zheng-Bo; Chen, Xiao-Hui; Huang, Yun-Jian; Guan, Yan-Fang; Yi, Xin; Lv, Tang-Feng; Zhu, Wei-Feng; Lu, Jian-Ping; Wang, Xiao-Jiang; Shi, Yi; Lin, Xian-Dong; Chen, Gang; Song, Yong

2018-04-11

ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements. A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent. Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion. VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.

Evaluation of Response to Intervention Practices for Elementary School Reading. NCEE 2016-4000

ERIC Educational Resources Information Center

Balu, Rekha; Zhu, Pei; Doolittle, Fred; Schiller, Ellen; Jenkins, Joseph; Gersten, Russell

2015-01-01

Response to Intervention (RtI) is a framework for collecting and using data to match students to interventions of varying intensity. This study examines the implementation of RtI in Grade 1-3 reading in 13 states during the 2011-12 school year, focusing on 146 schools that were experienced with RtI. Full implementation of the RtI framework in…

Investigating the Decision-Making of Response to Intervention (RtI) Teams within the School Setting

ERIC Educational Resources Information Center

Thur, Scott M.

2015-01-01

The purpose of this study was to measure decision-making influences within RtI teams. The study examined the factors that influence school personnel involved in three areas of RtI: determining which RtI measures and tools teams select and implement (i.e. Measures and Tools), evaluating the data-driven decisions that are made based on the…

Serum Proteome Signature of Radiation Response: Upregulation of Inflammation-Related Factors and Downregulation of Apolipoproteins and Coagulation Factors in Cancer Patients Treated With Radiation Therapy—A Pilot Study

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

Widlak, Piotr, E-mail: widlak@io.gliwice.pl; Jelonek, Karol; Wojakowska, Anna

Purpose: Ionizing radiation affects the proteome of irradiated cells and tissue, yet data concerning changes induced during radiation therapy (RT) in human blood are fragmentary and inconclusive. We aimed to identify features of serum proteome and associated processes involved in response to partial body irradiation during cancer treatment. Methods and Materials: Twenty patients with head and neck squamous cell cancer (HNSCC) and 20 patients with prostate cancer received definitive intensity modulated RT. Blood samples were collected before RT, just after RT, and 1 month after the end of RT. Complete serum proteome was analyzed in individual samples, using a shotgun liquidmore » chromatography-tandem mass spectrometry approach which allowed identification of approximately 450 proteins. Approximately 100 unique proteins were quantified in all samples after exclusion of immunoglobulins, and statistical significance of differences among consecutive samples was assessed. Processes associated with quantified proteins and their functional interactions were predicted using gene ontology tools. Results: RT-induced changes were marked in the HNSCC patient group: 22 upregulated and 33 downregulated proteins were detected in post-RT sera. Most of the changes reversed during follow-up, yet levels of some proteins remained affected 1 month after the end of RT. RT-upregulated proteins were associated with acute phase, inflammatory response, and complement activation. RT-downregulated proteins were associated with transport and metabolism of lipids (plasma apolipoproteins) and blood coagulation. RT-induced changes were much weaker in prostate cancer patients, which corresponded to differences in acute radiation toxicity observed in both groups. Nevertheless, general patterns of RT-induced sera proteome changes were similar in both of the groups of cancer patients. Conclusions: In this pilot study, we proposed to identify a molecular signature of radiation response, based on specific features of serum proteome. The signature included upregulation of factors involved in acute or inflammatory response but also downregulation of plasma apolipoproteins and factors involved in blood coagulation.« less

A Field-Tailored Reverse Transcription Loop-Mediated Isothermal Assay for High Sensitivity Detection of Plasmodium falciparum Infections

PubMed Central

Kemleu, Sylvie; Guelig, Dylan; Eboumbou Moukoko, Carole; Essangui, Estelle; Diesburg, Steven; Mouliom, Abas; Melingui, Bernard; Manga, Jeanne; Donkeu, Christiane; Epote, Annie; Texier, Gaëtan; LaBarre, Paul; Burton, Robert

2016-01-01

Highly sensitive and field deployable molecular diagnostic tools are critically needed for detecting submicroscopic, yet transmissible levels of malaria parasites prevalent in malaria endemic countries worldwide. A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and evaluated in comparison with thick blood smear microscopy, an antigen-based rapid diagnostic test (RDT), and an in-house RT-PCR targeting the same RT-LAMP transcript. The optimized assay detected Plasmodium falciparum infections in as little as 0.25ng of total parasite RNA, and exhibited a detection limit of 0.08 parasites/ μL when tested directly on infected whole blood lysates, or ~0.0008 parasites/ μL when using RNA extracts. Assay positivity was observed as early as eight minutes from initiation of the RT-LAMP and in most cases the reaction was complete before twenty minutes. Clinical evaluation of the assay on 132 suspected malaria cases resulted in a positivity rate of 90% for RT-LAMP using extracted RNA, and 85% when using whole blood lysates. The positivity rates were 70% for P. falciparum-specific RDT, 83% for RT-PCR, and 74% for thick blood smear microscopy (Mean parasite density = 36,986 parasites/ μL). Concordance rates between the developed RT-LAMP and comparator tests were greater than 75%, the lowest being with light microscopy (78%, McNemar’s test: P = 0.0002), and the highest was with RT-PCR (87%, McNemar’s test: P = 0.0523). Compared to reference RT-PCR, assay sensitivity was 90% for RT-LAMP on whole blood, and 96% for RT-LAMP using corresponding RNA extracts. Electricity-free heaters were further developed and evaluated in comparison with a battery-operated isothermal amplification machine for use with the developed test in resource-limited settings. Taken together, the data highlight the benefits of targeting high abundant RNA transcripts in molecular diagnosis, as well as the potential usefulness of the developed RT-LAMP-assay in malaria diagnosis in low to high parasite density settings. PMID:27824866

EL_PSSM-RT: DNA-binding residue prediction by integrating ensemble learning with PSSM Relation Transformation.

PubMed

Zhou, Jiyun; Lu, Qin; Xu, Ruifeng; He, Yulan; Wang, Hongpeng

2017-08-29

Prediction of DNA-binding residue is important for understanding the protein-DNA recognition mechanism. Many computational methods have been proposed for the prediction, but most of them do not consider the relationships of evolutionary information between residues. In this paper, we first propose a novel residue encoding method, referred to as the Position Specific Score Matrix (PSSM) Relation Transformation (PSSM-RT), to encode residues by utilizing the relationships of evolutionary information between residues. PDNA-62 and PDNA-224 are used to evaluate PSSM-RT and two existing PSSM encoding methods by five-fold cross-validation. Performance evaluations indicate that PSSM-RT is more effective than previous methods. This validates the point that the relationship of evolutionary information between residues is indeed useful in DNA-binding residue prediction. An ensemble learning classifier (EL_PSSM-RT) is also proposed by combining ensemble learning model and PSSM-RT to better handle the imbalance between binding and non-binding residues in datasets. EL_PSSM-RT is evaluated by five-fold cross-validation using PDNA-62 and PDNA-224 as well as two independent datasets TS-72 and TS-61. Performance comparisons with existing predictors on the four datasets demonstrate that EL_PSSM-RT is the best-performing method among all the predicting methods with improvement between 0.02-0.07 for MCC, 4.18-21.47% for ST and 0.013-0.131 for AUC. Furthermore, we analyze the importance of the pair-relationships extracted by PSSM-RT and the results validates the usefulness of PSSM-RT for encoding DNA-binding residues. We propose a novel prediction method for the prediction of DNA-binding residue with the inclusion of relationship of evolutionary information and ensemble learning. Performance evaluation shows that the relationship of evolutionary information between residues is indeed useful in DNA-binding residue prediction and ensemble learning can be used to address the data imbalance issue between binding and non-binding residues. A web service of EL_PSSM-RT ( http://hlt.hitsz.edu.cn:8080/PSSM-RT_SVM/ ) is provided for free access to the biological research community.

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy

PubMed Central

Ashton, Jeffrey R.; Castle, Katherine D.; Qi, Yi; Kirsch, David G.; West, Jennifer L.; Badea, Cristian T.

2018-01-01

Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented RT, and how this effect can be used to improve the delivery of nanoparticle chemotherapeutics. Methods: Dual-energy CT was used to quantify the accumulation of both liposomal iodine and AuNPs in tumors following AuNP-augmented RT in a mouse model of primary soft tissue sarcoma. Mice were injected with non-targeted AuNPs, RGD-functionalized AuNPs (vascular targeting), or no AuNPs, after which they were treated with varying doses of RT. The mice were injected with either liposomal iodine (for the imaging study) or liposomal doxorubicin (for the treatment study) 24 hours after RT. Increased tumor liposome accumulation was assessed by dual-energy CT (iodine) or by tracking tumor treatment response (doxorubicin). Results: A significant increase in vascular permeability was observed for all groups after 20 Gy RT, for the targeted and non-targeted AuNP groups after 10 Gy RT, and for the vascular-targeted AuNP group after 5 Gy RT. Combining targeted AuNPs with 5 Gy RT and liposomal doxorubicin led to a significant tumor growth delay (tumor doubling time ~ 8 days) compared to AuNP-augmented RT or chemotherapy alone (tumor doubling time ~3-4 days). Conclusions: The addition of vascular-targeted AuNPs significantly improved the treatment effect of liposomal doxorubicin after RT, consistent with the increased liposome accumulation observed in tumors in the imaging study. Using this approach with a liposomal drug delivery system can increase specific tumor delivery of chemotherapeutics, which has the potential to significantly improve tumor response and reduce the side effects of both RT and chemotherapy. PMID:29556356

Single-Fraction Versus 5-Fraction Radiation Therapy for Metastatic Epidural Spinal Cord Compression in Patients With Limited Survival Prognoses: Results of a Matched-Pair Analysis

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

Rades, Dirk, E-mail: Rades.Dirk@gmx.net; Huttenlocher, Stefan; Šegedin, Barbara

Purpose: This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. Methods and Materials: A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT onmore » motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. Results: Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. Conclusions: There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.« less

Decreased Lung Perfusion After Breast/Chest Wall Irradiation: Quantitative Results From a Prospective Clinical Trial

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

Liss, Adam L., E-mail: adamliss68@gmail.com; Marsh, Robin B.; Kapadia, Nirav S.

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial. Methods and Materials: As part of an institutional review board–approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanningmore » before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy. Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001). Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates.« less

Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients With Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408

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

Krauss, Daniel J., E-mail: dkrauss@beaumont.edu; Hu, Chen; Bahary, Jean-Paul

Purpose: The purpose of this study was to assess the association between positive post-radiation therapy (RT) biopsy results and subsequent clinical outcomes in males with localized prostate cancer. Methods and Materials: Radiation Therapy Oncology Group study 94-08 analyzed 1979 males with prostate cancer, stage T1b-T2b and prostate-specific antigen concentrations of ≤20 ng/dL, to investigate whether 4 months of total androgen suppression (TAS) added to RT improved survival compared to RT alone. Patients randomized to receive TAS received flutamide with luteinizing hormone releasing hormone (LHRH) agonist. According to protocol, patients without evidence of clinical recurrence or initiation of additional endocrine therapy underwent repeatmore » prostate biopsy 2 years after RT completion. Statistical analysis was performed to evaluate the impact of positive post-RT biopsy results on clinical outcomes. Results: A total of 831 patients underwent post-RT biopsy, 398 were treated with RT alone and 433 with RT plus TAS. Patients with positive post-RT biopsy results had higher rates of biochemical failure (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.3-2.1) and distant metastasis (HR = 2.4; 95% CI = 1.3-4.4) and inferior disease-specific survival (HR = 3.8; 95% CI = 1.9-7.5). Positive biopsy results remained predictive of such outcomes after correction for potential confounders such as Gleason score, tumor stage, and TAS administration. Prior TAS therapy did not prevent elevated risk of adverse outcome in the setting of post-RT positive biopsy results. Patients with Gleason score ≥7 with a positive biopsy result additionally had inferior overall survival compared to those with a negative biopsy result (HR = 1.56; 95% CI = 1.04-2.35). Conclusions: Positive post-RT biopsy is associated with increased rates of distant metastases and inferior disease-specific survival in patients treated with definitive RT and was associated with inferior overall survival in patients with high-grade tumors.« less

Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a highly sensitive detection of enterovirus in the stool samples of acute flaccid paralysis cases.

PubMed

Arita, Minetaro; Ling, Hua; Yan, Dongmei; Nishimura, Yorihiro; Yoshida, Hiromu; Wakita, Takaji; Shimizu, Hiroyuki

2009-12-16

In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV) from the stool samples of acute flaccid paralysis (AFP) cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV. A primer set was designed for RT-LAMP to detect enterovirus preferably those with PV-like 5'NTRs of the viral genome. The sensitivity of RT-LAMP system was evaluated with prototype strains of enterovirus. Detection of enterovirus from stool extracts was examined by using RT-LAMP system. We detected at least 400 copies of the viral genomes of PV(Sabin) strains within 90 min by RT-LAMP with the primer set. This RT-LAMP system showed a preference for Human enterovirus species C (HEV-C) strains including PV, but exhibited less sensitivity to the prototype strains of HEV-A and HEV-B (detection limits of 7,400 to 28,000 copies). Stool extracts, from which PV, HEV-C, or HEV-A was isolated in the cell culture system, were mostly positive by RT-LAMP method (positive rates of 15/16 (= 94%), 13/14 (= 93%), and 4/4 (= 100%), respectively). The positive rate of this RT-LAMP system for stool extracts from which HEV-B was isolated was lower than that of HEV-C (positive rate of 11/21 (= 52%)). In the stool samples, which were negative for enterovirus isolation by the cell culture system, we found that two samples were positive for RT-LAMP (positive rates of 2/38 (= 5.3%)). In these samples, enterovirus 96 was identified by sequence analysis utilizing a seminested PCR system. RT-LAMP system developed in this study showed a high sensitivity comparable to that of the cell culture system for the detection of PV, HEV-A, and HEV-C, but less sensitivity to HEV-B. This RT-LAMP system would be useful for the direct detection of enterovirus from the stool extracts.

Improved Survival With Radiation Therapy in Stage I-II Primary Mediastinal B Cell Lymphoma: A Surveillance, Epidemiology, and End Results Database Analysis

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

Jackson, Matthew W., E-mail: matthew.jackson@ucdenver.edu; Rusthoven, Chad G.; Jones, Bernard L.

Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes. Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overallmore » survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed. Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010. Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease.« less

Interval Between Hysterectomy and Start of Radiation Treatment Is Predictive of Recurrence in Patients With Endometrial Carcinoma

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

Cattaneo, Richard; Hanna, Rabbie K.; Jacobsen, Gordon

Purpose: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with endometrial carcinoma. We analyzed the impact of the time interval between hysterectomy and RT initiation in patients with endometrial carcinoma. Methods and Materials: In this institutional review board-approved study, we identified 308 patients with endometrial carcinoma who received adjuvant RT after hysterectomy. All patients had undergone hysterectomy, oophorectomy, and pelvic and para-aortic lymph node evaluation from 1988 to 2010. Patients' demographics, pathologic features, and treatments were compared. The time interval between hysterectomy and the start of RT was calculated. The effects of time interval onmore » recurrence-free (RFS), disease-specific (DSS), and overall survival (OS) were calculated. Following univariate analysis, multivariate modeling was performed. Results: The median age and follow-up for the study cohort was 65 years and 72 months, respectively. Eighty-five percent of the patients had endometrioid carcinoma. RT was delivered with high-dose-rate brachytherapy alone (29%), pelvic RT alone (20%), or both (51%). Median time interval to start RT was 42 days (range, 21-130 days). A total of 269 patients (74%) started their RT <9 weeks after undergoing hysterectomy (group 1) and 26% started ≥9 weeks after surgery (group 2). There were a total of 43 recurrences. Tumor recurrence was significantly associated with treatment delay of ≥9 weeks, with 5-year RFS of 90% for group 1 compared to only 39% for group 2 (P<.001). On multivariate analysis, RT delay of ≥9 weeks (P<.001), presence of lymphovascular space involvement (P=.001), and higher International Federation of Gynecology and Obstetrics grade (P=.012) were independent predictors of recurrence. In addition, RT delay of ≥9 weeks was an independent significant predictor for worse DSS and OS (P=.001 and P=.01, respectively). Conclusions: Delay in administering adjuvant RT after hysterectomy was associated with worse survival endpoints. Our data suggest that shorter time interval between hysterectomy and start of RT may be beneficial.« less

Detection of Helicobacter pylori by Real-Time PCR for 16s rRNA in Stools of NonInfected Healthy Children, Using ELISA Antigen Stool Test as the Gold Standard.

PubMed

George, Sergio; Mamani, Nora; Lucero, Yalda; Torres, Juan Pablo; Farfán, Mauricio; Lagomarcino, Anne J; Orellana, Andrea; O'Ryan, Miguel

2016-12-01

We previously detected Helicobacter pylori infection by stool antigen ELISA assay in 33-41% of asymptomatic Chilean children between 2-3 years of age, of which 11-20% had a transient infection and 21-22% a persistent infection. A total of 88% of ELISA-positive samples were also rtPCR positive, while 37/133 (33%) of ELISA-negative stool samples were rtPCR positive. The significance of a ELISA-negative/rtPCR-positive sample requires clarification. We aimed to determine whether rtPCR is able to detect persistent infections not detected by ELISA. We selected 36 children with an ELISA-negative/rtPCR-positive stool sample, of which 25 were never H. pylori infected according to ELISA, and 11 had a transient infection with an ELISA-positive sample before or after the discordant sample. At least two additional consecutive ELISA-negative samples per child were tested in duplicate by rtPCR for the 16s rRNA gene. A total of 14 of 78 (17.9%) rtPCR reactions were positive, but only 4/78 (5.1%) were positive in both duplicates, representing a total of 3/36 (8.3%) children with an additional rtPCR-positive sample, only one of whom was persistently negative by ELISA. One child with a transient infection had two positive rtPCR reactions despite negative ELISA samples. In H. pylori noninfected or transiently infected children, as determined by stool ELISA, additional ELISA-negative/rtPCR-positive stool samples were found in 8.3% of children, but a possible persistent infection was only identified in 2.7% of children. Thus, the characterization of infection dynamics in children is not being misrepresented by application of stool ELISA. Furthermore, rtPCR does not significantly improve dynamic characterization. © 2016 John Wiley & Sons Ltd.

A tumor-promoting mechanism mediated by retrotransposon-encoded reverse transcriptase is active in human transformed cell lines

PubMed Central

Sciamanna, Ilaria; Gualtieri, Alberto; Cossetti, Cristina; Osimo, Emanuele Felice; Ferracin, Manuela; Macchia, Gianfranco; Aricò, Eleonora; Prosseda, Gianni; Vitullo, Patrizia; Misteli, Tom; Spadafora, Corrado

2013-01-01

LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode a reverse transcriptase (RT) activity required for their own retrotranpsosition as well as that of non-autonomous Alu elements. LINE-1 are poorly expressed in normal cells and abundantly in cancer cells. Decreasing RT activity in cancer cells, by either LINE-1-specific RNA interference, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Here we have investigated how RT exerts these global regulatory functions. We report that the RT inhibitor efavirenz (EFV) selectively downregulates proliferation of transformed cell lines, while exerting only mild effects on non-transformed cells; this differential sensitivity matches a differential RT abundance, which is high in the former and undetectable in the latter. Using CsCl density gradients, we selectively identify Alu and LINE-1 containing DNA:RNA hybrid molecules in cancer but not in normal cells. Remarkably, hybrid molecules fail to form in tumor cells treated with EFV under the same conditions that repress proliferation and induce the reprogramming of expression profiles of coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alu sequences. The results suggest that LINE-1-encoded RT governs the balance between single-stranded and double-stranded RNA production. In cancer cells the abundant RT reverse-transcribes retroelement-derived mRNAs forming RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the ‘normal’ small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives a previously unrecognized mechanism crucial to the transformed state in tumor cells. PMID:24345856

Inflammatory biomarker C-reactive protein and radiotherapy-induced early adverse skin reactions in patients with breast cancer.

PubMed

Rodriguez-Gil, Jorge L; Takita, Cristiane; Wright, Jean; Reis, Isildinha M; Zhao, Wei; Lally, Brian E; Hu, Jennifer J

2014-09-01

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Postsurgery adjuvant radiotherapy (RT) significantly reduced the local recurrence rate. However, many patients develop early adverse skin reactions (EASR) that impact quality of life and treatment outcomes. We evaluated an inflammatory biomarker, C-reactive protein (CRP), in predicting RT-induced EASRs in 159 patients with breast cancer undergoing RT. In each patient, we measured pre- and post-RT plasma CRP levels using a highly sensitive ELISA CRP assay. RT-induced EASRs were assessed at weeks 3 and 6 using the National Cancer Institute Common Toxicity Criteria (v3.0). Associations between EASRs and CRP levels were assessed using logistic regression models after adjusting for potential confounders. RT-induced grade 2+ EASRs were observed in 8 (5%) and 80 (50%) patients at weeks 3 and 6 (end of RT), respectively. At the end of RT, a significantly higher proportion of African Americans developed grade 3 EASRs (13.8% vs. 2.3% in others); grade 2+ EASRs were significantly associated with: change of CRP > 1 mg/L [odds ratio (OR), 2.51; 95% confidence interval (CI), 1.06-5.95; P = 0.04], obesity (OR, 2.08; 95% CI, 1.03-4.21; P = 0.04), or combined both factors (OR, 5.21; 95% CI, 1.77-15.38; P = 0.003). This is the first study to demonstrate that an inflammatory biomarker CRP is associated with RT-induced EASRs, particularly combined with obesity. Future larger studies are warranted to validate our findings and facilitate the discovery and development of anti-inflammatory agents to protect normal tissue from RT-induced adverse effects and improve quality of life in patients with breast cancer undergoing RT. ©2014 American Association for Cancer Research.

Use of short-term real-time continuous glucose monitoring in type 1 diabetes patients on continuous intraperitoneal insulin infusion: a feasibility study.

PubMed

Logtenberg, Susan J J; Kleefstra, Nanne; Groenier, Klaas H; Gans, Rijk O B; Bilo, Henk J G

2009-05-01

In diabetes, strict glycemic control reduces risk of complications. One mode of therapy is continuous intraperitoneal insulin infusion (CIPII). With CIPII, like all intensified treatment strategies, frequent assessment of glucose levels is mandatory. Real-time (RT)-continuous glucose monitoring (CGM) gives RT information without the need for multiple invasive measurements. In theory, CIPII combined with RT-CGM could provide near normal glucose profiles. The objective of this study is to investigate effectiveness and safety of RT-CGM in patients treated with intraperitoneal insulin through an implanted pump. In an open-label, crossover, randomized study, effects of 6-day open RT-CGM use were studied in 12 type 1 diabetes patients on CIPII, with blinded RT-CGM used as a control. Primary outcome was time in euglycemia. Secondary outcomes included time in other glucose ranges, incidence of adverse events, and patient satisfaction. Agreement of self-measurement of blood glucose (SMBG) and RT-CGM measurements was assessed. Median time spent in euglycemia was 68.2% (55.9-72.3%) with open RT-CGM and 64.9% (55.3-71.2%) with blinded RT-CGM (P = 0.25). Time spent in other glucose ranges did not differ (P > 0.05). There were no serious adverse events. Patient satisfaction was good. Median relative absolute difference of SMBG and RT-CGM values was 13.9%. Bland-Altman analysis showed a mean difference of -0.31 mg/dL with lower and upper limits of agreement of -77.0 and +76.4 mg/dL, respectively. Short-term use of RT-CGM, although safe and with good patient satisfaction, does not result in more time spent in euglycemia, nor does it change time spent in other glucose ranges in our population of type 1 diabetes patients receiving CIPII.

Use of External Beam Radiotherapy Is Associated With Reduced Incidence of Second Primary Head and Neck Cancer: A SEER Database Analysis

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

Rusthoven, Kyle; Chen Changhu; Raben, David

2008-05-01

Purpose: Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA). Methods and Materials: The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined andmore » compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA. Results: Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91). Conclusion: For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.« less

The Effect of Two Different Concurrent Training Programs on Strength and Power Gains in Highly-Trained Individuals.

PubMed

Petré, Henrik; Löfving, Pontus; Psilander, Niklas

2018-06-01

The effects of concurrent strength and endurance training have been well studied in untrained and moderately-trained individuals. However, studies examining these effects in individuals with a long history of resistance training (RT) are lacking. Additionally, few studies have examined how strength and power are affected when different types of endurance training are added to an RT protocol. The purpose of the present study was to compare the effects of concurrent training incorporating either low-volume, high-intensity interval training (HIIT, 8-24 Tabata intervals at ~150% of VO 2max ) or high-volume, medium-intensity continuous endurance training (CT, 40-80 min at 70% of VO 2max ), on the strength and power of highly-trained individuals. Sixteen highly-trained ice-hockey and rugby players were divided into two groups that underwent either CT (n = 8) or HIIT (n = 8) in parallel with RT (2-6 sets of heavy parallel squats, > 80% of 1RM) during a 6-week period (3 sessions/wk). Parallel squat performance improved after both RT + CT and RT + HIIT (12 ± 8% and 14 ± 10% respectively, p < 0.01), with no difference between the groups. However, aerobic power (VO 2max ) only improved after RT + HIIT (4 ± 3%, p < 0.01). We conclude that strength gains can be obtained after both RT + CT and RT + HIIT in athletes with a prior history of RT. This indicates that the volume and/or intensity of the endurance training does not influence the magnitude of strength improvements during short periods of concurrent training, at least for highly-trained individuals when the endurance training is performed after RT. However, since VO 2max improved only after RT + HIIT and this is a time efficient protocol, we recommend this type of concurrent endurance training.

Rapid and Sensitive Salmonella Typhi Detection in Blood and Fecal Samples Using Reverse Transcription Loop-Mediated Isothermal Amplification.

PubMed

Fan, Fenxia; Yan, Meiying; Du, Pengcheng; Chen, Chen; Kan, Biao

2015-09-01

Typhoid fever caused by Salmonella enterica serovar Typhi remains a significant public health problem in developing countries. Although the main method for diagnosing typhoid fever is blood culture, the test is time consuming and not always able to detect infections. Thus, it is very difficult to distinguish typhoid from other infections in patients with nonspecific symptoms. A simple and sensitive laboratory detection method remains necessary. The purpose of this study is to establish and evaluate a rapid and sensitive reverse transcription-based loop-mediated isothermal amplification (RT-LAMP) method to detect Salmonella Typhi infection. In this study, a new specific gene marker, STY1607, was selected to develop a STY1607-RT-LAMP assay; this is the first report of specific RT-LAMP detection assay for typhoid. Human-simulated and clinical blood/stool samples were used to evaluate the performance of STY1607-RT-LAMP for RNA detection; this method was compared with STY1607-LAMP, reverse transcription real-time polymerase chain reaction (rRT-PCR), and bacterial culture methods for Salmonella Typhi detection. Using mRNA as the template, STY1607-RT-LAMP exhibited 50-fold greater sensitivity than STY1607-LAMP for DNA detection. The STY1607-RT-LAMP detection limit is 3 colony-forming units (CFU)/mL for both the pure Salmonella Typhi samples and Salmonella Typhi-simulated blood samples and was 30 CFU/g for the simulated stool samples, all of which were 10-fold more sensitive than the rRT-PCR method. RT-LAMP exhibited improved Salmonella Typhi detection sensitivity compared to culture methods and to rRT-PCR of clinical blood and stool specimens from suspected typhoid fever patients. Because it can be performed without sophisticated equipment or skilled personnel, RT-LAMP is a valuable tool for clinical laboratories in developing countries. This method can be applied in the clinical diagnosis and care of typhoid fever patients as well as for a quick public health response.

Whole-body hybrid imaging concept for the integration of PET/MR into radiation therapy treatment planning.

PubMed

Paulus, Daniel H; Oehmigen, Mark; Grüneisen, Johannes; Umutlu, Lale; Quick, Harald H

2016-05-07

Modern radiation therapy (RT) treatment planning is based on multimodality imaging. With the recent availability of whole-body PET/MR hybrid imaging new opportunities arise to improve target volume delineation in RT treatment planning. This, however, requires dedicated RT equipment for reproducible patient positioning on the PET/MR system, which has to be compatible with MR and PET imaging. A prototype flat RT table overlay, radiofrequency (RF) coil holders for head imaging, and RF body bridges for body imaging were developed and tested towards PET/MR system integration. Attenuation correction (AC) of all individual RT components was performed by generating 3D CT-based template models. A custom-built program for μ-map generation assembles all AC templates depending on the presence and position of each RT component. All RT devices were evaluated in phantom experiments with regards to MR and PET imaging compatibility, attenuation correction, PET quantification, and position accuracy. The entire RT setup was then evaluated in a first PET/MR patient study on five patients at different body regions. All tested devices are PET/MR compatible and do not produce visible artifacts or disturb image quality. The RT components showed a repositioning accuracy of better than 2 mm. Photon attenuation of  -11.8% in the top part of the phantom was observable, which was reduced to  -1.7% with AC using the μ-map generator. Active lesions of 3 subjects were evaluated in terms of SUVmean and an underestimation of  -10.0% and  -2.4% was calculated without and with AC of the RF body bridges, respectively. The new dedicated RT equipment for hybrid PET/MR imaging enables acquisitions in all body regions. It is compatible with PET/MR imaging and all hardware components can be corrected in hardware AC by using the suggested μ-map generator. These developments provide the technical and methodological basis for integration of PET/MR hybrid imaging into RT planning.

Template-independent DNA synthesis activity associated with the reverse transcriptase of the long terminal repeat retrotransposon Tf1.

PubMed

Oz-Gleenberg, Iris; Herzig, Eytan; Hizi, Amnon

2012-01-01

Reverse transcriptases (RTs) possess a non-templated addition (NTA) activity while synthesizing DNA with blunt-ended DNA primer/templates. Interestingly, the RT of the long terminal repeat retrotransposon Tf1 has an NTA activity that is substantially higher than that of HIV-1 or murine leukemia virus RTs. By performing steady state kinetics, we found that the differences between the NTA activities of Tf1 and HIV-1 RTs can be explained by the substantially lower K(M) value for the incoming dNTP of Tf1 RT (while the differences between the apparent k(cat) values of these two RTs are relatively small). Furthermore, the K(M) values, calculated for both RTs with the same dNTP, are much lower for the template-dependent synthesis (TDS) than those of NTA. However, TDS of HIV-1 RT is higher than that of Tf1 RT. The overall relative order of the apparent k(cat)/K(M) values for dATP is: HIV-1 RT (TDS) > Tf1 RT (TDS) > Tf1 RT (NTA) > HIV-1 RT (NTA). Under the employed conditions, Tf1 RT can add up to seven nucleotides to the blunt-ended substrate, while the other RTs add mostly a single nucleotide. The NTA activity of Tf1 RT is restricted to DNA primers. Furthermore, the NTA activity of Tf1 and HIV-1 RTs is suppressed by ATP, as it competes with the incoming dATP (although ATP is not incorporated by the NTA activity of the RTs). The unusually high NTA activity of Tf1 RT can explain why, after completing cDNA synthesis, the in vivo generated Tf1 cDNA has relatively long extra sequences beyond the highly conserved CA at its 3'-ends. © 2011 The Authors Journal compilation © 2011 FEBS.

Rapid detection and differentiation of dengue virus serotypes by NS1 specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay in patients presenting to a tertiary care hospital in Hyderabad, India.

PubMed

Neeraja, M; Lakshmi, V; Lavanya, Vanjari; Priyanka, E N; Parida, M M; Dash, P K; Sharma, Shashi; Rao, P V Lakshmana; Reddy, Gopal

2015-01-01

Early and rapid detection of dengue virus (DENV) infection during the acute phase of illness is crucial for proper patient management and prevention of the spread of the infection. In the present study, the standardization and validation of a one step, four tube reverse transcription loop-mediated isothermal amplification assay (RT-LAMP) for rapid detection and serotyping of the DENV targeting NS1 gene using the Genie® II flourometer was carried out. The performance of the RT-LAMP was compared to RT-PCR, CDC 1-4 Real time PCR and the NS1 antigen ELISA, IgM and IgG anti DENV antibodies. Acute DENV infection was confirmed in 250/300 patients suspected clinically of DENV infection. RT- LAMP and CDC 1-4 Real time PCR assay was positive in 148/250 patients, while 92/250 patients were positive for anti- Dengue IgM and IgG antibodies. The RT-LAMP assay and the CDC real-time RT-PCR assay showed high concordance (k=1.0). The detection rate of acute DENV infection improved to 96% (240/250) when the results of RT-LAMP were combined with NS1 Ag, IgM and IgG ELISA. The RT-LAMP had a detection limit of 100 copies for DEN-1 and DEN-2, 10 copies for DEN-3 and DEN-4 compared to 1000 copies for DEN-1 and DEN-2, 100 copies for DEN-3 and DEN-4 by the conventional RT-PCR. The assay showed 100% specificity. The RT-LAMP assay developed in this study has potential use for early clinical diagnosis, serotyping and surveillance of DENV infection in endemic countries such as India. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of simulated acid rain on soil respiration and its components in a subtropical mixed conifer and broadleaf forest in southern China.

PubMed

Liang, Guohua; Hui, Dafeng; Wu, Xiaoying; Wu, Jianping; Liu, Juxiu; Zhou, Guoyi; Zhang, Deqiang

2016-02-01

Soil respiration is a major pathway in the global carbon cycle and its response to environmental changes is an increasing concern. Here we explored how total soil respiration (RT) and its components respond to elevated acid rain in a mixed conifer and broadleaf forest, one of the major forest types in southern China. RT was measured twice a month in the first year under four treatment levels of simulated acid rain (SAR: CK, the local lake water, pH 4.7; T1, water pH 4.0; T2, water pH 3.25; and T3, water pH 2.5), and in the second year, RT, litter-free soil respiration (RS), and litter respiration (RL) were measured simultaneously. The results indicated that the mean rate of RT was 2.84 ± 0.20 μmol CO2 m(-2) s(-1) in the CK plots, and RS and RL contributed 60.7% and 39.3% to RT, respectively. SAR marginally reduced (P = 0.08) RT in the first year, but significantly reduced RT and its two components in the second year (P < 0.05). The negative effects were correlated with the decrease in soil microbial biomass and fine root biomass due to soil acidification under the SAR. The temperature coefficients (Q10) of RT and its two components generally decreased with increasing levels of the SAR, but only the decrease of RT and RL was significant (P < 0.05). In addition, the contribution of RL to RT decreased significantly under the SAR, indicating that RL was more sensitive to the SAR than RS. In the context of elevated acid rain, the decline trend of RT in the forests in southern China appears to be attributable to the decline of soil respiration in the litter layer.

Associations between adjuvant radiotherapy and different causes of death in a German breast cancer cohort.

PubMed

Obi, Nadia; Eulenburg, Christine; Seibold, Petra; Eilber, Ursula; Thöne, Kathrin; Behrens, Sabine; Chang-Claude, Jenny; Flesch-Janys, Dieter

2018-04-01

Studies of cohorts of breast cancer (BC) patients diagnosed before 1990 showed radiotherapy (RT) to be associated with increased cardiovascular (CVD) and lung cancer mortality many years after diagnosis. In the late 1990s, improvements in RT planning techniques reduced radiation doses to normal tissues. Recent studies did not consistently report higher RT-related mortality for CVD and second cancers. Aim of the study was to analyze specific causes of death after 3D-conformal RT in a recent BC cohort. Stage I-III BC patients diagnosed 2001-2005 and enrolled in the population based MARIEplus study were followed-up for 11.9 years (median). Associations between adjuvant RT and cause-specific mortality were analyzed by using competing risks models, yielding subdistribution hazard ratios (SHR) for RT directly related to cumulative incidences. Models were adjusted for differences in baseline characteristics applying inverse-probability-of-treatment-weighting (IPTW). Of the 2951 patients, 2439 (83.0%) received RT. No significant association of RT with lung cancer mortality (SHR IPTW 0.88, 0.35-2.12), other cancer mortality (SHR IPTW 1.04, 95% CI 0.62-1.73) or cardiac mortality was observed (SHR IPTW 1.57, 0.75-3.29). Mortality from lung and other diseases were significantly lower in irradiated women (SHR IPTW 0.39, 95% CI 0.17-0.90 and SHR IPTW 0.58, 95% CI 0.34-0.97, respectively). In line with recent studies, 3D-conformal RT did not significantly increase mortality from non-BC causes in the German MARIEplus cohort. Since long-term data are still sparse and event rates low in BC-cohorts, who received modern RT, investigation of possible late RT effects on mortality beyond 14 years of follow-up is warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

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

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Garg, Madhur K.; Aparo, Santiago

2013-06-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated frommore » survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy.« less

Treatment Guidelines for Preoperative Radiation Therapy for Retroperitoneal Sarcoma: Preliminary Consensus of an International Expert Panel

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

Baldini, Elizabeth H., E-mail: ebaldini@partners.org; Wang, Dian; Haas, Rick L.M.

Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematicmore » review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available. Results: Treatment guidelines for preoperative RT for RPS are presented. Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity.« less

Telephone interventions for adherence to colpocytological examination.

PubMed

Lima, Thais Marques; Nicolau, Ana Izabel Oliveira; Carvalho, Francisco Herlânio Costa; Vasconcelos, Camila Teixeira Moreira; Aquino, Priscila de Souza; Pinheiro, Ana Karina Bezerra

2017-02-06

to test the effects of behavioral and educational intervention by telephone on adherence of women with inappropriate periodicity to colpocytological examination. quasi-experimental study with a sample of 524 women, selected with the following inclusion criteria: be aged between 25 and 64 years, have initiated sexual activity, have inappropriate periodicity of examination and have mobile or landline phone. The women were divided into two groups for application of behavioral and educational intervention by telephone. It was used an intervention script according to the principles of Motivational Interviewing. on comparing the results before and after the behavioral and educational interventions, it was found that there was a statistically significant change (p = 0.0283) with increase of knowledge of women who participated in the educational intervention. There was no change in the attitude of women of any of the groups and there was an increase of adherence to colpocytological examination in both groups (p < 0.0001), with greater adherence of women participating in the behavioral group (66.8%). the behavioral and educational interventions by phone were effective in the adherence of women to colpocytological examination, representing important strategies for permanent health education and promotion of care for the prevention of cervical cancer. testar os efeitos de intervenção comportamental e educativa por telefone na adesão das mulheres com periodicidade inadequada ao exame colpocitológico. estudo quase-experimental, com amostra constituída por 524 mulheres selecionadas conforme os critérios de inclusão: estar na faixa etária entre 25 e 64 anos, ter iniciado atividade sexual, estar com a periodicidade do exame inadequada e possuir telefone móvel ou fixo. As mulheres foram divididas em dois grupos para aplicação da intervenção comportamental e educativa por telefone. Utilizou-se um roteiro de intervenção segundo os preceitos da Entrevista Motivacional. ao comparar antes e depois das intervenções comportamental e educativa constatou-se que houve uma mudança estatisticamente significativa (p = 0,0283) no aumento do conhecimento das mulheres que participaram da intervenção educativa; não houve mudança comprovada na atitude das mulheres de nenhum dos grupos e houve um aumento da adesão ao exame colpocitológico nos dois grupos (p < 0,0001), com maior adesão das mulheres que participaram do grupo comportamental (66,8%). as intervenções comportamentais e educativas por telefone foram eficazes na adesão das mulheres ao exame colpocitológico, representando estratégias importantes para educação permanente em saúde, promovendo a atenção para a prevenção do câncer cérvico-uterino. comprobar los efectos de intervención comportamental y educativa por teléfono en la adhesión de las mujeres, con periodicidad inadecuada, al examen de citología vaginal. estudio casi experimental, con muestra constituida por 524 mujeres seleccionadas conforme a los siguientes criterios de inclusión: estar en el intervalo etario entre 25 y 64 años, haber iniciado actividad sexual, estar con la periodicidad del examen inadecuada y poseer teléfono móvil o fijo. Las mujeres fueron divididas en dos grupos para aplicación de la intervención comportamental y educativa por teléfono. Se utilizó una guía de intervención según los preceptos de la Entrevista Motivacional. al comparar antes y después de la intervención comportamental y educativa se constató que hubo un cambio estadísticamente significativo (p = 0,0283) en el aumento del conocimiento de las mujeres que participaron de la intervención educativa; no hubo cambio comprobado en la actitud de las mujeres de ninguno de los grupos y hubo un aumento de la adhesión al examen de citología vaginal en los dos grupos (p < 0,0001), con mayor adhesión de las mujeres que participaron del grupo comportamental (66,8%). las intervenciones comportamentales y educativas por teléfono fueron eficaces en obtener la adhesión de las mujeres al examen de citología vaginal, representando estrategias importantes para una educación permanente en salud y promoviendo la atención para la prevención del cáncer del cuello uterino.

Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial

PubMed Central

Jagsi, Reshma; Chadha, Manjeet; Moni, Janaki; Ballman, Karla; Laurie, Fran; Buchholz, Thomas A.; Giuliano, Armando; Haffty, Bruce G.

2014-01-01

Purpose ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. Methods We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Results Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Conclusion Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone. PMID:25135994

Effects of Resistance Training in Youth Athletes on Muscular Fitness and Athletic Performance: A Conceptual Model for Long-Term Athlete Development

PubMed Central

Granacher, Urs; Lesinski, Melanie; Büsch, Dirk; Muehlbauer, Thomas; Prieske, Olaf; Puta, Christian; Gollhofer, Albert; Behm, David G.

2016-01-01

During the stages of long-term athlete development (LTAD), resistance training (RT) is an important means for (i) stimulating athletic development, (ii) tolerating the demands of long-term training and competition, and (iii) inducing long-term health promoting effects that are robust over time and track into adulthood. However, there is a gap in the literature with regards to optimal RT methods during LTAD and how RT is linked to biological age. Thus, the aims of this scoping review were (i) to describe and discuss the effects of RT on muscular fitness and athletic performance in youth athletes, (ii) to introduce a conceptual model on how to appropriately implement different types of RT within LTAD stages, and (iii) to identify research gaps from the existing literature by deducing implications for future research. In general, RT produced small-to-moderate effects on muscular fitness and athletic performance in youth athletes with muscular strength showing the largest improvement. Free weight, complex, and plyometric training appear to be well-suited to improve muscular fitness and athletic performance. In addition, balance training appears to be an important preparatory (facilitating) training program during all stages of LTAD but particularly during the early stages. As youth athletes become more mature, specificity, and intensity of RT methods increase. This scoping review identified research gaps that are summarized in the following and that should be addressed in future studies: (i) to elucidate the influence of gender and biological age on the adaptive potential following RT in youth athletes (especially in females), (ii) to describe RT protocols in more detail (i.e., always report stress and strain-based parameters), and (iii) to examine neuromuscular and tendomuscular adaptations following RT in youth athletes. PMID:27242538

Role of clinical and laboratory parameters for treatment choice in patients with inherited FVII deficiency undergoing surgical procedures: evidence from the STER registry.

PubMed

Di Minno, Matteo N D; Napolitano, Mariasanta; Dolce, Alberto; Mariani, Guglielmo

2018-02-01

Perioperative bleeding is a major concern in patients with factor VII (FVII) deficiency. Evaluating data of 95 FVII-deficient patients undergoing 110 surgical procedures (61 major, 49 minor), we assessed the impact of type of surgery, bleeding phenotype and FVII coagulant activity (FVII:C) levels on perioperative replacement therapy (RT). Compared to those with higher FVII:C levels, patients with <3% FVII:C received a higher number of RT doses (8 vs. 2, P = 0·003) for a longer RT duration (3 days vs. 1 day, P = 0·001), with no difference in RT dose. Similarly, patients with a history of major bleeds received a higher number of RT doses (8·5 vs. 2-3, P = 0·013) for a longer RT duration (2 days vs. 1 day, P = 0·005) as compared to those with a history of minor bleeds or to asymptomatic patients. No difference in RT was found among major and minor surgical procedures. Overall, multivariate analysis showed that history of major bleeding was the only independent predictor of number of RT doses (β = 0·352, P = 0·001) and RT duration (β = 0·405, P = 0·018). Overall, a ≈20 μg/kg perioperative RT was efficacious in 95·5% of cases. The infusion should be repeated ≈8 times in high-risk subsets (i.e. patients with a history of major bleeding). © 2017 John Wiley & Sons Ltd.

SCAR Radiologic Technologist Survey: analysis of technologist workforce and staffing.

PubMed

Reiner, Bruce; Siegel, Eliot; Carrino, John A; McElveny, Ceela

2002-09-01

One of the greatest dilemmas facing medical imaging departments today is the worsening personnel crisis in the radiologic technologist (RT) workforce. As the volume and complexity of medical imaging studies continues to increase, an unprecedented imbalance exists between RT supply and demand. A number of etiologic factors have been postulated to contribute to this RT shortage including decreasing morale, perceived inadequacies in compensation, decreasing number of training programs, and limitations in the career ladder. Previous studies have cited improved technologist productivity as imaging departments successfully transition from film-based to filmless operation. This study was undertaken to address the impact of digital technologies (information systems, PACS, digital radiography) on technologist productivity, in an attempt to determine whether these technologies can be used to positively affect the existing RT workforce imbalance. A total of 112 facilities participated in this nationwide study, with representation of imaging providers that paralleled the demographic profile of the marketplace as a whole. Survey results indicate the existing RT staffing shortage is greatest within academic and rural-based hospitals and is most severe in the area of general radiography, which accounts for 65-70% of imaging department volumes. For general radiography alone, respondents report an average shortage of 2 RT full-time equivalents (FTE's) per institution, when comparing the number of budgeted RT FTE's versus the actual number of RT FTE's. Preliminary results indicate that at this time, RT staffing shortages are not affected by the presence or absence of digital information technologies. Additional research is planned through a five-year longitudinal data collection, to better delineate the complex relationship that exists between implementation of digital technologies and RT staffing.

A DICOM-RT radiation oncology ePR with decision support utilizing a quantified knowledge base from historical data

NASA Astrophysics Data System (ADS)

Documet, Jorge R.; Liu, Brent; Le, Anh; Law, Maria

2008-03-01

During the last 2 years we have been working on developing a DICOM-RT (Radiation Therapy) ePR (Electronic Patient Record) with decision support that will allow physicists and radiation oncologists during their decision-making process. This ePR allows offline treatment dose calculations and plan evaluation, while at the same time it compares and quantifies treatment planning algorithms using DICOM-RT objects. The ePR framework permits the addition of visualization, processing, and analysis tools, which combined with the core functionality of reporting, importing and exporting of medical studies, creates a very powerful application that can improve the efficiency while planning cancer treatments. Usually a Radiation Oncology department will have disparate and complex data generated by the RT modalities as well as data scattered in RT Information/Management systems, Record & Verify systems, and Treatment Planning Systems (TPS) which can compromise the efficiency of the clinical workflow since the data crucial for a clinical decision may be time-consuming to retrieve, temporarily missing, or even lost. To address these shortcomings, the ACR-NEMA Standards Committee extended its DICOM (Digital Imaging & Communications in Medicine) standard from Radiology to RT by ratifying seven DICOM RT objects starting in 1997 [1,2]. However, they are not broadly used yet by the RT community in daily clinical operations. In the past, the research focus of an RT department has primarily been developing new protocols and devices to improve treatment process and outcomes of cancer patients with minimal effort dedicated to integration of imaging and information systems. Our attempt is to show a proof-of-concept that a DICOM-RT ePR system can be developed as a foundation to perform medical imaging informatics research in developing decision-support tools and knowledge base for future data mining applications.

Statistical models for incorporating data from routine HIV testing of pregnant women at antenatal clinics into HIV/AIDS epidemic estimates.

PubMed

Sheng, Ben; Marsh, Kimberly; Slavkovic, Aleksandra B; Gregson, Simon; Eaton, Jeffrey W; Bao, Le

2017-04-01

HIV prevalence data collected from routine HIV testing of pregnant women at antenatal clinics (ANC-RT) are potentially available from all facilities that offer testing services to pregnant women and can be used to improve estimates of national and subnational HIV prevalence trends. We develop methods to incorporate these new data source into the Joint United Nations Programme on AIDS Estimation and Projection Package in Spectrum 2017. We develop a new statistical model for incorporating ANC-RT HIV prevalence data, aggregated either to the health facility level (site-level) or regionally (census-level), to estimate HIV prevalence alongside existing sources of HIV prevalence data from ANC unlinked anonymous testing (ANC-UAT) and household-based national population surveys. Synthetic data are generated to understand how the availability of ANC-RT data affects the accuracy of various parameter estimates. We estimate HIV prevalence and additional parameters using both ANC-RT and other existing data. Fitting HIV prevalence using synthetic data generally gives precise estimates of the underlying trend and other parameters. More years of ANC-RT data should improve prevalence estimates. More ANC-RT sites and continuation with existing ANC-UAT sites may improve the estimate of calibration between ANC-UAT and ANC-RT sites. We have proposed methods to incorporate ANC-RT data into Spectrum to obtain more precise estimates of prevalence and other measures of the epidemic. Many assumptions about the accuracy, consistency, and representativeness of ANC-RT prevalence underlie the use of these data for monitoring HIV epidemic trends and should be tested as more data become available from national ANC-RT programs.

Statistical Models for Incorporating Data from Routine HIV Testing of Pregnant Women at Antenatal Clinics into HIV/AIDS Epidemic Estimates

PubMed Central

Sheng, Ben; Marsh, Kimberly; Slavkovic, Aleksandra B.; Gregson, Simon; Eaton, Jeffrey W.; Bao, Le

2017-01-01

Objective HIV prevalence data collected from routine HIV testing of pregnant women at antenatal clinics (ANC-RT) are potentially available from all facilities that offer testing services to pregnant women, and can be used to improve estimates of national and sub-national HIV prevalence trends. We develop methods to incorporate this new data source into the UNAIDS Estimation and Projection Package (EPP) in Spectrum 2017. Methods We develop a new statistical model for incorporating ANC-RT HIV prevalence data, aggregated either to the health facility level (‘site-level’) or regionally (‘census-level’), to estimate HIV prevalence alongside existing sources of HIV prevalence data from ANC unlinked anonymous testing (ANC-UAT) and household-based national population surveys. Synthetic data are generated to understand how the availability of ANC-RT data affects the accuracy of various parameter estimates. Results We estimate HIV prevalence and additional parameters using both ANC-RT and other existing data. Fitting HIV prevalence using synthetic data generally gives precise estimates of the underlying trend and other parameters. More years of ANC-RT data should improve prevalence estimates. More ANC-RT sites and continuation with existing ANC-UAT sites may improve the estimate of calibration between ANC-UAT and ANC-RT sites. Conclusion We have proposed methods to incorporate ANC-RT data into Spectrum to obtain more precise estimates of prevalence and other measures of the epidemic. Many assumptions about the accuracy, consistency, and representativeness of ANC-RT prevalence underlie the use of these data for monitoring HIV epidemic trends, and should be tested as more data become available from national ANC-RT programs. PMID:28296804

Temperature affects thrombolytic efficacy using rt-PA and eptifibatide, an in vitro study.

PubMed

Meunier, Jason M; Chang, Wan-Tsu W; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J; Shaw, George J

2012-09-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents.

Temperature Affects Thrombolytic Efficacy Using rt-PA and Eptifibatide, an In Vitro Study

PubMed Central

Chang, Wan-Tsu W.; Bluett, Brent; Wenker, Evan; Lindsell, Christopher J.; Shaw, George J.

2012-01-01

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature. Here, clot lysis during exposure to the combination of rt-PA and Epf is measured in an in vitro human clot model at hypothermic temperatures. The hypothesis is that lytic efficacy of rt-PA and Epf decreases with decreasing temperature. Whole blood clots from 31 volunteers were exposed to rt-PA (0.5 μg/mL) and Epf (0.63 μg/mL) in human fresh-frozen plasma (rt-PA+Epf ), rt-PA alone in plasma (rt-PA Alone), or to plasma alone (Control), at temperatures from 30°C to 37°C, for 30 minutes. Clot lysis was measured using a microscopic imaging technique; the mean fractional clot loss (FCL) at 30 minutes was used to determine lytic efficacy. Temperature had a significant impact on FCL in clots exposed to rt-PA+Epf, with the FCL being lower at 30°C to 36°C than at 37°C. The FCL remained significantly higher for rt-PA+Epf–treated clots than Controls regardless of temperature, with the exception of measurements made at 30°C when no significant differences in the FCL were observed between groups. The use of hypothermia as a neuroprotectant may negatively impact the therapeutic benefit of thrombolytic agents. PMID:23667777

Patterns of Radiotherapy Practice for Pancreatic Cancer in Japan: Results of the Japanese Radiation Oncology Study Group (JROSG) Survey

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

Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.j; Ito, Yoshinori; Karasawa, Katsuyuki

2010-07-01

Purpose: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. Methods and Materials: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. Results: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treatedmore » with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. Conclusion: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.« less

Enterovirus D68 detection in respiratory specimens: Association with severe disease.

PubMed

Engelmann, Ilka; Fatoux, Marie; Lazrek, Mouna; Alidjinou, Enagnon K; Mirand, Audrey; Henquell, Cécile; Dewilde, Anny; Hober, Didier

2017-07-01

Molecular techniques increased the number of documented respiratory infections. In a substantial number of cases the causative agent remains undetected. Since August 2014, an increase in Enterovirus(EV)-D68 infections was reported. We aimed to investigate epidemiology and clinical relevance of EV-D68. From June to December 2014 and from September to December 2015, 803 and 847 respiratory specimens, respectively, were tested for respiratory viruses with a multiplex RT-PCR. This multiplex RT-PCR does not detect EV-D68. Therefore, 457 (2014) and 343 (2015) specimens with negative results were submitted to an EV-specific-RT-PCR. EV-positive specimens were tested with an EV-D68-specific-RT-PCR and genotyped. Eleven specimens of 2014 tested positive in the EV-specific-RT-PCR and of these seven were positive in the EV-D68-specific-RT-PCR. Typing confirmed these as EV-D68. Median age of EV-D68-positive patients was 3 years (1 month-91 years). Common symptoms included fever (n = 6, 86%), respiratory distress (n = 5, 71%), and cough (n = 4, 57%). All EV-D68-positive patients were admitted to hospital, 4 (57%) were admitted to intensive care units and 6 (86%) received oxygen. One patient suffered from acute flaccid paralysis. Seven specimens of 2015 were positive in the EV-specific-RT-PCR but negative in the EV-D68-specific-RT-PCR. In conclusion, use of an EV-specific-RT-PCR allowed us to detect EV-D68 circulation in autumn 2014 that was not detected by the multiplex RT-PCR and was associated with severe disease. © 2017 Wiley Periodicals, Inc.

Beta-carotene Antioxidant Use During Radiation Therapy and Prostate Cancer Outcome in the Physicians' Health Study

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

Margalit, Danielle N., E-mail: dmargalit@lroc.harvard.edu; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

2012-05-01

Purpose: The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases. Methods and Materials: PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined asmore » prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT. Results: With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group. Conclusion: The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.« less

Experimental study of quantitative assessment of left ventricular mass with contrast enhanced real-time three-dimensional echocardiography.

PubMed

Zhuang, Lei; Wang, Xin-Fang; Xie, Ming-Xing; Chen, Li-Xin; Fei, Hong-Wen; Yang, Ying; Wang, Jing; Huang, Run-Qing; Chen, Ou-Di; Wang, Liang-Yu

2004-01-01

To evaluate the feasibility and accuracy of measurement of left ventricular mass with intravenous contrast enhanced real-time three-dimensional (RT3D) echocardiography in the experimental setting. RT3D echocardiography was performed in 13 open-chest mongrel dogs before and after intravenous infusion of a perfluorocarbon contrast agent. Left ventricular myocardium volume was measured according to the apical four-plane method provided by TomTec 4D cardio-View RT1.0 software, then the left ventricular mass was calculated as the myocardial volume multiplied by the relative density of myocardium. Correlative analysis and paired t-test were performed between left ventricular mass obtained from RT3D echocardiography and the anatomic measurements. Anatomic measurement of total left ventricular mass was 55.6 +/- 9.3 g, whereas RT3D echocardiographic calculation of left ventricular mass before and after intravenous perfluorocarbon contrast agent was 57.5 +/- 11.4 and 55.5 +/- 9.3 g, respectively. A significant correlation was observed between the RT3D echocardiographic estimates of total left ventricular mass and the corresponding anatomic measurements (r = 0.95). A strong correlation was found between RT3D echocardiographic estimates of left ventricular mass with perfluorocarbon contrast and the anatomic results (r = 0.99). Analysis of intraobserver and interobserver variability showed strong indexes of agreement in the measurement of left ventricular mass with pre and post-contrast RT3D echocardiography. Measurements of left ventricular mass derived from RT3D echocardiography with and without intravenous contrast showed a significant correlation with the anatomic results. Contrast enhanced RT3D echocardiography permitted better visualization of the endocardial border, which would provide a more accurate and reliable means of determining left ventricular myocardial mass in the experimental setting.

Obesity and Risk of Biochemical Failure for Patients Receiving Salvage Radiotherapy After Prostatectomy

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

King, Christopher R.; Spiotto, Michael T.; Kapp, Daniel S.

Purpose: Obesity has been proposed as an independent risk factor for patients undergoing surgery or radiotherapy (RT) for prostate cancer. Using body mass index (BMI) as a measure of obesity, we tested its role as a risk factor for patients receiving salvage RT after prostatectomy. Methods and Materials: Rates of subsequent biochemical relapse were examined in 90 patients who underwent salvage RT between 1984 and 2004 for biochemical failure after radical prostatectomy. Median follow-up was 3.7 years. The BMI was tested as a continuous and categorical variable (stratified as <25, 25-<30, and {>=}30 kg/m{sup 2}). Univariate and multivariate proportional hazardsmore » regression analyses were performed for clinical, pathologic, and treatment factors associated with time to relapse after salvage RT. Results: There were 40 biochemical failures after salvage RT with a median time to failure of 1.2 years. The BMI was not associated with adverse clinical, pathologic, or treatment factors. On multivariate analysis, obesity was independently significant (hazard ratio [HR], 1.2; p = 0.01), along with RT dose (HR, 0.7; p = 0.003) and pre-RT prostate-specific antigen level (HR, 1.2; p = 0.0003). Conclusions: This study is weakly suggestive that obesity may be a risk factor for salvage RT patients. Whether this results from greater biologic aggressiveness or technical inadequacies cannot be answered by this study. Given the very high failure rate observed for severely obese patients, we propose that technical difficulties with RT are at play. This hypothesis is supported by the RT literature and could be prospectively investigated. Techniques that optimize targeting, especially in obese patients, perhaps seem warranted at this time.« less

Enhanced control of dorsolateral prefrontal cortex neurophysiology with real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback training and working memory practice.

PubMed

Sherwood, Matthew S; Kane, Jessica H; Weisend, Michael P; Parker, Jason G

2016-01-01

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback can be used to train localized, conscious regulation of blood oxygen level-dependent (BOLD) signals. As a therapeutic technique, rt-fMRI neurofeedback reduces the symptoms of a variety of neurologic disorders. To date, few studies have investigated the use of self-regulation training using rt-fMRI neurofeedback to enhance cognitive performance. This work investigates the utility of rt-fMRI neurofeedback as a tool to enhance human cognition by training healthy individuals to consciously control activity in the left dorsolateral prefrontal cortex (DLPFC). A cohort of 18 healthy participants in the experimental group underwent rt-fMRI neurofeedback from the left DLPFC in five training sessions across two weeks while 7 participants in the control group underwent similar training outside the MRI and without rt-fMRI neurofeedback. Working memory (WM) performance was evaluated on two testing days separated by the five rt-fMRI neurofeedback sessions using two computerized tests. We investigated the ability to control the BOLD signal across training sessions and WM performance across the two testing days. The group with rt-fMRI neurofeedback demonstrated a significant increase in the ability to self-regulate the BOLD signal in the left DLPFC across sessions. WM performance showed differential improvement between testing days one and two across the groups with the highest increases observed in the rt-fMRI neurofeedback group. These results provide evidence that individuals can quickly gain the ability to consciously control the left DLPFC, and this training results in improvements of WM performance beyond that of training alone. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of Adjuvant External-Beam Radiation Therapy in Early-Stage Uterine Papillary Serous and Clear Cell Carcinoma

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

Kim, Anne, E-mail: akim2@health-quest.org; Schreiber, David; Rineer, Justin

2011-11-15

Purpose: Adjuvant radiation therapy (RT) in early-stage high- to intermediate-risk endometrioid adenocarcinoma is well established and has been shown to improve locoregional control. Its role in the management of early-stage clear cell carcinoma and uterine papillary serous carcinoma (UPSC) remains controversial. Methods and Materials: Using the Surveillance Epidemiology and End Results database, we identified women with American Joint Committee on Cancer Stage Sixth Edition. Stage IA-IIB clear cell carcinoma or UPSC who underwent hysterectomy with or without adjuvant RT between 1988 and 2003. We used Kaplan-Meier and Cox regression analysis to compare overall survival (OS) for all patients. Results: Wemore » identified 1,333 women of whom 451 had clear cell carcinoma and 882 had UPSC. Of those patients, 775 underwent surgery alone and 558 received adjuvant RT as well. For Stages I-IIB disease, the median OS with surgery alone was 106 months, vs. 151 months with adjuvant RT (p = 0.006). On subgroup analysis, we saw the benefit from adjuvant RT only in Stage IB-C patients. For Stage IB disease, patients undergoing surgery alone had a median OS of 117 months, vs. median survival not reached with the addition of RT (p = 0.006). For Stage IC disease, surgery alone had a median OS of 35 months vs. 120 months with RT (p = 0.001). Although the apparent benefit of RT diminished when measured via multivariate analysis, the impact of RT on survival did show a trend toward significance (hazard ration 0.808, confidence interval 95% 0.651-1.002, p = 0.052) Conclusion: In FIGO Stage IB-C papillary serous and clear cell uterine carcinoma, adjuvant RT seems to play an important role in improving survival.« less

The impact of lesion side on acute stroke treatment.

PubMed

Di Legge, Silvia; Fang, Jiming; Saposnik, Gustavo; Hachinski, Vladimir

2005-07-12

Only a small percentage of patients with acute stroke are treated with recombinant tissue plasminogen activator (rt-PA). To investigate why patients with right-hemisphere strokes seem at high risk of not receiving rt-PA. This study includes two phases. Phase 1: the authors compared demographic, clinical, and outcome measures between patients with right- and left-hemisphere strokes in the rt-PA Registry of Southwestern Ontario (RSWO); Phase 2: the authors tested the hypotheses generated in Phase 1 using the Registry of the Canadian Stroke Network (RCSN). A multiple logistic analysis was applied to detect independent predictors of rt-PA administration. Phase 1: of 179 rt-PA-treated patients, 39% had right-hemisphere syndrome. Patients with right-hemisphere strokes had a longer hospital stay (15 vs 9 days; p = 0.03). Phase 2: of 990 stroke patients in the RCSN, 505 (51%) had a right- and 485 (49%) a left-hemisphere syndrome. Of 110 rt-PA-treated patients, 37 (34%) had a right-hemisphere syndrome (p = 0.0001). Negative independent predictors of rt-PA administration were right-hemisphere stroke (OR, 0.55; CI: 0.31 to 0.96; p = 0.037), onset-to-emergency department time (OR, 0.99; CI 0.98 to 0.99; p = 0.04), and CNS score (OR, 0.78; CI 0.71 to 0.86; p < 0.0001). Neglect predicted rt-PA administration (OR, 2.32; CI 1.29 to 4.16; p = 0.004). Patients with right-hemisphere strokes are 45% less likely to be treated with recombinant tissue plasminogen activator (rt-PA) compared to patients with left-hemisphere strokes. The presence of neglect confers a twofold increased likelihood of rt-PA administration. Prehospital delay and lack of standardized scores for the neglect syndrome may limit accessibility of patients with right-hemisphere stroke to thrombolysis.

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.

PubMed

Grimaldi, Antonio M; Simeone, Ester; Giannarelli, Diana; Muto, Paolo; Falivene, Sara; Borzillo, Valentina; Giugliano, Francesca Maria; Sandomenico, Fabio; Petrillo, Antonella; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Palmieri, Giuseppe; Caracò, Corrado; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

2014-01-01

Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute "Fondazione G.Pascale" through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1-4). Median overall survival (OS) for all 21 patients was 13 months (range 6-26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5-50.3) vs. 8.3 months (range 7.6-9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Analysis of Patients With Oligometastases Undergoing Two or More Curative-Intent Stereotactic Radiotherapy Courses

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

Milano, Michael T.; Philip, Abraham; Okunieff, Paul

2009-03-01

Purpose: A subset of patients treated with curative-intent stereotactic radiotherapy (RT) for limited metastases (defined as five lesions or fewer) develop local failure and/or a small number of new lesions. We hypothesized that these patients would remain amenable to curative-intent treatment with additional RT courses. Methods and Materials: Of 121 prospective patients with five lesions or fewer treated with stereotactic RT, 32 underwent additional RT courses for local failure (n = 9) and/or new lesions (n = 29). Ten patients underwent three or more courses of RT. Results: The treated local failures developed a median of 20 months after RTmore » completion. For the new oligometastases, the interval between the first and second RT course was 1-71 months (median, 8). Of the 32 patients undergoing multiple courses of curative-intent RT, the 2-year overall survival and progression-free survival rate was 65% and 54%, respectively. The corresponding 4-year rates were 33% and 28%. Compared with the 89 patients who underwent one RT course, these patients experienced a trend toward improved overall survival (median, 32 vs. 21 months, p = 0.13) and significantly greater progression-free survival (median, 28 vs. 9 months, p = 0.008). Conclusion: The results of our study have shown that patients fare well with respect to survival and disease control with aggressive RT for limited metastases, even after local failure and/or the development of new metastases. Although patients amenable to multiple courses of curative-intent RT are arguably selected for more indolent disease, our hypothesis-generating analysis supports the notion of aggressively treating limited metastases, which, in some patients, might be curable and/or represent a chronic disease state.« less

Correlating Computed Tomography Perfusion Changes in the Pharyngeal Constrictor Muscles During Head-and-Neck Radiotherapy to Dysphagia Outcome

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

Truong, Minh Tam, E-mail: mitruong@bu.edu; Department of Radiology, Boston Medical Center and Boston University School of Medicine, Boston, MA; Lee, Richard

2012-02-01

Purpose: To measure changes in perfusion of the pharyngeal constrictor muscles (PCM) using CT perfusion (CTP) imaging during a course of definitive radiotherapy (RT) in head-and-neck cancer (HNC) patients and correlate with dysphagia outcome after RT. Methods and Materials: Fifteen HNC patients underwent CTP imaging of the PCM at baseline and Weeks 2, 4, and 6 during RT and 6 weeks after RT. Blood flow and blood volume were measured in the PCM, and percentage change from baseline scan was determined. A single physician-based assessment of dysphagia was performed every 3 months after RT using the Common Terminology Criteria formore » Adverse Events, version 3.0 grading system. Results: With a median follow-up of 28 months (range, 6-44 months), Grade 3 dysphagia was present in 7 of 15 patients, and 8 patients experienced Grade 0-2 dysphagia. The CTP parameters at Week 2 of RT demonstrated an increase in mean PCM blood flow of 161.9% vs. 12.3% (p = 0.007) and an increase in mean PCM blood volume of 96.6% vs. 8.7% (p = 0.039) in patients with 6-month post-RT Grade 3 dysphagia and Grade 0-2 dysphagia, respectively. On multivariate analysis, when adjusting for smoking history, tumor volume, and baseline dysphagia status, an increase in blood flow in the second week of RT was significant for 3- and 6-month Grade 3 dysphagia (p < 0.05). Conclusions: Perfusion changes in the PCM during Week 2 of RT in the PCM may predict the severity of dysphagia after HNC RT.« less

Clinical Outcome of Sacral Chordoma With Carbon Ion Radiotherapy Compared With Surgery

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

Nishida, Yoshihiro, E-mail: ynishida@med.nagoya-u.ac.j; Kamada, Tadashi; Imai, Reiko

Purpose: To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials: The records of 17 primary sacral chordoma patients treated since 1990 with surgery (n = 10) or carbon ion RT (n = 7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results: The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The medianmore » duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion: Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery.« less

Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus.

PubMed

Yue, Xiao Dan; Wang, Jing Yu; Zhang, Xin Rong; Yang, Ju Hong; Shan, Chun Yan; Zheng, Miao Yan; Ren, Hui Zhu; Zhang, Yi; Yang, Shao Hua; Guo, Zhen Hong; Chang, Bai; Chang, Bao Cheng

2017-04-01

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RT(G) was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors. © 2017 The Korean Academy of Medical Sciences.

Barriers to the Implementation of Surveillance for Stage I Testicular Seminoma

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

Arvold, Nils D.; Catalano, Paul J.; Sweeney, Christopher J.

2012-10-01

Purpose: Postorchiectomy adjuvant radiotherapy (RT) for Stage I seminoma can be associated with long-term toxicity, and management strategies with a lower treatment burden achieve the same excellent cure rate. Because studies suggest that radiation oncologists in the United States continue to recommend RT for these patients, we sought to identify factors associated with management recommendations. Methods and Materials: We conducted a one-time internet-based survey among 491 randomly selected American radiation oncologists self-described as specializing in genitourinary oncology. Results: Response rate was 53% (n = 261). Forty-nine percent of respondents worked in university-affiliated practices. Sixty-two percent of respondents always/usually recommended adjuvantmore » RT for patients with Stage I seminoma, whereas 21% always/usually recommended surveillance and 3% always/usually recommended chemotherapy. One third (33%) expressed concerns that patients who experienced relapse during surveillance could not be salvaged. Although 88% of physicians were aware of an increased risk of second malignant neoplasms (SMN) after adjuvant RT, 85% underestimated its magnitude. Compared with physicians not typically recommending RT, physicians who always/usually recommended RT were more likely to believe that patients might not be salvaged at relapse during surveillance (p = 0.008) and were less aware of the association between RT and SMN (p = 0.04). Conclusions: Respondents who always/usually recommend postorchiectomy RT for patients with Stage I seminoma are more likely to underestimate late RT morbidity and to believe that surveillance is associated with increased mortality. Given the equivalent efficacy and reduced morbidity of surveillance compared with RT, our findings underscore the need for ongoing physician education to increase appropriate clinical implementation of surveillance strategies.« less

Enzymatic and viability RT-qPCR assays for evaluation of enterovirus, hepatitis A virus and norovirus inactivation: Implications for public health risk assessment.

PubMed

Monteiro, S; Santos, R

2018-04-01

To assess the potential of a viability dye and an enzymatic reverse transcription quantitative PCR (RT-qPCR) pretreatment to discriminate between infectious and noninfectious enteric viruses. Enterovirus (EntV), norovirus (NoV) GII.4 and hepatitis A virus (HAV) were inactivated at 95°C for 10 min, and four methods were used to compare the efficiency of inactivation: (i) cell culture plaque assay for HAV and EntV, (ii) RT-qPCR alone, (iii) RT-qPCR assay preceded by RNase treatment, and (iv) pretreatment with a viability dye (reagent D (RD)) followed by RT-qPCR. In addition, heat-inactivated NoV was treated with RD coupled with surfactants to increase the efficiency of the viability dye. No treatment was able to completely discriminate infectious from noninfectious viruses. RD-RT-qPCR reduced more efficiently the detection of noninfectious viruses with little to no removal observed with RNase. RD-RT-qPCR method was the closest to cell culture assay. The combination of surfactants and RD did not show relevant improvements on the removal of inactivated viruses signal compared with viability RT-qPCR, with the exception of Triton X-100. The use of surfactant/RD-RT-qPCR, although not being able to completely remove the signal from noninfectious viral particles, yielded a better estimation of viral infectivity. Surfactant/RD-RT-qPCR may be an advantageous tool for a better detection of infectious viruses with potential significant impact in the risk assessment of the presence of enteric viruses. © 2017 The Society for Applied Microbiology.

Salvage surgery in the treatment of local recurrences of nasopharyngeal carcinomas.

PubMed

Salom, María Cecilia; López, Fernando; Pacheco, Esteban; Muñoz, Gabriela; García-Cabo, Patricia; Fernández, Laura; Suárez, Vanessa; Llorente, José Luis

2018-04-03

Chemoradiotherapy is the treatment of choice for nasopharyngeal carcinoma. Local recurrences are one of the leading causes of death in these patients, and surgical salvage the treatment of choice. Our goal was to evaluate and compare the results of salvage surgery in the treatment of local recurrence of nasopharyngeal carcinomas comparing endoscopic to open approaches. Twenty patients with local recurrence of nasopharyngeal carcinomas underwent surgery: 12 patients underwent open surgery and 8 endoscopic endonasal transpterygoid nasopharyngectomy. One patient was classified as rT1; 3 as rT2;2 as rT3; and 6 as rT4 in the group of open approaches; in the endoscopic series, 2 patients were rT1, 5 rT2 and one rT3. In 3 patients (25%) operated by an open approach (one rT4, one rT3 and one rT2) a complete gross resection was not achieved. Gross total resection was achieved in patients operated by endoscopic surgery. The complication rate in the group operated by an open approach was 92% (5 minor complications, 5 moderate complications, and one serious complication) and in the group that underwent endoscopic surgery all patients had some complication (7 had minor complications and one patient developed a severe complication). Survival at 3 and 5 years was 53% and 42% with the open approach and 100% and 50% with the endoscopic approach, respectively. Endoscopic approaches decrease the morbidity associated with open approaches and allow for favourable oncological control. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma.

PubMed

Wang, Zhong-He; Yan, Chao; Zhang, Zhi-Yuan; Zhang, Chen-Ping; Hu, Hai-Sheng; Tu, Wen-Yong; Kirwan, Jessica; Mendenhall, William M

2014-10-01

We compared outcomes and xerostomia grade after postoperative intensity-modulated radiation therapy (IMRT) and conventional radiotherapy (RT) in patients with oral and oropharyngeal carcinoma. Eighty-eight patients with oral cavity (n = 77) and oropharyngeal (n = 11) carcinoma underwent postoperative IMRT (n = 44) or conventional RT (n = 44). Outcomes, failure patterns, volume, doses, salivary gland V30, and xerostomia grade were evaluated. The median follow-up was 53 months (range, 48-58 months). The median interval from surgery to RT was 4 weeks (range, 3-6 weeks). Twenty-one patients (7 and 14 for the IMRT and conventional RT groups, respectively) experienced local-regional failure. For the IMRT group, all 7 local-regional failures occurred in the high-dose target volumes. For the conventional RT group, there were 12 in-field failures, 1 at the margin, and 1 out-of-field. Nine patients experienced distant failure (5 and 4 for the IMRT and conventional RT groups, respectively). The 4-year local-regional control, disease-free survival (DFS), overall survival (OS), and distant-metastasis rates for the IMRT and conventional RT groups were 84.1% versus 68.2% (p = .055), 68.2% versus 52.3% (p = .091), 70.5% versus 56.8% (p = .124), and 11.4% versus 9.1% (p = .927), respectively. Xerostomia grade after RT was lower for IMRT compared to conventional RT (p < .001). Postoperative IMRT for oral and oropharyngeal carcinoma significantly improves mean dose, salivary gland V30, and xerostomia grade when compared to conventional RT. The predominant failure pattern was local. No differences were found in survival outcomes between both groups. There was a marginal difference in local-regional control. © 2014 Wiley Periodicals, Inc.

The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes.

PubMed

Fonda, Stephanie J; Graham, Claudia; Munakata, Julie; Powers, Julia M; Price, David; Vigersky, Robert A

2016-07-01

This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients' behavior. The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base-case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM "refresher" after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a "refresher" were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness. © 2016 Diabetes Technology Society.

Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

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

Martinez, Steve R., E-mail: steve.martinez@ucdmc.ucdavis.ed; Beal, Shannon H.; Chen, Steven L.

2010-11-01

Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximatelymore » half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.« less

High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.

PubMed

Okano, Hiroyuki; Baba, Misato; Kawato, Katsuhiro; Hidese, Ryota; Yanagihara, Itaru; Kojima, Kenji; Takita, Teisuke; Fujiwara, Shinsuke; Yasukawa, Kiyoshi

2018-03-01

One-step RT-PCR has not been widely used even though some thermostable DNA polymerases with reverse transcriptase (RT) activity were developed from bacterial and archaeal polymerases, which is owing to low cDNA synthesis activity from RNA. In the present study, we developed highly-sensitive one-step RT-PCR using the single variant of family A DNA polymerase with RT activity, K4pol L329A (L329A), from the hyperthermophilic bacterium Thermotoga petrophila K4 or the 16-tuple variant of family B DNA polymerase with RT activity, RTX, from the hyperthermophilic archaeon Thermococcus kodakarensis. Optimization of reaction condition revealed that the activities for cDNA synthesis and PCR of K4pol L329A and RTX were highly affected by the concentrations of MgCl 2 and Mn(OCOCH 3 ) 2 as well as those of K4pol L329A or RTX. Under the optimized condition, 300 copies/μl of target RNA in 10 μl reaction volumes were successfully detected by the one-step RT-PCR with K4pol L329A or RTX, which was almost equally sensitive enough compared with the current RT-PCR condition using retroviral RT and thermostable DNA polymerase. Considering that K4pol L329A and RTX are stable even at 90-100°C, our results suggest that the one-step RT-PCR with K4pol L329A or RTX is more advantageous than the current one. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

Jebsen, Nina L.; Department of Oncology, Haukeland University Hospital, Bergen; Trovik, Clement S.

Purpose: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. Methods and Materials: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986-1991, 1992-1997, and 1998-2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. Results: The use ofmore » RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. Conclusion: The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.« less

Development of duplex RT-PCR-ELISA for the simultaneous detection of hepatitis A virus and hepatitis E virus.

PubMed

Tahk, Hongmin; Lee, Min Hwa; Lee, Kang Bum; Cheon, Doo-Sung; Choi, Changsun

2011-07-01

This study aimed to develop a specific and sensitive duplex reverse transcription polymerase chain reaction enzyme-linked immunosorbent assay (duplex RT-PCR-ELISA) for hepatitis A virus (HAV) and hepatitis E virus (HEV). Duplex RT-PCR-ELISA could detect and differentiate HAV and HEV with specific probes. When ELISA technique was used to detect probe-bound RT-PCR products, duplex RT-PCR-ELISA could detect as little as 0.1 ng/μL HAV and HEV from clinical samples. Human norovirus, enterovirus, poliovirus, murine norovirus and feline calicivirus were used for the specificity test; all were negative. Therefore duplex RT-PCR-ELISA can be used for the simultaneous detection of HAV and HEV in contaminated fecal samples. Copyright © 2011 Elsevier B.V. All rights reserved.

The future of image-guided radiotherapy will be MR guided

PubMed Central

Wen, Zhifei; Sadagopan, Ramaswamy; Wang, Jihong; Ibbott, Geoffrey S

2017-01-01

Advances in image-guided radiotherapy (RT) have allowed for dose escalation and more precise radiation treatment delivery. Each decade brings new imaging technologies to help improve RT patient setup. Currently, the most frequently used method of three-dimensional pre-treatment image verification is performed with cone beam CT. However, more recent developments have provided RT with the ability to have on-board MRI coupled to the teleradiotherapy unit. This latest tool for treating cancer is known as MR-guided RT. Several varieties of these units have been designed and installed in centres across the globe. Their prevalence, history, advantages and disadvantages are discussed in this review article. In preparation for the next generation of image-guided RT, this review also covers where MR-guided RT might be heading in the near future. PMID:28256898

Development of Virtual Airspace Simulation Technology - Real-Time (VAST-RT) Capability 2 and Experimental Plans

NASA Technical Reports Server (NTRS)

Lehmer, R.; Ingram, C.; Jovic, S.; Alderete, J.; Brown, D.; Carpenter, D.; LaForce, S.; Panda, R.; Walker, J.; Chaplin, P.;

Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

PubMed

Gualberto, F A S; Gonçalves, M G; Fukasawa, L O; Santos, A M Ramos Dos; Sacchi, C T; Harrison, L H; Boulware, D R; Vidal, J E

2017-10-01

Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Melatonin prevents radiation-induced oxidative stress and periodontal tissue breakdown in irradiated rats with experimental periodontitis.

PubMed

Köse, O; Arabaci, T; Kizildag, A; Erdemci, B; Özkal Eminoğlu, D; Gedikli, S; Özkanlar, S; Zihni, M; Albayrak, M; Kara, A; Kermen, E

2017-06-01

The aim of this study was to analyze the biochemical and histochemical effects of radiation therapy and protective melatonin administration on periodontal tissues in rats with experimental periodontitis. Sixty male Sprague Dawley rats were divided into six groups, as follows: control; experimental periodontitis (Ped); radiotherapy administration (Rt); experimental periodontitis and exposure to irradiation (Ped-Rt); radiotherapy and protective melatonin administration (Rt-Mel); and periodontitis, radiation therapy and protective melatonin administration (Ped-Rt-Mel). The rats were killed at the end of the experimental procedure, and the oxidative stress level and periodontal destruction were compared among the groups. The oxidative stress index and the levels of 8-hydroxy-2'-deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen were found to be significantly higher in the Ped-Rt group compared with the Ped group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05). It was found that radiotherapy increased oxidative stress, the periodontal attachment level and alveolar bone loss, and protective melatonin administration significantly reduced the oxidative parameters and prevented periodontal damage in irradiated rats with experimental periodontitis. Further research is needed regarding the use of systemic melatonin administration before radiation therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cortical afferents onto the nucleus Reticularis thalami promote plasticity of low-threshold excitability through GluN2C-NMDARs.

PubMed

Fernandez, Laura M J; Pellegrini, Chiara; Vantomme, Gil; Béard, Elidie; Lüthi, Anita; Astori, Simone

2017-09-25

Thalamus and cortex represent a highly integrated processing unit that elaborates sensory representations. Interposed between cortex and thalamus, the nucleus Reticularis thalami (nRt) receives strong cortical glutamatergic input and mediates top-down inhibitory feedback to thalamus. Despite growing appreciation that the nRt is integral for thalamocortical functions from sleep to attentional wakefulness, we still face considerable gaps in the synaptic bases for cortico-nRt communication and plastic regulation. Here, we examined modulation of nRt excitability by cortical synaptic drive in Ntsr1-Cre x ChR2 tg/+ mice expressing Channelrhodopsin2 in layer 6 corticothalamic cells. We found that cortico-nRt synapses express a major portion of NMDA receptors containing the GluN2C subunit (GluN2C-NMDARs). Upon repetitive photoactivation (10 Hz trains), GluN2C-NMDARs induced a long-term increase in nRt excitability involving a potentiated recruitment of T-type Ca 2+ channels. In anaesthetized mice, analogous stimulation of cortical afferents onto nRt produced long-lasting changes in cortical local field potentials (LFPs), with delta oscillations being augmented at the expense of slow oscillations. This shift in LFP spectral composition was sensitive to NMDAR blockade in the nRt. Our data reveal a novel mechanism involving plastic modification of synaptically recruited T-type Ca 2+ channels and nRt bursting and indicate a critical role for GluN2C-NMDARs in thalamocortical rhythmogenesis.

Short-Term Prediction Research and Transition (SPoRT) Center: Transitioning Satellite Data to Operations

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley

2012-01-01

The Short-term Prediction Research and Transition (SPoRT) Center located at NASA Marshall Space Flight Center has been conducting testbed activities aimed at transitioning satellite products to National Weather Service operational end users for the last 10 years. SPoRT is a NASA/NOAA funded project that has set the bar for transition of products to operational end users through a paradigm of understanding forecast challenges and forecaster needs, displaying products in end users decision support systems, actively assessing the operational impact of these products, and improving products based on forecaster feedback. Aiming for quality partnerships rather than a large quantity of data users, SPoRT has become a community leader in training operational forecasters on the use of up-and-coming satellite data through the use of legacy instruments and proxy data. Traditionally, SPoRT has supplied satellite imagery and products from NASA instruments such as the Moderate-resolution Imaging Spectroradiometer (MODIS) and the Atmospheric Infrared Sounder (AIRS). However, recently, SPoRT has been funded by the GOES-R and Joint Polar Satellite System (JPSS) Proving Grounds to accelerate the transition of selected imagery and products to help improve forecaster awareness of upcoming operational data from the Visible Infrared Imager Radiometer Suite (VIIRS), Cross-track Infrared Sounder (CrIS), Advanced Baseline Imager (ABI), and Geostationary Lightning Mapper (GLM). This presentation provides background on the SPoRT Center, the SPoRT paradigm, and some example products that SPoRT is excited to work with forecasters to evaluate.

Detection of Papaya leaf distortion mosaic virus by reverse-transcription loop-mediated isothermal amplification.

PubMed

Shen, Wentao; Tuo, Decai; Yan, Pu; Li, Xiaoying; Zhou, Peng

2014-01-01

Papaya leaf distortion mosaic virus (PLDMV) can infect transgenic papaya resistant to a related pathogen, Papaya ringspot virus (PRSV), posing a substantial threat to papaya production in China. Current detection methods, however, are unable to be used for rapid detection in the field. Here, a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of PLDMV, using a set of four RT-LAMP primers designed based on the conserved sequence of PLDMV CP. The RT-LAMP method detected specifically PLDMV and was highly sensitive, with a detection limit of 1.32×10(-6) μg of total RNA per reaction. Indeed, the reaction was 10 times more sensitive than one-step RT-PCR, while also requiring significantly less time and equipment. The effectiveness of RT-LAMP and one-step RT-PCR in detecting the virus were compared using 90 field samples of non-transgenic papaya and 90 field samples of commercialized PRSV-resistant transgenic papaya from Hainan Island. None of the non-transgenic papaya tested positive for PLDMV using either method. In contrast, 19 of the commercialized PRSV-resistant transgenic papaya samples tested positive by RT-LAMP assay, and 6 of those tested negative by RT-PCR. Therefore, the PLDMV-specific RT-LAMP is a simple, rapid, sensitive, and cost-effective tool in the field diagnosis and control of PLDMV. Copyright © 2013 Elsevier B.V. All rights reserved.

RAYLEIGH–TAYLOR UNSTABLE FLAMES—FAST OR FASTER?

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

Hicks, E. P., E-mail: eph2001@columbia.edu

2015-04-20

Rayleigh–Taylor (RT) unstable flames play a key role in the explosions of supernovae Ia. However, the dynamics of these flames are still not well understood. RT unstable flames are affected by both the RT instability of the flame front and by RT-generated turbulence. The coexistence of these factors complicates the choice of flame speed subgrid models for full-star Type Ia simulations. Both processes can stretch and wrinkle the flame surface, increasing its area and, therefore, the burning rate. In past research, subgrid models have been based on either the RT instability or turbulence setting the flame speed. We evaluate bothmore » models, checking their assumptions and their ability to correctly predict the turbulent flame speed. Specifically, we analyze a large parameter study of 3D direct numerical simulations of RT unstable model flames. This study varies both the simulation domain width and the gravity in order to probe a wide range of flame behaviors. We show that RT unstable flames are different from traditional turbulent flames: they are thinner rather than thicker when turbulence is stronger. We also show that none of the several different types of turbulent flame speed models accurately predicts measured flame speeds. In addition, we find that the RT flame speed model only correctly predicts the measured flame speed in a certain parameter regime. Finally, we propose that the formation of cusps may be the factor causing the flame to propagate more quickly than predicted by the RT model.« less

A Guideline to Family-Wide Comparative State-of-the-Art Quantitative RT-PCR Analysis Exemplified with a Brassicaceae Cross-Species Seed Germination Case Study[W][OA

PubMed Central

Graeber, Kai; Linkies, Ada; Wood, Andrew T.A.; Leubner-Metzger, Gerhard

2011-01-01

Comparative biology includes the comparison of transcriptome and quantitative real-time RT-PCR (qRT-PCR) data sets in a range of species to detect evolutionarily conserved and divergent processes. Transcript abundance analysis of target genes by qRT-PCR requires a highly accurate and robust workflow. This includes reference genes with high expression stability (i.e., low intersample transcript abundance variation) for correct target gene normalization. Cross-species qRT-PCR for proper comparative transcript quantification requires reference genes suitable for different species. We addressed this issue using tissue-specific transcriptome data sets of germinating Lepidium sativum seeds to identify new candidate reference genes. We investigated their expression stability in germinating seeds of L. sativum and Arabidopsis thaliana by qRT-PCR, combined with in silico analysis of Arabidopsis and Brassica napus microarray data sets. This revealed that reference gene expression stability is higher for a given developmental process between distinct species than for distinct developmental processes within a given single species. The identified superior cross-species reference genes may be used for family-wide comparative qRT-PCR analysis of Brassicaceae seed germination. Furthermore, using germinating seeds, we exemplify optimization of the qRT-PCR workflow for challenging tissues regarding RNA quality, transcript stability, and tissue abundance. Our work therefore can serve as a guideline for moving beyond Arabidopsis by establishing high-quality cross-species qRT-PCR. PMID:21666000

Rayleigh-Taylor Unstable Flames -- Fast or Faster?

NASA Astrophysics Data System (ADS)

Hicks, E. P.

2015-04-01

Rayleigh-Taylor (RT) unstable flames play a key role in the explosions of supernovae Ia. However, the dynamics of these flames are still not well understood. RT unstable flames are affected by both the RT instability of the flame front and by RT-generated turbulence. The coexistence of these factors complicates the choice of flame speed subgrid models for full-star Type Ia simulations. Both processes can stretch and wrinkle the flame surface, increasing its area and, therefore, the burning rate. In past research, subgrid models have been based on either the RT instability or turbulence setting the flame speed. We evaluate both models, checking their assumptions and their ability to correctly predict the turbulent flame speed. Specifically, we analyze a large parameter study of 3D direct numerical simulations of RT unstable model flames. This study varies both the simulation domain width and the gravity in order to probe a wide range of flame behaviors. We show that RT unstable flames are different from traditional turbulent flames: they are thinner rather than thicker when turbulence is stronger. We also show that none of the several different types of turbulent flame speed models accurately predicts measured flame speeds. In addition, we find that the RT flame speed model only correctly predicts the measured flame speed in a certain parameter regime. Finally, we propose that the formation of cusps may be the factor causing the flame to propagate more quickly than predicted by the RT model.

New Breast Cancer Radiotherapy Technology Confers Higher Complications and Costs Before Effectiveness Proven: A Medicare Data Analysis

PubMed Central

Walter, Dawn; Tousimis, Eleni; Hayes, Mary Katherine

2018-01-01

A new breast cancer treatment, brachytherapy-based accelerated partial breast radiotherapy (RT), was adopted before long-term effectiveness evidence, potentially increasing morbidity and costs compared with whole breast RT. The aim of this study was to estimate complication rates and RT-specific and 1-year costs for a cohort of female Medicare beneficiaries diagnosed with breast cancer (N = 47 969). We analyzed 2005-2007 Medicare claims using multivariable logistic regression for complications and generalized linear models (log link, gamma distribution) for costs. Overall, 11% (n = 5296) underwent brachytherapy-based RT; 9.4% had complications. Odds of any complication were higher (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.49-1.76) for brachytherapy versus whole breast RT, similarly to seroma (OR: 2.85; 95% CI: 1.97-4.13), wound complication/infection (OR: 1.72; 95% CI: 1.52-1.95), cellulitis (OR: 1.48; 95% CI: 1.27-1.73), and necrosis (OR: 2.07; 95% CI: 1.55-2.75). Mean RT-specific and 1-year total costs for whole breast RT were $6375, and $19 917, $4886, and $4803 lower than brachytherapy (P < .0001). Multivariable analyses indicated brachytherapy yielded 76% higher RT costs (risk ratio: 1.76; 95% CI: 1.74-1.78, P < .0001) compared with whole breast RT. Brachytherapy had higher complications and costs before long-term evidence proved its effectiveness. Policies should require treatment registries with reimbursement incentives to capture surveillance data for new technologies. PMID:29502466

Propagation Aspects of Frequency Sharing, Interference and System Diversity

DTIC Science & Technology

1983-03-01

DRSEL-COM-RN-1 Fort Monmouth, N.J. 07703 USA 11.Pages 432 12. Distribution Statement This document is distributed in accordance with AGARD policies ...OD ■rtCMCO •«^ CD CD -rt ■rtCU -T CD coo-^in vinNoi CDCOOO cDhvcno CMCUOO cncD o o oooo oooo CO oo o -rtCOCD N N X X 2: z o o in o

Evaluation of Response to Intervention Practices for Elementary School Reading. Executive Summary. NCEE 2016-4000

ERIC Educational Resources Information Center

Balu, Rekha; Zhu, Pei; Doolittle, Fred; Schiller, Ellen; Jenkins, Joseph; Gersten, Russell

2015-01-01

Response to Intervention (RtI) is a framework for collecting and using data to match students to interventions of varying intensity. This study examines the implementation of RtI in Grade 1-3 reading in 13 states during the 2011-12 school year, focusing on 146 schools that were experienced with RtI. Full implementation of the RtI framework in…

RT-qPCR Demonstrates Light-Dependent AtRBCS1A and AtRBCS3B mRNA Expressions in "Arabidopsis thaliana" Leaves

ERIC Educational Resources Information Center

Chang, Ming-Mei; Li, Anna; Feissner, Robert; Ahmad, Talal

2016-01-01

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is widely used in diagnosis and research to determine specific mRNA expressions in cells. As RT-qPCR applications increase, it is necessary to provide undergraduates hands-on experience of this modern technique. Here, we report a 3-week laboratory exercise using RT-qPCR to…

Rapid group-, serotype-, and vaccine strain-specific identification of poliovirus isolates by real-time reverse transcription-PCR using degenerate primers and probes containing deoxyinosine residues.

PubMed

Kilpatrick, David R; Yang, Chen-Fu; Ching, Karen; Vincent, Annelet; Iber, Jane; Campagnoli, Ray; Mandelbaum, Mark; De, Lina; Yang, Su-Ju; Nix, Allan; Kew, Olen M

2009-06-01

We have adapted our previously described poliovirus diagnostic reverse transcription-PCR (RT-PCR) assays to a real-time RT-PCR (rRT-PCR) format. Our highly specific assays and rRT-PCR reagents are designed for use in the WHO Global Polio Laboratory Network for rapid and large-scale identification of poliovirus field isolates.

Computer Simulation of a 155-mm Projectile in a Scat Gun Assembly

DTIC Science & Technology

2008-09-01

piston increases its kinetic energy as it is displaced a distance X. X X X MpsV2s /2 = f((P- vRT )/(Lpw -X))A - F)dx = (- vRT /(Lpw - X))AdY + f(PA -F...piston is displaced x, the critical displacement can be calculated using the Ideal Gas Law PV = vRT . YD = vRT /(A(Lp;v - x,i)) (ALpwv - x(,.ij

Influence of limited proteolysis, detergent treatment and lyophilization on the phenoloxidase activity of Rapana thomasiana hemocyanin.

PubMed

Idakieva, Krassimira; Siddiqui, Nurul Islam; Meersman, Filip; De Maeyer, Marc; Chakarska, Irena; Gielens, Constant

2009-08-01

The intrinsic and inducible phenoloxidase (PO) activity of Rapana thomasiana hemocyanin (RtH) and its substructures were studied. With catechol as substrate, a weak o-diPO activity was measured for the didecameric RtH and its subunits. Some activation of the o-diPO activity of RtH was achieved by limited treatment with subtilisin and by incubation of RtH with 2.9 mM sodium dodecyl sulphate (SDS), suggesting an enhanced substrate access to the active sites. The highest artificial induction of o-diPO activity in RtH, however, was obtained by lyophilization of the protein. This is ascribed to conformational changes during the lyophilization process of the didecameric RtH molecules, affecting the accessibility of the active sites. These conformational changes must be very small, since Fourier-transform infrared and circular dichroism spectroscopies did not reveal any changes in secondary structure of lyophilized RtH. The difference in accessibility of the copper containing active site for substrates between catechol oxidase and functional unit RtH2-e was demonstrated by molecular modeling and surface area accessibility calculations. The low level of intrinsic PO activity in the investigated hemocyanin is related to the inaccessibility of the binuclear copper active sites to the substrates.

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

Hicks, E. P.; Rosner, R., E-mail: eph2001@columbia.edu

In this paper, we provide support for the Rayleigh-Taylor-(RT)-based subgrid model used in full-star simulations of deflagrations in Type Ia supernovae explosions. We use the results of a parameter study of two-dimensional direct numerical simulations of an RT unstable model flame to distinguish between the two main types of subgrid models (RT or turbulence dominated) in the flamelet regime. First, we give scalings for the turbulent flame speed, the Reynolds number, the viscous scale, and the size of the burning region as the non-dimensional gravity (G) is varied. The flame speed is well predicted by an RT-based flame speed model.more » Next, the above scalings are used to calculate the Karlovitz number (Ka) and to discuss appropriate combustion regimes. No transition to thin reaction zones is seen at Ka = 1, although such a transition is expected by turbulence-dominated subgrid models. Finally, we confirm a basic physical premise of the RT subgrid model, namely, that the flame is fractal, and thus self-similar. By modeling the turbulent flame speed, we demonstrate that it is affected more by large-scale RT stretching than by small-scale turbulent wrinkling. In this way, the RT instability controls the flame directly from the large scales. Overall, these results support the RT subgrid model.« less

Sexual Function in Males After Radiotherapy for Rectal Cancer

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

Bruheim, Kjersti, E-mail: Kjersti.bruheim@medisin.uio.n; Guren, Marianne G.; Dahl, Alv A.

Purpose: Knowledge of sexual problems after pre- or postoperative radiotherapy (RT) with 50 Gy for rectal cancer is limited. In this study, we aimed to compare self-rated sexual functioning in irradiated (RT+) and nonirradiated (RT-) male patients at least 2 years after surgery for rectal cancer. Methods and Materials: Patients diagnosed with rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Male patients without recurrence at the time of the study. The International Index of Erectile Function, a self-rated instrument, was used to assess sexual functioning, and serum levels of serum testosterone were measured. Results:more » Questionnaires were returned from 241 patients a median of 4.5 years after surgery. The median age was 67 years at survey. RT+ patients (n = 108) had significantly poorer scores for erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction with sex life compared with RT- patients (n = 133). In multiple age-adjusted analysis, the odds ratio for moderate-severe erectile dysfunction in RT+ patients was 7.3 compared with RT- patients (p <0.001). Furthermore, erectile dysfunction of this degree was associated with low serum testosterone (p = 0.01). Conclusion: RT for rectal cancer is associated with significant long-term effects on sexual function in males.« less

Evaluation of digital PCR for absolute RNA quantification.

PubMed

Sanders, Rebecca; Mason, Deborah J; Foy, Carole A; Huggett, Jim F

2013-01-01

Gene expression measurements detailing mRNA quantities are widely employed in molecular biology and are increasingly important in diagnostic fields. Reverse transcription (RT), necessary for generating complementary DNA, can be both inefficient and imprecise, but remains a quintessential RNA analysis tool using qPCR. This study developed a Transcriptomic Calibration Material and assessed the RT reaction using digital (d)PCR for RNA measurement. While many studies characterise dPCR capabilities for DNA quantification, less work has been performed investigating similar parameters using RT-dPCR for RNA analysis. RT-dPCR measurement using three, one-step RT-qPCR kits was evaluated using single and multiplex formats when measuring endogenous and synthetic RNAs. The best performing kit was compared to UV quantification and sensitivity and technical reproducibility investigated. Our results demonstrate assay and kit dependent RT-dPCR measurements differed significantly compared to UV quantification. Different values were reported by different kits for each target, despite evaluation of identical samples using the same instrument. RT-dPCR did not display the strong inter-assay agreement previously described when analysing DNA. This study demonstrates that, as with DNA measurement, RT-dPCR is capable of accurate quantification of low copy RNA targets, but the results are both kit and target dependent supporting the need for calibration controls.

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage

PubMed Central

Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone (p = 0.002) and placebo treated clots (p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times. PMID:28459065

Palliative radiation therapy practice for advanced esophageal carcinoma in Africa.

PubMed

Sharma, V; Gaye, P M; Wahab, S A; Ndlovu, N; Ngoma, T; Vanderpuye, V; Sowuhami, A; Dawotola, D A; Kigula-Mugambe, J; Jeremic, B

2010-04-01

While numerous surveys of pattern of practices of palliative radiotherapy (RT) in advanced esophageal cancers have been published in developed countries, there is no such survey in African countries. During and after a regional training course by the International Atomic Energy Agency (IAEA) in palliative cancer care, a questionnaire was distributed to African RT centers to gather information about infrastructure and human resources available, and the pattern of practice of palliative RT for esophageal cancers. Twenty-four of the 35 centers (60%) completed the questionnaire. Twenty out of 23 (87%) centers treat patients with esophageal cancer presenting with dysphagia using external beam RT (16 centers external beam RT alone and 4 centers also use brachytherapy as a boost). Twelve (60%) centers prescribe RT doses of 30 Gy in 10 fractions and 2 centers 20 Gy in 5 fractions. Eighteen centers (78%) have low dose rate (LDR) brachytherapy, and 9 (39%) centers have high dose rate (HDR) brachytherapy. One center only used HDR brachytherapy alone to a dose of 16 Gy in 2 fractions over 8 days. RT remains a major component of treatment of patients with esophageal cancers in African countries. Still, there is a great variety among centers in both indications for RT and its characteristics for a treatment indication.

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage.

PubMed

Keric, Naureen; Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone ( p = 0.002) and placebo treated clots ( p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times.

Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy

NASA Astrophysics Data System (ADS)

Blockhuys, Stéphanie; Agarwal, Nisha Rani; Hildesjö, Camilla; Jarlsfelt, Ingvar; Wittung-Stafshede, Pernilla; Sun, Xiao-Feng

2017-10-01

Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer.

Characterization of rtSH3p13 gene encoding a development protein involved in vesicular traffic in spermiogenesis.

PubMed

Qiao, Yuan; Yang, Ju Xiang; Zhang, Xiao Dong L; Liu, Yu; Zhang, Jian Chao; Zong, Shu Dong; Miao, Shi Ying; Wang, Lin Fang; Koide, Samuel S

2004-06-01

A cDNA, designated as rtSH3p13, was isolated from a rat testis cDNA library. It consists of 1463 bp nuclear acids, which encodes a protein of 312 amino acids and was assigned the GenBank accession number AF227439. The deduced rtSH3p13 protein is a truncated isoform of SH3p13 as a result of mRNA alternative splicing. It is mainly expressed in the rat testis, detected in spermatids at the steps 8-19 of spermiogenesis, and found around the acrosome. During postnatal development, rtSH3p13 appears on day 18 and reaches maximum on day 60. Further experimental results suggested that rtSH3p13 forms a complex with activated epidermal growth factor receptor (EGFR) and interacts with synaptojanin I. Surprisingly, similar to SH3 domain, the V region of rtSH3p13 also inhibits endocytosis in CHO cells. Our results reveal a link between an rtSH3p13-synaptojanin-clathrin complex-mediated formation of pits and the process of spermiogenesis.

Evaluation of a sensitive reverse transcription PCR-enzymelinked immunosorbent assay for detection of hepatitis A virus in oysters (Saccostrea glomerata) on the east coast of the Gulf of Thailand.

PubMed

Intamaso, Uraiwan; Ketkhunthod, Sitthisak

2014-05-01

Hepatitis A virus (HAV) contamination in food can lead to major health problems. We developed a combination reverse transcription (RT) PCR method plus enzyme-linked immunosorbent assay (ELISA) to detect HAV in fresh oysters harvested along the east coast of the Gulf of Thailand. Viral nucleic acid was extracted via the glycine-arginine-polyethylene glycol method followed by RT-PCR amplification with specifically designed primers against HAV and an ELISA to detect the digoxigenin-labeled RT-PCR products. The ELISA in concert with the RT-PCR protocol further increased the detection sensitivity by 100-fold for the HAV genome and 10-fold in artificially contaminated oysters. The overall sensitivity of the RT-PCR in combination with the ELISA was 31.88 pg and 16 PFU/g, respectively. The ELISA increases the specificity of the RT-PCR assay for detecting naturally occurring HAV in oysters. This combined RT-PCR-ELISA approach is a practical and sensitive method for HAV detection and can be utilized in routine screening for HAV in shellfish.

Comparison of 2 Assays for Diagnosing Rotavirus and Evaluating Vaccine Effectiveness in Children with Gastroenteritis

PubMed Central

Mijatovic-Rustempasic, Slavica; Tam, Ka Ian; Lyde, Freda C.; Payne, Daniel C.; Szilagyi, Peter; Edwards, Kathryn; Staat, Mary Allen; Weinberg, Geoffrey A.; Hall, Caroline B.; Chappell, James; McNeal, Monica; Gentsch, Jon R.; Bowen, Michael D.; Parashar, Umesh D.

2013-01-01

We compared rotavirus detection rates in children with acute gastroenteritis (AGE) and in healthy controls using enzyme immunoassays (EIAs) and semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated rotavirus vaccine effectiveness using different laboratory-based case definitions to determine which best identified the proportion of disease that was vaccine preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative. Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive. Rotavirus vaccine was highly effective (84% [95% CI 71%–91%]) in EIA-positive children but offered no significant protection (14% [95% CI −105% to 64%]) in EIA-negative children for whom virus was detected by qRT-PCR alone. Children with rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination, suggesting that rotavirus detected by qRT-PCR alone might not be causally associated with AGE in all patients. PMID:23876518

Advanced ECCD based NTM control in closed-loop operation at ASDEX Upgrade (AUG)

NASA Astrophysics Data System (ADS)

Reich, Matthias; Barrera-Orte, Laura; Behler, Karl; Bock, Alexander; Giannone, Louis; Maraschek, Marc; Poli, Emanuele; Rapson, Chris; Stober, Jörg; Treutterer, Wolfgang

2012-10-01

In high performance plasmas, Neoclassical Tearing Modes (NTMs) are regularly observed at reactor-grade beta-values. They limit the achievable normalized beta, which is undesirable because fusion performance scales as beta squared. The method of choice for controlling and avoiding NTMs at AUG is the deposition of ECCD inside the magnetic island for stabilization in real-time (rt). Our approach to tackling such complex control problems using real-time diagnostics allows rigorous optimization of all subsystems. Recent progress in rt-equilibrium reconstruction (< 3.5 ms), rt-localization of NTMs (< 8 ms) and rt beam tracing (< 25 ms) allows closed-loop feedback operation using multiple movable mirrors as the ECCD deposition actuator. The rt-equilibrium uses function parametrization or a fast Grad-Shafranov solver with an option to include rt-MSE measurements. The island localization is based on a correlation of ECE and filtered Mirnov signals. The rt beam-tracing module provides deposition locations and their derivative versus actuator position of multiple gyrotrons. The ``MHD controller'' finally drives the actuators. Results utilizing closed-loop operation with multiple gyrotrons and their effect on NTMs are shown.

TMPA Products 3B42RT & 3B42V6: Evaluation and Application in Qinghai-Tibet Plateau

NASA Astrophysics Data System (ADS)

Hao, Z.; Sun, L.; Wang, J.

2012-04-01

Hydrological researchers in Qinghai-Tibet Plateau tend to be haunted by deficiency of station gauged precipitation data for the sparse and uneven distribution of local meteorological stations. Fortunately, alternative data can be obtained from TRMM (Tropic Rainfall Measurement Mission) satellite. Preliminary evaluation and necessary correction of TRMM satellite rainfall products is required for the sake of reliability and suitability considering that TRMM precipitation is unconventional and natural condition in Qinghai-Tibet Plateau is unusually complicated. 3B42RT and 3B42V6 products from TRMM Multisatellite Precipitation Analysis(TMPA) are evaluated in northeast Qinghai-Tibet Plateau with 50 stations quality-controlled gauged daily precipitation as the benchmark precipitation set. It is found that the RT data overestimates the actual precipitation greatly while V6 only overestimates it slightly. RT data shows different seasonal and inter-annual accuracies. Summer and autumn see better accuracies than winter and spring and wet years see higher accuracies than dry years. Latitude is believed to be an important factor that influences the accuracy of satellite precipitation. Both RT and V6 can reflect the general pattern of the spatial distribution of precipitation even though RT overestimates the quantity greatly. A new parameter, accumulated precipitation weight point (APWP), was introduced to describe the temporal-spatial pattern evolution of precipitation. The APWP of both RT and V6 were moving from south to north in the past decade, but they are all in the west of station gauged precipitation APWP(s).V6 APWP track fit gauged precipitation perfectly while RT APWP track has over-exaggerated legs, indicating that spatial distribution of RT precipitation experienced unreasonable sharp changes. A practical and operational procedure to correct satellite precipitation data is developed. For RT, there are two steps. Step 1, the downscaling, original daily precipitation was multiplied by a ratio of its monthly satellite/station precipitation gauged precipitation. Step2, objective analysis, Barnes/Cressman successive correction as well as Optimal Interpolation was applied to refine the processed daily results. Step 1 is unnecessary for V6 correction. The accuracy of RT can be improved significantly and the spatial details of satellite precipitation can be obtained as much as possible while quite little improvement showed in V6 correction. Besides, the iteration of successive correction should not be more than twice and the ideal influence radius for Optimal Interpolation is R=5. The original/corrected RT and V6 data sets were used as precipitation inputs to drive a newly developed hydrological model DHM-SP in the headwater region of the Yellow river so as to assess their applicability in simulating the daily runoff. V6 simulation result is qualified even though it is uncorrected. The bias in RT is too much to make use of RT as model input directly while quite satisfied results can be derived from corrected RT input. The simulation results of corrected RT are even better than that of station gauged and V6.

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.

PubMed

Gautam, Rashi; Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86-89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix® and RotaTeq® vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains.

Factors associated with the rectal temperature of Holstein dairy cows during the first 10 days in milk.

PubMed

Wenz, J R; Moore, D A; Kasimanickam, R

2011-04-01

Daily evaluation of rectal temperature (RT) during the first 10 d in milk (DIM) is used to facilitate the early identification of postpartum complications, particularly metritis in dairy cows. The factors associated with RT of postpartum dairy cows have not been clearly established and the RT threshold used to define fever has been variable. The objectives were to identify factors associated with the RT of postpartum dairy cows and provide descriptive statistics of the RT during the first 10 DIM to clarify the normal range of RT for cows. Daily RT was evaluated from 1 to 10 DIM for all cows calving during 2 consecutive summers on a single 1,500-cow Holstein dairy. Cows were placed into metabolic/digestive (METB), infectious (INF), and no recorded disease (NONE) groups based on disease diagnoses during the first 10 DIM. Cows were grouped based on calving difficulty and parity. Multiple linear regression models with repeated measures were used to evaluate the factors associated with RT. Three hundred and ninety-two cows were evaluated, of which 45% were primiparous and 32% required assistance at calving. No difference was observed in calving assistance by parity. First disease diagnoses peaked in the INF and METB groups at 3 and 1 DIM, respectively. The RT of primiparous cows was 0.1 to 0.2°C higher than that of multiparous cows from 1 to 8 DIM, accounting for calving difficulty, twin births, month of calving, and disease group in the model. The INF group cows had a higher RT than did NONE group cows (38.9±0.04 to 39.2±0.73 vs. 38.7±0.03°C, respectively) on each of the first 10 DIM, which was approximately 0.6°C higher from 3 to 5 DIM. The RT of cows with metritis was at least 0.1°C higher (38.8±0.05°C) than that of NONE group cows beginning 4 d before diagnosis. The mean RT of primiparous, defined healthy (NONE group) cows was 38.8±0.02°C, with an upper normal limit (mean+2 SD) of 39.6°C. The mean RT of multiparous cows in the NONE group during the first 10 DIM was 38.7±0.01°C, with an upper normal limit of 39.5°C. The RT of dairy cattle during the first 10 DIM was associated with parity, month of calving, and an infectious disease diagnosis, particularly the diagnosis of metritis. The normal RT of dairy cattle in the immediate postpartum period, during the warm summer months, is potentially higher than that generally reported. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples

PubMed Central

Mijatovic-Rustempasic, Slavica; Esona, Mathew D.; Tam, Ka Ian; Quaye, Osbourne; Bowen, Michael D.

2016-01-01

Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq® and Rotarix®, has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix® and RotaTeq®) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix® NSP2 and RotaTeq® VP6 qRT-PCRs for detection of Rotarix® and RotaTeq® vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8–100% sensitivity, 99.7–100% specificity, 85–95% efficiency and a limit of detection of 4–60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81–92% efficiency and limit of detection of 150–600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8–100% sensitivity, 100% specificity, 86–89% efficiency and a limit of detection of 12–400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82–90% efficiency and limit of detection of 120–4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix® and RotaTeq® vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains. PMID:26839745

Deployment of a Reverse Transcription Loop-Mediated Isothermal Amplification Test for Ebola Virus Surveillance in Remote Areas in Guinea.

PubMed

Kurosaki, Yohei; Magassouba, N'Faly; Bah, Hadja Aïssatou; Soropogui, Barré; Doré, Amadou; Kourouma, Fodé; Cherif, Mahamoud Sama; Keita, Sakoba; Yasuda, Jiro

2016-10-15

To strengthen the laboratory diagnostic capacity for Ebola virus disease (EVD) in the remote areas of Guinea, we deployed a mobile field laboratory and implemented reverse transcription loop-mediated isothermal amplification (RT-LAMP) for postmortem testing. We tested 896 oral swab specimens and 21 serum samples, using both RT-LAMP and reverse transcription-polymerase chain reaction (RT-PCR). Neither test yielded a positive result, and the results from RT-LAMP and RT-PCR were consistent. More than 95% of the samples were tested within 2 days of sample collection. These results highlight the usefulness of the RT-LAMP assay as an EVD diagnostic testing method in the field or remote areas. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Designing cylindrical implosion experiments on NIF to study deceleration phase of Rayleigh-Taylor

NASA Astrophysics Data System (ADS)

Vazirani, N.; Kline, J. L.; Loomis, E.; Sauppe, J. P.; Palaniyappan, S.; Flippo, K.; Srinivasan, B.; Malka, E.; Bose, A.; Shvarts, D.

2017-10-01

The Rayleigh-Taylor (RT) hydrodynamic instability occurs when a lower density fluid pushes on a higher density fluid. This occurs in inertial confinement fusion (ICF) implosions at each of the capsule interfaces during the initial acceleration and the deceleration as it stagnates. The RT instabilities mix capsule material into the fusion fuel degrading the Deuterium-Tritium reactivity and ultimately play a key role in limiting target performance. While significant effort has focused on understanding RT at the outer capsule surface, little work has gone into understanding the inner surface RT instability growth during the deceleration phase. Direct measurements of the RT instability are difficult to make at high convergence in a spherical implosion. Here we present the design of a cylindrical implosion system for the National Ignition Facility for studying deceleration phase RT. We will discuss the experimental design, the estimated instability growth, and our outstanding concerns.

Assessing medication effects in the MTA study using neuropsychological outcomes.

PubMed

Epstein, Jeffery N; Conners, C Keith; Hervey, Aaron S; Tonev, Simon T; Arnold, L Eugene; Abikoff, Howard B; Elliott, Glen; Greenhill, Laurence L; Hechtman, Lily; Hoagwood, Kimberly; Hinshaw, Stephen P; Hoza, Betsy; Jensen, Peter S; March, John S; Newcorn, Jeffrey H; Pelham, William E; Severe, Joanne B; Swanson, James M; Wells, Karen; Vitiello, Benedetto; Wigal, Timothy

2006-05-01

While studies have increasingly investigated deficits in reaction time (RT) and RT variability in children with attention deficit/hyperactivity disorder (ADHD), few studies have examined the effects of stimulant medication on these important neuropsychological outcome measures. 316 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA) completed the Conners' Continuous Performance Test (CPT) at the 24-month assessment point. Outcome measures included standard CPT outcomes (e.g., errors of commission, mean hit reaction time (RT)) and RT indicators derived from an Ex-Gaussian distributional model (i.e., mu, sigma, and tau). Analyses revealed significant effects of medication across all neuropsychological outcome measures. Results on the Ex-Gaussian outcome measures revealed that stimulant medication slows RT and reduces RT variability. This demonstrates the importance of including analytic strategies that can accurately model the actual distributional pattern, including the positive skew. Further, the results of the study relate to several theoretical models of ADHD.

Potential Utility of the Real-Time TMPA-RT Precipitation Estimates in Streamflow Prediction

NASA Technical Reports Server (NTRS)

Su, Fengge; Gao, Huilin; Huffman, George J.; Lettenmaier, Dennis P.

2010-01-01

We investigate the potential utility of the real-time Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA-RT) data for streamflow prediction, both through direct comparisons of TMPA-RT estimates with a gridded gauge product, and through evaluation of streamflow simulations over four tributaries of La Plata Basin (LPB) in South America using the two precipitation products. Our assessments indicate that the relative accuracy and the hydrologic performance of TMPA-RT-based streamflow simulations generally improved after February 2005. The improvements in TMPA-RT since 2005 are closely related to upgrades in the TMPA-RT algorithm in early February, 2005 which include use of additional microwave sensors (AMSR-E and AMSU-B) and implementation of different calibration schemes. Our work suggests considerable potential for hydrologic prediction using purely satellite-derived precipitation estimates (no adjustments by in situ gauges) in parts of the globe where in situ observations are sparse.

Cardiovascular Adaptations Induced by Resistance Training in Animal Models.

PubMed

Melo, S F S; da Silva Júnior, N D; Barauna, V G; Oliveira, E M

2018-01-01

In the last 10 years the number of studies showing the benefits of resistance training (RT) to the cardiovascular system, have grown. In comparison to aerobic training, RT-induced favorable adaptations to the cardiovascular system have been ignored for many years, thus the mechanisms of the RT-induced cardiovascular adaptations are still uncovered. The lack of animal models with comparable protocols to the RT performed by humans hampers the knowledge. We have used squat-exercise model, which is widely used by many others laboratories. However, to a lesser extent, other models are also employed to investigate the cardiovascular adaptations. In the subsequent sections we will review the information regarding cardiac morphological adaptations, signaling pathway of the cardiac cell, cardiac function and the vascular adaptation induced by RT using this animal model developed by Tamaki et al. in 1992. Furthermore, we also describe cardiovascular findings observed using other animal models of RT.

Is reticular temperature a useful indicator of heat stress in dairy cattle?

PubMed

Ammer, S; Lambertz, C; Gauly, M

2016-12-01

The present study investigated whether reticular temperature (RT) in dairy cattle is a useful indicator of heat stress considering the effects of milk yield and water intake (WI). In total, 28 Holstein-Friesian dairy cows raised on 3 farms in Lower Saxony, Germany, were studied from March to December 2013. During the study, RT and barn climate parameters (air temperature, relative humidity) were measured continuously and individual milk yield was recorded daily. Both the daily temperature-humidity index (THI) and the daily median RT per cow were calculated. Additionally, the individual WI (amount and frequency) of 10 cows during 100d of the study was recorded on 1 farm. Averaged over all farms, daily THI ranged between 35.4 and 78.9 with a mean (±standard deviation) of 60.2 (±8.7). Dairy cows were on average (±standard deviation) 110.9d in milk (±79.3) with a mean (±standard deviation) milk yield of 35.2kg/d (±9.1). The RT was affected by THI, milk yield, days in milk, and WI. Up to a THI threshold of 65, RT remained constant at 39.2°C. Above this threshold, RT increased to 39.3°C and further to 39.4°C when THI ≥70. The correlation between THI ≥70 and RT was 0.22, whereas the coefficient ranged between r=-0.08 to +0.06 when THI <70. With increasing milk yield, RT decreased slightly from 39.3°C (<30kg/d) to 39.2°C (≥40kg/d). For daily milk yields of ≥40kg, the median RT and daily milk yield were correlated at r=-0.18. The RT was greater when dairy cows yielded ≥30kg/d and THI ≥70 (39.5°C) compared with milk yields <30kg and THI <70 (39.3°C). The WI, which averaged (±standard deviation) 11.5 l (±5.7) per drinking bout, caused a mean decrease in RT of 3.2°C and was affected by the amount of WI (r=0.60). After WI, it took up to 2h until RT reached the initial level before drinking. In conclusion, RT increased when the THI threshold of 65 was exceeded. A further increase was noted when THI ≥70. Nevertheless, the effects of WI and milk yield have to be considered carefully when RT is used to detect hyperthermia in dairy cattle. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

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

Rusthoven, Chad G., E-mail: Chad.Rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overallmore » survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. Conclusions: In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.« less

Reverse transcription loop-mediated isothermal amplification assays for rapid identification of eastern and western strains of bluetongue virus in India.

PubMed

Maan, S; Maan, N S; Batra, K; Kumar, A; Gupta, A; Rao, Panduranga P; Hemadri, Divakar; Reddy, Yella Narasimha; Guimera, M; Belaganahalli, M N; Mertens, P P C

2016-08-01

Bluetongue virus (BTV) infects all ruminants, including cattle, goats and camelids, causing bluetongue disease (BT) that is often severe in naïve deer and sheep. Reverse-transcription-loop-mediated-isothermal-amplification (RT-LAMP) assays were developed to detect eastern or western topotype of BTV strains circulating in India. Each assay uses four primers recognizing six distinct sequences of BTV genome-segment 1 (Seg-1). The eastern (e)RT-LAMP and western (w)RT-LAMP assay detected BTV RNA in all positive isolates that were tested (n=52, including Indian BTV-1, -2, -3, -5, -9, -10, -16, -21 -23, and -24 strains) with high specificity and efficiency. The analytical sensitivity of the RT-LAMP assays is comparable to real-time RT-PCR, but higher than conventional RT-PCR. The accelerated eRT-LAMP and wRT-LAMP assays generated detectable levels of amplified DNA, down to 0.216 fg of BTV RNA template or 108 fg of BTV RNA template within 60-90min respectively. The assays gave negative results with RNA from foot-and-mouth-disease virus (FMDV), peste des petits ruminants virus (PPRV), or DNA from Capripox viruses and Orf virus (n=10), all of which can cause clinical signs similar to BT. Both RT-LAMP assays did not show any cross-reaction among themselves. The assays are rapid, easy to perform, could be adapted as a 'penside' test making them suitable for 'front-line' diagnosis, helping to identify and contain field outbreaks of BTV. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the RT-LAMP and LAMP methods for detection of Mycobacterium tuberculosis.

PubMed

Wu, Dandan; Kang, Jiwen; Li, Baosheng; Sun, Dianxing

2018-05-01

The current methods for detecting Mycobacterium tuberculosis (Mtb) are not clinically optimal. Standard culture methods (SCMs) are slow, costly, or unreliable, and loop-mediated isothermal amplification (LAMP) cannot differentiate live Mtb. This study compared reverse transcription (RT)-LAMP, LAMP, and an SCM for detecting Mtb. A first experiment tested the sensitivity and specificity of primers for 9 species of Mycobacterium (H37Rv, M. intracellulare, M. marinum, M. kansasii, M. avium, M. flavescens, M. smegmatis, M. fortuitum, and M. chelonae); and 3 non-Mycobacterium species (Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae). A second experiment tested sputum specimens for the presence of Mtb, from 100 patients with tuberculosis (clinical) and 22 from patients without tuberculosis (control), using Roche solid culture (SCM), LAMP, and RT-LAMP. In the clinical samples. The rates of positivity for Mtb of the SCM, LAMP, and RT-LAMP methods were 88%, 92%, and 100%, respectively. The difference in detection rate was significant between RT-LAMP and SCM, but RT-LAMP and LAMP were comparable. In the control group, the detection rates were nil for all three methods. The specificities of the methods were similar. The sensitivity of RT-LAMP was ~10-fold higher than that of LAMP for detecting Mtb. Unlike LAMP, RT-LAMP could identify viable bacteria, and was able to detect a single copy of Mtb. Among SCM, LAMP, and RT-LAMP, the latter is the most suitable for wide use in the lower-level hospitals and clinics of China for detecting Mtb in sputum samples. © 2017 Wiley Periodicals, Inc.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats

PubMed Central

Combs, Hannah L.; Jones, Theresa A.; Kozlowski, Dorothy A.

2016-01-01

Abstract Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI. PMID:26421759

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

PubMed

Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

A Graphics Processing Unit Accelerated Motion Correction Algorithm and Modular System for Real-time fMRI

PubMed Central

Scheinost, Dustin; Hampson, Michelle; Qiu, Maolin; Bhawnani, Jitendra; Constable, R. Todd; Papademetris, Xenophon

2013-01-01

Real-time functional magnetic resonance imaging (rt-fMRI) has recently gained interest as a possible means to facilitate the learning of certain behaviors. However, rt-fMRI is limited by processing speed and available software, and continued development is needed for rt-fMRI to progress further and become feasible for clinical use. In this work, we present an open-source rt-fMRI system for biofeedback powered by a novel Graphics Processing Unit (GPU) accelerated motion correction strategy as part of the BioImage Suite project (www.bioimagesuite.org). Our system contributes to the development of rt-fMRI by presenting a motion correction algorithm that provides an estimate of motion with essentially no processing delay as well as a modular rt-fMRI system design. Using empirical data from rt-fMRI scans, we assessed the quality of motion correction in this new system. The present algorithm performed comparably to standard (non real-time) offline methods and outperformed other real-time methods based on zero order interpolation of motion parameters. The modular approach to the rt-fMRI system allows the system to be flexible to the experiment and feedback design, a valuable feature for many applications. We illustrate the flexibility of the system by describing several of our ongoing studies. Our hope is that continuing development of open-source rt-fMRI algorithms and software will make this new technology more accessible and adaptable, and will thereby accelerate its application in the clinical and cognitive neurosciences. PMID:23319241

Development of Fluorescent Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) using Quenching Probes for the Detection of the Middle East Respiratory Syndrome Coronavirus.

PubMed

Shirato, Kazuya; Semba, Shohei; El-Kafrawy, Sherif A; Hassan, Ahmed M; Tolah, Ahmed M; Takayama, Ikuyo; Kageyama, Tsutomu; Notomi, Tsugunori; Kamitani, Wataru; Matsuyama, Shutoku; Azhar, Esam Ibraheem

2018-05-12

Clinical detection of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in patients is achieved using genetic diagnostic methods, such as real-time RT-PCR assay. Previously, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of MERS-CoV [Virol J. 2014. 11:139]. Generally, amplification of RT-LAMP is monitored by the turbidity induced by precipitation of magnesium pyrophosphate with newly synthesized DNA. However, this mechanism cannot completely exclude the possibility of unexpected reactions. Therefore, in this study, fluorescent RT-LAMP assays using quenching probes (QProbes) were developed specifically to monitor only primer-derived signals. Two primer sets (targeting nucleocapsid and ORF1a sequences) were constructed to confirm MERS cases by RT-LAMP assay only. Our data indicate that both primer sets were capable of detecting MERS-CoV RNA to the same level as existing genetic diagnostic methods, and that both were highly specific with no cross-reactivity observed with other respiratory viruses. These primer sets were highly efficient in amplifying target sequences derived from different MERS-CoV strains, including camel MERS-CoV. In addition, the detection efficacy of QProbe RT-LAMP was comparable to that of real-time RT-PCR assay using clinical specimens from patients in Saudi Arabia. Altogether, these results indicate that QProbe RT-LAMP assays described here can be used as powerful diagnostic tools for rapid detection and surveillance of MERS-CoV infections. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Randomized Trial of Vitamin C/E Complex for Prevention of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer.

PubMed

Chung, Man Ki; Kim, Do Hun; Ahn, Yong Chan; Choi, Joon Young; Kim, Eun Hye; Son, Young-Ik

2016-09-01

The present study was conducted to determine the preventive efficacy of vitamin C/E complex supplementation for radiotherapy (RT)-induced xerostomia in patients with head and neck cancer. Prospective, double-blinded, randomized, placebo-controlled study. A single tertiary referral institution. The trial group (n = 25) received antioxidant supplements (100 IU of vitamin E + 500 mg of vitamin C) twice per day during RT, while the control group (n = 20) received an identical placebo. Pre-RT and 1 and 6 months post-RT, patient-reported xerostomia questionnaires, observer-rated xerostomia score, and salivary scintigraphy were serially obtained to compare xerostomia severity between the 2 groups. The trial group showed greater improvements in xerostomia questionnaire and score at 6 months post-RT when compared with those at 1 month post-RT (P = .007 and .008, respectively). In contrast, the control group showed no changes between 1 and 6 months post-RT. By salivary scintigraphy, there was no difference in maximal accumulation or ejection fraction between the 2 groups. However, the trial group maintained significantly better oral indices at the prestimulatory (P = .01) and poststimulatory (P = .009) stages at 1 month post-RT, compared with the control group. At the final follow-up, there was no difference in overall survival and disease-free survival between the 2 groups. Our data suggest that short-term supplementation with an antioxidant vitamin E/C complex exerts a protective effect against RT-induced xerostomia. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Thermostable ricin vaccine protects rhesus macaques against aerosolized ricin: Epitope-specific neutralizing antibodies correlate with protection.

PubMed

Roy, Chad J; Brey, Robert N; Mantis, Nicholas J; Mapes, Kelly; Pop, Iliodora V; Pop, Laurentiu M; Ruback, Stephen; Killeen, Stephanie Z; Doyle-Meyers, Lara; Vinet-Oliphant, Heather S; Didier, Peter J; Vitetta, Ellen S

2015-03-24

Ricin toxin (RT) is the second most lethal toxin known; it has been designated by the CDC as a select agent. RT is made by the castor bean plant; an estimated 50,000 tons of RT are produced annually as a by-product of castor oil. RT has two subunits, a ribotoxic A chain (RTA) and galactose-binding B chain (RTB). RT binds to all mammalian cells and once internalized, a single RTA catalytically inactivates all of the ribosomes in a cell. Administered as an aerosol, RT causes rapid lung damage and fibrosis followed by death. There are no Food and Drug Administration-approved vaccines and treatments are only effective in the first few hours after exposure. We have developed a recombinant RTA vaccine that has two mutations V76M/Y80A (RiVax). The protein is expressed in Escherichia coli and is nontoxic and immunogenic in mice, rabbits, and humans. When vaccinated mice are challenged with injected, aerosolized, or orally administered (gavaged) RT, they are completely protected. We have now developed a thermostable, aluminum-adjuvant-containing formulation of RiVax and tested it in rhesus macaques. After three injections, the animals developed antibodies that completely protected them from a lethal dose of aerosolized RT. These antibodies neutralized RT and competed to varying degrees with a panel of neutralizing and nonneutralizing mouse monoclonal antibodies known to recognize specific epitopes on native RTA. The resulting antibody competition profile could represent an immunologic signature of protection. Importantly, the same signature was observed using sera from RiVax-immunized humans.

Apatinib alone or combined with radiotherapy in metastatic prostate cancer: Results from a pilot, multicenter study.

PubMed

Zhao, Feng; Tian, Wei; Zeng, Ming; Xia, Jianling; Hu, Honglin; Hao, Xinbao; Han, Liangfu; Liu, Hao; He, Yangke; Zhu, Xueqiang; Liang, Liang; Ao, Rui; Wei, Min; Deng, Lili; Wei, Yuquan

2017-12-19

To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation and pain relief. In phase I study, common apatinib-related AEs (arAEs) were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN). Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study, combination apatinib with RT cohorts, AEs events increased comparing with either apatinib alone or RT alone; at the same time, combination cohorts showed PSA declines of ≥50% in 12 patients, and stable disease in 6 patients. Combination cohorts had pain control significantly improved in both level and duration comparing with RT alone. In SBPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg daily in combining with RT synergized pain control, the overall AEs were manageable. Further studies are needed in large sample size future trials.

Impact of aerobic and anaerobic exercise training on oxidative stress and antioxidant defense in athletes.

PubMed

Park, Song-Young; Kwak, Yi-Sub

2016-04-01

Exercise mediates an excessive free radical production leading to oxidative stress (OS). The body has natural antioxidant systems that help decrease OS, and these systems may be enhanced with exercise training. However, only a few studies have investigated the differences in resting OS and antioxidant capacity (AOC) between aerobically trained athletes (ET), anaerobically trained athletes (RT), and untrained individuals (UT). Therefore, this study sought to investigate the resting and postexercise OS and AOC in ET, RT, and UT. Sixty healthy young males (26.6±0.8 yr) participated in this study. Subjects were divided into three groups, ET, RT, and UT by distinct training background. Resting plasma malondialdehyde (MDA) and protein carbonyls (PC) were not significantly different in ET, RT, and UT. However, MDA and PC were significantly increased following a graded exercise test (GXT) in UT but not in ET and RT. Resting total antioxidant capacity (TAC) levels and TAC were not different in ET, RT, and UT. Interestingly, TAC levels significantly decreased after the GXT in all groups. Additionally, UT showed lower post-exercise TAC levels compared to ET and RT. These results showed that ET, RT, and UT have similar OS and AOC at rest. However, both ET and RT have greater AOC against exercise mediated OS compared to UT. These findings may explain, at least in part, why both aerobic and anaerobic types of exercise training improve redox balance. However, it appears there is no specific exercise type effect in terms of redox balance.

The role of phenylalanine-119 of the reverse transcriptase of mouse mammary tumour virus in DNA synthesis, ribose selection and drug resistance.

PubMed

Entin-Meer, Michal; Sevilya, Ziv; Hizi, Amnon

2002-10-15

Phe-119 in the reverse transcriptase (RT) of mouse mammary tumour virus (MMTV) is homologous with Tyr-115 in HIV type 1 (HIV-1) RT and to Phe-155 in murine leukaemia virus (MLV) RT. By mutating these residues in HIV-1 and MLV RTs (which are strict DNA polymerases) the enzymes were shown to function also as RNA polymerases. Owing to the uniqueness of MMTV as a type B retrovirus, we have generated a Phe-119-Val mutant of MMTV RT to study the involvement of this residue in affecting the catalytic features of this RT. The data presented here show that the mutant MMTV RT can incorporate both deoxyribonucleosides and ribonucleosides while copying either RNA or DNA. In addition, this mutant RT shows resistance to nucleoside analogues and an enhanced fidelity of DNA synthesis; all relative to the wild-type enzyme. The Phe-119-Val mutant is also different from the wild-type enzyme in its preference for most template primers tested and in its ability to synthesize DNA under non-processive and processive conditions. Overall, it is likely that the aromatic side chain of Phe-119 is located at the dNTP-binding site of MMTV RT and thus might be part of a putative "steric gate" that prevents the incorporation of nucleoside triphosphates. Since the only three-dimensional structures of RTs published so far are those of HIV-1 and MLV, it is likely that MMTV RT folds quite similarly to these RTs.

A graphics processing unit accelerated motion correction algorithm and modular system for real-time fMRI.

PubMed

Scheinost, Dustin; Hampson, Michelle; Qiu, Maolin; Bhawnani, Jitendra; Constable, R Todd; Papademetris, Xenophon

2013-07-01

Real-time functional magnetic resonance imaging (rt-fMRI) has recently gained interest as a possible means to facilitate the learning of certain behaviors. However, rt-fMRI is limited by processing speed and available software, and continued development is needed for rt-fMRI to progress further and become feasible for clinical use. In this work, we present an open-source rt-fMRI system for biofeedback powered by a novel Graphics Processing Unit (GPU) accelerated motion correction strategy as part of the BioImage Suite project ( www.bioimagesuite.org ). Our system contributes to the development of rt-fMRI by presenting a motion correction algorithm that provides an estimate of motion with essentially no processing delay as well as a modular rt-fMRI system design. Using empirical data from rt-fMRI scans, we assessed the quality of motion correction in this new system. The present algorithm performed comparably to standard (non real-time) offline methods and outperformed other real-time methods based on zero order interpolation of motion parameters. The modular approach to the rt-fMRI system allows the system to be flexible to the experiment and feedback design, a valuable feature for many applications. We illustrate the flexibility of the system by describing several of our ongoing studies. Our hope is that continuing development of open-source rt-fMRI algorithms and software will make this new technology more accessible and adaptable, and will thereby accelerate its application in the clinical and cognitive neurosciences.

Clinical Practice Patterns of Radiotherapy in Patients with Hepatocellular Carcinoma: A Korean Radiation Oncology Group Study (KROG 14-07)

PubMed Central

Cha, Hyejung; Park, Hee Chul; Yu, Jeong Il; Kim, Tae Hyun; Nam, Taek-Keun; Yoon, Sang Min; Yoon, Won Sup; Kim, Jun Won; Kim, Mi Sook; Jang, Hong Seok; Choi, Youngmin; Kim, Jin Hee; Kay, Chul Seung; Jung, Inkyung; Seong, Jinsil

2017-01-01

Purpose The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). Materials and Methods We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. Results The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. Conclusion Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival. PMID:27338036

Patterns of Practice in Palliative Radiotherapy for Painful Bone Metastases: Impact of a Regional Rapid Access Clinic on Access to Care

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

Wu, Jackson S.Y., E-mail: jackson.wu@cancerboard.ab.c; Kerba, Marc; Wong, Rebecca K.S.

2010-10-01

Purpose: External beam radiotherapy (RT) is commonly indicated for the palliation of symptomatic bone metastases, but there is evidence of underutilization of this treatment modality in palliative care for cancer populations. This study was conducted to investigate factors that influenced the use of palliative RT services at a regional comprehensive cancer center. Methods and Materials: A cohort of patients with radiographically confirmed bone metastases and first-time users of palliative RT between 2003 and 2005 was retrospectively reviewed from the time of initial diagnosis of bone metastases to death or last follow-up. Type of radiation treatment service provider used (rapid accessmore » or routine access) and patient-, tumor-, and treatment-related factors were analyzed for their influences on the number of treatment courses given over the duration of disease. Results: A total of 887 patients received 1,354 courses of palliative RT for bone metastases at a median interval of 4.0 months between courses. Thirty-three percent of patients required more than one RT course. Increased age and travel distance reduced the likelihood and number of treatment courses, while service through a rapid access clinic was independently associated with an increase in subsequent use of palliative RT. Conclusions: A rapid access service model for palliative RT facilitated access to RT. Travel distance and other factors remained substantial barriers to use of palliative RT services. The pattern of practice suggests an unmet need for symptom control in patients with bone metastases.« less

Association of childhood trauma with fatigue, depression, stress, and inflammation in breast cancer patients undergoing radiotherapy.

PubMed

Han, Tatiana J; Felger, Jennifer C; Lee, Anna; Mister, Donna; Miller, Andrew H; Torres, Mylin A

2016-02-01

This pilot study examined whether breast cancer patients with childhood trauma exhibit increased fatigue, depression, and stress in association with inflammation as a result of whole breast radiotherapy (RT). Twenty breast cancer patients were enrolled in a prospective, longitudinal study of fatigue, depression, and perceived stress prior to RT, week 6 of RT, and 6 weeks post-RT. Six weeks after RT, subjects completed the childhood trauma questionnaire (CTQ). Patients were also administered the multidimensional fatigue inventory, inventory of depressive symptomatology-self-reported, and perceived stress scale at all three time-points and underwent blood sampling prior to RT for gene expression and inflammatory markers previously associated with childhood trauma and behavioral symptoms in breast cancer patients. Eight subjects (40%) had past childhood trauma (CTQ+). Compared to CTQ- patients, CTQ+ patients had significantly higher fatigue, depression, and stress scores before, during, and after RT (p < 0.05); however, RT did not increase these symptoms in either group. CTQ+ patients also exhibited increased baseline expression of gene transcripts related to inflammatory signaling, and baseline inflammatory markers including c-reactive protein, interleukin (IL)-6, and IL-1 receptor antagonist were positively correlated with depression, fatigue, and stress scores in CTQ+ but not CTQ- patients. Childhood trauma was prevalent and was associated with increased symptoms of fatigue, depression, and stress irrespective of RT. Increased symptoms in CTQ+ patients were also associated with baseline inflammatory markers. Treatments targeting childhood trauma and related inflammation may improve symptoms in breast cancer patients. Copyright © 2015 John Wiley & Sons, Ltd.

Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG).

PubMed

Deng, Xiu-Wen; Wu, Jun-Xin; Wu, Tao; Zhu, Su-Yu; Shi, Mei; Su, Hang; Wang, Ying; He, Xia; Xu, Li-Ming; Yuan, Zhi-Yong; Zhang, Li-Ling; Wu, Gang; Qu, Bao-Lin; Qian, Li-Ting; Hou, Xiao-Rong; Zhang, Fu-Quan; Zhang, Yu-Jing; Zhu, Yuan; Cao, Jian-Zhong; Lan, Sheng-Min; Dong, Mei; Qi, Shu-Nan; Yang, Yong; Li, Ye-Xiong

2018-05-05

This study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). Of 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). Compared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028). For patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival. Copyright © 2018 Elsevier B.V. All rights reserved.

The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

NASA Astrophysics Data System (ADS)

Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

2016-02-01

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial.

PubMed

van Hezewijk, Marjan; Bastiaannet, Esther; Putter, Hein; Scholten, Astrid N; Liefers, Gerrit-Jan; Rea, Daniel; Hasenburg, Annette; Paridaens, Robert; Hozumi, Yasuo; Markopoulos, Christos; Seynaeve, Caroline; Jones, Stephen E; Marijnen, Corrie A M; van de Velde, Cornelis J H

2013-08-01

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population. Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS+RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST+RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n=199), and patients treated by lumpectomy without radiotherapy (n=349) were excluded. After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3-4.9%) for MST-only, 3.4% (95% CI 2.4-4.2%) for MST+RT and 1.9% (95% CI 1.5-2.3%) for BCS+RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS+RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10-2.11), not for MST+RT (HR 0.78; 95% CI 0.50-1.22). This explorative analysis showed a higher LRR risk after MST-only than after BCS+RT, even after adjustment for prognostic factors. As this effect was not seen for MST+RT versus BCS+RT, it might be explained by the beneficial effects of radiation treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An analysis of needs for respiratory therapists in northeast Ohio and development of strategies to meet increased recruitment demands.

PubMed

Orens, Douglas K; Chatburn, Robert L; Volsko, Teresa A; Stoller, James K

2007-12-01

The 2005 American Association for Respiratory Care Human Resources Survey suggested that the national demand for respiratory therapists (RTs) exceeds the supply. At the Cleveland Clinic an expected hospital expansion of 350 beds by 2008 has increased the need for RT staff. This report describes a strategy by which we developed a plan, in concert with local RT colleges, to recruit RTs. Local RT managers were surveyed regarding demand for RTs. We developed a recruitment plan, based on discussions with RT program directors. The survey data and models estimated an annual mean of 33.4 new positions in northeast Ohio. Despite the fact that approximately 84 people graduated from northeast Ohio RT programs yearly in 2004 to 2007, the growth in demand for RTs exceeded the estimated supply. The main factor that caused RT schools to limit the supply of RTs was the paucity of clinical sites. Our analysis shows the schools could achieve a 40% increase in student output, and that if the Cleveland Clinic could essentially double its graduate hires, all RT staff needs in our hospital would be met by 2010. To assure a needed supply of RTs, this work shows the value of modeling supply and demand scenarios, coupled with surveying local RT leaders and fostering dialog between local RT leaders in hospitals and colleges. The product of this activity was a strategy for achieving recruitment goals while assuring that other regional demands for RTs are also met. We recommend this approach to colleagues facing similar challenges.

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012; the difference between 1998-2004 and 2005-2010 was not statistically significant. Fewer than half of patients with high-intermediate-risk endometrial cancer by Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria received adjuvant RT despite evidence demonstrating improved local control. Both patient- and tumor-related factors are associated with delivery of adjuvant RT and the modality selected.

Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a highly sensitive detection of enterovirus in the stool samples of acute flaccid paralysis cases

PubMed Central

2009-01-01

Background In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV) from the stool samples of acute flaccid paralysis (AFP) cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV. Methods A primer set was designed for RT-LAMP to detect enterovirus preferably those with PV-like 5'NTRs of the viral genome. The sensitivity of RT-LAMP system was evaluated with prototype strains of enterovirus. Detection of enterovirus from stool extracts was examined by using RT-LAMP system. Results We detected at least 400 copies of the viral genomes of PV(Sabin) strains within 90 min by RT-LAMP with the primer set. This RT-LAMP system showed a preference for Human enterovirus species C (HEV-C) strains including PV, but exhibited less sensitivity to the prototype strains of HEV-A and HEV-B (detection limits of 7,400 to 28,000 copies). Stool extracts, from which PV, HEV-C, or HEV-A was isolated in the cell culture system, were mostly positive by RT-LAMP method (positive rates of 15/16 (= 94%), 13/14 (= 93%), and 4/4 (= 100%), respectively). The positive rate of this RT-LAMP system for stool extracts from which HEV-B was isolated was lower than that of HEV-C (positive rate of 11/21 (= 52%)). In the stool samples, which were negative for enterovirus isolation by the cell culture system, we found that two samples were positive for RT-LAMP (positive rates of 2/38 (= 5.3%)). In these samples, enterovirus 96 was identified by sequence analysis utilizing a seminested PCR system. Conclusions RT-LAMP system developed in this study showed a high sensitivity comparable to that of the cell culture system for the detection of PV, HEV-A, and HEV-C, but less sensitivity to HEV-B. This RT-LAMP system would be useful for the direct detection of enterovirus from the stool extracts. PMID:20015403

Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance

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

Das, Kalyan; Martinez, Sergio E.; Arnold, Eddy

HIV-1 reverse transcriptase (RT) is targeted by multiple drugs. RT mutations that confer resistance to nucleoside RT inhibitors (NRTIs) emerge during clinical use. Q151M and four associated mutations, A62V, V75I, F77L, and F116Y, were detected in patients failing therapies with dideoxynucleosides (didanosine [ddI], zalcitabine [ddC]) and/or zidovudine (AZT). The cluster of the five mutations is referred to as the Q151M complex (Q151Mc), and an RT or virus containing Q151Mc exhibits resistance to multiple NRTIs. To understand the structural basis for Q151M and Q151Mc resistance, we systematically determined the crystal structures of the wild-type RT/double-stranded DNA (dsDNA)/dATP (complex I), wild-type RT/dsDNA/ddATPmore » (complex II), Q151M RT/dsDNA/dATP (complex III), Q151Mc RT/dsDNA/dATP (complex IV), and Q151Mc RT/dsDNA/ddATP (complex V) ternary complexes. The structures revealed that the deoxyribose rings of dATP and ddATP have 3'-endo and 3'-exo conformations, respectively. The single mutation Q151M introduces conformational perturbation at the deoxynucleoside triphosphate (dNTP)-binding pocket, and the mutated pocket may exist in multiple conformations. The compensatory set of mutations in Q151Mc, particularly F116Y, restricts the side chain flexibility of M151 and helps restore the DNA polymerization efficiency of the enzyme. The altered dNTP-binding pocket in Q151Mc RT has the Q151-R72 hydrogen bond removed and has a switched conformation for the key conserved residue R72 compared to that in wild-type RT. On the basis of a modeled structure of hepatitis B virus (HBV) polymerase, the residues R72, Y116, M151, and M184 in Q151Mc HIV-1 RT are conserved in wild-type HBV polymerase as residues R41, Y89, M171, and M204, respectively; functionally, both Q151Mc HIV-1 and wild-type HBV are resistant to dideoxynucleoside analogs.« less

Development of a one-step RT-PCR assay for detection of pancoronaviruses (α-, β-, γ-, and δ-coronaviruses) using newly designed degenerate primers for porcine and avian `fecal samples.

PubMed

Hu, Hui; Jung, Kwonil; Wang, Qiuhong; Saif, Linda J; Vlasova, Anastasia N

2018-06-01

Coronaviruses (CoVs) are critical human and animal pathogens because of their potential to cause severe epidemics of respiratory or enteric diseases. In pigs, the newly emerged porcine deltacoronavirus (PDCoV) and re-emerged porcine epidemic diarrhea virus (PEDV) reported in the US and Asia, as well as the discovery of novel CoVs in wild bats or birds, has necessitated development of improved detection and control measures for these CoVs. Because the previous pancoronavirus (panCoV) RT-PCR established in our laboratory in 2007-2011 did not detect deltacoronaviruses (δ-CoVs) in swine fecal and serum samples, our goal was to develop a new panCoV RT-PCR assay to detect known human and animal CoVs, including δ-CoVs. In this study, we designed a new primer set to amplify a 668 bp-region within the RNA-dependent RNA polymerase (RdRP) gene that encodes the most conserved protein domain of α-, β-, γ-, and δ-CoVs. We established a one-step panCoV RT-PCR assay and standardized the assay conditions. The newly established panCoV RT-PCR assay was demonstrated to have a high sensitivity and specificity. Using a panel of 60 swine biological samples (feces, intestinal contents, and sera) characterized by PEDV, PDCoV and transmissible gastroenteritis virus-specific RT-PCR assays, we demonstrated that sensitivity and specificity of the newly established panCoV RT-PCR assay were 100%. 400 avian fecal (RNA) samples were further tested simultaneously for CoV by the new panCoV RT-PCR and a one-step RT-PCR assay with the δ-CoV nucleocapsid-specific universal primers. Four of 400 avian samples were positive for CoV, three of which were positive for δ-CoV by the conventional RT-PCR. PanCoV RT-PCR fragments for 3 of the 4 CoVs were sequenced. Phylogenetic analysis revealed the presence of one γ-CoV and two δ-CoV in the sequenced samples. The newly designed panCoV RT-PCR assay should be useful for the detection of currently known CoVs in animal biological samples. Copyright © 2018 Elsevier B.V. All rights reserved.

NASA/SPoRt: GOES-R Activities in Support of Product Development, Management, and Training

NASA Technical Reports Server (NTRS)

Fuell, Kevin; Jedlovec, Gary; Molthan, Andrew; Stano, Geoffrey

2012-01-01

SPoRT is using current capabilities of MODIS and VIIRS, combined with current GOES (i.e. Hybrid Imagery) to demonstrate mesoscale capabilities of future ABI instrument. SPoRT is transitioning RGBs from EUMETSAT standard "recipes" to demonstrate a method to more efficiently handle the increase channels/frequency of ABI. Challenges for RGB production exist. Internal vs. external production, Bit depth needed, Adding quantitative information, etc. SPoRT forming group to address these issues. SPoRT is leading efforts on the application of total lightning in operations and to educate users of this new capability. Training in many forms is used to support testbed activities and is a key part to the transition process.

Applications of NASA and NOAA Satellite Observations by NASA's Short-term Prediction Research and Transition (SPoRT) Center in Response to Natural Disasters

NASA Technical Reports Server (NTRS)

Molthan, Andrew L.; Burks, Jason E.; McGrath, Kevin M.; Jedlovec, Gary J.

2012-01-01

NASA s Short-term Prediction Research and Transition (SPoRT) Center supports the transition of unique NASA and NOAA research activities to the operational weather forecasting community. SPoRT emphasizes real-time analysis and prediction out to 48 hours. SPoRT partners with NOAA s National Weather Service (NWS) Weather Forecast Offices (WFOs) and National Centers to improve current products, demonstrate future satellite capabilities and explore new data assimilation techniques. Recently, the SPoRT Center has been involved in several activities related to disaster response, in collaboration with NOAA s National Weather Service, NASA s Applied Sciences Disasters Program, and other partners.

The ViewRay system: magnetic resonance-guided and controlled radiotherapy.

PubMed

Mutic, Sasa; Dempsey, James F

2014-07-01

A description of the first commercially available magnetic resonance imaging (MRI)-guided radiation therapy (RT) system is provided. The system consists of a split 0.35-T MR scanner straddling 3 (60)Co heads mounted on a ring gantry, each head equipped with independent doubly focused multileaf collimators. The MR and RT systems share a common isocenter, enabling simultaneous and continuous MRI during RT delivery. An on-couch adaptive RT treatment-planning system and integrated MRI-guided RT control system allow for rapid adaptive planning and beam delivery control based on the visualization of soft tissues. Treatment of patients with this system commenced at Washington University in January 2014. Copyright © 2014 Elsevier Inc. All rights reserved.

Entropy Based Classifier Combination for Sentence Segmentation

DTIC Science & Technology

2007-01-01

speaker diarization system to divide the audio data into hypothetical speakers [17...the prosodic feature also includes turn-based features which describe the position of a word in relation to diarization seg- mentation. The speaker ...ro- bust speaker segmentation: the ICSI-SRI fall 2004 diarization system,” in Proc. RT-04F Workshop, 2004. [18] “The rich transcription fall 2003,” http://nist.gov/speech/tests/rt/rt2003/fall/docs/rt03-fall-eval- plan-v9.pdf.

General Aviation Activity and Avionics Survey. Calendar Year 1991

DTIC Science & Technology

1991-01-01

Prfee The U.S. Government Printing Office ( GPO ) operates U.S. Government bookstores all around the country where you can browse through the shelves...783-3238, or contact any of the following GPO Bookstores. Addresses are listed for ordering purposes. ATLANTA, GA 275 Peachtree Street, NE, Room...rt« rt« rt« M» O» *• p>m rto m io »r- oo »roi rHM om »C4 »M »rt

One-step cross-genogroup multiplex RT-qPCR with an internal control system for the detection of infectious pancreatic necrosis virus (IPNV).

PubMed

Hoferer, Marc; Braun, Anne; Skrypski, Julia; Bock, Sabine; Thalheim, Sabine; Sting, Reinhard

2017-09-01

Infectious pancreatic necrosis virus (IPNV) causes great losses in fish hatcheries world-wide. The detection of IPNV can be challenging in certain circumstances, particularly due to low viral load and the genetic variability of this RNA virus. For the first time, this project created a quantitative triplex real-time reverse transcription PCR (RT-qPCR), including an endogenous control system, for specific, sensitive and rapid detection of IPNV in routine diagnostics. Multiple sequence alignment of 46 nucleotide sequences of the segment A genome obtained from the NCBI database allowed the design of two RT-qPCR systems covering the IPNV genogroup 1 and genogroups 2-5, respectively. The completed triplex RT-qPCR including a salmonid-specific endogenous control showed high specificity and an analytical sensitivity of 20-40 oligonucleotide copies. Testing of dilution series of virus-loaded cell culture suspensions proved equality of the triplex RT-qPCR with virus detection in cell culture and a higher sensitivity than conventional RT-PCR in field samples. In comparative studies of a total of 77 field samples tested, 51 showed identical positive and 19 identical negative results in cell culture and the triplex RT-qPCR. However, seven other samples yielded positive results in the triplex RT-qPCR, but negative results in cell culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a rapid and sensitive one-step reverse transcription-nested polymerase chain reaction in a single tube using the droplet-polymerase chain reaction machine.

PubMed

Yamaguchi, Akemi; Matsuda, Kazuyuki; Sueki, Akane; Taira, Chiaki; Uehara, Masayuki; Saito, Yasunori; Honda, Takayuki

2015-08-25

Reverse transcription (RT)-nested polymerase chain reaction (PCR) is a time-consuming procedure because it has several handling steps and is associated with the risk of cross-contamination during each step. Therefore, a rapid and sensitive one-step RT-nested PCR was developed that could be performed in a single tube using a droplet-PCR machine. The K562 BCR-ABL mRNA-positive cell line as well as bone marrow aspirates from 5 patients with chronic myelogenous leukemia (CML) and 5 controls without CML were used. We evaluated one-step RT-nested PCR using the droplet-PCR machine. One-step RT-nested PCR performed in a single tube using the droplet-PCR machine enabled the detection of BCR-ABL mRNA within 40min, which was 10(3)-fold superior to conventional RT nested PCR using three steps in separate tubes. The sensitivity of the one-step RT-nested PCR was 0.001%, with sample reactivity comparable to that of the conventional assay. One-step RT-nested PCR was developed using the droplet-PCR machine, which enabled all reactions to be performed in a single tube accurately and rapidly and with high sensitivity. This one-step RT-nested PCR may be applicable to a wide spectrum of genetic tests in clinical laboratories. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa

PubMed Central

Loo, Shining; Kam, Antony; Xiao, Tianshu; Nguyen, Giang K. T.; Liu, Chuan Fa; Tam, James P.

2016-01-01

Plant knottins are of therapeutic interest due to their high metabolic stability and inhibitory activity against proteinases involved in human diseases. The only knottin-type proteinase inhibitor against porcine pancreatic elastase was first identified from the squash family in 1989. Here, we report the identification and characterization of a knottin-type human neutrophil elastase inhibitor from Hibiscus sabdariffa of the Malvaceae family. Combining proteomic and transcriptomic methods, we identified a panel of novel cysteine-rich peptides, roseltides (rT1-rT8), which range from 27 to 39 residues with six conserved cysteine residues. The 27-residue roseltide rT1 contains a cysteine spacing and amino acid sequence that is different from the squash knottin-type elastase inhibitor. NMR analysis demonstrated that roseltide rT1 adopts a cystine-knot fold. Transcriptome analyses suggested that roseltides are bioprocessed by asparagine endopeptidases from a three-domain precursor. The cystine-knot structure of roseltide rT1 confers its high resistance against degradation by endopeptidases, 0.2 N HCl, and human serum. Roseltide rT1 was shown to inhibit human neutrophil elastase using enzymatic and pull-down assays. Additionally, roseltide rT1 ameliorates neutrophil elastase-stimulated cAMP accumulation in vitro. Taken together, our findings demonstrate that roseltide rT1 is a novel knottin-type neutrophil elastase inhibitor with therapeutic potential for neutrophil elastase associated diseases. PMID:27991569

Prevalence and correlates of resistance training skill competence in adolescents.

PubMed

Smith, Jordan J; DeMarco, Matthew; Kennedy, Sarah G; Kelson, Mark; Barnett, Lisa M; Faigenbaum, Avery D; Lubans, David R

2018-06-01

The aim of this study is to examine the prevalence and correlates of adolescents' resistance training (RT) skill competence. Participants were 548 adolescents (14.1 ± 0.5 years) from 16 schools in New South Wales, Australia. RT skills were assessed using the Resistance Training Skills Battery. Demographics, BMI, muscular fitness, perceived strength, RT self-efficacy, and motivation for RT were also assessed. The proportion demonstrating "competence" and "near competence" in each of the six RT skills were calculated and sex differences explored. Associations between the combined RT skill score and potential correlates were examined using multi-level linear mixed models. Overall, the prevalence of competence was low (range = 3.3% to 27.9%). Females outperformed males on the squat, lunge and overhead press, whereas males performed better on the push-up (p < .05). Significant associations were seen for a number of correlates, which largely differed by sex. Muscular fitness was moderately and positively associated with RT skills among both males (β = 0.34, 95%CIs = 0.23 to 0.46) and females (β = 0.36, 95%CIs = 0.23 to 0.48). Our findings support a link between RT skills and muscular fitness. Other associations were statistically significant but small in magnitude, and should therefore be interpreted cautiously.

Nucleic Acid Research Group (NARG) 2009-2010 Study : Optimal Priming Strategies for cDNA Synthesis in Real-Time RT-qPCR

PubMed Central

Hunter, T.C.; Knudtson, K.L.; Nadella, V.; Sol-Church, K.; Taylor, W.L.; Tighe, S.; Yueng, A.T.; Chittur, S.

2010-01-01

r1-1 Real-time reverse transcriptase quantitative PCR (RT-qPCR) is a widely used technique for measuring transcript levels. Priming strategy and reverse transcriptase enzyme are key elements that affect sensitivity and variability of RT-qPCR and microarray results. Previously, the Nucleic Acid Research Group (NARG) had conducted preliminary studies within the group to examine the effects of priming strategy on generating cDNA for use with qPCR. This year's study was an open study in which the qPCR community was invited to participate. Participants received the RT primers and RNA template and were asked to perform the RT reaction using their preferred reaction conditions. Each participating laboratory was provided at least two RNA templates of varying quality. The RT products were returned to the NARG and all RT reactions were used in a qPCR reaction. The qPCR assays looked at three genes of varying abundance, b-actin (high copy), b-glucuronidase (medium copy) and TATA binding protein (low copy) as well as varying distance from the 3? end for each transcript. Results from participating laboratories will be evaluated to determine the impact of priming strategy, assay chemistry and experimental setup on the RT step. Additionally, we will address the impact of RNA integrity on cDNA synthesis.

Improved local and regional control with radiotherapy for Merkel cell carcinoma of the head and neck.

PubMed

Strom, Tobin; Naghavi, Arash O; Messina, Jane L; Kim, Sungjune; Torres-Roca, Javier F; Russell, Jeffery; Sondak, Vernon K; Padhya, Tapan A; Trotti, Andy M; Caudell, Jimmy J; Harrison, Louis B

2017-01-01

We hypothesized that radiotherapy (RT) would improve both local and regional control with Merkel cell carcinoma of the head and neck. A single-institution institutional review board-approved study was performed including 113 patients with nonmetastatic Merkel cell carcinoma of the head and neck. Postoperative RT was delivered to the primary tumor bed (71.7% cases) ± draining lymphatics (33.3% RT cases). Postoperative local RT was associated with improved local control (3-year actuarial local control 89.4% vs 68.1%; p = .005; Cox hazard ratio [HR] 0.18; 95% confidence interval [CI] = 0.06-0.55; p = .002). Similarly, regional RT was associated with improved regional control (3-year actuarial regional control 95.0% vs 66.7%; p = .008; Cox HR = 0.09; 95% CI = 0.01-0.69; p = .02). Regional RT played an important role for both clinical node-negative patients (3-year regional control 100% vs 44.7%; p = .03) and clinical/pathological node-positive patients (3-year regional control 90.9% vs 55.6%; p = .047). Local RT was beneficial for all patients with Merkel cell carcinoma of the head and neck, whereas regional RT was beneficial for clinical node-negative and clinical/pathological node-positive patients. © 2016 Wiley Periodicals, Inc. Head Neck 39: 48-55, 2017. © 2016 Wiley Periodicals, Inc.

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PubMed

Nishimura, Y; Nakai, A; Yoshimasu, T; Yagyu, Y; Nakamatsu, K; Shindo, H; Ishida, O

2000-01-01

The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Ring trial 2016 for Bluetongue virus detection by real-time RT-PCR in France.

PubMed

Sailleau, Corinne; Viarouge, Cyril; Breard, Emmanuel; Vitour, Damien; Zientara, Stephan

2017-05-01

Since the unexpected emergence of BTV-8 in Northern Europe and the incursion of BTV-8 and 1 in France in 2006-2007, molecular diagnosis has considerably evolved. Several real-time RT-PCR (rtRT-PCR) methods have been developed and published, and are currently being used in many countries across Europe for BTV detection and typing. In France, the national reference laboratory (NRL) for orbiviruses develops and validates 'ready-to-use' kits with private companies for viral RNA detection. The regional laboratories network that was set up to deal with a heavy demand for analyses has used these available kits. From 2007, ring tests were organized to monitor the performance of the French laboratories. This study presents the results of 63 regional laboratories in the ring trial organized in 2016. Blood samples were sent to the laboratories. Participants were asked to use the rtRT-PCR methods in place in their laboratory, for detection of all BTV serotypes and specifically BTV-8. The French regional laboratories are able to detect and genotype BTV in affected animals. Despite the use of several methods (i.e. RNA extraction and different commercial rtRT-PCRs), the network is homogeneous. The ring trial demonstrated that the French regional veterinary laboratories have reliable and robust BTV diagnostic tools for BTV genome detection.

Radiotherapeutic Management of Non-Small Cell Lung Cancer in the Minimal Resource Setting.

PubMed

Rodin, Danielle; Grover, Surbhi; Xu, Melody J; Hanna, Timothy P; Olson, Robert; Schreiner, L John; Munshi, Anusheel; Mornex, Francoise; Palma, David; Gaspar, Laurie E

2016-01-01

Lung cancer is the most common cancer worldwide and the fifth most common cause of death globally. Its incidence continues to increase, especially within low- and middle-income countries (LMICs), which have limited capacity to address the growing need for treatment. The standard of care for lung cancer treatment often involves radiation therapy (RT), which plays an important therapeutic role in curative-intent treatment of early-stage to locally advanced disease, as well as in palliation. The infrastructure, equipment, and human resources required for RT may be limited in LMICs. However, this narrative review discusses the scope of the problem of lung cancer in LMICs, the role of RT technologies in lung cancer treatment, and RT capacity in developing countries. Strategies are presented for maximizing the availability and impact of RT in settings with minimal resource availability, and areas for potential future innovation are identified. Priorities for LMICs involve increasing access to RT equipment and trained health care professionals, ensuring quality of care, providing guidance on priority setting with limited resources, and encouraging innovation to increase the economic efficiency of RT delivery. Several international initiatives are currently under way and represent important first steps toward scaling up RT in LMICs to treat lung cancer. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Long-term outcomes of late course accelerated hyper-fractionated radiotherapy for localized esophageal carcinoma in Mainland China: a meta-analysis.

PubMed

Zhang, Y W; Chen, L; Bai, Y; Zheng, X

2011-09-01

Published data on the long-term survival results of patients with localized esophageal carcinoma receiving late course accelerated hyper-fractionated radiotherapy (LCAF RT) versus conventional fractionated radiotherapy (CF RT) are inconclusive. In order to derive a more precise estimation of the both treatment-regimes, a meta-analysis based on systematic review of published articles was performed. A meta-analysis was performed using trials identified through Pubmed and Chinese national knowledge infrastructure. Results in 5-year survival and 5-year local control were collected from randomized trials comparing LCAF RT with CF RT. Review Manager (The Cochrane Collaboration, Oxford, England) and Stata software (Stata Corporation, College Station, TX, USA) were used for data management. A total of 11 trials were involved in this analysis with 572 cases and 567 controls. Our results showed that LCAF RT, compared with CF RT, significantly improved the 5-year survival (odds ratio [OR]= 2.93, 95% confidence interval [CI]: 2.15-4.00, P < 0.00001) and 5-year local control (OR = 3.96, 95% CI: 2.91-5.38, P < 0.00001). LCAF RT was more therapeutically beneficial than CF RT in the localized esophageal carcinoma. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Radiation therapy in the last month of life.

PubMed

Patel, Anand; Dunmore-Griffith, Jacquelyn; Lutz, Stephen; Johnstone, Peter A S

2014-05-01

We sought to survey a large, multi-center patient sample to better characterize/quantify RT utilization at the end of life. Few objective data exist for radiation therapy (RT) delivery at end of life (EOL). Data were retrieved for all patients receiving RT in calendar year 2010 in the Department of Radiation Oncology at Indiana University (IU) and Howard University (HU) hospitals. Specific attention was made of the group of patients receiving RT in the last 30 days of life. A total of 852 patients received all or part of their RT during 2010 (HU: 139, IU: 713). At time of analysis in early 2012, 179 patients had died (21%). Fifty-four patients (6.3% of total; 30% of expired patients) died within 30 days of receiving their last treatment. Twenty patients (2.3% of total; 11.2% of expired patients) received RT within their last week of life. For both sites, the median time until death from completion of therapy was 12.5 days (range 2-30 days). Radiation in the last month of life is likely to provide minimal palliation or survival benefit. This, coupled with the financial implications, time investment, and physical costs, suggests that physicians and patients should more strongly consider hospice, and minimize duration of palliative RT courses as far as possible. As with chemotherapy, RT utilization at EOL should be considered for collection as an overuse metric.

A novel RT-PCR for the detection of Helicobacter pylori and identification of clarithromycin resistance mediated by mutations in the 23S rRNA gene.

PubMed

Redondo, Javier Jareño; Keller, Peter M; Zbinden, Reinhard; Wagner, Karoline

2018-01-01

In this study we evaluated the commercially available LightMix® RT-PCR assay for Helicobacter pylori detection and identification of clarithromycin (CLR) resistance in culture and clinical specimens (gastric biopsies and stool). The H. pylori LightMix® RT-PCR detects a 97bp long fragment of the 23S rRNA gene and allows the identification of 3 distinct point mutations conferring CLR resistance via melting curve analysis. The performance of the H. pylori LightMix® RT-PCR was evaluated using a set of 60 H. pylori strains showing phenotypical CLR susceptibility or CLR resistance (Minimum inhibitory concentrations from 0.016 to 256mg/L). We found high concordance (95%) between phenotypical CLR resistance screening by E-Test® and the Lightmix® RT-PCR. Discrepant results were verified by sequencing of the 23S rRNA gene that always confirmed the results obtained by Lightmix® RT-PCR. Furthermore, H. pylori was detected in clinical biopsy and stool specimens by Lightmix® RT-PCR that identified the correct H. pylori genotype. The LightMix® RT-PCR is an accurate, sensitive and easy to use test for H. pylori and CLR resistance detection and can therefore be readily implemented in any diagnostic laboratory. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of ALK gene rearrangement in central nervous system metastases of non-small-cell lung cancer using two-step RT-PCR technique.

PubMed

Nicoś, M; Krawczyk, P; Wojas-Krawczyk, K; Bożyk, A; Jarosz, B; Sawicki, M; Trojanowski, T; Milanowski, J

2017-12-01

RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status. 21% of CNS metastases of NSCLC (30/145) showed presence of mRNA containing abnormal ALK sequences. FISH and IHC tests confirmed the presence of ALK gene rearrangement and expression of ALK abnormal protein in seven patients with positive result of RT-PCR analysis (4.8% of all patients, 20% of RT-PCR positive patients). RT-PCR method compared to FISH analysis achieved 100% of sensitivity and only 82.7% of specificity. IHC method compared to FISH method indicated 100% of sensitivity and 97.8% of specificity. In comparison to IHC, RT-PCR showed identical sensitivity with high number of false positive results. Utility of RT-PCR technique in screening of ALK abnormalities and in qualification patients for molecularly targeted therapies needs further validation.

Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

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

Oliveira Lopes, Carlos; Callera, Fernando, E-mail: fcallera@gmail.com

Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrastmore » with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.« less

Intracellular flow cytometry may be combined with good quality and high sensitivity RT-qPCR analysis.

PubMed

Sandstedt, Mikael; Jonsson, Marianne; Asp, Julia; Dellgren, Göran; Lindahl, Anders; Jeppsson, Anders; Sandstedt, Joakim

2015-12-01

Flow cytometry (FCM) has become a well-established method for analysis of both intracellular and cell-surface proteins, while quantitative RT-PCR (RT-qPCR) is used to determine gene expression with high sensitivity and specificity. Combining these two methods would be of great value. The effects of intracellular staining on RNA integrity and RT-qPCR sensitivity and quality have not, however, been fully examined. We, therefore, intended to assess these effects further. Cells from the human lung cancer cell line A549 were fixed, permeabilized and sorted by FCM. Sorted cells were analyzed using RT-qPCR. RNA integrity was determined by RNA quality indicator analysis. A549 cells were then mixed with cells of the mouse cardiomyocyte cell line HL-1. A549 cells were identified by the cell surface marker ABCG2, while HL-1 cells were identified by intracellular cTnT. Cells were sorted and analyzed by RT-qPCR. Finally, cell cultures from human atrial biopsies were used to evaluate the effects of fixation and permeabilization on RT-qPCR analysis of nonimmortalized cells stored prior to analysis by FCM. A large amount of RNA could be extracted even when cells had been fixed and permeabilized. Permeabilization resulted in increased RNA degradation and a moderate decrease in RT-qPCR sensitivity. Gene expression levels were also affected to a moderate extent. Sorted populations from the mixed A549 and HL-1 cell samples showed gene expression patterns that corresponded to FCM data. When samples were stored before FCM sorting, the RT-qPCR analysis could still be performed with high sensitivity and quality. In summary, our results show that intracellular FCM may be performed with only minor impairment of the RT-qPCR sensitivity and quality when analyzing sorted cells; however, these effects should be considered when comparing RT-qPCR data of not fixed samples with those of fixed and permeabilized samples. © 2015 International Society for Advancement of Cytometry.

Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database.

PubMed

Gharzai, Laila; Verma, Vivek; Denniston, Kyle A; Bhirud, Abhijeet R; Bennion, Nathan R; Lin, Chi

2016-01-01

Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973-2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255-367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03-1.47, HR 1.961, 95% CI 1.466-2.624). Lower esophageal subsite (33-40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect.

Association Between White Blood Cell Count Following Radiation Therapy With Radiation Pneumonitis in Non-Small Cell Lung Cancer

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

Tang, Chad; Gomez, Daniel R.; Wang, Hongmei

Purpose: Radiation pneumonitis (RP) is an inflammatory response to radiation therapy (RT). We assessed the association between RP and white blood cell (WBC) count, an established metric of systemic inflammation, after RT for non-small cell lung cancer. Methods and Materials: We retrospectively analyzed 366 patients with non-small cell lung cancer who received ≥60 Gy as definitive therapy. The primary endpoint was whether WBC count after RT (defined as 2 weeks through 3 months after RT completion) was associated with grade ≥3 or grade ≥2 RP. Median lung volume receiving ≥20 Gy (V{sub 20}) was 31%, and post-RT WBC counts rangedmore » from 1.7 to 21.2 × 10{sup 3} WBCs/μL. Odds ratios (ORs) associating clinical variables and post-RT WBC counts with RP were calculated via logistic regression. A recursive-partitioning algorithm was used to define optimal post-RT WBC count cut points. Results: Post-RT WBC counts were significantly higher in patients with grade ≥3 RP than without (P<.05). Optimal cut points for post-RT WBC count were found to be 7.4 and 8.0 × 10{sup 3}/μL for grade ≥3 and ≥2 RP, respectively. Univariate analysis revealed significant associations between post-RT WBC count and grade ≥3 (n=46, OR=2.6, 95% confidence interval [CI] 1.4‒4.9, P=.003) and grade ≥2 RP (n=164, OR=2.0, 95% CI 1.2‒3.4, P=.01). This association held in a stepwise multivariate regression. Of note, V{sub 20} was found to be significantly associated with grade ≥2 RP (OR=2.2, 95% CI 1.2‒3.4, P=.01) and trended toward significance for grade ≥3 RP (OR=1.9, 95% CI 1.0-3.5, P=.06). Conclusions: Post-RT WBC counts were significantly and independently associated with RP and have potential utility as a diagnostic or predictive marker for this toxicity.« less

WE-AB-202-03: Quantifying Ventilation Change Due to Radiation Therapy Using 4DCT Jacobian Calculations

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

Patton, T; Du, K; Bayouth, J

Purpose: Four-dimensional computed tomography (4DCT) and image registration can be used to determine regional lung ventilation changes after radiation therapy (RT). This study aimed to determine if lung ventilation change following radiation therapy was affected by the pre-RT ventilation of the lung. Methods: 13 subjects had three 4DCT scans: two repeat scans acquired before RT and one three months after RT. Regional ventilation was computed using Jacobian determinant calculations on the registered 4DCT images. The post-RT ventilation map was divided by the pre-RT ventilation map to get a voxel-by-voxel Jacobian ratio map depicting ventilation change over the course of RT.more » Jacobian ratio change was compared over the range of delivered doses. The first pre-RT ventilation image was divided by the second to establish a control for Jacobian ratio change without radiation delivered. The functional change between scans was assessed using histograms of the Jacobian ratios. Results: There were significantly (p < 0.05) more voxels that had a large decrease in Jacobian ratio in the post-RT divided by pre-RT map (15.6%) than the control (13.2%). There were also significantly (p < .01) more voxels that had a large increase in Jacobian ratio (16.2%) when compared to control (13.3%). Lung regions with low function (<10% expansion by Jacobian) showed a slight linear reduction in expansion (0.2%/10 Gy delivered), while high function regions (>10% expansion) showed a greater response (1.2% reduction/10 Gy). Contiguous high function regions > 1 liter occurred in 11 of 13 subjects. Conclusion: There is a significant change in regional ventilation following a course of radiation therapy. The change in Jacobian following RT is dependent both on the delivered dose and the initial ventilation of the lung tissue: high functioning lung has greater ventilation loss for equivalent radiation doses. Substantial regions of high function lung tissue are prevalent. Research support from NIH grants CA166119 and CA166703, a gift from Roger Koch, and a Pilot Grant from University of Iowa Carver College of Medicine.« less

Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

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

Haffty, Bruce G., E-mail: hafftybg@cinj.rutgers.edu; McCall, Linda M.; Ballman, Karla V.

2016-03-01

Purpose: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. Methods and Materials: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors. Results: Of 401 node-positive patients, mastectomy was performed inmore » 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node-positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group. Conclusions: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice patterns conflict with expert recommendations and ongoing trial guidelines. There is a significant need for greater uniformity and guidelines regarding RT following NAC.« less

Radioprotection of the Brain White Matter by Mn(III) N-Butoxyethylpyridylporphyrin-Based Superoxide Dismutase Mimic MnTnBuOE-2-PyP5+

PubMed Central

Weitzel, Douglas H.; Tovmasyan, Artak; Ashcraft, Kathleen A.; Rajic, Zrinka; Weitner, Tin; Liu, Chunlei; Li, Wei; Buckley, Anne F.; Prasad, Mark R.; Young, Kenneth H.; Rodriguiz, Ramona M.; Wetsel, William C.; Peters, Katherine B.; Spasojevic, Ivan; Herndon, James E.; Batinic-Haberle, Ines; Dewhirst, Mark W.

2015-01-01

Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is thought to contribute to cognitive decline. We evaluated the effectiveness of a novel mimic of superoxide dismutase enzyme (SOD), MnTnBuOE-2-PyP5+ (Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin), to provide long-term neuroprotection following 8 Gy of whole brain irradiation. Long-term RT damage can only be assessed by brain imaging and neurocognitive studies. C57BL/6J mice were treated with MnTnBuOE-2-PyP5+ before and after RT and evaluated three months later. At this time point, drug concentration in the brain was 25 nmol/L. Mice treated with MnTnBuOE-2-PyP5+/RT exhibited MRI evidence for myelin preservation in the corpus callosum compared with saline/RT treatment. Corpus callosum histology demonstrated a significant loss of axons in the saline/RT group that was rescued in the MnTnBuOE-2-PyP5+/RT group. In addition, the saline/RT groups exhibited deficits in motor proficiency as assessed by the rotorod test and running wheel tests. These deficits were ameliorated in groups treated with MnTnBuOE-2-PyP5+/RT. Our data demonstrate that MnTnBuOE-2-PyP5+ is neuroprotective for oxidative stress damage caused by radiation exposure. In addition, glioblastoma cells were not protected by MnTnBuOE-2-PyP5+ combination with radiation in vitro. Likewise, the combination of MnTnBuOE-2-PyP5+ with radiation inhibited tumor growth more than RT alone in flank tumors. In summary, MnTnBuOE-2-PyP5+ has dual activity as a neuroprotector and a tumor radiosensitizer. Thus, it is an attractive candidate for adjuvant therapy with RT in future studies with patients with brain cancer. PMID:25319393

Automated segmentation of the parotid gland based on atlas registration and machine learning: a longitudinal MRI study in head-and-neck radiation therapy.

PubMed

Yang, Xiaofeng; Wu, Ning; Cheng, Guanghui; Zhou, Zhengyang; Yu, David S; Beitler, Jonathan J; Curran, Walter J; Liu, Tian

2014-12-01

To develop an automated magnetic resonance imaging (MRI) parotid segmentation method to monitor radiation-induced parotid gland changes in patients after head and neck radiation therapy (RT). The proposed method combines the atlas registration method, which captures the global variation of anatomy, with a machine learning technology, which captures the local statistical features, to automatically segment the parotid glands from the MRIs. The segmentation method consists of 3 major steps. First, an atlas (pre-RT MRI and manually contoured parotid gland mask) is built for each patient. A hybrid deformable image registration is used to map the pre-RT MRI to the post-RT MRI, and the transformation is applied to the pre-RT parotid volume. Second, the kernel support vector machine (SVM) is trained with the subject-specific atlas pair consisting of multiple features (intensity, gradient, and others) from the aligned pre-RT MRI and the transformed parotid volume. Third, the well-trained kernel SVM is used to differentiate the parotid from surrounding tissues in the post-RT MRIs by statistically matching multiple texture features. A longitudinal study of 15 patients undergoing head and neck RT was conducted: baseline MRI was acquired prior to RT, and the post-RT MRIs were acquired at 3-, 6-, and 12-month follow-up examinations. The resulting segmentations were compared with the physicians' manual contours. Successful parotid segmentation was achieved for all 15 patients (42 post-RT MRIs). The average percentage of volume differences between the automated segmentations and those of the physicians' manual contours were 7.98% for the left parotid and 8.12% for the right parotid. The average volume overlap was 91.1% ± 1.6% for the left parotid and 90.5% ± 2.4% for the right parotid. The parotid gland volume reduction at follow-up was 25% at 3 months, 27% at 6 months, and 16% at 12 months. We have validated our automated parotid segmentation algorithm in a longitudinal study. This segmentation method may be useful in future studies to address radiation-induced xerostomia in head and neck radiation therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

The SPoRT-WRF: Evaluating the Impact of NASA Datasets on Convective Forecasts

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Case, Jonathan; Kozlowski, Danielle; Molthan, Andrew

2012-01-01

The Short-term Prediction Research and Transition Center (SPoRT) is a collaborative partnership between NASA and operational forecasting entities, including a number of National Weather Service offices. SPoRT transitions real-time NASA products and capabilities to its partners to address specific operational forecast challenges. One challenge that forecasters face is applying convection-allowing numerical models to predict mesoscale convective weather. In order to address this specific forecast challenge, SPoRT produces real-time mesoscale model forecasts using the Weather Research and Forecasting (WRF) model that includes unique NASA products and capabilities. Currently, the SPoRT configuration of the WRF model (SPoRT-WRF) incorporates the 4-km Land Information System (LIS) land surface data, 1-km SPoRT sea surface temperature analysis and 1-km Moderate resolution Imaging Spectroradiometer (MODIS) greenness vegetation fraction (GVF) analysis, and retrieved thermodynamic profiles from the Atmospheric Infrared Sounder (AIRS). The LIS, SST, and GVF data are all integrated into the SPoRT-WRF through adjustments to the initial and boundary conditions, and the AIRS data are assimilated into a 9-hour SPoRT WRF forecast each day at 0900 UTC. This study dissects the overall impact of the NASA datasets and the individual surface and atmospheric component datasets on daily mesoscale forecasts. A case study covering the super tornado outbreak across the Ce ntral and Southeastern United States during 25-27 April 2011 is examined. Three different forecasts are analyzed including the SPoRT-WRF (NASA surface and atmospheric data), the SPoRT WRF without AIRS (NASA surface data only), and the operational National Severe Storms Laboratory (NSSL) WRF (control with no NASA data). The forecasts are compared qualitatively by examining simulated versus observed radar reflectivity. Differences between the simulated reflectivity are further investigated using convective parameters along with model soundings to determine the impacts of the various NASA datasets. Additionally, quantitative evaluation of select meteorological parameters is performed using the Meteorological Evaluation Tools model verification package to compare forecasts to in situ surface and upper air observations.

JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma.

PubMed

Wakabayashi, Toshihiko; Natsume, Atsushi; Mizusawa, Junki; Katayama, Hiroshi; Fukuda, Haruhiko; Sumi, Minako; Nishikawa, Ryo; Narita, Yoshitaka; Muragaki, Yoshihiro; Maruyama, Takashi; Ito, Tamio; Beppu, Takaaki; Nakamura, Hideo; Kayama, Takamasa; Sato, Shinya; Nagane, Motoo; Mishima, Kazuhiko; Nakasu, Yoko; Kurisu, Kaoru; Yamasaki, Fumiyuki; Sugiyama, Kazuhiko; Onishi, Takanori; Iwadate, Yasuo; Terasaki, Mizuhiko; Kobayashi, Hiroyuki; Matsumura, Akira; Ishikawa, Eiichi; Sasaki, Hikaru; Mukasa, Akitake; Matsuo, Takayuki; Hirano, Hirofumi; Kumabe, Toshihiro; Shinoura, Nobusada; Hashimoto, Naoya; Aoki, Tomokazu; Asai, Akio; Abe, Tatsuya; Yoshino, Atsuo; Arakawa, Yoshiki; Asano, Kenichiro; Yoshimoto, Koji; Shibui, Soichiro

2018-07-01

This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2.0 Gy/fr/day, 30 fr) with TMZ (75 mg/m 2 , daily) followed by TMZ maintenance (100-200 mg/m 2 /day, days 1-5, every 4 weeks) for 2 years. Patients in the TMZ + IFNβ + RT arm intravenously received IFNβ (3 MU/body, alternative days during RT and day 1, every 4 weeks during maintenance period) and TMZ + RT. The primary endpoint was overall survival (OS). The planned sample size was 120 (one-sided alpha 0.2; power 0.8). Between Apr 2010 and Jan 2012, 122 patients were randomized. The median OS with TMZ + RT and TMZ + IFNβ + RT was 20.3 and 24.0 months (HR 1.00, 95% CI 0.65-1.55; one-sided log rank P = 0.51). The median progression-free survival times were 10.1 and 8.5 months (HR 1.25, 95% CI 0.85-1.84). The incidence of neutropenia with the TMZ + RT and the TMZ + IFNβ + RT (grade 3-4, CTCAE version 3.0) was 12.7 versus 20.7% during concomitant period and was 3.6 versus 9.3% during maintenance period. The incidence of lymphopenia was 54.0 versus 63.8% and 34.5 versus 41.9%. TMZ + IFNβ + RT is not considered as a candidate for the following phase III trial, and TMZ + RT remained to be a most promising treatment. This trial was registered with the UMIN Clinical Trials Registry: UMIN000003466.

Management Trends and Outcomes for Stage I to II Mantle Cell Lymphoma Using the National Cancer Data Base: Ascertaining the Ideal Treatment Paradigm

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

Gill, Beant S.; Vargo, John A.; Pai, Sarah S.

Purpose: Mantle cell lymphoma (MCL) is a rare, albeit aggressive subset of non-Hodgkin lymphoma, resulting in varied treatment approaches. Given the paucity of data defining the optimal management for early-stage MCL, we conducted an analysis using the National Cancer Data Base (NCDB) to identify practice patterns and outcomes. Methods and Materials: The NCDB was queried for patients with stage I to II MCL diagnosed from 1998 to 2012 receiving chemotherapy (CT) or radiation therapy (RT), or both (CT+RT). Univariate and multivariable analyses for factors associated with treatment selection were completed using logistic regression. Propensity scores with inverse probability treatment weightingmore » (IPTW) were calculated based on the conditional probability of receiving CT+RT. The log-rank test and Cox proportional hazards modeling with IPTW adjustment were conducted for the survival analyses. Results: In total, 2539 patients were identified. The key characteristics were as follows: 69% were male, 71% were aged ≥60 years, 28% had extranodal involvement, and 51% had stage I disease. Of the 2539 patients, 70% underwent CT, 11% underwent RT, and 19% underwent CT+RT. The use of CT+RT decreased from 23.1% to 14.1% in 1998 to 2002 and 2010 to 2012 (P<.001). CT+RT usage was lower for patients with the following characteristics: age ≥60 years, female sex, stage II disease, and the presence of B symptoms. With a median follow-up period of 42.8 months, the unadjusted 3-year overall survival estimates for patients receiving CT, RT, or CT+RT were 67.8%, 72.4%, and 79.8%, respectively (P<.001). After correcting for indication bias through IPTW-adjusted modeling, CT+RT reduced the risk of overall mortality compared with monotherapy (hazard ratio 0.65, P=.029). Conclusions: Although uncommon, patients with stage I-II MCL can have favorable outcomes. Despite a continued decline in the usage of consolidative RT, combined modality therapy improves survival in this cohort compared with monotherapy.« less

Ejaculation profiles of men following radiation therapy for prostate cancer.

PubMed

Sullivan, John F; Stember, Doron S; Deveci, Serkan; Akin-Olugbade, Yemi; Mulhall, John P

2013-05-01

Radical prostatectomy (RP) is associated with anejaculation, which for some men is a source of bother and sexual dissatisfaction. Clinical experience has shown us some men after pelvic radiation therapy (RT) also experience anejaculation. This analysis was conducted to define the ejaculation profiles of men after RT for prostate cancer (PCa). As a routine part of the sexual health evaluation for post-RT patients, men provided information regarding their ejaculatory function and orgasm. Analysis was conducted of a sexual medicine database reviewing demographic data, PCa factors, erectile, ejaculatory, and orgasmic function. Men with prior history of RP, cryotherapy, focal therapies, and androgen deprivation therapy (ADT) were excluded. Patients completed the International Index of Erectile Function (IIEF) questionnaire at follow-up visits commencing with the first posttreatment visit and specific attention was paid to the IIEF orgasm domain. Three hundred and sixty-four consecutive patients were included. Two hundred and fifty-two patients had external beam, and 112 patients had brachytherapy (BT). Mean age was 64 ± 11 (42-78) years and mean follow-up after RT was 6 ± 4.5 years. Mean prostate size at time of RT was 42 ± 21 g. Of the entire population, 72% lost the ability to ejaculate in an antegrade fashion after prostate RT by their last visit. The proportion experiencing anejaculation at 1, 3, and 5 years after RT was 16%, 69%, and 89%, respectively. For men with at least two IIEF questionnaires completed, the orgasm domain scores decreased dramatically over the follow-up period; orgasm domain scores (0-10): <12 months post-RT 7.4, 13-24 months 5.4, 25-36 months 3.2, >36 months 2.8 (P < 0.01). Multivariable analysis identified several factors predictive of failure to ejaculate: older age, ADT, RT dose > 100 Gy, and smaller prostates at the time of RT. The vast majority of men after prostate RT will experience anejaculation and should be counseled accordingly prior to undergoing therapy. We have identified predictive factors. © 2013 International Society for Sexual Medicine.

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.

PubMed

Chang, Susan; Zhang, Peixin; Cairncross, J Gregory; Gilbert, Mark R; Bahary, Jean-Paul; Dolinskas, Carol A; Chakravarti, Arnab; Aldape, Kenneth D; Bell, Erica H; Schiff, David; Jaeckle, Kurt; Brown, Paul D; Barger, Geoffrey R; Werner-Wasik, Maria; Shih, Helen; Brachman, David; Penas-Prado, Marta; Robins, H Ian; Belanger, Karl; Schultz, Christopher; Hunter, Grant; Mehta, Minesh

2017-02-01

The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome. Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met. Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81). RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Genetic parameters of rumination time and feed efficiency traits in primiparous Holstein cows under research and commercial conditions.

PubMed

Byskov, M V; Fogh, A; Løvendahl, P

2017-12-01

Feed efficiency has the potential to be improved both through feeding, management, and breeding. Including feed efficiency in a selection index is limited by the fact that dry matter intake (DMI) recording is only feasible under research facilities, resulting in small data sets and, consequently, uncertain genetic parameter estimates. As a result, the need to record DMI indicator traits on a larger scale exists. Rumination time (RT), which is already recorded in commercial dairy herds by a sensor-based system, has been suggested as a potential DMI indicator. However, RT can only be a DMI indicator if it is heritable, correlates with DMI, and if the genetic parameters of RT in commercial herd settings are similar to those in research facilities. Therefore, the objective of our study was to estimate genetic parameters for RT and the related traits of DMI in primiparous Holstein cows, and to compare genetic parameters of rumination data between a research herd and 72 commercial herds. The estimated heritability values were all moderate for DMI (0.32-0.49), residual feed intake (0.23-0.36), energy-corrected milk (ECM) yield (0.49-0.70), and RT (0.14-0.44) found in the research herd. The estimated heritability values for ECM were lower for the commercial herds (0.08-0.35) than that for the research herd. The estimated heritability values for RT were similar for the 2 herd types (0.28-0.32). For the research herd, we found negative individual level correlations between RT and DMI (-0.24 to -0.09) and between RT and RFI (-0.34 to -0.03), and we found both positive and negative correlations between RT and ECM (-0.08 to 0.09). For the commercial herds, genetic correlations between RT and ECM were both positive and negative (-0.27 to 0.10). In conclusion, RT was not found to be a suitable indicator trait for feed intake and only a weak indicator of feed efficiency. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer

PubMed Central

Kim, Yi-Jun; Min, Seog Ki; Nam, Eun Mi

2017-01-01

Objective: To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer. Methods: From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45–61 Gy). Results: With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100–0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219–1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051–18.344; and HR for R2 18.551, 95% CI 3.680–93.520; p < 0.001) and OS (HR for R1 1.816, 95% CI 0.853–3.867; and HR for R2 3.564, 95% CI 1.175–10.809; p = 0.054). Conclusion: RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group. PMID:28118028

Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay.

PubMed

Lyu, Xiaodong; Wang, Xianwei; Zhang, Lina; Chen, Zhenzhu; Zhao, Yu; Hu, Jieying; Fan, Ruihua; Song, Yongping

2017-07-25

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management. We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization. Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL). We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

Evaluating the Impact of Atmospheric Infrared Sounder (AIRS) Data On Convective Forecasts

NASA Technical Reports Server (NTRS)

Kozlowski, Danielle; Zavodsky, Bradley

2011-01-01

The Short-term Prediction Research and Transition Center (SPoRT) is a collaborative partnership between NASA and operational forecasting partners, including a number of National Weather Service (NWS) offices. SPoRT provides real-time NASA products and capabilities to its partners to address specific operational forecast challenges. The mission of SPoRT is to transition observations and research capabilities into operations to help improve short-term weather forecasts on a regional scale. Two areas of focus are data assimilation and modeling, which can to help accomplish SPoRT's programmatic goals of transitioning NASA data to operational users. Forecasting convective weather is one challenge that faces operational forecasters. Current numerical weather prediction (NWP) models that operational forecasters use struggle to properly forecast location, timing, intensity and/or mode of convection. Given the proper atmospheric conditions, convection can lead to severe weather. SPoRT's partners in the National Oceanic and Atmospheric Administration (NOAA) have a mission to protect the life and property of American citizens. This mission has been tested as recently as this 2011 severe weather season, which has seen more than 300 fatalities and injuries and total damages exceeding $10 billion. In fact, during the three day period from 25-27 April, 1,265 storms reports (362 tornado reports) were collected making this three day period one of most active in American history. To address the forecast challenge of convective weather, SPoRT produces a real-time NWP model called the SPoRT Weather Research and Forecasting (SPoRT-WRF), which incorporates unique NASA data sets. One of the NASA assets used in this unique model configuration is retrieved profiles from the Atmospheric Infrared Sounder (AIRS).The goal of this project is to determine the impact that these AIRS profiles have on the SPoRT-WRF forecasts by comparing to a current operational model and a control SPoRT-WRF model that does not contain AIRS profiles.

Emergence of a New Population of Rathayibacter toxicus: An Ecologically Complex, Geographically Isolated Bacterium

PubMed Central

Arif, Mohammad; Busot, Grethel Y.; Mann, Rachel; Rodoni, Brendan; Liu, Sanzhen; Stack, James P.

2016-01-01

Rathayibacter toxicus is a gram-positive bacterium that infects the floral parts of several Poaceae species in Australia. Bacterial ooze is often produced on the surface of infected plants and bacterial galls are produced in place of seed. R. toxicus is a regulated plant pathogen in the U.S. yet reliable detection and diagnostic tools are lacking. To better understand this geographically-isolated plant pathogen, genetic variation as a function of geographic location, host species, and date of isolation was determined for isolates collected over a forty-year period. Discriminant analyses of recently collected and archived isolates using Multi-Locus Sequence Typing (MLST) and Inter-Simple Sequence Repeats (ISSR) identified three populations of R. toxicus; RT-I and RT-II from South Australia and RT-III from Western Australia. Population RT-I, detected in 2013 and 2014 from the Yorke Peninsula in South Australia, is a newly emerged population of R. toxicus not previously reported. Commonly used housekeeping genes failed to discriminate among the R. toxicus isolates. However, strategically selected and genome-dispersed MLST genes representing an array of cellular functions from chromosome replication, antibiotic resistance and biosynthetic pathways to bacterial acquired immunity were discriminative. Genetic variation among isolates within the RT-I population was less than the within-population variation for the previously reported RT-II and RT-III populations. The lower relative genetic variation within the RT-I population and its absence from sampling over the past 40 years suggest its recent emergence. RT-I was the dominant population on the Yorke Peninsula during the 2013–2014 sampling period perhaps indicating a competitive advantage over the previously detected RT-II population. The potential for introduction of this bacterial plant pathogen into new geographic areas provide a rationale for understanding the ecological and evolutionary trajectories of R. toxicus. PMID:27219107

Emergence of a New Population of Rathayibacter toxicus: An Ecologically Complex, Geographically Isolated Bacterium.

PubMed

Arif, Mohammad; Busot, Grethel Y; Mann, Rachel; Rodoni, Brendan; Liu, Sanzhen; Stack, James P

2016-01-01

Rathayibacter toxicus is a gram-positive bacterium that infects the floral parts of several Poaceae species in Australia. Bacterial ooze is often produced on the surface of infected plants and bacterial galls are produced in place of seed. R. toxicus is a regulated plant pathogen in the U.S. yet reliable detection and diagnostic tools are lacking. To better understand this geographically-isolated plant pathogen, genetic variation as a function of geographic location, host species, and date of isolation was determined for isolates collected over a forty-year period. Discriminant analyses of recently collected and archived isolates using Multi-Locus Sequence Typing (MLST) and Inter-Simple Sequence Repeats (ISSR) identified three populations of R. toxicus; RT-I and RT-II from South Australia and RT-III from Western Australia. Population RT-I, detected in 2013 and 2014 from the Yorke Peninsula in South Australia, is a newly emerged population of R. toxicus not previously reported. Commonly used housekeeping genes failed to discriminate among the R. toxicus isolates. However, strategically selected and genome-dispersed MLST genes representing an array of cellular functions from chromosome replication, antibiotic resistance and biosynthetic pathways to bacterial acquired immunity were discriminative. Genetic variation among isolates within the RT-I population was less than the within-population variation for the previously reported RT-II and RT-III populations. The lower relative genetic variation within the RT-I population and its absence from sampling over the past 40 years suggest its recent emergence. RT-I was the dominant population on the Yorke Peninsula during the 2013-2014 sampling period perhaps indicating a competitive advantage over the previously detected RT-II population. The potential for introduction of this bacterial plant pathogen into new geographic areas provide a rationale for understanding the ecological and evolutionary trajectories of R. toxicus.

Radiation-induced moyamoya syndrome

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

Desai, Snehal S.; Paulino, Arnold C.; Mai, Wei Y.

2006-07-15

Purpose: The moyamoya syndrome is an uncommon late complication after radiotherapy (RT). Methods and Materials: A PubMed search of English-language articles, with radiation, radiotherapy, and moyamoya syndrome used as search key words, yielded 33 articles from 1967 to 2002. Results: The series included 54 patients with a median age at initial RT of 3.8 years (range, 0.4 to 47). Age at RT was less than 5 years in 56.3%, 5 to 10 years in 22.9%, 11 to 20 years in 8.3%, 21 to 30 years in 6.3%, 31 to 40 years in 2.1%, and 41 to 50 years in 4.2%.more » Fourteen of 54 patients (25.9%) were diagnosed with neurofibromatosis type 1 (NF-1). The most common tumor treated with RT was low-grade glioma in 37 tumors (68.5%) of which 29 were optic-pathway glioma. The average RT dose was 46.5 Gy (range, 22-120 Gy). For NF-1-positive patients, the average RT dose was 46.5 Gy, and for NF-1-negative patients, it was 58.1 Gy. The median latent period for development of moyamoya syndrome was 40 months after RT (range, 4-240). Radiation-induced moyamoya syndrome occurred in 27.7% of patients by 2 years, 53.2% of patients by 4 years, 74.5% of patients by 6 years, and 95.7% of patients by 12 years after RT. Conclusions: Patients who received RT to the parasellar region at a young age (<5 years) are the most susceptible to moyamoya syndrome. The incidence for moyamoya syndrome continues to increase with time, with half of cases occurring within 4 years of RT and 95% of cases occurring within 12 years. Patients with NF-1 have a lower radiation-dose threshold for development of moyamoya syndrome.« less

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

PubMed

Mowery, Yvonne M; Salama, Joseph K; Zafar, S Yousuf; Moore, Harvey G; Willett, Christopher G; Czito, Brian G; Hopkins, M Benjamin; Palta, Manisha

2017-04-15

Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434-1441. © 2016 American Cancer Society. © 2016 American Cancer Society.

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer.

PubMed

Jeremić, Branislav; Milicić, Biljana

2008-02-15

The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.

Disparities in the Initial Local Treatment of Older Women with Early-Stage Breast Cancer: A Population-Based Study.

PubMed

LeMasters, Traci J; Madhavan, Suresh S; Sambamoorthi, Usha; Vyas, Ami M

2017-07-01

Although breast cancer is most prevalent among older women, the majority are diagnosed at an early stage. When diagnosed at an early stage, women have the option of breast-conserving surgery (BCS) plus radiation therapy (RT) or mastectomy for the treatment of early-stage breast cancer (ESBC). Omission of RT when receiving BCS increases the risk for recurrence and poor survival. Yet, a small subset of older women may omit RT after BCS. This study examines the current patterns of local treatment for ESBC among older women. This study conducted a retrospective observational analysis using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset of women age ≥66 diagnosed with stage I-II breast cancer in 2003-2009. SEER-Medicare data was additionally linked with data from the Area Resource File (ARF) to examine the association between area-level healthcare resources and treatment. Two logistic regression models were used to estimate how study factors were associated with receiving (1) BCS versus BCS+RT and (2) Mastectomy versus BCS+RT. A stratified analysis was also conducted among women aged <70 years. Among 45,924 patients, 55% received BCS+RT, 23% received mastectomy, and 22% received BCS only. Women of increasing age, comorbidity, primary care provider visits, stage II disease, and nonwhite race were more likely to have mastectomy or BCS only, than BCS+RT. Women diagnosed in 2004-2006, treated by an oncology surgeon, residing in metro areas, areas of greater education and income, were less likely to receive mastectomy or BCS only, than BCS+RT. While women aged <70 years were more likely to receive BCS+RT, socioeconomic and physician specialties were associated with receiving BCS only. Over half of older women with ESBC initially receive BCS+RT. The likelihood for mastectomy and BCS only increases with age, comorbidity, and vulnerable socio-demographic characteristics. Findings demonstrate continued treatment disparities among certain vulnerable populations.

Validation of the RT3 triaxial accelerometer for the assessment of physical activity.

PubMed

Rowlands, Ann V; Thomas, Philip W M; Eston, Roger G; Topping, Rodney

2004-03-01

The aims of this study were to assess and compare the validity of the RT3 accelerometer for the assessment of physical activity in boys and men, to compare RT3 and Tritrac accelerometer counts, and to determine count cut-off values for moderate (> or =3 < 6 METs) and vigorous (> or =6 METs) activity. Nineteen boys (age: 9.5 +/- 0.8 yr) and 15 men (age: 20.7 +/- 1.4 yr) walked and ran on a treadmill, kicked a ball to and fro, played hopscotch, and sat quietly. An RT3 was worn on the right hip; boys also wore a Tritrac on the left hip. Oxygen consumption was expressed as a ratio of body mass raised to the power of 0.75 (S VO2). RT3 counts correlated significantly with S VO2 in boys (r = 0.87, P < 0.01) and men (r = 0.85, P < 0.01). However, during treadmill activities, RT3 counts were significantly higher for boys (P < 0.05). RT3 counts corresponding to "moderate" and "vigorous" activity were similar for boys and men for all activities (moderate = 970.2 for boys and 984.0 for men; vigorous = 2333.0 for boys and 2340.8 for men) but approximately 400 counts lower in men when only treadmill activities were considered. Tritrac counts correlated significantly with S VO2 in boys (r = 0.87, P < 0.01), but were significantly lower than RT3 counts across most activities (P < 0.05). The RT3 accelerometer is a good measure of physical activity for boys and men. However, moderate and vigorous intensity count thresholds differ for boys and men when the predominant activities are walking and running. RT3 counts are significantly higher than Tritrac counts for a number of activities. These findings have implications when comparing activity counts between studies using the different instruments.

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

Swaminath, Anand; Knox, Jennifer J.; Brierley, James D.

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT).more » Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.« less

For-profit hospital ownership status and use of brachytherapy after breast-conserving surgery.

PubMed

Sen, Sounok; Soulos, Pamela R; Herrin, Jeph; Roberts, Kenneth B; Yu, James B; Lesnikoski, Beth-Ann; Ross, Joseph S; Krumholz, Harlan M; Gross, Cary P

2014-05-01

Little is known about the relationship between operative care for breast cancer at for-profit hospitals and subsequent use of adjuvant radiation therapy (RT). Among Medicare beneficiaries, we examined whether hospital ownership status is associated with the use of breast brachytherapy--a newer and more expensive modality--as well as overall RT. We conducted a retrospective study of female Medicare beneficiaries who received breast-conserving surgery for invasive breast cancer in 2008 and 2009. We assessed the relationship between hospital ownership and receipt of brachytherapy or overall RT by using hierarchical generalized linear models. The sample consisted of 35,118 women, 8.0% of whom had breast-conserving operations at for-profit hospitals. Among patients who received RT, those who underwent operation at for-profit hospitals were more likely to receive brachytherapy (20.2%) than patients treated at not-for-profit hospitals (15.2%; odds ratio [OR] for for-profit versus not-for-profit: 1.50; 95% confidence interval [95% CI] 1.23-1.84; P < .001). Among women aged 66-79 years, there was no relationship between hospital ownership status and overall use of RT. Among women ages 80-94 years of age--the group least likely to benefit from RT due to shorter life expectancy--undergoing breast-conserving operations at a for-profit hospital was associated with greater overall use of RT (OR 1.22; 95% CI 1.03-1.45, P = .03) and brachytherapy use (OR 1.66; 95% CI 1.18-2.34, P = .003). Operative care at for-profit hospitals was associated with increased use of the newer and more expensive RT modality, brachytherapy. Among the oldest women who are least likely to benefit from RT, operative care at a for-profit hospital was associated with greater overall use of RT, with this difference largely driven by the use of brachytherapy. Copyright © 2014 Mosby, Inc. All rights reserved.

For-Profit Hospital Ownership Status and Use of Brachytherapy after Breast-Conserving Surgery

PubMed Central

Sen, Sounok; Soulos, Pamela R.; Herrin, Jeph; Roberts, Kenneth B.; Yu, James B.; Lesnikoski, Beth-Ann; Ross, Joseph S.; Krumholz, Harlan M.; Gross, Cary P.

2014-01-01

BACKGROUND Little is known about the relation between surgical care for breast cancer at for-profit hospitals and subsequent use of adjuvant radiation therapy (RT). Among Medicare beneficiaries, we examined whether hospital ownership status is associated with the use of breast brachytherapy – a newer and more expensive modality – as well as overall RT. METHODS We conducted a retrospective study of female Medicare beneficiaries receiving breast-conserving surgery for invasive breast cancer in 2008 and 2009. We assessed the relationship between hospital ownership and receipt of brachytherapy or overall RT using hierarchical generalized linear models. RESULTS The sample consisted of 35,118 women, 8.0% of whom had surgery at for-profit hospitals. Among patients who received RT, those who underwent surgery at for-profit hospitals were significantly more likely to receive brachytherapy (20.2%) than patients treated at not-for-profit hospitals (15.2%; OR for for-profit vs. not-for-profit: 1.50; 95%CI: 1.23–1.84; p<0.001). Among women aged 66–79, there was no relation between hospital ownership status and overall RT use. Among women aged 80–94 years old – the group least likely to benefit from RT due to shorter life expectancy – receipt of surgery at a for-profit hospital was significantly associated with higher overall RT use (OR: 1.22; 95%CI: 1.03–1.45, p=0.03) and brachytherapy use (OR: 1.66; 95%CI: 1.18–2.34, p=0.003). CONCLUSIONS Surgical care at for-profit hospitals was associated with increased use of the newer and more expensive RT modality, brachytherapy. Among the oldest women, who are least likely to benefit from RT, surgical care at a for-profit hospital was associated with higher overall RT use, with this difference largely driven by the use of brachytherapy. PMID:24787104

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

Acharya, Sahaja; Hsieh, Samantha; Michalski, Jeff M.

Purpose: Breast-conserving therapy (BCT) is a recommended alternative to mastectomy (MT) for early-stage breast cancer. Limited access to radiation therapy (RT) may result in higher rates of MT. We assessed the association between distance to the nearest RT facility and the use of MT, in a modern cohort of women. Methods and Materials: Women with stage 0-II breast cancer eligible for BCT diagnosed from 2004 to 2010 were identified from the Florida Cancer Data System (FCDS). Distances from patient census tracts to the nearest RT facility census tract were calculated. Multivariate logistic regression was used to identify explanatory variables thatmore » influenced MT use. Results: Of the 27,489 eligible women, 32.1% (n=8841) underwent MT, and 67.8% (n=18,648) underwent BCS. Thirty-two percent of patients lived in a census tract that was >5 miles from an RT facility. MT use increased with increasing distance to RT facility (31.1% at ≤5 miles, 33.8% at >5 to <15 miles, 34.9% at 15 to <40 miles, and 51% at ≥40 miles, P<.001). The likelihood was that MT was independently associated with increasing distance to RT facility on multivariate analysis (P<.001). Compared to patients living <5 miles away from an RT facility, patients living 15 to <40 miles away were 1.2 times more likely to be treated with MT (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.05-1.35, P<.01), and those living ≥40 miles away were more than twice as likely to be treated with MT (OR: 2.17, 95% CI: 1.48-3.17, P<.001). However, in patients younger than 50 years (n=5179), MT use was not associated with distance to RT facility (P=.235). Conclusions: MT use in a modern cohort of women is independently associated with distance to RT facility. However, for young patients, distance to RT is not a significant explanatory variable for MT use.« less

Accuracy evaluation of a new real-time continuous glucose monitoring algorithm in hypoglycemia.

PubMed

Mahmoudi, Zeinab; Jensen, Morten Hasselstrøm; Dencker Johansen, Mette; Christensen, Toke Folke; Tarnow, Lise; Christiansen, Jens Sandahl; Hejlesen, Ole

2014-10-01

The purpose of this study was to evaluate the performance of a new continuous glucose monitoring (CGM) calibration algorithm and to compare it with the Guardian(®) REAL-Time (RT) (Medtronic Diabetes, Northridge, CA) calibration algorithm in hypoglycemia. CGM data were obtained from 10 type 1 diabetes patients undergoing insulin-induced hypoglycemia. Data were obtained in two separate sessions using the Guardian RT CGM device. Data from the same CGM sensor were calibrated by two different algorithms: the Guardian RT algorithm and a new calibration algorithm. The accuracy of the two algorithms was compared using four performance metrics. The median (mean) of absolute relative deviation in the whole range of plasma glucose was 20.2% (32.1%) for the Guardian RT calibration and 17.4% (25.9%) for the new calibration algorithm. The mean (SD) sample-based sensitivity for the hypoglycemic threshold of 70 mg/dL was 31% (33%) for the Guardian RT algorithm and 70% (33%) for the new algorithm. The mean (SD) sample-based specificity at the same hypoglycemic threshold was 95% (8%) for the Guardian RT algorithm and 90% (16%) for the new calibration algorithm. The sensitivity of the event-based hypoglycemia detection for the hypoglycemic threshold of 70 mg/dL was 61% for the Guardian RT calibration and 89% for the new calibration algorithm. Application of the new calibration caused one false-positive instance for the event-based hypoglycemia detection, whereas the Guardian RT caused no false-positive instances. The overestimation of plasma glucose by CGM was corrected from 33.2 mg/dL in the Guardian RT algorithm to 21.9 mg/dL in the new calibration algorithm. The results suggest that the new algorithm may reduce the inaccuracy of Guardian RT CGM system within the hypoglycemic range; however, data from a larger number of patients are required to compare the clinical reliability of the two algorithms.

The use of refused tea as litter material for broiler chickens.

PubMed

Atapattu, N S B M; Wickramasinghe, K P

2007-05-01

A completely randomized design experiment was conducted to determine the suitability of refused tea (RT) as a litter material for broiler chickens. Physiochemical properties of RT were compared with paddy husk (PH). Subsequently, broilers were raised on RT- or PH-based litter to compare the performances and litter qualities. Twenty-day-old broiler chicks (n = 150) were randomly allocated into 6 deep litter pens so that each treatment had 3 replicates. Chicks received 0.8 ft(2) of floor spacing until d 28 and 1.3 ft(2) thereafter. Each cage had a feeder and a drinker. Litter materials and litter samples taken on 28, 35, and 39 d were analyzed for bulk density, moisture, ash, and N. Chick mortality was low (1.3%) and similar on 2 types of litters. Live weights on d 28, 35, 39, and weight gains, feed intakes, dressing percentages, and feed conversion ratios were not affected by the type of litter material. The bulk density, moisture level, and pH of the RT were comparable with PH. Even though the water-holding capacity of PH (213%) was significantly higher (P < 0.01) than RT (70%), the latter material had significantly higher (P < 0.01) water-releasing capacity compared with the former (17.9 vs. 13.6%). Throughout the experiment the RT litter had around 10% units higher moisture level than PH litter. By d 39, the moisture content of the RT litter was (48%) significantly higher (P = 0.05) than PH litter (37%). The N contents of RT litter were higher (P < 0.05) than those of PH on d 28, 35, and 39, being 8.1, 7.8, and 7% and 3.4, 3.6, and 3%, respectively. It was concluded that RT could be successfully used as an alternative litter material for broilers. A higher N content in RT-based spent broiler litter would make it be a better organic fertilizer and ruminant feed compared with PH-based litter.

The Population Benefit of Radiotherapy for Malignant Brain Tumors: Local Control and Survival Estimates for Guideline-Based Use.

PubMed

Hanna, Timothy Paul; Delaney, Geoffrey Paul; Barton, Michael Bernard

2016-09-01

To estimate the population benefit of radiotherapy (RT) for primary malignant brain tumors if evidence-based guidelines were routinely followed. This study investigated 5-year local control (LC) and 2- and 5-year overall survival (OS) benefits. RT benefit was the absolute proportional benefit of RT alone over no RT for radical indications, and over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemotherapy and RT over RT alone. Decision tree models were adapted to define the incidence of each indication. Citation databases were systematically queried for the highest level of evidence defining indication benefits. Meta-analysis was performed if there were multiple sources of the same evidence level, and deterministic and probabilistic sensitivity analysis was also performed. Among all patients with malignant brain tumors, 82% had indications for curative- or adjuvant-intent RT. The magnitude of benefit was based on level I or II evidence in 44% of all patients. A total of 25 relevant studies were used to quantify indication benefits. All RT benefit included in the model was irreplaceable. For malignant brain tumors, the estimated population benefit for RT alone was 9% for 5-year LC (95% CI, 7%-10%), 9% for 2-year OS (95% CI, 8%-11%), and 5% for 5-year OS (95% CI, 4%-5%). The incremental benefit of CRT was 1% for 5-year LC (95% CI, 0%-2%), 7% for 2-year OS (95% CI, 4%-11%), and 3% for 5-year OS (95% CI, 1%-5%). The model was robust in sensitivity analysis. When optimally used, RT provides an important benefit for many patients with malignant brain tumors. The model provided a robust means for estimating the magnitude of this benefit. Copyright © 2016 by the National Comprehensive Cancer Network.

Annual Research Review: Reaction time variability in ADHD and autism spectrum disorders: measurement and mechanisms of a proposed trans-diagnostic phenotype

PubMed Central

Karalunas, Sarah L.; Geurts, Hilde M.; Konrad, Kerstin; Bender, Stephan; Nigg, Joel T.

2014-01-01

Background Intraindividual variability in reaction time (RT) has received extensive discussion as an indicator of cognitive performance, a putative intermediate phenotype of many clinical disorders, and a possible trans-diagnostic phenotype that may elucidate shared risk factors for mechanisms of psychiatric illnesses. Scope and Methodology Using the examples of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), we discuss RT variability. We first present a new meta-analysis of RT variability in ASD with and without comorbid ADHD. We then discuss potential mechanisms that may account for RT variability and statistical models that disentangle the cognitive processes affecting RTs. We then report a second meta-analysis comparing ADHD and non-ADHD children on diffusion model parameters. We consider how findings inform the search for neural correlates of RT variability. Findings Results suggest that RT variability is increased in ASD only when children with comorbid ADHD are included in the sample. Furthermore, RT variability in ADHD is explained by moderate to large increases (d = 0.63–0.99) in the ex-Gaussian parameter τ and the diffusion parameter drift rate, as well as by smaller differences (d = 0.32) in the diffusion parameter of nondecision time. The former may suggest problems in state regulation or arousal and difficulty detecting signal from noise, whereas the latter may reflect contributions from deficits in motor organization or output. The neuroimaging literature converges with this multicomponent interpretation and also highlights the role of top-down control circuits. Conclusion We underscore the importance of considering the interactions between top-down control, state regulation (e.g. arousal), and motor preparation when interpreting RT variability and conclude that decomposition of the RT signal provides superior interpretive power and suggests mechanisms convergent with those implicated using other cognitive paradigms. We conclude with specific recommendations for the field for next steps in the study of RT variability in neurodevelopmental disorders. PMID:24628425

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy

PubMed Central

Grimaldi, Antonio M; Simeone, Ester; Giannarelli, Diana; Muto, Paolo; Falivene, Sara; Borzillo, Valentina; Giugliano, Francesca Maria; Sandomenico, Fabio; Petrillo, Antonella; Curvietto, Marcello; Esposito, Assunta; Paone, Miriam; Palla, Marco; Palmieri, Giuseppe; Caracò, Corrado; Ciliberto, Gennaro; Mozzillo, Nicola; Ascierto, Paolo A

2014-01-01

Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results. PMID:25083318

Effects of Treatment Intensification on Acute Local Toxicity During Radiotherapy for Head and Neck Cancer: Prospective Observational Study Validating CTCAE, Version 3.0, Scoring System

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

Palazzi, Mauro; Tomatis, Stefano; Orlandi, Ester

2008-02-01

Purpose: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. Methods and Materials: Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventionalmore » fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. Results: Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the 'low-burden' class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the 'high-burden' class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. Conclusions: The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant.« less