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Sample records for mrc rt01 isrctn47772397

  1. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

    SciTech Connect

    Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R.; Graham, John D.; Dearnaley, David P.

    2010-07-01

    Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

  2. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  3. MRC testing and results

    NASA Astrophysics Data System (ADS)

    Akins, A. J.; Romano, B. C.; Waugh, C. W.

    A media resource controller (MRC) advanced development model (ADM) has been developed. The MRC is a device that provides adaptive routing of data and voice traffic over a multimedia, packet switch network. Five MRC ADMs and a network evaluator and simulator (which allows the simulation of additional MRC nodes) will provide a testbed evaluation capability. The testbed is being used to investigate the operational benefits that can be gained by using a multimedia tactical communications network and to evaluate the performance characteristics of the MRC. An overview is given of the MRC design, with an emphasis on the relationship between operational goals and design choices. The test approach, evaluation criteria, and preliminary test results are discussed.

  4. Novel MRC algorithms using GPGPU

    NASA Astrophysics Data System (ADS)

    Kato, Kokoro; Taniguchi, Yoshiyuki; Inoue, Tadao; Kadota, Kazuya

    2012-06-01

    GPGPU (General Purpose Graphic Processor Unit) has been attracting many engineers and scientists who develop their own software for massive numerical computation. With hundreds of core-processors and tens of thousands of threads operating concurrently, GPGPU programs can run significantly fast if their software architecture is well optimized. The basic program model used in GPGPU is SIMD (Single Instruction Multiple Data stream), and one must adapt his programming model to SIMD. However, conditional branching is fundamentally not allowed in SIMD and this limitation is quite challenging to apply GPGPU to photomask related software such as MDP or MRC. In this paper unique methods are proposed to utilize GPU for MRC operation. We explain novel algorithms of mask layout verification by GPGPU.

  5. Combining Dosimetry & Toxicity: Analysis of two UK Phase III Clinical trials

    NASA Astrophysics Data System (ADS)

    Gulliford, Sarah L.

    2014-03-01

    There are many advantages to performing a clinical trial when implementing a novel radiotherapy technique. The clinical trials framework enables the safety and efficacy of the "experimental arm" to be tested and ensures practical support, rigorous quality control and data monitoring for participating centres. In addition to the clinical and follow-up data collected from patients within the trial, it is also possible to collect 3-D dosimetric information from the corresponding radiotherapy treatment plans. Analysing the combination of dosimetric, clinical and follow-up data enhances the understanding of the relationship between the dose delivered to both the target and normal tissue structures and reported outcomes & toxicity. Aspects of the collection, collation and analysis of data from two UK multicentre Phase III radiotherapy trials are presented here. MRC-RT01 dose-escalation prostate radiotherapy trial ISRCTN47772397 was one of the first UK multi-centre radiotherapy trials to collect 3-D dosimetric data. A number of different analysis methodologies were implemented to investigate the relationship between the dose distribution to the rectum and specific rectal toxicities. More recently data was collected from the PARSPORT trial (Parotid Sparing IMRT vs conventional head and neck radiotherapy) ISRCTN48243537. In addition to the planned analysis, dosimetric analysis was employed to investigate an unexpected finding that acute fatigue was more prevalent in the IMRT arm of the trial. It can be challenging to collect 3-D dosimetric information from multicentre radiotherapy trials. However, analysing the relationship between dosimetric and toxicity data provides invaluable information which can influence the next generation of radiotherapy techniques.

  6. Characterization of SWIR cameras by MRC measurements

    NASA Astrophysics Data System (ADS)

    Gerken, M.; Schlemmer, H.; Haan, Hubertus A.; Siemens, Christofer; Münzberg, M.

    2014-05-01

    Cameras for the SWIR wavelength range are becoming more and more important because of the better observation range for day-light operation under adverse weather conditions (haze, fog, rain). In order to choose the best suitable SWIR camera or to qualify a camera for a given application, characterization of the camera by means of the Minimum Resolvable Contrast MRC concept is favorable as the MRC comprises all relevant properties of the instrument. With the MRC known for a given camera device the achievable observation range can be calculated for every combination of target size, illumination level or weather conditions. MRC measurements in the SWIR wavelength band can be performed widely along the guidelines of the MRC measurements of a visual camera. Typically measurements are performed with a set of resolution targets (e.g. USAF 1951 target) manufactured with different contrast values from 50% down to less than 1%. For a given illumination level the achievable spatial resolution is then measured for each target. The resulting curve is showing the minimum contrast that is necessary to resolve the structure of a target as a function of spatial frequency. To perform MRC measurements for SWIR cameras at first the irradiation parameters have to be given in radiometric instead of photometric units which are limited in their use to the visible range. In order to do so, SWIR illumination levels for typical daylight and twilight conditions have to be defined. At second, a radiation source is necessary with appropriate emission in the SWIR range (e.g. incandescent lamp) and the irradiance has to be measured in W/m2 instead of Lux = Lumen/m2. At third, the contrast values of the targets have to be calibrated newly for the SWIR range because they typically differ from the values determined for the visual range. Measured MRC values of three cameras are compared to the specified performance data of the devices and the results of a multi-band in-house designed Vis-SWIR camera

  7. [Confusion about MRC dyspnea scales in Japan--which MRC dyspnea scale should we employ?].

    PubMed

    Miyamoto, Kenji

    2008-08-01

    Though the Hugh-Jones dyspnea scale has been widely used in Japan, the British Medical Research Council (MRC) dyspnea scale and/or modified MRC dyspnea scales have been used in many other countries. One of these modified MRC dyspnea scales was translated into Japanese and appeared in both the "Japanese Manual of Respiratory Rehabilitation (2003)" and the "Japanese Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease (2004)" which were published by the Japanese Respiratory Society. Subsequently, the MRC dyspnea scale appeared in a textbook and in review articles published in Japan. However, this dyspnea scale, which was translated into Japanese, is not used by the British Thoracic Society, American Thoracic Society, European Respiratory Society, Canadian Respiratory Society, or Global Initiative for Chronic Obstructive Lung Disease (GOLD). The Japanese version of the MRC dyspnea scale has two serious problems: 1) normal healthy subjects have to be classified into dyspnea grade 0 or grade 1, and 2) incorrect Japanese translation of the scale. The Japanese Respiratory Society has to decide which MRC dyspnea scale should be employed, with a well-thought-out translation.

  8. MRC for compression of Blake Archive images

    NASA Astrophysics Data System (ADS)

    Misic, Vladimir; Kraus, Kari; Eaves, Morris; Parker, Kevin J.; Buckley, Robert R.

    2002-11-01

    The William Blake Archive is part of an emerging class of electronic projects in the humanities that may be described as hypermedia archives. It provides structured access to high-quality electronic reproductions of rare and often unique primary source materials, in this case the work of poet and painter William Blake. Due to the extensive high frequency content of Blake's paintings (namely, colored engravings), they are not suitable for very efficient compression that meets both rate and distortion criteria at the same time. Resolving that problem, the authors utilized modified Mixed Raster Content (MRC) compression scheme -- originally developed for compression of compound documents -- for the compression of colored engravings. In this paper, for the first time, we have been able to demonstrate the successful use of the MRC compression approach for the compression of colored, engraved images. Additional, but not less important benefits of the MRC image representation for Blake scholars are presented: because the applied segmentation method can essentially lift the color overlay of an impression, it provides the student of Blake the unique opportunity to recreate the underlying copperplate image, model the artist's coloring process, and study them separately.

  9. Reduction of MRC error review time through the simplified and classified MRC result

    NASA Astrophysics Data System (ADS)

    Lee, Casper W.; Lin, Jason C.; Chen, Frank F.

    2009-04-01

    As the Manufacturing Rule Check (MRC) error counts are very huge, it has been getting difficult to review by each point and maybe some of the design errors will be ignored. It's necessary to reduce the review error counts and improve the checking methods. The paper presents an error classification function and auto-waived mechanism for decreasing the repeated MRC errors in MRC report. In auto-waived mechanism, the report will omit the error point if it is same as previous report and the defect location output will keep all of the error points for Do Not Inspection Area (DNIR) reference. (DNIR needs customer's approval). Furthermore, it is possible to develop an auto-waived function to skip the confirmed errors which is provided by customer with a marking information table or GDS/OASIS database. Besides, this paper also presents how these errors can be grouping and reducing checking time.

  10. A new method of ICCD imaging system MRC measurement

    NASA Astrophysics Data System (ADS)

    Li, Sheng-cai; Jin, Wei-qi; Wang, Xia; Zhang, Wei-qiang; Dong, Hai-yan

    2005-02-01

    Based on analysis of the working principle of ICCD imaging system, the paper develops a new testing system for synthetic performance of ICCD imaging system. With the help of this testing system for integrative performance and the theory of Weibull psychometric function, a new method for MRC measurement of Space Light Modulation (SLM) is proposed, and the paper firstly implements measurement for minimum resolvable contrast performance of ICCD imaging system. The method provides reference for MRC performance measurement of other imaging system.

  11. Mask manufacturing rules checking (MRC) as a DFM strategy

    NASA Astrophysics Data System (ADS)

    Buck, Peter; Gladhill, Richard; Straub, Joseph

    2007-03-01

    Mask Manufacturing Rules Checking (MRC) has been established as an automated process to detect mask pattern data that will cause mask inspection problems. This methodology is unique from the Design Rule Checking (DRC) or Design for Manufacturing (DFM) checks typically performed before sending pattern data to the mask manufacturer in that it examines the entire mask layout and the spatial relationship between multiple patterns in their final orientation, scale, and tone. In contrast, DRC and DFM checks are usually performed on individual pattern files. Also, DRC and DFM checks are not always performed after all pattern transformations are complete, and errors can be introduced that are not caught until the mask is eventually printed on wafers. Therefore, MRC can often be the only comprehensive geometric integrity test performed before the mask is manufactured and the last opportunity to catch critical errors that might have disastrous consequences to yield and consequently to product schedules. In this paper we review the concepts and implementation of MRC in a merchant mask manufacturing enterprise and introduce methods to empower DFM decisions by mask customers based on MRC results.

  12. Differences in physical activity according to mMRC grade in patients with COPD

    PubMed Central

    Hayata, Atsushi; Minakata, Yoshiaki; Matsunaga, Kazuto; Nakanishi, Masanori; Yamamoto, Nobuyuki

    2016-01-01

    Background Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness. The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD. Objectives We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD. Methods A cross-sectional study was performed on stable outpatients with COPD. PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale. Results Ninety-eight patients were recruited. Significant differences in PA duration were observed at all intensities according to the mMRC grade. Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day. COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4). Conclusion PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL. Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD. PMID:27695306

  13. Series solutions for π/4-DQPSK BER with MRC

    NASA Astrophysics Data System (ADS)

    Chandra, Aniruddha; Bose, Chayanika

    2012-03-01

    Simple series expressions for bit error rate (BER) of π/4 shifted differential quaternary phase-shift keying (π/4-DQPSK) over some common fading environments (Rayleigh, Rician and Nakagami-m) are derived. Both single- and multi-channel reception scenarios are considered. In case of multi-antenna reception, it is assumed that the fading is independent and identically distributed (IID), and the receiver follows optimum maximal ratio combining (MRC). The derived expressions, computed through probability density function (PDF)-based approach, give an exact match with moment-generating function (MGF)-based solutions but get rid of numerical integrations involved in MGF approach. Further, the analytical results presented in this article consist of finite or rapidly converging infinite series and thus a trade-off between precision and complexity can be easily realised by choosing a specific number of terms. Bounds on the error resulting from truncation of the infinite series are also derived. Moreover, it was shown that the series solutions, when reasonably truncated, still provide better approximations than the previous attempts.

  14. Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro.

    PubMed

    Soleymanifard, Shokouhozaman; Toossi, Mohammad Taghi Bahreyni; Samani, Roghayeh Kamran; Mohebbi, Shokoufeh

    2014-04-01

    Radiation-induced bystander effect (RIBE) has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5), and a human lung tumor cell line (QU-DB) were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells.

  15. Isolation of influenza virus in human lung embryonated fibroblast cells (MRC-5) from clinical samples.

    PubMed Central

    de Oña, M; Melón, S; de la Iglesia, P; Hidalgo, F; Verdugo, A F

    1995-01-01

    Ninety-four pharyngeal swab samples corresponding to 94 patients with suspected influenza virus infection were inoculated in Madin-Darby canine kidney (MDCK) cells, the conventional cell system for the isolation of influenza virus, and in fibroblastic human embryo lung (MRC-5) cells, a cell system less commonly used for this purpose but one frequently used in clinical virology laboratories. Both cell preparations were treated with trypsin. Influenza virus was recovered from 15% of the samples inoculated in MDCK cells and from 18% of those inoculated in MRC-5 cells. The use of MRC-5 cells can simplify the search for respiratory viruses and would assist in the rapid detection of influenza virus during new epidemics. PMID:7665680

  16. Performance analysis of MRC spatial diversity receiver system for satellite-to-ground downlink optical transmissions

    NASA Astrophysics Data System (ADS)

    Li, Kangning; Ma, Jing; Tan, Liying; Yu, Siyuan; Cao, Yubin

    2016-10-01

    The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed turbulence are studied for multiple apertures receiver system. Maximum ratio combining (MRC) technique is considered as a combining scheme to mitigate the atmospheric turbulence under thermal noise limited conditions. Bit-error rate (BER) performances for on-off keying (OOK) modulated direct detection optical communications are analyzed for MRC diversity receptions through an approximation method. To show the net diversity gain of multiple apertures receiver system, BER performances of MRC receiver system are compared with a single monolithic aperture receiver system with the same total aperture area (same average total incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are also verified by Monte-Carlo (MC) simulations.

  17. Three-dimensional computer reconstruction of large tissue volumes based on composing series of high-resolution confocal images by GlueMRC and LinkMRC software.

    PubMed

    Karen, Petr; Jirkovská, Marie; Tomori, Zoltán; Demjénová, Erna; Janácek, Jirí; Kubínová, Lucie

    2003-12-01

    Computer-based visualization of large tissue volumes with high resolution based on composing series of high-resolution confocal images is presented. GlueMRC and LinkMRC programs are introduced, implementing composition of overlapping series of optical sections captured by a confocal microscope, registration and subsequent composition of successive confocal stacks. Both programs are using an interactive approach in combination with automatic algorithms for image registration. Further, the method for obtaining surface renderings of microscopical structure under study is described. For this purpose, structure contours visible in the sections are interactively digitized using a Colon plug-in module running in Ellipse environment. Then the coordinates of the contours are processed by special modules in the graphic programming environment IRIS Explorer and the structure surface is rendered. The method is shown on the 3-D reconstruction of the capillary bed of human placental villi and chick embryonic gut and its vascular bed. Copyright 2003 Wiley-Liss, Inc.

  18. Automobile exhaust particle-induced apoptosis and necrosis in MRC-5 cells.

    PubMed

    Zhao, X H; Wang, X L; Li, X Y

    2001-05-31

    To study the effect of particulate extracts (PE) collected from a heavy traffic road in Lanzhou City, on MRC-5 cell apoptosis, and to explore the toxicity action of PE and its mechanism. Cultured MRC-5 cells were incubated in the extracts of different concentrations. Inhibition of proliferation was measured with a colorimetric 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological assessment of apoptosis was performed with fluorescence microscopy and electronic microscopy. Extracted DNA from the cells was electrophoresed on agarose gel in order to observe DNA fragmentation. The amount of apoptotic cells was measured by flow cytometry. The results indicated that exposure of exponentially growing MRC-5 cells exposed to PE 5-160 microg l(-1) for 24-96 h resulted in dose- and time-dependent reduction of survival of MRC-5 cells. After treatment with PE, markedly morphological changes of MRC-5 cells including "apoptotic bodies", were observed with a fluorescence microscope. Agarose gel electrophoresis of DNA from the cells treated with PE for 48 and 72 h revealed a "ladder" pattern. PE induced apoptosis in low doses but necrosis in high doses. Apoptotic rates were 12.95, 17.40 and 29.80% after treatment with PE 5, 10, and 20 microg l(-1), respectively. A typical sub-diploid apoptosis peak was demonstrated in MRC-5 cells treated with PE. A significant dose-effect response and time-effect correlation could be found between apoptosis rates and PE. All results confirmed that the PE could induce and accelerate apoptosis in low doses but necrosis in high doses.

  19. Advanced manufacturing rules check (MRC) for fully automated assessment of complex reticle designs: Part II

    NASA Astrophysics Data System (ADS)

    Straub, J. A.; Aguilar, D.; Buck, P. D.; Dawkins, D.; Gladhill, R.; Nolke, S.; Riddick, J.

    2006-10-01

    Advanced electronic design automation (EDA) tools, with their simulation, modeling, design rule checking, and optical proximity correction capabilities, have facilitated the improvement of first pass wafer yields. While the data produced by these tools may have been processed for optimal wafer manufacturing, it is possible for the same data to be far from ideal for photomask manufacturing, particularly at lithography and inspection stages, resulting in production delays and increased costs. The same EDA tools used to produce the data can be used to detect potential problems for photomask manufacturing in the data. In the previous paper, it was shown how photomask MRC is used to uncover data related problems prior to automated defect inspection. It was demonstrated how jobs which are likely to have problems at inspection could be identified and separated from those which are not. The use of photomask MRC in production was shown to reduce time lost to aborted runs and troubleshooting due to data issues. In this paper, the effectiveness of this photomask MRC program in a high volume photomask factory over the course of a year as applied to more than ten thousand jobs will be shown. Statistics on the results of the MRC runs will be presented along with the associated impact to the automated defect inspection process. Common design problems will be shown as well as their impact to mask manufacturing throughput and productivity. Finally, solutions to the most common and most severe problems will be offered and discussed.

  20. Tolerance-based OPC and solution to MRC-constrained OPC

    NASA Astrophysics Data System (ADS)

    Ping, Yang; Li, Xiaohai; Jang, Stephen; Kwa, Denny; Zhang, Yunqiang; Lugg, Robert

    2011-04-01

    Model based optical proximity correction (MB-OPC) has been widely used in advanced lithography process today. However controlling the edge placement error (EPE) and critical dimension (CD) has become harder as the k1 process factor decreases and design complexity increases. Especially, for high-NA lithography using strong off-axis illumination (OAI), ringing effects on 2D layout makes CD control difficult. In addition, mask rule check (MRC) limits also prevent good OPC convergence where two segment edges are corrected towards each other to form a correction-conflicting scenario because traditional OPC only consider the impact of the current edge when calculating the edge movement. A more sophisticated OPC algorithm that considers the interaction between segments is necessary to find a solution that is both MRC and convergence compliant. This paper first analyzes the phenomenon of MRC-constrained OPC. Then two multiple segment correction techniques for tolerance-based OPC and MRC-constrained OPC are discussed. These correction techniques can be applied to selected areas with different lithographic specifications. The feasibility of these techniques is demonstrated by quantifying the EPE convergence through iterations and by comparing the simulated contour results.

  1. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study.

    PubMed

    Huang, Wei-Chang; Wu, Ming-Feng; Chen, Hui-Chen; Hsu, Jeng-Yuan

    2015-11-05

    The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used. This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC. This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed. Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0-1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment. The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD.

  2. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study

    PubMed Central

    Huang, Wei-Chang; Wu, Ming-Feng; Chen, Hui-Chen; Hsu, Jeng-Yuan

    2015-01-01

    Background: The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used. Aims: This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC. Methods: This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed. Results: Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0–1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment. Conclusions: The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD. PMID:26538368

  3. Paeonol attenuates aging MRC-5 cells and inhibits epithelial-mesenchymal transition of premalignant HaCaT cells induced by aging MRC-5 cell-conditioned medium.

    PubMed

    Yang, Lihua; Xing, Shangping; Wang, Kun; Yi, Hua; Du, Biaoyan

    2017-08-12

    Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear. In this study, we first established a senescent human fetal lung fibroblast MRC-5 cell model using hydrogen peroxide evaluated by senescence-associated β-galactosidase assay. Upon paeonol treatment, intracellular reactive oxygen species levels in aging MRC-5 cells were significantly decreased via regulation of nuclear translocation of Nrf2. Then we curiously studied whether the aging MRC-5 cell-conditioned medium could induce EMT in premalignant HaCaT cells, and the results showed that paeonol significantly reduced the clonogenic, migratory, and invasive capacities of premalignant HaCaT cells potentially induced by IL-6 and IL-8. Moreover, we found that paeonol notably altered pluripotency of EMT-associated markers via the modulation of ERK and TGF-β1/Smad pathway in premalignant HaCaT cells. These findings suggest that paeonol may be used as an adjuvant therapy for SASP factor-mediated EMT in premalignant lesion.

  4. High Genetic Stability of Dengue Virus Propagated in MRC-5 Cells as Compared to the Virus Propagated in Vero Cells

    PubMed Central

    Butler, Michael; Wu, Suh-Chin

    2008-01-01

    This work investigated the replication kinetics of the four dengue virus serotypes (DEN-1 to DEN-4), including dengue virus type 4 (DEN-4) recovered from an infectious cDNA clone, in Vero cells and in MRC-5 cells grown on Cytodex 1 microcarriers. DEN-1 strain Hawaii, DEN-2 strain NGC, DEN-3 strain H-87, and DEN-4 strain H-241 , and DEN-4 strain 814669 derived from cloned DNA, were used to infect Vero cells and MRC-5 cells grown in serum-free or serum-containing microcarrier cultures. Serum-free and serum-containing cultures were found to yield comparable titers of these viruses. The cloned DNA-derived DEN-4 started genetically more homogeneous was used to investigate the genetic stability of the virus propagated in Vero cells and MRC-5 cells. Sequence analysis revealed that the DEN-4 propagated in MRC-5 cells maintained a high genetic stability, compared to the virus propagated in Vero cells. Amino acid substitutions of Gly104Cys and Phe108Ile were detected at 70%, 60%, respectively, in the envelope (E) protein of DEN-4 propagated in Vero cells, whereas a single mutation of Glu345Lys was detected at 50% in E of the virus propagated in MRC-5 cells. Sequencing of multiple clones of three separate DNA fragments spanning 40% of the genome also indicated that DEN-4 propagated in Vero cells contained a higher number of mutations than the virus growing in MRC-5 cells. Although Vero cells yielded a peak virus titer approximately 1 to 17 folds higher than MRC-5 cells, cloned DEN-4 from MRC-5 cells maintained a greater stability than the virus from Vero cells. Serum-free microcarrier cultures of MRC-5 cells offer a potentially valuable system for the large-scale production of live-attenuated DEN vaccines. PMID:18350148

  5. Simulation study of the dynamic performance of a MRC plant with refrigerant charged or leaked

    NASA Astrophysics Data System (ADS)

    Sun, Heng; Shu, Dan; Jiang, Zhihua

    2012-01-01

    The running condition of a MRC plant is affected by the charge or leakage of the refrigerant. It is significant for the design and operation of the plant. A new model which is established based on the process simulation, mass conservation and characteristics of the system was employed to study the dynamic performance in these cases. The results show that the light composition mainly affects the pressure and the heavy composition affects the liquid level of vessel more obviously. This is due to the fact that the light composition mainly stays in the vapor phase and the heavies stay in the liquid phase mostly. The case when leakages occur at different location was also studied. The results can provide useful information for the adjustment of mixture refrigerant and operation of a MRC plant.

  6. Outage Capacity Analysis of TAS/MRC Systems over Arbitrary Nakagami-m Fading Channels

    NASA Astrophysics Data System (ADS)

    Hung, Chia-Chun; Chiang, Ching-Tai; Lin, Shyh-Neng; Wu, Rong-Ching

    A simple closed-form approximation for the outage capacity of Transmit Antenna Selection/Maximal-Ratio Combining (TAS/MRC) systems over independent and identically distributed (i.i.d) Nakagami-m fading channels is derived while the fading index is a positive integer. When the Nakagami-m fading index is not an integer, the approximate outage capacity is derived as a single infinite series of Gamma function. Computer simulations verify the accuracy of the approximate results.

  7. Protein crystallization screens developed at the MRC Laboratory of Molecular Biology.

    PubMed

    Gorrec, Fabrice

    2016-05-01

    In order to solve increasingly challenging protein structures with crystallography, crystallization reagents and screen formulations are regularly investigated. Here, we briefly describe 96-condition screens developed at the MRC Laboratory of Molecular Biology: the LMB sparse matrix screen, Pi incomplete factorial screens, the MORPHEUS grid screens and the ANGSTROM optimization screen. In this short review, we also discuss the difficulties and advantages associated with the development of protein crystallization screens.

  8. The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and interdependence

    PubMed Central

    2014-01-01

    Background The S-phase checkpoint aims to prevent cells from generation of extensive single-stranded DNA that predisposes to genome instability. The S. cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase when DNA synthesis is prohibited. Keeping the replication machinery intact allows restart of the replication fork when the block is relieved. Although the subunits of the Tof1/Csm3/Mrc1 complex are well studied, the impact of every single subunit on the triple complex formation and function needs to be established. Findings This work studies the cellular localization and the chromatin binding of GFP-tagged subunits when the complex is intact and when a subunit is missing. We demonstrate that the complex is formed in cell nucleus, not the cytoplasm, as Tof1, Csm3 and Mrc1 enter the nucleus independently from one another. Via in situ chromatin binding assay we show that a Tof1-Csm3 dimer formation and chromatin binding is required to ensure the attachment of Mrc1 to chromatin. Our study indicates that the translocation into the nucleus is not the process to regulate the timing of chromatin association of Mrc1. We also studied the nuclear behavior of Mrc1 subunit in the process of adaptation to the presence hydroxyurea. Our results indicate that after prolonged HU incubation, cells bypass the S-phase checkpoint and proceed throughout the cell cycle. This process is accompanied by Mrc1 chromatin detachment and Rad53 dephosphorylation. Conclusions In S. cerevisiae the subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3 independently enter the cell nucleus, where a Tof1-Csm3 dimer is formed to ensure the chromatin binding of Mrc1 and favor DNA replication and S-phase checkpoint fork arrest. In the process of adaptation to the presence of hydroxyurea Mrc1 is detached from chromatin and Rad53 checkpoint activity is diminished in order to allow S-phase checkpoint escape and completion of the cell cycle. PMID:25379053

  9. RT-01FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR PITUITARY ADENOMA WITH NOVALIS

    PubMed Central

    Arakawa, Yoshiki; Mizowaki, Takashi; Ogura, Kengo; Sakanaka, Katsuyuki; Hojo, Masato; Hiraoka, Masahiro; Miyamoto, Susumu; Murata, Daiki

    2014-01-01

    BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.

  10. Chronic Resveratrol Treatment Inhibits MRC5 Fibroblast SASP-Related Protumoral Effects on Melanoma Cells.

    PubMed

    Menicacci, Beatrice; Laurenzana, Anna; Chillà, Anastasia; Margheri, Francesca; Peppicelli, Silvia; Tanganelli, Elisabetta; Fibbi, Gabriella; Giovannelli, Lisa; Del Rosso, Mario; Mocali, Alessandra

    2017-09-01

    Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4. The cellular nuclear-factor-kB (NF-kB) protein level was also reduced, confirming its role in the induction of SASP. Resveratrol pretreated MRC5 fibroblasts were resistant to activation by TGFβ. Resveratrol treatment of senescent MRC5 induced the production of conditioned media (CM) which counteracted the protumoral effect of senescent CM on A375 and A375-M6 melanoma cell proliferation and invasiveness, and reduced the expression of epithelial-to-mesenchymal transition markers related to malignant features. This experimental approach proposes a treatment that targets the senescent stromal cell phenotype to induce an anti-tumor hosting microenvironment, which is suitable for both preventive and therapeutic purposes. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Inverse lithography technology (ILT): keep the balance between SRAF and MRC at 45 and 32 nm

    NASA Astrophysics Data System (ADS)

    Pang, Linyong; Liu, Yong; Dam, Thuc; Mihic, Kresimir; Cecil, Thomas; Abrams, Dan

    2007-10-01

    In this paper, we present the Luminescent's ILT approach that can rapidly solve for the optimal photomask design. We will discuss the latest development of ILT at Luminescent in the areas of sub-resolution assist feature (SRAF) generation and optimization to improve process window, and mask rule compliance (MRC). Results collected internally and from customers demonstrate that ILT is not only an R&D tool, but also a tool quickly maturing for production qualification at advanced technology nodes. By enforcing the proper constraints while optimizing the masks, ILT can improve process windows while maintaining mask costs at a reasonable level.

  12. Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis.

    PubMed Central

    Skinner, G R; Woodman, C B; Hartley, C E; Buchan, A; Fuller, A; Durham, J; Synnott, M; Clay, J C; Melling, J; Wiblin, C; Wilkins, J

    1982-01-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC, was used to prevent primary herpes genitalis in 60 subjects considered to be at risk of this infection. There was no evidence of serious local or general side effects. Neutralising antibody responses were detected in 59% and 90% of subjects receiving the low and high doses of vaccine respectively; immunoprecipitating antibody was detected at a lower frequency, namely in 23% and 43% of subjects receiving the low and high doses respectively. After a mean follow-up period of 18 months none of the vaccinated subjects contracted herpes genitalis after completing the vaccination course. Images PMID:6293640

  13. Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis.

    PubMed

    Skinner, G R; Woodman, C B; Hartley, C E; Buchan, A; Fuller, A; Durham, J; Synnott, M; Clay, J C; Melling, J; Wiblin, C; Wilkins, J

    1982-12-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC, was used to prevent primary herpes genitalis in 60 subjects considered to be at risk of this infection. There was no evidence of serious local or general side effects. Neutralising antibody responses were detected in 59% and 90% of subjects receiving the low and high doses of vaccine respectively; immunoprecipitating antibody was detected at a lower frequency, namely in 23% and 43% of subjects receiving the low and high doses respectively. After a mean follow-up period of 18 months none of the vaccinated subjects contracted herpes genitalis after completing the vaccination course.

  14. The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress

    PubMed Central

    Melnik, Andre; Wilson-Zbinden, Caroline; Schellhaas, René; Kastner, Lisa; Piwko, Wojciech; Dees, Martina; Picotti, Paola; Maric, Marija; Labib, Karim; Luke, Brian; Peter, Matthias

    2016-01-01

    Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1’s replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks. PMID:26849847

  15. Outage Probability of MRC for κ-μ Shadowed Fading Channels under Co-Channel Interference

    PubMed Central

    Chen, Changfang; Shu, Minglei; Wang, Yinglong; Yang, Ming; Zhang, Chongqing

    2016-01-01

    In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-μ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-μ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-μ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications. PMID:27851817

  16. Error Probability of MRC in Frequency Selective Nakagami Fading in the Presence of CCI and ACI

    NASA Astrophysics Data System (ADS)

    Rahman, Mohammad Azizur; Sum, Chin-Sean; Funada, Ryuhei; Sasaki, Shigenobu; Baykas, Tuncer; Wang, Junyi; Harada, Hiroshi; Kato, Shuzo

    An exact expression of error rate is developed for maximal ratio combining (MRC) in an independent but not necessarily identically distributed frequency selective Nakagami fading channel taking into account inter-symbol, co-channel and adjacent channel interferences (ISI, CCI and ACI respectively). The characteristic function (CF) method is adopted. While accurate analysis of MRC performance cannot be seen in frequency selective channel taking ISI (and CCI) into account, such analysis for ACI has not been addressed yet. The general analysis presented in this paper solves a problem of past and present interest, which has so far been studied either approximately or in simulations. The exact method presented also lets us obtain an approximate error rate expression based on Gaussian approximation (GA) of the interferences. It is shown, especially while the channel is lightly faded, has fewer multipath components and a decaying delay profile, the GA may be substantially inaccurate at high signal-to-noise ratio. However, the exact results also reveal an important finding that there is a range of parameters where the simpler GA is reasonably accurate and hence, we don't have to go for more involved exact expression.

  17. Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line

    PubMed Central

    Petrache Voicu, Sorina Nicoleta; Dinu, Diana; Sima, Cornelia; Hermenean, Anca; Ardelean, Aurel; Codrici, Elena; Stan, Miruna Silvia; Zărnescu, Otilia; Dinischiotu, Anca

    2015-01-01

    This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO2 NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area electron diffraction and X-ray diffraction. Our study showed a decreased cell viability and the induction of cellular oxidative stress as evidenced by an increased level of reactive oxygen species (ROS), carbonyl groups, and advanced oxidation protein products after 24, 48, and 72 h, as well as a decreased concentration of glutathione (GSH) and protein sulfhydryl groups. The protein expression of Hsp27, Hsp60, and Hsp90 decreased at all time intervals, while the level of protein Hsp70 remained unchanged during the exposure. Similarly, the expression of p53, MDM2 and Bcl-2 was significantly decreased for all time intervals, while the expression of Bax, a marker for apoptosis, was insignificantly downregulated. These results correlated with the increase of pro-caspase 3 expression. The role of autophagy in cellular response to SiO2 NPs was demonstrated by a fluorescence-labeled method and by an increased level of LC3-II/LC3-I ratio. Taken together, our data suggested that SiO2 NPs induced ROS-mediated autophagy in MRC-5 cells as a possible mechanism of cell survival. PMID:26690408

  18. SMO applied to contact layers at the 32nm node and below with consideration of MEEF and MRC

    NASA Astrophysics Data System (ADS)

    Wu, Te-Hung; Sinn, Robert; Gleason, Bob; Kim, JongDoo; Hong, Jiyoung; Park, Sejin; Lee, Sukjoo

    2011-11-01

    An illuminator and mask patterns were optimized (SMO) to minimize CD variation of a set of contact patterns selected from logic layouts and an array of SRAM cells. MEEF and defocus characteristics of the target patterns were modeled as functions of constraints on minimum mask features and spaces (MRC). This process was then repeated after linearly shrinking the input patterns by 10%. Common statistical measures of CD control worsen as MRC becomes more restrictive, but these are weak indicators compared to behavior at points in the image that exhibit high MEEF or low depth of focus. SMO solutions for minimum MEEF and maximum depth of focus are different, so some compromise is necessary. By including exposure time among the variables to be optimized, some control over local mask bias is made available to minimize MEEF and loss of litho quality due to MRC.

  19. Inhibition of connective tissue growth factor attenuates paraquat-induced lung fibrosis in a human MRC-5 cell line.

    PubMed

    Huang, Min; Yang, Huifang; Zhu, Lingqin; Li, Honghui; Zhou, Jian; Zhou, Zhijun

    2016-11-01

    Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016.

  20. Evaluation of novel biodegradable cyclic carbonate polyester copolymers for cytocompatibility using MRC-5 cells.

    PubMed

    Longino, J; Mullen, B; Benghuzzi, H; Tucci, M; Tang, C; Storey, R; Puckett, A

    2003-01-01

    The objective of this work was to synthesize and characterize a novel series of biodegradable cyclic carbonate polyester copolymers based on lactide and 5-methyl-5-benzyloxy-carbonyl-1,3-dioxan-2-one (MBC). Two compositions were selected for characterization. One copolymer was based on a racemic mixture of 1-lactide with 15.4 mole % MBC and the other was based on 1-lactide with 8.2 mole % MBC. These polymers contain carboxylic acid moieties along the backbone that may be used for tethering bioactive agents, forming ionic crosslinks or be reacted with vinyl containing monomers to allow free radical crosslinking. The initial materials evaluated have the carboxylic acid functionalities blocked with benzene. These polymers and the de-blocked versions may have potential applications for hard and soft tissue scaffolds, control drug delivery matrixes or a variety of other applications in medicine. The copolymer samples were pressed into 7.0-mm diameter disk using a KBr press. The disks were then sterilized using U.V radiation under a laminar flow hood. After sterilization, the copolymer disks were submerged in 2 ml of media and placed in a CO2 regulated incubator at 37 degrees C. A total of six groups per phase (n = 7 test tubes per group) were used in this study. Test tubes in groups I and III were plated with MRC-5 and subsequently treated with media alone (controls). Test tubes in groups II and IV were plated with MRC-5 and subsequently treated with media before being introduced to copolymer samples. Cell number, as well as, biochemical markers such as protein and malondialdehyde (MDA) were determined at the end of the 24, 48 and 72-hour time periods. Representative test tubes were subjected to an H&E staining procedure for microscopic morphological evaluation. The results of this evaluation suggest that the exposure of both copolymers produced a non-cytotoxic environment with the MRC-5 cell line. Although both copolymers are non-cytotoxic, the sample having the higher

  1. Outage Probability and Ergodic Capacity of Spectrum-Sharing Systems with MRC Diversity

    NASA Astrophysics Data System (ADS)

    Jarrouj, Jiana; Blagojevic, Vesna; Ivanis, Predrag

    2016-03-01

    The spectrum sharing system employing maximum ratio combining (MRC) is analyzed in Nakagami fading environment, for the case when the interference from the primary user is present at the input of the secondary user receiver. The closed-form expressions for the probability density function of the signal-to-interference-and-noise ratio, the outage probability and the ergodic capacity of the SU link are derived under both peak interference and maximal transmit power constraints. Asymptotical expressions are provided for the important region where peak interference power constraint dominates and the case when the interference from the primary user's is dominant compared to the noise at the secondary user's receiver. The obtained expressions are presented for both cases of outdated and mean-value based power allocation and verified by using Monte Carlo simulation method.

  2. Isolation of eastern equine encephalitis virus in A549 and MRC-5 cell cultures.

    PubMed

    Sotomayor, E A; Josephson, S L

    1999-07-01

    Eastern equine encephalitis (EEE) has been diagnosed either serologically or by virus isolation. Until now, the recovery of EEE virus has been delegated to reference laboratories with the expertise and resources needed to amplify the virus in a susceptible vertebrate host and/or to isolate and identify the virus in cell culture. We report a case in which EEE virus was recovered directly from a patient's cerebrospinal fluid in A549 and MRC-5 cell cultures. Many clinical virology laboratories routinely use these cells to recover adenovirus, herpes simplex virus, and enterovirus. To the best of our knowledge, this is the first report of isolation of EEE virus in A549 cell culture. This report demonstrates the possibility of recovery of EEE virus in cell culture without the necessity of bioamplification or maintaining unusual cell lines.

  3. Rac2-MRC-cIII–generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors

    PubMed Central

    Nieborowska-Skorska, Margaret; Kopinski, Piotr K.; Ray, Regina; Hoser, Grazyna; Ngaba, Danielle; Flis, Sylwia; Cramer, Kimberly; Reddy, Mamatha M.; Koptyra, Mateusz; Penserga, Tyrone; Glodkowska-Mrowka, Eliza; Bolton, Elisabeth; Holyoake, Tessa L.; Eaves, Connie J.; Cerny-Reiterer, Sabine; Valent, Peter; Hochhaus, Andreas; Hughes, Timothy P.; van der Kuip, Heiko; Sattler, Martin; Wiktor-Jedrzejczak, Wieslaw; Richardson, Christine; Dorrance, Adrienne; Stoklosa, Tomasz; Williams, David A.

    2012-01-01

    Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII–generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor–resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)–positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML. PMID:22411871

  4. Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors.

    PubMed

    Nieborowska-Skorska, Margaret; Kopinski, Piotr K; Ray, Regina; Hoser, Grazyna; Ngaba, Danielle; Flis, Sylwia; Cramer, Kimberly; Reddy, Mamatha M; Koptyra, Mateusz; Penserga, Tyrone; Glodkowska-Mrowka, Eliza; Bolton, Elisabeth; Holyoake, Tessa L; Eaves, Connie J; Cerny-Reiterer, Sabine; Valent, Peter; Hochhaus, Andreas; Hughes, Timothy P; van der Kuip, Heiko; Sattler, Martin; Wiktor-Jedrzejczak, Wieslaw; Richardson, Christine; Dorrance, Adrienne; Stoklosa, Tomasz; Williams, David A; Skorski, Tomasz

    2012-05-03

    Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII-generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor-resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)-positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML.

  5. Role of protein kinase C-η in cigarette smoke extract-induced apoptosis in MRC-5-cells.

    PubMed

    Son, E S; Kyung, S Y; Lee, S P; Jeong, S H; Shin, J Y; Ohba, M; Yeo, E J; Park, J W

    2015-09-01

    Cigarette smoke (CS) is a major risk factor for emphysema, which causes cell death in structural cells of the lung by mechanisms that are still not completely understood. We demonstrated previously that CS extract (CSE) induces caspase activation in MRC-5 human lung fibroblasts, activated protein kinase C-η (PKC-η), and translocated PKC-η from the cytosol to the membrane. The objective of this study was to investigate the involvement of PKC-η activation in a CSE-induced extrinsic apoptotic pathway. We determined that CSE increases expression of caspase 3 and 8 cleavage in MRC-5 cells and overexpression of PKC-η significantly increased expression of caspase 3 and 8 cleavage compared with control LacZ-infected cells. In contrast, dominant negative (dn) PKC-η inhibited apoptosis in MRC-5 cells exposed to CSE and decreased expression of caspase 3 and 8 compared with control cells. Exposure to 10% CSE for >8 h significantly increased lactate dehydrogenase release in PKC-η-infected cells compared with LacZ-infected cells. Additionally, PKC-η-infected cells had an increased number of Hoechst 33342 stained nuclei compared with LacZ-infected cells, while dn PKC-η-infected cells exhibited fewer morphological changes than LacZ-infected cells under phase-contrast microscopy. In conclusion, PKC-η activation plays a pro-apoptotic role in CSE-induced extrinsic apoptotic pathway in MRC-5 cells. These results suggest that modulation of PKC-η may be a useful tool for regulating the extrinsic apoptosis of MRC-5 cells by CSE and may have therapeutic potential in the treatment of CS-induced lung injury.

  6. NASA'S SERVIR Gulf of Mexico Project: The Gulf of Mexico Regional Collaborative (GoMRC)

    NASA Technical Reports Server (NTRS)

    Quattrochi, Dale A.; Irwin, Daniel; Presson, Joan; Estes, Maury; Estes, Sue; Judd, Kathleen

    2006-01-01

    The Gulf of Mexico Regional Collaborative (GoMRC) is a NASA-funded project that has as its goal to develop an integrated, working, prototype IT infrastructure for Earth science data, knowledge and models for the five Gulf U.S. states and Mexico, and to demonstrate its ability to help decision-makers better understand critical Gulf-scale issues. Within this preview, the mission of this project is to provide cross cutting solution network and rapid prototyping capability for the Gulf of Mexico region, in order to demonstrate substantial, collaborative, multi-agency research and transitional capabilities using unique NASA data sets and models to address regional problems. SERVIR Mesoamerica is seen as an excellent existing framework that can be used to integrate observational and GIs data bases, provide a sensor web interface, visualization and interactive analysis tools, archival functions, data dissemination and product generation within a Rapid Prototyping concept to assist decision-makers in better understanding Gulf-scale environmental issues.

  7. NASA'S SERVIR Gulf of Mexico Project: The Gulf of Mexico Regional Collaborative (GoMRC)

    NASA Technical Reports Server (NTRS)

    Quattrochi, Dale A.; Irwin, Daniel; Presson, Joan; Estes, Maury; Estes, Sue; Judd, Kathleen

    2006-01-01

    The Gulf of Mexico Regional Collaborative (GoMRC) is a NASA-funded project that has as its goal to develop an integrated, working, prototype IT infrastructure for Earth science data, knowledge and models for the five Gulf U.S. states and Mexico, and to demonstrate its ability to help decision-makers better understand critical Gulf-scale issues. Within this preview, the mission of this project is to provide cross cutting solution network and rapid prototyping capability for the Gulf of Mexico region, in order to demonstrate substantial, collaborative, multi-agency research and transitional capabilities using unique NASA data sets and models to address regional problems. SERVIR Mesoamerica is seen as an excellent existing framework that can be used to integrate observational and GIs data bases, provide a sensor web interface, visualization and interactive analysis tools, archival functions, data dissemination and product generation within a Rapid Prototyping concept to assist decision-makers in better understanding Gulf-scale environmental issues.

  8. Properties of Lya Emitters Around the Radio Galaxy MRC 0316-257

    SciTech Connect

    Venemans, B; Rottgering, H; Miley, G; Kurk, J; De Breuck, C; van Breugel, W; Carilli, C; Ford, H; Heckman, T; Pentericci, L; McCarthy, P

    2004-08-12

    Observations of the radio galaxy MRC 0316-257 at z = 3.13 and the surrounding field are presented. Using narrow- and broad-band imaging obtained with the VLT*, 92 candidate Ly{alpha} emitters with a rest-frame equivalent width of > 15 AngstromS were selected in a {approx} 7{prime} x 7{prime} field around the radio galaxy. Spectroscopy of 40 candidate emitters resulted in the discovery of 33 emission line galaxies of which 31 are Ly{alpha} emitters with redshifts similar to that of the radio galaxy, while the remaining two galaxies turned out to be [{omicron} II] emitters. The Ly{alpha} profiles had widths (FWHM) corresponding to 120-800 kms{sup -1},with a median of 260 kms{sup -1}. Where the signal-to-noise spectra was large enough, the Ly{alpha} profiles are found to be asymmetric, with apparent absorption troughs blueward of the profile peaks, indicative of absorption along the line of sight of an {Eta}{Iota} mass of 1-5000 {mu}{circle_dot}. Besides that of the radio galaxy and one of the emitters that is an QSO, the continuum of the emitters is faint, with luminosities ranging from 1.3 L{sub *} to < 0.03 L{sub *}.The colors of the confirmed emitters are, on average, very blue. The median UV continuum slope is {beta}=-1.65, bluer than the average slope of LBGs with Ly{alpha} emitters is 2.6 {Mu}{circle_dot}{sup -1} as measured by the Ly{alpha} emission line or < 3.9 {Mu}{circle_dot}{sup -1} as measured by the UV continuum. The properties of the Ly{alpha} galaxies (faint, blue and small) are consistent with young star forming galaxies which are nearly dust free. The density of Ly{alpha} emitting galaxies in the field around MRC 0316-257 is a factor of 3.3{sup +0.5}{sub -0.4} larger compared with the density of Ly{alpha} emitters at that redshift. The velocity distribution of the spectroscopically confirmed emitters has a dispersion of 640 km s{sup -1}, corresponding to a FWHM of 1510 km s{sup -1}, which is substantially smaller than the width of the narrow

  9. Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy

    PubMed Central

    Verlut, Clotilde; Mouillet, Guillaume; Magnin, Eloi; Buffet-Miny, Joëlle; Viennet, Gabriel; Cattin, Françoise; Billon-Grand, Nora Clelia; Bonnet, Emilie; Servagi-Vernat, Stéphanie; Godard, Joël; Billon-Grand, Romain; Petit, Antoine; Moulin, Thierry; Cals, Laurent; Pivot, Xavier; Curtit, Elsa

    2016-01-01

    INTRODUCTION Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m2 per day, followed by six cycles of maintenance temozolomide (150–200 mg/m2, five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5–15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3–4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3–4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients. PMID:27559302

  10. The effect of prepartum antibiotics on the type of neonatal bacteraemia: insights from the MRC ORACLE trials.

    PubMed

    Gilbert, R E; Pike, K; Kenyon, S L; Tarnow-Mordi, W; Taylor, D J

    2005-06-01

    We analysed the type of bacteraemia before discharge from Neonatal Intensive Care Units in babies born to women randomised to the MRC ORACLE Trials. There was no evidence for an effect of oral antibiotics given prior to delivery on bacteraemia due to gram negative or enterococci bacteria, but Group B streptococcal (GBS) bacteraemia was significantly reduced in women with preterm prelabour rupture of the membranes (1.58% to 0.55%, relative risk 0.34; 95% CI: 0.17-0.70). There was no detectable effect in women in spontaneous preterm labour with intact membranes as the risk of GBS bacteraemia in their babies was very small regardless of treatment.

  11. Numerical study of flow, combustion and emissions characteristics in a 625 MWe tangentially fired boiler with composition of coal 70% LRC and 30% MRC

    NASA Astrophysics Data System (ADS)

    Sa'adiyah, Devy; Bangga, Galih; Widodo, Wawan; Ikhwan, Nur

    2017-08-01

    Tangential fired boiler is one of the methods that can produce more complete combustion. This method applied in Suralaya Power Plant, Indonesia. However, the boiler where supposed to use low rank coal (LRC), but at a given time must be mixed with medium rank coal (MRC) from another unit because of lack of LRC coal. Accordingly to the situation, the study about choosing the right position of LRC and MRC in the burner elevation must be investigated. The composition of coal is 70%LRC / 30%MRC where MRC will be placed at the lower (A & C - Case I)) or higher (E & G - Case II) elevation as the cases in this study. The study is carried out using Computational Fluid Dynamics (CFD) method. The simulation with original case (100%LRC) has a good agreement with the measurement data. As the results, MRC is more recommended at the burner elevation A & C rather than burner elevation E & G because it has closer temperature (880 K) compared with 100%LRC and has smaller local heating area between upper side wall and front wall with the range of temperature 1900 - 2000 K. For emissions, case I has smaller NOx and higher CO2 with 104 ppm and 15,6%. Moreover, it has samller O2 residue with 5,8% due to more complete combustion.

  12. Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation

    PubMed Central

    Troughton, Jacqui; Chatterjee, Sudesna; Hill, Siân E.; Daly, Heather; Martin Stacey, Lorraine; Stone, Margaret A.; Patel, Naina; Khunti, Kamlesh; Yates, Thomas; Gray, Laura J.; Davies, Melanie J.

    2016-01-01

    Background We report development of a group-based lifestyle intervention, Let's Prevent, using the UK Medical Research Council (MRC) framework, and delivered by structured education to prevent type 2 diabetes mellitus (T2DM) in people with impaired glucose regulation (IGR) in a UK multi-ethnic population. Methods Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national T2DM programme that meets National Institute for Health and Care Excellence criteria and formed the basis for Let's Prevent. An iterative cycle of initial development, piloting, collecting and collating qualitative and quantitative data, and reflection and modification, was used to inform and refine lifestyle intervention until it was fit for evaluation in a definitive randomized controlled trial (RCT). The programme encouraged IGR self-management using simple, non-technical language and visual aids. Results Qualitative and quantitative data suggested that intervention resulted in beneficial short-term behaviour change such as healthier eating patterns, improved health beliefs and greater participant motivation and empowerment. We also demonstrated that recruitment strategy and data collection methods were feasible for RCT implementation. Conclusions Let's Prevent was developed following successful application of MRC framework criteria and the subsequent RCT will determine whether it is feasible, reliable and transferable from research into a real-world NHS primary healthcare setting. Trial Registration ISRCTN80605705. PMID:26311822

  13. MRC5 and QU-DB bystander cells can produce bystander factors and induce radiation bystander effect.

    PubMed

    Toossi, Mohammad Taghi Bahreyni; Mohebbi, Shokoufeh; Samani, Roghayeh Kamran; Soleymanifard, Shokouhozaman

    2014-07-01

    Radiation damages initiated by radiation-induced bystander effect (RIBE) are not limited to the first or immediate neighbors of the irradiated cells, but the effects have been observed in the cells far from the irradiation site. It has been postulated that bystander cells, by producing bystander factors, are actively involved in the propagation of bystander effect in the regions beyond the initial irradiated site. Current study was planned to test the hypothesis. MRC5 and QU-DB cell lines were irradiated, and successive medium transfer technique was performed to induce bystander effects in two bystander cell groups. Conditioned medium extracted from the target cells was transferred to the bystander cells (first bystander cells). After one hour, conditioned medium was substituted by fresh medium. Two hours later, the fresh medium was transferred to a second group of non-irradiated cells (second bystander cells). Micronucleated cells (MC) were counted to quantify damages induced in the first and second bystander cell groups. Radiation effect was observed in the second bystander cells as well as in the first ones. Statistical analyses revealed that the number of MC in second bystander subgroups was significantly more than the corresponding value observed in control groups, but in most cases it was equal to the number of MC observed in the first bystander cells. MRC5 and QU-DB bystander cells can produce and release bystander signals in the culture medium and affect non-irradiated cells. Therefore, they may contribute to the RIBE propagation.

  14. MRC5 and QU-DB bystander cells can produce bystander factors and induce radiation bystander effect

    PubMed Central

    Toossi, Mohammad Taghi Bahreyni; Mohebbi, Shokoufeh; Samani, Roghayeh Kamran; Soleymanifard, Shokouhozaman

    2014-01-01

    Radiation damages initiated by radiation-induced bystander effect (RIBE) are not limited to the first or immediate neighbors of the irradiated cells, but the effects have been observed in the cells far from the irradiation site. It has been postulated that bystander cells, by producing bystander factors, are actively involved in the propagation of bystander effect in the regions beyond the initial irradiated site. Current study was planned to test the hypothesis. MRC5 and QU-DB cell lines were irradiated, and successive medium transfer technique was performed to induce bystander effects in two bystander cell groups. Conditioned medium extracted from the target cells was transferred to the bystander cells (first bystander cells). After one hour, conditioned medium was substituted by fresh medium. Two hours later, the fresh medium was transferred to a second group of non-irradiated cells (second bystander cells). Micronucleated cells (MC) were counted to quantify damages induced in the first and second bystander cell groups. Radiation effect was observed in the second bystander cells as well as in the first ones. Statistical analyses revealed that the number of MC in second bystander subgroups was significantly more than the corresponding value observed in control groups, but in most cases it was equal to the number of MC observed in the first bystander cells. MRC5 and QU-DB bystander cells can produce and release bystander signals in the culture medium and affect non-irradiated cells. Therefore, they may contribute to the RIBE propagation. PMID:25190998

  15. SER Performance of Enhanced Spatial Multiplexing Codes with ZF/MRC Receiver in Time-Varying Rayleigh Fading Channels

    PubMed Central

    Lee, In-Ho

    2014-01-01

    We propose enhanced spatial multiplexing codes (E-SMCs) to enable various encoding rates. The symbol error rate (SER) performance of the E-SMC is investigated when zero-forcing (ZF) and maximal-ratio combining (MRC) techniques are used at a receiver. The proposed E-SMC allows a transmitted symbol to be repeated over time to achieve further diversity gain at the cost of the encoding rate. With the spatial correlation between transmit antennas, SER equations for M-ary QAM and PSK constellations are derived by using a moment generating function (MGF) approximation of a signal-to-noise ratio (SNR), based on the assumption of independent zero-forced SNRs. Analytic and simulated results are compared for time-varying and spatially correlated Rayleigh fading channels that are modelled as first-order Markovian channels. Furthermore, we can find an optimal block length for the E-SMC that meets a required SER. PMID:25114969

  16. Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination

    PubMed Central

    Prado, Félix

    2014-01-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. PMID:24615940

  17. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

    PubMed Central

    Wei, Chunyan; Mei, Jie; Tang, Lingli; Liu, Yukai; Li, Dajin; Li, Mingqing; Zhu, Xiaoyong

    2016-01-01

    Foxp3+ regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of Treg cells, mainly IL-10+ Treg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated Treg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of Treg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for Treg differentiation in the ectopic lesion, especially that for CD4high Treg. Therefore, MRC2-silenced ESCs-educated Treg manifested a stronger suppressive function in vitro. Consistently, the percentage of Treg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of Treg and is involved in the development of endometriosis. Thus

  18. Discovery of an Obscured Broad-Line Region in the High-Redshift Radio Galaxy MRC 2025-218.

    PubMed

    Larkin; McLean; Graham; Becklin; Figer; Gilbert; Levenson; Teplitz; Wilcox; Glassman

    2000-04-10

    This Letter presents infrared spectra taken with the newly commissioned near-infrared spectrometer (NIRSPEC) on the Keck II telescope of the high-redshift radio galaxy MRC 2025-218 (z=2.63). These observations represent the deepest infrared spectra of a radio galaxy to date and have allowed for the detection of Hbeta, [O iii] lambdalambda4959, 5007, [O i] lambda6300, Halpha, [N ii] lambdalambda6548, 6583, and [S ii] lambdalambda6716, 6713. The Halpha emission is very broad (FWHM=9300 km s-1) and luminous (2.6x1044 ergs s-1), and it is very comparable to the line widths and strengths of radio-loud quasars at the same redshift. This strongly supports active galactic nucleus unification models linking radio galaxies and quasars, although we discuss some of the outstanding differences. The line [O iii] lambda5007 is extremely strong and has extended emission with large relative velocities toward the nucleus. We also derive that if the extended emission is due to star formation, each knot has a star formation rate comparable to a Lyman-break galaxy at the same redshift.

  19. Halomethane-induced cytotoxicity and cell proliferation in human lung MRC-5 fibroblasts and NL20-TA epithelial cells.

    PubMed

    Nájera-Martínez, Minerva; García-Latorre, Ethel A; Reyes-Maldonado, Elba; Domínguez-López, M Lilia; Vega-López, Armando

    2012-09-01

    Halomethanes (HMs) can be formed during the chlorination process to obtain drinking water. In liver cells, HMs had been shown to be mutagenic and carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required. Although inhalation is the most common pathway of exposure, reports on the toxic effects induced by HMs in human lung are contradictory. The aim of this study was therefore to evaluate in vitro cytotoxicity and cell proliferation induced by CH(2)Cl(2), CHCl(3) and BrCHCl(2) in human lung NL20-TA epithelial cells and MRC-5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High concentrations of these HMs induced cytotoxicity, particularly in cells treated with BrCHCl(2). Low concentrations of BrCHCl(2) stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl(2) exhibited low levels of CYP 2E1 activity suggesting that released bromine is able to alter this activity by affecting the active site or auto regulating the activity itself. GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating that potential lung damage is due to formation of pro-carcinogens such as formaldehyde.

  20. Dosimetry comparison and characterisation of an Al K ultrasoft x-ray beam from an MRC cold-cathode source.

    PubMed

    Hoshi, M; Goodhead, D T; Brenner, D J; Bance, D A; Chmielewski, J J; Paciotti, M A; Bradbury, J N

    1985-10-01

    Ultrasoft x-rays of 0.3-5 keV have provided a unique tool for the investigation of intracellular mechanisms of radiation action in biological organisms, including mammalian cells. However, their use presents unique practical problems in dosimetry and experimental design. Detailed interpretation of the biological results requires reliable dosimetry and well characterised monoenergetic beams. This paper presents a comparison between two fundamentally different dosimetric techniques, namely the ionisation current in an extrapolation chamber and photon counts in a proportional counter. Agreement within 7% was obtained when these two methods were applied to an Al K x-ray beam (1.5 keV) from an MRC cold-cathode transmission target discharge tube as previously used in many biological experiments. Photographic film was calibrated as a relative dosimetric technique and used for investigation of the intensity uniformity of the radiation field. These techniques provide a comprehensive characterisation of the beam in the position of the biological cells, including photon flux (or absorbed dose rate), spectral purity (showing much less than 1% bremsstrahlung relative to characteristic Al x-rays) and uniformity over the irradiation area (within about 5% for mammalian cell irradiations).

  1. Early experience with "antigenoid" vaccine Ac NFU1(S-) MRC towards prevention or modification of herpes genitalis.

    PubMed

    Skinner, G R; Woodman, C; Hartley, C; Buchan, A; Fuller, A; Wiblin, C; Wilkins, G; Melling, J

    1982-01-01

    The preparation and early clinical experience with "antigenoid" vaccine Ac NFU1(S-) MRC is described. A neutralising antibody response against both type 1 and type 2 herpes simplex virus was stimulated in 19 of 21 and 25 of 60 patients who received the high and low dosage of vaccine, respectively: immunoprecipitating antibody against type-common virus antigen "band II", a virus antigen of major importance in neutralization of herpes simplex virus, was detected in 12 of 19 and 2 of consorts who received the high and low dosage vaccine, respectively. To date, after a mean follow-up period of one year, none of the 42 consorts have contracted herpes genitalis: following a mean follow-up period of 6 months, only 1 patient vaccinated after the initial clinical episode has reported a recurrence of herpetic disease. These results compare favourably with the rates of consort transmission and first year recurrences in unvaccinated subjects. Seventeen of 24 patients with recurrent herpetic disease reported an "improvement" in terms of modification of the frequency, severity or extent of herpetic lesions. There were no important side-effects from vaccination: most patients experienced a degree of minor local reaction at the vaccination site for 24-72 hours and 3 patients reported a mild transient "flu-like" syndrome which disappeared within 48 hours of vaccination. It is intended to subject these data to the scrutiny of a placebo-controlled trial with an objective system of clinical assessment.

  2. The preparation, efficacy and safety of 'antigenoid' vaccine NFU1 (S-L+) MRC toward prevention of herpes simplex virus infections in human subjects.

    PubMed

    Skinner, G R; Buchan, A; Hartley, C E; Turner, S P; Williams, D R

    1980-01-01

    Vaccine NFU1 (S-L+) MRC was prepared by high multiplicity infection of serum-deprived human embryonic lung (MRC 5) cells with type 1 Herpes simplex virus. The preparative process removed inoculum virus particles and virus DNA while virus particle and DNA synthesis was inhibited by the presence of lithium chloride in the cell culture medium. The vaccine stimulated neutralising antibody in vaccinated mice and provided long-term protection against intra-vaginal challenge with type 2 herpes virus. The safety of the vaccine was confirmed by inoculation into newborn mice and cell lines of human, mammalian, and rodent origin. There was no evidence of cell transformation in vitro or of oncogenicity or teratogenicity in rodent species. It is intended to investigate the efficiency of this vaccine in human subjects.

  3. Extracellular Caspase-8 Dependent Apoptosis on HeLa Cancer Cells and MRC-5 Normal Cells by ICD-85 (Venom Derived Peptides)

    PubMed Central

    Zare-Mirakabadi, Abbas; Sarzaeem, Ali

    2012-01-01

    Background Our previous studies revealed an inhibitory effect of ICD-85 (venom derived peptides) on MDA-MB231 and HL-60 cell lines, through induction of apoptosis. The purpose of this study was to investigate apoptosis-induced mechanism on HeLa and MRC-5 cells by ICD-85 through activation of caspase-8. Methods Cell viability, cytosolic enzyme Lactate Dehydrogenase (LDH) and cell morphology were assessed under unexposed and ICD-85 exposed conditions.Caspase-8 activity was assayed by caspase-8 colorimetric assay Kit. Results The results show that Inhibitory Concentration 50% (IC50) value of ICD-85 for HeLa cells at 24 h was estimated and found to be 25.32±2.15 µg/mL. Furthermore, treatment of HeLa cells with ICD-85 at concentrations of 1.6×10 and 2.6×10 µg/mL did not significantly increase LDH release. Morphological changes in HeLa cells on treatment with ICD-85 compared with untreated HeLa cells consistent with an apoptotic mechanism of cell death, such as cell shrinkage which finally results in the generation of apoptotic bodies. However, when MRC-5 cells were exposed to ICD-85, no significant changes in cell morphology and LDH were observed at concentrations below 2.6×10µg/ml. Also, the apoptosis-induction mechanism by ICD-85 on HeLa cells was found through activation of caspase-8 and the activity of caspase-8 in HeLa cells was 1.5 folds more than its activity on MRC-5 cells. Conclusion Therefore, the apoptosis-induced mechanisms by ICD-85 are through activation of caspase-8 and concerning the least cytotoxic effect on MRC-5 cells, ICD-85 may be used as anticancer compound to inhibit growth of cancer cells. PMID:25352970

  4. Dengue Type Four Viruses with E-Glu345Lys Adaptive Mutation from MRC-5 Cells Induce Low Viremia but Elicit Potent Neutralizing Antibodies in Rhesus Monkeys

    PubMed Central

    Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development. PMID:24959738

  5. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    PubMed

    Lin, Hsiao-Han; Lee, Hsiang-Chi; Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

  6. Mental health triage tools for medically cleared disaster survivors: an evaluation by MRC volunteers and public health workers.

    PubMed

    Brannen, Donald E; Barcus, Robert; McDonnell, Mark A; Price, Andrea; Alsept, Corey; Caudill, Kimberly

    2013-02-01

    Psychological assessment after disasters determines which survivors are acutely distressed or medically compromised and what kind of assistance is needed (whether practical or psychological). A mental health triage tool can help direct more people to the appropriate type of help. The purpose of this study was to determine the effectiveness of the Fast Mental Health Triage Tool (FMHT) and the Alsept-Price Mental Health Scale (APMHS) among public health workers and Medical Reserve Corps (MRC) volunteers in conducting mental health triage. Both tools screen for ability to follow simple commands, chronic medical conditions, mental health conditions and services, occult injuries, and traumatic events in the past year. Both were designed for use in disasters where mental health resources are scarce and survivors are already medically triaged. Volunteers (n = 204) and workers (n = 66) were randomized into 3 groups, with 79 participating. Fifty-nine raters completed 20 each of 1180 mental health clinical vignettes of disaster survivors. The survey presenting the vignettes was highly reliable at 0.771; the study model was parallel between baseline and treatment; and the interclass correlation among the raters was high at 0.852. Each rater triaged the same cases, but the rater was randomly assigned to use FMHT, APMHS, or no tool or scale. Between-subject effect for the tools used was significant (P = .039). The FMHT was significantly better than no tool in correct mental health triage, 67.3% to 51.5% (P = .028). The incorporation of a temporal component should be evaluated for potential inclusion in existing mental health triage systems.

  7. Integration of the NASA Land Information System as an Application Framework into the MRC Rapid Prototyping Capabilities Infrastructure

    NASA Astrophysics Data System (ADS)

    Anantharaj, V.; Peters-Lidard, C.; Houser, P.; Mostovoy, G.; Haupt, T.; Moorhead, R.; Kumar, S.

    2006-12-01

    The Mississippi Research Consortium (MRC) is implementing a computational Rapid Prototyping Capabilities (RPC) infrastructure, based on a systems engineering concept, advocated by the NASA Applied Sciences Program, in order to identify, evaluate, and integrate research results for applications. The NASA Land Information System (LIS) is a "functional Land Data Assimilation System (LDAS)" that incorporates a suite of land models in an interoperable computational framework. LIS currently is comprised of a LIS core, a number of community land models, data servers, and visualization systems - integrated in a high-performance computing environment. LIS uses model independent software frameworks, such as the Earth Systems Modeling Framework (ESMF) and Assistance for Land Modeling Activities (ALMA), in order to enable interactions with other earth system model and decision support systems (DSS). The LIS user interface (UI) can be used to query, browse, and download LIS derived products. Besides, any clients that support OpenDAP can be used to access the model results. NASA LIS has been identified to be integrated into the RPC infrastructure as a cross-cutting applications framework (AF). The land models in LIS incorporate surface and atmospheric parameters of temperature, snow/water, vegetation, albedo, soil conditions, topography, and radiation. Many of these parameters are available from in- situ observations, numerical model analysis, and from NASA, NOAA, and other remote sensing satellite platforms at various spatial and temporal resolutions. Since the land models in LIS require normal spin-up times of 5 years or more for most experiments, the necessary multi-year retrospective initialization and forcing fields (estimated to grow to 10 TB in size) are also stored and managed in the RPC infrastructure. The computational resources, available to LIS via the RPC infrastructure, support e-Science experiments involving the global modeling of land-atmosphere studies at 1km

  8. Extreme Gas Kinematics in the z=2.2 Powerful Radio Galaxy MRC 1138-262: Evidence for Efficient Active Galactic Nucleus Feedback in the Early Universe?

    NASA Astrophysics Data System (ADS)

    Nesvadba, N. P. H.; Lehnert, M. D.; Eisenhauer, F.; Gilbert, A.; Tecza, M.; Abuter, R.

    2006-10-01

    To explain the properties of the most massive low-redshift galaxies and the shape of their mass function, recent models of galaxy evolution include strong AGN feedback to complement starburst-driven feedback in massive galaxies. Using the near-infrared integral-field spectrograph SPIFFI on the VLT, we searched for direct evidence for such feedback in the optical emission line gas around the z=2.16 powerful radio galaxy MRC 1138-262, likely a massive galaxy in formation. The kiloparsec-scale kinematics, with FWHMs and relative velocities <~2400 km s-1 and nearly spherical spatial distribution, do not resemble large-scale gravitational motion or starburst-driven winds. Order-of-magnitude timescale and energy arguments favor the AGN as the only plausible candidate to accelerate the gas, with a total energy injection of a few ×1060 ergs or more, necessary to power the outflow, and relatively efficient coupling between radio jet and ISM. Observed outflow properties are in gross agreement with the models and suggest that AGN winds might have a cosmological significance that is similar to, or perhaps larger than, starburst-driven winds if MRC 1138-262 is indeed archetypal. Moreover, the outflow has the potential to remove significant gas fractions (<~50%) from a >L* galaxy within a few tens to 100 Myr, fast enough to preserve the observed [α/Fe] overabundance in massive galaxies at low redshift. Using simple arguments, it appears that feedback like that observed in MRC 1138-262 may have sufficient energy to inhibit material from infalling into the dark matter halo and thus regulate galaxy growth as required in some recent models of hierarchical structure formation. Based on observations collected at the European Southern Observatory, Very Large Telescope Array, Cerro Paranal; program Nos. 70.B-0545, 70.A-0229, and 076.A-0684.

  9. Ultrasonographic diaphragmatic excursion is inaccurate and not better than the MRC score for predicting weaning-failure in mechanically ventilated patients.

    PubMed

    Carrie, Cédric; Gisbert-Mora, Chloé; Bonnardel, Eline; Gauche, Bernard; Biais, Matthieu; Vargas, Frédéric; Hilbert, Gilles

    2017-02-01

    To assess the ability of diaphragmatic ultrasound (US) to predict weaning failure in mechanically ventilated patients undergoing a first spontaneous breathing trial (SBT). During a 4-month period, 67 consecutive patients eligible for a first SBT underwent US measurements of maximal diaphragmatic excursion (MDE) by a right anterior subcostal approach. Weaning failure was defined as either the failure of SBT or the need for resumption of ventilatory support for acute respiratory failure or death within 48h following successful extubation. The accuracy of diaphragmatic ultrasound and the Medical Research Council (MRC) score when predicting weaning failure was assessed via a receiver operating curve analysis. The feasibility rate for the ultrasound measurements was 63%. Mean values of MDE were significantly higher in patients who succeeded at their first weaning attempt (4.1±2.1 versus 3±1.8cm, P=0.04). Using a threshold of MDE≤2.7cm, the sensitivity and specificity of diaphragmatic ultrasound in predicting weaning failure were 59% [39-77%] and 71% [57-82%] with an AUC at 0.65 [0.51-0.78]. There was no significant difference between MDE values and MRC scores for predicting weaning failure (P=0.73). A decrease in MDE values may be associated with an unfavourable weaning outcome. Diaphragmatic excursion measured by ultrasound is however unable by itself to predict weaning failure at the bedside of patients undergoing a first spontaneous breathing trial and does not provide any additional value compared to the MRC score. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Extreme Gas Kinematics in the z=2.2 Powerful Radio Galaxy MRC1138-262: Evidence for Efficient AGN Feedback in the Early Universe?

    SciTech Connect

    Nesvadba, N H; Lehnert, M D; Eisenhauer, F; Gilbert, A M; Tecza, M; Abuter, R

    2007-06-26

    To explain the properties of the most massive low-redshift galaxies and the shape of their mass function, recent models of galaxy evolution include strong AGN feedback to complement starburst-driven feedback in massive galaxies. Using the near-infrared integral-field spectrograph SPIFFI on the VLT, we searched for direct evidence for such a feedback in the optical emission line gas around the z = 2.16 powerful radio galaxy MRC1138-262, likely a massive galaxy in formation. The kpc-scale kinematics, with FWHMs and relative velocities {approx}< 2400 km s{sup -1} and nearly spherical spatial distribution, do not resemble large-scale gravitational motion or starburst-driven winds. Order-of-magnitude timescale and energy arguments favor the AGN as the only plausible candidate to accelerate the gas, with a total energy injection of {approx} few x 10{sup 60} ergs or more, necessary to power the outflow, and relatively efficient coupling between radio jet and ISM. Observed outflow properties are in gross agreement with the models, and suggest that AGN winds might have a similar, or perhaps larger, cosmological significance than starburst-driven winds, if MRC1138-262 is indeed archetypal. Moreover, the outflow has the potential to remove significant gas fractions ({approx}< 50%) from a > L* galaxy within a few 10 to 100 Myrs, fast enough to preserve the observed [{alpha}/Fe] overabundance in massive galaxies at low redshift. Using simple arguments, it appears that feedback like that observed in MRC1138-262 may have sufficient energy to inhibit material from infalling into the dark matter halo and thus regulate galaxy growth as required in some recent models of hierarchical structure formation.

  11. Average bit error rate performance analysis of subcarrier intensity modulated MRC and EGC FSO systems with dual branches over M distribution turbulence channels

    NASA Astrophysics Data System (ADS)

    Wang, Ran-ran; Wang, Ping; Cao, Tian; Guo, Li-xin; Yang, Yintang

    2015-07-01

    Based on the space diversity reception, the binary phase-shift keying (BPSK) modulated free space optical (FSO) system over Málaga (M) fading channels is investigated in detail. Under independently and identically distributed and independently and non-identically distributed dual branches, the analytical average bit error rate (ABER) expressions in terms of H-Fox function for maximal ratio combining (MRC) and equal gain combining (EGC) diversity techniques are derived, respectively, by transforming the modified Bessel function of the second kind into the integral form of Meijer G-function. Monte Carlo (MC) simulation is also provided to verify the accuracy of the presented models.

  12. Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

    PubMed

    Woodman, C B; Buchan, A; Fuller, A; Hartley, C; Skinner, G R; Stocker, D; Sugrue, D; Clay, J C; Wilkins, G; Wiblin, C

    1983-10-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population.

  13. Immunogenicity and Protective Efficacy in a Rhesus Monkey Model of Vaccine Ac NFU1(S-) MRC Against Primary Type 2 Herpes Simplex Virus Infection

    PubMed Central

    Skinner, G. R. B.; Buchan, A.; Williams, D.; Marsden, J.; Hartley, C.; Wilbanks, G.; Turyk, M.; Namkoong, E. S.

    1982-01-01

    Adult and juvenile Rhesus monkeys were vaccinated with sub-unit formaldehyde-inactivated vaccine Ac NFU1(S-) MRC; no local or systemic side-effects followed vaccination. Vaccinated monkeys developed neutralizing and immunoprecipitating antibody to both type 1 and 2 herpes simplex virus. Antibody levels declined with time but were re-stimulated after virus challenge and to a lesser extent after attempted virus reactivation. There was evidence of protection against s.c. challenge with live type 2 herpes simplex virus. PMID:6295430

  14. Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

    PubMed Central

    Woodman, C B; Buchan, A; Fuller, A; Hartley, C; Skinner, G R; Stocker, D; Sugrue, D; Clay, J C; Wilkins, G; Wiblin, C

    1983-01-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population. PMID:6311322

  15. Low concentration of PDGF-AB shows synergism with IFN-α in induction of IFN-β and -γ in MRC5 fibroblasts.

    PubMed

    Šantak, G; Šantak, M; Forčić, D

    2013-11-01

    Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. Also it has been reported as a strong suppressor of interferon (IFN) expression. IFN-α has opposite effect on fibroblast function and IFN induction. Here is our early report on the effect of low concentration of PDGF-AB alone or in combination with IFN-α on IFN mRNA production in MRC5 fibroblasts. MRC5 cells incubated with IFN-α or PDGF-AB, alone or in combination, produced significant induction of IFN-α, -β and -γ mRNA in comparison with untreated cells. The induction was dose-dependent, with higher effect in cells treated with lower concentrations of PDGF-AB. Also, low concentration of PDGF-AB showed synergism with IFN-α in IFN-β and -γ induction. Results presented here open new possibilities in multi-cytokine therapy and expand previous results on PDGF activity.

  16. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  17. Inactivation of p16INK4a, with retention of pRB and p53/p21cip1 function, in human MRC5 fibroblasts that overcome a telomere-independent crisis during immortalization.

    PubMed

    Taylor, Lisa M; James, Alexander; Schuller, Christine E; Brce, Jesena; Lock, Richard B; Mackenzie, Karen L

    2004-10-15

    Recent investigations, including our own, have shown that specific strains of fibroblasts expressing telomerase reverse transcriptase (hTERT) have an extended lifespan, but are not immortal. We previously demonstrated that hTERT-transduced MRC5 fetal lung fibroblasts (MRC5hTERTs) bypassed senescence but eventually succumbed to a second mortality barrier (crisis). In the present study, 67 MRC5hTERT clones were established by limiting dilution of a mass culture. Whereas 39/67 clones had an extended lifespan, all 39 extended lifespan clones underwent crisis. 11 of 39 clones escaped crisis and were immortalized. There was no apparent relationship between the fate of clones at crisis and the level of telomerase activity. Telomeres were hyperextended in the majority of the clones analyzed. There was no difference in telomere length of pre-crisis compared with post-crisis and immortal clones, indicating that hyperextended telomeres were conducive for immortalization and confirming that crisis was independent of telomere length. Immortalization of MRC5hTERT cells was associated with repression of the cyclin-dependent kinase inhibitor p16INK4a and up-regulation of pRB. However, the regulation of pRB phosphorylation and the response of the p53/p21cip1/waf1 pathway were normal in immortal cells subject to genotoxic stress. Overexpression of oncogenic ras failed to de-repress p16INK4a in immortal cells. Furthermore, expression of ras enforced senescent-like growth arrest in p16INK4a-positive, but not p16INK4a-negative MRC5hTERT cells. Immortal cells expressing ras formed small, infrequent colonies in soft agarose, but were non-tumorigenic. Overall, these results implicate the inactivation of p16INK4a as a critical event for overcoming telomere-independent crisis, immortalizing MRC5 fibroblasts and overcoming ras-induced premature senescence.

  18. Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle.

    PubMed

    Fasquelle, Corinne; Sartelet, Arnaud; Li, Wanbo; Dive, Marc; Tamma, Nico; Michaux, Charles; Druet, Tom; Huijbers, Ivo J; Isacke, Clare M; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2009-09-01

    We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed.

  19. MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes

    PubMed Central

    Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

    2008-01-01

    Background The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. Methods The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. Discussion This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. Trial registration The ORACLE Trial and Children Study is registered in the

  20. MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes.

    PubMed

    Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

    2008-04-24

    The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660.

  1. Assessing the survival of MRC5 and a549 cell lines upon exposure to pyruvic Acid, sodium citrate and sodium bicarbonate - biomed 2013.

    PubMed

    Farah, Ibrahim O; Lewis, Veshell L; Ayensu, Wellington K; Cameron, Joseph A

    2013-01-01

    Lung cancer is among the most prevalent and deadly cancers in United States. In general, cancer cells are known to exhibit higher rates of glycolysis in comparison to normal cells. In attempting to exploit this unique cancer-dependent ATP generation phenomenon, it was our hypothesis that upon exposure to organic inhibitors of glycolysis, cancer cells would not survive normally and that their growth and viability would be vastly decreased; essential glycolytic ATP production will be exhausted to the point of collapsing energy utilization. Furthermore, we hypothesize that no negative effect would be seen with exposures to organic inhibitors for normal lung cells. The human lung fibroblast MRC-5 and the human A549 alveolar epithelial cell lines were used as in vitro models of normal lung and lung cancers respectively. Using standard methods, both cell lines were maintained and exposed to pyruvic acid, sodium citrate and sodium bicarbonate reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging for parallel morphological displays of any changes in the course of their vitality and metabolic activities. Our results indicate that exposure of both cell lines to these organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Pyruvic acid, sodium citrate and sodium bicarbonate showed statistically significant (p<0.05) differential negative effects on the A549 cell line in comparison to its unexposed control as well as to their effects on the MRC-5 cell line, presenting a potential promise for their use as cancer biotherapeutics.

  2. Protective Effect of Crocodile Hemoglobin and Whole Blood Against Hydrogen Peroxide-Induced Oxidative Damage in Human Lung Fibroblasts (MRC-5) and Inflammation in Mice.

    PubMed

    Phosri, Santi; Jangpromma, Nisachon; Patramanon, Rina; Kongyingyoes, Bunkerd; Mahakunakorn, Pramote; Klaynongsruang, Sompong

    2017-02-01

    A putative protective effect of cHb and cWb against H2O2-induced oxidative damage was evaluated in detail using MRC-5 cells. In addition, the carrageenan (Carr)-induced mouse paw edema model and the cotton pellet-induced granuloma model were employed to examine the in vivo anti-inflammatory activity of cHb and cWb in mice. It was demonstrated that both cHb and cWb treatments significantly increased cell viability and inhibited morphology alterations in MRC-5 cells exposed to H2O2. Orally administered cHb and cWb significantly reduced Carr-induced paw edema volume and cotton pellet-induced granuloma formation. Moreover, cHb and cWb decreased the expression levels of important pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), while only cWb was found to increase the expression of the anti-inflammatory cytokine IL-10 significantly. Finally, the activity of antioxidant enzymes (SOD, CAT, and GPx) in the liver improved after cHb and cWb treatment under acute and chronic inflammation. Taken collectively, the results of this study suggest that both cHb and cWb protect against hydrogen peroxide-induced damage in fibroblast cells. Moreover, cHb and cWb were found to exhibit anti-inflammatory activity in both the acute and chronic stages of inflammation and appear to enhance antioxidant enzyme activity and decrease lipid peroxidation in the livers of mice. Therefore, this study indicates that cHb and cWb have great potential to be used in the development of dietary supplements for the prevention of oxidative stress related to inflammatory disorders.

  3. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

    PubMed Central

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d’Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components. PMID:26762783

  4. Resistance Prediction in AML: Analysis of 4,601 Patients from MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center

    PubMed Central

    Walter, Roland B.; Othus, Megan; Burnett, Alan K.; Löwenberg, Bob; Kantarjian, Hagop M.; Ossenkoppele, Gert J.; Hills, Robert K.; Ravandi, Farhad; Pabst, Thomas; Evans, Anna; Pierce, Sherry R.; Vekemans, Marie-Christiane; Appelbaum, Frederick R.; Estey, Elihu H.

    2014-01-01

    Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver operator characteristic curves (AUC) to quantify our ability to predict therapeutic resistance in individual patients where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4,601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in MRC/NCRI, HOVON, SWOG, and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk, and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (“primary refractoriness”). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival (RFS), was even more difficult. Our ability to forecast resistance based on routinely available pre-treatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and post-treatment data to optimize resistance prediction in AML. PMID:25113226

  5. The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

    PubMed Central

    Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

    2016-01-01

    Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

  6. The MRC National Survey of Health and Development reaches age 70: maintaining participation at older ages in a birth cohort study.

    PubMed

    Kuh, Diana; Wong, Andrew; Shah, Imran; Moore, Adam; Popham, Maria; Curran, Philip; Davis, Daniel; Sharma, Nikhil; Richards, Marcus; Stafford, Mai; Hardy, Rebecca; Cooper, Rachel

    2016-11-01

    A life course approach to ageing relies on maintaining participation rates in national birth cohorts and other long-term longitudinal studies. This reduces the risk of selective attrition biasing associations between lifetime risk factors and health outcomes in later life and ensures the studies remain as representative as possible of the original population. We report the participation patterns for a postal questionnaire and home visit at 68-69 years of study members in the MRC National Survey of Health and Development, the oldest and longest-running British birth cohort study. We investigated how participation varied by lifetime and recent contact, health status, previous clinical feedback and study engagement, taking account of prior socioeconomic and cognitive characteristics. Overall participation and home visit participation remained high (94 and 80%, respectively) and there were no gender differences. Participation was higher in those with higher levels of prior contact and lower in those with the poorest health status. Having previously received clinical feedback on actionable blood results was associated with reduced home visit participation but other forms of clinical feedback were not associated with subsequent participation. Activities that fostered study engagement were associated with increased home visit participation. These findings inform strategies to maintain participation in life course studies.

  7. Prospective associations of psychosocial adversity in childhood with risk factors for cardiovascular disease in adulthood: the MRC National Survey of Health and Development.

    PubMed

    Anderson, Emma L; Caleyachetty, Rishi; Stafford, Mai; Kuh, Diana; Hardy, Rebecca; Lawlor, Debbie A; Fraser, Abigail; Howe, Laura D

    2017-09-07

    Studies assessing associations of childhood psychosocial adversity (e.g. sexual abuse, physical neglect, parental death), as opposed to socioeconomic adversity, with cardiovascular disease (CVD) risk factors in adulthood are scarce. We aimed to assess associations of various forms of psychosocial adversity and cumulative adversity in childhood, with multiple CVD risk factors in mid-life. Participants were from the MRC National Survey of Health and Development. Childhood psychosocial risk factors were reported prospectively by parents from 1950-1957, and retrospectively by participants at mean age 43 years in 1989. CVD risk factors were assessed at mean age 60-64 years in 2006-2011. Associations of a summary score of total psychosocial adversity and CVD risk in adulthood were assessed. There was no consistent evidence that cumulative psychosocial adversity, nor any specific form of psychosocial adversity in childhood, was associated with CVD risk factors in late adulthood. There was some evidence that parental death in the first 15 years was associated with higher SBP (Beta: 0.23, 95% confidence interval: 0.06 to 0.40, P=0.01) and DBP (Beta: 0.15, 95% confidence interval: -0.01 to 0.32, P=0.07). We found no evidence that exposure to greater psychosocial adversity, or specific forms of psychosocial adversity during childhood is associated with adult CVD risk factors. Further large population studies are needed to clarify whether parental death is associated with higher systolic and diastolic blood pressure.

  8. Identification of a highly conserved arginine-rich gene (MRC) from human chromosomal band 3p21.1 that contains point mutations in many renal cell carcinomas

    SciTech Connect

    Shridhar, V.; Golembieski, W.; Bostick, L.

    1994-09-01

    Sequences from the short arm of human chromosome 3, band 3p21, are frequently deleted during the development of a variety of different solid tumors, including lung cancer and renal cell carcinoma. The gene for aminoacylase-1 (ACY1), localized in 3p21.1, was previously shown to have lower levels of expression in many small call lung carcinoma cell lines. We focused our efforts on the isolation of genes from the region surrounding ACY1 in an attempt to identify candidate tumor suppressor genes. We report here the isolation of an arginine-rich gene encoded by sequences 600 Kb distal to ACY1. Although this gene is not deleted in any tested lung cancers or renal cell carcinomas, we have detected nucleotide substitutions within a 90 bp region of this gene that encodes multiple arginines in many sporadic renal cell carcinomas. The region, rich in arginines, was found to be remarkably conserved, showing 100% nucleotide sequence identity between humans and chickens. We have therefore identified a new arginine-rich gene in 3p21.1, a region that is frequently deleted in both lung and renal cell carcinomas, containing highly conserved sequences with subtle mutations in many sporadic renal cell carcinomas. We are calling this gene MRC for Mutated in Renal cell Carcinoma. The mutations observed in this gene do not seem to be due to a general replication error phenotype, as no microsatellite instabilities were seen in various di, tri, or tetranucleotides tested.

  9. The influence of non-DNA-targeted effects on carbon ion-induced low-dose hyper-radiosensitivity in MRC-5 cells.

    PubMed

    Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

    2016-03-01

    Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation-induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion-induced LDHRS. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  10. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field.

    PubMed

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d'Angelo, Raffaele; Zeni, Olga

    2016-01-14

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components.

  11. Rmi1 functions in S phase-mediated cohesion establishment via a pathway involving the Ctf18-RFC complex and Mrc1.

    PubMed

    Lai, Mong Sing; Seki, Masayuki; Tada, Shusuke; Enomoto, Takemi

    2012-10-26

    Saccharomyces cerevisiae RecQ helicase (Sgs1) combines with DNA topoisomerase III (Top3) and RecQ-mediated genome instability 1 (Rmi1) to form an evolutionarily conserved complex that is required for processing homologous recombination intermediates and restarting collapsed replication forks. It was previously reported that Rmi1 contributes to sister chromatid cohesion; however, the underlying molecular mechanism has been unclear. In the present study, Rmi1 was found to be enriched at the region close to an early-firing replication origin when replication forks were arrested near their origins in the presence of hydroxyurea. Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. On the other hand, Rmi1 seemed to function in a pathway involving the Ctf18-RFC complex and Mrc1, which were previously predicted to regulate leading-strand DNA replication.

  12. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

    NASA Astrophysics Data System (ADS)

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; D’Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components.

  13. Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination: homologous recombination tolerates replicative stress by Mrc1-regulated replication and repair activities operating at S and G2 in distinct subnuclear compartments.

    PubMed

    Prado, Félix

    2014-05-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

  14. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.

    PubMed

    Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

    2011-06-18

    In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3-29·2] in the control group vs 17·0 months [9·4-30·1] in the cetuximab group; HR 1·04, 95% CI 0·87-1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0-12·5] in the control group vs 8·6 months [5·1-13·8] in the cetuximab group; HR 0·96, 0·82-1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with

  15. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

    PubMed Central

    Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

    2011-01-01

    Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209

  16. The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast.

    PubMed

    LeClere, Andrea R; Yang, John K; Kirkpatrick, David T

    2013-01-01

    Double-stranded break (DSB) repair during meiotic recombination in yeast Saccharomyces cerevisiae leads to the formation of heteroduplex DNA, a hybrid DNA molecule composed of single strands from two homologous chromosomes. Differences in sequence between the strands within heteroduplex DNA generate mismatches or large unpaired loops that are substrates for repair. At least two pathways function to repair large loops that form within heteroduplex DNA: the RAD1-dependent large loop repair (LLR) pathway and another as yet uncharacterized RAD1-independent LLR pathway. Repair of large loops during meiotic recombination is especially important for the genomic stability of the repetitive DNA sequences known as minisatellites. Minisatellite DNA tracts are generally stable during mitotic cell divisions but frequently alter in length during meiosis. Using a yeast minisatellite system in which the human minisatellite associated with the HRAS1 proto-oncogene has been inserted into the recombination hotspot region upstream of HIS4 in S. cerevisiae, our lab previously showed that the RAD1-dependent LLR pathway controls minisatellite length expansions, but not contractions. Here we show that minisatellite length expansions are controlled by the products of the CSM3 and TOF1 genes, while contractions are controlled by MRC1. By examining meiotic segregation patterns in yeast strains heterozygous for the 26bp his4-lopd insert, we found that deleting CSM3 caused a loss of LLR activity similar to that seen in a RAD1 mutant. Double mutant analysis revealed that failure to repair loops is exacerbated upon deleting both RAD1 and CSM3 - specifically the type of repair that fills in loops, which would generate minisatellite length expansions. A model for minisatellite length alteration based on these results is presented.

  17. Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial

    PubMed Central

    Hale, Matthew D.; Nankivell, Matthew; Hutchins, Gordon G.; Stenning, Sally P.; Langley, Ruth E.; Mueller, Wolfram; West, Nicholas P.; Wright, Alexander I.; Treanor, Darren; Hewitt, Lindsay C.; Allum, William H.; Cunningham, David; Hayden, Jeremy D.; Grabsch, Heike I.

    2016-01-01

    Background Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. Patients and methods PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. Results PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT<40%, N=39, HR:1.25 (0.66-2.35); PoT>70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. Conclusions This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification. PMID:27769054

  18. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

    PubMed

    Rees, J K; Gray, R G; Wheatley, K

    1996-07-01

    Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more

  19. Impact of adherence to GOLD guidelines on 6-minute walk distance, MRC dyspnea scale score, lung function decline, quality of life, and quality-adjusted life years in a Shanghai suburb.

    PubMed

    Jiang, Y Q; Zhu, Y X; Chen, X L; Xu, X; Li, F; Fu, H J; Shen, C Y; Lu, Y Y; Zhuang, Q J; Xu, G; Cai, Y Y; Zhang, Y; Liu, S S; Zhu, M Y; Li, S H

    2015-08-03

    We performed a 1-year cluster-randomized field trial to assess the effect of standardized management of chronic obstructive pulmonary disease (COPD) on lung function and quality of life (QOL) measures in patients in China. We used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines and assessed indexes including pulmonary function, QOL, quality-adjusted life years (QALY), Medical Research Council (MRC) dyspnea scale, 6-min walk distance (6-MWD), number of emergency visits, and frequency of hospitalization. Of a total of 711 patients with chronic cough and asthma, 132 were diagnosed as having COPD and 102 participated in this study [intervention group (N = 47); control group (N = 55)]. We found that adherence to GOLD guidelines had a perceivable impact on 6-MWD, MRC dyspnea scale score, and QOL. The average QALY increased by 1.42/person/year in the intervention group, but declined by 0.95/person/year in the control group. We conclude that standardized management improves disease severity, QOL, and QALY in COPD patients when treatment protocols adhere to GOLD guidelines.

  20. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial.

    PubMed

    Adams, Richard A; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Madi, Ayman; Fisher, David; Kenny, Sarah L; Kay, Edward; Hodgkinson, Elizabeth; Pope, Malcolm; Rogers, Penny; Wasan, Harpreet; Falk, Stephen; Gollins, Simon; Hickish, Tamas; Bessell, Eric M; Propper, David; Kennedy, M John; Kaplan, Richard; Maughan, Timothy S

    2011-07-01

    When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1.162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15.8 months (IQR 9.4-26.1) in arm A and 14.4 months (8.0-24.7) in arm C (hazard ratio [HR] 1.084, 80% CI 1.008-1.165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19.6 months (13.0-28.1) in arm A and 18.0 months (12.1-29.3) in arm C (HR 1.087, 0.986-1.198). The upper limits of CIs for HRs in both analyses were greater than the predefined non

  1. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

    PubMed Central

    Adams, Richard A; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Madi, Ayman; Fisher, David; Kenny, Sarah L; Kay, Edward; Hodgkinson, Elizabeth; Pope, Malcolm; Rogers, Penny; Wasan, Harpreet; Falk, Stephen; Gollins, Simon; Hickish, Tamas; Bessell, Eric M; Propper, David; Kennedy, M John; Kaplan, Richard; Maughan, Timothy S

    2011-01-01

    Summary Background When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4–26·1) in arm A and 14·4 months (8·0–24·7) in arm C (hazard ratio [HR] 1·084, 80% CI 1·008–1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0–28·1) in arm A and 18·0 months (12·1–29·3) in arm C (HR 1·087, 0·986–1·198). The upper limits of CIs for HRs

  2. Novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus -1: an in vitro study on virally infected Vero and MRC-5 cell lines.

    PubMed

    Hafidh, Rand R; Abdulamir, Ahmed S; Abu Bakar, Fatimah; Sekawi, Zamberi; Jahansheri, Fatemeh; Jalilian, Farid Azizi

    2015-06-11

    New sources for discovering novel antiviral agents are desperately needed. The current antiviral products are both expensive and not very effective. The antiviral activity of methanol extract of mung bean sprouts (MBS), compared to Ribavarin and Acyclovir, on respiratory syncytial virus (RSV) and Herpes Simplex virus -1 (HSV-1) was investigated using cytotoxicity, virus yield reduction, virucidal activity, and prophylactic activity assays on Vero and MRC-5 cell lines. Moreover, the level of antiviral cytokines, IFNβ, TNFα, IL-1, and IL-6 was assessed in MBS-treated, virally infected, virally infected MBS-treated, and control groups of MRC-5 cells using ELISA. MBS extract showed reduction factors (RF) 2.2 × 10 and 0.5 × 10(2) for RSV and HSV-1, respectively. The 2 h incubation virucidal and prophylactic selectivity indices (SI) of MBS on RSV were 14.18 and 12.82 versus Ribavarin SI of 23.39 and 21.95, respectively, and on HSV-1, SI were 18.23 and 10.9 versus Acyclovir, 22.56 and 15.04, respectively. All SI values were >10 indicating that MBS has a good direct antiviral and prophylactic activities on both RSV and HSV-1. Moreover, interestingly, MBS extract induced vigorously IFNβ, TNFα, IL-1, and IL-6 cytokines in MRC-5 infected-treated group far more than other groups (P < 0.05) and induced TNFα and IL-6 in treated group more than infected group (P < 0.05). MBS extract has potent antiviral and to a lesser extent, prophylactic activities against both RSV and HSV-1, and in case of HSV-1, these activities were comparable to Acyclovir. Part of the underlying mechanism(s) of these activities is attributed to MBS potential to remarkably induce antiviral cytokines in human cells. Hence, we infer that MBS methanol extract could be used as such or as purified active component in protecting and treating RSV and HSV-1 infections. More studies are needed to pinpoint the exact active components responsible for the MBS antiviral activities.

  3. The "Methyl-CpG Binding Domain protein 2" plays a repressive role in relation to the promoter CpG content in the normal human cell line MRC5.

    PubMed

    Perriaud, Laury; Lachuer, Joel; Dante, Robert

    2014-01-01

    In cancer cells, methylation-dependent gene silencing is at least partly mediated by the "Methyl-CpG-Binding Domain protein 2" (MBD2 protein), via the recruitment of chromatin remodeling complexes. However this repressive role was poorly investigated in normal cells. To identify the genes repressed by MBD2 in these cells, we have determined the impact of MBD2 depletion on gene expression in human embryonic MRC5 fibroblasts, using RNA inference combined with microarray analysis. The up-regulation of some randomly selected genes was confirmed and a direct association between gene repression and MBD2 binding on methylated promoters associated to these genes was subsequently established. This control of gene expression appears to depend on the CpG content of promoters as MBD2 depletion was not sufficient to induce the expression of silent genes associated with High-CpG promoters, but it was required to achieve the methyl-dependent transcriptional locking of the genes associated with promoters exhibiting intermediate CpG content. Therefore, MBD2 seems to play a selective role in gene repression depending on the CpG content of the promoter regions.

  4. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial.

    PubMed

    Milligan, Donald W; Wheatley, Keith; Littlewood, Timothy; Craig, Jenny I O; Burnett, Alan K

    2006-06-15

    The optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia (relapsed, resistant/refractory, or adverse genetic disease) is uncertain. The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE). Patients were also randomly assigned to receive filgrastim (G-CSF) from day 0 until neutrophil count was greater than 0.5 x 10(9)/L (or for a maximum of 28 days) and all-trans retinoic acid (ATRA) for 90 days. Between 1998 and 2003, 405 patients were entered: 250 were randomly assigned between FLA and ADE; 356 to G-CSF versus no G-CSF; 362 to ATRA versus no ATRA. The complete remission rate was 61% with 4-year disease-free survival of 29%. There were no significant differences in the CR rate, deaths in CR, relapse rate, or DFS between ADE and FLA, although survival at 4 years was worse with FLA (16% versus 27%, P = .05). Neither the addition of ATRA nor G-CSF demonstrated any differences in the CR rate, relapse rate, DFS, or overall survival between the groups. In conclusion these findings indicate that FLA may be inferior to standard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA.

  5. Relationship of Self-Rated Health to Stroke Incidence and Mortality in Older Individuals with and without a History of Stroke: A Longitudinal Study of the MRC Cognitive Function and Ageing (CFAS) Population

    PubMed Central

    Mavaddat, Nahal; van der Linde, Rianne; Parker, Richard; Savva, George; Kinmonth, Ann Louise; Brayne, Carol; Mant, Jonathan

    2016-01-01

    Introduction Poor self-rated health (SRH) has been associated with increased risk of death and poor health outcomes even after adjusting for confounders. However its’ relationship with disease-specific mortality and morbidity has been less studied. SRH may also be particularly predictive of health outcomes in those with pre-existing conditions. We studied whether SRH predicts new stroke in older people who have never had a stroke, or a recurrence in those with a prior history of stroke. Methods MRC CFAS I is a multicentre cohort study of a population representative sample of people in their 65th year and older. A comprehensive interview at baseline included questions about presence of stroke, self-rated health and functional disability. Follow-up at 2 years included self-report of stroke and stroke death obtained from death certificates. Multiple logistical regression determined odds of stroke at 2 years adjusting for confounders including disability and health behaviours. Survival analysis was performed until June 2014 with follow-up for up to 13 years. Results 11,957 participants were included, of whom 11,181 (93.8%) had no history of stroke and 776 (6.2%) one or more previous strokes. Fewer with no history of stroke reported poor SRH than those with stroke (5 versus 21%). In those with no history of stroke, poor self-rated health predicted stroke incidence (OR 1.5 (1.1–1.9)), but not stroke mortality (OR 1.2 (0.8–1.9)) at 2 years nor for up to 13 years (OR 1.2(0.9–1.7)). In those with a history of stroke, self-rated health did not predict stroke incidence (OR 0.9(0.6–1.4)), stroke mortality (OR 1.1(0.5–2.5)), or survival (OR 1.1(0.6–2.1)). Conclusions Poor self-rated health predicts risk of stroke at 2 years but not stroke mortality among the older population without a previous history of stroke. SRH may be helpful in predicting who may be at risk of developing a stroke in the near future. PMID:26928666

  6. Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development

    PubMed Central

    Bann, D; Wills, A; Cooper, R; Hardy, R; Aihie Sayer, A; Adams, J; Kuh, D

    2014-01-01

    Objective: High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. Subjects: A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60–64 years. Methods: Associations of birth weight and standardised weight and height (0–2 (weight only), 2–4, 4–7, 7–11, 11–15, 15–20 years) gain velocities with outcome measures were examined. Results: Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60–64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. Conclusion: Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios. PMID:23779050

  7. Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells

    PubMed Central

    Invernizzi, F.; D'Amato, I.; Jensen, P.B.; Ravaglia, S.; Zeviani, M.; Tiranti, V.

    2012-01-01

    Given the complexity of the respiratory chain structure, assembly and regulation, the diagnostic workout for the identification of defects of oxidative phosphorylation (OXPHOS) is a major challenge. Spectrophotometric assays, that measure the activity of individual respiratory complexes in tissue and cell homogenates or isolated mitochondria, are highly specific, but their utilization is limited by the availability of sufficient biological material and intrinsic sensitivity. A further limitation is tissue specificity, which usually determines attenuation, or disappearance, in cultured fibroblasts, of defects detected in muscle or liver. We used numerous fibroblast cell lines derived from patients with OXPHOS deficiencies to set up experimental protocols required for the direct readout of cellular respiration using the Seahorse XF96 apparatus, which measures oxygen consumption rate (OCR) and extra-cellular acidification rate (ECAR) in 96 well plates. Results demonstrate that first level screening based on microscale oxygraphy is more sensitive, cheaper and rapid than spectrophotometry for the biochemical evaluation of cells from patients with suspected mitochondrial disorders. PMID:22310368

  8. Costs of formal care for frail older people in England: the resource implications study of the MRC cognitive function and ageing study (RIS MRC CFAS).

    PubMed

    McNamee, P; Gregson, B A; Buck, D; Bamford, C H; Bond, J; Wright, K

    1999-02-01

    The aim of this paper is to quantify service use and costs of supporting frail older people at home in the community, using data collected in a longitudinal multicentre stratified randomised study for 1055 mentally frail, physically frail, and mentally and physically frail subjects. Average costs per person per week were found to total 64.45 Pounds Sterling, with a small number of services accounting for a large proportion of the total costs. The level of services offered by the nonstatutory voluntary and private sectors was found to be small. To highlight issues for policy makers, the extent of cost variations between a number of different subgroups were calculated. These bivariate analyses revealed substantial variation in costs, especially according to household structure, type of frailty, whether admission to continuing care accommodation occurred and survival. Multiple regression analysis demonstrated that 26% of the variation in log average weekly costs could be explained by a number of socio-demographic and health status variables. A particularly close relationship was observed between costs and whether admission to continuing care accommodation occurred, highlighting a need for policy-makers to examine the nature and scale of provision of alternative community based care packages. The results demonstrate that descriptive cost data such as those presented can provide information useful to the planning process, enabling more informed choices to be made over the provision of services for particular groups of people.

  9. Quantification of minerals from ATR-FTIR spectra with spectral interferences using the MRC method

    NASA Astrophysics Data System (ADS)

    Bosch-Reig, Francisco; Gimeno-Adelantado, José Vicente; Bosch-Mossi, Francisco; Doménech-Carbó, Antonio

    2017-06-01

    A method for quantifying the individual components of mineral samples based on attenuated total reflectance - Fourier transform infrared spectroscopy (ATR-FTIR) is described, extending the constant ratio (CR) method to analytes absorbing in a common range of wavenumbers. Absorbance values in the spectral region where the analytes absorb relative to the absorbance of an internal standard absorbing at a wavenumber where the analytes do not absorb, permits the quantification of N analytes using measurements at N fixed wavenumbers. The method was tested for mixtures of albite, orthoclase, kaolin and quartz.

  10. Be skeptical about unexpected large apparent treatment effects: the case of an MRC AML12 randomization.

    PubMed

    Wheatley, Keith; Clayton, David

    2003-02-01

    The preliminary results of the twelfth Medical Research Council acute myeloid leukemia trial show no evidence of a survival advantage for five courses of therapy compared to four courses in a randomized comparison involving 1078 patients (hazard ratio 1.09, 95% confidence interval [CI] 0.87-1.37, p=0.4). However, the data presented to the independent data monitoring and ethics committee (DMEC) at both its reviews in 1998 suggested large benefits for the additional course with hazard ratios of 0.47 and 0.55 (95% CIs 0.29-0.77 and 0.38-0.80, p=0.003 and p=0.002, respectively). Despite these highly significant findings, the DMEC did not recommend closure of the randomization, a decision vindicated by the subsequent reversion to a null result. The main reason for not closing the randomization was that the treatment effects observed in 1998 (53% and 45% reductions in the odds of death) were considered too large to be clinically plausible, despite the p-values associated with them. Investigations have not identified any clinical explanations, such as different types of patients in the early and later parts of the trial, to explain the loss of benefit as the trial progressed. Thus, the most likely current explanation for the large benefit observed early on is the play of chance. Lessons to be learned from this example are that: fixed stopping rules based on some predetermined p-value should not be used and the decision to close a randomization or not should take account of other factors such as the medical plausibility of the magnitude of the treatment effect; chance effects do occur and happen more frequently than many clinicians realize; it is important that DMEC members are experienced in the interpretation of clinical trial evidence and aware of the dangers of early stopping without wholly convincing evidence.

  11. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study.

    PubMed

    Kitchener, H; Swart, A M C; Qian, Q; Amos, C; Parmar, M K B

    2009-01-10

    Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.

  12. Modular Research-Based Composably Trustworthy Mission-Oriented Resilient Clouds (MRC2)

    DTIC Science & Technology

    2016-02-01

    malware , external attacks, insider misuse, power outages, and animals chewing through cables, etc. It is just one more characteristic that must be...software – dramatically reducing the security risks from malware , intentional misuse, and human errors, without interfering with overall system...construct an efficient countermeasure application, which monitors security alerts from a range of legacy IDS and anti- malware applications and

  13. Robotic nanolitre protein crystallisation at the MRC Laboratory of Molecular Biology.

    PubMed

    Stock, Daniela; Perisic, Olga; Löwe, Jan

    2005-07-01

    We have set up high-throughput robotic systems to screen and optimise crystallisation conditions of biological macromolecules with the aim to make difficult structural biology projects easier. The initial screening involves two robots. A Tecan Genesis liquid handler is used to transfer commercially available crystallisation reagents from 15 ml test tubes into the reservoirs of 96-well crystallisation plates. This step is fully automated and includes a carousel for intermediate plate storage, a Beckman plate sealer and a robotic arm, which transfers plates in between steps. For adding the sample, we use a second robot, a 17-tip Cartesian Technologies PixSys 4200 SynQuad liquid handler, which uses a syringe/solenoid valve combination to dispense small quantities of liquid (typically 100 nl) without touching the surface of the plate. Sixteen of the tips are used to transfer the reservoir solution to the crystallisation wells, while the 17th tip is used to dispense the protein. The screening of our standard set of 1440 conditions takes about 3 h and requires 300 microl of protein solution. Once crystallisation conditions have been found, they are optimised using a second Tecan Genesis liquid handler, which is programmed to pipette gradients from four different corner solutions into a wide range of crystallisation plate formats. For 96-well plates, the Cartesian robot can be used to add the sample. The methods described are now used almost exclusively for obtaining diffraction quality crystals in our laboratory with a throughput of several thousand plates per year. Our set-up has been copied in many institutions worldwide.

  14. On the Secure Energy Efficiency of TAS/MRC With Relaying and Jamming Strategies

    NASA Astrophysics Data System (ADS)

    Farhat, Jamil; Brante, Glauber; Souza, Richard Demo

    2017-08-01

    In this paper we investigate the secure energy efficiency (SEE) in a cooperative scenario where all nodes are equipped with multiple antennas. Moreover, we employ secrecy rate and power allocation at Alice and at the relay in order to maximize the SEE, subjected to a constraint in terms of a minimal required secrecy outage probability. Only the channel state information (CSI) with respect to the legitimate nodes is available. Then, we compare the Artificial-Noise (AN) scheme with CSI-Aided Decode-and-Forward (CSI-DF), which exploits the CSI to choose the best communication path (direct or cooperative). Our results show that CSI-DF outperforms AN in terms of SEE in most scenarios, except when Eve is closer to the relay or with the increase of antennas at Eve. Additionally, we also show that the maximization of SEE implies in an optimal number of antennas to be used at each node, which is due to the trade-off between secure throughput and power consumption.

  15. Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses.

    PubMed

    Draak, Thomas H P; Vanhoutte, Els K; van Nes, Sonja I; Gorson, Kenneth C; Van der Pol, W-Ludo; Notermans, Nicolette C; Nobile-Orazio, Eduardo; Lewis, Richard A; Léger, Jean-Marc; Van den Bergh, Peter Y K; Lauria, Giuseppe; Bril, Vera; Katzberg, Hans; Lunn, Michael P T; Pouget, Jean; van der Kooi, Anneke J; Hahn, Angelika F; van den Berg, Leonard H; van Doorn, Pieter A; Cornblath, David R; Faber, Catharina G; Merkies, Ingemar S J

    2015-09-01

    We performed a comparison between Neuropathy Impairment Scale-sensory (NISs) vs. the modified Inflammatory Neuropathy Cause and Treatment sensory scale (mISS), and NIS-motor vs. the Medical Research Council sum score in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and IgM monoclonal gammopathy of undetermined significance-related polyneuropathy (MGUSP). The ordinal data were subjected to Rasch analyses, creating Rasch-transformed (RT)-intervals for all measures. Comparison between measures was based on validity/reliability with an emphasis on responsiveness (using the patient's level of change related to the individually obtained varying SE for minimum clinically important difference). Eighty stable patients (GBS: 30, CIDP: 30, and MGUSP: 20) were assessed twice (entry: two observers; 2-4 weeks later: one observer), and 137 newly diagnosed or relapsing patients (GBS: 55, CIDP: 59, and IgM-MGUSP: 23) were serially examined with 12 months follow-up. Data modifications were needed to improve model fit for all measures. The sensory and motor scales demonstrated approximately equal and acceptable validity and reliability scores. Responsiveness scores were poor but slightly higher in RT-mISS compared to RT-NISs. Responsiveness was equal for the RT-motor scales, but higher in GBS compared to CIDP; responsiveness was poor in patients with MGUSP, suggesting a longer duration of follow-up in the latter group of patients. © 2015 Peripheral Nerve Society.

  16. MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.

    PubMed Central

    1985-01-01

    The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2861880

  17. Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development.

    PubMed

    Lacey, Rebecca E; Kumari, Meena; Sacker, Amanda; Stafford, Mai; Kuh, Diana; McMunn, Anne

    2016-01-01

    The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers-waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin-in mid-life. We used data from the Medical Research Council's National Survey of Health and Development-the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16-51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn't have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women.

  18. Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development

    PubMed Central

    Kumari, Meena; Sacker, Amanda; Stafford, Mai; Kuh, Diana; McMunn, Anne

    2016-01-01

    The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers—waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin—in mid-life. We used data from the Medical Research Council’s National Survey of Health and Development—the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16–51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn’t have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women. PMID:27563726

  19. Multi-Hop Link Capacity of Multi-Route Multi-Hop MRC Diversity for a Virtual Cellular Network

    NASA Astrophysics Data System (ADS)

    Daou, Imane; Kudoh, Eisuke; Adachi, Fumiyuki

    In virtual cellular network (VCN), proposed for high-speed mobile communications, the signal transmitted from a mobile terminal is received by some wireless ports distributed in each virtual cell and relayed to the central port that acts as a gateway to the core network. In this paper, we apply the multi-route MHMRC diversity in order to decrease the transmit power and increase the multi-hop link capacity. The transmit power, the interference power and the link capacity are evaluated for DS-CDMA multi-hop VCN by computer simulation. The multi-route MHMRC diversity can be applied to not only DS-CDMA but also other access schemes (i. e. MC-CDMA, OFDM, etc.).

  20. Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial)

    PubMed Central

    Franks, P J; Bosanquet, N; Thorpe, H; Brown, J M; Copeland, J; Smith, A M H; Quirke, P; Guillou, P J

    2006-01-01

    The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), £1703 vs £1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (£2930 vs £3176). The average cost to individuals for reoperations was higher in the lap group (£762 vs £553). Overall costs were slightly higher in the lap group (£6899 vs £6631), with mean difference of £268 (95%CI −689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (£8259 vs £5586) and open procedures (£7820 vs £5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery. PMID:16755298

  1. Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank.

    PubMed

    Millar, T; Walker, R; Arango, J-C; Ironside, J W; Harrison, D J; MacIntyre, D J; Blackwood, D; Smith, C; Bell, J E

    2007-12-01

    Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile.

  2. Prognostic features in the third MRC myelomatosis trial. Medical Research Council's Working Party on Leukaemia in Adults.

    PubMed Central

    1980-01-01

    This paper reports the prognostic significance of clinical and laboratory features recorded at presentation in 485 patients entered into the Medical Research Council's 3rd therapeutic trial in myelomatosis between July 1975 and August 1978. The data were complete up to 1 January 1980, with a median follow-up time of 36 months. The 3 major determinants of prognosis were the blood urea concentration (BUC), the haemoglobin concentration ([Hb]), and the clinical performance status. Three prognostic groups based on these determinants were specified. The groups contained 22%, 56% and 22% of the patients and gave 2-year survival probabilities of 76%, 50% and 9% respectively. Patients in the good-prognosis group had a BUC less than or equal to 8 mM. [Hb] greater than or equal to 100 g/l, and no or minimal symptoms. Those in the poor-prognosis group had either [Hb] less than or equal to 75 g/l or a BUC greater than 10 mM and restricted clinical activity. Patients who had combinations of the 3 determinant features which excluded them from these 2 groups were classified into an intermediate prognosis group. PMID:7459218

  3. A commentary on the NH&MRC Draft Values and Ethics in Aboriginal and Torres Strait Islander Health Research.

    PubMed

    Gillam, Lynn; Pyett, Priscilla

    2003-10-01

    In this paper, we discuss and critically evaluate the National Health and Medical Research Council's recently released document entitled 'Draft Values and Ethics in Aboriginal and Torres Strait Islander Health Research'. We provide a brief account of its development, philosophy and contents, and then consider how the document could be used by HRECs. We recommend that three specially targeted documents be developed from this one document, to meet the particular needs of HRECs, Indigenous people and researchers. We propose a system of Indigenous ethics advisors as a way to implement the central ideas of the new draft guidelines, without falling into the legalism and rule-following that these guidelines explicitly aim to avoid.

  4. Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping

    SciTech Connect

    Eichbaum, Q.; Clerc, P.; Bruns, G.

    1994-08-01

    Tissue macrophages form a latticework beneath epithelial surfaces and play a pivotal role in first line host defense. The macrophage mannose receptor is highly expressed on these terminally differentiated cells, but is not expressed on circulating monocytes. Although originally defined as an endocytic receptor, the predominant physiological role for this 170-kDa transmembrane protein appears to be phagocytosis of microorganisms, such as Candida albicans and Pneumocystis carinii. The characterization of cDNAs that encode the human and mouse mannose receptors reveals that the ectodomain contains a cysteine-rich NH{sub 2} domain that appears to resemble the b subunit of ricin D. This domain is followed by a fibronectin type 2 domain. A tandem array of eight carbohydrate recognition domains bear approximately 30% homology to one another. A short hydrophobic region is followed by a 45-amino-acid cytoplasmic tail. Comparison of the human and mouse encoded proteins reveals an average homology of 80%. Of interest is the fact that the murine and human genes both span about 70 kb that contains 30 exons interrupted by 29 introns. The position of the introns and the size of the exons are identical in the mouse and human genes. 15 refs., 2 figs.

  5. Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial

    PubMed Central

    Fairbank, Jeremy; Frost, Helen; Wilson-MacDonald, James; Yu, Ly-Mee; Barker, Karen; Collins, Rory

    2005-01-01

    Objectives To assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain. Design Multicentre randomised controlled trial. Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom. Participants 349 participants aged 18-55 with chronic low back pain of at least one year's duration who were considered candidates for spinal fusion. Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy. Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after randomisation. The SF-36 instrument was used as a secondary outcome measure. Results 176 participants were assigned to surgery and 173 to rehabilitation. 284 (81%) provided follow-up data at 24 months. The mean Oswestry disability index changed favourably from 46.5 (SD 14.6) to 34.0 (SD 21.1) in the surgery group and from 44.8 (SD14.8) to 36.1 (SD 20.6) in the rehabilitation group. The estimated mean difference between the groups was –4.1 (95% confidence interval –8.1 to –0.1, P = 0.045) in favour of surgery. No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures. Conclusions Both groups reported reductions in disability during two years of follow-up, possibly unrelated to the interventions. The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference, and the potential risk and additional cost of surgery also need to be considered. No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation. PMID:15911537

  6. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center.

    PubMed

    Walter, R B; Othus, M; Burnett, A K; Löwenberg, B; Kantarjian, H M; Ossenkoppele, G J; Hills, R K; Ravandi, F; Pabst, T; Evans, A; Pierce, S R; Vekemans, M-C; Appelbaum, F R; Estey, E H

    2015-02-01

    Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

  7. Child Behavior Research. A Survey of British Research Into Child Psychiatric Disorder and Normal Social Development. A Report to the MRC Child Psychiatry Sub-Committee.

    ERIC Educational Resources Information Center

    Shaffer, D., Comp.

    Approximately 250 abstracts of currently active (1975-1976) British research into child psychiatric disorder and normal social development are presented. It is explained that the information was gathered from a 1974 survey of research and education organizations, child psychiatrists at medical schools, and the heads of academic departments of…

  8. The descriptive epidemiology of delirium symptoms in a large population-based cohort study: results from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

    PubMed

    Davis, Daniel H J; Barnes, Linda E; Stephan, Blossom C M; MacLullich, Alasdair M J; Meagher, David; Copeland, John; Matthews, Fiona E; Brayne, Carol

    2014-07-28

    In the general population, the epidemiological relationships between delirium and adverse outcomes are not well defined. The aims of this study were to: (1) construct an algorithm for the diagnosis of delirium using the Geriatric Mental State (GMS) examination; (2) test the criterion validity of this algorithm against mortality and dementia risk; (3) report the age-specific prevalence of delirium as determined by this algorithm. Participant and informant data in a randomly weighted subsample of the Cognitive Function and Ageing Study were taken from a standardized assessment battery. The algorithmic definition of delirium was based on the DSM-IV classification. Outcomes were: proportional hazard ratios for death; odds ratios of dementia at 2-year follow-up. Data from 2197 persons (representative of 13,004) were used, median age 77 years, 64% women. Study-defined delirium was associated with a new dementia diagnosis at two years (OR 8.82, 95% CI 2.76 to 28.2) and death (HR 1.28, 95% CI 1.03 to 1.60), even after adjustment for acute illness severity. Similar associations were seen for study-defined subsyndromal delirium. Age-specific prevalence as determined by the algorithm increased with age from 1.8% in the 65-69 year age group to 10.1% in the ≥85 age group (p < 0.01 for trend). For study-defined subsyndromal delirium, age-specific period prevalence ranged from 8.2% (65-69 years) to 36.1% (≥85 years). These results demonstrate the possibility of constructing an algorithmic diagnosis for study-defined delirium using data from the GMS schedule, with predictive criterion validity for mortality and dementia risk. These are the first population-based analyses able to account prospectively for both illness severity and an earlier study diagnosis of dementia.

  9. Obesity History and Daily Patterns of Physical Activity at Age 60-64 Years: Findings From the MRC National Survey of Health and Development.

    PubMed

    Cooper, Rachel; Huang, Lei; Hardy, Rebecca; Crainiceanu, Adina; Harris, Tamara; Schrack, Jennifer A; Crainiceanu, Ciprian; Kuh, Diana

    2017-10-01

    The aim of this study was to investigate associations of current body mass index (BMI) and obesity history with daily patterns of physical activity. At age 60-64, participants from a British birth cohort study wore accelerometers for 5 days. Accelerometry counts were log-transformed and mean log-counts were used to derive a summary variable indicating total daily log-activity counts. Among those with complete data (n = 1,388) the associations of current BMI and age of first obesity were examined with: (a) total daily log-activity counts and (b) total log-activity counts in four segments of the day. Higher current BMI and younger age at obesity were strongly associated with lower levels of total daily activity at age 60-64 even after adjustment for sex, socioeconomic factors, and health status. The fully-adjusted mean difference in total daily log-activity counts was -581.7 (95% confidence interval: -757.2, -406.3) when comparing BMI ≥35 kg/m2 with <25 kg/m2, representing an 18.4% difference. Participants who had been obese since early adulthood had the lowest levels of activity (mean difference in total daily log-activity counts was -413.1 (-638.1, -188.2) when comparing those who were obese by age 26 or 36 with those who were never obese, representing a 13.1% difference). Obese older adults may require targeted interventions and additional support to improve their daily activity levels. As younger generations with greater lifetime exposure to obesity reach old age the proportion of adults achieving sufficient levels of activity to realize its associated health benefits is likely to decline.

  10. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial

    PubMed Central

    Sydes, Matthew R; Parmar, Mahesh KB; James, Nicholas D; Clarke, Noel W; Dearnaley, David P; Mason, Malcolm D; Morgan, Rachel C; Sanders, Karen; Royston, Patrick

    2009-01-01

    Background The multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm. MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally designed trials. Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive, advanced disease as quickly as possible. The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases. Methods STAMPEDE is an open-label, 5-stage, 6-arm randomised controlled trial using MAMS methodology for men with prostate cancer. It is the first trial of this design to use multiple arms and stages synchronously. Results The practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials. These issues include the choice of intermediate and final outcome measures, sample size calculations and the impact of varying the assumptions, the process for moving between trial stages, stopping accrual to each trial arm and overall, and issues around perceived trial complexity. Conclusion It is possible to use the MAMS design to initiate and undertake large scale cancer trials. The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other researchers will use this exciting and efficient method to perform further randomised controlled trials. Trial registration ISRCTN78818544, NCT00268476 PMID:19519885

  11. The distribution of Mini-Mental State Examination scores in an older UK African-Caribbean population compared to MRC CFA study norms.

    PubMed

    Stewart, Robert; Johnson, Jo; Richards, Marcus; Brayne, Carol; Mann, Anthony

    2002-08-01

    to describe normative data for the Mini-Mental State Examination (MMSE) in a UK African-Caribbean population and compare these with norms for white UK-born elders. a comparison of MMSE data from two cross-sectional surveys. the MMSE had been administered to a community UK African-Caribbean population and scores were compared to norms from the Medical Research Council Cognitive Function and Ageing Study (CFAS). MMSE data were analysed for 248 African-Caribbean participants aged 55-75 and 5379 CFAS participants aged 65-74, without visual or auditory problems. Distributions of scores were tabulated and error rates for individual items compared. Median MMSE scores were 25 (interquartile range 22-27) for the whole African-Caribbean sample, 24 (22-27) for those aged 65-75 in the African-Caribbean sample, and 27 (25-29) for CFAS. Differences in error rates were specific to particular items: naming the season, serial seven subtraction, phrase repetition, three-stage command, and copying intersecting pentagons. These differences persisted when both samples were restricted to those with statutory duration of education, who were literate and who had worked in non-manual occupations. Normative data are displayed for MMSE scores in both groups. different distributions of MMSE scores between UK African-Caribbean and Caucasian groups can be principally explained by cultural bias in certain items. If the MMSE is to be administered to older African-Caribbean people, specific normative data should be referred to or else a culturally modified version of the instrument should be used. Copyright 2002 John Wiley & Sons, Ltd.

  12. Comparison of 1 + 5 DAT and 3 + 10 DAT followed by COAP or MAZE consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial.

    PubMed

    Rees, J K; Gray, R

    1987-06-01

    This trial, which will probably accrue over 1,000 patients before it closes, has already demonstrated that high remission rates are attainable in large multicenter studies using 'conventional' doses of ara-C. The results in the group aged less than 40 are comparable with many single-center studies. There is, at the moment, only a borderline difference in the remission rates between the two forms of induction therapy but the more intensive regimen of DAT 3 + 10 achieves remission more quickly and requires less supportive care. Analysis of the reasons for failure to enter remission continues to show that inadequate supportive care remains an important reason why the remission rates are not higher. Drug-related deaths in remission, though decreasing gradually in this study, are a disturbing consequence of increasing the intensity of consolidation treatment.

  13. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

    PubMed

    Blake, P; Swart, Ann Marie; Orton, J; Kitchener, H; Whelan, T; Lukka, H; Eisenhauer, E; Bacon, M; Tu, D; Parmar, M K B; Amos, C; Murray, C; Qian, W

    2009-01-10

    Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

  14. An Integrational Model of Quality of Life in Older Age. Results from the Esrc/mrc Hsrc Quality of Life Survey in Britain.(author Abstract)

    ERIC Educational Resources Information Center

    Bowling, Ann; Gabriel, Zahava

    2004-01-01

    This paper is based on the results of a national survey of the quality of life of 999 randomly sampled people aged 65 and over, living at home in Britain. The survey was semi-structured, and a sample of survey respondents was followed up and interviewed in-depth in order to explore their perceptions of quality of life in full. Comparisons are made…

  15. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial

    PubMed Central

    Seymour, Matthew T; Thompson, Lindsay C; Wasan, Harpreet S; Middleton, Gary; Brewster, Alison E; Shepherd, Stephen F; O'Mahony, M Sinead; Maughan, Timothy S; Parmar, Mahesh; Langley, Ruth E

    2011-01-01

    Summary Background Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. Methods We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. Findings 459 patients were randomly assigned (115 to each of groups A–C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3–7·5] vs 4·5 months [2·8–6·4]; hazard ratio 0·84, 95% CI 0·69–1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14–1·52), less widespread disease (1·51, 1·05–2·19), and use of oxaliplatin (0·57, 0·39–0·82) were predictive of better OTU. Interpretation FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. Funding Cancer Research UK and the Medical Research Council. PMID:21570111

  16. GoMRC Website ‘Meta-analysis Report: Land-use and submerged aquatic vegetation change in the Gulf of Mexico’

    SciTech Connect

    Judd, Chaeli; Stefansson, Emily S.; Brushnahan, Heather

    2007-12-06

    Over the past century, health and spatial extent of seagrasses has decreased dramatically in the Gulf of Mexico. While some of the changes can be explained by direct impacts to the seagrass beds, we hypothesize that changes in the land use in the watersheds can also be correlated with the decline of seagrasses. Through this meta-analysis, we researched historical and compared trends in seagrass populations and land use in five bays and their watersheds within the Gulf of Mexico: Mobile Bay, Perdido Bay, Tampa Bay, Charlotte Harbor, and Galveston Bay. Using both historical records and spatial datasets, we examined land use and seagrass trends in these five areas.

  17. An Integrational Model of Quality of Life in Older Age. Results from the Esrc/mrc Hsrc Quality of Life Survey in Britain.(author Abstract)

    ERIC Educational Resources Information Center

    Bowling, Ann; Gabriel, Zahava

    2004-01-01

    This paper is based on the results of a national survey of the quality of life of 999 randomly sampled people aged 65 and over, living at home in Britain. The survey was semi-structured, and a sample of survey respondents was followed up and interviewed in-depth in order to explore their perceptions of quality of life in full. Comparisons are made…

  18. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

    PubMed Central

    Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

    2012-01-01

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111) PMID:22058209

  19. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  20. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial.

    PubMed

    Boyd, K D; Ross, F M; Chiecchio, L; Dagrada, G P; Konn, Z J; Tapper, W J; Walker, B A; Wardell, C P; Gregory, W M; Szubert, A J; Bell, S E; Child, J A; Jackson, G H; Davies, F E; Morgan, G J

    2012-02-01

    The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.

  1. Ethnic differences in overweight and obesity in early adolescence in the MRC DASH study: the role of adolescent and parental lifestyle.

    PubMed

    Harding, Seeromanie; Teyhan, Alison; Maynard, Maria J; Cruickshank, J Kennedy

    2008-02-01

    Ethnicity is a consistent correlate of excess weight in youth. We examine the influence of lifestyles on ethnic differences in excess weight in early adolescence in the UK. Data were collected from 6599 pupils, aged 11-13 years in 51 schools, on dietary practices and physical activity, parental smoking and overweight, and on overweight and obesity (using International Obesity Task Force criteria). Skipping breakfast [girls odds ratio (OR) 1.74, 95% confidence interval (CI) 1.30-2.34; boys OR 2.06; CI 1.57-2.70], maternal smoking (girls OR 2.04, CI 1.49-2.79; boys OR 1.63, CI 1.21-2.21) and maternal overweight (girls OR 2.01, CI 1.29-3.13; boys OR 2.47, CI 1.63-3.73) were associated with obesity. Skipping breakfast, more common among girls, was associated with other poor dietary practices. Compared with White UK peers, Black Caribbeans (girls OR 1.62, CI 1.24-2.12; boys OR 1.49, CI 1.15-1.95) and Black Africans (girls OR 1.96, CI 1.52-2.53; boys OR 2.50, CI 1.92-3.27) were more likely to skip breakfast and engage in other poor dietary practices, and Indians were least likely. White Other boys reported more maternal smoking (OR 1.37, CI 1.03-1.82). All these reports were more common among those born in the UK than those born elsewhere. Black Caribbean girls were more likely to be overweight (OR 1.38, CI 1.02-1.87) and obese (OR 1.65, CI 1.05-2.58), Black African girls to be overweight (OR 1.35, CI 1.02-1.79) and White Other boys to be overweight (OR 1.37, CI 1.00-1.88) and obese (OR 1.86, CI 1.15-3.00). Adverse dietary habits and being born in the UK contributed to these patterns. These findings signal a potential exacerbating effect on ethnic differences in obesity if adverse dietary habits persist. Combined adolescent and parent-focused interventions should be considered.

  2. Superior heat transfer fluids for solar heating and cooling applications. Final report, 21 August 1978-31 December 1979. Report MRC-DA-953

    SciTech Connect

    Parts, L; Miller, D R; Leffingwell, J W; Thompson, Q E

    1980-09-01

    The major objective of this program was the identification of superior, currently available organic heat transfer fluids for solar collector applications. Organic fluids used in the form of aqueous solutions were also to be identified. The required design and handling properties of the fluids were determined through a survey in which 115 designers and manufacturers of solar collectors and collection systems participated. A state-of-the-art survey of commercially available organic heat transfer fluids provided information on fifty fluids. These were grouped into nine classes. This report contains information on limiting, design, and handling properties of these fluids. The limiting properties affix the use temperature ranges of the fluids. The design properties include the following thermophysical data: densities, vapor pressures, viscosities, specific heats, thermal conductivities, heats of vaporization, and coefficients of thermal expansion. The handling properties include: compatibility and incompatibility, with construction materials, chemical sensitivity, ignitability, physiological effects, and biodegradability characteristics. Mutagenicity tests with Salmonella typhimurium bacteria, and ignitability tests were conducted with a number of fluids in this program. The properties of the fluids were analyzed with reference to the required design and handling properties established in the survey of collector manufacturers. Guidelines are provided for the selection of superior fluids to meet specific collector operational and compatibility requirements. These guidelines include the use of heat transfer efficiency factors, that were calculated or the temperature ranges for which thermophysical data were available.

  3. Six key topics informal carers of patients with breathlessness in advanced disease want to learn about and why: MRC phase I study to inform an educational intervention.

    PubMed

    Farquhar, Morag; Penfold, Clarissa; Benson, John; Lovick, Roberta; Mahadeva, Ravi; Howson, Sophie; Burkin, Julie; Booth, Sara; Gilligan, David; Todd, Christopher; Ewing, Gail

    2017-01-01

    Breathlessness is a common symptom of advanced disease placing a huge burden on patients, health systems and informal carers (families and friends providing daily help and support). It causes distress and isolation. Carers provide complex personal, practical and emotional support yet often feel ill-prepared to care. They lack knowledge and confidence in their caring role. The need to educate carers and families about breathlessness is established, yet we lack robustly developed carer-targeted educational interventions to meet their needs. We conducted a qualitative interview study with twenty five purposively-sampled patient-carer dyads living with breathlessness in advanced disease (half living with advanced cancer and half with advanced chronic obstructive pulmonary disease (COPD). We sought to identify carers' educational needs (including what they wanted to learn about) and explore differences by diagnostic group in order to inform an educational intervention for carers of patients with breathlessness in advanced disease. There was a strong desire among carers for an educational intervention on breathlessness. Six key topics emerged as salient for them: 1) understanding breathlessness, 2) managing anxiety, panic and breathlessness, 3) managing infections, 4) keeping active, 5) living positively and 6) knowing what to expect in the future. A cross-cutting theme was relationship management: there were tensions within dyads resulting from mismatched expectations related to most topics. Carers felt that knowledge-gains would not only help them to support the patient better, but also help them to manage their own frustrations, anxieties, and quality of life. Different drivers for education need were identified by diagnostic group, possibly related to differences in caring role duration and resulting impacts. Meeting the educational needs of carers requires robustly developed and evaluated interventions. This study provides the evidence-base for the content of an educational intervention for carers of patients with breathlessness in advanced disease.

  4. Births in Great Britain resulting from assisted conception, 1978-87. MRC Working Party on Children Conceived by In Vitro Fertilisation.

    PubMed Central

    1990-01-01

    OBJECTIVE--To describe the characteristics at birth of children conceived by in vitro fertilisation (IVF) or by gamete intrafallopian transfer (GIFT) and to assess whether they differ from those of children conceived naturally. DESIGN--Survey of children resulting from IVF or GIFT and comparison of their characteristics at birth with national statistics. SETTING--England, Scotland, and Wales from 1978 to 1987. SUBJECTS--1267 Pregnancies conceived by IVF or GIFT, which resulted in 1581 liveborn or stillborn children. MAIN OUTCOME MEASURES--Sex ratio, multiplicity, gestational age at birth, birth weight, stillbirth rate, perinatal and infant mortality, and prevalence of congenital malformations. RESULTS--The ratio of male to female births was 1.07:1; 23% (249/1092) of the deliveries were multiple births compared with 1% for natural conceptions; 24% (278) of 1015 deliveries were preterm compared with 6% in England and Wales; 32% (406) of 1269 babies weighed less than 2500 g compared with 7% in England and Wales. The high percentage of preterm deliveries and of low birthweight babies was largely, but not entirely, due to the high frequency of multiple births. The rate of stillbirth, perinatal mortality, and infant mortality were twice the national average, these excesses being due to the high frequency of multiple births. One or more major congenital malformations were detected during the first week of life in 35 (2.2%) of 1581 babies. This figure is comparable with population based estimates of the prevalence of congenital malformations. The types of malformations reported varied, and the number of each specific type was small. The health of the children was not evaluated beyond the perinatal period. CONCLUSIONS--Multiple pregnancies often result from assisted conception and are the main determinant of the outcome of the pregnancies and of the health of the children at the time of birth. Congenital malformations are comparatively rare, so larger numbers of children need to be studied before firm conclusions can be drawn. The pooling of data from different countries is recommended. PMID:2354290

  5. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

    SciTech Connect

    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-11-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  6. Associations of behavioural risk factors and health status with changes in physical capability over 10 years of follow-up: the MRC National Survey of Health and Development.

    PubMed

    Cooper, Rachel; Muniz-Terrera, Graciela; Kuh, Diana

    2016-04-18

    (1) To describe changes in objective measures of physical capability between ages 53 and 60-64 years; (2) to investigate the associations of behavioural risk factors (obesity, physical inactivity, smoking) and number of health conditions (range 0-4: hand osteoarthritis (OA); knee OA; severe respiratory symptoms; other disabling or life-threatening conditions (ie, cancer, cardiovascular disease, diabetes)) at age 53 years with these changes. Nationally representative prospective birth cohort study. England, Scotland and Wales. Up to 2093 men and women from the Medical Research Council National Survey of Health and Development, who have been followed-up since birth in 1946, and underwent physical capability assessments performed by nurses following standard protocols in 1999 and 2006-2010. Grip strength and chair rise speed were assessed at ages 53 and 60-64 years. Four categories of change in grip strength and chair rise speed were identified: decline, stable high, stable low, a reference group who maintained physical capability within a 'normal' range. Less healthy behavioural risk scores and an increase in the number of health conditions experienced were associated in a stepwise fashion with increased risk of decline in physical capability, and also of having low levels at baseline and remaining low. For example, the sex and mutually adjusted relative-risk ratios (95% CI) of being in the stable low versus reference category of chair rise speed were 1.58 (1.35-1.86) and 1.97 (1.57-2.47) per 1 unit change in behavioural risk score and health indicator count, respectively. These findings provide evidence of the associations of a range of modifiable factors with age-related changes in physical capability. They suggest the need to target multiple risk factors at least as early as mid-life when aiming to promote maintenance and prevent decline in physical capability in later life. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

    PubMed Central

    Sebag-Montefiore, David; Stephens, Richard J; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Quirke, Phil; Couture, Jean; de Metz, Catherine; Myint, Arthur Sun; Bessell, Eric; Griffiths, Gareth; Thompson, Lindsay C; Parmar, Mahesh

    2009-01-01

    Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. Methods We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. Findings At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI 0·73–1·13, p=0·40). Interpretation Taken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer. Funding Medical Research Council (UK) and the National Cancer Institute of Canada. PMID:19269519

  8. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial).

    PubMed

    Mead, Graham M; Barrans, Sharon L; Qian, Wendi; Walewski, Jan; Radford, John A; Wolf, Max; Clawson, Simon M; Stenning, Sally P; Yule, Claire L; Jack, Andrew S

    2008-09-15

    This prospective study aimed to develop reproducible diagnostic criteria for sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these criteria. The study was open to patients with an aggressive B-cell lymphoma with an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ hybridization (FISH) were used to separate BL from other aggressive B-cell lymphomas. BL was characterized by the presence of a cMYC rearrangement as a sole cytogenetic abnormality occurring in patients with a germinal center phenotype with absence of BCL-2 expression and abnormal TP53 expression. A total of 128 patients were eligible for the study, of whom 58 were considered to have BL and 70 to have diffuse large B-cell lymphoma (DLBCL). There were 110 clinically fit patients who received dmCODOX-M (methotrexate, dose 3 g/m(2)) with or without IVAC according to risk group. The 2-year progression-free survival was 64% (95% confidence interval [CI] 51%-77%) for BL, 55% (95% CI 42%-66%) for DLBCL, 85% (95% CI 73%-97%) for low risk, and 49% (95% CI 38%-60%) for high-risk patients. The observed differences in outcome and other clinical features validate the proposed diagnostic criteria. Compared with the previous trial LY06 with full-dose methotrexate (6.7 g/m(2)), there was a reduction in toxicity with comparable outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.

  9. A randomised phase 2 trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor-prognosis germ cell tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604).

    PubMed

    Huddart, Robert A; Gabe, Rhian; Cafferty, Fay H; Pollock, Philip; White, Jeff D; Shamash, Jonathan; Cullen, Michael H; Stenning, Sally P

    2015-03-01

    Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. BEP (bleomycin 30,000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2×CBOP, 2×BO, and 3×BEP (bleomycin 15,000 IU). Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61-85) with CBOP/BEP, 61% with BEP (90% CI, 48-73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33-1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial. In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration. ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Delays in postremission chemotherapy for Philadelphia chromosome negative acute lymphoblastic leukemia are associated with inferior outcomes in patients who undergo allogeneic transplant: An analysis from ECOG 2993/MRC UK ALLXII.

    PubMed

    Kumar, Anita J; Gimotty, Phyllis A; Gelfand, Joel M; Buck, Georgina; Rowe, Jacob M; Goldstone, Anthony H; Fielding, Adele; Marks, David I; Litzow, Mark; Paietta, Elisabeth; Lazarus, Hillard M; Tallman, Martin S; Luger, Selina M; Loren, Alison W

    2016-11-01

    Adults with acute lymphoblastic leukemia (ALL) have a poorer prognosis than children due to a high risk of relapse. One explanation may be variable adherence to dose-intense chemotherapy. However, little is known about risk factors for delays in therapy and their impact on survival. We conducted an analysis of ECOG 2993/UKALLXII trial to study delays in postremission chemotherapy in adults with newly diagnosed ALL. Logistic regression was used to identify risk factors for a very long delay (VLD, >4 weeks) in start of intensification therapy. Cox regression was used to evaluate the impact of delays on overall survival (OS) and event-free survival (EFS). We evaluated 1076 Philadelphia chromosome negative (Ph-) patients who completed induction chemotherapy, achieved complete remission, and started intensification. Factors independently associated with VLD included duration of hospitalization (odds ratio [OR] = 1.2, P < 0.001) during Phase I; thrombocytopenia during Phase I (OR = 1.16, P = 0.004) or Phase II (OR 1.13, P = 0.001); chemotherapy dose reductions during Induction Phase I (OR = 1.72, P < 0.014); female sex (OR = 1.53, P = 0.010); Black (OR = 3.24, P = 0.003) and Asian (OR = 2.26, P = 0.021) race; and increasing age (OR = 1.31, P < 0.001). In multivariate Cox regression, patients who underwent allogeneic stem cell transplant (alloHCT) had significantly worse OS (HR 1.4, P = 0.03) and EFS (HR 1.4, P = 0.02) after experiencing a VLD compared to alloHCT patients who experienced ≤4 weeks delay. Specific populations (female, older, Black, and Asian patients) were more likely to experience delays in chemotherapy, as were those with significant toxicity during induction. VLDs in therapy negatively affected outcomes in patients undergoing allografting. Am. J. Hematol. 91:1107-1112, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

    PubMed Central

    Mead, G. M.; Russell, M.; Clark, P.; Harland, S. J.; Harper, P. G.; Cowan, R.; Roberts, J. T.; Uscinska, B. M.; Griffiths, G. O.; Parmar, M. K.

    1998-01-01

    Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity. PMID:9792152

  12. Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, multi-stage platform, umbrella and basket protocols.

    PubMed

    Parmar, Mahesh Kb; Cafferty, Fay H; Sydes, Matthew R; Choodari-Oskooei, Babak; Langley, Ruth E; Brown, Louise; Phillips, Patrick Pj; Spears, Melissa R; Rowley, Sam; Kaplan, Richard; James, Nicholas D; Maughan, Timothy; Paton, Nicholas; Royston, Patrick J

    2017-08-01

    There is real need to change how we do some of our clinical trials, as currently the testing and development process is too slow, too costly and too failure-prone - often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II trials. In this paper we present examples of new methods for improving the design of phase III trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol. The four principles underlying these solutions are: evaluate many primary hypotheses/treatments within the same protocol if there is a pilot/feasibility/phase II part of the process, aim to have a seamless run through to the phase III part of the process whenever possible and appropriate, conduct an adaptive trial, with the adaptations being major ones such as adding or dropping arms in situations where we are considering subgroups of a specific disease, often biomarker-defined, aim to include questions testing new treatments in all (or most) subgroups, using an adaptive approach. We present some examples of the application of these principles to particular areas, and show how they have led us to develop and launch multi-arm, multi-stage platform, umbrella and basket protocols: STAMPEDE, TRUNCATE-TB, FOCUS-4 and Add-Aspirin. There are clear challenges when embarking on such protocols. They include the need: to garner large scale collaboration bringing large parts of the research community together; to obtain significant and long-term funding; to obtain long term commitment from the key research leaders; to ensure that responsibilities (and also acclaim) are shared as widely as possible; and to have operational structures and systems which allow the implementation of such long-term adaptive protocols. These challenges need to be addressed when the protocol is at the design stage, as they will need to be resolved before any funding is likely to be approved and released. Through these designs our aim is to change the fundamental goal of a single clinical protocol from the typical 2-arm randomised trial of 'testing a new treatment' to 'testing many treatments and hence improving outcomes as rapidly as possible'. We are exploring opportunities to develop such protocols in areas such as Alzheimer's disease, multiple sclerosis, HIV prevention, hepatitis C and wound healing, to speed the process of testing new therapies, and we urge others involved in the design of new trials to follow this way of thinking.

  13. Associations of behavioural risk factors and health status with changes in physical capability over 10 years of follow-up: the MRC National Survey of Health and Development

    PubMed Central

    Cooper, Rachel; Muniz-Terrera, Graciela; Kuh, Diana

    2016-01-01

    Objectives (1) To describe changes in objective measures of physical capability between ages 53 and 60–64 years; (2) to investigate the associations of behavioural risk factors (obesity, physical inactivity, smoking) and number of health conditions (range 0–4: hand osteoarthritis (OA); knee OA; severe respiratory symptoms; other disabling or life-threatening conditions (ie, cancer, cardiovascular disease, diabetes)) at age 53 years with these changes. Design Nationally representative prospective birth cohort study. Setting England, Scotland and Wales. Participants Up to 2093 men and women from the Medical Research Council National Survey of Health and Development, who have been followed-up since birth in 1946, and underwent physical capability assessments performed by nurses following standard protocols in 1999 and 2006–2010. Main outcome measures Grip strength and chair rise speed were assessed at ages 53 and 60–64 years. Four categories of change in grip strength and chair rise speed were identified: decline, stable high, stable low, a reference group who maintained physical capability within a ‘normal’ range. Results Less healthy behavioural risk scores and an increase in the number of health conditions experienced were associated in a stepwise fashion with increased risk of decline in physical capability, and also of having low levels at baseline and remaining low. For example, the sex and mutually adjusted relative-risk ratios (95% CI) of being in the stable low versus reference category of chair rise speed were 1.58 (1.35–1.86) and 1.97 (1.57–2.47) per 1 unit change in behavioural risk score and health indicator count, respectively. Conclusions These findings provide evidence of the associations of a range of modifiable factors with age-related changes in physical capability. They suggest the need to target multiple risk factors at least as early as mid-life when aiming to promote maintenance and prevent decline in physical capability in later life. PMID:27091818

  14. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial

    PubMed Central

    Gore, Martin E; Griffin, Clare L; Hancock, Barry; Patel, Poulam M; Pyle, Lynda; Aitchison, Michael; James, Nicholas; Oliver, Roderick TD; Mardiak, Jozef; Hussain, Tahera; Sylvester, Richard; Parmar, Mahesh KB; Royston, Patrick; Mulders, Peter FA

    2010-01-01

    Summary Background In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8–52·3). Median overall survival was 18·8 months (17·0–23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5–20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90–1·21], p=0·55; absolute difference 0·3% (−5·1 to 5·6) at 1 year and 2·7% (−8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. Funding UK Medical Research Council. PMID:20153039

  15. The efficiency of Gd-EOB-DTPA-enhanced magnetic resonance cholangiography in living donor liver transplantation: a preliminary study.

    PubMed

    Ogul, Hayri; Kantarci, Mecit; Pirimoglu, Berhan; Karaca, Leyla; Aydinli, Bulent; Okur, Aylin; Ozturk, Gurkan; Kizrak, Yesim

    2014-03-01

    The aim of this study was to evaluate utility of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) for the detection of biliary complications after living donor liver transplantation (LDLT). A total of 18 patients with suspected biliary complications underwent MRC. T2-weighted MRC and contrast-enhanced MRC (CE-MRC) were used to identify the biliary complications. MRC included routine breath-hold T2-weighted MRC using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences and Gd-EOB-DTPA-enhanced MRC T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences. Before confirming the biliary complications, one observer reviewed the MRC images and the CE-MRC images separately. The verification procedures and MRC findings were compared, and the sensitivity, specificity, and accuracy of both techniques were calculated for the identification of biliary complications. The observer found six of seven biliary complications using CE-MRC. The sensitivity was 85.7% and the accuracy was 94.4%. Using MRC alone, sensitivity was 57.1% and accuracy was 55.5%. The accuracy of Gd-EOB-DTPA-enhanced MRC was superior to MRC in locating biliary leaks (p < 0.05). The usage of Gd-EOB-DTPA-enhanced MRC yields information that complements the MRC findings that improve the identification of biliary complications. We recommend the use of MRC in addition to Gd-EOB-DTPA-enhanced MRC to increase the preoperative accuracy when assessing the biliary complications after LDLT.

  16. 77 FR 70443 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ... provided to MRC units. In addition, the data serves as an important recruitment tool for the individual MRC... train personnel and to be able to respond to a collection of information, to search data sources, to...

  17. Ride Motion Simulator Safety Assessment Report

    DTIC Science & Technology

    2013-07-01

    concrete and rests on compacted soil . Anchor plates and tie rods built into the structure provide the mechanical interface for the RMS actuator base...in the ‘Retracted” position Switch contact on Crane support 7 SafetyPLC Heartbeat Lost The Watchdog between MRC and the Safety PLC (PILZ) has been...lost MRC Software Detected Failure 8 Host Communication Lost The Watchdog between MRC and the Host computer has been lost MRC Software Detected

  18. Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies

    PubMed Central

    1988-01-01

    Rat T cells and thymocytes were induced to proliferate by a pair of mAbs, MRC OX-54 and MRC OX-55, directed against rat CD2. Accessory cells were required but their role was not simply for crosslinking of the two mAbs, as neither MRC OX-54 nor MRC OX-55 alone, in the presence of a crosslinking second antibody, caused T cell mitogenesis. Nor could the phorbol ester PMA replace either antibody. The two mAbs recognized distinct epitopes on rat CD2; however, MRC OX-54 could partially block MRC OX-55 binding whereas the reverse situation was not seen. A further CD2 epitope was recognized by two mutually competitive mAbs, MRC OX-34 and MRC OX-53, which were not mitogenic. Neither MRC OX-34 nor MRC OX- 53 affected the binding of MRC OX-54 or MRC OX-55, yet they prevented the mitogenic effect induced by these mAbs. The presence of mAbs against CD4 and the IL-2-R also abrogated this mitogenesis, whereas an anti-CD5 mAb augmented the CD2-induced proliferation. PMID:3133442

  19. Impact Evaluation of the Minnesota Reading Corps K-3 Program

    ERIC Educational Resources Information Center

    Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

    2014-01-01

    Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. To meet this goal, the MRC program, and its host organization, ServeMinnesota Action Network, recruit, train, place and…

  20. A Constructive Method for Computing Generalized Manley-Rowe Constants of Motion

    NASA Astrophysics Data System (ADS)

    Kartashova, Elena; Tec, Loredana

    2013-10-01

    The Manley--Rowe constants of motion (MRC) are conservation laws written out for a dynamical system describing the time evolution of the amplitudes in resonant triad. In this paper we extend the concept of MRC to resonance clusters of any form yielding generalized Manley--Rowe constants (gMRC) and give a constructive method how to compute them. We also give details of a \\emph{Mathematica} implementation of this method. While MRC provide integrability of the underlying dynamical system, gMRC generally do not but may be used for qualitative and numerical study of dynamical systems describing generic resonance clusters.

  1. Evolution of an expanded mannose receptor gene family.

    PubMed

    Staines, Karen; Hunt, Lawrence G; Young, John R; Butter, Colin

    2014-01-01

    Sequences of peptides from a protein specifically immunoprecipitated by an antibody, KUL01, that recognises chicken macrophages, identified a homologue of the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the genomic environment of the chicken gene revealed an array of five paralogous genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either side of the single MRC1 gene in mammals. Transcripts of all five genes were detected in RNA from a macrophage cell line and other RNAs, whose sequences allowed the precise definition of spliced exons, confirming or correcting existing bioinformatic annotation. The confirmed gene structures were used to locate orthologues of all five genes in the genomes of two other avian species and of the painted turtle, all with intact coding sequences. The lizard genome had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L-B antigen gene resulting from a recent duplication. The Xenopus genome, like that of most mammals, had only a single MRC1-like gene at the corresponding locus. MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative of similar subcellular migration and functions. Cytoplasmic regions of the other three genes were very divergent, possibly indicating the evolution of a new functional repertoire for this family of molecules, which might include novel interactions with pathogens.

  2. Strengthening Research Portfolio Evaluation at the Medical Research Council: Developing a Survey for the Collection of Information About Research Outputs.

    PubMed

    Ismail, Sharif; Tiessen, Jan; Wooding, Steven

    2012-01-01

    The Medical Research Council (MRC) wished to better understand the wider impact of MRC research output on society and the economy. The MRC wanted to compare the strengths of different types of funding and areas of research and identify the good news stories and successes it can learn from. As an initial step in this process RAND Europe: (1) examined the range of output and outcome information MRC already collected; and (2) used that analysis to suggest how data collection could be improved. This article outlines the approach taken to the second part of this exercise and focuses on the development of a new survey instrument to support the MRC's data collection approach. Readers should bear in mind that some later stages of survey development and implementation were conducted exclusively by the MRC and are not reported here.

  3. Medical reserve corps volunteers in disasters: a survey of their roles, experiences, and challenges.

    PubMed

    Watson, Matthew; Selck, Frederic; Rambhia, Kunal; Morhard, Ryan; Franco, Crystal; Toner, Eric

    2014-01-01

    The Medical Reserve Corps (MRC) was established in the Office of the Surgeon General in response to the spontaneous but disorganized outpouring of medical volunteers following the terrorist attacks of 2001. The mission of the federal MRC office is to provide organizational structure and guidance to the nearly 1,000 locally organized and funded MRC units that have grown up across the country and the more than 200,000 volunteer health professionals that staff these units. Despite the large size of this program and its numerous activations over the past decade, including in the Boston Marathon bombing and Hurricane Sandy, relatively little is known about the MRC, including the make-up of the units, the ways units have been used, and the challenges faced by MRC units and their volunteers. Here we report the results of a mixed-methods investigation of MRC unit organization, activities, and challenges.

  4. Beam and Plasma Physics Research

    DTIC Science & Technology

    1990-06-01

    relativistic klystron amplifiers, virtual cathode oscillators, magnetically insulated transmission lines, transvertrons and vircator phase/frequency...Computational Physics Studies III MRC/ABQ-R-1278 101 03-08 SPHC Manual MRC/ABQ-R-1237 103 03-09 Diagnostic White Paper Contributions MRC/ABQ-N-451 106 9 2.2...magnetically insulated transmission line (MITL). Computations were performed using the particle-in-cell code CCUBE, developed originally by Los

  5. Developing strong response capacity: training volunteers in the medical reserve corps.

    PubMed

    Ye, Jiali; Stanford, Stacy; Gousse, Tahlia; Tosatto, Robert J

    2014-12-01

    The success of the Medical Reserve Corps (MRC) is dependent on the ability of volunteers to respond in a timely and effective manner. This study aimed to assess the current status of MRC volunteer training and to examine the association between MRC characteristics and provision of training. The data for this study were drawn from the 2013 Network Profile Survey of the MRC, which was administered to active MRC unit leaders or designated alternates of 962 units across the country in April to May of 2013. Over 80% of MRCs had a training plan. Ninety-one percent of MRCs offered one or more training courses to volunteers, and 73% indicated requirements for mandatory training. Approximately 84% of MRC units collaborated with other organizations to conduct trainings. Units with more volunteers (>150) were 3 times as likely to have a plan for volunteer training as were those with fewer volunteers (≤50). Compared to units with a full-time leader, those with leaders who were volunteers were only 0.57 times as likely to have a training plan. An overwhelming majority of MRC units provide critical training to their volunteers prior to an emergency deployment. To further strengthen the overall MRC capacities, it is important for MRC units to have a training plan tailored to their community needs and features, make full use of available training resources, and collaborate with partner organizations.

  6. Explosive safety criteria at a Department of Energy contractor facility

    SciTech Connect

    Krach, F.

    1984-08-01

    Monsanto Research Corporation (MRC) operates the Mound facility in Miamisburg, Ohio, for the Department of Energy. Small explosive components are manufactured at MRC, and stringent explosive safety criteria have been developed for their manufacturing. The goals of these standards are to reduce employee injuries and eliminate fenceline impacts resulting from accidental detonations. This paper will describe the manner in which these criteria were developed and what DOD standards were incorporated into MRC's own design criteria. These design requirements are applicable to all new construction at MRC. An example of the development of the design of a Component Test Facility will be presented to illustrate the application of the criteria.

  7. Explosive safety criteria at a Department of Energy contractor facility

    NASA Astrophysics Data System (ADS)

    Krach, F.

    1984-08-01

    Monsanto Research Corporation (MRC) operates the Mound facility in Miamisburg, Ohio, for the Department of Energy. Small explosive components are manufactured at MRC, and stringent explosive safety criteria have been developed for their manufacturing. The goals of these standards are to reduce employee injuries and eliminate fenceline impacts resulting from accidental detonations. The manner in which these criteria were developed and what DOD standards were incorporated into MRC's own design criteria are described. These design requirements are applicable to all new construction at MRC. An example of the development of the design of a Component Test Facility is presented to illustrate the application of the criteria.

  8. Mutagenicity in Salmonella of a Simulated Urban-Smog Atmosphere Generated Using a Mobile Reaction Chamber

    EPA Science Inventory

    The EPA Mobile Reaction Chamber (MRC) is a 24-foot trailer containing a 14.3-m3 Teflon lined photochemical chamber used to generate simulated urban atmospheres. Photochemistry in the MRC is catalyzed by 120 fluorescent bulbs evenly mixed with black light bulbs and UV bulbs (300 &...

  9. Using pedotransfer functions to estimate the van Genuchten-Mualem soil hydraulic properties: A review

    USDA-ARS?s Scientific Manuscript database

    In this paper, we review the use of the van Genuchten Mualem (VGM) model to parameterize the soil moisture retention characteristic (MRC) and the nsaturated hydraulic conductivity curve (HCC), as well as its use in developing pedotransfer functions (PFTs). Analysis of literature data showed that MRC...

  10. Attentional Demands on Motor-Respiratory Coordination

    ERIC Educational Resources Information Center

    Hessler, Eric E.; Amazeen, Polemnia G.

    2009-01-01

    Athletic performance requires the pacing of breathing with exercise, known as motor-respiratory coordination (MRC). In this study, we added cognitive and physical constraints while participants intentionally controlled their breathing locations during rhythmic arm movement. This is the first study to examine a cognitive constraint on MRC.…

  11. Attentional Demands on Motor-Respiratory Coordination

    ERIC Educational Resources Information Center

    Hessler, Eric E.; Amazeen, Polemnia G.

    2009-01-01

    Athletic performance requires the pacing of breathing with exercise, known as motor-respiratory coordination (MRC). In this study, we added cognitive and physical constraints while participants intentionally controlled their breathing locations during rhythmic arm movement. This is the first study to examine a cognitive constraint on MRC.…

  12. Magnetic resonance imaging in evaluation of the common bile duct.

    PubMed

    Musella, M; Barbalace, G; Capparelli, G; Carrano, A; Castaldo, P; Tamburrini, O; Musella, S

    1998-01-01

    The ideal method for evaluation of the common bile duct (CBD) before or during cholecystectomy remains controversial. Magnetic resonance cholangiography (MRC) is a new, promising technique. A prospective evaluation is reported. Sixty-one patients (45 women) were studied by MRC. There were 29 patients with symptomatic gallstone disease and without clinical, biochemical or ultrasonographic evidence of CBD stones (group 1); 28 of them also underwent intraoperative cholangiography (IOC). In addition, there were 21 patients with symptomatic gallstone disease, with mild biochemical and ultrasonographic signs of CBD involvement (group 2), of whom 19 underwent IOC, and 11 patients with symptomatic CBD stones (group 3), nine of whom had preoperative endoscopic retrograde cholangiopancreatography (ERCP) following MRC. MRC showed that no patient in group 1 and three patients in group 2 had CBD stones. Three patients (one in group 1, two in group 2) did not undergo IOC because of technical or clinical problems. In group 3, ERCP confirmed the results of MRC in nine patients. Two patients underwent open surgery because of ultrasonographic, MRC and radiographic signs of pancreatic malignancy. MRC could replace IOC and ERCP for identification of asymptomatic CBD stones. In symptomatic patients MRC combined with other non-invasive imaging techniques can direct the surgeon to appropriate management.

  13. Development of Ab-initio Multibody Energy Expansions for the Design of Metallic Materials with Extremal Properties

    DTIC Science & Technology

    2010-10-31

    algebra software like MAGMA [32]. In this work, we follow the Monomial Symmetrization Approach (MSA) of [8] to construct the polynomials. To introduce...doi:10.1002/mrc.1242. URL http://onlinelibrary.wiley.com/doi/10.1002/mrc.1242/pdf [32] W. Bosma, J. J. Cannon, C. Playoust, The Magma Algebra System I

  14. The Relative Importance of Children's Criteria for Representational Adequacy in the Perception of Simple Sonic Stimuli

    ERIC Educational Resources Information Center

    Verschaffel, Lieven; Reybrouck, Mark; Degraeuwe, Goedele; Van Dooren, Wim

    2013-01-01

    This study investigates children's metarepresentational competence (MRC) with regard to listening to and making sense of simple sonic stimuli. Using diSessa's (2002) seminal work on MRC in mathematics and sciences as background, it aims to assess the relative importance children attribute to several criteria for representational adequacy…

  15. Impact Evaluation: Minnesota Reading Corps K-3 Program. Appendices

    ERIC Educational Resources Information Center

    Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

    2014-01-01

    Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. Starting in 2011, the "Corporation for National and Community Service" (CNCS) sponsored a randomized controlled…

  16. Mutagenicity in Salmonella of a Simulated Urban-Smog Atmosphere Generated Using a Mobile Reaction Chamber

    EPA Science Inventory

    The EPA Mobile Reaction Chamber (MRC) is a 24-foot trailer containing a 14.3-m3 Teflon lined photochemical chamber used to generate simulated urban atmospheres. Photochemistry in the MRC is catalyzed by 120 fluorescent bulbs evenly mixed with black light bulbs and UV bulbs (300 &...

  17. Female and male chronic obstructive pulmonary disease patients with severe dyspnea do not profit less from pulmonary rehabilitation.

    PubMed

    Lizak, Maria Karolina; Singh, Sally; Lubina, Szymon; Zembala, Marian

    2008-01-01

    Pulmonary rehabilitation (PR) is an established component of COPD management. The lack of exercise performance improvement (EPI) in severely dyspnoeic patients (Medical Research Council [MRC] score 5) has been questioned. The data on the gender impact on EPI after PR remain scarce. The impact of dyspnea severity on PR outcomes was investigated and a question was raised whether severe dyspnea at training onset limits the profit from PR in COPD patients. Additionally, the impact of gender on PR results was analyzed. 263 consecutive COPD patients underwent outpatient PR. Exercise capacity was assessed by the incremental shuttle walking test (SWT) and dyspnea with the MRC dyspnea score at inclusion (preSWT, preMRC) and at the end of PR (postSWT, postMRC). The data were analyzed in groups according to preMRC. The grade of improvement (deltaSWT, deltaSWT% and deltaMRC) was compared between groups. The influence of gender was analyzed in 138 men and 125 women. A significant absolute increase in SWT and a decrease in MRC score were shown in all groups and for both sexes (p < 0.05) with no significant intergroup differences (p > 0.05). deltaSWT% rose significantly with preMRC score and exceeded the values of a clinically important increase (exception: group 2 with preMRC score 2). No significant differences between men and women were observed (deltaMRC: -0.6 vs. -0.7, deltaSWT: 66.7 vs. 56.0 m, deltaSWT%: 63.7 vs. 58.1%, p > 0.05, respectively). Patients with severe dyspnea did not benefit less from PR. Gender did not influence PR outcome in this study.

  18. Differential diagnosis of sclerosing cholangitis with autoimmune pancreatitis and periductal infiltrating cancer in the common bile duct at dynamic CT, endoscopic retrograde cholangiography and MR cholangiography.

    PubMed

    Kim, Jin Hee; Byun, Jae Ho; Lee, So Jung; Park, Seong Ho; Kim, Hyoung Jung; Lee, Seung Soo; Kim, Myung-Hwan; Kim, Jihun; Lee, Moon-Gyu

    2012-11-01

    To compare findings at dynamic computed tomography (CT), endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiography (MRC) in patients with sclerosing cholangitis with autoimmune pancreatitis (SC-AIP) and periductal infiltrating cancer in the common bile duct (CBD), and to evaluate the diagnostic performance of ERC and MRC in differentiating between the two diseases. Bile duct changes at dynamic CT, ERC and MRC were compared in 58 patients with SC-AIP and CBD involvement and 93 patients with periductal infiltrating CBD cancer. Two radiologists rated their confidence in differentiating between the two diseases and the diagnostic performances of ERC and MRC were compared. At CT, SC-AIP was more frequently associated with intrapancreatic CBD involvement, thinner CBD walls, concentric wall thickening, smooth outer margins, and lower degrees of upstream ductal dilatation and contrast enhancement (P ≤ 0.05) than CBD cancer. At ERC and MRC, SC-AIP was more frequently associated with smooth margins, gradual and symmetric narrowing, multifocal involvement and hourglass appearance (P ≤ 0.027) than CBD cancer. MRC showed good diagnostic performance comparable to ERC. Dynamic CT, ERC and MRC can be helpful in distinguishing SC-AIP from periductal infiltrating CBD cancer. MRC may be a useful diagnostic alternative to ERC in differentiating between the two diseases. • SC-AIP often mimics periductal infiltrating ductal cancer. • Imaging findings of SC-AIP and periductal infiltrating CBD cancer can be similar. • Dynamic CT, ERC and MRC help differentiate between these two diseases. • MRC may be a useful diagnostic alternative to ERC.

  19. Use of Medical Reserve Corps Volunteers in a Hospital-based Disaster Exercise.

    PubMed

    Gist, Ramon; Daniel, Pia; Grock, Andrew; Lin, Chou-Jui; Bryant, Clarence; Kohlhoff, Stephan; Roblin, Patricia; Arquilla, Bonnie

    2016-06-01

    Introduction The Medical Reserve Corps (MRC) is a national network of community-based volunteer groups created in 2002 by the Office of the United States Surgeon General (Rockville, Maryland USA) to augment the nation's ability to respond to medical and public health emergencies. However, there is little evidence-based literature available to guide hospitals on the optimal use of medical volunteers and hesitancy on the part of hospitals to use them. Hypothesis/Problem This study sought to determine how MRC volunteers can be used in hospital-based disasters through their participation in a full-scale exercise. A full-scale exercise was designed as a "Disaster Olympics," in which the Emergency Medicine residents were divided into teams tasked with completing one of the following five challenges: victim decontamination, mass casualty/decontamination tent assembly, patient triage and registration during a disaster, point of distribution (POD) site set-up and operation, and infection control management. A surge of patients potentially exposed to avian influenza was the scenario created for the latter three challenges. Some MRC volunteers were assigned clinical roles. These roles included serving as members of the suit support team for victim decontamination, distributing medications at the POD, and managing infection control. Other MRC volunteers functioned as "victim evaluators," who portrayed the potential avian influenza victims while simultaneously evaluating various aspects of the disaster response. The MRC volunteers provided feedback on their experience and evaluators provided feedback on the performance of the MRC volunteers using evaluation tools. Twenty-eight (90%) MRC volunteers reported that they worked well with the residents and hospital staff, felt the exercise was useful, and were assigned clearly defined roles. However, only 21 (67%) reported that their qualifications were assessed prior to role assignment. For those MRC members who functioned as

  20. The route of passive chloride movement across amphibian skin: localization and regulatory mechanisms.

    PubMed

    Nagel, Wolfram; Somieski, Petra; Katz, Uri

    2002-11-13

    Transepithelial Cl(-) conductance (G(Cl)) in amphibian skin can be activated in several species by serosa positive potentials. Mitochondria-rich cells (MRC) or tight junctions (TJ) between the epithelial cells are possible sites for this pathway. The properties and the techniques used to investigate this pathway are reviewed in the present paper. In situ techniques are preferable, since specific properties of the MRC are apparently not maintained in isolated cells. Volume measurements and electronprobe microanalysis of intracellular ions suggest the localization of voltage-activated G(Cl) to MRC. G(Cl) correlates poorly with the density of MRC. The vibrating voltage probe allows quantitative correlation of the local Cl(-) current through morphologically identified structures and the transepithelial Cl(-) current. Our analysis shows that 80% of the voltage-activated Cl(-) current is accounted for by current through MRC or their immediate vicinity. The activation patterns of this current and the inhibition by the alpha(1)-adrenergic agonist, epinephrine, conform to those of the transepithelial current. However, less than 20% of the MRC are active at a certain moment and the activity is spontaneously variable with time. The molecular nature of this pathway, physiological control mechanisms and their relation to the temporal activity of MRC remain to be studied.

  1. Development of model reference adaptive control theory for electric power plant control applications

    SciTech Connect

    Mabius, L.E.

    1982-09-15

    The scope of this effort includes the theoretical development of a multi-input, multi-output (MIMO) Model Reference Control (MRC) algorithm, (i.e., model following control law), Model Reference Adaptive Control (MRAC) algorithm and the formulation of a nonlinear model of a typical electric power plant. Previous single-input, single-output MRAC algorithm designs have been generalized to MIMO MRAC designs using the MIMO MRC algorithm. This MRC algorithm, which has been developed using Command Generator Tracker methodologies, represents the steady state behavior (in the adaptive sense) of the MRAC algorithm. The MRC algorithm is a fundamental component in the MRAC design and stability analysis. An enhanced MRC algorithm, which has been developed for systems with more controls than regulated outputs, alleviates the MRC stability constraint of stable plant transmission zeroes. The nonlinear power plant model is based on the Cromby model with the addition of a governor valve management algorithm, turbine dynamics and turbine interactions with extraction flows. An application of the MRC algorithm to a linearization of this model demonstrates its applicability to power plant systems. In particular, the generated power changes at 7% per minute while throttle pressure and temperature, reheat temperature and drum level are held constant with a reasonable level of control. The enhanced algorithm reduces significantly control fluctuations without modifying the output response.

  2. Confident diagnosis of bronchobiliary fistula using contrast-enhanced magnetic resonance cholangiography.

    PubMed

    Karabulut, Nevzat; Cakmak, Vefa; Kiter, Göksel

    2010-01-01

    We report the utility of contrast-enhanced magnetic resonance cholangiography (MRC) using gadoxetic acid (Gd-EOB-DTPA) in the diagnosis of bronchobiliary fistula associated with liver hydatid cyst. Contrast-enhanced MRC clearly delineated the leakage of contrast agent from the biliary duct and its communication with the bronchial tree. Providing functional information about physiologic or pathologic biliary flow in addition to the display of biliary anatomy, contrast-enhanced MRC stands as a robust technique in confidently detecting bronchobiliary fistula and bile leaks.

  3. Mental time travel ability and the Mental Reinstatement of Context for crime witnesses.

    PubMed

    Smith-Spark, James H; Bartimus, Joshua; Wilcock, Rachel

    2017-02-01

    Mental time travel ability marks how well the phenomenological aspects of events are mentally re-experienced during recall. The Cognitive Interview (CI) elicits eyewitness information. One of its techniques, Mental Reinstatement of Context (MRC), asks eyewitnesses to reinstate the incident's context mentally before recall. Fifty-six participants watched a simulated crime video. Self-report measures were then taken to estimate general mental time travel ability. Participants were questioned subsequently about the video. Eyewitness performance under MRC was compared with the CI's Report Everything (RE) technique, wherein eyewitnesses recall everything they can but with no invitation to mentally reinstate the context. There was no effect of interview condition on accuracy of recall; however, general mental time travel ability was positively associated with the amount of correct and incorrect information produced under MRC, but not RE, conditions. This is the first empirical demonstration that MRC instructions engage the mental time travel capacities they purport to.

  4. Building for the future

    PubMed Central

    2013-01-01

    As the staff of the MRC Laboratory of Molecular Biology settle into their new building in Cambridge, its director Hugh Pelham explains the challenges of living up to its prestigious past. PMID:23741620

  5. 78 FR 17763 - Housatonic Railroad Company, Inc., Maybrook Railroad Company, and Housatonic Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... Surface Transportation Board Housatonic Railroad Company, Inc., Maybrook Railroad Company, and Housatonic Transportation Company--Intra-Corporate Family Transaction Exemption Housatonic Railroad Company, Inc. (HRRC), Maybrook Railroad Company (MRC), and Housatonic Transportation Company (HTC) (collectively,...

  6. Receive Diversity Combining Techniques for SC-FDMA-Based Cooperative Relays

    NASA Astrophysics Data System (ADS)

    Woo, Kyung-Soo; Kim, Yeong-Jun; Yoo, Hyun-Il; Kim, Jaekwon; Yun, Sangboh; Cho, Yong-Soo

    In this letter, two receive diversity combining techniques are proposed for cooperative relay systems based on single-carrier frequency division multiple access (SC-FDMA) when relay station (RS) transmits the received signals from multiple mobile stations (MSs) together using one large size discrete Fourier transform (DFT). A simplified-MRC (S-MRC) technique performs diversity combining in the time-domain by using the estimated channel weights and initial estimates obtained by the SC-FDMA signal detector. An interference rejection-MRC (IR-MRC) technique performs diversity combining in the frequency-domain by adjusting the DFT spreading size at the receiver. It is shown by computer simulation that the proposed receive combining techniques achieve a significant diversity gain over the conventional techniques.

  7. Outage Performance and Average Symbol Error Rate of M-QAM for Maximum Ratio Combining with Multiple Interferers

    NASA Astrophysics Data System (ADS)

    Ahn, Kyung Seung

    In this paper, we investigate the performance of maximum ratio combining (MRC) in the presence of multiple cochannel interferences over a flat Rayleigh fading channel. Closed-form expressions of signal-to-interference-plus-noise ratio (SINK), outage probability, and average symbol error rate (SER) of quadrature amplitude modulation (QAM) with Mary signaling are obtained for unequal-power interference-to-noise ratio (INR). We also provide an upper-bound for the average SER using moment generating function (MGF) of the SINR. Moreover, we quantify the array gain loss between pure MRC (MRC system in the absence of CCI) and MRC system in the presence of CCI. Finally, we verify our analytical results by numerical simulations.

  8. 78 FR 59994 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... Change to Revise OCC By-Laws and Rules to Make Structural Changes to OCC's Membership/Risk Committee...-Laws and Rules to make structural changes to OCC's Membership/Risk Committee (``MRC'') regarding Public...

  9. Evaluation of Laser Stabilization and Imaging Systems for LCLS-II - Oral Presentation

    SciTech Connect

    Barry, Matthew

    2015-08-19

    This presentation covers data collected on two commercial laser stabilization systems, Guidestar-II and MRC, and two optical imaging systems. Additionally, general information about LCLS-II and how to go about continuing-testing is covered.

  10. Discrepancies between modified Medical Research Council dyspnea score and COPD assessment test score in patients with COPD

    PubMed Central

    Rhee, Chin Kook; Kim, Jin Woo; Hwang, Yong Il; Lee, Jin Hwa; Jung, Ki-Suck; Lee, Myung Goo; Yoo, Kwang Ha; Lee, Sang Haak; Shin, Kyeong-Cheol; Yoon, Hyoung Kyu

    2015-01-01

    Background and objective According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score. Methods A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A–D using symptom cutoff points. A κ-coefficient was calculated. Results For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70–0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72–0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43). Conclusion A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A–D. However, a discrepancy remains between the CAT and mMRC scoring systems. PMID:26316736

  11. Preparation of magnetic, macro-reticulated cross-linked chitosan for tetracycline removal from aquatic systems.

    PubMed

    Oladoja, N A; Adelagun, R O A; Ahmad, A L; Unuabonah, E I; Bello, H A

    2014-05-01

    A novel adsorbent, magnetic, macro-reticulated cross-linked chitosan (MRC) was synthesised for the removal of tetracycline (TC) from water using a source of biogenic waste (gastropod shells) as a pore-forming agent. The insertion of crosslinks into the chitosan frame was confirmed by FTIR analysis, while the stability of the MRC was demonstrated via a stability test performed in an acidic solution. The enhanced porosity of the MRC was confirmed by the evaluation of its porosity, a swelling test and the determination of its specific surface area. The time-concentration profile of the sorption of TC onto the MRC demonstrated that equilibrium was attained relatively quickly (120 min), and the data obtained fitted a pseudo second order (r(2)>0.99) kinetic equation better than a pseudo first order or reversible first order kinetic equation. The optimisation of process variables indicated that the sorption of TC onto the MRC was favoured at a low solution pH and that the presence of organics (simulated by the addition of humic acid) negatively impacted the magnitude of TC removal. The area of coverage of TC on the MRC (2.51 m(2)/g) was low compared to the specific surface area of the MRC (47.95 m(2)/g). The value of the calculated energy of adsorption of TC onto the MRC was 100 kJ/mol, which is far above the range of 1-16 kJ/mol stipulated for physical adsorption. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Strategic Vision for Spectrum

    DTIC Science & Technology

    2010-01-01

    phore, and international flag hoists. Ultraviolet This wavelength supports efforts like water purification in remote areas, bioanalysis of soils ...enemy missiles). Currently threat- ened by proposed spectrum reallocation is the Marine Corps’ extensive inventory of MRC -142 radios that operate in...the 1710 to 1850 MHz band. Used by virtually all Marine Corps components, the MRC -142 is the only reliable transmission means for robust data

  13. Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives.

    PubMed

    Sorra, Kumaraswamy; Chang, Chi-Fen; Pusuluri, Srinivas; Mukkanti, Khagga; Laiu, Min-Chiau; Bao, Bo-Ying; Su, Chia-Hao; Chuang, Ta-Hsien

    2012-07-25

    A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

  14. Upward Altitudinal Shifts in Habitat Suitability of Mountain Vipers since the Last Glacial Maximum

    PubMed Central

    Yousefi, Masoud; Ahmadi, Mohsen; Nourani, Elham; Behrooz, Roozbeh; Rajabizadeh, Mehdi; Geniez, Philippe; Kaboli, Mohammad

    2015-01-01

    We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC) that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago) and under two scenarios in the future (to 2070). These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region. PMID:26367126

  15. Upward Altitudinal Shifts in Habitat Suitability of Mountain Vipers since the Last Glacial Maximum.

    PubMed

    Yousefi, Masoud; Ahmadi, Mohsen; Nourani, Elham; Behrooz, Roozbeh; Rajabizadeh, Mehdi; Geniez, Philippe; Kaboli, Mohammad

    2015-01-01

    We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC) that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago) and under two scenarios in the future (to 2070). These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region.

  16. After slow start, project to channel drug company funds to universities builds steam.

    PubMed

    Berkowitz, P

    1996-08-01

    Drug companies appear to have been listening when researchers began complaining about their lack of participation in the MRC/PMAC Health Program, for the 30-month-old project appears to have taken on new life. It is designed to increase collaboration between university and pharmaceutical industry researchers by directing more of the industry's growing investment in Canada through the MRC's peer-review process. By mid-May, program commitments stood at $60 million.

  17. [Evolution in muscle strength in critical patients with invasive mechanical ventilation].

    PubMed

    Via Clavero, G; Sanjuán Naváis, M; Menéndez Albuixech, M; Corral Ansa, L; Martínez Estalella, G; Díaz-Prieto-Huidobro, A

    2013-01-01

    To assess the evolution of muscle strength in critically ill patients with mechanical ventilation (MV) from withdrawal of sedatives to hospital discharge. A cohort study was conducted in two intensive care units in the Hospital Universitari de Bellvitge from November 2011 to March 2012. Consecutive patients with MV > 72h. Dependent outcome: Muscle strength measured with the Medical Research Council (MRC) scale beginning on the first day the patient was able to answer 3 out of 5 simple orders (day 1), every week, at ICU discharge and at hospital discharge or at day 60 Independent outcomes: factors associated with muscle strength loss, ventilator-free days, ICU length of stay and hospital length of stay. The patients were distributed into two groups (MRC< 48, MRC ≥ 48) after the first measurement. Thirty-four patients were assessed. Independent outcomes associated with muscle strength weakness were: days with cardiovascular SOFA >2 (P<.001) and days with costicosteroids (P<.001). Initial MRC in MRC<48 group was 38 (27-43), and 52 (50-54) in MRC ≥ 48. The largest muscle strength gain was obtained the first week (31% versus 52%). A MRC < 48 value was associated with more MV days (P<.007) and a longer ICU stay. (P<.003). The greatest muscle strength gain after withdrawing of the sedatives was achieved in the first week. Muscle strength loss was associated with a cardiovascular SOFA > 2 and costicosteroids. Patients with a MRC < 48 required more days with MV and a longer ICU stay. Copyright © 2013 Elsevier España, S.L. y SEEIUC. All rights reserved.

  18. Mississippi Medical Reserve Corps: Moving Mississippi From Emergency Planning to Response Ready.

    PubMed

    McCormick, Lisa C; Fifolt, Matthew; Mercer, Caroline; Pevear, Jesse; Wilson, Jonathan

    The purpose of this study was to identify factors that might impact a Medical Reserve Corps (MRC) volunteer's decision to respond to an emergency event. The 2 primary goals of this survey were to (1) establish realistic planning assumptions regarding the use of volunteers in health care emergency responses, and (2) determine whether barriers to volunteer participation could be addressed by MRC units to improve volunteer response rates. An anonymous online survey instrument was made available via Qualtrics through a customized URL. For the purpose of distribution, the Mississippi State Department of Health sent an electronic message that included the survey link to all MRC volunteers who were registered with the Mississippi Responder Management System (MRMS) as of September 2014. Approximately 15% of those surveyed indicated they would be available and able to deploy within 24 hours. The most common factors reported in terms of respondent decisions to deploy included risk to personal health (61.2%), length of deployment (58.8%), and the security of the deployment area (55.3%). In addition, 67% of respondents indicated that extended periods of deployment would have a negative financial impact on their lives. Respondents who have had training or previous deployment experience reported having greater knowledge of potential response roles, increased comfort in their ability to respond with the MRC, and increased confidence in responding to differing public health emergencies. Barriers to MRC volunteers being able to deploy should be addressed by each MRC unit. Issues such as risk to personal safety while on deployment, site security, and length of deployment should be considered by planners and those solutions communicated to MRC members during trainings. Emergency plans utilizing MRC volunteers will require significant evaluation to assess the risk of relying on an expected resource that could be severely limited during an actual emergency.

  19. Gallbladder opacification on gadoxetate disodium-enhanced CT scan.

    PubMed

    Karam, Adib R; Scortegagna, Eduardo; Chen, Byron Y; Dupuis, Carolyn S; Coughlin, Dennis D

    2017-04-01

    This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.

  20. Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Ban, Wooho; Lee, Jong Min; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyeon Hui; Rhee, Chin Kook; Moon, Hwa Sik

    2016-01-01

    Purpose To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). Materials and Methods From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. Results In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. Conclusion Dyspnea could be a significant prognostic factor in patients with NSCLC. PMID:27401635

  1. Analysis And Synthesis Of Model Reference Controller For Variable Speed Wind Generators Inertial Support

    NASA Astrophysics Data System (ADS)

    Bećirović, Elvisa; Osmić, Jakub; Kušljugić, Mirza; Perić, Nedjeljko

    2015-01-01

    Model Reference Controller (MRC) for contribution of Variable Speed Wind Generators (VSWG) in inertial response of Electrical Power System (EPS) is presented and analyzed in this paper. MRC is synthesized based on a model of Generating Unit With non-Reheat Steam Turbine (GUNRST) thus enabling VSWG to emulate GUNRST response during the initial stage of dynamic frequency response ie inertial phase. Very important property of conventional steam generating units is that its contribution to inertial phase response is independent from the initial generating power. By using MRC in VSWG it is accomplished that in most common wind speed region (3-12 m/s) VSWG inertial support is almost independent from wind speed. Since in most EPSs VSWG replaces conventional steam generators, application of MRC algorithm provides that the characteristics of EPS in terms of inertial response are preserved, regardless of the growing trend of introducing VSWG. Evaluation analysis of the proposed MRC is performed on modified nine bus power system when VSWG with MRC is connected to one of the power system buses.

  2. Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation

    PubMed Central

    Baker, Charli D.; Basu Ball, Writoban; Pryce, Erin N.; Gohil, Vishal M.

    2016-01-01

    Mitochondrial membrane phospholipid composition affects mitochondrial function by influencing the assembly of the mitochondrial respiratory chain (MRC) complexes into supercomplexes. For example, the loss of cardiolipin (CL), a signature non–bilayer-forming phospholipid of mitochondria, results in disruption of MRC supercomplexes. However, the functions of the most abundant mitochondrial phospholipids, bilayer-forming phosphatidylcholine (PC) and non–bilayer-forming phosphatidylethanolamine (PE), are not clearly defined. Using yeast mutants of PE and PC biosynthetic pathways, we show a specific requirement for mitochondrial PE in MRC complex III and IV activities but not for their formation, whereas loss of PC does not affect MRC function or formation. Unlike CL, mitochondrial PE or PC is not required for MRC supercomplex formation, emphasizing the specific requirement of CL in supercomplex assembly. Of interest, PE biosynthesized in the endoplasmic reticulum (ER) can functionally substitute for the lack of mitochondrial PE biosynthesis, suggesting the existence of PE transport pathway from ER to mitochondria. To understand the mechanism of PE transport, we disrupted ER–mitochondrial contact sites formed by the ERMES complex and found that, although not essential for PE transport, ERMES facilitates the efficient rescue of mitochondrial PE deficiency. Our work highlights specific roles of non–bilayer-forming phospholipids in MRC function and formation. PMID:27226479

  3. Modified Medical Research Council Dyspnea Scale in GOLD Classification Better Reflects Physical Activities of Daily Living.

    PubMed

    Munari, Anelise B; Gulart, Aline A; Dos Santos, Karoliny; Venâncio, Raysa S; Karloh, Manuela; Mayer, Anamaria F

    2017-09-05

    In multidimensional Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, the choice of the symptom assessment instrument (modified Medical Research Council dyspnea scale [mMRC] or COPD assessment test [CAT]) can lead to a different distribution of patients in each quadrant. Considering that physical activities of daily living (PADL) is an important functional outcome in COPD, the objective of this study was to determine which symptom assessment instrument is more strongly associated with and differentiates better the PADL of patients with COPD. The study included 115 subjects with COPD (GOLD 2-4), who were submitted to spirometry, the mMRC, the CAT, and monitoring of PADL (triaxial accelerometer). Subjects were divided into 2 groups using the cutoffs proposed by the multidimensional GOLD classification: mMRC <2and ≥2 and CAT <10 and ≥10. Both mMRC and CAT reflected the PADL of COPD subjects. Subjects with mMRC <2 and CAT <10 spent less time in physical activities <1.5 metabolic equivalents of task (METs) (mean of the difference [95% CI] = -62.9 [-94.4 to -31.4], P < .001 vs -71.0 [-116 to -25.9], P = .002) and had a higher number of steps (3,076 [1,999-4,153], P < .001 vs 2,688 [1,042-4,333], P = .002) than subjects with mMRC >2 and CAT >10, respectively. Physical activities ≥3 METs differed only between mMRC <2 and mMRC ≥2 (39.2 [18.8-59.6], P < .001). Furthermore, only the mMRC was able to predict the PADL alone (time active, r(2) = 0.16; time sedentary, r(2) = 0.12; time ≥ 3 METs, r(2) = 0.12) and associated with lung function (number of steps, r(2) = 0.35; walking time, r(2) = 0.37; time <1.5 METs, r(2) = 0.25). The mMRC should be adopted as the classification criterion for symptom assessment in the GOLD ABCD system when focusing on PADL. Copyright © 2017 by Daedalus Enterprises.

  4. Comparison of the predictability of refractive cylinder correction by laser in situ keratomileusis in eyes with low or high ocular residual astigmatism.

    PubMed

    Archer, Timothy J; Reinstein, Dan Z; Piñero, David P; Gobbe, Marine; Carp, Glenn I

    2015-07-01

    To compare the manifest refractive cylinder (MRC) predictability of myopic astigmatism laser in situ keratomileusis (LASIK) between eyes with low and high ocular residual astigmatism (ORA). London Vision Clinic, London, United Kingdom. Retrospective case study. The ORA was considered the vector difference between the MRC and the corneal astigmatism. The index of success (IoS), difference vector ÷ MRC, was analyzed for different groups as follows: stage 1, low ORA (ORA ÷ MRC <1), high ORA (ORA ÷ MRC ≥1); stage 2, low ORA group reduced to match the high ORA group for MRC; stage 3, grouped by ORA magnitude with low ORA (<0.50 diopters [D]), mid ORA (0.50 to 1.24 D), and high ORA (≥1.25 D); stage 4, high ORA group subdivided into low (<0.75 D) and high (≥0.75 D) corneal astigmatism. For stage 1, the mean preoperative MRC and mean IoS were -1.32 D ± 0.65 (SD) (range -0.55 to -3.77 D) and 0.27, respectively, for low ORA and -0.79 ± 0.20 D (range -0.56 to -2.05 D) and 0.37, respectively, for high ORA. For stage 2, the mean IoS increased to 0.32 for low ORA. For stage 3, the mean IoS was 0.28, 0.29, and 0.31 for low ORA, mid ORA, and high ORA, respectively. For stage 4, the mean IoS was 0.20 for high ORA/low corneal astigmatism and 0.35 for high ORA/high corneal astigmatism. The MRC predictability was slightly worse in eyes with high ORA when grouped by the ORA ÷ MRC. Matching for the MRC and grouping by ORA magnitude resulted in similar predictability; however, eyes with high ORA and high corneal astigmatism were less predictable. Dr. Reinstein is a consultant to Carl Zeiss Meditec AG, has a proprietary interest in the Artemis technology (Arcscan, Inc.), and is an author of patents related to very-high-frequency digital ultrasound administered by the Center for Technology Licensing at Cornell University, Ithaca, New York, USA. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS

  5. Dissection of Two Complex Clusters of Resistance Genes in Lettuce (Lactuca sativa).

    PubMed

    Christopoulou, Marilena; McHale, Leah K; Kozik, Alex; Reyes-Chin Wo, Sebastian; Wroblewski, Tadeusz; Michelmore, Richard W

    2015-07-01

    Of the over 50 phenotypic resistance genes mapped in lettuce, 25 colocalize to three major resistance clusters (MRC) on chromosomes 1, 2, and 4. Similarly, the majority of candidate resistance genes encoding nucleotide binding-leucine rich repeat (NLR) proteins genetically colocalize with phenotypic resistance loci. MRC1 and MRC4 span over 66 and 63 Mb containing 84 and 21 NLR-encoding genes, respectively, as well as 765 and 627 genes that are not related to NLR genes. Forward and reverse genetic approaches were applied to dissect MRC1 and MRC4. Transgenic lines exhibiting silencing were selected using silencing of β-glucuronidase as a reporter. Silencing of two of five NLR-encoding gene families resulted in abrogation of nine of 14 tested resistance phenotypes mapping to these two regions. At MRC1, members of the coiled coil-NLR-encoding RGC1 gene family were implicated in host and nonhost resistance through requirement for Dm5/8- and Dm45-mediated resistance to downy mildew caused by Bremia lactucae as well as the hypersensitive response to effectors AvrB, AvrRpm1, and AvrRpt2 of the nonpathogen Pseudomonas syringae. At MRC4, RGC12 family members, which encode toll interleukin receptor-NLR proteins, were implicated in Dm4-, Dm7-, Dm11-, and Dm44-mediated resistance to B. lactucae. Lesions were identified in the sequence of a candidate gene within dm7 loss-of-resistance mutant lines, confirming that RGC12G confers Dm7.

  6. MR cholangiography in potential liver donors: quantitative and qualitative improvement with administration of an oral effervescent agent.

    PubMed

    Kwon, Heon-Ju; Kim, Kyoung Won; Choi, Sang Hyun; Jung, Jin-Hee; Kim, So Yeon; Kim, Se-Young; Lee, Jeongjin; Jung, Dong-Hwan; Ha, Tae-Yong; Song, Gi-Won; Lee, Sung-Gyu

    2017-03-23

    To determine whether an oral effervescent agent improves magnetic resonance cholangiography (MRC) images, both qualitatively and quantitatively, in potential live liver donors. This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Seventy potential liver donors underwent 2D MRC before and after administration of an oral effervescent agent. One radiologist measured relative contrast ratio (rC) and relative signal intensity (rS) for right and left intrahepatic ducts (RHD and LHD), and common hepatic duct (CHD). After assessment of overall image quality, two other radiologists independently scored visualization of five ductal segments (RHD, LHD, CHD, cystic, and common bile duct) and assessed the preferred image set. In consensus, they assessed the biliary anatomy. The data were analyzed using a paired t-test, Wilcoxon's signed-rank test, and chi-square test. Both rC and rS of RHD and CHD were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.03). The overall image quality grades and biliary visualization scores for all five duct segments were significantly higher on MRC images after administration of an oral effervescent agent than before (P < 0.0001). Between these images, both readers more often preferred MRC images with an effervescent agent rather than those without this agent (reader 1: 56/70, 80.0%; reader 2: 55/70, 78.6%; P = 0.0003). The readers correctly assessed second-order biliary tract anatomy in two more subjects on MRC after administration of an effervescent agent than before. Oral administration of an effervescent agent improves MRC images, both qualitatively and quantitatively, in live liver donors. 3 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  7. Diagnostic accuracy of cone-beam CT compared with panoramic images in predicting retromolar canal during extraction of impacted mandibular third molars

    PubMed Central

    Sisman, Yıldıray; Payveren-Arıkan, Mehtap; Sahman, Halil

    2015-01-01

    Objectives: The clinical significance of the existence of a retromolar canal and of its neurovascular content is not yet clear.The aim of the present study was to assess the visibility, diameter and course of the mandibular retromolarcanal (MRC) using cone beam computed tomography (CBCT) scan -had been taken for pre-operative radiographic evaluation of impacted mandibular third molars- compared to panoramic radiographs. Study Design: Subjects eligible for study enrollment were those who underwent preoperative CBCT scan for the extraction of impactedmandibular third molars were determined to be extremely close to the mandibular canal on panoramic radiographs. Radiographs were screened for the presence and course of retromolar canals, and linear measurements. Results: 947hemimandibles in 632 patients were examined.A total of 253 MRCs (144 left, 109 right) were detected with CBCT images (26.7%). Only 29 of these canals were also seen on the corresponding panoramic radiographs. Most MRCs had a vertical course (type VI, 28.46%), followed by slightly curved (type I, 26.09%). The visibility of the MRC on the OPGs, according to the increase in the diameter, was not statistically significant for both sides (p>.05).Statistically difference were found for the width at the point of origin from the mandibular canal (p: .037), the mean distance from the MRC to the second molar (p: .042) and height of MRC when compared the gender. Conclusions: The findings suggest that the MRC isn’t a rare anatomical structure. This study therefore clearly establishes the incidence and importance of the MRC. The detection of the presence of the MRC using CBCT may be crucial for extraction of mandibular third molars. Key words:Accessory innervation, cone beam computed tomography, mandibular anatomy, panoramic radiographs, retromolar canal, retromolar foramen. PMID:25475767

  8. Forecasting the Marine Corps’ Enlisted Classification Plan: Assessment of An Alternative Model

    DTIC Science & Technology

    2012-03-01

    8217·"’ - rt01 ’·"’ ’"" ,..,. .... "" .... - rvO & ~. . 1.116 .... "’’ .... ,..., -+-N111 ,.., ~,,., Ull ..,. ,..., l,,ll - rvw ,.,, ""’ 1.914 1.$1$ 1

  9. Optimization of mask manufacturing rule check constraint for model based assist feature generation

    NASA Astrophysics Data System (ADS)

    Shim, Seongbo; Kim, Young-chang; Chun, Yong-jin; Lee, Seong-Woo; Lee, Suk-joo; Choi, Seong-woon; Han, Woo-sung; Chang, Seong-hoon; Yoon, Seok-chan; Kim, Hee-bom; Ki, Won-tai; Woo, Sang-gyun; Cho, Han-gu

    2008-11-01

    SRAF (sub-resolution assist feature) generation technology has been a popular resolution enhancement technique in photo-lithography past sub-65nm node. It helps to increase the process window, and these are some times called ILT(inverse lithography technology). Also, many studies have been presented on how to determine the best positions of SRAFs, and optimize its size. According to these reports, the generation of SRAF can be formulated as a constrained optimization problem. The constraints are the side lobe suppression and allowable minimum feature size or MRC (mask manufacturing rule check). As we know, bigger SRAF gives better contribution to main feature but susceptible to SRAF side lobe issue. Thus, we finally have no choice but to trade-off the advantages of the ideally optimized mask that contains very complicated SRAF patterns to the layout that has been MRC imposed applied to it. The above dilemma can be resolved by simultaneously using lower dose (high threshold) and cleaning up by smaller MRC. This solution makes the room between threshold (side lobe limitation) and MRC constraint (minimum feature limitation) wider. In order to use smaller MRC restriction without considering the mask writing and inspection issue, it is also appropriate to identify the exact mask writing limitation and find the smart mask constraints that well reflect the mask manufacturability and the e-beam lithography characteristics. In this article, we discuss two main topics on mask optimizations with SRAF. The first topic is on the experimental work to find what behavior of the mask writing ability is in term of several MRC parameters, and we propose more effective MRC constraint for aggressive generation of SRAF. The next topic is on finding the optimum MRC condition in practical case, 3X nm node DRAM contact layer. In fact, it is not easy to encompass the mask writing capability for very complicate real SRAF pattern by using the current MRC constraint based on the only width and

  10. MIDWESTERN REGIONAL CENTER OF THE DOE NATIONAL INSTITUTE FOR CLIMATIC CHANGE RESEARCH

    SciTech Connect

    Burton, Andrew J.

    2014-02-28

    The goal of NICCR (National Institute for Climatic Change Research) was to mobilize university researchers, from all regions of the country, in support of the climatic change research objectives of DOE/BER. The NICCR Midwestern Regional Center (MRC) supported work in the following states: North Dakota, South Dakota, Nebraska, Kansas, Oklahoma, Minnesota, Iowa, Missouri, Wisconsin, Illinois, Michigan, Indiana, and Ohio. The MRC of NICCR was able to support nearly $8 million in climatic change research, including $6,671,303 for twenty projects solicited and selected by the MRC over five requests for proposals (RFPs) and $1,051,666 for the final year of ten projects from the discontinued DOE NIGEC (National Institute for Global Environmental Change) program. The projects selected and funded by the MRC resulted in 135 peer-reviewed publications and supported the training of 25 PhD students and 23 Masters students. Another 36 publications were generated by the final year of continuing NIGEC projects supported by the MRC. The projects funded by the MRC used a variety of approaches to answer questions relevant to the DOE’s climate change research program. These included experiments that manipulated temperature, moisture and other global change factors; studies that sought to understand how the distribution of species and ecosystems might change under future climates; studies that used measurements and modeling to examine current ecosystem fluxes of energy and mass and those that would exist under future conditions; and studies that synthesized existing data sets to improve our understanding of the effects of climatic change on terrestrial ecosystems. In all of these efforts, the MRC specifically sought to identify and quantify responses of terrestrial ecosystems that were not well understood or not well modeled by current efforts. The MRC also sought to better understand and model important feedbacks between terrestrial ecosystems, atmospheric chemistry, and regional

  11. Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors

    PubMed Central

    Kim, Do Young; Vallejo, Johana; Rho, Jong M

    2010-01-01

    Abstract Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation. PMID:20374433

  12. The maximum reservoir capacity of soils for persistent organic pollutants: implications for global cycling.

    PubMed

    Dalla Valle, M; Jurado, E; Dachs, J; Sweetman, A J; Jones, K C

    2005-03-01

    The concept of maximum reservoir capacity (MRC), the ratio of the capacities of the surface soil and of the atmospheric mixed layer (AML) to hold chemical under equilibrium conditions, is applied to selected persistent organic pollutants (POPs) in the surface 'skin' (1 mm) of soils. MRC is calculated as a function of soil organic matter (SOM) content and temperature-dependent K(OA) and mapped globally for selected PCB congeners (PCB-28; -153; -180) and HCB, to identify regions with a higher tendency to retain POPs. It is shown to vary over many orders of magnitude, between compounds, locations and time (seasonally/diurnally). The MRC approach emphasises the very large capacity of soils as a storage compartment for POPs. The theoretical MRC concept is compared to reality and its implications for the global cycling of POPs are discussed. Sharp gradients in soil MRC can exist in mountainous areas and between the land and ocean. Exchanges between oceans and land masses via the atmosphere is likely to be an important driver to the global cycling of these compounds, and net ocean-land transfers could occur in some areas.

  13. An Improved Technique for dry Soil Moisture Release Curves to Determine Soil Mineralogical and Physical Properties

    NASA Astrophysics Data System (ADS)

    Campbell, G. S.; Campbell, C. S.; Cobos, D. R.

    2008-12-01

    Soil moisture release curves (MRC) or moisture sorption isotherms, which relate the amount of water in soil to its water potential or water activity, have many applications in soil physics and geotechnical engineering including determining soil water flow, specific surface area, swelling potential, and clay mineralogy and activity. Although research showing MRC for various soils dates back more than 50 years, limitations with the measurement technique have made developing MRC time consuming and inaccurate, especially in dry soils. Recently, an instrument was developed to create moisture sorption isotherms for various food and pharmaceutical products. The objective of this research was to investigate its use in soils for obtaining MRC in dry soils simply and accurately. Several different soil types were tested in the instrument from pure sand to bentonite and smectite clays. From the MRC of these soils, we were able to develop good correlations between actual and derived clay activity, surface area, and swelling potential. In addition, we were able to see hysteresis in dry soil water uptake for all soils, including sand. According to our tests, this new instrument will provide a powerful tool to investigate several soil physical properties simply and accurately.

  14. Correlation Between Bile Reflux Gastritis and Biliary Excreted Contrast Media in the Stomach.

    PubMed

    Hyun, Jong Jin; Yeom, Suk Keu; Shim, Euddeum; Cha, Jaehyung; Choi, Inyoung; Lee, Seung Hwa; Chung, Hwan Hoon; Cha, Sang Hoon; Lee, Chang Hee

    This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis. Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test. Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension. Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

  15. Coordinating research and practice: challenges testing messages to increase medical reserve corps participation in local health department activities.

    PubMed

    Klaiman, Tamar; Higdon, Melissa; Galarce, Ezequiel

    2013-04-01

    Local health departments (LHDs) increasingly depend on volunteers, often Medical Reserve Corps (MRC) volunteers, to assist with a variety of functions. While LHDs have extensive lists of volunteers, only about 10 % are actively involved in LHD activities. Psychological literature has shown that well-designed messages can motivate behavior among individuals. Key to this theory is the concept of "framing," defined as the influence the characterization of an issue can have on its understanding. Research has been conducted on how to frame and disseminate both political and public health messages to alter individual behavior. We aimed to design and test appropriate evidence-based messages to increase volunteer participation rates in LHD flu clinics. After inviting over 900 MRC units to participate during the 2011-2012 influenza season, five were able to collect and report data to the research team. Using a randomized trial design, we tested messages among the five participating MRC units consisting of a total of 2,020 volunteers. Chi Square analysis showed no difference in attendance between those who received either of the test messages versus the control message (p = .305). Our small sample size of MRC units likely biased our sample and reduced the external validity of our study. Our experience in conducting research with MRC coordinators and volunteers highlights the challenges of conducting research with practitioners who lack the time, infrastructure and resources necessary to work with researchers. There is a strong need for more supportive infrastructure for conducting research with practitioners.

  16. Frequent p16 CpG island hypermethylation in primary remnant gastric cancer suggesting an independent carcinogenic pathway.

    PubMed

    Mino, Aya; Onoda, Naoyoshi; Yashiro, Masakazu; Aya, Makoto; Fujiwara, Ichiro; Kubo, Naoshi; Sawada, Tetsuji; Ohira, Masaichi; Kato, Yasuyuki; Hirakawa, Kosei

    2006-03-01

    Cancer found in the post-operative remnant stomach includes both newly developed cancer after surgery for benign-disease (PRC) and metachronous multiple cancer (MRC). Differences in the carcinogenic pathway between PRC and MRC have been suspected from clinical studies. However, no study has demonstrated the difference in molecular alteration between these diseases. P16 is inactivated predominantly by epigenetic change, rather than genetic alteration. We analyzed the methylation status and protein expression of the p16 gene in cancers of the remnant stomach. Eleven lesions of PRC, 24 lesions of MRC and corresponding non-cancerous tissue, as well as 13 primary gastric cancer (PC) lesions were examined. DNA was extracted by the micro-dissection method from paraffin-embedded surgical specimens. The methylation status of the promoter CpG island of the p16 gene was examined by using a methylation-specific polymerase chain reaction technique. To detect protein expression, immunohistochemical staining was employed. p16 promoter hypermethylation was observed more often in remnant gastric cancer than in PC. A significantly more frequent hypermethylation in the p16 gene was found in PRC (64%) than in MRC (21%) or PC (23%). Moreover, a significant correlation was found between p16 promoter hypermethylation and diminishment of protein expression in cancers of the remnant stomach. Silencing of the p16 gene by methylation of its promoter CpG island was suggested as a unique molecular mechanism in the carcinogenesis of PRC compared with MRC or PC.

  17. Leaf cuticular wax amount and crystal morphology regulate post-harvest water loss in mulberry (Morus species).

    PubMed

    Mamrutha, H M; Mogili, T; Jhansi Lakshmi, K; Rama, N; Kosma, Dylan; Udaya Kumar, M; Jenks, Matthew A; Nataraja, Karaba N

    2010-08-01

    Mulberry leaves are the sole source of food for silkworms (Bombyx mori), and moisture content of the detached leaves fed to silkworms determines silkworm growth and cocoon yield. Since leaf dehydration in commercial sericulture is a serious problem, development of new methods that minimize post-harvest water loss are greatly needed. In the present study, variability in moisture retention capacity (MRC, measured as leaf relative water content after one to 5 h of air-drying) was examined by screening 290 diverse mulberry accessions and the relationship between MRC and leaf surface (cuticular) wax amount was determined. Leaf MRC varied significantly among accessions, and was found to correlate strongly with leaf wax amount. Scanning electron microscopic analysis indicated that leaves having crystalline surface waxes of increased facet size and density were associated with high MRC accessions. Leaf MRC at 5 h after harvest was not related to other parameters such as specific leaf weight, and stomatal frequency and index. This study suggests that mulberry accessions having elevated leaf surface wax amount and crystal size and density exhibit reduced leaf post-harvest water loss, and could provide the foundation for selective breeding of improved cultivars.

  18. Anti-irritative effect of methylrosaniline chloride (Gentian violet).

    PubMed

    Gloor, M; Wolnicki, D

    2001-01-01

    There are no published studies of the effect of methylrosaniline chloride (MRC) on inflammation when used at the concentration recommended in the New German Formulary. A tissue-damaging effect has been described in animal studies and at higher concentrations in humans. To determine whether 0.5% MRC increases or reduces skin damage in irritative dermatitis. The study was carried out on the sodium lauryl sulfate (SLS) skin irritation model in 18 healthy volunteers. The impact of intermittent treatment with 0.5% MRC or drug-free vehicle on three SLS exposure effects was determined: reduction of stratum corneum water content (corneometry), increase in subpapillary blood flow (laser Doppler method) and barrier damage (transepidermal water loss). MRC produced significant reductions in all three SLS exposure effects. Treatment of irritative dermatitis with 0.5% MRC is expected to produce a high clinical efficacy not only because of the compound's established antimicrobial activity, but also because of its anti-irritative effect. Copyright 2001 S. Karger AG, Basel

  19. Prescriptions for medical research. I--Management within the Medical Research Council.

    PubMed Central

    Gillett, R; Harrow, J

    1993-01-01

    In their submission to the government in advance of the white paper on science policy in the United Kingdom the Medical Research Council commends the MRC's own approach to managing directly funded research. But a series of semi-structured interviews with the directors of some of the MRC's units suggests a gap between the MRC's model of managed research and the reality. Although such units are theoretically managed from MRC head office (and units are charged an overhead for this), in practice each unit runs its own affairs. Between major reviews average contact time with the head office contact person is seven hours a year. The first paper argues that a purchaser-provider split would recognise the benefits of decentralisation and allow units to bid for research funds from several sources, the successful ones guaranteeing their survival through a rolling series of research programmes. The second paper criticises the MRC's cumbersome peer review system. Reliance on outside experts atrophies the scientific skills of head office staff and builds delays into decision making. A purchaser-provider model would allow the head office scientific staff to act like commercial research and development managers, commissioning research, and using the outcome, rather than peer review, as a criterion for continued funding. PMID:8324441

  20. Detection of human cytomegalovirus in clinical specimens by centrifugation culture with a nonhuman cell line.

    PubMed Central

    Gleaves, C A; Hursh, D A; Meyers, J D

    1992-01-01

    The sensitivities of MRC-5 and mink lung (ML) cells in centrifugation culture were compared simultaneously for the detection of cytomegalovirus (CMV) IE antigen (immediate-early antigen) from clinical specimens. Of 413 samples assayed, 51 (12%) were positive for CMV by both centrifugation and standard cell culture. At 20 h postinoculation (p.i.), 46 of 51 (90.2%) CMV-positive specimens were detected in ML cells. At 40 h p.i., 50 of 51 (98.0%) CMV-positive specimens were detected in ML cells, compared with 48 of 51 (94.0%) in MRC-5 cells. There was no significant difference in the detection of CMV in either cell line by centrifugation culture. However, in 19 of 23 positive samples that had countable foci at 20 h p.i., there was a 25% increase in the number of positive foci observed for ML cells compared with MRC-5 cells. Less toxicity was also noted for ML cells than for MRC cells, particularly in viral blood specimens. These data suggest that ML cells are comparable to MRC-5 cells for the rapid detection of CMV by centrifugation culture. PMID:1315330

  1. Comparing the level of bystander effect in a couple of tumor and normal cell lines.

    PubMed

    Soleymanifard, Shokouhozaman; Bahreyni, Mohammad T Toossi

    2012-04-01

    Radiation-induced bystander effect refers to radiation responses which occur in non-irradiated cells. The purpose of this study was to compare the level of bystander effect in a couple of tumor and normal cell lines (QU-DB and MRC5). To induce bystander effect, cells were irradiated with 0.5, 2, and 4 Gy of (60)Co gamma rays and their media were transferred to non-irradiated (bystander) cells of the same type. Cells containing micronuclei were counted in bystander subgroups, non-irradiated, and 0.5 Gy irradiated cells. Frequencies of cells containing micronuclei in QU-DB bystander subgroups were higher than in bystander subgroups of MRC5 cells (P < 0.001). The number of micronucleated cells counted in non-irradiated and 0.5 Gy irradiated QU-DB cells was also higher than the corresponding values for MRC5 cells (P < 0.001). Another difference between the two cell lines was that in QU-DB bystander cells, a dose-dependent increase in the number of micronucleated cells was observed as the dose increased, but at all doses the number of micronucleated cells in MRC5 bystander cells was constant. It is concluded that QU-DB cells are more susceptible than MRC5 cells to be affected by bystander effect, and in the two cell lines there is a positive correlation between DNA damages induced directly and those induced due to bystander effect.

  2. Revised minimum reciprocity configuration and actualization methodology of interferometric all-fiber-optic gyroscopes.

    PubMed

    Wang, Xinyue; Wang, Ziyu

    2011-05-01

    We propose a revised minimum reciprocity configuration (MRC) of an interferometric all-fiber-optic gyroscope (all-fiber I-FOG), based on our design of a fused-taper polarization-maintaining fiber coupler. This MRC reduces the insertion loss and production cost of the optical path, yet maintains the principle of reciprocity. Experimental results show that this I-FOG with five optical components exhibits better performance than a conventional I-FOG with six optical components. Using the revised MRC, the angle random walk and the bias instability of an I-FOG are improved from 0.025 deg/√hr to 0.011 deg/√hr, and 0.48 deg/hr to 0.21 deg/hr, respectively.

  3. Response Simulation of a Micro Reinforced Concrete Target Under Ballistic Impact

    NASA Astrophysics Data System (ADS)

    Mohan, V.; Rajasankar, J.; Iyer, N. R.

    2014-05-01

    The response of concrete structures subjected to impact loading has received extensive attention in both civil and military applications. Research on improving the shock resistance of concrete has led to the development of cementitious composites. Micro Reinforced Concrete (MRC), a type of cementitious composite, is a concrete matrix embedded with multilayered steel wire meshes. This paper presents 3D hydrocode simulations of MRC panels subjected to impact under a ballistic range. A finite element model based on Lagrange formulation is used to represent both a 300 mm × 300 mm × 100 mm target with 30 layers of wire mesh and a 5.56 × 45 mm projectile in simulations. Penetration depth and damage patterns of the MRC mesh cement composite panel are numerically compared with those of the field experiment. The results show a relatively good agreement.

  4. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome.

    PubMed

    Kleyweg, R P; van der Meché, F G; Schmitz, P I

    1991-11-01

    In studies of Guillain-Barré syndrome, functional deficit is usually assessed according to a functional scale consisting of several categories. The level of interobserver agreement in this scoring method is not known; furthermore, this method seems to be insensitive when applied to bedridden and artificially ventilated patients. We have developed an additional score (MRC-sumscore), reflecting muscle strength in general. Both scoring methods, tested in Guillain-Barré patients, have an almost perfect interobserver agreement. For the functional score kappa = 0.85, and for the MRC-sumscore r2 = 0.96. The MRC-sumscore is easily assessed and more sensitive than the functional score when patients are bedridden or artificially ventilated.

  5. The Multi-Resolution CLEAN and its application to the short-spacing problem in interferometry

    NASA Astrophysics Data System (ADS)

    Wakker, B. P.; Schwarz, U. J.

    1988-07-01

    A modification of the CLEAN algorithm is described which alleviates the difficulties occurring in CLEAN for extended sources. This is accomplished by appropriately combining the results of a number of conventional CLEAN operations with optimized parameters, each done at a different resolution. This algorithm can properly be called "Multi-Resolution CLEAN" or "MRC". Experiments on model sources show that this deconvolution method works well even when the source is so large that the usual CLEAN becomes impractical. Further, for observations of extended sources, MRC enhances the signal-to-noise ratio, resulting in an easier definition of the area of signal. Moreover, MRC is in principle faster than a standard CLEAN because less δ-functions are needed.

  6. Rapid detection of herpes simplex virus with fluorescein-labeled Helix pomatia lectin.

    PubMed Central

    Slifkin, M; Cumbie, R

    1989-01-01

    The use of fluorescein-conjugated Helix pomatia lectin was shown to be as effective as fluorescein-conjugated monoclonal antibody reagents for the detection and differentiation of herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in MRC-5 cell culture. Cells infected with HSV-1 generally displayed a pattern of nongranular or diffuse fluorescence, while cells infected with HSV-2 were identified by the production of fluorescent grains and flecks. This unique nonimmunological reagent, when used in combination with low-speed centrifugation, provides a remarkably specific, sensitive, rapid, and cost-effective means to detect HSV-infected MRC-5 or BHK-21 cells as early as 20 h postinoculation. In contrast to the immunofluorescence method, the serotypes of HSV can be differentiated with only one fluorescein-H. pomatia reagent in MRC-5 cell cultures. Images PMID:2545739

  7. Proposal for a New LoD and Multi-Representation Concept for CityGML

    NASA Astrophysics Data System (ADS)

    Löwner, M.-O.; Gröger, G.; Benner, J.; Biljecki, F.; Nagel, C.

    2016-10-01

    The Open Geospatial Consortium (OGC) CityGML standard offers a Level of Detail (LoD) concept that enables the representation of CityGML features from a very detailed to a less detailed description. Due to a rising application variety, the current LoD concept seems to be too inflexible. Here, we present a multi representation concept (MRC) that enables a user-defined definition of LoDs. Because CityGML is an international standard, official profiles of the MRC are proposed. However, encoding of the defined profiles reveals many problems including mapping the conceptual model to the normative encoding, missing technologies and so on. Therefore, we propose to use the MRC as a meta model for the further definition of an LoD concept for CityGML 3.0.

  8. Performance analysis of satellite-to-ground downlink coherent optical communications with spatial diversity over Gamma-Gamma atmospheric turbulence.

    PubMed

    Ma, Jing; Li, Kangning; Tan, Liying; Yu, Siyuan; Cao, Yubin

    2015-09-01

    The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed atmospheric turbulence are studied for a coherent detection receiving system with spatial diversity. Maximum ratio combining (MRC) and selection combining (SC) techniques are considered as practical schemes to mitigate the atmospheric turbulence. Bit-error rate (BER) performances for binary phase-shift keying modulated coherent detection and outage probabilities are analyzed and compared for SC diversity using analytical results and for MRC diversity through an approximation method with different numbers of receiving aperture each with the same aperture area. To show the net diversity gain of a multiple aperture receiver system, BER performances and outage probabilities of MRC and SC multiple aperture receiver systems are compared with a single monolithic aperture with the same total aperture area (same total average incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are verified by Monte-Carlo simulations.

  9. Relative sensitivity of three cell substrates to the Sabin poliovirus strains.

    PubMed

    Kado, G

    Poliovirus types 1, 2 and 3 (Sabin strains) were titrated using microtissue culture plates in three different cell substrates: Hep 2C, Vero and MRC-5 human diploid cells. Each type of poliovirus was titrated 60 times. The virus dilutions were inoculated in the three cell substrates and the titres (TCID50/ml) calculated by the Spearman-Kärber method. The results were analyzed by the U-test (Mann and Whitney procedure) in a Wang 600 computer. For poliovirus type 1 the differences in titres observed between Hep 2C and Vero cells were not statistically significant at p = 0.01, but the differences in titres between Hep 2C and MRC-5 human diploid cells and between Vero and MRC-5 cells were statistically highly significant (p = 0.001). For poliovirus types 2 and 3 the observed differences in titres were highly significant (p = 0.001) between Hep 2C and Vero cells, Hep 2C and MRC-5 and also between Vero and MRC-5 cells, with higher titres on Hep 2C cells. Accordingly with these results Hep 2C and Vero cells showed the same susceptibility to poliovirus type 1. In MCR-5 cells the average titre (G.M.T.) was 1 log10 below the average titres (G.M.T.) from Hep 2C or Vero cells. With poliovirus types 2 and 3 the higher titres were obtained on Hep 2C cells with significant differences to the titres observed in Vero and MRC-5 human diploid cells, which showed less susceptibility.

  10. Biodiversity of Spongosorites coralliophaga (Stephens, 1915) on coral rubble at two contrasting cold-water coral reef settings

    NASA Astrophysics Data System (ADS)

    Kazanidis, Georgios; Henry, Lea-Anne; Roberts, J. Murray; Witte, Ursula F. M.

    2016-03-01

    Cold-water coral reefs (CWRs) in the northeast Atlantic harbor diverse sponge communities. Knowledge of deep-sea sponge ecology is limited and this leaves us with a fragmented understanding of the ecological roles that sponges play in CWR ecosystems. We present the first study of faunal biodiversity associated with the massive demosponge Spongosorites coralliophaga (Stephens, 1915) that typically colonizes coral debris fields of CWRs. Our study focused on the sessile fauna inhabiting sponges mixed with coral rubble at two contrasting settings in the northeast Atlantic: the shallow inshore (120-190 m water depth) Mingulay Reef Complex (MRC) and the deep offshore (500-1200 m) Logachev Mound (LM) coral province. MRC is dominated by the scleractinian Lophelia pertusa, while LM is dominated by L. pertusa and Madrepora oculata. Nine sponge-coral rubble associations were collected from MRC and four from LM. Measurements of abundance, species richness, diversity, evenness, dry biomass, and composition of sessile fauna on sponge and coral rubble microhabitats were undertaken. Differences in community composition between the two regions were mainly a response to changes in fauna with depth. Fauna composition was also different between sponge and coral rubble within each region. Infauna constituted a minor component of the sponge-associated fauna in MRC but had a higher contribution in LM. Sponge and coral rubble sessile fauna in both regions was mainly composed of cnidarians and molluscs, similarly to some previous studies. Sponges' outer surfaces at MRC were colonized by a species-rich community with high abundance and biomass suggesting that S. coralliophaga at MRC acts as a settlement surface for various organisms but such a role is not the case at LM. This difference in the role of S. coralliophaga as a biological structure is probably related to differences in fauna composition with depth, bottom current speed, and the quantity/quality of food supplied to the benthos.

  11. The Radio Spectral Energy Distribution and Star-formation Rate Calibration in Galaxies

    NASA Astrophysics Data System (ADS)

    Tabatabaei, F. S.; Schinnerer, E.; Krause, M.; Dumas, G.; Meidt, S.; Damas-Segovia, A.; Beck, R.; Murphy, E. J.; Mulcahy, D. D.; Groves, B.; Bolatto, A.; Dale, D.; Galametz, M.; Sandstrom, K.; Boquien, M.; Calzetti, D.; Kennicutt, R. C.; Hunt, L. K.; De Looze, I.; Pellegrini, E. W.

    2017-02-01

    We study the spectral energy distribution (SED) of the radio continuum (RC) emission from the Key Insight in Nearby Galaxies Emitting in Radio (KINGFISHER) sample of nearby galaxies to understand the energetics and origin of this emission. Effelsberg multi-wavelength observations at 1.4, 4.8, 8.4, and 10.5 GHz combined with archive data allow us, for the first time, to determine the mid-RC (1–10 GHz, MRC) bolometric luminosities and further present calibration relations versus the monochromatic radio luminosities. The 1–10 GHz radio SED is fitted using a Bayesian Markov Chain Monte Carlo technique leading to measurements for the nonthermal spectral index ({S}ν ∼ {ν }-{α {nt}}) and the thermal fraction ({f}{th}) with mean values of {α }{nt}=0.97 +/- 0.16(0.79 +/- 0.15 for the total spectral index) and {f}{th} = (10 ± 9)% at 1.4 GHz. The MRC luminosity changes over ∼3 orders of magnitude in the sample, 4.3× {10}2 {L}ȯ < MRC < 3.9× {10}5 {L}ȯ . The thermal emission is responsible for ∼23% of the MRC on average. We also compare the extinction-corrected diagnostics of the star-formation rate (SFR) with the thermal and nonthermal radio tracers and derive the first star-formation calibration relations using the MRC radio luminosity. The nonthermal spectral index flattens with increasing SFR surface density, indicating the effect of the star-formation feedback on the cosmic-ray electron population in galaxies. Comparing the radio and IR SEDs, we find that the FIR-to-MRC ratio could decrease with SFR, due to the amplification of the magnetic fields in star-forming regions. This particularly implies a decrease in the ratio at high redshifts, where mostly luminous/star-forming galaxies are detected.

  12. Progress toward the development of a genetically engineered attenuated hepatitis A virus vaccine.

    PubMed Central

    Funkhouser, A W; Raychaudhuri, G; Purcell, R H; Govindarajan, S; Elkins, R; Emerson, S U

    1996-01-01

    Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cells suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' noncoding (NC) region. These 5' NC mutations and a separate group of 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals. PMID:8892918

  13. Progress toward the development of a genetically engineered attenuated hepatitis A virus vaccine.

    PubMed

    Funkhouser, A W; Raychaudhuri, G; Purcell, R H; Govindarajan, S; Elkins, R; Emerson, S U

    1996-11-01

    Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cells suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' noncoding (NC) region. These 5' NC mutations and a separate group of 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals.

  14. Radiologic validation of a fast neutron multileaf collimator

    SciTech Connect

    Farr, J. B.; Maughan, R. L.; Yudelev, M.; Blosser, E.; Brandon, J.; Horste, T.; Forman, J. D.

    2007-09-15

    Teletherapy with high linear energy transfer radiations (LET), perhaps more than with low LET types, requires careful beam collimation to limit effects to normal structures. Intensity modulated techniques may also hold promise in this regard. Accordingly, a remote computer-controlled, high-resolution multileaf collimator (MLC) is placed into service at the Gershenson Radiation Oncology Center's fast neutron therapy center of the Karmanos Cancer Institute, Detroit, Michigan. Prior to clinical application the basic radiological properties of the fast neutron MLC are studied. Complicating the evaluation is the mixed neutron and gamma radiation field environment encountered with fast neutron beams. As a reference the MLC performance is compared to an existing multirod collimator (MRC) used at the facility for more than ten years. The MLC aggregate transmission is found to be about 4%, slightly outperforming the MRC. The measured gamma component for a closed collimator is 1.5 times higher for the MLC, compared with the MRC. The different materials used for attenuation, steel and tungsten, respectively account for the difference. The geometry for the MRC is double focused whereas that for the MLC is single focused. The resulting penumbrae agree between the focused axis of the MLC and both axes of the MRC. Penumbra differences between the focused and unfocused axes were not observable at small field sizes and a maximum of about 1 cm for a 25x25 cm{sup 2} field at 2.5 cm depth in water. For a 10x10 cm{sup 2} field the focused penumbra is 9 mm, and the unfocused is 12 mm. The many benefits of the fully automatic MLC over the semimanual MRC are considered to justify this compromise.

  15. Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971

    PubMed Central

    Johnson, Martin H.; Franklin, Sarah B.; Cottingham, Matthew; Hopwood, Nick

    2010-01-01

    BACKGROUND In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical ‘Studies on Human Reproduction’. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology. METHODS The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision. RESULTS We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants’ high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support. CONCLUSIONS This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research. PMID:20657027

  16. Exercise capacity and physical activity in patients with COPD and healthy subjects classified as Medical Research Council dyspnea scale grade 2.

    PubMed

    Johnson-Warrington, Vicki; Harrison, Samantha; Mitchell, Katy; Steiner, Mick; Morgan, Mike; Singh, Sally

    2014-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are often classified by Medical Research Council (MRC) dyspnea grade and comparisons thus made to healthy individuals. The MRC grade of a healthy population is assumed to be grade 1, although this may be inaccurate. Physical activity and exercise capacity are not well-defined for those with MRC grade 2. This study was undertaken to establish whether there are differences in physical activity and exercise capacity between individuals with COPD and healthy controls, who have all assessed themselves as MRC grade 2. Patients with COPD (n = 83) and 19 healthy controls, with a self-selected MRC grade of 2, completed the Incremental Shuttle Walk Test (ISWT) and wore a SenseWear (BodyMedia, Pittsburgh, PA) activity monitor for 12 hours for 2 weekdays. Adjusting for age, step count and ISWT were significantly reduced for those with COPD, compared with healthy controls (P < .05). Patients with COPD achieved mean (SD) 425.5 (131.3) m on ISWT and took 6022 (3276) steps per day compared with 647.8 (146.3) m and 9462 (4141) steps per day for healthy controls. For subjects achieving 10 000 steps per day, 8 (42.11%) healthy controls achieved this level compared with 7 (8.43%) patients with COPD (P < .01). Healthy individuals may report functional limitations and categorize themselves as MRC grade 2. However, despite both groups subjectively considering themselves similarly functionally limited, exercise capacity and physical activity were significantly reduced in patients with COPD compared with healthy participants. This highlights the importance of early interventions to increase physical performance and prevent functional decline for patients with COPD.

  17. Structural analysis of mitochondrial mutations reveals a role for bigenomic protein interactions in human disease.

    PubMed

    Lloyd, Rhiannon E; McGeehan, John E

    2013-01-01

    Mitochondria are the energy producing organelles of the cell, and mutations within their genome can cause numerous and often severe human diseases. At the heart of every mitochondrion is a set of five large multi-protein machines collectively known as the mitochondrial respiratory chain (MRC). This cellular machinery is central to several processes important for maintaining homeostasis within cells, including the production of ATP. The MRC is unique due to the bigenomic origin of its interacting proteins, which are encoded in the nucleus and mitochondria. It is this, in combination with the sheer number of protein-protein interactions that occur both within and between the MRC complexes, which makes the prediction of function and pathological outcome from primary sequence mutation data extremely challenging. Here we demonstrate how 3D structural analysis can be employed to predict the functional importance of mutations in mtDNA protein-coding genes. We mined the MITOMAP database and, utilizing the latest structural data, classified mutation sites based on their location within the MRC complexes III and IV. Using this approach, four structural classes of mutation were identified, including one underexplored class that interferes with nuclear-mitochondrial protein interactions. We demonstrate that this class currently eludes existing predictive approaches that do not take into account the quaternary structural organization inherent within and between the MRC complexes. The systematic and detailed structural analysis of disease-associated mutations in the mitochondrial Complex III and IV genes significantly enhances the predictive power of existing approaches and our understanding of how such mutations contribute to various pathologies. Given the general lack of any successful therapeutic approaches for disorders of the MRC, these findings may inform the development of new diagnostic and prognostic biomarkers, as well as new drugs and targets for gene therapy.

  18. Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation.

    PubMed

    Baker, Charli D; Basu Ball, Writoban; Pryce, Erin N; Gohil, Vishal M

    2016-07-15

    Mitochondrial membrane phospholipid composition affects mitochondrial function by influencing the assembly of the mitochondrial respiratory chain (MRC) complexes into supercomplexes. For example, the loss of cardiolipin (CL), a signature non-bilayer-forming phospholipid of mitochondria, results in disruption of MRC supercomplexes. However, the functions of the most abundant mitochondrial phospholipids, bilayer-forming phosphatidylcholine (PC) and non-bilayer-forming phosphatidylethanolamine (PE), are not clearly defined. Using yeast mutants of PE and PC biosynthetic pathways, we show a specific requirement for mitochondrial PE in MRC complex III and IV activities but not for their formation, whereas loss of PC does not affect MRC function or formation. Unlike CL, mitochondrial PE or PC is not required for MRC supercomplex formation, emphasizing the specific requirement of CL in supercomplex assembly. Of interest, PE biosynthesized in the endoplasmic reticulum (ER) can functionally substitute for the lack of mitochondrial PE biosynthesis, suggesting the existence of PE transport pathway from ER to mitochondria. To understand the mechanism of PE transport, we disrupted ER-mitochondrial contact sites formed by the ERMES complex and found that, although not essential for PE transport, ERMES facilitates the efficient rescue of mitochondrial PE deficiency. Our work highlights specific roles of non-bilayer-forming phospholipids in MRC function and formation. © 2016 Baker et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. The potential of imaging techniques as a screening tool for colorectal cancer: a cost-effectiveness analysis

    PubMed Central

    Berkhof, Johannes; Fijneman, Remond J A; Demirel, Erhan; Lew, Jie-Bin; Meijer, Gerrit A; Stoker, Jaap; Coupé, Veerle M H

    2016-01-01

    Objective: Imaging may be promising for colorectal cancer (CRC) screening, since it has test characteristics comparable with colonoscopy but is less invasive. We aimed to assess the potential of CT colonography (CTC) and MR colonography (MRC) in terms of (cost-effectiveness) using the Adenoma and Serrated pathway to Colorectal CAncer model. Methods: We compared several CTC and MRC strategies with 5- or 10-yearly screening intervals with no screening, 10-yearly colonoscopy screening and biennial faecal immunochemical test (FIT) screening. We assumed trial-based participation rates in the base-case analyses and varied the rates in sensitivity analyses. Incremental lifetime costs and health effects were estimated from a healthcare perspective. Results: The health gain of CTC and MRC was similar and ranged from 0.031 to 0.048 life-year gained compared with no screening, for 2–5 screening rounds. Lifetime costs per person for MRC strategies were €60–110 higher than those for CTC strategies with an equal number of screening rounds. All imaging-based strategies were cost-effective compared with no screening. FIT screening was the dominant screening strategy, leading to most LYG and highest cost-savings. Compared with three rounds of colonoscopy screening, CTC with five rounds was found to be cost-effective in an incremental analysis of imaging strategies. Assumptions on screening participation have a major influence on the ordering of strategies in terms of costs and effects. Conclusion: CTC and MRC have potential for CRC screening, compared with no screening and compared with three rounds of 10-yearly colonoscopy screening. When taking FIT screening as the reference, imaging is not cost-effective. Participation is an important driver of effectiveness and cost estimates. Advances in knowledge: This is the first study to assess the cost-effectiveness of MRC screening for CRC. PMID:27194458

  20. Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971.

    PubMed

    Johnson, Martin H; Franklin, Sarah B; Cottingham, Matthew; Hopwood, Nick

    2010-09-01

    In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical 'Studies on Human Reproduction'. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology. The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision. We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants' high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support. This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research.

  1. Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis.

    PubMed

    Jagtap, Sujit Abajirao; Kuruvilla, Abraham; Govind, Preetha; Nair, Muralidharan D; Sarada, C; Varma, Ravi Prasad

    2014-07-01

    Monitoring the disease progression in amyotrophic lateral sclerosis (ALS) is a challenge due to different rates of progression between patients. Besides clinical methods to monitor disease progression, such as the ALS functional rating scale (ALSFRS) and the medical research council (MRC) sum score, quantitative methods like motor unit number estimation (MUNE) are of interest. The objective of the present study is to evaluate the rate of progression in ALS using multipoint incremental MUNE and to compare MUNE, ALSFRS and MRC sum score at baseline and at 6 months for progression of the disease. Multipoint incremental MUNE using median nerve, ALS-FRS and MRC sum score was carried out in 29 ALS patients at baseline and then at 6 months. Of the 29 ALS patients studied, the mean MUNE at baseline was 21.80 (standard deviation [SD]: 19.46, range 4-73), 15.9 in the spinal onset group (SD: 14.60) and 30.16 (SD: 22.89) in the bulbar onset group. Spinal onset patients had 74.02% of baseline MUNE value while bulbar onset patients had only 24.74% baseline value MUNE at 6 months follow-up (Unpaired t-test, P = 0.001). ALSFRS and MRC sum score showed statistically significant decline (P < 0.001) at 6 months follow-up. MUNE had the highest sensitivity for progression of the disease when compared to the ALS FRS and MRC sum score. Multipoint incremental MUNE is a valuable tool for outcome measure in ALS and other diseases characterized by motor unit loss. The rate of decline of multipoint incremental MUNE is more sensitive than that of MRC sum score and ALSFRS-R, when expressed as the percentage change from baseline.

  2. Thread sign in biliary intraductal papillary mucinous neoplasm: a novel specific finding for MRI.

    PubMed

    Hong, Gil-Sun; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Seung Soo; Hong, Seung-Mo; Lee, Moon-Gyu

    2016-09-01

    To evaluate thread sign of biliary intraductal papillary mucinous neoplasm (B-IPMN) on magnetic resonance imaging (MRI). Thread sign was defined as intraductal linear or curvilinear hypointense striations. Two radiologists independently evaluated the presence and location of thread sign on MR cholangiography (thin-slice, thick-slab and 3D MRC) and axial MR images (T2 TSE, T2 HASTE and DWI) in patients with B-IPMN (n = 38) and in matched control groups with benign (n = 36) or malignant (n = 35) biliary diseases. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of thread sign for diagnosing B-IPMN were evaluated. Thread sign was observed only in patients with B-IPMN on MRC (44.7-52.6 % [17/38-20/38], P < 0.001) and axial MR images (31.6 % [12/38], P < 0.001), except in one patient with recurrent pyogenic cholangitis on MRC (2.8 %, 1/36). The sensitivity, specificity, accuracy, PPV and NPV of thread sign for diagnosing B-IPMN on MRC were 0.53, 0.99, 0.83, 0.95 and 0.80, respectively (reader 1) and 0.45, 1.0, 0.81, 1.0 and 0.77, respectively (reader 2). Thread sign was detected mainly at the extrahepatic bile duct (52.6 %, 20/38). B-IPMN can manifest thread sign, a novel specific MR finding, mainly at the extrahepatic bile duct on MRI, especially on MRC. • Some B-IPMNs manifest thread sign within the bile ducts on MRI. • Thread sign is a highly specific finding for B-IPMN on MRI. • MRC is superior to axial T2WI and DWI for detecting thread sign.

  3. Allocating Marine Expeditionary Unit Equipment to Minimize Shortfalls. Third Edition

    DTIC Science & Technology

    2015-01-01

    destroyed port facilities downstream of Dhaka, which, combined with the 150 nm distance from Dhaka to the mouth of the Bay of Bengal, necessitated an...Counternarcotic or counterdrug operations include activi- ties to detect , interdict, or eliminate the cultivation, processing, trans- port, or sale of illegal...SENADOR ACCESSORY KIT   2 26633 GUN POD COFFIN (EMPTY)   3 7070 MISSION KIT   4 A0067 AN/MRC-148 A0067-AN/MRC-148 (HF/ VHF) 5 A0234 SWAN BOX   6 A0243

  4. Gerald Loewi: A Major Contributor to the New Era of Rheumatology Thinking

    PubMed Central

    Denman, Michael

    2017-01-01

    Dr Gerald Loewi was Senior Research Scientist and Consultant Pathologist at the Medical Research Council (MRC) Rheumatism Research Unit at Taplow, England and subsequently the MRC Clinical Research Centre, Harrow, England. An immunologist with a background in pathology, he made major contributions to our understanding of the immunopathology of rheumatoid arthritis and other rheumatic disorders. With his colleagues, he developed a more sophisticated concept of what were initially thought to be primary autoimmune or degenerative diseases but are now recognized as much more complex disease processes. He was one of the first to initiate close collaboration between clinicians and scientists in rheumatology research and practice. PMID:28178437

  5. Determination of functional prognosis in hospitalized patients following an intensive care admission

    PubMed Central

    Ferreira, Natália A; Lopes, Agnaldo José; Ferreira, Arthur S; Ntoumenopoulos, George; Dias, Jerffesson; Guimaraes, Fernando S

    2016-01-01

    AIM To investigate the factors associated with the functional progress of hospitalized patients following an intensive care admission. METHODS Retrospective study including data from a cohort of 198 hospitalized patients following an intensive care admission and not requiring mechanical ventilation in a single tertiary referral hospital. A generalized linear model was used to identify the main effects of clinical and demographic variables on the outcomes of functionality (KATZ Index of Independence in Activities of Daily Living) and muscle strength (MRC Scale). The covariates identified as independent predictors were analysed using the receiver operating characteristic curves. The analysis differentiated the periods in the intensive care unit (ICU), in the Ward (WARD) and the total time of hospital stay (TOT). RESULTS Considering the functional outcome (ΔKATZ), the variables that significantly contributed to the model (P < 0.05) were the KATZ and MRC on admission, age, sepsis (no), and total length of stay (TLS). Regarding the muscle strength outcome model (ΔMRC), the predictors were MRC on admission, Simplified Acute Physiology Score III, previous stroke, TLS, and sex (female). The variable age (AUC = 0.664) discriminated the ΔKATZICU. The variables age (AUC = 0.712), KATZ in ICU (AUC = 0.590) and on ward admission (AUC = 0.746), and MRC on ward admission (AUC = 0.721) were discriminative for ΔKATZWARD. For ΔKATZTOT the variables KATZ on ICU admission (AUC = 0.621) and TLS (AUC = 0.617) were discriminative. For ΔMRCICU the variables SAPSIII (AUC = 0.661) and MRC on ICU admission (AUC = 0.653) were discriminative. MRC on ICU (AUC = 0.681) and ward admission (AUC = 0.553) were discriminative for ΔMRCWARD. TLS (AUC = 0.649) and MRC on ward admission (AUC = 0.696) discriminative for the ΔMRCTOT. CONCLUSION Specific functional, clinical and demographical variables at ICU admission are associated with the functional prognosis during the hospitalization period

  6. Fingers in a Hele-Shaw Cell with Surface Tension.

    DTIC Science & Technology

    1983-05-01

    A138 548 FINGERS IN A HELE-SHAid CELL WITH SURFACE TENSION (U) i/i WISCONSIN UN! V-*MADISON MATHEMATICS RESEARCH CENTER J YANDEN-BROECI( MAY 83 MRC...NATIONAL BUREAU OF STANDARDS-1963-A A-4" MRC Technical Simimary Report #2518 i. FINGERS IN A HELE-SHAW CELLQ WITH SURFACE TENSION V=4 Jean-Marc...H CENTER "’ FINGERS IN A HXLZ-SHAW CELL WITH SURFACE TENSION Jean-Marc Vanden-Broeck Technical Summary Report #2518 May 1983 ABSTRACT McLean and

  7. The Impact of Gd-Eob-Dtpa-Enhanced MR Cholangiography in Biliary Diseases: Comparison with T2-Weighted MR Cholangiopancreatography

    PubMed Central

    Özmen, Evrim; Algın, Oktay; Evrimler, Şehnaz; Arslan, Halil

    2016-01-01

    Background: Contrast enhanced magnetic resonance cholangiography is a novel technique and promising method in demonstrating biliary tree anatomy and evaluating biliary disorders. However, to date, there are a limited number of studies that have focused on the impact of this technique. Aims: We aimed to evaluate the additional role of contrast enhanced MR cholangiography (MRC) and compare contrast enhanced MRC with T2-weighted (w) magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary disorders. Study Design: Diagnostic accuracy study. Methods: The T2w-MRCP and contrast enhanced MRC sequences of 31 patients whose gold standard test results were available were scored visually for the existence of pathological findings with regard to any of the biliary diseases. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) was used as the contrast agent. The correlation values were determined according to the statistical analysis made from those scores and the sensitivity, specificity and accuracy values of each sequence were detected as well. Results: We detected that the correlation values with gold standard methods of contrast enhanced MRC sequences were significantly higher than the ones of T2w-MRCP sequences. The correlation ratios of T2w-MRCP sequences were between 26 and 34%, while those for contrast enhanced MRC sequences were between 81 and 83% for the first reader and the correlation ratios of T2w-MRCP sequences were between 10 and 61%, whereas those of contrast enhanced MRC were between 79 and 81% for the second reader The mean sensitivity, specificity and accuracy values of T2w-MRCP sequences were 14.3–42.5%, 85–89.2% and 59.3–72.5%, respectively, while the mean sensitivity, specificity and accuracy values of contrast enhanced MRC sequences were 100%, 86.7% and 93.2–93.3%, respectively. Conclusion: We suggest that obtaining of contrast enhanced MRC sequences in addition to the T2w-MRCP can be useful in the

  8. Homography-Based Correction of Positional Errors in MRT Survey

    NASA Astrophysics Data System (ADS)

    Nayak, A.; Daiboo, S.; Udaya Shankar, N.

    2009-09-01

    The Mauritius Radio Telescope (MRT) images show systematics in the positional errors of sources when compared to source positions in the Molonglo Reference Catalogue (MRC). We have applied two-dimensional homography to correct positional errors in the image domain and avoid re-processing the visibility data. Positions of bright (above 15 σ) sources, common to MRT and MRC catalogues, are used to set up an over-determined system to solve for the 2-D homography matrix. After correction, the errors are found to be within 10% of the beamwidth for these bright sources and the systematics are eliminated from the images.

  9. The F100 Engine Purchasing and Supply Chain Management Demonstration: Findings from Air Force Spend Analyses

    DTIC Science & Technology

    2006-01-01

    spend for both spares and repairs went to the top five suppli- ers (see Table 4.1). Only two of the five, AB SKF and MPB Corpora- tion (Timken),3 were...tracts Number of NSNsa 1 United Technologies Corp. 3.8 37 96 4 16 2 AB SKF (MRC Bearings)b 1.6 16 13 10 9 3 MPB Corp. (Timken)b 1.5 15 3 5 5 4 Canadian...of Dollars Spent with Sole- Source Contracts Num- ber of Con- tracts Number of NSNs 1 AB SKF (MRC Bearings)a 4.4 24 19 31 27 2 Honeywell

  10. Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg) Kausel).

    PubMed

    Calloni, Caroline; Silva Santos, Luciana Fernandes; Martínez, Luana Soares; Salvador, Mirian

    2016-03-01

    Jaboticaba (Plinia trunciflora (O. Berg) Kausel) is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase) activity and ATP biosynthesis of human lung fibroblast cells (MRC-5) treated with amiodarone. The data presented in this article demonstrate that the polyphenols-rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells.

  11. Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg) Kausel)

    PubMed Central

    Calloni, Caroline; Silva Santos, Luciana Fernandes; Martínez, Luana Soares; Salvador, Mirian

    2016-01-01

    Jaboticaba (Plinia trunciflora (O. Berg) Kausel) is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase) activity and ATP biosynthesis of human lung fibroblast cells (MRC-5) treated with amiodarone. The data presented in this article demonstrate that the polyphenols-rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells. PMID:26870757

  12. A subspace-based parameter estimation algorithm for Nakagami-m fading channels

    NASA Astrophysics Data System (ADS)

    Dianat, Sohail; Rao, Raghuveer

    2010-04-01

    Estimation of channel fading parameters is an important task in the design of communication links such as maximum ratio combining (MRC). The MRC weights are directly related to the fading channel coefficients. In this paper, we propose a subspace based parameter estimation algorithm for the estimation of the parameters of Nakagami-m fading channels in the presence of additive white Gaussian noise. Comparisons of our proposed approach are made with other techniques available in the literature. The performance of the algorithm with respect to the Cramer-Rao bound (CRB) is investigated. Computer simulation results for different signal to noise ratios (SNR) are presented.

  13. A visual basic spreadsheet macro for recession curve analysis.

    PubMed

    Posavec, Kristijan; Bacani, Andrea; Nakić, Zoran

    2006-01-01

    A Visual Basic program for an Excel spreadsheet was written to construct a master recession curve (MRC), using the adapted matching strip method, for recession analysis of ground water level time series. The program uses five different linear/nonlinear regression models to adjust individual recession segments to their proper positions in the MRC. The program can also be used to analyze the recession segments of other time series, such as daily stream discharge or stage. Some examples of field data from Croatia are used to illustrate the usefulness of its application.

  14. Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI.

    PubMed

    Stawicki, Piotr; Gembler, Felix; Volosyak, Ivan

    2016-01-01

    Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system.

  15. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke.

    PubMed

    Oviedo, Alberto; Lebrun, Stefan; Kogel, Ulrike; Ho, Jenny; Tan, Wei Teck; Titz, Bjoern; Leroy, Patrice; Vuillaume, Gregory; Bera, Monali; Martin, Florian; Rodrigo, Gregory; Esposito, Marco; Dempsey, Ruth; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F.

  16. Improving the Representational Strategies of Children in a Music-Listening and Playing Task: An Intervention-Based Study

    ERIC Educational Resources Information Center

    Gil, Vicent; Reybrouck, Mark; Tejada, Jesús; Verschaffel, Lieven

    2015-01-01

    This intervention-based study focuses on the relation between music and its graphic representation from a meta-representational point of view. It aims to determine whether middle school students show an increase in meta-representational competence (MRC) after an educational intervention. Three classes of 11 to 14-year-old students participated in…

  17. Relationships between impulse oscillometry, spirometry and dyspnoea in COPD.

    PubMed

    Anderson, W J; Lipworth, B J

    2012-06-01

    Severity of chronic obstructive pulmonary disease (COPD) is based either on symptoms/disability or lung function, which have no discernible correlation. We hypothesised that impulse oscillometry (IOS), a non-effort-dependent measure of central and peripheral airway mechanics, could correlate to dyspnoea in COPD. We analysed screening data from 57 COPD patients who had spirometry, IOS and Medical Research Council dyspnoea score (MRC) measurements. We searched for predictors or correlations of MRC from IOS, spirometry and demographics. MRC had no significant predictors or correlations from IOS, spirometry or demographics (possibly excepting smoking history, p=0.05). IOS correlated significantly with spirometry: FEV1 and FEF25-75 vs. R5-R20 (peripheral airway resistance), r= -0.499, p > 0.001 and r= -0.397, p= 0.002 respectively. MRC is not related to IOS or spirometry in COPD. IOS correlates well with spirometry, particularly peripheral airway resistance (R5-R20). IOS is useful, but does not provide a link between symptoms and pulmonary function measurements.

  18. Calculable People? Standardising Assessment Guidelines for Alzheimer's Disease in 1980s Britain.

    PubMed

    Wilson, Duncan

    2017-10-01

    This article shows how funding research on Alzheimer's disease became a priority for the British Medical Research Council (MRC) in the late 1970s and 1980s, thanks to work that isolated new pathological and biochemical markers and showed that the disease affected a significant proportion of the elderly population. In contrast to histories that focus on the emergence of new and competing theories of disease causation in this period, I argue that concerns over the use of different assessment methods ensured the MRC's immediate priority was standardising the ways in which researchers identified and recorded symptoms of Alzheimer's disease in potential research subjects. I detail how the rationale behind the development of standard assessment guidelines was less about arriving at a firm diagnosis and more about facilitating research by generating data that could be easily compared across the disciplines and sites that constitute modern biomedicine. Drawing on criticism of specific tests in the MRC's guidelines, which some psychiatrists argued were 'middle class biased', I also show that debates over standardisation did not simply reflect concerns specific to the fields or areas of research that the MRC sought to govern. Questions about the validity of standard assessment guidelines for Alzheimer's disease embodied broader concerns about education and social class, which ensured that distinguishing normal from pathological in old age remained a contested and historically contingent process.

  19. Has the US Military in the Horn of Africa Been a Force that Embraces Strategic Knowledge and Perspective in Countering Violent Extremism and Assisting with Sustainable Development?

    DTIC Science & Technology

    2013-01-01

    which was supposed to counter the Mombasa Republican Council ( MRC ) and other militant groups. 63 There were efforts to enable CA teams to have access...need for soil and load-bearing analyses. CA teams were promising $8,000 latrines to local populations, and the Seabees found that they were

  20. 78 FR 65027 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-30

    ... Change Concerning Charters for the Board of Directors, the Membership/Risk Committee, the Audit Committee...''), Audit Committee (``AC Charter'') and Performance Committee (``PC Charter'') of OCC's Board of Directors... proposed rule change concerns the Board, Membership/Risk Committee (``MRC''), Audit Committee (``AC'') and...

  1. Acylated pregnane glycosides from Caralluma tuberculata and their antiparasitic activity.

    PubMed

    Abdel-Sattar, Essam; Harraz, Fathalla M; Al-ansari, Soliman Mohammed Abdullah; El-Mekkawy, Sahar; Ichino, Chikara; Kiyohara, Hiroaki; Ishiyama, Aki; Otoguro, Kazuhiko; Omura, Satoshi; Yamada, Haruki

    2008-08-01

    Five pregnane glycosides were isolated from Caralluma tuberculata (1-5), in addition to a known one (russelioside E, 6). The structures of the isolated compounds were elucidated by the analysis of NMR data and FAB-MS experiments. All the isolated compounds were tested for their antimalarial and antitrypanosomal activities as well as their cytotoxicity against human diploid embryonic cell line (MRC5).

  2. March 2011 DMM Podcast: an interview with Nick Hastie

    PubMed Central

    2012-01-01

    SUMMARY Excerpts from an interview with Nick Hastie, Director of the MRC Human Genetics Centre in Edinburgh, discussing his early career, his involvement in large-scale genetic studies and his exciting new findings on WT1. Narrated by Sarah E. Allan. To listen to this podcast, visit http://www.biologists.com/DMM/podcasts/index.html.

  3. Students' Big Three Personality Traits, Perceptions of Teacher Interpersonal Behavior, and Mathematics Achievement: An Application of the Model of Reciprocal Causation

    ERIC Educational Resources Information Center

    Charalampous, Kyriakos; Kokkinos, Constantinos M.

    2014-01-01

    The purpose of the present study was to investigate the application of the Model of Reciprocal Causation (MRC) in examining the relationship between student personality (personal factors), student-perceived teacher interpersonal behavior (environment), and Mathematics achievement (behavior), with the simultaneous investigation of mediating effects…

  4. The Effects of Level of Counselor Education on Client Outcomes in the Public Vocational Rehabilitation System of New Jersey

    ERIC Educational Resources Information Center

    Rehabilitation Research, Policy, and Education, 2013

    2013-01-01

    To fulfill the goal of having counselors qualified through the Comprehensive System of Personnel Development (CSPD), the Division of Vocational Rehabilitation Services in New Jersey (DVRS-NJ) committed to have selected counselors attend a Master's Degree in Rehabilitation Counseling (MRC) graduate program. This study examines 14 student/counselors…

  5. Strategy optimization for mask rule check in wafer fab

    NASA Astrophysics Data System (ADS)

    Yang, Chuen Huei; Lin, Shaina; Lin, Roger; Wang, Alice; Lee, Rachel; Deng, Erwin

    2015-07-01

    Photolithography process is getting more and more sophisticated for wafer production following Moore's law. Therefore, for wafer fab, consolidated and close cooperation with mask house is a key to achieve silicon wafer success. However, generally speaking, it is not easy to preserve such partnership because many engineering efforts and frequent communication are indispensable. The inattentive connection is obvious in mask rule check (MRC). Mask houses will do their own MRC at job deck stage, but the checking is only for identification of mask process limitation including writing, etching, inspection, metrology, etc. No further checking in terms of wafer process concerned mask data errors will be implemented after data files of whole mask are composed in mask house. There are still many potential data errors even post-OPC verification has been done for main circuits. What mentioned here are the kinds of errors which will only occur as main circuits combined with frame and dummy patterns to form whole reticle. Therefore, strategy optimization is on-going in UMC to evaluate MRC especially for wafer fab concerned errors. The prerequisite is that no impact on mask delivery cycle time even adding this extra checking. A full-mask checking based on job deck in gds or oasis format is necessary in order to secure acceptable run time. Form of the summarized error report generated by this checking is also crucial because user friendly interface will shorten engineers' judgment time to release mask for writing. This paper will survey the key factors of MRC in wafer fab.

  6. Two Simulated-Smog Atmospheres with Different Chemical Compositions Produce Contrasting Mutagenicity in Salmonella**

    EPA Science Inventory

    Ozone (O3), particulate matter (PM), and nitrogen dioxide (NO2) are criteria pollutants used to evaluate air quality. Using EPA’s Mobile Reaction Chamber (MRC), we generated 2 simulated-smog atmospheres (SSA-1 & SSA-2) with different concentrations of these criteria pol...

  7. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    SciTech Connect

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-09-15

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  8. Identifying Mechanisms of Change in a Conversation Therapy for Aphasia Using Behaviour Change Theory and Qualitative Methods

    ERIC Educational Resources Information Center

    Johnson, Fiona M.; Best, Wendy; Beckley, Firle Christina; Maxim, Jane; Beeke, Suzanne

    2017-01-01

    Background: Conversation therapy for aphasia is a complex intervention comprising multiple components and targeting multiple outcomes. UK Medical Research Council (MRC) guidelines published in 2008 recommend that in addition to measuring the outcomes of complex interventions, evaluation should seek to clarify how such outcomes are produced,…

  9. The Diagnosis and Management of Auditory Processing Disorder

    ERIC Educational Resources Information Center

    Moore, David R.

    2011-01-01

    Purpose: To provide a personal perspective on auditory processing disorder (APD), with reference to the recent clinical forum on APD and the needs of clinical speech-language pathologists and audiologists. Method: The Medical Research Council-Institute of Hearing Research (MRC-IHR) has been engaged in research into APD and auditory learning for 8…

  10. Tunable filter imaging of high-redshift quasar fields

    NASA Astrophysics Data System (ADS)

    Swinbank, John; Baker, Joanne; Barr, Jordi; Hook, Isobel; Bland-Hawthorn, Joss

    2012-06-01

    We have used the Taurus Tunable Filter to search for Lyα emitters in the fields of three high-redshift quasars: two at z˜ 2.2 (MRC B1256-243 and MRC B2158-206) and one at z˜ 4.5 (BR B0019-1522). Our observations had a field of view of around 35 arcmin2, and reached AB magnitudes of ˜21 (MRC B1256-243), ˜22 (MRC B2158-206) and ˜22.6 (BR B0019-1522) depending on wavelength. We have identified candidate emission-line galaxies in all the three fields, with the higher redshift field being by far the richest. By combining our observations with simulations of the instrumental response, we estimate the total density of emission-line galaxies in each field. 17 candidate emission-line galaxies were found within 1.5 Mpc of BR B0019-1522, a number density of (4.9 ± 1.2) × 10-3 Mpc-3, suggesting a significant galaxy overdensity at z˜ 4.5.

  11. Improving the Representational Strategies of Children in a Music-Listening and Playing Task: An Intervention-Based Study

    ERIC Educational Resources Information Center

    Gil, Vicent; Reybrouck, Mark; Tejada, Jesús; Verschaffel, Lieven

    2015-01-01

    This intervention-based study focuses on the relation between music and its graphic representation from a meta-representational point of view. It aims to determine whether middle school students show an increase in meta-representational competence (MRC) after an educational intervention. Three classes of 11 to 14-year-old students participated in…

  12. Improvement of the Corrosion Resistance of Turbine Engine Bearings

    DTIC Science & Technology

    1986-04-01

    Armoloy- hydrogen embrittlement ; nickel sputtering - elevated substrate temperatures. Points were awarded as follows: a CRB7 - 15 points a MRC2001 - 15...nodestructive lelst ( NDI )T inspection results of the Ml(2001 rings are summarized below: * 35-mm Inner Rings (20 Required) All 34 rings were considered usable

  13. Anti-infective mannose receptor immune mechanism in large yellow croaker (Larimichthys crocea).

    PubMed

    Dong, Xiangli; Li, Jiji; He, Jianyu; Liu, Wei; Jiang, Lihua; Ye, Yingying; Wu, Changwen

    2016-07-01

    Mannose receptor (MR) is a pattern recognition receptor (PRR) that plays a significant role in immunity responses. Its role has been described extensively in mammals, but very rarely in fish. Recently, with the rapid development of an aquaculture industry cultivating large yellow croaker (Larimichthys crocea), infectious diseases caused by viruses, bacteria and parasites are becoming more frequent and more severe, in particular bacterial infections caused by Vibrio anguillarum, resulting in great economical losses. Extensive use of antibiotics as conventional treatment has led to microenvironment imbalances, development of drug-resistant bacteria and deposition of drug residues, which cause environmental pollution and ultimately affect human health. The purpose of this pilot study was to detect the transcriptional levels of C-type mannose receptor genes MRC1 (4710-bp ORF; encoding 1437 aa; a signal peptide, a SMART RICIN domain, a SMART FN2 domain, eight SMART CLECT domain, and a transmembrane helix region) and MRC2 (3996-bp ORF; encoding 1484 aa; a SMART FN2 domain, eight SMART CLECT domains, and a transmembrane region) in the liver, kidney and spleen tissues of L. crocea challenged by V. anguillarum, to explore the effective domain and the molecular response mechanisms of MRC1 and MRC2, and, ultimately, to explore the possibility of developing a vaccine targeting V. anguillarum infections.

  14. Molecular anatomy of tunicate senescence: reversible function of mitochondrial and nuclear genes associated with budding cycles.

    PubMed

    Kawamura, Kaz; Kitamura, Seigo; Sekida, Satoko; Tsuda, Masayuki; Sunanaga, Takeshi

    2012-11-01

    Zooids of the asexual strain of Polyandrocarpa misakiensis have a lifespan of 4-5 months; before dying, they produce many buds, enabling continuation of the strain. This study was designed to investigate the nature of gene inactivation and reactivation during this continuous process of senescence and budding. During senescence, the zooidal epidermis showed acid β-galactosidase activity, lost proliferating cell nuclear antigen immunoreactivity and became ultrastructurally worn, indicating that the epidermis is a major tissue affected by the ageing process. Semi-quantitative PCR analysis showed that the genes encoding mitochondrial respiratory chains (MRCs) engaged in decreased transcriptional activity in senescent adults compared with younger adults. The results of in situ hybridization showed that the epidermis dramatically attenuates MRC expression during ageing but restores gene activity when budding commences. During budding and ageing, the nuclear gene Eed (a polycomb group component) was activated and inactivated in a pattern similar to that observed in MRCs. In buds, RNA interference (RNAi) of Eed attenuated Eed transcripts but did not affect the gene expression of pre-activated MRCs. A tunicate humoral factor, TC14-3, could induce Eed, accompanying the reactivation of MRC in adult zooids. When RNAi of Eed and Eed induction were performed simultaneously, zooidal cells and tissues failed to engage in MRC reactivation, indicating the involvement of Eed in MRC activation. Results of this study provide evidence that the mitochondrial gene activities of Polyandrocarpa can be reversed during senescence and budding, suggesting that they are regulated by nuclear polycomb group genes.

  15. Prooxidant action of chebulinic acid and tellimagrandin I: causing copper-dependent DNA strand breaks.

    PubMed

    Yi, Zong-Chun; Liu, Yan-Ze; Li, Hai-Xia; Wang, Zhao

    2009-04-01

    The prooxidant activity of two hydrolysable tannins, chebulinic acid and tellimagrandin I, on plasmid DNA and genomic DNA of cultured MRC-5 human embryo lung fibroblasts was assessed. The results revealed that both hydrolysable tannins in combination with Cu(II) induced DNA strand breaks in pBR322 plasmid DNA in a concentration-dependent manner. Chebulinic acid and tellimagrandin I also induced genomic DNA strand breaks of MRC-5 human embryo lung fibroblasts in the presence of Cu(II). After treatment with chebulinic acid or tellimagrandin I alone, the pBR322 plasmid DNA and genomic DNA in MRC-5 cells kept intact. In addition, addition of Cu(I) reagent bathocuproinedisulfonic acid or catalase markedly inhibited the copper-dependent DNA strand breaks by both tannins. However, three typical hydroxyl radical scavengers, DMSO, ethanol and mannitol, did not inhibit the DNA strand breaks. Both tannins were able to reduce Cu(II) to Cu(I). These results indicated that chebulinic acid and tellimagrandin I induced the copper-dependent strand breaks of pBR322 plasmid DNA and MRC-5 genomic DNA with prooxidant action, in which Cu(II)/Cu(I) redox cycle and H(2)O(2) were involved and hydroxyl radical formation is important in the hypothetical mechanism by which DNA strand breaks are formed.

  16. What Can a Woman Do to Promote a Healthy Pregnancy Before She Gets Pregnant?

    MedlinePlus

    ... MRC Vitamin Study Research Group. (1991). Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet, 338 (8760), 131–137. PMID: 1677062 and see Centers for Disease Control and Prevention. (2011, February). National Center on Birth ...

  17. Focused Magnetic Resonance Coupling Coils for Electromagnetic Therapy Applications.

    PubMed

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-11-01

    This paper presents the design and construction of a pair of figure-of-eight coils, coupled by magnetic resonance coupling (MRC), which could generate (150 V/m per Ampere) electric field at the focal points for electromagnetic therapy related applications. The E field generated at the targeted site would be significantly enhanced under the same amount of current flowing through the MRC figure-of-eight coils compared to normal coils, due to the superposition of E field contributed by the coils. Furthermore, the MRC figure-of-eight coil is designed and the results are verified in theory, simulation, and experiments. In the ex vivo tissue measurement, 35% current and 82% ohmic power improvements were observed. Since it can enhance the current and ohmic power, the MRC figure-of-eight coils are promising solutions for electromagnetic therapy applications. The potential applications of the coils include noninvasive radio frequency (RF) stimulation, thermoacoustic imaging, electromagnetic field therapies, and RF ablation, etc.

  18. Reliability of TMS metrics in patients with chronic incomplete spinal cord injury.

    PubMed

    Potter-Baker, K A; Janini, D P; Frost, F S; Chabra, P; Varnerin, N; Cunningham, D A; Sankarasubramanian, V; Plow, E B

    2016-11-01

    Test-retest reliability analysis in individuals with chronic incomplete spinal cord injury (iSCI). The purpose of this study was to examine the reliability of neurophysiological metrics acquired with transcranial magnetic stimulation (TMS) in individuals with chronic incomplete tetraplegia. Cleveland Clinic Foundation, Cleveland, Ohio, USA. TMS metrics of corticospinal excitability, output, inhibition and motor map distribution were collected in muscles with a higher MRC grade and muscles with a lower MRC grade on the more affected side of the body. Metrics denoting upper limb function were also collected. All metrics were collected at two sessions separated by a minimum of two weeks. Reliability between sessions was determined using Spearman's correlation coefficients and concordance correlation coefficients (CCCs). We found that TMS metrics that were acquired in higher MRC grade muscles were approximately two times more reliable than those collected in lower MRC grade muscles. TMS metrics of motor map output, however, demonstrated poor reliability regardless of muscle choice (P=0.34; CCC=0.51). Correlation analysis indicated that patients with more baseline impairment and/or those in a more chronic phase of iSCI demonstrated greater variability of metrics. In iSCI, reliability of TMS metrics varies depending on the muscle grade of the tested muscle. Variability is also influenced by factors such as baseline motor function and time post SCI. Future studies that use TMS metrics in longitudinal study designs to understand functional recovery should be cautious as choice of muscle and clinical characteristics can influence reliability.

  19. The Effects of Level of Counselor Education on Client Outcomes in the Public Vocational Rehabilitation System of New Jersey

    ERIC Educational Resources Information Center

    Rehabilitation Research, Policy, and Education, 2013

    2013-01-01

    To fulfill the goal of having counselors qualified through the Comprehensive System of Personnel Development (CSPD), the Division of Vocational Rehabilitation Services in New Jersey (DVRS-NJ) committed to have selected counselors attend a Master's Degree in Rehabilitation Counseling (MRC) graduate program. This study examines 14 student/counselors…

  20. A role for p53 in selenium-induced senescence

    USDA-ARS?s Scientific Manuscript database

    The tumor suppressor p53 and the ataxia-telangiectasia mutated (ATM) kinase play important roles in the senescence response to oncogene activation and DNA damage. We have previously shown that selenium-containing compounds can activate an ATM-dependent senescence response in MRC-5 normal fibroblasts...

  1. Two Simulated-Smog Atmospheres with Different Chemical Compositions Produce Contrasting Mutagenicity in Salmonella**

    EPA Science Inventory

    Ozone (O3), particulate matter (PM), and nitrogen dioxide (NO2) are criteria pollutants used to evaluate air quality. Using EPA’s Mobile Reaction Chamber (MRC), we generated 2 simulated-smog atmospheres (SSA-1 & SSA-2) with different concentrations of these criteria pol...

  2. Pre- and postprocessing for multilayer compression of scanned documents

    NASA Astrophysics Data System (ADS)

    Zaghetto, Alexandre; de Queiroz, Ricardo L.

    2011-10-01

    The mixed raster content (MRC) document-compression standard (ITU T.44) specifies a multilayer representation of a document image. The model is very efficient for representing sharp text and graphics over a background. However, its binary selection layer compromises the representation of scanned data and soft edges. Typical segmentation algorithms that split up the document into layers tend to lift letter colors to the foreground, so that soft edge transitions may not fully belong either to the foreground or background layers, causing ``halos'' around objects that impair compression performance. We present a method that sharpens the document before compression and softens its edges after MRC-based reconstruction. It builds an edge-sharpening map and estimates the original edge softness at the encoder. The generated map and softness parameters are then used to reconstruct the original soft edges at the decoder. An MRC encoding and decoding scheme based on H.264/AVC and JBIG2 has been used. Experimental results show that, for lower bit rates, the proposed pre-/postprocessing method can improve both subjective and objective compression performance over regular MRC.

  3. An Analysis of Transport, Dispersion, and Deposition from Two Above-Ground Nuclear Tests in China

    DTIC Science & Technology

    1999-04-14

    resulting distribution of radioactive material to the Second-order Closure Integrated PUFF ( SCIPUFF ) model to perform the transport and diffusion of the...Corp, MRC-R-243, Dec 1975 Sykes, R.I., "PC- SCIPUFF Version 0.2 Technical Documentation, Titan Corporation, DNA-TR-96-27, April 1997 Tripoli, G.J

  4. Adaptation of the Medical Research Council Dyspnea Scale and the Oxygen Cost Diagram for its use in Puerto Rico.

    PubMed

    Serrano, Jahaira; De Jesús-Berríos, Yohana; Santos, Ruth A; Dexter, Donald; Nazario, Cruz María; Montalvo, Francisco

    2007-06-01

    Dyspnea is a common and disabling symptom for patients with chronic lung diseases. The Medical Research Council Dyspnea Scale (MRC) and the Oxygen Cost Diagram (OCD) are widely used instruments validated in English to measure breathlessness. To translate and culturally adapt the MRC and the OCD for its use in Puerto Rico. The scales were translated to Spanish and back translated. They were tested in patients attending a pulmonary clinic to assess its relevance and comprehension. Subjects answered the instruments, had a structured clinical interview and provided feedback. A multidisciplinary committee analyzed the source of misunderstanding using the input of the subjects, the clinical physicians, and the evaluators; made adjustments, and retested the instruments until inconsistencies were not observed. Placing emphasis on time spent walking instead of distance traveled improved the discrimination between grade two and three in the MRC. In the OCD, placing the activities to the right side eased the interpretation of the scale. Numerical symbols were eliminated to minimize discomfort in the severely impaired subjects reluctant to mark the line near zero. Reversing the order of both scales encouraged a thorough reading of the activities from minimal to high energy demanding eliciting a more fitting response compared to structured clinical interview especially in the severely ill patient. Using cross-cultural research methodologies to translate the MRC and OCD allowed the identification of differences in conceptualization when assessing the severity of dyspnea in Puerto Rico. Further testing is needed to confirm psychometric properties.

  5. The Medical Reserve Corps as part of the federal medical and public health response in disaster settings.

    PubMed

    Frasca, Dominic R

    2010-09-01

    The Secretary of the Department of Health and Human Services (HHS), through the Office of the Assistant Secretary for Preparedness and Response (ASPR), coordinates federal Emergency Support Function (ESF) #8 preparedness, response, and recovery actions. To address these needs, the ASPR can draw on trained personnel from a variety of sources, both from within and outside HHS. Among the resources under the domain of HHS is the Medical Reserve Corps (MRC), directed by the Office of the Civilian Volunteer Medical Reserve Corps (OCVMRC) in the Office of the Surgeon General. MRC units are community based and function as a way to locally organize and utilize medical and public health professionals, such as physicians, nurses, pharmacists, dentists, veterinarians, and epidemiologists. Nonclinical volunteers, such as interpreters, chaplains, office workers, legal advisors, and others, can fill logistical and support roles in MRC units. This article discusses locally controlled (Hurricanes Gustav and Ike) and federalized (Hurricanes Katrina and Rita) MRC activations, and it describes the advantages of using medical volunteers in a large-scale disaster response setting.

  6. Stuart Gatehouse: A Personal Appreciation

    PubMed Central

    Haggard, Mark

    2008-01-01

    Stuart Gatehouse worked in the MRC Institute of Hearing Research Scottish Section for 29 years until his untimely death in 2007. The former director records a personal appreciation but also an explanation, for those who did not know him well, of the mixture of qualities that made him an outstanding applied scientist. PMID:18567588

  7. Molecular Detection of Minimal Residual Cancer in Surgical Margins of Head and Neck Cancer Patients

    PubMed Central

    Graveland, A. Peggy; de Maaker, Michiel; Braakhuis, Boudewijn J. M.; de Bree, Remco; Eerenstein, Simone E. J.; Bloemena, Elisabeth; Leemans, C. René; Brakenhoff, Ruud H.

    2009-01-01

    A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins. Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters. A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p < 0.001), and the group of patients with histopathological tumor-free surgical margins (p = 0.001). This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising. PMID:19633367

  8. Watershed Analysis Results for Mendocino Redwood Company Lands in Coastal Mendocino and Sonoma Counties

    Treesearch

    Christopher G. Surfleet

    2007-01-01

    To assess the needs for conservation, restoration and condition of aquatic habitat within its land Mendocino Redwood Company (MRC) has been conducting watershed analysis. From watershed analysis completed to date, we estimate 73percent of the total sediment inputs over the last 30 to 40 years are road and skid trail associated. Of that percentage 30 percent is road and...

  9. Motor unit number estimation as a complementary test to routine electromyography in the diagnosis of amyotrophic lateral sclerosis.

    PubMed

    Gawel, Malgorzata; Zalewska, Ewa; Lipowska, Marta; Kostera-Pruszczyk, Anna; Szmidt-Salkowska, Elzbieta; Kaminska, Anna

    2016-02-01

    Electromyographic (EMG) abnormalities that reveal denervation and reinnervation caused by lower motor neuron degeneration do not reflect the number of motor units that determines muscle strength. Consequently, motor unit activity potential (MUAP) parameters do not reflect muscle dysfunction. The aim of the study was to compare the value of motor unit number estimation (MUNE) and MUAP parameters as indicators of clinical muscle dysfunction in patients with amyotrophic lateral sclerosis (ALS), and to analyze the role of MUNE as a supplement to the EMG criteria for the diagnosis of ALS. In 25 patients with ALS, MUNE by the multipoint incremental method in the abductor digiti minimi (ADM) and quantitative EMG in the first dorsal interosseous (FDI) were obtained. The Medical Research Council (MRC) scale was used to evaluate clinical muscle dysfunction. A strong correlation between the number of motor units evaluated by MUNE and ADM clinical function by the MRC scale was found (P<0.001). An increased value of surface-detected single motor action potential was associated with a decreased MRC score for ADM (P<0.1). No relation was found between MUAP parameters in FDI and MRC scores. Our data support the value of the MUNE method for the detection of motor unit loss in ALS, and it could be postulated that MUNE studies may be considered complementary tests for ALS in a future revision of ALS criteria.

  10. Regulation of Mitochondrial Respiratory Chain Biogenesis by Estrogens/Estrogen Receptors and Physiological, Pathological and Pharmacological Implications

    PubMed Central

    Chen, Jin-Qiang; Cammarata, Patrick R.; Baines, Christopher P.; Yager, James D.

    2009-01-01

    There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17β-estradiol(E2) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E2-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ERα and ERβ and their co-activators on the coordinate regulation of both nuclear DNA- and mitochondrial DNA-encoded genes for MRC proteins. In this paper, we have: 1) comprehensively reviewed studies that reveal a novel role of estrogens and ERs in the regulation of MRC biogenesis; 2) discussed their physiological, pathological and pharmacological implications in the control of cell proliferation and apoptosis in relation to estrogen-mediated carcinogenesis, anticancer drug resistance in human breast cancer cells, neuro-protection for Alzheimer’s disease and Parkinson’s disease in brain, cardiovascular protection in human heart and their beneficial effects in lens physiology related to cataract in the eye; and 3) pointed out new research directions to address the key questions in this important and newly emerging area. We also suggest a novel conceptual approach that will contribute to innovative regimines for the prevention or treatment of a wide variety of medical complications based on E2/ER-mediated MRC biogenesis pathway. PMID:19559056

  11. Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI

    PubMed Central

    2016-01-01

    Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system. PMID:27528864

  12. Students' Big Three Personality Traits, Perceptions of Teacher Interpersonal Behavior, and Mathematics Achievement: An Application of the Model of Reciprocal Causation

    ERIC Educational Resources Information Center

    Charalampous, Kyriakos; Kokkinos, Constantinos M.

    2014-01-01

    The purpose of the present study was to investigate the application of the Model of Reciprocal Causation (MRC) in examining the relationship between student personality (personal factors), student-perceived teacher interpersonal behavior (environment), and Mathematics achievement (behavior), with the simultaneous investigation of mediating effects…

  13. Patterned ion exchange membranes for improved power production in microbial reverse-electrodialysis cells

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Geise, Geoffrey M.; Luo, Xi; Hou, Huijie; Zhang, Fang; Feng, Yujie; Hickner, Michael A.; Logan, Bruce E.

    2014-12-01

    Power production in microbial reverse-electrodialysis cells (MRCs) can be limited by the internal resistance of the reverse electrodialysis stack. Typical MRC stacks use non-conductive spacers that block ion transport by the so-called spacer shadow effect. These spacers can be relatively thick compared to the membrane, and thus they increase internal stack resistance due to high solution (ohmic) resistance associated with a thick spacer. New types of patterned anion and cation exchange membranes were developed by casting membranes to create hemispherical protrusions on the membranes, enabling fluid flow between the membranes without the need for a non-conductive spacer. The use of the patterned membrane decreased the MRC stack resistance by ∼22 Ω, resulting in a 38% increase in power density from 2.50 ± 0.04 W m-2 (non-patterned membrane with a non-conductive spacer) to 3.44 ± 0.02 W m-2 (patterned membrane). The COD removal rate, coulombic efficiency, and energy efficiency of the MRC also increased using the patterned membranes compared to the non-patterned membranes. These results demonstrate that these patterned ion exchange membranes can be used to improve performance of an MRC.

  14. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    NASA Astrophysics Data System (ADS)

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-09-01

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  15. The MORPHEUS protein crystallization screen.

    PubMed

    Gorrec, Fabrice

    2009-12-01

    A 96-condition initial screen for protein crystallization, called MORPHEUS, has been developed at the MRC Laboratory of Molecular Biology, Cambridge, England (MRC-LMB). The concept integrates several innovative approaches, such as chemically compatible mixes of potential ligands, new buffer systems and precipitant mixes that also act as cryoprotectants. Instead of gathering a set of crystallization conditions that have already been successful, a selection of molecules frequently observed in the Protein Data Bank (PDB) to co-crystallize with proteins has been made. These have been put together in mixes of similar chemical behaviour and structure, and combined with buffers and precipitant mixes that were also derived from PDB searches, to build the screen de novo. Observations made at the MRC-LMB and many practical aspects were also taken into account when formulating the screen. The resulting screen is easy to use, comprehensive yet small, and has already yielded a list of crystallization hits using both known and novel samples. As an indicator of success, the screen has now become one of the standard screens used routinely at the MRC-LMB when searching initial crystallization conditions for biological macromolecules.

  16. "Safe Schools within Safe Communities: A Regional Summit in the Heartland." Policy Briefs Special Report.

    ERIC Educational Resources Information Center

    Huertas, Aurelio, Jr.; Sullivan, Carol

    This report documents the proceedings of a regional policy seminar hosted by the Iowa Department of Education with support from the North Central Regional Educational Laboratory (NCREL) and the Midwest Regional Center for Drug-Free Schools and Communities (MRC). The seminar, "Safe Schools Within Safe Communities," was held on September 19-20,…

  17. Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images

    PubMed Central

    Inano, Rika; Oishi, Naoya; Kunieda, Takeharu; Arakawa, Yoshiki; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu

    2016-01-01

    Preoperative glioma grading is important for therapeutic strategies and influences prognosis. Intratumoral heterogeneity can cause an underestimation of grading because of the sampling error in biopsies. We developed a voxel-based unsupervised clustering method with multiple magnetic resonance imaging (MRI)-derived features using a self-organizing map followed by K-means. This method produced novel magnetic resonance-based clustered images (MRcIs) that enabled the visualization of glioma grades in 36 patients. The 12-class MRcIs revealed the highest classification performance for the prediction of glioma grading (area under the receiver operating characteristic curve = 0.928; 95% confidential interval = 0.920–0.936). Furthermore, we also created 12-class MRcIs in four new patients using the previous data from the 36 patients as training data and obtained tissue sections of the classes 11 and 12, which were significantly higher in high-grade gliomas (HGGs), and those of classes 4, 5 and 9, which were not significantly different between HGGs and low-grade gliomas (LGGs), according to a MRcI-based navigational system. The tissues of classes 11 and 12 showed features of malignant glioma, whereas those of classes 4, 5 and 9 showed LGGs without anaplastic features. These results suggest that the proposed voxel-based clustering method provides new insights into preoperative regional glioma grading. PMID:27456199

  18. Real-world characterization and differentiation of the Global Initiative for Chronic Obstructive Lung Disease strategy classification

    PubMed Central

    Price, David B; Baker, Christine L; Zou, Kelly H; Higgins, Victoria S; Bailey, James T; Pike, James S

    2014-01-01

    Background This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC) and chronic obstructive pulmonary disease (COPD) assessment test (CAT). Methods Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US. Matched data from physicians and patients included CAT and mMRC scores. Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement (“movers”) within GOLD groups A–D, depending on the tool used. Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers. Results Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively), there were 890 (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A and C (using mMRC) to more symptomatic groups B and D (using CAT). For receiver operating characteristic (area under the curve: 0.82, P<0.001) and kappa (maximized: 0.45) recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively. Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05). Within movers, direction of movement was significantly associated with the same variables (all P<0.05). Conclusion Use of current mMRC or CAT cut points leads to inconsistencies for COPD assessment classification. It is recommended that cut points are aligned and both tools administered simultaneously for optimal patient care and to allow for closer management of movers. Our research may suggest an opportunity to investigate a combined score approach to patient management based on the worst result of mMRC and CAT. The reduced

  19. Identifying adults at risk of COPD who need confirmatory spirometry in primary care

    PubMed Central

    Hill, Kylie; Hodder, Richard; Blouin, Maria; Heels-Ansdell, Diane; Guyatt, Gordon; Goldstein, Roger

    2011-01-01

    Abstract Objective To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care. Design Cross-sectional study. Setting Three community primary care practices in Ontario. Participants Men and women 40 years of age and older with a smoking history of 20 pack-years or more. Main outcome measures We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores. Results Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores. Conclusion In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who

  20. Chronic obstructive pulmonary disease (COPD) assessment test scores corresponding to modified Medical Research Council grades among COPD patients.

    PubMed

    Lee, Chang-Hoon; Lee, Jinwoo; Park, Young Sik; Lee, Sang-Min; Yim, Jae-Joon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu

    2015-09-01

    In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade ≥ 2 versus < 2 was evaluated by comparing the area under the receiver operating curve (AUROC) and by classification and regression tree (CART) analysis. Among 428 COPD patients, the percentages of patients classified into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score ≥ 15 predicted an mMRC grade ≥ 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores < 10, but they did have a lower exacerbation risk compared to those with CAT scores of 15 to 19. A CAT score ≥ 15 is a better indicator for the 'more symptoms group' in the management of COPD patients.

  1. Validation of the Modified Pulmonary Functional Status and Dyspnea Questionnaire and the Medical Research Council scale for use in Brazilian patients with chronic obstructive pulmonary disease.

    PubMed

    Kovelis, Demetria; Segretti, Nicoli Oldemberg; Probst, Vanessa Suziane; Lareau, Suzanne Claire; Brunetto, Antônio Fernando; Pitta, Fábio

    2008-12-01

    To determine the validity and reproducibility of two subjective instruments to assess limitations in activities of daily living (ADLs) in patients with chronic obstructive pulmonary disease (COPD) in Brazil: the Pulmonary Functional Status and Dyspnea Questionnaire - Modified version (PFSDQ-M) and the Medical Research Council (MRC) scale. Thirty patients with COPD (age, 67 +/- 10 years; males, 17; forced expiratory volume in one second, 42% +/- 13% of predicted) completed the Portuguese-language versions of the two instruments on two occasions, one week apart. The PFSDQ-M has three components: influence of dyspnea on ADLs, influence of fatigue on ADLs change in ADLs experienced by the patient. The MRC scale is simple, with only five items, in which patients report the degree to which dyspnea limits their performance of ADLs. The traditional Saint George's Respiratory Questionnaire (SGRQ), previously validated for use in Brazil, was used as a validation criterion. The test-retest reliability (intraclass correlation coefficient) of the PFSDQ-M was 0.93, 0.92 and 0.90 for dyspnea, fatigue and change components, respectively, compared with 0.83 for the MRC scale. Bland-Altman plots showed good test-retest agreement for the PFSDQ-M. The components of the PFSDQ-M and the MRC scale correlated significantly with all of the domains and the total score of the SGRQ (0.49 < r < 0.80; p < 0.01 for all). The Portuguese-language versions of the PFSDQ-M and the MRC scale proved reproducible and valid for use in patients with COPD in Brazil.

  2. Production mask composition checking flow

    NASA Astrophysics Data System (ADS)

    Ma, Shou-Yuan; Yang, Chuen-Huei; Tsai, Joe; Wang, Alice; Lin, Roger; Lee, Rachel; Deng, Erwin; Lin, Ling-Chieh; Liao, Hung-Yueh; Tsai, Jenny; Bowhill, Amanda; Vu, Hien; Russell, Gordon

    2016-05-01

    The mask composition checking flow is an evolution of the traditional mask rule check (MRC). In order to differentiate the flow from MRC, we call it Mask Data Correctness Check (MDCC). The mask house does MRC only to identify process limitations including writing, etching, metrology, etc. There still exist many potential errors that could occur when the frame, main circuit and dummies all together form a whole reticle. The MDCC flow combines the design rule check (DRC) and MRC concepts to adapt to the complex patterns in today's wafer production technologies. Although photomask data has unique characteristics, the MRC tool in Calibre® MDP can easily achieve mask composition by using the Extended MEBES job deck (EJB) format. In EJB format, we can customize the combination of any input layers in an IC design layout format, such as OASIS. Calibre MDP provides section-based processing for many standard verification rule format (SVRF) commands that support DRC-like checks on mask data. Integrating DRC-like checking with EJB for layer composition, we actually perform reticle-level DRC, which is the essence of MDCC. The flow also provides an early review environment before the photomask pattern files are available. Furthermore, to incorporate the MDCC in our production flow, runtime is one of the most important indexes we consider. When the MDCC is included in the tape-out flow, the runtime impact is very limited. Calibre, with its multi-threaded processes and good scalability, is the key to achieving acceptable runtime. In this paper, we present real case runtime data for 28nm and 14nm technology nodes, and prove the practicability of placing MDCC into mass production.

  3. Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population

    PubMed Central

    Kuehle, Christiane A; Langhorst, Jost; Ladd, Susanne C; Zoepf, Thomas; Nuefer, Michael; Grabellus, Florian; Barkhausen, Joerg; Gerken, Guido; Lauenstein, Thomas C

    2007-01-01

    Background and aim To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. Methods 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. Results In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. Conclusions Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed. PMID:17341542

  4. Outcomes of clinical decision support (CDS) and correlates of CDS use for home care patients with high medication regimen complexity: A randomized trial

    PubMed Central

    McDonald, Margaret V.; Feldman, Penny H.; Barrón-Vayá, Yolanda; Peng, Timothy R.; Sridharan, Sridevi; Pezzin, Liliana E.

    2017-01-01

    Objective To assess the outcomes of a clinical decision support (CDS) intervention designed for home care patients with high medication regimen complexity (MRC) and to examine the correlates of CDS use and its relationship to patient outcomes. Method The intervention randomized nurses upon identification of an eligible patient. The CDS consisted of a computerized algorithm that identified high MRC patients, electronic clinician alerts, and a care management module. Analyses were completed on full intention to treat and intervention group-only samples. Regression-adjusted outcomes were hospitalization, emergency department use and reduction in MRC. Data sources included health records and administrative data. Results Five hundred nurses were randomized with 7,919 of their patients. Approximately 20% of the intervention group was hospitalized versus 21% in the control group; 16.5% of the intervention group had an emergency department visit versus 16.7% in the control group; and 6% in each group dropped below the high MRC threshold. No statistically significant differences were found in the intention to treat analysis. Eighty-two percent of intervention nurses used the CDS but for only 42% of their patients. Among intervention patients, CDS use (versus non-use) was associated with reduced MRC and hospitalization. CDS use was more likely among older nurses, those with higher study-patient caseload and, marginally, among salaried nurses and those with longer tenure. Significant patient characteristics were clinical conditions, payer, episode length, care continuity and race. Conclusion CDS use was limited, thus negating the impact of the intervention overall. The findings on correlates of CDS use and the relationship between CDS use and positive outcomes suggest that CDS use and outcomes could be enhanced by avoiding very short patient lengths of stay, improving continuity of care, increasing reliance on salaried nurses and/or increasing per diem nurses’ incentives to

  5. Who Will Experience the Most Alcohol Problems in College? The Roles of Middle and High School Drinking Tendencies.

    PubMed

    Scaglione, Nichole M; Mallett, Kimberly A; Turrisi, Rob; Reavy, Racheal; Cleveland, Michael J; Ackerman, Sarah

    2015-10-01

    Previous work examining college drinking tendencies has identified a disproportionately small (20%), but uniquely high-risk group of students who experience nearly 50% of the reported alcohol-related consequences (i.e., the multiple repeated consequences, or MRC, group). With the goal of reducing drinking-related consequences later in college, this study sought to identify potential MRC group members in their first semester by examining: (i) early-risk subgroups based on analysis of early-risk screening constructs (e.g., age of drinking onset, middle school alcohol exposure, high school drinking, and consequences); and (ii) their association with MRC criteria early in the first semester of college. A random sample of 2,021 first-year college student drinkers (56% female) completed a web-based drinking survey in their first semester on campus. Latent class analysis revealed 4 early-risk subgroups: (i) an early-onset risk group who endorsed early age of drinking onset and engaged in heavy middle and high school drinking (10%); (ii) a late-onset risk group who engaged in weekend drinking and drunkenness and experienced 6 or more unique consequences as seniors in high school (32%); (iii) an early-onset limited risk group who only endorsed early age of onset and middle school drinking (3%); and (iv) a minimal risk group who did not engage in any early-risk behaviors (55%). Members of both the early- and late-onset risk groups had significantly higher odds of MRC membership in their first semester of college (9.85 and 6.79 greater, respectively). Results suggest age of onset, middle and high school drinking and drunkenness, and frequency of unique consequences could be particularly useful in brief screening tools. Further, findings support early screening and prevention efforts for MRC membership prior to college matriculation. Copyright © 2015 by the Research Society on Alcoholism.

  6. Clinical Outcomes following median to radial nerve transfers

    PubMed Central

    Ray, Wilson Z.; Mackinnon, Susan E.

    2010-01-01

    Purpose In this study the authors evaluate the clinical outcomes in patients with radial nerve palsy who underwent nerve transfers utilizing redundant fascicles of median nerve (innervating the flexor digitorum superficialis and flexor carpi radialis muscles) to the posterior interosseous nerve and the nerve to the extensor carpi radialis brevis. Methods A retrospective review of the clinical records of 19 patients with radial nerve injuries who underwent nerve transfer procedures using the median nerve as a donor nerve were included. All patients were evaluated using the Medical Research Council (MRC) grading system. Results The mean age of patients was 41 years (range 17 – 78 years). All patients received at least 12 months of follow-up (20.3 ± 5.8 months). Surgery was performed at a mean of 5.7 ± 1.9 months post-injury. Post-operative functional evaluation was graded according to the following scale: grades MRC 0/5 - MRC 2/5 were considered poor outcomes, while MRC of 3/5 was a fair result, MRC grade 4/5 was a good result, and grade 4+/5 was considered an excellent outcome. Seventeen patients (89%) had a complete radial nerve palsy while two patients (11%) had intact wrist extension but no finger or thumb extension. Post-operatively all patients except one had good to excellent recovery of wrist extension. Twelve patients recovered good to excellent finger and thumb extension, two patients had fair recovery, five patients had a poor recovery. Conclusions The radial nerve is a commonly injured nerve, causing significant morbidity in affected patients. The median nerve provides a reliable source of donor nerve fascicles for radial nerve reinnervation. This transfer was first performed in 1999 and evolved over the subsequent decade. The important nuances of both surgical technique and motor re-education critical for to the success of this transfer have been identified and are discussed. PMID:21168979

  7. A toolkit to assess Medical Reserve Corps units' performance.

    PubMed

    Savoia, Elena; Massin-Short, Sarah; Higdon, Melissa Ann; Tallon, Lindsay; Matechi, Emmanuel; Stoto, Michael A

    2010-10-01

    The Medical Reserve Corps (MRC) is a national network of community-based units created to promote the local identification, recruitment, training, and activation of volunteers to assist local health departments in public health activities. This study aimed to develop a toolkit for MRC coordinators to assess and monitor volunteer units' performance and identify barriers limiting volunteerism. In 2008 and 2009, MRC volunteers asked to participate in influenza clinics were surveyed in 7 different locations throughout the United States. Two survey instruments were used to assess the performance of the volunteers who were able to participate, the specific barriers that prevented some volunteers from participating, and the overall attitudes of those who participated and those who did not. Validity and reliability of the instruments were assessed through the use of factor analysis and Cronbach's alpha. Two survey instruments were developed: the Volunteer Self-Assessment Questionnaire and the Barriers to Volunteering Questionnaire. Data were collected from a total of 1059 subjects, 758 participated in the influenza clinics and 301 were unable to attend. Data from the 2 instruments were determined to be suitable for factor analysis. Factor solutions and inter-item correlations supported the hypothesized domain structure for both survey questionnaires. Results on volunteers' performance were consistent with observations of both local health departments' staff and external observers. The survey instruments developed for this study appear to be valid and reliable means to assess the performance and attitudes of MRC volunteers and barriers to their participation. This study found these instruments to have face and content validity and practicality. MRC coordinators can use these questionnaires to monitor their ability to engage volunteers in public health activities.

  8. Ultrahigh-field imaging of the biliary tract at 7 T: initial results of gadoxetic acid-enhanced magnetic resonance cholangiography.

    PubMed

    Fischer, Anja; Kraff, Oliver; Orzada, Stephan; Nensa, Felix; Schäfer, Lena C; Ladd, Mark E; Umutlu, Lale; Lauenstein, Thomas C

    2014-05-01

    The objectives of this study were to assess the feasibility of magnetic resonance cholangiography (MRC) using biliary-secreted gadoxetic acid at 7 T and to compare it with T2-weighted (w) MRC at 3 T. Ten healthy volunteers were examined on a 7-T whole-body magnetic resonance system. T2-weighted turbo-spin-echo sequence, T1-w volume-interpolated breath-hold examination (VIBE), and fast low-angle shot (FLASH) with inversion recovery (IR) were acquired in coronal orientation. For dynamic imaging, gadoxetic acid was administrated and data were collected for a period of 5 to 40 minutes after injection. The volunteers underwent subsequent T2-w respiratory-gated MRC at 3 T. For qualitative analysis, a 5-point scale was used. Contrast ratios (CRs) were calculated for quantitative assessment. Contrast-enhanced T1-w MRC at 7 T showed a homogeneous depiction of the intrahepatic and extrahepatic biliary tract with a maximum enhancement of 20 minutes after contrast. Volume-interpolated breath-hold examination and FLASH IR provided a good image quality for the intrahepatic (VIBE, 3.60; FLASH IR, 3.67) and extrahepatic bile ducts (VIBE, 3.50; FLASH IR, 3.72). The quantitative analysis revealed high CR values for FLASH IR (intrahepatic CR, 0.41; extrahepatic CR, 0.45) because of an effective suppression of hepatic tissue and vessels. The T2-w TSE at 7 T showed only a poor image quality without diagnostic potential (intrahepatic, 2.22; extrahepatic, 1.93). Seven-tesla VIBE and FLASH revealed superiority in the depiction of the intrahepatic bile ducts, whereas 3-T MRC was superior in the delineation of the extrahepatic biliary tract. Our results demonstrate the feasibility of contrast-enhanced imaging of the biliary ducts at 7 T.

  9. High spatial resolution 3D MR cholangiography with high sampling efficiency technique (SPACE): comparison of 3T vs. 1.5T.

    PubMed

    Arizono, Shigeki; Isoda, Hiroyoshi; Maetani, Yoji S; Hirokawa, Yuusuke; Shimada, Kotaro; Nakamoto, Yuji; Shibata, Toshiya; Togashi, Kaori

    2010-01-01

    The aim of this study was to evaluate image quality of 3D MR cholangiography (MRC) using high sampling efficiency technique (SPACE) at 3T compared with 1.5T. An IRB approved prospective study was performed with 17 healthy volunteers using both 3 and 1.5T MR scanners. MRC images were obtained with free-breathing navigator-triggered 3D T2-weighted turbo spin-echo sequence with SPACE (TR, >2700ms; TE, 780ms at 3T and 801ms at 1.5T; echo-train length, 121; voxel size, 1.1mmx1.0mmx0.84mm). The common bile duct (CBD) to liver contrast-to-noise ratios (CNRs) were compared between 3 and 1.5T. A five-point scale was used to compare overall image quality and visualization of the third branches of bile duct (B2, B6, and B8). The depiction of cystic duct insertion and the highest order of bile duct visible were also compared. The results were compared using the Wilcoxon signed-ranks test. CNR between the CBD and liver was significantly higher at 3T than 1.5T (p=0.0006). MRC at 3T showed a significantly higher overall image quality (p=0.0215) and clearer visualization of B2 (p=0.0183) and B6 (p=0.0106) than at 1.5T. In all analyses of duct visibility, 3T showed higher scores than 1.5T. 3T MRC using SPACE offered better image quality than 1.5T. SPACE technique facilitated high-resolution 3D MRC with excellent image quality at 3T. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  10. Magnetic Resonance Colonography for Fibrosis Assessment in Rats with Chronic Colitis

    PubMed Central

    Melchior, Chloé; Loeuillard, Emilien; Marion-Letellier, Rachel; Nicol, Lionel; Mulder, Paul; Guerin, Charlène; Bôle-Feysot, Christine; Aziz, Moutaz; Déchelotte, Pierre; Vera, Pierre; Savoye, Guillaume; Savoye-Collet, Céline

    2014-01-01

    Background Magnetic resonance colonography (MRC) has been developed to assess inflammatory bowel diseases. We aimed to assess the feasibility of MRC in rats with TNBS-induced chronic colitis and to confront imaging results with fibrosis and stenosing features of the model. Materials and Methods Chronic colitis was induced in 12 rats by weekly intra-rectal injection of increasing doses of TNBS for 6 weeks, while 8 control rats received the vehicle. At week 7, MRC was performed. Fibrosis scores were assessed and fibrosis mediators measured. Results Chronic colitis was associated with significant body weight loss (p<0.0001) and higher colon weight/length compared to controls (p = 0.0004). Fibrosis mediators and histological scores were significantly higher in rats with TNBS than in controls: α-SMA expression (0.9 versus 0.61, p = 0.0311) and fibrosis score (p = 0.0308). Colon wall thickness was higher in rats with TNBS than in controls: maximal thickness (2.38 versus 0.74 mm, p<0.0001) and minimal thickness (1.33 versus 0.48 mm, p<0.0001). Wall signal intensity on T2w images was higher in rats with TNBS than in controls (9040 versus 6192, p = 0.0101) and correlated with fibrosis score (r = 0.5214; p = 0.04). Luminal narrowing was higher in rats with TNBS (50.08 versus 10.33%, p<0.0001) and correlated with α-SMA expression (r = 0.5618; p = 0.01). Stenosis was observed in 7/9 rats with TNBS and in no controls (p = 0.0053). Conclusions MRC is feasible and easily distinguishes rats with colitis from controls. MRC signs correlated with fibrosis parameters. MRC evaluation may be part of a new anti-fibrosis drug assessment in experimental models of chronic colitis. PMID:25000184

  11. Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice.

    PubMed

    Lee, Hsiang-Chi; Yen, Yu-Ting; Chen, Wen-Yu; Wu-Hsieh, Betty A; Wu, Suh-Chin

    2011-01-01

    Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3' NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q(438)H, E-V(463)L, NS2B-Q(78)H, and NS2B-A(113)T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development.

  12. Dengue Type 4 Live-Attenuated Vaccine Viruses Passaged in Vero Cells Affect Genetic Stability and Dengue-Induced Hemorrhaging in Mice

    PubMed Central

    Lee, Hsiang-Chi; Yen, Yu-Ting; Chen, Wen-Yu; Wu-Hsieh, Betty A.; Wu, Suh-Chin

    2011-01-01

    Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3′ NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q438H, E-V463L, NS2B-Q78H, and NS2B-A113T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development. PMID:22053180

  13. Diaphragmatic dysfunction in patients with ICU-acquired weakness and its impact on extubation failure.

    PubMed

    Jung, Boris; Moury, Pierre Henri; Mahul, Martin; de Jong, Audrey; Galia, Fabrice; Prades, Albert; Albaladejo, Pierre; Chanques, Gerald; Molinari, Nicolas; Jaber, Samir

    2016-05-01

    Diaphragm function is rarely studied in intensive care patients with unit-acquired weakness (ICUAW) in whom weaning from mechanical ventilation is challenging. The aim of the present study was to evaluate the diaphragm function and the outcome using a multimodal approach in ICUAW patients. Patients were eligible if they were diagnosed for ICUAW [Medical Research Council (MRC) Score <48], mechanically ventilated for at least 48 h and were undergoing a spontaneous breathing trial. Diaphragm function was assessed using magnetic stimulation of the phrenic nerves (change in endotracheal tube pressure), maximal inspiratory pressure and ultrasonographically (thickening fraction). Diaphragmatic dysfunction was defined by a change in endotracheal tube pressure below 11 cmH2O. The endpoints were to describe the correlation between diaphragm function and ICUAW and its impact on extubation. Among 185 consecutive patients ventilated for more than 48 h, 40 (22 %) with a MRC score of 31 [20-36] were included. Diaphragm dysfunction was observed with ICUAW in 32 patients (80 %). Change in endotracheal tube pressure and MRC score were not correlated. Maximal inspiratory pressure was correlated with change in endotracheal tube pressure after magnetic stimulation of the phrenic nerves (r = 0.43; p = 0.005) and MRC score (r = 0.34; p = 0.02). Thickening fraction was less than 20 % in 70 % of the patients and was statistically correlated with change in endotracheal tube pressure (r = 0.4; p = 0.02) but not with MRC score. Half of the patients could be extubated without needing reintubation within 72 h. Diaphragm dysfunction is frequent in patients with ICU-acquired weakness (80 %) but poorly correlated with the ICU-acquired weakness MRC score. Half of the patients with ICU-acquired weakness were successfully extubated. Half of the patients who failed the weaning process died during the ICU stay.

  14. Relationship between muscle strength and motor function in Duchenne muscular dystrophy.

    PubMed

    Nunes, Milene F; Hukuda, Michele E; Favero, Francis M; Oliveira, Acary B; Voos, Mariana C; Caromano, Fátima A

    2016-07-01

    To investigate the relationship between muscle strength and motor function and between these variables and age. Muscle strength was measured by Medical Research Council (MRC) scale and motor function, by Motor Function Measure (MFM), in 40 non-ambulatory patients. Spearman tests investigated the relationships between muscle strength, motor function and age. Total MRC and MFM scores were strongly related to each other (r = 0.94; p < 0.001), but not to age (r = -0.19, r = -0.31, respectively; p > 0.05). Strong and moderate relationships between partial muscle strength and motor function scores were found. Higher correlation coefficients were found between total scores and Dimensions 2 (axial/ proximal control) and 3 (distal control) of MFM. Muscle strength and motor function are strongly correlated and seem to decrease proportionally in DMD.

  15. Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

    PubMed Central

    Prudovsky, Igor; Kumar, Thallapuranam Krishnaswamy Suresh; Sterling, Sarah; Neivandt, David

    2013-01-01

    Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i) Phenomenon of nonclassical protein release and its biological significance; (ii) Composition of the FGF1 multiprotein release complex (MRC); (iii) The relationship between FGF1 export and acidic phospholipid externalization; (iv) Interactions of FGF1 MRC components with acidic phospholipids; (v) Methods to study the transmembrane translocation of proteins; (vi) Membrane models to study nonclassical protein release. PMID:23396106

  16. Optical diversity transmission using WDM signal and phase-conjugate lights through multi-core fiber.

    PubMed

    Koga, Masafumi; Moroi, Mitsuki; Takara, Hidehiko

    2016-05-02

    This paper proposes a maximum-ratio combining (MRC) scheme for a WDM signal and phase-conjugate pair (PCP) diversity transmission to cancel nonlinear phase-shift. A transfer function approximation for nonlinear phase-shift cancellation is formulated. It shows, with the help of a numerical calculation, that span-by-span chromatic dispersion compensation is more effective than the lumped equivalent at the receiver. This is confirmed in a 2-core diversity 5 channel WDM transmission experiment over 3-spans of 60km MCF with 25 Gbit/s-QPSK PCP. The peak Q-value was enhanced by 3.6dB through MRC, resulting in superior bitrate-distance product and optical power density limit, compared to twice the single core transmission.

  17. Synthesis and biological evaluation of the pirfenidone derivatives as antifibrotic agents.

    PubMed

    Ma, Zhen; Pan, Youlu; Huang, Wenhai; Yang, Yewei; Wang, Zunyuan; Li, Qin; Zhao, Yin; Zhang, Xinyue; Shen, Zhengrong

    2014-01-01

    A total of 24 pirfenidone derivatives were designed, synthesized and evaluated for their inhibitory activity against the human lung fibroblast cell line MRC-5. These compounds showed the remarkable proliferation inhibition against MRC-5 compared to pirfenidone as the positive control. The possible mechanism of this kind of derivatives as antifibrotic agents was explored. The molecular docking and p38 binding affinity assays demonstrated that the antifibrotic potential of the pirfenidone derivatives was possibly through the inhibition of p38 MAPK signaling pathway. The data from this study suggested that p38 might be a potential therapeutic target for the new generation antifibrotics. All the pirfenidone derivatives are reported here for the first time.

  18. An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines.

    PubMed

    Rourou, Samia; Ben Ayed, Yousr; Trabelsi, Khaled; Majoul, Samy; Kallel, Héla

    2014-05-19

    IPT-AFM is a proprietary animal component free medium that was developed for rabies virus (strain LP 2061) production in Vero cells. In the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. Here, three models were presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines were first adapted to grow in IPT-AFM, by progressive reduction of the amount of serum in the culture medium. After their adaptation, BHK-21 cells grew in suspension by forming clumps, whereas MRC-5 cells remained adherent. Then, kinetics of cell growth were studied in agitated cultures for both cell lines. In addition, kinetics of virus replication were investigated.

  19. Research on diversity receive technology for wireless optical communication using PPM in weak turbulence atmosphere channel

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Guo-an

    2014-09-01

    In order to mitigate atmospheric turbulence, the free space optical (FSO) system model with spatial diversity is analyzed based on intensity detection pulse position modulation (PPM) in the weak turbulence atmosphere. The slot error rate (SER) calculating formula of the system without diversity is derived under pulse position modulation firstly. Then as a benchmark, independent of identical distribution, the average slot error rates of the three linear combining technologies, which are the maximal ratio combining (MRC), equal gain combining (EGC) and selection combining (SelC), are compared. Simulation results show that the performance of system is the best improved by MRC, followed by EGC, and is poor by SelC, but SelC is simpler and more convenient. Spatial diversity is efficient to improve the performance and has strong ability on resistance to atmospheric channel decline. The above scheme is more suitable for optical wireless communication systems.

  20. UNOCAL Parachute Creek Shale Oil Project. Monitoring review committee meeting report. Annual meeting, 1987-1988

    SciTech Connect

    Not Available

    1988-05-25

    The Energy Security Act of 1980 established a program to provide financial assistance to private industry in the construction and operation of commercial-scale synthetic fuels plants. The Parachute Creek Shale Oil Program is one of four projects awarded financial assistance. The support agreement included development of an Environmental Monitoring Plan incorporating existing compliance monitoring and twenty-two supplemental monitoring points for water, air, solid waste, worker health and safety, and socio-economic impacts during the period 1986-1993. A Monitoring Review Committee (MRC) comprised of representatives from the Project, U.S. Department of Treasury, U.S. Department of Energy, U.S. Environmental Protection Agency, and the state convene each year to discuss monitoring information and trends in environmental and health surveillance. This report documents the first annual MRC meeting, held at the Project.

  1. Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune-mediated neuropathies.

    PubMed

    Gallia, Francesca; Balducci, Claudia; Nobile-Orazio, Eduardo

    2016-06-01

    High-dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25-60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.

  2. The nature and ethics of natural experiments.

    PubMed

    Dawson, Angus; Sim, Julius

    2015-10-01

    Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance.

  3. Hypoxic-Ischemic Injury in the Developing Brain: The Role of Reactive Oxygen Species Originating in Mitochondria

    PubMed Central

    Ten, Vadim S.; Starkov, Anatoly

    2012-01-01

    Mitochondrial dysfunction is the most fundamental mechanism of cell damage in cerebral hypoxia-ischemia and reperfusion. Mitochondrial respiratory chain (MRC) is increasingly recognized as a source for reactive oxygen species (ROS) in the postischemic tissue. Potentially, ROS originating in MRC can contribute to the reperfusion-driven oxidative stress, promoting mitochondrial membrane permeabilization. The loss of mitochondrial membranes integrity during reperfusion is considered as the major mechanism of secondary energy failure. This paper focuses on current data that support a pathogenic role of ROS originating from mitochondrial respiratory chain in the promotion of secondary energy failure and proposes potential therapeutic strategy against reperfusion-driven oxidative stress following hypoxia-ischemia-reperfusion injury of the developing brain. PMID:22548167

  4. Hypoxic-ischemic injury in the developing brain: the role of reactive oxygen species originating in mitochondria.

    PubMed

    Ten, Vadim S; Starkov, Anatoly

    2012-01-01

    Mitochondrial dysfunction is the most fundamental mechanism of cell damage in cerebral hypoxia-ischemia and reperfusion. Mitochondrial respiratory chain (MRC) is increasingly recognized as a source for reactive oxygen species (ROS) in the postischemic tissue. Potentially, ROS originating in MRC can contribute to the reperfusion-driven oxidative stress, promoting mitochondrial membrane permeabilization. The loss of mitochondrial membranes integrity during reperfusion is considered as the major mechanism of secondary energy failure. This paper focuses on current data that support a pathogenic role of ROS originating from mitochondrial respiratory chain in the promotion of secondary energy failure and proposes potential therapeutic strategy against reperfusion-driven oxidative stress following hypoxia-ischemia-reperfusion injury of the developing brain.

  5. A Multirobot Path-Planning Strategy for Autonomous Wilderness Search and Rescue.

    PubMed

    Macwan, Ashish; Vilela, Julio; Nejat, Goldie; Benhabib, Beno

    2015-09-01

    This paper presents a novel strategy for the on-line planning of optimal motion-paths for a team of autonomous ground robots engaged in wilderness search and rescue (WiSAR). The proposed strategy, which forms part of an overall multirobot coordination (MRC) methodology, addresses the dynamic nature of WiSAR by: 1) planning initial, time-optimal, and piecewise polynomial paths for all robots; 2) implementing and regularly evaluating the optimality of the paths through a set of checks that gauge feasibility of path-completion within the available time; and 3) replanning paths, on-line, whenever deemed necessary. The fundamental principle of maintaining the optimal deployment of the robots throughout the search guides the MRC methodology. The proposed path-planning strategy is illustrated through a simulated realistic WiSAR example, and compared to an alternative, nonprobabilistic approach.

  6. Performance analysis of generalized QAM modulation under η-μ and κ-μ fading

    NASA Astrophysics Data System (ADS)

    L Queiroz, Wamberto J.; Madeiro, Francisco; A Lopes, Waslon T.; Alencar, Marcelo S.

    2013-12-01

    This paper presents new closed-form expressions for the symbol error probability (SEP) of θ-QAM modulation with maximum ratio combining (MRC) receiver under η- μ and κ- μ fading. The SEP formulae, obtained from the definite integrals of the moment generating function (MGF) of the signal-to-noise ratio (SNR) at the input of the MRC receiver, are written in terms of Lauricella functions. The numerical evaluation of the expressions is carried out for the η- μ distribution, which includes important distributions as special cases, such as Hoyt, Nakagami- m, Rayleigh, and one-sided Gaussian, as well as for the κ- μ distribution, which includes Rice, Nakagami- m, Rayleigh, and one-sided Gaussian as special cases.

  7. Detection of Food Allergens by Phage-Displayed Produced Antibodies.

    PubMed

    Madrid, Raquel; de la Cruz, Silvia; García, Aina; Martín, Rosario; González, Isabel; García, Teresa

    2017-01-01

    Phage display is a powerful tool to produce recombinant antibodies against a given antigen without animal immunization. This technology employs libraries of recombinant bacteriophages that display billions of different functional antibody fragments on their surface. They are selected by panning in vitro against the target antigen in search for specific binders. In this chapter, we describe the selection of single chain variable fragment (scFv) antibodies to be used for detection of allergenic proteins from nuts in food products. The artificial libraries TomLinson I+J (MRC Laboratory of Molecular Biology and MRC Centre for Protein Engineering) were employed that resulted in successful phage-ELISA systems for detection of almond and walnut proteins in commercial food products.

  8. In Vitro Anti-Cytomegalovirus Activity of Kampo (Japanese Herbal) Medicine

    PubMed Central

    2004-01-01

    We examined the effect of three types of Kampo medicines on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with at least 0.01 μg/ml of Kampo medicines inhibited the cytopathic effects of CMV-infected MRC-5 cells. Moreover, Kampo medicine decreased the replication of CMV without affecting the inhibition of host cells, with a concomitant decrease in CMV DNA levels. However, Kampo medicine demonstrated no virocidal effect on cell-free CMV. Furthermore, western blotting analysis demonstrated that the Kampo medicine decreased the amount of 65 kDa late antigen expression in the infected cells. These results suggest that Kampo medicine may be sufficient to inhibit viral DNA replication and late protein synthesis, resulting in anti-CMV effects. Therefore, these three Kampo medicines have the potential of being a source of new powerful anti-CMV compounds. PMID:15841262

  9. The availability of health information in South Africa.

    PubMed

    Pienaar, E D

    1995-01-01

    The South African Medical Research Council (MRC) has provided access to on-line health and biomedical information since 1976, when the MRC became an international partner of NLM. This was done to support research and health care when the Institute of Biomedical Communication was established. The institute has since reorganized and is now the Information Systems Division in the Research Systems Support Group MRC. he MRC and medical libraries in South Africa are able to access various automated services via telecommunication. The major systems available are MEDLARS, DIALOG, DATASTAR and BRS, with ECRI being the latest addition; most used are MEDLARS and DIALOG. New technologies (e.g., CD-ROM) have given more people access. This technology is not available to many people working in Primary Health Care (PHC), as they do not have access to computer networks. Beyond on-line is statistical and printed information, called "Gray Literature," not accessible through on-line systems as it is not published in conventional sources used to build databases. With a shift to Essential National Health Research and the focus on PHC and preventative medicine, demand for health information and "gray literature" is growing. The MRC collects and produces this material and has its own database called SAMED, which is to be made available to others as our contribution to health. It is hoped to make this available for inclusion in the proposed African Index Medicus presently investigated by the World Health Organization. Africa as a continent, and South Africa as a country, are experiencing major changes in health care and medical practice, and inevitably, provision of health information services. With South Africa's re-entry into the global village and its acceptance by the rest of Africa, it can be a key player in information provision to the rest of the continent. The MRC, as a major provider of Health information, can play a vital role in the information flow throughout Africa by

  10. MATRIS Indexing and Retrieval Thesaurus (MIRT): Keyword Out of Context (KWOC)

    DTIC Science & Technology

    1994-08-01

    BREATHING Mrc 18 -B- I I I -- BRIDGE BRIDGE control systems Xeic BRIDGE control simulator Epqc i BRIGS Military BRIGS Feua I BROADCAST BROADCAST media Ys I I...CHANGE Gei Social CHANGE effects Fiqia CHANGES Social trends / CHANGES Bok CHANNELS Career promotion CHANNELS Fceg CHAPLAINRY Religious programs...m Attitudes of COMMUNITIES Mfem COMMUNITY I COMMUNITY / social -related factors Fiqi COMMUNITY relations skills Sim COMPANIES COMPANIES Gcka COMPANY

  11. Combining cell lines to optimize isolation of human enterovirus from clinical specimens: report of 25 years of experience.

    PubMed

    Prim, Núria; Rodríguez, Graciela; Margall, Núria; Del Cuerpo, Margarita; Trallero, Gloria; Rabella, Núria

    2013-01-01

    Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A total of 521 HEVs were characterized, and HEV-B was the most frequent species (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs.

  12. Current and Historical Sediment Loads in the Lower Mississippi River

    DTIC Science & Technology

    2008-07-01

    been affected by changes in land-use and river management; increasing in the 19th and early-20th Centuries, before decreasing due to soil ...System IL Illinois xx KY Kentucky LA Louisiana LCA Louisiana Coastal Area MO Missouri MRC Mississippi River Commission MR&T Mississippi River...before decreasing due to soil conservation and improved land management. The supply of sediment from tributaries is also believed to have decreased

  13. The Misperception of Contingency Contracting

    DTIC Science & Technology

    2011-05-01

    images of military men and women carrying bags full of money executing purchases on foreign soil . While these images are not totally inaccurate, they are...Mission Ready Contracting Officer Course ( MRC ) for Air Force officers and civilians (on a space-available basis). As most deployed contingency contracting...Hurricane Katrina was, in all probability, spared because operations were conducted on U.S. soil . The FAR is applicable to all contingency operations

  14. A Preliminary Anthropometry Standard for Australian Army Equipment Evaluation

    DTIC Science & Technology

    2014-08-01

    Cowan University in 2004. For the following three years she worked as a Research Officer for NH&MRC funded physiotherapy and ergonomic research...of head size? Clearance Does the system prevent undesirable contact with the body Performance - if users are immobilised then they will be...unable to continue working. If access to controls are impinged, then the user’s ability to operate the system will be reduced Safety - injury may be

  15. Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis.

    PubMed

    Koulouris, N G; Retsou, S; Kosmas, E; Dimakou, K; Malagari, K; Mantzikopoulos, G; Koutsoukou, A; Milic-Emili, J; Jordanoglou, J

    2003-05-01

    In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WRmax and FL were assessed in 23 stable caucasian patients (six males) aged 56 +/- 17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WRmax was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WRmax (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

  16. Polymeric micellar co-delivery of resveratrol and curcumin to mitigate in vitro doxorubicin-induced cardiotoxicity.

    PubMed

    Carlson, Lisa Janssen; Cote, Brianna; Alani, Adam Wg; Rao, Deepa A

    2014-08-01

    Resveratrol (RES) and curcumin (CUR) have free radical scavenging ability and potential chemosensitizing effects. Doxorubicin hydrochloride (DH) is a potent chemotherapeutic with severe cardiotoxicity. We hypothesize that RES and CUR co-loaded in Pluronic(®) micelles and co-administered with DH will result in cardioprotective effects while maintaining/improving DH anti-proliferative effect in vitro. RES-CUR at a molar ratio of 5:1 in F127 micelles (mRC) were prepared and characterized for size, drug loading, and release. In vitro cell viability and apoptosis assays in ovarian cancer cells (SKOV-3) and cardiomyocytes (H9C2) with either individual drugs or RES-CUR or mRC in combination with DH were conducted. Combination index (CI) analysis was performed to determine combination effects. Reactive oxygen species (ROS) were quantified in H9C2 for DH, and combinations. The mRC solubilized 2.96 and 0.97 mg/mL of RES and CUR, respectively. Cell viability and CI studies indicated that the combinations were synergistic in SKOV-3 and antagonistic in H9C2 cells. Caspase 3/7 activity in combination treatments was lower than with DH alone in both cell lines. ROS activity was restored to baseline in H9C2 cells in the micelle combination groups. Co-administration of mRC with DH in vitro mitigates DH-induced cardiotoxicity through reduction in apoptosis and ROS while improving DH potency in ovarian cancer cells. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. VizieR Online Data Catalog: Spiderweb galaxy 870um and 1.4GHz images (Dannerbauer+, 2014)

    NASA Astrophysics Data System (ADS)

    Dannerbauer, H.; Kurk, J. D.; De Breuck, C.; Wylezalek, D.; Santos, J. S.; Koyama, Y.; Seymour, N.; Tanaka, M.; Hatch, N.; Altieri, B.; Coia, D.; Galametz, A.; Kodama, T.; Miley, G.; Roettgering, H.; Sanchez-Portal, M.; Valtchanov, I.; Venemans, B.; Ziegler, B.

    2014-11-01

    We provide both the APEX LABOCA 870um and the EVLA 1.4GHz signal map of the field around the high-z radio galaxy MRC1138-262. In addition, we make the integration and signal-to-noise map of the LABOCA observations available. The LABOCA signal and S/N map are in Jy, the integration map in seconds and the VLA 1.4GHz signal map is in uJy. (2 data files).

  18. Production Team Maintenance: Systemic Constraints Impacting Implementation

    DTIC Science & Technology

    1997-05-01

    that may lend insight to factors inhibiting PTM implementation. Chapter four highlights alternatives and options that may improve implementation efforts...17). The two-MRC requirement is considered the "principal urgent diet " of the military. Efforts are focused on organizing, training, and equipping...maintenance AGS under the LG 1997: (Apr) CONUS C-130s realigned under AMC and AMOGs restructured The implementation of PTM followed suit--its structure

  19. The Impact of Changes in State Identity on Alliance Cohesion in Northeast Asia

    DTIC Science & Technology

    2009-12-01

    School, Sun Zhe at Tsinghua University, and Zhan Debin at Fudan University, began to publicly express their new perceptions of the capabilities...Rin 4 al Hong Xuezhi 1 henyang MRC Wang Ke General Kim Hak Sam 994 DDM Kim Jong Kak COGS Choe Kwang General Oh Yong Bang 5 S 1995 MDN DFAB Sun...Qixiang AMS PC Zhang Gong Guangzhou MRPC Shi Yuxia DDM Kim Jong Kak 4 1996 ILD Deputy Director Dai Bingguo North Sea FC Wang Jiying

  20. A Systematic Review of Outcomes of Contralateral C7 for the Treatment of Traumatic Brachial Plexus Injury: Part 1-Overall outcomes of contralateral C7 transfer for traumatic brachial plexus injury

    PubMed Central

    Yang, Guang; Chang, Kate W.-C.; Chung, Kevin C.

    2015-01-01

    Background Contralateral C7 (CC7) transfer has been used for treating traumatic brachial plexus injury. However, the effectiveness of CC7 transfer remains a subject of debate. We performed a systematic review to study the overall outcomes of CC7 transfer to different recipient nerves in traumatic brachial plexus injuries. Methods A literature search was conducted using PubMed and EMBASE databases to identify original articles related to CC7 transfer for traumatic brachial plexus injury. The data extracted were study/ patient characteristics, and objective outcomes of CC7 transfer to the recipient nerves. We normalized modifications of MRC and other outcome measures into an MRC-based outcome scale for comparisons. Results Thirty-nine studies were identified. The outcomes were categorized based on the three major recipient nerves: median, musculocutaneous, and radial/triceps nerves. Regarding overall functional recovery, 11% of patients achieved MRC grade M4 wrist flexion and 38% achieved M3. Grade M4 finger flexion was achieved by 7% of patients whereas 36% achieved M3. Finally, 56% of patients achieved ≥S3 sensory recovery in the median nerve territories. In the musculocutaneous nerve group, 38% of patients regained elbow flexor strength to M4 and 37% regained to M3. In the radial/triceps nerve group, 25% regained elbow or wrist extension strength to an MRC grade M4 and 25% regained to M3. Conclusions Outcome measures in the included studies were not consistently reported to uncover true patient-related benefits from the CC7 transfer. Reliable and validated outcome instruments should be applied to critically evaluate patients undergoing CC7 transfer. PMID:26397253

  1. Validation of Rules to Predict Emergent Surgical Intervention in Pediatric Trauma Patients

    PubMed Central

    Boatright, Dowin H; Byyny, Richard L; Hopkins, Emily; Bakes, Katherine; Hissett, Jennifer; Tunson, Java; Easter, Joshua S; Vogel, Jody A; Bensard, Denis; Haukoos, Jason S

    2014-01-01

    Background Trauma centers use guidelines to determine when a trauma surgeon is needed in the emergency department (ED) on patient arrival. A decision rule from Loma Linda University identified patients with penetrating injury and tachycardia as requiring emergent surgical intervention. Our goal was to validate this rule and to compare it to the American College of Surgeons’ Major Resuscitation Criteria (MRC). Study Design We used data from 1993 through 2010 from two Level 1 trauma centers in Denver, Colorado. Patient demographics, injury severity, times of ED arrival and surgical intervention, and all variables of the Loma Linda Rule and the MRC were obtained. The outcome, emergent intervention (defined as requiring operative intervention by a trauma surgeon within one hour of arrival to the ED or performance of cricothyroidotomy or thoracotomy in the ED) was confirmed using standardized abstraction. Sensitivities, specificities, and 95% confidence intervals (CIs) were calculated. Results 8,078 patients were included and 47 (0.6%) required emergent intervention. Of the 47 patients, the median age was 11 years (IQR: 7–14), 70% were male, 30% had penetrating mechanisms, and the median ISS was 25 (IQR: 9–41). At the two institutions, the Loma Linda Rule had a sensitivity and specificity of 69% (95% CI: 45%–94%) and 76% (95% CI: 69%–83%), respectively, and the MRC had a sensitivity and specificity of 80% (95% CI: 70%–92%) and 81% (95% CI: 77%–85%), respectively. Conclusions Emergent surgical intervention is rare in the pediatric trauma population. Although precision of predictive accuracies of the Loma Linda Rule and MRC were limited by small numbers of outcomes, neither set of criteria appears to be sufficiently accurate to recommend their routine use. PMID:23623222

  2. Powder-Metallurgical Bearings For Turbopumps

    NASA Technical Reports Server (NTRS)

    Bhat, B. N.; Humphries, T. S.; Thom, R. L.; Moxson, V.; Friedman, G. I.; Dolan, F. J.; Shipley, R. J.

    1993-01-01

    Bearings fabricated by powder metallurgy developed for use in machines subjected to extremes of temperature, rolling-contact cyclic stresses, and oxidizing or otherwise corrosive fluids. Bearings also extend operating lives of other machines in which bearings required to resist extreme thermal, mechanical, and chemical stresses. One alloy exhibiting outstanding properties was MRC-2001. Resistance to fatigue, stress corrosion cracking, and wear found superior to that of 440C stainless steel.

  3. VizieR Online Data Catalog: Gunn photometry of seven clusters of galaxies (Molinari+ 1996)

    NASA Astrophysics Data System (ADS)

    Molinari, E.; Buzzoni, A.; Chincarini, G.

    1996-04-01

    Gunn g, r, i photometry for the 7 clusters MRC0254-274, Cl0317+15, MS0418.3-3 844, Cl1141-283, A1689, A3594, S0781B is presented. For each cluster we derived the spatial distribution properties obtaining the core radius and the concentration parameters. Color properties of the cluster galaxy population are also briefly discussed. (7 data files).

  4. Magnetic resonance cholangiography in assessing biliary anatomy in living donors: a meta-analysis.

    PubMed

    Xu, Yu-Biao; Bai, Yu-Long; Min, Zhi-Gang; Qin, Shan-Yu

    2013-12-07

    To establish the role of magnetic resonance cholangiography (MRC) in diagnosis of biliary anatomy in living-donor liver transplantation (LDLT) donors. A systematic review was performed by searching electronic bibliographic databases prior to March 2013. Studies with diagnostic results and fulfilled inclusion criteria were included. The methodological quality of the studies was assessed. Sensitivity, specificity and other measures of the accuracy of MRC for diagnosis of biliary anatomy in LDLT donors were summarized using a random-effects model or a fixed-effects model. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Publication bias was assessed using Deek's funnel plot asymmetry test. Sensitivity analysis was adopted to explore the potential sources of heterogeneity. Twelve studies involving 869 subjects were eligible to the analysis. The scores of Quality Assessment of Diagnostic Accuracy Studies for the included studies ranged from 11 to 14. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR of MRC in diagnosis of biliary anatomy in LDLT donor were 0.88 (95%CI: 0.84-0.92), 0.95 (95%CI: 0.93-0.97), 15.33 (95%CI: 10.70-21.95), 0.15 (95%CI: 0.11-0.20) and 130.77 (95%CI: 75.91-225.27), respectively. No significant heterogeneity was detected in all the above four measures. Area under SROC curve was 0.971. Little publication bias was noted across the studies (P = 0.557). Sensitivity analysis excluding a study with possible heterogeneity got a similar overall result, which suggested the little influence of this study on the overall results. Our results suggest that MRC is a high specificity but moderate sensitivity technique in diagnosis of biliary anatomy in LDLT donors. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.

  5. Assessment of Medical Reserve Corps Volunteers' Emergency Response Willingness Using a Threat- and Efficacy-Based Model

    PubMed Central

    Barnett, Daniel J.; Thompson, Carol B.; Tosatto, Rob; Austin, Brad; Schaffzin, Samuel; Ansari, Armin; Semon, Natalie L.; Balicer, Ran D.; Links, Jonathan M.

    2013-01-01

    The goal of this study was to investigate the willingness of Medical Reserve Corps (MRC) volunteers to participate in public health emergency–related activities by assessing their attitudes and beliefs. MRC volunteers responded to an online survey organized around the Extended Parallel Process Model (EPPM). Respondents reported agreement with attitude/belief statements representing perceived threat, perceived efficacy, and personal/organizational preparedness in 4 scenarios: a weather-related disaster, a pandemic influenza emergency, a radiological (“dirty bomb”) emergency, and an inhalational anthrax bioterrorism emergency. Logistic regression analyses were used to evaluate predictors of volunteer response willingness. In 2 response contexts (if asked and regardless of severity), self-reported willingness to respond was higher among those with a high perceived self-efficacy than among those with low perceived self-efficacy. Analyses of the association between attitude/belief statements and the EPPM profiles indicated that, under all 4 scenarios and with few exceptions, those with a perceived high threat/high efficacy EPPM profile had statistically higher odds of agreement with the attitude/belief statements than those with a perceived low threat/low efficacy EPPM profile. The radiological emergency consistently received the lowest agreement rates for the attitude/belief statements and response willingness across scenarios. The findings suggest that enrollment with an MRC unit is not automatically predictive of willingness to respond in these types of scenarios. While MRC volunteers' self-reported willingness to respond was found to differ across scenarios and among different attitude and belief statements, the identification of self-efficacy as the primary predictor of willingness to respond regardless of severity and if asked highlights the critical role of efficacy in an organized volunteer response context. PMID:23477632

  6. Standardized Training to Improve Readiness of the Medical Reserve Corps: A Department of Health and Human Services Program under the Direction of the Office of the Surgeon General

    DTIC Science & Technology

    2006-09-01

    dress code , reporting and deployment. Finally, all MRC volunteers should know the policy and procedures of their local unit. This content area is... dress code for attending training or for duty assignments it should be included as well. Policy and procedures are also necessary for deployments and...Procedures • Attendance • Licensing and certification • Training • Deployment process • Reporting • Dress code 62

  7. Biophysical Aspects of Cyclodextrin Interaction with Paraoxon

    DTIC Science & Technology

    2013-12-19

    Institute of Chemical Defense ATTN: MCMR-CDR-I 3100 Ricketts Point Road Aberdeen Proving Ground, MD 21010-5400 USAMRICD-P13-018 9...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Rapid communication Received: 9 August 2013 Revised: 14 November 2013 Accepted: 18 November... 2013 Published online in Wiley Online Library: 19 December 2013 (wileyonlinelibrary.com) DOI 10.1002/mrc.4036Biophysical aspects of cyclodextrin

  8. Enhancing Floodplain Management in the Lower Mekong River Basin Using Vegetation and Water Cycle Satellite Observations

    NASA Astrophysics Data System (ADS)

    Bolten, J. D.; Spruce, J.; Wilson, R.; Strauch, K.; Doyle, T.; Srinivan, R.; Lakshmi, V.; Gupta, M.

    2014-12-01

    The Lower Mekong River Basin shared by China, Burma, Laos, Thailand, Cambodia, and Vietnam, is considered the lifeblood of Southeast Asia. The Mekong Basin is subject to large hydrological fluctuations on a seasonal and inter-annual basis. The basin remains prone to severe annual floods that continue to cause widespread damage and endanger food security and the livelihood of the millions who dwell in the region. Also the placement of newly planned dams primarily for hydropower in the Lower Mekong Basin may cause damaging social, agriculture and fisheries impacts to the region where we may now likely be at a critical 'tipping point'. The primary goal of this project is to apply NASA and USGS products, tools, and information for improved flood and water management in the Lower Mekong River Basin to help characterize, understand, and predict future changes on the basin. Specifically, we are providing and helping transfer to the Mekong River Commission (MRC) and the member countries of Thailand, Cambodia, Lao, Vietnam, and Burma the enhanced Soil and Water Assessment Tool (SWAT) using remotely sensed surface, ground water, and root zone soil moisture along with improved Land Use and Land Cover (LULC) maps. In order to estimate the flood potential and constrain the SWAT Available Water Capacity model parameter over the region, we are assimilated GRACE Terrestrial Water Storage observations into the Catchment Land Surface Model. In addition, a Graphic Visualization Tool (GVT) as been developed to work in concert with the output of the SWAT model parameterized for the Mekong Basin as an adjunct tool of the MRC Decision Support Framework. The project requires a close coordination of the development and assessment of the enhanced MRC SWAT with the guidance of MRC resource managers and technical advisors. This presentation will evaluate the skill of the enhanced SWAT model using qualitative (i.e., MODIS change detection) and quantitative (e.g., streamflow) metrics over one

  9. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    PubMed Central

    Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

    2016-01-01

    Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients’ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2–4 in the distal muscles (the MRC score before the treatment was 3–4 and 1–3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment. PMID:27857755

  10. Processing of Novel Nanoparticle Dispersion Strengthened Ceramics for Improved Mechanical Performance

    DTIC Science & Technology

    1993-12-14

    A2751 1 965 Eeto liii Optics MRC Materials Education M CLiaison Program Mchanical Polymers Behavior SECOND ANNUAL REPORT PROCESSING OF NOVEL...NANOPARTICLE DISPERSION STRENGTHENE D CERAMICS FOR IMPROVED MECHANICAL PE RFORMANCE Professors 11. M . Chan, (P.1.), M . P. Harmer (Co-P.I.), ___ and...Institute ONR Grant No.: N00014-92-J-1635 Mod. P00002 EPRI Contract: RP2426-54 Amend. 1 Re ,ort Period: 15 December 1992 - 14 December 1993 M ateral R

  11. Cost-effectiveness analysis of establishing a distance-education programme for health personnel in Swaziland.

    PubMed

    Kirigia, Joses M; Sambo, Luis G; Phiri, Margaret; Matsembula, Gladys; Awases, Magda

    2002-01-01

    There is a growing conviction among policy-makers that the availability of adequate numbers of well-trained and motivated human resources is a key determinant of health system' s capacity to achieve their health, responsiveness and fairness-improving goals. The objective of this study was to estimate the cost, effectiveness and incremental cost-effectiveness ratios of various distance-education strategies for the health sector in Swaziland; and recommend the most cost-effective option. The distance-education strategies evaluated included: Mobile library services (MLS); micro-resources centers WITHOUT video conferencing in five health centers and four regional hospitals (MRC-VC); micro-resources centers WITH video conferencing in five health centers and four regional hospitals (MRC+VC); centralized resource center WITHOUT video conferencing (CRC-VC); centralized resource center WITH video conferencing (CRC+VC); and status quo (SQ). The incremental cost-effectiveness ratio for MLS was Emalangeni (E) 41,846; MRC-VC was E42,696; MRC+VC was E45,569; CRC-VC was E43,578; CRC+VC was E40,827; the latter being the most cost-effective distance-education strategy. According to policy-makers, this study served to clarify the various distance-education strategies, their costs and their benefits/effectiveness. There is a need for developing in Africa a culture of basing policy and management decisions of such kind on systematic analyses. Of course, economic evaluation will, at most, be a guide to policy- and decision-making, and thus, the onus of decision-making will always be on policy-makers and health-care managers.

  12. Comparison of intermittent positive pressure breathing and temporary positive expiratory pressure in patients with severe chronic obstructive pulmonary disease.

    PubMed

    Nicolini, Antonello; Mollar, Elena; Grecchi, Bruna; Landucci, Norma

    2014-01-01

    Results supporting the use and the effectiveness of positive expiratory, pressure devices in chronic obstructive pulmonary disease (COPD) patients are still controversial, We have tested the hypothesis that adding TPEP or IPPB to standard pharmacological therapy may provide additional clinical benefit over, pharmacological therapy only in patients with severe COPD. Fourty-five patients were randomized in three groups: a group was treated; with IPPB,a group was treated with TPEP and a group with pharmacological; therapy alone (control group). Primary outcome measures included the measurement of scale or, questionnaire concerning dyspnea (MRC scale),dyspnea,cough, and, sputum (BCSS) and quality of life (COPD assessment test) (CAT). Secondary, outcome measures were respiratory function testing,arterial blood gas,analysis,and hematological examinations. Both patients in the IPPB group and in the TPEP group showed a significant, improvement in two of three tests (MRC,CAT) compared to the control, group.However,in the group comparison analysis for, the same variables between IPPB group and TPEP group we observed a, significant improvement in the IPPB group (P≤.05 for MRC and P≤.01 for, CAT). The difference of action of the two techniques are evident in the results of, pulmonary function testing: IPPB increases FVC, FEV1, and MIP; this reflects, its capacity to increase lung volume. Also TPEP increases FVC and FEV1 (less, than IPPB), but increases MEP, while decreasing total lung capacity and, residual volume. The two techniques (IPPB and TPEP) improves significantly dyspnea; quality of; life tools and lung function in patients with severe COPD. IPPB demonstrated a greater effectiveness to improve dyspnea and quality of life tools (MRC, CAT) than TPEP. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  13. [Determination and characterization on the capacity of humic acid for the reduction of divalent mercury].

    PubMed

    Jiang, Tao; Wet, Shi-Qiang; Li, Xue-Mei; Lu, Song; Li, Meng-Jie; Luo, Chang

    2012-01-01

    Reduction capacity (RC) has been recognized as an important parameter for evaluating the redox role of humic acid (HA). Thus, for understanding the capacity of HA for the reduction of mercury (Hg2+), chemical reduction capacity (CRC), microbial reduction capacity (MRC) and native reduction capacity (NRC) for mercury reduction by three types of HAs extracted from various sources (SH, TJ and JY) were measured respectively, following the pre-treatment of the HA samples by saturated hydrogen oscillation, soil solution incubation and the control (without any pretreatment). Three electron acceptors including mercuric chloride (HgCl2), mercuric nitrate [Hg(NO3)3] and ferric citrate (FeCit) as a reference were adapted respectively based on the Fe3+ reduction method. The principal results indicated that: (1) the capacity of HA for the reduction of Hg was significantly affected by various electron acceptors, with the RC values obtained under FeCit condition were all greatly higher than those in the conditions of Hg(NO3)2 and HgCl2, which suggested that the RC obtained using Fe3+ reduction method could exaggerate the actual capacity of HA for the reduction of Hg2+; (2) significant differences existed for the reduction capacity of Hg2+ by different HAs, with those of JY were the highest, which were (0.95 +/- 0.03) mmol(c) x mol(-1) (NRC), (5.95 +/- 0.63) mmol(c) x mol(-1) (CRC) and (6.26 +/- 0.51) mmol(c) x mol(-1) (MRC) respectively; (3) HA in solution forms had approximately 100% - 691.67% higher reduction capacity than those as solid forms. Meanwhile, through comparison of the differences among three RC indices, higher CRC and MRC values than NRC were observed, but no significant difference between CRC and MRC was concluded. Thus, CRC may not be applicable to comprehensively represent the real reduction capacity of HA for Hg reduction under microbial condition.

  14. Perceived Urgency of Warning Signals Determined Using a Forced Choice Pair Comparison Technique

    DTIC Science & Technology

    1988-11-01

    Lk\\ I UUi~ TECH. MEMO UNLIMITED TECH. MEMO MM 12 mm 12 ROYAL AEROSPACE ESTABLISHMENT 0 PERCEIVED URGENCY OF WARNING SIGNALS DETERMINED USING A FORCED...Farnborough), ISVR (Southampton University) and APU (MRC, Cambridge) a set of 40 high urgency warning signals were designed for RAE. The spectral...was designed to select, from these 40 signals, the six which were perceived as conveying the greatest urgency , and then, to assess these in a set

  15. The Role of Mms22p in DNA Damage Response in Candida albicans

    PubMed Central

    Yan, Lan; Xiong, Juan; Lu, Hui; Lv, Quan-zhen; Ma, Qian-yao; Côte, Pierre; Whiteway, Malcolm; Jiang, Yuan-ying

    2015-01-01

    To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans. In this pathogen, Mms22p is important for recovery from DNA replication damage induced by agents including methylmethane sulfonate, camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has been identified in C. albicans, loss of either Mms22p or Rtt101p generates similar damage sensitivity, consistent with a common function. In S. cerevisiae, the Mrc1p−Csm3p−Tof1p complex stabilizes stalled replication forks and activates a replication checkpoint and interacts with Mms22p. A similar complex in S. pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants. In C. albicans, although the loss of RAD57 greatly impairs response in the pathogen to many DNA-damaging agents, lethality due to camptothecin damage requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only essential for homologous recombination induced by camptothecin. These results establish that although C. albicans uses conserved cellular modules to respond to DNA damage and replication blocks, the specific details of these modules differ significantly from the S. cerevisiae model. PMID:26438292

  16. On the Existence of Periodic Solutions for a Class of Symmetric Hamiltonian Systems.

    DTIC Science & Technology

    1986-01-01

    AMD-R167 487 ON THE EXISTENCE OF PERIODIC SOLUTIONS FOR R CLRSS OF u1 SYNNETRIC HNMILTONI.. (U) NISCONSIN UNIY-MDISON IITHEMATICS RESERRCH CENTER P...1,,... 1.,.1...-,....-.I- - ; :. . : < : ’..p .. . . MRC Technical Summary Report #2901 ON THE EXISTENCE OF PERIODIC SOLUTIONS FOR A CLASS OF...MADISON , MATHEMATICS RESEARCH CENTER -%>."S.- ON THE EXISTENCE OF PERIODIC SOLUTIONS FOR A CLASS OF SYMMETRIC HAMILTONIAN SYSTEMS Paul R. Rabinowitz

  17. Degenerate Systems of Conservation Laws.

    DTIC Science & Technology

    1985-09-01

    uI, ..., un ) u(x,t) , f " (fl’ "**’ fn) and x c R, t ) 0. Such equations arise in applications of gas dynamics, elasticity, oil reservoir ... simulation and other areas of engineering when diffusion is neglected. In solutions of (1), information travels at speeds Xi given by the eigenvalues of...laws which is not strictly hyperbolic", MRC Technical Summary Report #2184, December 29, 1980. [13] Peaceman, D. W., Fundamentals of Numerical Reservoir

  18. Phylogeography and genetic structure of the oriental river prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) in East Asia

    PubMed Central

    Chu, Ta-Jen; Lee, Ying-Chou

    2017-01-01

    The oriental river prawn (Macrobrachium nipponense) is mainly distributed in East Asia. The phylogeography, population genetic structure and historical demography of this species in the East Asia were examined by using partial sequences of the cytochrome oxidase subunit I (COI) and 16S rRNA in mitochondrial DNA. Ten populations that included 239 individuals were collected from Taiwan (Shihmen Reservoir, SMR, Mingte Reservoir, MTR and Chengching Lake Reservoir, CLR), mainland China (Taihu Lake, TLC, Min River, MRC, Jiulong River, JRC and Shenzhen Reservoir, SRC), Japan (Biwa Lake, BLJ and Kasumigaura Lake, KLJ) and Korea (Han River, HRK). The nucleotide diversity (π) of all individuals was 0.01134, with values ranging from 0.0089 (BLJ, Japan) to 0.01425 (MTR, Taiwan). A total of 83 haplotypes were obtained, and the haplotypes were divided into 2 main lineages: lineage A included the specimens from BLJ, KLJ, CLR, MTR, TLC, MRC and JRC, and lineage B comprised the ones from HRK, SRC, SMR, MTR, TLC, MRC and JRC. Lineage A could be further divided two sub-lineages (A1 and A2). Individuals of lineage A2 were only from TLC. Demographic expansion was observed in each lineage, starting within the second-to-latest interglacial period for lineage A and within the last glacial period for lineage B. All FST values among the ten populations were significantly different, except for the values between MRC and JRC, and SMR and SRC. The phylogeography and genetic structure of M. nipponense in East Asia might be influenced by Pleistocene glacial cycles, lake isolation and human introduction. The possible dispersal routes of M. nipponense in the East Asia were also discussed. PMID:28267807

  19. Damage-based finite-element vertebroplasty simulations.

    PubMed

    Kosmopoulos, V; Keller, T S

    2004-11-01

    The objectives of this study were to quantify the efficacy of vertebroplasty according to: (1) damage and (2) cement quantity (fill) and modulus. Vertebral body damage was numerically simulated using a previously validated two-dimensional finite-element model coupled with an elasto-plastic modulus reduction (EPMR) scheme. The effects of cement fill (% marrow replaced by cement, % MRC) and cement modulus on vertebral apparent modulus and trabecular bone tissue stress concentrations were parametrically assessed for four EPMR damage models (19%, 33%, 60%, and 91% modulus reduction). For this analysis, the elastic modulus of the trabecular bone tissue and marrow elements were assumed to be 10 GPa and 10 kPa, respectively. The effect of cement modulus (varied in the range 1 GPa to 9 GPa) on vertebral apparent modulus was also examined for partial fill (39% MRC) and complete fill (100% MRC) using the 33% modulus reduction damage model. In the case of polymethylmethacrylate (PMMA cement modulus = 2.16 GPa), restoration of the thoracic vertebral body (T10) apparent modulus to undamaged levels required 71% and 100% cement fill for the 19-33% and 60-91% modulus reduction damage models, respectively. Variations in cement modulus had no appreciable effect on the recovery of vertebral apparent modulus to undamaged levels for simulations of partial cement fill (39% MRC). For complete cement fill, however, a PMMA cement modulus produced approximately a 2-fold increase (82%) in vertebral apparent modulus relative to the undamaged vertebral body. Increasing the cement modulus to 9 GPa increased the vertebral apparent modulus over 2.5-fold (158%) relative to the undamaged state. The EPMR damage scheme and repair simulations performed in this study will help clinicians and cement manufacturers to improve vertebroplasty procedures.

  20. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

    PubMed Central

    Demeyer, Heleen; Gimeno-Santos, Elena; Rabinovich, Roberto A.; Hornikx, Miek; Louvaris, Zafeiris; de Boer, Willem I.; Karlsson, Niklas; de Jong, Corina; Van der Molen, Thys; Vogiatzis, Ioannis; Janssens, Wim; Garcia-Aymerich, Judith; Troosters, Thierry; Polkey, Michael I.

    2016-01-01

    Background The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used. Methods 136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. Results GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. Conclusions Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. Clinical Trial Registration ClinicalTrials.gov NCT01388218 PMID:26974332

  1. Relationship between histologic grade and cytofluorometric cellular DNA and RNA content in primary bone tumors.

    PubMed

    Takeshita, H; Kusuzaki, K; Kuzuhara, A; Tsuji, Y; Ashihara, T; Gebhardt, M C; Mankin, H J; Springfield, D S; Hirasawa, Y

    2001-01-01

    The diagnosis and grading of bone tumors remains a challenging problem. We studied the relationship between histologic grade and cytofluorometric cellular DNA and RNA content in 108 primary bone tumors. The data included DNA ploidy, mean DNA content (MDC), S-phase fraction (SPF), mean RNA content (MRC) and RNA/DNA ratio (RDR; MRC/MDC) which represents the RNA content normalized for the DNA content. Benign tumors had a diploid stem line with low MDC (mean; 1.04), low SPF (0.9), high MRC (2.41) and high RDR (2.31). Giant cell tumors of bone, which are locally aggressive benign tumors, showed diploidy with relatively higher MDC (1.07, p < 0.01) and SPF (2.6, p < 0.01) and lower MRC (1.81, p < 0.01) and RDR (1.69, p < 0.01). Similar results were obtained in low-grade sarcomas. In high-grade sarcomas, the data depended on the histologic findings. Pleomorphic sarcomas such as osteosarcomas revealed aneuploidy with remarkably higher MDC (1.70 in osteosarcomas, p < 0.01) and SPF (6.5, p < 0.01), but lower RDR (1.70, p < 0.01). In contrast, small cell sarcomas, such as Ewing's sarcomas, showed diploidy with low MDC (1.11 in Ewing's sarcomas, N.S.) and SPF (2.5, p < 0.01) and extremely low RDR (1.34, p < 0.01). The RDR value was higher in well-differentiated tumors than in primitive tumors, rendering it useful in grading bone tumors with a diploid stem line. By combining the RDR value with the MDC value, 96% of diploid sarcomas could be distinguished from benign tumors. These results indicate that cellular DNA and RNA content analysis may be of value in assessing the malignant potential of diploid as well as aneuploid bone sarcomas.

  2. Correlation between ICDAS and histology: Differences between stereomicroscopy and microradiography with contrast solution as histological techniques

    PubMed Central

    Campos, Samara de Azevedo Gomes; Vieira, Maria Lúcia Oliveira

    2017-01-01

    Detection of occlusal caries with visual examination using ICDAS correlates strongly with histology under stereomicroscopy (SM), but dentin aspects under SM are ambiguous regarding mineral content. Thus, our aim was to test two null hypotheses: SM and microradiography result in similar correlations between ICDAS and histology; SM and microradiography result in similar positive (PPV) and negative predictive values (NPV) of ICDAS cut-off 1–2 (scores 0–2 as sound) with histological threshold D3 (demineralization in the inner third of dentin). Occlusal surfaces of extracted permanent teeth (n = 115) were scored using ICDAS. Undemineralized ground sections were histologically scored using both SM without contrast solution and microradiography after immersion in Thoulet’s solution 1.47 for 24 h (MRC). Correlation between ICDAS and histology differed from SM (0.782) to MRC (0.511) (p = 0.0002), with a large effect size “q” of 0.49 (95% CI: 0.638/0.338). For ICDAS cut-off 1–2 and D3, PPV from MRC (0.56) was higher than that from SM (0.28) (p< 0.00001; effect size h = 0.81), and NPV from MRC (0.72) was lower than that from SM (1,00) (p < 0.00001; effect size h = 1.58). In conclusion, SM overestimated the correlation between ICDAS and lesion depth, and underestimated the number of occlusal surfaces with ICDAS cut-off 1–2 and deep dentin demineralization. PMID:28841688

  3. Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells

    PubMed Central

    ODEWUMI, CAROLINE; LATINWO, LEKAN M.; SINCLAIR, ANDRE; BADISA, VEERA L.D.; ABDULLAH, AHKINYALA; BADISA, RAMESH B.

    2015-01-01

    Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl2) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl2 compared with the normal MRC-9 lung cells. In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl2 concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl2 concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl2 affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity. PMID:26397147

  4. Developing Vibrant State Defense Forces: A Successful Medical and Health Service Model

    DTIC Science & Technology

    2006-01-01

    MEDICAL AND HEALTH SERVICE MODEL Colonel (MD) H. Wayne Nelson, Ph.D. Colonel (MD) Robert Barish, M.D. Brigadier General (MD) Frederic Smalkin, J.D...Its Deputy Commander and MRC project action officer was (one of the authors, Nelson), a professor in the Health Science Department in Towson ...Director COL Wayne Nelson, to select “medically-qualified soldiers” who would accept assignment to “participate in humanitarian missions in response and

  5. Memphis Harbor, Mississippi River: Model Investigation

    DTIC Science & Technology

    1950-12-01

    MEMORANDUM NO. 2 -320 CONDUCTED F OR THE PRESIDENT, MISSISSIPPI RIVER COMMISSION ARMY·MRC.VICKSBURG. MISS. CORPS OF ENGINEERS, U. S. ARMY BY...failing to comply with a collection of information if it does not display a currently valid OMB control number 1. REPORT DATE DEC 1950 2 . REPORT TYPE...second wrapper indorsement to Waterways Experiment Station letter dated 2 October 1946, subject: "Proposed Model Study, Presidents Island, Mississippi

  6. Current Methods for Evaluation of Physical Security System Effectiveness.

    DTIC Science & Technology

    1981-05-01

    Method (Mission Research Corporation ) FSNM Fixed Site Neutralization Model (Vector Research, Inc., for Sandia Laboratories, Albuquerque) PROSE...METHODS a. Security System Performance Assessment Method (SSPAM) (Mission Research Corporation )--The SSPAM concept is an ambitious attempt to carry...Descriptions; Volume III: SSPAM Results; MRC-R-564, Mission Research Corporation , April 1980 Sanderlin, J.C., and Rathman, C.E., A Concept for

  7. Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL.

    PubMed

    N' Guessan, Benoit Banga; Sanchez, Hervé; Zoll, Joffrey; Ribera, Florence; Dufour, Stéphane; Lampert, Eliane; Kindo, Michel; Geny, Bernard; Ventura-Clapier, Renée; Mettauer, Bertrand

    2014-04-01

    Chronic immunosuppressive treatment was suspected to alter maximal muscle oxidative capacity (Vmax ) of heart transplant recipients, leading to a limitation of their exercise tolerance. It remains undefined whether the mitochondrial respiratory chain (MRC) of right ventricle (RV) and vastus lateralis (VL) muscles were altered by immunosuppressants and/or their vehicles. Vmax was measured polarographically in saponin-skinned fibres of RV and VL biopsies of patients and compared with Vmax of healthy VL and myocardium. Effects of increasing concentrations (1-10-100 μM) of Sandimmune(®) , its vehicle, Cyclosporine (CsA) in ethanol (EtOH), or EtOH alone were tested. The vehicle's effects on MRC complexes were investigated using specific substrates and inhibitors. Ten months after grafting, Vmax of RV and VL of immunosuppressed patients were similar to their Vmax at time of transplantation and to that of control tissues. In Vitro, Sandimmune(®) significantly decreased Vmax while CsA in EtOH or EtOH exerted small and similar effects. Effects of the vehicle were higher than (RV) or identical to (VL) those of Sandimmune(®) . The sites of action of the vehicle on MRC were located on complexes I and IV. While unchanged under chronic immunosuppressive therapy, Vmax of RV and VL muscles was depressed by acute exposure to intravenous Sandimmune(®) in vitro, an effect attributed to its vehicle by inhibition of complexes I and IV of the MRC. This work provides an in vitro proof of a toxic effect on the mitochondria respiratory chain of the vehicle used in the intravenous formulation of Sandimmune(®) but with no clinical consequences in chronically immunosuppressed patients. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  8. Antibody reactivity with Skinner HSV vaccine.

    PubMed

    Muniu, E M; Durham, J; Shariff, D; Hartley, C E; Fuller, A; Melling, J; Wiblin, C; Wilkins, G; Buchan, A; Skinner, G R

    1987-01-01

    Antibody reactivity against herpes simplex virus (HSV) was investigated in 15 subjects who received three subcutaneous immunisations with Skinner HSV vaccine. Humoral antibody responses were detected against type 1 HSV in every subject and against type 2 HSV in all but one subject; immuno-precipitating antibody responses were infrequently detected. There was no antibody reactivity against host-cell (MRC-5), foetal calf serum or rubella virus antigen. None of the vaccinated subjects developed clinical evidence of herpes genitalis.

  9. On the Two-Dimensional Periodic Surface Waves Occurring in Rectangular Vessels: Theory Versus Experiment.

    DTIC Science & Technology

    1985-10-01

    8217.; .:: -,. ".-::", -. ,.-- .i - -,J .- ,il-:l,-,.,,’- , :. 0 MRC Technical summary Report #2878 Thomas J. Bridges University of Wisconsin-Madison 610 Walnut Street D I Madison...without special software. In addition, the analyzer can be programmed to run the experiment and input and analyze the various sensory measurements...PROGRAM ELEMENT. PROJECT. TASK AREA & WORK UNIT NUMBERS *; * ~Mathematics Research Center, University of wr ntNme *610 Walnut Street Wisconsin Physical

  10. Magnetic resonance cholangiography in assessing biliary anatomy in living donors: A meta-analysis

    PubMed Central

    Xu, Yu-Biao; Bai, Yu-Long; Min, Zhi-Gang; Qin, Shan-Yu

    2013-01-01

    AIM: To establish the role of magnetic resonance cholangiography (MRC) in diagnosis of biliary anatomy in living-donor liver transplantation (LDLT) donors. METHODS: A systematic review was performed by searching electronic bibliographic databases prior to March 2013. Studies with diagnostic results and fulfilled inclusion criteria were included. The methodological quality of the studies was assessed. Sensitivity, specificity and other measures of the accuracy of MRC for diagnosis of biliary anatomy in LDLT donors were summarized using a random-effects model or a fixed-effects model. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Publication bias was assessed using Deek’s funnel plot asymmetry test. Sensitivity analysis was adopted to explore the potential sources of heterogeneity. RESULTS: Twelve studies involving 869 subjects were eligible to the analysis. The scores of Quality Assessment of Diagnostic Accuracy Studies for the included studies ranged from 11 to 14. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic OR of MRC in diagnosis of biliary anatomy in LDLT donor were 0.88 (95%CI: 0.84-0.92), 0.95 (95%CI: 0.93-0.97), 15.33 (95%CI: 10.70-21.95), 0.15 (95%CI: 0.11-0.20) and 130.77 (95%CI: 75.91-225.27), respectively. No significant heterogeneity was detected in all the above four measures. Area under SROC curve was 0.971. Little publication bias was noted across the studies (P = 0.557). Sensitivity analysis excluding a study with possible heterogeneity got a similar overall result, which suggested the little influence of this study on the overall results. CONCLUSION: Our results suggest that MRC is a high specificity but moderate sensitivity technique in diagnosis of biliary anatomy in LDLT donors. PMID:24363536

  11. Nonlinear Parabolic Equations Involving Measures as Initial Conditions.

    DTIC Science & Technology

    1981-09-01

    CHART N N N Afl4Uf’t 1N II Il MRC Technical Summary Report # 2277 0 NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS I Haim Brezis ...NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS Haim Brezis and Avner Friedman Technical Summary Report #2277 September 1981...with NRC, and not with the authors of this report. * 𔃾s ’a * ’ 4| NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS Haim Brezis

  12. The Role of Target and Bystander Cells in Dose-Response Relationship of Radiation-Induced Bystander Effects in Two Cell Lines

    PubMed Central

    Soleymanifard, Shokouhozaman; Bahreyni Toossi, Mohammad Taghi; Sazgarnia, Ameneh; Mohebbi, Shokoufe

    2013-01-01

    Objective(s): Radiation effect induced in nonirradiated cells which are adjacent or far from irradiated cells is termed radiation-induced bystander effect (RIBE). Published data on dose-response relationship of RIBE is controversial. In the present study the role of targeted and bystander cells in RIBE dose-response relationship of two cell lines have been investigated. Materials and Methods: Two cell lines (QU-DB and MRC5) which had previously exhibited different dose-response relationship were selected. In the previous study the two cell lines received medium from autologous irradiated cells and the results showed that the magnitude of damages induced in QU-DB cells was dependent on dose unlike MRC5 cells. In the present study, the same cells irradiated with 0.5, 2 and 4 Gy gamma rays and their conditioned media were transferred to nonautologous bystander cells; such that the bystander effects due to cross-interaction between them were studied. Micronucleus assay was performed to measure the magnitude of damages induced in bystander cells (RIBE level). Results: QU-DB cells exhibited a dose-dependent response. RIBE level in MRC5 cells which received medium from 0.5 and 2 Gy QU-DB irradiated cells was not statistically different, but surprisingly when they received medium from 4Gy irradiated QU-DB cells, RIBE was abrogated. Conclusion: Results pertaining to QU-DB and MRC5 cells indicated that both target and bystander cells determined the outcome. Triggering the bystander effect depended on the radiation dose and the target cell-type, but when RIBE was triggered, dose-response relationship was predominantly determined by the bystander cell type. PMID:24298387

  13. High-spatial-resolution three-dimensional MR cholangiography using a high-sampling-efficiency technique (SPACE) at 3T: comparison with the conventional constant flip angle sequence in healthy volunteers.

    PubMed

    Arizono, Shigeki; Isoda, Hiroyoshi; Maetani, Yoji S; Hirokawa, Yuusuke; Shimada, Kotaro; Nakamoto, Yuji; Togashi, Kaori

    2008-09-01

    To evaluate the image quality of high-spatial-resolution three-dimensional magnetic resonance cholangiography (MRC) with a high-sampling-efficiency technique (sampling perfection with application optimized contrasts using different flip angle evolutions [SPACE]) in comparison with a conventional constant flip angle (FA) sequence at 3T. Eighteen volunteers were examined on a 3T MR unit using MRC imaging performed with three different free-breathing three-dimensional T2-weighted turbo spin-echo (TSE) sequences: 1) SPACE (spatial resolution, 1.1x1.0x0.84 mm), 2) constant FA (1.1x1.0x0.84 mm), and 3) SPACE at a higher resolution (SPACE HR; 1.0x0.9x0.644 mm). A five-point scale was used to compare overall image quality and visualization of the third branches of the bile duct (B2, B6, and B8). Depictions of cystic duct insertion and the highest order of bile duct visible were also compared. MRC with SPACE and SPACE HR sequences produced significantly better overall image quality than the constant FA sequence. In all analyses of duct visibility, SPACE and SPACE HR sequences showed higher scores than the constant FA sequence. High-resolution three-dimensional MRC with SPACE at 3T allows high-quality imaging of the biliary tract, and has the ability to depict nondilated intrahepatic bile ducts (IHBD) in healthy volunteers. Copyright (c) 2008 Wiley-Liss, Inc.

  14. Dyspnea in COPD: beyond the modified Medical Research Council scale.

    PubMed

    Camargo, Lilia Azzi Collet da Rocha; Pereira, Carlos Alberto de Castro

    2010-01-01

    To determine the correlations among various dyspnea scales, spirometric data, exercise tolerance data, and the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index in patients with COPD. Between March of 2008 and July of 2009, 79 patients with COPD were recruited, and 50 of those patients were included in the study. After being regularly treated with formoterol for one month, the patients completed the modified Medical Research Council (mMRC, dyspnea scale), Baseline Dyspnea Index (BDI), Oxygen Cost Diagram (OCD), and Shortness Of Breath Questionnaire (SOBQ). Subsequently, the patients underwent spirometry and six-minute walk tests (6MWTs), with determination of the six-minute walk distance (6MWD), as well as initial and final SpO2. All patients also completed the Visual Analogue Scale (VAS) and the Borg scale. The best correlations were between the Borg scale and the VAS (r s = 0.79) and between the BDI and the SOBQ (r s = -0.73). Among the one-dimensional scales (the VAS, mMRC, OCD, and Borg scale), only the VAS correlated with the spirometric parameters, whereas the multidimensional scales BDI and SOBQ did correlate, but poorly. The MRC, BDI, and SOBQ correlated well with 6MWD. Among the spirometric data, inspiratory capacity (IC) and FVC had the strongest correlations with 6MWD. In the multivariate analysis, BDI and IC were selected as the best predictors of 6MWD. Multidimensional dyspnea scales should be applied in the evaluation of COPD patients.

  15. [A comparison of several measurement scales for assessing dyspnea in their daily activities in patients with chronic obstructive lung disease].

    PubMed

    Ruiz de Oña Lacasta, J M; Puente Maestu, L; Rodríguez Hermosa, J L; Tatay Martí, E; Cubillo Marcos, J M

    2000-01-01

    The objective of this study was to compare two instruments for measuring dyspnea to functional capacity, defined as maximal oxygen uptake in a stress test limited by symptoms. We carried out a descriptive study to determine correlation between the methods. Subjects with severe chronic obstructive pulmonary disease were enrolled and dyspnea during daily activities was evaluated using the Medical Research Council (MRC) scale and the chronic respiratory disease health perception questionnaire (CRQ). Dyspnea was also assessed on a visual analog scale (VAS) and the Borg scale. Patients performed a progressive treadmill test limited by symptoms to measure peak VO2 and VE. Correlation analysis of the two measures of dyspnea and the objective measures of functional capacity (peak VO2 and VE) showed that the clinical dyspnea measures (CRQ and MRC) correlated well with peak aerobic capacity and with maximal ventilation, whereas the VAS and Borg scale were not significantly related to the aforementioned variables. We also observed that the clinical scales for dyspnea correlated with each other, as did the VAS and Borg scale, but that there was no correlation between the two types of measurement. We conclude that clinical dyspnea indexes (CRQ and MRC) correlate well with maximal aerobic capacity and with each other. However, the VAS and Borg scale do not correlate with functional capacity measured by peak VO2 and VE.

  16. Eutectic Experiment Development for Space Processing

    NASA Technical Reports Server (NTRS)

    Hopkins, R. H.

    1972-01-01

    A ground base test plan and a specimen evaluation scheme have been developed for the aluminum-copper eutectic solidification experiment to be run in the M518 multipurpose electric furnace during the Skylab mission. Besides thermal and solidification studies a detailed description is given of the quantitative metallographic technique which is appropriate for characterizing eutectic structures. This method should prove a key tool for evaluating specimen microstructure which is the most sensitive indicator of changes produced during solidification. It has been recommended that single grain pre-frozen eutectic specimens be used to simplify microstructural evaluation and to eliminate any porosity in the as-cast eutectic specimens. High purity (99.999%) materials from one supplier should be employed for all experiments. Laboratory studies indicate that porosity occurs in the MRC as-cast eutectic ingots but that this porosity can be eliminated by directional freezing. Chemical analysis shows that the MRC ingots are slightly Al rich and contain about .03% impurity. Because of the impurity content the lower cooldown rate (1.2 C/min) should be used for eutectic freezing if MRC material is used in the M518 furnace.

  17. Maximum reservoir capacity of vegetation for persistent organic pollutants: Implications for global cycling

    NASA Astrophysics Data System (ADS)

    Dalla Valle, Matteo; Dachs, Jordi; Sweetman, Andrew J.; Jones, Kevin C.

    2004-12-01

    The concept of maximum reservoir capacity (MRC) or "equilibrium capacity ratio," the ratio of the capacities of the vegetation and of the atmospheric mixed layer (AML) to hold chemical under equilibrium conditions, is applied to selected persistent organic pollutants (POPs) in vegetation in order to assess its importance for the global cycling of POPs. Vegetation is found to have a significant storage capacity, and because of its intimate contact with the atmosphere may play an important role in global cycling of POPs. The vegetation MRC is calculated for some representative PCB congeners (PCB-28; -152; -180) at the global scale with a spatial resolution of 0.25° × 0.25°. It is shown to be comparable to that of the skin layer of the soil and to vary over many orders of magnitude, between compounds, locations, and time (seasonally/diurnally), depending on the vegetation type and on the temperature. The highest MRC values are observed in areas with low temperatures and coniferous forests (e.g., Siberia, Canada, Scandinavia), while the lowest values are typically located in warm and desert areas (e.g., Sahara). Large differences were also observed at the regional scale. Implications for the global cycling and long-range atmospheric transport (LRAT) of POPs are discussed, including comparisons with soil and ocean MRCs, which will drive net transfers of POPs between media and regions.

  18. Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein

    PubMed Central

    Brzoska, Anthony J.; Jensen, Slade O.; Barton, Deborah A.; Davies, Danielle S.; Overall, Robyn L.; Skurray, Ronald A.; Firth, Neville

    2016-01-01

    Actin-like proteins (Alps) are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments. PMID:27310470

  19. Heterologous expression of phaC2 gene and poly-3-hydroxyalkanoate production by recombinant Cupriavidus necator strains using canola oil as carbon source.

    PubMed

    Valdés, J; Kutralam-Muniasamy, G; Vergara-Porras, B; Marsch, R; Pérez-Guevara, F; López-Cuellar, M R

    2017-08-19

    Many heterologous transformation studies have been carried out using the Cupriavidus necator PHB(-4) strain to investigate the expression characteristics of various polyhydroxyalkanoate (PHA) synthase enzymes. In this study, we generated a recombinant C. necator PHB(-4) strain by transforming a plasmid (pMRC03) harbouring the synthetic phaC2 gene of Pseudomonas putida CA-3. Under conditions favourable for expression of the phaC2 P.putCA-3 gene, canola oil was used as carbon source for the synthesis of PHAs. The expressed synthase polymerised monomers of 3-hydroxybutyrate (3-HB), 3-hydroxyvalerate (3-HV) and 3-hydroxyhexanoate (3-HHx) in the recombinant C. necator PHB(-4) (pMRC03) strain. We then co-expressed the phaC2P.putCA-3 gene with the native phaC1C.ne gene in wild type Cupriavidus necator H16 (C. necator H16 (pMRC03)). This co-expression produced a PHA blend of 3-HB, 3-HV, 3-HHx and 3-hydroxyoctanoate (3-HO) monomers in the presence of canola oil. Gas chromatography analysis revealed the presence of 94mol% 3-HB, 1mol% 3-HV, 4mol% 3-HHx and 1mol% 3-HO in a tetra-polymer. Thus, we confirmed that a synthetic phaC2 gene encoding the synthase enzyme is functionally active with substrates ranging from short to medium chain length PHAs. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Fully automated objective-based method for master recession curve separation.

    PubMed

    Posavec, Kristijan; Parlov, Jelena; Nakić, Zoran

    2010-01-01

    The fully automated objective-based method for master recession curve (MRC) separation was developed by using Microsoft Excel spreadsheet and Visual Basic for Applications (VBA) code. The core of the program code is used to construct an MRC by using the adapted matching strip method (Posavec et al. 2006). Criteria for separating the MRC into two or three segments are determined from the flow-duration curve and are represented as the probable range of percent of flow rate duration. Successive separations are performed automatically on two and three MRCs using sets of percent of flow rate duration from selected ranges and an optimal separation model scenario, having the highest average coefficient of determination R(2), is selected as the most appropriate one. The resulting separated master recession curves are presented graphically, whereas the statistics are presented numerically, all in separate sheets. Examples of field data obtained from two springs in Istria, Croatia, are used to illustrate its application. The freely available Excel spreadsheet and VBA program ensures the ease of use and applicability for larger data sets.

  1. Dynamic Monitoring of Mechano-Sensing of Cells by Gold Nanoslit Surface Plasmon Resonance Sensor

    PubMed Central

    Wu, Shu-Han; Lee, Kuang-Li; Weng, Ruei-Hung; Zheng, Zhao-Xian; Chiou, Arthur; Wei, Pei-Kuen

    2014-01-01

    We demonstrated a real-time monitoring of live cells upon laminar shear stress stimulation via surface plasmon resonance (SPR) in gold nanoslit array. A large-area gold nanostructure consisted of 500-nm-period nanoslits was fabricated on a plastic film using the thermal-annealed template-stripping method. The SPR in the gold nanoslit array provides high surface sensitivity to monitor cell adhesion changes near the sensor surface. The human non-small cell lung cancer (CL1-0), human lung fibroblast (MRC-5), and human dermal fibroblast (Hs68) were cultured on the gold nanoslits and their dynamic responses to laminar shear stress were measured under different stress magnitudes from 0 to 30 dyne/cm2. Cell adhesion was increased in CL1-0 under shear flow stimulation. No adhesion recovery was observed after stopping the flow. On the other hand, MRC-5 and Hs68 decreased adhesion and recovered from the shear stress. The degree of recovery was around 70% for MRC-5. This device provides dynamic study and early detection of cell adhesion changes under shear flow conditions. PMID:24586846

  2. Cytotoxic constituents of Pachyrhizus tuberosus from Peruvian amazon.

    PubMed

    Leuner, Olga; Havlik, Jaroslav; Budesinsky, Milos; Vrkoslav, Vladimir; Chu, Jessica; Bradshaw, Tracey D; Hummelova, Jana; Miksatkova, Petra; Lapcik, Oldrich; Valterova, Irena; Kokoska, Ladislav

    2013-10-01

    Investigations into the chemical constituents of the seeds of the neglected tuber crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2), erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin [pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were isolated using several chromatography techniques and characterized and verified by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic effects of the methanolic P. tuberosus extract and isolated compounds in two human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non-transformed human fibroblasts (MRC-5); IC50 values were calculated. The methanolic P. tuberosus extract displayed respectable cytotoxic effects against HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 microg/mL, respectively. Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the cancer cell lines tested, yielding IC50 values of 0.3 microg/mL against both MCF-7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts. Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8 microg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5 mirog/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy of further antitumor investigation.

  3. Cytotoxicity of Dental Adhesives In Vitro

    PubMed Central

    Koulaouzidou, Elisabeth A.; Helvatjoglu-Antoniades, Maria; Palaghias, George; Karanika-Kouma, Artemis; Antoniades, Dimitrios

    2009-01-01

    Objectives The purpose of this study was to evaluate the cytotoxic effect of six dental adhesives (Admira Bond, Clearfil Liner Bond 2V, ED Primer II, Fuji Bond LC, Gluma Comfort Bond, and NanoBond) applied to cell cultures. Methods The experiments were performed on two cell lines, rat pulp cells (RPC-C2A) and human lung fibroblasts (MRC5). Samples of the adhesives were light-cured and placed in culture medium for 24 hours. The extraction media was applied on the RPC-C2A and the MRC5 cells. Complete medium was used as a control. Cytotoxicity was evaluated with a modified sulforhodamine B (SRB) assay after 24 hours of exposure. Results The cell survival of RPC-C2A cells exposed to Fuji Bond LC, NanoBond, Clearfil Liner Bond 2V, ED Primer II, Admira Bond and Gluma Comfort Bond was 73%, 67%, 50%, 20%, 18% and 5% respectively, relative to the cell survival with the control medium. In the MRC5 cell line, the relative survival was 98%, 80%, 72%, 41%, 19% and 7% after exposure to NanoBond, Fuji Bond LC, Clearfil Liner Bond 2V, ED Primer II, Admira Bond and Gluma Comfort Bond, respectively. Conclusions Different types of dental adhesives showed different cytotoxic effects on cells in vitro. The self-etch adhesives were superior in terms of cytotoxicity. The different cytotoxic effects of dental adhesives should be considered when selecting an appropriate adhesive for operative restorations. PMID:19262725

  4. Identification of shared antigenic determinants of different polypeptides from Davis and Towne cytomegalovirus strains with monoclonal antibodies.

    PubMed

    Chardonnet, Y; Léry, X; Revillard, J P

    1983-01-01

    Six colonies producing antibodies were obtained by fusing mouse myeloma SP2-O cells with spleen cells from mice immunized with cytomegalovirus Davis strain. Among 88 surviving clones, 29 produced antibodies detectable by immunofluorescence on infected MRC5 cells and 2 others produced neutralizing antibodies against a homologous virus. Supernatants from these 31 positive clones and 4 others which were negative in immunofluorescence or neutralization were tested for their capacity to bind polypeptides from labelled Davis-infected cell extracts. Only 8 were found to be positive: five clones (A8, E3, F2, F8 and F20) precipitated 76 K, 60 K and 54 K bands; three others (A4, B9 and C24) precipitated 76 K and 54 K only. Surprisingly, these 8 monoclonal antibodies recognized a unique polypeptide 67 K of Towne-infected MRC5 cells. No correlation was found between (1) the pattern of fluorescence on MRC5 cells infected with Davis strain, (2) the neutralizing activity, and (3) the polypeptides recognized by the monoclonal antibodies.

  5. A quantitative assessment of the functional recovery of flexion of the elbow after nerve transfer in patients with a brachial plexus injury.

    PubMed

    Quick, T J; Singh, A K; Fox, M; Sinisi, M; MacQuillan, A

    2016-11-01

    Improvements in the evaluation of outcome after nerve transfers are required. The assessment of force using the Medical Research Council (MRC) grades (0 to 5) is not suitable for this purpose. A ceiling effect is encountered within MRC grade 4/5 rendering this tool insensitive. Our aim was to show how the strength of flexion of the elbow could be assessed in patients who have undergone a re-innervation procedure using a continuous measurement scale. A total of 26 patients, 23 men and three women, with a mean age of 37.3 years (16 to 66), at the time of presentation, attended for review from a cohort of 52 patients who had undergone surgery to restore flexion of the elbow after a brachial plexus injury and were included in this retrospective study. The mean follow-up after nerve transfer was 56 months (28 to 101, standard deviation (sd) 20.79). The strength of flexion of the elbow was measured in a standard outpatient environment with a static dynamometer. In total, 21 patients (81%) gained MRC grade 4 strength of flexion of the elbow. The mean force of flexion was 7.2 kgf (3 to 15.5, sd 3.3). This study establishes that the dynamometer may be used for assessing the strength of flexion of the elbow in the outpatient department after nerve reconstructive surgery. Cite this article: Bone Joint J 2016;98-B:1517-20. ©2016 The British Editorial Society of Bone & Joint Surgery.

  6. Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control

    NASA Astrophysics Data System (ADS)

    Bercich, Rebecca A.; Wang, Zhi; Mei, Henry; Hammer, Lauren H.; Seburn, Kevin L.; Hargrove, Levi J.; Irazoqui, Pedro P.

    2016-08-01

    Objective. A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. Approach. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. Main results. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject’s forearm. Significance. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device’s programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system’s functional protocol for patient- or algorithm-specific needs.

  7. DINO (Diet In Nutrients Out) – An integrated dietary assessment system

    PubMed Central

    Fitt, Emily; Cole, Darren; Ziauddeen, Nida; Pell, David; Stickley, Elizabeth; Harvey, Anna; Stephen, Alison M.

    2016-01-01

    Objective This paper describes Diet In Nutrients Out (DINO), an integrated dietary assessment system incorporating dietary data entry and nutritional analysis within one platform for use in dietary assessment in small scale intervention studies to national surveys. Design DINO contains >6000 food items, mostly aggregated composites of branded foods, across 31 main food groups divided into 151 subsidiary groups for detailed reporting requirements, with 53 core nutrient fields. Setting MRC Human Nutrition Research (HNR), Cambridge and MRC Keneba, Gambia. Subjects DINO is used across dietary assessment projects at HNR and MRC Keneba. Results DINO contains macro- and micronutrients as well as additional variables of current research and policy interest, such as caffeine, wholegrain, vitamin K and added sugars. Disaggregated data are available for fruit, vegetable, meat, fish and cheese in composite foods, enabling greater accuracy when reporting food consumption or assessing adherence to dietary recommendations. Portion sizes are categorised in metric and imperial weights, with standardised portion sizes for each age group. Regular reviews are undertaken for portion sizes and food composition to ensure contemporary relevance. A training programme and checking schedule is adhered to for quality assurance purposes, covering users and data. Eating context questions are integrated to record where and with whom the respondent is eating, allowing examination between these factors and the foods consumed. Conclusions An up to date quality assured system for dietary assessment is crucial for nutritional surveillance and research, but needs to have the flexibility to be tailored to address specific research questions. PMID:24674815

  8. Results of ulnar nerve neurotization to biceps brachii muscle in brachial plexus injury

    PubMed Central

    Rezende, Marcelo Rosa De; Rabelo, Neylor Teofilo Araújo; Silveira, Clóvis Castanho; Petersen, Pedro Araújo; Paula, Emygdio José Leomil De; Mattar, Rames

    2012-01-01

    OBJECTIVE: To evaluate the factors influencing the results of ulnar nerve neurotization at the motor branch of the brachii biceps muscle, aiming at the restoration of elbow flexion in patients with brachial plexus injury. METHODS: 19 patients, with 18 men and 1 woman, mean age 28.7 years. Eight patients had injury to roots C5-C6 and 11, to roots C5-C6-C7. The average time interval between injury and surgery was 7.5 months. Four patients had cervical fractures associated with brachial plexus injury. The postoperative follow-up was 15.7 months. RESULTS: Eight patients recovered elbow flexion strength MRC grade 4; two, MRC grade 3 and nine, MRC <3. There was no impairment of the previous ulnar nerve function. CONCLUSION: The surgical results of ulnar nerve neurotization at the motor branch of brachii biceps muscle are dependent on the interval between brachial plexus injury and surgical treatment, the presence of associated fractures of the cervical spine and occipital condyle, residual function of the C8-T1 roots after the injury and the involvement of the C7 root. Signs of reinnervation manifested up to 3 months after surgery showed better results in the long term. Level of Evidence: IV, Case Series. PMID:24453624

  9. Paraquat increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity.

    PubMed

    Zhang, N; Xie, Y-P; Pang, L; Zang, X-X; Wang, J; Shi, D; Wu, Y; Liu, X-L; Wang, G-H

    2014-12-01

    This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat's effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner (p < 0.05) and to significantly impair the viscoelastic properties in a time-independent manner (p < 0.05). Exposure to paraquat led to a significant and time-dependent increase in CTGF expression (p < 0.05) and induced changes in the morphology and biomechanical characteristics of the MRC-5 cells. These findings not only provide novel insights into the mechanisms of paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning.

  10. The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

    PubMed

    Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

    2010-06-01

    The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p < 0.05). The results suggest a complex inhibitory mechanism of the extract. Inhibition of the succinate oxidase system was competitive (K(i) = 0.23 microg/ml), whereas isolated cytochrome oxidase was inhibited noncompetitively (K(i) = 126 microg/ml). The results of this study suggest that the salubrious effects of artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

  11. Nerve Ultrasound and Electrophysiology for Therapy Monitoring in Chronic Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Kerasnoudis, Antonios; Pitarokoili, Kalliopi; Gold, Ralf; Yoon, Min-Suk

    2015-01-01

    We evaluated prospectively nerve ultrasound and electrophysiology as monitoring methods of intravenous immunoglobulin (IVIG) therapy in chronic inflammatory demyelinating polyneuropathy (CIDP). Overall 15 healthy subjects and 11 CIDP patients undergoing IVIG therapy were recruited in the study. All patients underwent clinical, ultrasound, and electrophysiological evaluation at the time point of first onset of symptoms (<6 weeks of symptoms) and 4, 8, and 12 months after onset. The intranerve cross-sectional area (CSA) variability of each nerve, but not the CSA alone, correlated with the MRC Scale score during 12-month follow-up. On the other hand, none of the electrophysiological parameters correlated with the MRC Scale Score in each of the peripheral nerves. Interestingly, in ¾ of the CIDP patients, the resolution of the conduction block correlated with the improvement in the MRC Sum score. Nerve ultrasound and in particular the intranerve CSA variability seems to be a useful method in monitoring CIDP patients. Although the sample size is small, the intranerve CSA variability seems to be more promising than neurophysiology. Copyright © 2015 by the American Society of Neuroimaging.

  12. Antioxidant and Antigenotoxic Activities of the Brazilian Pine Araucaria angustifolia (Bert.) O. Kuntze

    PubMed Central

    Souza, Márcia O.; Branco, Cátia S.; Sene, Juliane; DallAgnol, Rafaela; Agostini, Fabiana; Moura, Sidnei; Salvador, Mirian

    2014-01-01

    Polyphenols are natural products with recognized potential in drug discovery and development. We aimed to evaluate the polyphenolic profile of Araucaria angustifolia bracts, and their ability to scavenge reactive species. The antioxidant and antigenotoxic effects of A. angustifolia polyphenols in MRC5 human lung fibroblast cells were also explored. The total polyphenol extract of A. angustifolia was determined by the Folin–Ciocalteu reagent and the chemical composition was confirmed by HPLC. Reactive oxygen species’ scavenging ability was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and superoxide dismutase- and catalase-like activities. The protective effect of the extract in MRC5 cells was carried out by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and the determination of oxidative lipids, protein, and DNA (alkaline and enzymatic comet assay) damage. Total phenolic content of the A. angustifolia extract was 1586 ± 14.53 mg gallic acid equivalents/100 g of bracts. Catechin, epicatechin, quercetin, and apigenin were the major polyphenols. The extract was able to scavenge DPPH radicals and exhibited potent superoxide dismutase and catalase-like activities. Moreover, A. angustifolia extract significantly protected MRC5 cells against H2O2-induced mortality and oxidative damage to lipids, proteins, and DNA. Therefore, A. angustifolia has potential as a source of bioactive chemical compounds. PMID:26784661

  13. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    NASA Astrophysics Data System (ADS)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  14. Particulate matter (PM) 2.5 levels in ETS emissions of a Marlboro Red cigarette in comparison to the 3R4F reference cigarette under open- and closed-door condition

    PubMed Central

    2012-01-01

    Introduction Potential health damage by environmental emission of tobacco smoke (environmental tobacco smoke, ETS) has been demonstrated convincingly in numerous studies. People, especially children, are still exposed to ETS in the small space of private cars. Although major amounts of toxic compounds from ETS are likely transported into the distal lung via particulate matter (PM), few studies have quantified the amount of PM in ETS. Study aim The aim of this study was to determine the ETS-dependent concentration of PM from both a 3R4F reference cigarette (RC) as well as a Marlboro Red brand cigarette (MRC) in a small enclosed space under different conditions of ventilation to model car exposure. Method In order to create ETS reproducibly, an emitter (ETSE) was constructed and mounted on to an outdoor telephone booth with an inner volume of 1.75 m3. Cigarettes were smoked under open- and closed-door condition to imitate different ventilation scenarios. PM2.5 concentration was quantified by a laser aerosol spectrometer (Grimm; Model 1.109), and data were adjusted for baseline values. Simultaneously indoor and outdoor climate parameters were recorded. The time of smoking was divided into the ETS generation phase (subset “emission”) and a declining phase of PM concentration (subset “elimination”); measurement was terminated after 10 min. For all three time periods the average concentration of PM2.5 (Cmean-PM2.5) and the area under the PM2.5 concentration curve (AUC-PM2.5) was calculated. The maximum concentration (Cmax-PM2.5) was taken from the total interval. Results For both cigarette types open-door ventilation reduced the AUC-PM2.5 (RC: from 59 400 ± 14 600 to 5 550 ± 3 900 μg*sec/m3; MRC: from 86 500 ± 32 000 to 7 300 ± 2 400 μg*sec/m3; p < 0.001) and Cmean-PM2.5 (RC: from 600 ± 150 to 56 ± 40 μg/m3, MRC from 870 ± 320 to 75 ± 25 μg/m3; p < 0.001) by about 90%. Cmax-PM2.5 was reduced by about 80% (RC

  15. [Development of an activity of daily living scale for patients with COPD: the Activity of Daily Living Dyspnea scale].

    PubMed

    Yoza, Yoshiyasu; Ariyoshi, Koya; Honda, Sumihisa; Taniguchi, Hiroyuki; Senjyu, Hideaki

    2009-10-01

    Patients with COPD often experience restriction in their activities of daily living (ADL) due to dyspnea. This type of restriction is unique to patients with COPD and cannot be adequately evaluated by the generic ADL scales. This study developed an ADL scale (the Activity of Daily Living Dyspnea scale [ADL-D scale]) for patients with COPD and investigated its validity and internal consistency. Patients with stable COPD were recruited and completed a pilot 26-item questionnaire. Patients also performed the Incremental Shuttle Walk Test (ISWT), and completed the St George's Respiratory Questionnaire (SGRQ), and Medical Research Council (MRC) dyspnea grade. There were 83 male participants who completed the pilot questionnaire. Following the pilot, 8 items that were not undertaken by the majority of subjects, and 3 items judged to be of low clinical importance by physical therapists were removed from the pilot questionnaire. The final ADL-D scale contained 15 items. Scores obtained with the ADL-D scale were significantly correlated with the MRC dyspnea grades, distance walked on the ISWT and SGRQ scores. The ADL-D scores were significantly different across the five grades of the MRC dyspnea grade. The ADL-D scale showed high consistency (Chronbach's alpha coefficient of 0.96). The ADL-D scale is a useful scale for assessing impairments in ADL in Japanese male patients with COPD.

  16. Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control.

    PubMed

    Bercich, Rebecca A; Wang, Zhi; Mei, Henry; Hammer, Lauren H; Seburn, Kevin L; Hargrove, Levi J; Irazoqui, Pedro P

    2016-08-01

    A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject's forearm. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device's programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system's functional protocol for patient- or algorithm-specific needs.

  17. Performance analysis of free space optical system with spatial modulation and diversity combiners over the Gamma Gamma atmospheric turbulence

    NASA Astrophysics Data System (ADS)

    Odeyemi, Kehinde O.; Owolawi, Pius A.; Srivastava, Viranjay M.

    2017-01-01

    Atmospheric turbulence is a major impairment that degrades the performance of free space optical (FSO) communication systems. Spatial modulation (SM) with receive spatial diversity is considered as a powerful technique to mitigate the fading effect induced by atmospheric turbulence. In this paper, the performance of free space optical spatial modulation (FSO-SM) system under Gamma-Gamma atmospheric turbulence is presented. We studied the Average Bit Error Rate (ABER) for the system by employing spatial diversity combiners such Maximum Ratio Combining (MRC) and Equal Gain Combining (EGC) at the receiving end. In particular, we provide a theoretical framework for the system error by deriving Average Pairwise Error Probability (APEP) expression using a generalized infinite power series expansion approach and union bounding technique is applied to obtain the ABER for each combiner. Based on this study, it was found that spatial diversity combiner significantly improved the system error rate where MRC outperforms the EGC. The performance of this system is also compared with other well established diversity combiner systems. The proposed system performance is further improved by convolutional coding technique and our analysis confirmed that the system performance of MRC coded system is enhanced by approximately 20 dB while EGC falls within 17 dB.

  18. The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation.

    PubMed

    Potter, Christopher S; Pruett, Nathanael D; Kern, Michael J; Baybo, Mary Ann; Godwin, Alan R; Potter, Kathleen A; Peterson, Ron L; Sundberg, John P; Awgulewitsch, Alexander

    2011-04-01

    Among the Hox genes, homeobox C13 (Hoxc13) has been shown to be essential for proper hair shaft differentiation, as Hoxc13 gene-targeted (Hoxc13(tm1Mrc)) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1(nu) (nude) mutant mice, we sought to determine whether Hoxc13 and forkhead box N1 (Foxn1) might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13(tm1Mrc) and Foxn1(nu) mice is because of strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13(tm1Mrc) mice identified Foxn1 as significantly downregulated along with numerous hair keratin genes. This Foxn1 downregulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers.

  19. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2014-01-06

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  20. Design and development of a film-based intervention about teenage men and unintended pregnancy: applying the Medical Research Council framework in practice.

    PubMed

    Aventin, Áine; Lohan, Maria; O'Halloran, Peter; Henderson, Marion

    2015-04-01

    Following the UK Medical Research Council's (MRC) guidelines for the development and evaluation of complex interventions, this study aimed to design, develop and optimise an educational intervention about young men and unintended teenage pregnancy based around an interactive film. The process involved identification of the relevant evidence base, development of a theoretical understanding of the phenomenon of unintended teenage pregnancy in relation to young men, and exploratory mixed methods research. The result was an evidence-based, theory-informed, user-endorsed intervention designed to meet the much neglected pregnancy education needs of teenage men and intended to increase both boys' and girls' intentions to avoid an unplanned pregnancy during adolescence. In prioritising the development phase, this paper addresses a gap in the literature on the processes of research-informed intervention design. It illustrates the application of the MRC guidelines in practice while offering a critique and additional guidance to programme developers on the MRC prescribed processes of developing interventions. Key lessons learned were: (1) know and engage the target population and engage gatekeepers in addressing contextual complexities; (2) know the targeted behaviours and model a process of change; and (3) look beyond development to evaluation and implementation.

  1. ROS-mediated cytotoxic effect of copper(II) hydrazone complexes against human glioma cells.

    PubMed

    Recio Despaigne, Angel A; Da Silva, Jeferson G; da Costa, Pryscila R; Dos Santos, Raquel G; Beraldo, Heloisa

    2014-10-27

    2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

  2. Can neurologic examination predict pathophysiology of ulnar neuropathy at the elbow?

    PubMed

    Omejec, Gregor; Žgur, Tomaž; Podnar, Simon

    2016-10-01

    To explore the utility of neurologic examination to predict the pathophysiology of ulnar nerve lesions in patients with ulnar neuropathies at the elbow (UNE). We prospectively recruited consecutive patients with suspected UNE. Four blinded investigators took a history and performed neurologic, electrodiagnostic (EDx) and ultrasonographic (US) examinations. In patients with axonal UNE, conduction block and conduction slowing, the pathophysiologies of UNE and neurologic examination findings were compared. We found significant differences in muscle bulk and strength of the ulnar hand muscles between 96 arms with axonal UNE, 34 with conduction block, and 45 with isolated conduction slowing. Severe muscle atrophy and weakness (0-3/5 on MRC) predicted axonal UNE, and moderate weakness (-4/5 on MRC) with normal muscle bulk predicted UNE with conduction block. Using more restrictive criteria for axonal and conduction block UNE, muscle strength of 4-5/5 on MRC was predictive of isolated conduction slowing. Although we found significant differences in patterns of muscle bulk and strength between groups of UNE patients with different UNE pathophysiologies, in the majority of arms, neurologic examination could not reliably predict UNE pathophysiology. Results confirm that nerve conduction studies are essential for determination of the pathophysiology of ulnar neuropathy at the elbow. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  3. Dynamic Potential Barrier Effects in Hydrogen Tunneling in Trans-cis Isomerizations

    DTIC Science & Technology

    1993-05-07

    for the cis. As the molecular transla- Schrodinger equation for a molecule to be separated lion and rotation are sepaiated out, the static poten- into...tunneling in multi-dimensional eluding cis and trans conformers of HSiOH. systems semiclassically . However, it is often neces- HSi’ 8OH. HSiOD, and HSi"OD...two equations , liat can he written generally as 1 (r, r. r. (, , V, where rt, 01, and (p, describe the first H-atom. and r., fl, and p2 the second

  4. The modified Medical Research Council scale for the assessment of dyspnea in daily living in obesity: a pilot study.

    PubMed

    Launois, Claire; Barbe, Coralie; Bertin, Eric; Nardi, Julie; Perotin, Jeanne-Marie; Dury, Sandra; Lebargy, François; Deslee, Gaëtan

    2012-10-01

    Dyspnea is very frequent in obese subjects. However, its assessment is complex in clinical practice. The modified Medical Research Council scale (mMRC scale) is largely used in the assessment of dyspnea in chronic respiratory diseases, but has not been validated in obesity. The objectives of this study were to evaluate the use of the mMRC scale in the assessment of dyspnea in obese subjects and to analyze its relationships with the 6-minute walk test (6MWT), lung function and biological parameters. Forty-five obese subjects (17 M/28 F, BMI: 43 ± 9 kg/m2) were included in this pilot study. Dyspnea in daily living was evaluated by the mMRC scale and exertional dyspnea was evaluated by the Borg scale after 6MWT. Pulmonary function tests included spirometry, plethysmography, diffusing capacity of carbon monoxide and arterial blood gases. Fasting blood glucose, total cholesterol, triglyceride, N-terminal pro brain natriuretic peptide, C-reactive protein and hemoglobin levels were analyzed. Eighty-four percent of patients had a mMRC ≥ 1 and 40% a mMRC ≥ 2. Compared to subjects with no dyspnea (mMRC = 0), a mMRC ≥ 1 was associated with a higher BMI (44 ± 9 vs 36 ± 5 kg/m2, p = 0.01), and a lower expiratory reserve volume (ERV) (50 ± 31 vs 91 ± 32%, p = 0.004), forced expiratory volume in one second (FEV1) (86 ± 17 vs 101 ± 16%, p = 0.04) and distance covered in 6MWT (401 ± 107 vs 524 ± 72 m, p = 0.007). A mMRC ≥ 2 was associated with a higher Borg score after the 6MWT (4.7 ± 2.5 vs 6.5 ± 1.5, p < 0.05). This study confirms that dyspnea is very frequent in obese subjects. The differences between the "dyspneic" and the "non dyspneic" groups assessed by the mMRC scale for BMI, ERV, FEV1 and distance covered in 6MWT suggests that the mMRC scale might be an useful and easy-to-use tool to assess dyspnea in daily living in obese subjects.

  5. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

    PubMed

    Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  6. Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

    PubMed Central

    Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  7. Is it safe to omit neoadjuvant chemo-radiation in mucinous rectal carcinoma?

    PubMed

    Madbouly, Khaled M; Mashhour, Abdrabou N; Omar, Waleed

    2015-11-01

    Purpose was to compare the oncologic outcome of neoadjuvant chemoradiotherapy (nCXRT) versus postoperative chemoradiotherapy (pCXRT) for locally advanced mucinous rectal carcinoma (MRC) having curative total mesorectal excision (TME). One hundred and two patients with MRC (T3-4 and/or N1-2) of middle and lower third rectum were included. Patients were non-randomly divided into 2 groups: Group A (N = 61) had nCXRT followed by total mesorectal excision (TME) after 8-11 weeks and Group B (N = 41) had TME followed by pCXRT. Primary end points were disease free survival (DFS) and overall survival (OS). Secondary endpoints were tumor regression grade (TRG) and morbidity. In group A, 29 patients had partial response after nCXRT, 26 patients showed no change and 6 patients had progression. TME was done in 55 patients in group A and 41 patients in group B. Six patients in group A turned to be unresectable after nCXRT due to progressive disease. Mean follow-up was 53 months. In patients received TME, Four-year DFS was higher in group A compared to group B yet not statistically significant (DFS 0.69 [95% CI 0.54-0.85] vs. 0.67 [95% CI 0.47-0.87]; P = 0.39). However, actuarial 4 years OS was comparable in both groups (0.72 [95% CI 0.59-0.91] vs. 0.70 [95% CI 0.55-0.88]; P = 0.46 in groups A and B respectively). Multivariate analysis revealed that age <40, and N2 were risk factors of recurrence. Whilst accepting that the numbers are small, there was no statistical difference in outcome (DFS and OS) between patients receiving pre- or post-operative chemo-radiotherapy. In most MRC patients, tumor regression is not significant after nCXRT and there is considerable possibility of tumor progression during nCXRT treatment. So, nCXRT should be used with close follow-up in MRC for early detection of possible tumor progression. If the patient cannot tolerate nCXRT, it is possibly safe to do surgery followed by pCXRT. Prospective study is needed to study the value of nCXRT in MRC

  8. Does the MUNIX Method Reflect Clinical Dysfunction in Amyotrophic Lateral Sclerosis: A Practical Experience.

    PubMed

    Gawel, Malgorzata; Kuzma-Kozakiewicz, Magdalena

    2016-05-01

    The aim of our study was to assess the usefulness of the MUNIX method in reflecting the clinical dysfunction in patients with amyotrophic lateral sclerosis (ALS), as well as to assess an intra-rater reproducibility of MUNIX. The study group consisted of a total of 15 ALS patients. The mean age of symptoms onset was 55 years, and the mean disease duration was 10 months. The muscle strength and patients' functional status were assessed according to the Medical Research Council (MRC) and by ALS functional rating scale revised (ALSFRS-R), respectively. The MUNIX was performed in 6 muscles: abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), tibial anterior (TA), extensor digitorum brevis (EDB), and abductor hallucis (AH), unilaterally, at a less affected side. Both muscle-specific and global MRC and MUNIX scores were calculated. In 11 patients, the study protocol was repeated at least twice every 3 months. An additional testing of the intra-rater reliability was performed at the first visit.There were no significant differences between MUNIX test and re-test values in the APB, ADM, BB, TA, EDB, and AH muscles (P >0.05). The highest variability of the test-retest values was found in the BB muscle (7.53%). Although there was a significant test-retest difference in the global MUNIX score (P = 0.02), the variability of the results was as low as 1.26%. The MUNIX value correlated with the muscle-specific MRC score in ABP, ADM, TA, EDB and AH (P <0.05), and the global MUNIX values correlated with global MRC scores (P <0.05). There was also a significant correlation between the global MUNIX score and the clinical dysfunction measured by the ALSFRS-R scale (P <0.05). The global MUNIX showed a higher monthly decline (4.3%) as compared with ALFRS-R (0.7%) and the MRC global score (0.5%).This study confirms that the MUNIX method is a sensitive, reliable, and accurate tool reflecting both motor dysfunction and disease progression in ALS

  9. Evaluation of different continuous cell lines in the isolation of mumps virus by the shell vial method from clinical samples

    PubMed Central

    Reina, J; Ballesteros, F; Mari, M; Munar, M

    2001-01-01

    Aims—To compare prospectively the efficacy of the Vero, LLC-MK2, MDCK, Hep-2, and MRC-5 cell lines in the isolation of the mumps virus from clinical samples by means of the shell vial method. Methods—During an epidemic outbreak of parotiditis 48 clinical samples (saliva swabs and CSF) were studied. Two vials of the Vero, LLC-MK2, MDCK, MRC-5, and Hep-2 cell lines were inoculated with 0.2 ml of the samples by the shell vial assay. The vials were incubated at 36°C for two and five days. The vials were then fixed with acetone at -20°C for 10 minutes and stained by a monoclonal antibody against mumps virus by means of an indirect immunofluorescence assay. Results—The mumps virus was isolated from 36 samples. The Vero and LLC-MK2 cell lines showed a 100% isolation capacity, MDCK showed 77.7%, MRC-5 showed 44.4%, and Hep-2 showed 22.2%. The Vero and LLC-MK2 lines were significantly different to the other cell lines (p < 0.001). The sensitivity for the Vero and LLC-MK2 lines at two and five days of incubation was identical (100%). The values obtained in the study of the quantitative isolation capacity (positive isolation with > 5 infectious foci) were 94.4% for Vero, 97.2% for LLC-MK2, 5.5% for MDCK, 5.5% for Hep-2, and 0% for MRC-5. Conclusions—The Vero and LLC-MK2 cell lines are equally efficient at two and five days incubation for the isolation of the mumps virus from clinical samples, and the use of the shell vial method considerably shortens the time of aetiological diagnosis with higher specificity. Key Words: mumps virus • Vero cell line • LLC-MK2 cell line • MDCK cell line • Hep-2 cell line • MRC-5 cell line • isolation • shell vial PMID:11729211

  10. Mars Rover Curriculum: Teacher Self Reporting of Increased Frequency and Confidence in their Science and Language Arts Instruction

    NASA Astrophysics Data System (ADS)

    Bering, E. A.; Carlson, C.; Nieser, K.; Slagle, E.

    2013-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 65 Mars Rover teachers from the 2012-2013 cohort were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. In total, 29 teachers participated in the survey. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. In addition, they were asked to rate the degree to which they felt their confidence increased in the past year as a result of their participation in the MRC program. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching 'Earth and the solar system and universe' increased 'Quite a bit' as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. In addition, the vast majority reported believing that their confidence increased somewhat to quite a bit as a result of their

  11. [An experimental study on targeting suicide gene therapy for lung cancer with HSV-TK driven by hTERT promoter].

    PubMed

    Wang, Yan-ping; Tang, Xiao-jun; Zhou, Qing-hua; Che, Guo-wei; Chen, Xiao-he; Zhu, Da-xing

    2008-09-01

    To study the approach of targeting expression of suicide gene HSV-TK driven by human telomerase catalytic subunit (hTERT) promoter in lung cancer cells, and to investigate inhibitory effect of HSV-TK/GCV driven by hTERT promoter on proliferation of lung cancer cell line A549 in vitro and in vivo. (1) Recombinant expression vectors of HSV-TK driven by hTERT promoter and SV40 promoter (pGL3-hTp-TK and pGL3-SV40-TK) were transfected into telomerase-positive human lung adenocarcinoma cell A549 and telomerase-negative human embryonic lung fibroblast cell MRC-5. The mRNA expression of TK gene was detected with RT-PCR method; (2) With the treatment of GCV, the proliferation of above transfected cells was investigated by MTT assay; Influence of GCV on apoptosis and cell cycle of these cells was evaluated with flow cytometry; (3) After the subcutaneously transplantation of A549 cells into nude mice, intra-tumor injection of plasmid-liposome as well as intra-peritoneal injection of GCV were performed to stUdy anti-tumor effects of pGL3-hTp-TK/GCV and pGL3-SV40-TK/GCV in vivo. (1) Enzyme digestion and PCR suggested that recombinant plasmids of pGL3-hTp-TK and pGL3-SV40-TK were successfully constructed; TK mRNA expression was detected in both A549 and MRC-5 cells transfected with pGL3-SV40-TK, also in A549 transfected with pGL3-hTp-TK, but not in MRC-5 transfected with pGL3-hTp-TK; (2) GCV showed significant inhibition effect on proliferation of A549 and MRC-5 transfected with pGL3-SV40-TK in vitro, also on that of A549 transfected with pGL3-hTp-TK, but not of MRC-5 transfected with pGL3-hTp-TK; With the treatment of GCV, apoptosis index (AI) of A549 cells transfected with pGL3-SV40-TK and pGL3-hTp-TK (21.58% and 23.19% respectively) increased significantly, compared with that of A549 transfected with pGL3-hTp and blank control; GCV enhanced the effects on AI in MRC-5 transfected with pGL3-SV40-TK (9.35%), but not with pGL3-hTp-TK (0.88%); (3) Inhibition ratio of pGL3-SV40-TK

  12. Microcirculation alterations in experimentally induced gingivitis in dogs.

    PubMed

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

  13. Improved quality of life in patients with malignant pleural effusion following videoassisted thoracoscopic talc pleurodesis. Preliminary results.

    PubMed

    Basso, Stefano M M; Mazza, Francesco; Marzano, Bernardo; Santeufemia, Davide A; Chiara, Giordano B; Lumachi, Franco

    2012-11-01

    Malignant pleural effusion (MPE) is a common, debilitating complication of several types of advanced malignancy, which may significantly reduce the quality of life of patients. There are several options to treat MPE, including thoracentesis, placement of a long-term indwelling pleural catheter and chemical pleurodesis. The best treatment is still debated, but talc remains the agent of choice to achieve pleurodesis. Forty-six patients (28 men and 18 women; median age 67 years, range 47-82 years) with MPE related to different malignancies underwent video-assisted thoracoscopy talc pleurodesis. There were 26 (56.5%) patients with non-small cell lung cancer, 8 (17.4%) with breast cancer, 7 (15.2%) with pleural mesothelioma and 5 (10.9%) with other malignancies. The average operative time was 28±8 minutes, and the duration of chest tube drainage was 9.4±4.1 days. Side-effects were mild (temporary pain, fever for 2-3 days), affecting only three (12%) patients. Two patients (8%) died during hospitalization, due to progression of disease. Overall, pre- and postoperative Karnofsky performance index (KI) and Medical Research Council (MRC) dyspnea score were 62.1±12.2 vs. 71.3±13.2 (p=0.014), and 4.2±0.8 vs. 2.7±1.0 (p<0.001), respectively. A significant relationship between total amount of preoperative pleural effusion and both KI (R=-0.54, p=0.002) and MRC (R=0.64, p=0.0001) was found. No correlation (p=NS, log-rank test) was found between preoperative KI or MRC and underlying malignancy related to MPE. In conclusion, thoracoscopic large-particle talc pleurodesis is a feasible and effective treatment for MPE, significantly improving quality of life of patients.

  14. Short-Term Prognosis of Mechanically Ventilated Patients With Guillain–Barré Syndrome Is Worsened by Corticosteroids as an Add-On Therapy

    PubMed Central

    Wu, Xiujuan; Zhang, Bing; Li, Chunrong; Shen, Donghui; Liu, Kangding; Zhu, Jie; Zhang, Hong-Liang

    2015-01-01

    Abstract Intravenous immunoglobulin (IVIg) has been proven most effective in treating Guillain–Barré syndrome (GBS). Corticosteroids as an add-on therapy have been prescribed in severe GBS cases. However, the efficacy of intravenous corticosteroids combined with IVIg in dealing with severe GBS remains unclear. We explored the therapeutic effects of different therapeutic regimens on the short-term prognosis of GBS patients, especially the severe cases. We retrospectively analyzed the clinical data of 527 adult patients with GBS who were prescribed to different treatments from 2003 to 2014. The therapeutic effect of a treatment was evaluated by the improvement of Hughes Functional Grading Scale (HFGS) and Medical Research Council (MRC) sum score. With comparable incidence of infectious complications (P > 0.05), more mechanically ventilated patients were found improvement after IVIg treatment than combination IVIg with intravenous corticosteroids (MRC: 97% vs. 72.4%, P < 0.05; HFGS: 97% vs. 72.4%, P < 0.05). As to bedridden patients without mechanical ventilation, incidence of infectious complications (P > 0.05) and ratio of patients who were improved after IVIg were insignificantly different from the combination therapy (MRC: 89.6% vs. 86.5%; HFGS: 69.6% vs. 61.5%; both P > 0.05), even if the intravenous corticosteroids were initiated within 7 days after onset (P > 0.05). In addition, supportive treatment was sufficient for patients who were able to walk with help (HFGS = 3) and mildly affected (HFGS < 3) when compared with IVIg and intravenous corticosteroids. IVIg is sufficient to GBS patients who are unable to walk (HFGS > 3), while corticosteroids are detrimental for short-term prognosis in mechanically ventilated patients when used in combination with IVIg. Further prospective and randomized studies are warranted to validate this finding. PMID:26512609

  15. Method and Excel VBA Algorithm for Modeling Master Recession Curve Using Trigonometry Approach.

    PubMed

    Posavec, Kristijan; Giacopetti, Marco; Materazzi, Marco; Birk, Steffen

    2017-06-26

    A new method was developed and implemented into an Excel Visual Basic for Applications (VBAs) algorithm utilizing trigonometry laws in an innovative way to overlap recession segments of time series and create master recession curves (MRCs). Based on a trigonometry approach, the algorithm horizontally translates succeeding recession segments of time series, placing their vertex, that is, the highest recorded value of each recession segment, directly onto the appropriate connection line defined by measurement points of a preceding recession segment. The new method and algorithm continues the development of methods and algorithms for the generation of MRC, where the first published method was based on a multiple linear/nonlinear regression model approach (Posavec et al. ). The newly developed trigonometry-based method was tested on real case study examples and compared with the previously published multiple linear/nonlinear regression model-based method. The results show that in some cases, that is, for some time series, the trigonometry-based method creates narrower overlaps of the recession segments, resulting in higher coefficients of determination R(2) , while in other cases the multiple linear/nonlinear regression model-based method remains superior. The Excel VBA algorithm for modeling MRC using the trigonometry approach is implemented into a spreadsheet tool (MRCTools v3.0 written by and available from Kristijan Posavec, Zagreb, Croatia) containing the previously published VBA algorithms for MRC generation and separation. All algorithms within the MRCTools v3.0 are open access and available free of charge, supporting the idea of running science on available, open, and free of charge software. © 2017, National Ground Water Association.

  16. Ozone affects leaf physiology and causes injury to foliage of native tree species from the tropical Atlantic Forest of southern Brazil.

    PubMed

    Moura, Bárbara Baêsso; Alves, Edenise Segala; Marabesi, Mauro Alexandre; de Souza, Silvia Ribeiro; Schaub, Marcus; Vollenweider, Pierre

    2017-08-19

    In southern Brazil, the recent increase in tropospheric ozone (O3) concentrations poses an additional threat to the biodiverse but endangered and fragmented remnants of the Atlantic Forest. Given the mostly unknown sensitivity of tropical species to oxidative stress, the principal objective of this study was to determine whether the current O3 levels in the Metropolitan Region of Campinas (MRC), downwind of São Paulo, affect the native vegetation of forest remnants. Foliar responses to O3 of three tree species typical of the MRC forests were investigated using indoor chamber exposure experiments under controlled conditions and a field survey. Exposure to 70ppb O3 reduced assimilation and leaf conductance but increased respiration in Astronium graveolens while gas exchange in Croton floribundus was little affected. Both A. graveolens and Piptadenia gonoacantha developed characteristic O3-induced injury in the foliage, similar to visible symptoms observed in >30% of trees assessed in the MRC, while C. floribundus remained asymptomatic. The underlying structural symptoms in both O3-exposed and field samples were indicative of oxidative burst, hypersensitive responses, accelerated cell senescence and, primarily in field samples, interaction with photo-oxidative stress. The markers of O3 stress were thus mostly similar to those observed in other regions of the world. Further research is needed, to estimate the proportion of sensitive forest species, the O3 impact on tree growth and stand stability and to detect O3 hot spots where woody species in the Atlantic Forest are mostly affected. Copyright © 2017. Published by Elsevier B.V.

  17. Long-term follow-up after bronchoscopic lung volume reduction treatment with coils in patients with severe emphysema

    PubMed Central

    Hartman, Jorine E; Klooster, Karin; Gortzak, Kiki; ten Hacken, Nick HT; Slebos, Dirk-Jan

    2015-01-01

    Background and objective Bronchoscopic lung volume reduction coil (LVR-coil) treatment has been shown to be safe and clinically effective in patients with severe emphysema in the short term; however, long-term safety and effectiveness has not been evaluated. The aim of this study was to investigate the long-term safety and effectiveness of LVR-coil treatment in patients with severe emphysema. Methods Thirty-eight patients with severe emphysema (median age is 59 years, forced expiratory volume in 1 s is 27% predicted) who were treated in LVR-coil clinical trials were invited for a voluntary annual visit. Safety was evaluated by chest X-ray and recording of adverse events and by efficacy by pulmonary function testing, 6-min walk distance (6MWD) and questionnaires. Results Thirty-five patients visited the hospital 1 year, 27 patients 2 years and 22 patients 3 years following coil placement. No coil migrations were observed on X-rays. At 1-year follow-up, all clinical outcomes significantly improved compared with baseline. At 2 years, residual volume % pred, modified Medical Research Council (mMRC) and the SGRQ score were still significantly improved. At 3 years, a significant improvement in mMRC score remained, with 40% of the patients reaching the 6MWD minimal important difference, and 59% for the St George's Respiratory Questionnaire (SGRQ) minimal important difference. Conclusions Follow-up of the patients treated with LVR-coils in our pilot studies showed that the coil treatment is safe with no late pneumothoraces, coil migrations or unexpected adverse events. Clinical benefit gradually declines over time; at 3 years post-treatment, around 50% of the patients maintained improvement in 6MWD, SGRQ and mMRC. PMID:25418910

  18. Comparative study of phrenic and intercostal nerve transfers for elbow flexion after global brachial plexus injury.

    PubMed

    Liu, Yuzhou; Lao, Jie; Zhao, Xin

    2015-04-01

    Global brachial plexus injuries (BPIs) are devastating events frequently resulting in severe functional impairment. The widely used nerve transfer sources for elbow flexion in patients with global BPIs include intercostal and phrenic nerves. The aim of this study was to compare phrenic and intercostal nerve transfers for elbow flexion after global BPI. A retrospective review of 33 patients treated with phrenic and intercostal nerve transfer for elbow flexion in posttraumatic global root avulsion BPI was carried out. In the phrenic nerve transfer group, the phrenic nerve was transferred to the anterolateral bundle of the anterior division of the upper trunk (23 patients); in the intercostal nerve transfer group, three intercostal nerves were coapted to the anterolateral bundles of the musculocutaneous nerve. The British Medical Research Council (MRC) grading system, angle of elbow flexion, and electromyography (EMG) were used to evaluate the recovery of elbow flexion at least 3 years postoperatively. The efficiency of motor function in the phrenic nerve transfer group was 83%, while it was 70% in the intercostal nerve transfer group. The two groups were not statistically different in terms of the MRC grade (p=0.646) and EMG results (p=0.646). The outstanding rates of angle of elbow flexion were 48% and 40% in the phrenic and intercostal nerve transfer groups, respectively. There was no significant difference of outstanding rates in the angle of elbow flexion between the two groups. Phrenic nerve transfer had a higher proportion of good prognosis for elbow flexion than intercostal nerve transfer, but the effective and outstanding rate had no significant difference for biceps reinnervation between the two groups according to MRC grading, angle of elbow flexion, and EMG. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Catechin and epicatechin reduce mitochondrial dysfunction and oxidative stress induced by amiodarone in human lung fibroblasts.

    PubMed

    Silva Santos, Luciana Fernandes; Stolfo, Adriana; Calloni, Caroline; Salvador, Mirian

    2017-06-01

    Amiodarone (AMD) and its metabolite N-desethylamiodarone can cause some adverse effects, which include pulmonary toxicity. Some studies suggest that mitochondrial dysfunction and oxidative stress may play a role in these adverse effects. Catechin and epicatechin are recognized as important phenolic compounds with the ability to decrease oxidative stress. Therefore, the aim of this study was to evaluate the potential of catechin and epicatechin to modulate mitochondrial dysfunction and oxidative damage caused by AMD in human lung fibroblast cells (MRC-5). Mitochondrial dysfunction was assessed through the activity of mitochondrial complex I and ATP biosynthesis. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Superoxide dismutase and catalase activity were measured spectrophotometrically at 480 and 240 nm, respectively. Lipid and protein oxidative levels were determined by thiobarbituric reactive substances and protein carbonyl assays, respectively. Nitric oxide (NO) levels were evaluated using the Griess reaction method. AMD was able to inhibit the activity of mitochondrial complex I and ATP biosynthesis in MRC-5 cells. Lipid and protein oxidative markers increased along with cell death, while superoxide dismutase and catalase activities and NO production decreased with AMD treatment. Both catechin and epicatechin circumvented mitochondrial dysfunction, thereby restoring the activity of mitochondrial complex I and ATP biosynthesis. Furthermore, the phenolic compounds were able to restore the imbalance in superoxide dismutase and catalase activities as well as the decrease in NO levels induced by AMD. Protein and lipid oxidative damage and cell death were reduced by catechin and epicatechin in AMD-treated cells. Catechin and epicatechin reduced mitochondrial dysfunction and oxidative stress caused by AMD in MRC-5 cells.

  20. Evaluation of Laser Stabilization and Imaging Systems for LCLS-II - Final Paper

    SciTech Connect

    Barry, Matthew

    2015-08-20

    By combining the top performing commercial laser beam stabilization system with the most ideal optical imaging configuration, the beamline for the Linear Accelerator Coherent Light Source II (LCLS-II) will deliver the highest quality and most stable beam to the cathode. To determine the optimal combination, LCLS-II beamline conditions were replicated and the systems tested with a He-Ne laser. The Guidestar-II and MRC active laser beam stabilization systems were evaluated for their ideal positioning and stability. Both a two and four lens optical imaging configuration was then evaluated for beam imaging quality, magnification properties, and natural stability. In their best performances when tested over fifteen hours, Guidestar-II kept the beam stable over approximately 70-110um while the MRC system kept it stable over approximately 90-100um. During short periods of time, Guidestar-II kept the beam stable between 10-20um, but was more susceptible to drift over time, while the MRC system maintained the beam between 30-50um with less overall drift. The best optical imaging configuration proved to be a four lens system that images to the iris located in the cathode room and from there, imaged to the cathode. The magnification from the iris to the cathode was 2:1, within an acceptable tolerance to the expected 2.1:1 magnification. The two lens configuration was slightly more stable in small periods of time (less than 10 minutes) without the assistance of a stability system, approximately 55um compared to approximately 70um, but the four lens configurations beam image had a significantly flatter intensity distribution compared to the two lens configuration which had a Gaussian distribution. A final test still needs to be run with both stability systems running at the same time through the four lens system. With this data, the optimal laser beam stabilization system can be determined for the beamline of LCLS-II.

  1. Mapping wetlands in the Lower Mekong Basin for wetland resource and conservation management using Landsat ETM images and field survey data.

    PubMed

    MacAlister, Charlotte; Mahaxay, Manithaphone

    2009-05-01

    The Mekong River Basin is considered to be the second most species rich river basin in the world. The 795,000 km(2) catchment encompasses several ecoregions, incorporating biodiverse and productive wetland systems. Eighty percent of the rapidly expanding population of the Lower Mekong Basin (LMB), made up in part by Lao PDR, Thailand, Cambodia and Viet Nam, live in rural areas and are heavily reliant on wetland resources. As the populations of Cambodia and Lao PDR will double in the next 20 years, pressure on natural resources and particularly wetlands can only increase. For development planning, resource and conservation management to incorporate wetland issues, information on the distribution and character of Mekong wetlands is essential. The existing but outdated wetland maps were compiled from secondary landuse-landcover data, have limited coverage, poor thematic accuracy and no meta-data. Therefore the Mekong River Commission (MRC) undertook to produce new wetland coverage for the LMB. As resources, funding and regional capacity are limited, it was determined that the method applied should use existing facilities, be easily adaptable, and replicable locally. For the product to be useful it must be accepted by local governments and decision makers. The results must be of acceptable accuracy (>75%) and the methodology should be relatively understandable to non-experts. In the first stage of this exercise, field survey was conducted at five pilot sites covering a range of typical wetland habitats (MRC wetland classification) to supply data for a supervised classification of Landsat ETM images from the existing MRC archive. Images were analysed using ERDAS IMAGINE and applying Maximum Likelihood Classification. Field data were reserved to apply formal accuracy assessment to the final wetland habitat maps, with resulting accuracy ranging from 77 to 94%. The maps produced are now in use at a Provincial and National level in three countries for resource and

  2. Optimal isolation and xeno-free culture conditions for limbal stem cell function.

    PubMed

    Stasi, Kalliopi; Goings, DaVida; Huang, Jiayan; Herman, Lindsay; Pinto, Filipa; Addis, Russell C; Klein, Dahlia; Massaro-Giordano, Giacomina; Gearhart, John D

    2014-01-20

    To preserve limbal stem cell (LSC) function in vitro with xenobiotic-free culture conditions. Limbal epithelial cells were isolated from 139 donors using 15 variations of three dissociation solutions. All culture conditions were compared to the baseline condition of murine 3T3-J3 feeders with xenobiotic (Xeno) keratinocyte growth medium at 20% O2. Five Xeno and Xeno-free media with increasing concentrations of calcium and epidermal growth factor (EGF) were evaluated at 5%, 14%, and 20% O2. Human MRC-5, dermal (fetal, neonatal, or adult), and limbal stromal fibroblasts were compared. Statistical analysis was performed on the number of maximum serial weekly passages, percentage of aborted colonies, colony-forming efficiency (CFE), p63α(bright) cells, and RT-PCR ratio of p63α/K12. Immunocytochemistry and RT-PCR for p63α, ABCG2, Bmi1, C/EBPδ , K12, and MUC1 were performed to evaluate phenotype. Dispase/TrypLE was the isolation method that consistently showed the best yield, viability, and CFE. On 3T3-J2 feeders, Xeno-free medium with calcium 0.1 mM and EGF 10 ng/mL at 20% O2 supported more passages with equivalent percentage of aborted colonies, p63α(bright) cells, and p63α/K12 RT-PCR ratio compared to baseline Xeno-media. With this Xeno-free medium, MRC-5 feeders showed the best performance, followed by fetal, neonatal, adult HDF, and limbal fibroblasts. MRC-5 feeders supported serial passages with sustained high expression of progenitor cell markers at levels as robust as the baseline condition without significant difference between 20% and 5% O2. The LSC function can be maintained in vitro under appropriate Xeno-free conditions.

  3. The physical function intensive care test: implementation in survivors of critical illness.

    PubMed

    Nordon-Craft, Amy; Schenkman, Margaret; Edbrooke, Lara; Malone, Daniel J; Moss, Marc; Denehy, Linda

    2014-10-01

    Recent studies have demonstrated safety, feasibility, and decreased hospital length of stay for patients with weakness acquired in the intensive care unit (ICU) who receive early physical rehabilitation. The scored Physical Function in Intensive Care Test (PFIT-s) was specifically designed for this population and demonstrated excellent psychometrics in an Australian ICU population. The purpose of this study was to determine the responsiveness and predictive capabilities of the PFIT-s in patients in the United States admitted to the ICU who required mechanical ventilation (MV) for 4 days or longer. This nested study within a randomized trial administered the PFIT-s, Medical Research Council (MRC) sum score, and grip strength test at ICU recruitment and then weekly until hospital discharge, including at ICU discharge. Spearman rho was used to determine validity. The effect size index was used to calculate measurement responsiveness for the PFIT-s. The receiver operating characteristic curve was used in predicting participants' ability to perform functional components of the PFIT-s. From August 2009 to July 2012, 51 patients were recruited from 4 ICUs in the Denver, Colorado, metro area. At ICU discharge, PFIT-s scores were highly correlated to MRC sum scores (rho=.923) and grip strength (rho=.763) (P<.0005). Using baseline test with ICU discharge (26 pairs), test responsiveness was large (1.14). At ICU discharge, an MRC sum score cut-point of 41.5 predicted participants' ability to perform the standing components of the PFIT-s. The small sample size was a limitation. However, the findings are consistent with those in a larger sample from Australia. The PFIT-s is a feasible and valid measure of function for individuals who require MV for 4 days or longer and who are alert, able to follow commands, and have sufficient strength to participate. © 2014 American Physical Therapy Association.

  4. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.

    PubMed

    Grimwade, D; Walker, H; Harrison, G; Oliver, F; Chatters, S; Harrison, C J; Wheatley, K; Burnett, A K; Goldstone, A H

    2001-09-01

    Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor in the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to induction therapy and overall survival (OS). Those with t(15;17), t(8;21), or inv(16) composed the favorable risk group. Overall, these abnormalities predicted a superior complete remission (CR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS, 15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11 (n = 2677) revealed that the most favorable changes were rarer in older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups. Furthermore, it highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches.

  5. Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo

    PubMed Central

    Kalia, Shagun; Walter, Neha Sylvia; Bagai, Upma

    2015-01-01

    Background & objectives: Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). Methods: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC50) of extract against HeLa cells was evaluated. Median lethal dose (LD50) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. Results: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC50 of 8.2 μg/ml (MRC2) and 5.1 μg/ml (RKL9). CC50 of extract on HeLa cell line was calculated to be >1000 μg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant (P<0.001) schizonticidal activity at 1000 mg/kg with ED50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. Interpretation & conclusions: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further. PMID:26905234

  6. Optimal Isolation and Xeno-Free Culture Conditions for Limbal Stem Cell Function

    PubMed Central

    Stasi, Kalliopi; Goings, DaVida; Huang, Jiayan; Herman, Lindsay; Pinto, Filipa; Addis, Russell C.; Klein, Dahlia; Massaro-Giordano, Giacomina; Gearhart, John D.

    2014-01-01

    Purpose. To preserve limbal stem cell (LSC) function in vitro with xenobiotic-free culture conditions. Methods. Limbal epithelial cells were isolated from 139 donors using 15 variations of three dissociation solutions. All culture conditions were compared to the baseline condition of murine 3T3-J3 feeders with xenobiotic (Xeno) keratinocyte growth medium at 20% O2. Five Xeno and Xeno-free media with increasing concentrations of calcium and epidermal growth factor (EGF) were evaluated at 5%, 14%, and 20% O2. Human MRC-5, dermal (fetal, neonatal, or adult), and limbal stromal fibroblasts were compared. Statistical analysis was performed on the number of maximum serial weekly passages, percentage of aborted colonies, colony-forming efficiency (CFE), p63αbright cells, and RT-PCR ratio of p63α/K12. Immunocytochemistry and RT-PCR for p63α, ABCG2, Bmi1, C/EBPδ , K12, and MUC1 were performed to evaluate phenotype. Results. Dispase/TrypLE was the isolation method that consistently showed the best yield, viability, and CFE. On 3T3-J2 feeders, Xeno-free medium with calcium 0.1 mM and EGF 10 ng/mL at 20% O2 supported more passages with equivalent percentage of aborted colonies, p63αbright cells, and p63α/K12 RT-PCR ratio compared to baseline Xeno-media. With this Xeno-free medium, MRC-5 feeders showed the best performance, followed by fetal, neonatal, adult HDF, and limbal fibroblasts. MRC-5 feeders supported serial passages with sustained high expression of progenitor cell markers at levels as robust as the baseline condition without significant difference between 20% and 5% O2. Conclusions. The LSC function can be maintained in vitro under appropriate Xeno-free conditions. PMID:24030457

  7. Fatigue and plasma cytokine concentrations at rest and during exercise in patients with sarcoidosis.

    PubMed

    Baydur, Ahmet; Alavy, Bahram; Nawathe, Amar; Liu, Shanshan; Louie, Stan; Sharma, Om Prakash

    2011-07-01

    Patients with sarcoidosis exhibit exercise intolerance-related fatigue and increased levels of circulating proinflammatory cytokines at rest. Exercise may result in increased plasma cytokine levels (PCLs) in healthy adults, but such a relationship has not been studied in sarcoidosis patients. To assess relationship of fatigue in sarcoidosis with PCLs at rest and with cardiopulmonary exercise testing (CPET). We assessed lung function, CPET data, multidimensional fatigue inventory, plasma tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations before, immediately after, and 4-6 h following CPET in 22 sarcoidosis patients (13 receiving immunomodulatory drugs) and 22 controls. Patients exhibited greater fatigue, reduced cardiorespiratory function, higher Medical Research Council (MRC) scores and higher plasma TNF-α concentrations than controls at all times. Plasma IL-1β levels did not differ between cohorts. Patients exhibited a 28% increase (statistically not significant) in TNF-α level immediately post exercise. Plasma IL-β concentrations did not change among cohorts. Treated patients exhibited higher MRC and physical fatigue scores and lower breathing reserve, but no differences in cardiorespiratory function or PCLs compared to untreated patients. In treated patients, pre-exercise plasma IL-1β correlated with physical fatigue, reduced motivation and total fatigue; TNF-α levels only correlated with general fatigue score. Treated sarcoidosis patients exhibit a relation between physical fatigue, reduced motivation and total fatigue and pre-exercise plasma IL-1β concentrations. Acute exercise does not increase PCLs. Whether the reduced MRC score and physical fatigue in treated patients is related to the therapy or to the underlying inflammatory process is difficult to determine. © 2010 Blackwell Publishing Ltd.

  8. HST Grism Confirmation of Two z ˜ 2 Structures from the Clusters around Radio-loud AGN (CARLA) Survey

    NASA Astrophysics Data System (ADS)

    Noirot, Gaël; Vernet, Joël; De Breuck, Carlos; Wylezalek, Dominika; Galametz, Audrey; Stern, Daniel; Mei, Simona; Brodwin, Mark; Cooke, Elizabeth A.; Gonzalez, Anthony H.; Hatch, Nina A.; Rettura, Alessandro; Stanford, Spencer Adam

    2016-10-01

    Using Hubble Space Telescope slitless grism data, we report the spectroscopic confirmation of two distant structures at z˜ 2 associated with powerful high-redshift radio-loud active galactic nuclei (AGNs). These rich structures, likely (forming) clusters, are among the most distant structures currently known, and were identified on the basis of Spitzer/IRAC [3.6]-[4.5] color. We spectroscopically confirm nine members in the field of MRC 2036-254, comprising eight star-forming galaxies and the targeted radio galaxy. The median redshift is z = 2.000. We spectroscopically confirm 10 members in the field of B3 0756+406, comprising 8 star-forming galaxies and 2 AGNs, including the targeted radio-loud quasar. The median redshift is z = 1.986. All confirmed members are within 500 kpc (1 arcmin) of the targeted AGNs. We derive median (mean) star-formation rates of ˜ 35 {M}⊙ {{yr}}-1 (˜ 50 {M}⊙ {{yr}}-1) for the confirmed star-forming members of both structures based on their [O iii]λ 5007 luminosities, and estimate average galaxy stellar masses ≲ 1× {10}11 {M}⊙ based on mid-infrared fluxes and spectral energy distribution modeling. Most of our confirmed members are located above the star-forming main sequence toward starburst galaxies, consistent with clusters at these early epochs being the sites of significant levels of star formation. The structure around MRC 2036-254 shows an overdensity of IRAC-selected candidate galaxy cluster members consistent with being quiescent galaxies, while the structure around B3 0756+406 shows field values, albeit with many lower limits to colors that could allow an overdensity of faint red quiescent galaxies. The structure around MRC 2036-254 shows a red sequence of passive galaxy candidates.

  9. A computer program for predicting recharge with a master recession curve

    USGS Publications Warehouse

    Heppner, Christopher S.; Nimmo, John R.

    2005-01-01

    Water-table fluctuations occur in unconfined aquifers owing to ground-water recharge following precipitation and infiltration, and ground-water discharge to streams between storm events. Ground-water recharge can be estimated from well hydrograph data using the water-table fluctuation (WTF) principle, which states that recharge is equal to the product of the water-table rise and the specific yield of the subsurface porous medium. The water-table rise, however, must be expressed relative to the water level that would have occurred in the absence of recharge. This requires a means for estimating the recession pattern of the water-table at the site. For a given site there is often a characteristic relation between the water-table elevation and the water-table decline rate following a recharge event. A computer program was written which extracts the relation between decline rate and water-table elevation from well hydrograph data and uses it to construct a master recession curve (MRC). The MRC is a characteristic water-table recession hydrograph, representing the average behavior for a declining water-table at that site. The program then calculates recharge using the WTF method by comparing the measured well hydrograph with the hydrograph predicted by the MRC and multiplying the difference at each time step by the specific yield. This approach can be used to estimate recharge in a continuous fashion from long-term well records. Presented here is a description of the code including the WTF theory and instructions for running it to estimate recharge with continuous well hydrograph data.

  10. Away-from-home family dinner sources and associations with weight status, body composition and related biomarkers of chronic disease among adolescents and their parents

    PubMed Central

    Farbakhsh, Kian; Lytle, Leslie; Hearst, Mary O.; Dengel, Donald R.; Pasch, Keryn E.; Kubik, Martha Y.

    2011-01-01

    Information regarding associations between types of away-from-home family meal sources and obesity and other chronic diseases could help guide dietitians. The present study describes the purchase frequency of away-from-home food sources for family dinner (fast food, other restaurant purchases, home delivery, and take-out foods) and associations with weight status and percent body fat among adolescents (n=723) and parents (n=723) and related biomarkers of chronic disease among adolescents (n=367). A cross-sectional study design was used with baseline parent surveys and anthropometry/fasting blood samples from two community-based obesity studies (2006–2008) in Minnesota. Logistic regression and general linear modeling assessed associations between frequency of family dinner sources (weekly versus none in past week) and outcomes (parent and adolescent overweight/obesity and percent body fat; adolescent metabolic risk cluster z-score (MRC), cholesterol, HDL-C, LDL, triglycerides, fasting glucose, insulin and systolic blood pressure. Models accounted for clustering and adjusted for study allocation, baseline meal frequency and demographic characteristics. The odds of overweight/obesity were significantly greater when families reported at least one away-from-home dinner purchase in the past week (OR=1.2–2.6). Mean percent body fat, MRC z-scores and insulin levels were significantly greater with weekly purchases of family dinner from fast food restaurants (p’s < .05). Mean percent body fat, MRC z-scores and HDL levels were significantly higher for families who purchased weekly family dinner from take-out sources (p’s < .05). Although frequent family dinners may be beneficial for adolescents, the source of dinners is likely as important in maintaining a healthy weight. Interventions should focus on encouragement of healthful family meals. PMID:22117665

  11. Morphological responses of mitochondria-rich cells to hypersaline environment in the Australian mudskipper, Periophthalmus minutus.

    PubMed

    Itoki, Naoko; Sakamoto, Tatsuya; Hayashi, Masahiro; Takeda, Tatsusuke; Ishimatsu, Atsushi

    2012-07-01

    A population of the Australian mudskipper, Periophthalmus minutus, was found to inhabit mudflat that remained uncovered by tide for more than 20 days in some neap tides. During these prolonged emersion periods, P. minutus retreated into burrows containing little water, with a highest recorded salinity of 84 ± 7.4 psu (practical salinity unit). To explore the mechanical basis for this salinity tolerance in P. minutus, we determined the densities of mitochondria-rich cells (MRCs) in the inner and outer opercula and the pectoral fin skin, in comparison with P. takita, [corrected] from an adjacent lower intertidal habitat, and studied morphological responses of MRCs to exposure to freshwater (FW), and 100% (34-35 psu) and 200% seawater (SW). Periophthalmus minutus showed a higher density of MRCs in the inner operculum (3365 ± 821 cells mm(-2)) than in the pectoral fin skin (1428 ± 161) or the outer operculum (1100 ± 986), all of which were higher than the MRC densities in p. takita. [corrected]. No mortality occurred in 100% or 200% SW, but half of the fish died within four days in FW. Neither 200% SW nor FW exposure affected MRC density. Transfer to 200% SW doubled MRC size after 9-14 days with no change in the proportion of MRCs with apical pits or plasma sodium concentration. In contrast, transfer to FW resulted in a rapid closing of pits and a significant reduction in plasma sodium concentration. These results suggest that P. minutus has evolved morphological and physiological mechanisms to withstand hypersaline conditions that they may encounter in their habitat.

  12. Predictive value of median-SSEP in early phase of stroke: a comparison in supratentorial infarction and hemorrhage.

    PubMed

    Tzvetanov, Plamen; Rousseff, Rossen T

    2005-10-01

    To compare the prognostic value of median somatosensory evoked potentials (M-SSEP) changes in the early phase of supratentorial infarction and hemorrhage. This study includes 130 patients (mean age 62+/-11.4 years, 43 women, large middle cerebral artery territory infarction in 36 patients, restricted/lacunar in 55, massive supratentorial hemorrhage in 10, small/medium size hemorrhage in 31). M-SSEP were recorded early (0-7 days in ischemia, 0-21 days in hemorrhage) and patients stratified into groups with absent, abnormal, normal response. Clinical state was determined by the Medical Research Council (MRC) scale, Barthel Index and Rankin score and followed for at least 6 months. Moderate prognostic correlation was established between N20-P25 amplitudes (r=0.34, p<0.05) and N20-P25 amplitude ratio (r=0.45, p<0.01) and Barthel Index at 6 months in patients with ischemic stroke. Moderate relationship (r=-0.34, p<0.05) exists also between N20-P25 ratio and Rankin score at 6 months in patients with small/medium size hemorrhage. In large infarctions and small/medium size cerebral hemorrhages correlations with all clinical indices of outcome are weak. In massive hemorrhage, only a weak correlation (r=-0.19, p<0.05) between amplitude ratio and Rankin score was found. The combination of initial MRC and N20-P25 amplitude ratio has 10% (in hemorrhage) to 15% (in infarction) greater prognostic value (p<0.05) than initial alone. M-SSEP have independent predictive value regarding functional recovery in ischemic stroke and small/medium size cerebral hemorrhage. Combined assessment of initial MRC and M-SSEP substantially improves prognosis in acute stroke.

  13. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions.

    PubMed

    Coffelt, Seth B; Tal, Andrea O; Scholz, Alexander; De Palma, Michele; Patel, Sunil; Urbich, Carmen; Biswas, Subhra K; Murdoch, Craig; Plate, Karl H; Reiss, Yvonne; Lewis, Claire E

    2010-07-01

    TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2(-) monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three "alternatively activated" (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2(-) macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2-TEM axis may represent a new target for antiangiogenic cancer therapies.

  14. Inhibitory effects of alkaline extract of Citrus reticulata on pulmonary fibrosis.

    PubMed

    Zhou, Xian-Mei; Wen, Gao-Yan; Zhao, Yang; Liu, Yu-Mei; Li, Jian-Xin

    2013-03-07

    The pericarp of Citrus reticulata possesses medical functions of regulating Qi and expelling phlegm, and has been clinically used for the treatment of lung related diseases in traditional Chinese medicine for a long time. Our previous research revealed that Citrus reticulata exhibited inhibitory effects on pulmonary fibrosis; however, its active principles are still unclear. To investigate the inhibitory effects on pulmonary fibrosis of alkaline extract from ethanol extract of Citrus reticulata and clarify its possible mechanism. The citrus alkaline extract (CAE) was prepared from ethanol extract of Citrus reticulata and MRC-5 cells were used for the evaluation of inhibitory activity in vitro. CAE was further orally administrated to bleomycin (BLM)-induced pulmonary fibrosis rats. The rat body weight, hydroxyproline levels in serum and lung, pathological changes of lung, as well as mRNA and protein expressions of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tumor necrosis factor-α (TNF-α) in rat lung tissues were analyzed. CAE dose-dependently inhibited the proliferation of MRC-5 cells, and the LDH assay clearly revealed that the inhibitory activity of CAE was not due to its cytotoxicity. CAE treatment significantly increased rat weight gain, ameliorated alveolitis and pulmonary fibrosis degree, and lowered hydroxyproline contents in both serum and lung tissues. RT-PCR and western blot revealed that mRNA and protein expressions of MMP-9 were significantly elevated, while mRNA and protein levels of TIMP-1 and TNF-α were markedly decreased in lung tissues of CAE treated rats. The results collectively demonstrated that CAE possessed an inhibitory activity on the proliferation of MRC-5 and a preventive effect on BLM-induced pulmonary fibrosis in rats. The preliminary mechanisms of the effects may be through upregulation of MMP-9 expression and inhibition of the expressions of TNF-α and TIMP-1. Copyright © 2013 Elsevier

  15. Exploring the impact of mask making constraints on double patterning design rules

    NASA Astrophysics Data System (ADS)

    Dam, Thuc; Sinn, Robert; Rissman, Paul; Gleason, Bob

    2011-11-01

    In order to achieve an economical design-to-mask (DTM) development cycle in the low k1 domain, designers, lithographers, and mask makers needed to move away from many sequentially isolated developmental activities onto one collaborative environment managed by a computational lithography platform that integrates their respective ecosystems. 1,2 A successful development cycle used to be achievable by designers providing designs to lithographers, who then provided RET/OPC solutions to realize designs, but once k1 fell below a certain level, the lithographers could not provide solutions to realize some critical designs, which then required feedback to designers for further redesigns requiring further lithographic evaluation cycles. So collaboration and automations between lithographers and designers became necessary to reduce feedback loops and development cycle time. RET and design solutions also were impacted by mask making, and so mask maker's feedback on MRC and other constraints needed to be integrated for all three groups to achieve an economical DTM. As many lithographers attempted to print sub-80 nm pitches with 193 nm wavelength, it became necessary to use double patterning to achieve feature resolution. With the effective pitch doubling on each split layer, there could be significant increased design rule freedom for certain complex design situations. Using an integrated computational lithographic platform, one could find design space sweet spots that could further achieve optimal lithographic performance. In this paper, the optimization of design rules (DRD) for double pattern designs (~60 nm pitch) was explored with the mask maker's perspective. The experiment to be presented started with a 2x nm design set of clips. Each set of clips underwent size/width/space/pitch variations to generate a design space, and then each design space underwent SMO with an inverse lithography technology (ILT) engine using various mask MRC's and manhattan segmentations. The

  16. Comparison of the effects of neuromuscular electrical stimulation and endurance training in patients with severe chronic obstructive pulmonary disease.

    PubMed

    Kaymaz, Dicle; Ergün, Pınar; Demirci, Ebru; Demir, Neşe

    2015-01-01

    In severely disabled patients who are not capable of following formal pulmonary rehabilitation (PR) and/or tolerating higher training intensities, neuromuscular electrical stimulation (NMES) has been successfully utilized as a localized training method. In this non-randomized controlled observational study 50 patients with severe chronic obstructive pulmonary disease (COPD), who were allocated into two groups. Endurance training group (ET) (n= 27) and NMES group (n= 23). To compare the effects of NMES and ET on health-related quality of life (HRQOL), exercise capacity, muscle strength, dyspnea, psychological status, and body composition in patients with severe COPD. Before and after PR program, the study parameters were assessed using the Medical Research Council (MRC) scale, incremental and endurance shuttle walking tests (ISWT, ESWT), manual muscle testing (MMT), the St. George's Respiratory Questionnaire (SGRQ), bioelectrical impedance analysis, and the Hospital Anxiety and Depression Scale (HADS). After the PR program, walking distance and endurance time significantly increased in both groups (p< 0.001 for each), whereas the MRC scores of both groups significantly decreased (p< 0.001 for each). In the ET group, significant decreases were noted in all domains of SGRQ and HADS. In the NMES group, significant improvements were observed in the HADS scores and in all SGRQ domain except symptom domain. No significant differences were observed between the NMES and ET groups regarding the changes from baseline to after PR program in walking distance (p= 0.140), endurance time (p= 0.376), the MRC (p= 0.540), HRQOL (p> 0.05) and HADS (p> 0.05) scores, body-mass index (BMI) (p= 0.49), fat-free mass (FFM) (p= 0.50) and fat-free mass index (FFMI) (p= 0.94). NMES can be used as an effective treatment strategy in PR programs for peripheral muscle training in patients with severe COPD.

  17. Mode of Action of (1′S,2′R)-9-{[1′,2′-Bis(hydroxymethyl) cycloprop-1′-yl]methyl}guanine (A-5021) against Herpes Simplex Virus Type 1 and Type 2 and Varicella-Zoster Virus

    PubMed Central

    Ono, Nobukazu; Iwayama, Satoshi; Suzuki, Katsuya; Sekiyama, Takaaki; Nakazawa, Harumi; Tsuji, Takashi; Okunishi, Masahiko; Daikoku, Tohru; Nishiyama, Yukihiro

    1998-01-01

    The mode of action of (1′S,2′R)-9-{[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) was studied. A-5021 was monophosphorylated at the 2′ site by viral thymidine kinases (TKs). The 50% inhibitory values for thymidine phosphorylation of A-5021 by HSV-1 TK and HSV-2 TK were comparable to those for penciclovir (PCV) and lower than those for acyclovir (ACV). Of these three agents, A-5021 inhibited VZV TK most efficiently. A-5021 was phosphorylated to a mono-, di-, and triphosphate in MRC-5 cells infected with HSV-1, HSV-2, and VZV. A-5021 triphosphate accumulated more than ACV triphosphate but less than PCV triphosphate in MRC-5 cells infected with HSV-1 or VZV, whereas HSV-2-infected MRC-5 cells had comparable levels of A-5021 and ACV triphosphates. The intracellular half-life of A-5021 triphosphate was considerably longer than that of ACV triphosphate and shorter than that of PCV triphosphate. A-5021 triphosphate competitively inhibited HSV DNA polymerases with respect to dGTP. Inhibition was strongest with ACV triphosphate, followed by A-5021 triphosphate and then (R,S)-PCV triphosphate. A DNA chain elongation experiment revealed that A-5021 triphosphate was incorporated into DNA instead of dGTP and terminated elongation, although limited chain extension was observed. Thus, the strong antiviral activity of A-5021 appears to depend on a more rapid and stable accumulation of its triphosphate in infected cells than that of ACV and on stronger inhibition of viral DNA polymerase by its triphosphate than that of PCV. PMID:9687413

  18. Complete genome analyses of the first porcine rotavirus group H identified from a South African pig does not provide evidence for recent interspecies transmission events.

    PubMed

    Nyaga, Martin M; Peenze, Ina; Potgieter, Christiaan A; Seheri, L Mapaseka; Page, Nicola A; Yinda, Claude K; Steele, A Duncan; Matthijnssens, Jelle; Mphahlele, M Jeffrey

    2016-03-01

    Rotaviruses (RVs) are classified into eight species/groups (RVA-RVH) according to the migration patterns of their 11 genome segments, as well as by serological and molecular properties of Viral Protein 6 (VP6). In 1997 a new unclassified RV was reported infecting adults in Bangladesh and China. This virus was initially named novel adult diarrhoea rotavirus (ADRV-N), but later renamed as RVH. Since then, RVH has been detected in humans only very sporadically. However, RVH is increasingly being detected in pig populations in the USA, Brazil and Japan, but not yet in Africa. Unfortunately, whole genome sequence data of porcine RVH strains in GenBank is currently restricted to a single strain (SKA-1) from Japan. Porcine diarrhoeic samples were collected in South Africa and analysed for rotavirus using an RVA ELISA and electropherotyping by PAGE. One sample displayed a 4:2:1:1:1:1:1 migration pattern, typical for RVH. In order to further investigate this strain, sequence-independent amplification followed by random sequencing using the 454/Roche GS FLX Sequencer was performed, resulting in the second complete porcine RVH strain (MRC-DPRU1575) available in databases. Phylogenetically, all segments of MRC-DPRU1575 clustered closely with the SKA-1 strain and in some segments with known porcine RVH strains from Brazil and the USA. In contrast, the porcine RVH strains were only distantly related to human RVH strains from Asia and a partial RVH-like strain recently detected in bats from Cameroon. Overall, strain MRC-DPRU1575 is the first complete genome of a porcine RVH from Africa and allows for the development of improved RVH screening methods. Our analyses indicate that RVH strains cluster according to their host species, not suggesting any evidence of recent interspecies transmission events. However, more RVH genomes from a wider host range are needed to better understand their evolutionary pathways and zoonotic potential.

  19. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients.

    PubMed

    Dres, Martin; Dubé, Bruno-Pierre; Mayaux, Julien; Delemazure, Julie; Reuter, Danielle; Brochard, Laurent; Similowski, Thomas; Demoule, Alexandre

    2017-01-01

    Intensive care unit (ICU)- and mechanical ventilation (MV)-acquired limb muscle and diaphragm dysfunction may both be associated with longer length of stay and worse outcome. Whether they are two aspects of the same entity or have a different prevalence and prognostic impact remains unclear. To quantify the prevalence and coexistence of these two forms of ICU-acquired weakness and their impact on outcome. In patients undergoing a first spontaneous breathing trial after at least 24 hours of MV, diaphragm dysfunction was evaluated using twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (a pressure <11 cm H2O defined dysfunction) and ultrasonography (thickening fraction [TFdi] and excursion). Limb muscle weakness was defined as a Medical Research Council (MRC) score less than 48. Seventy-six patients were assessed at their first spontaneous breathing trial: 63% had diaphragm dysfunction, 34% had limb muscle weakness, and 21% had both. There was a significant but weak correlation between MRC score and twitch pressure (ρ = 0.26; P = 0.03) and TFdi (ρ = 0.28; P = 0.01), respectively. Low twitch pressure (odds ratio, 0.60; 95% confidence interval, 0.45-0.79; P < 0.001) and TFdi (odds ratio, 0.84; 95% confidence interval, 0.76-0.92; P < 0.001) were independently associated with weaning failure, but the MRC score was not. Diaphragm dysfunction was associated with higher ICU and hospital mortality, and limb muscle weakness was associated with longer duration of MV and hospital stay. Diaphragm dysfunction is twice as frequent as limb muscle weakness and has a direct negative impact on weaning outcome. The two types of muscle weakness have only limited overlap.

  20. Classification of chronic obstructive pulmonary disease severity according to the new Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines: COPD assessment test versus modified Medical Research Council scale.

    PubMed

    Rieger-Reyes, Cristina; García-Tirado, Francisco Javier; Rubio-Galán, Francisco Javier; Marín-Trigo, José María

    2014-04-01

    The GOLD2011 revision proposes to stratify patients with chronic obstructive pulmonary disease (COPD) by measuring the impact of the disease using the modified Medical Research Council (mMRC) scale or COPD assessment test (CAT). Our aim was to determine whether both methods are equivalent. Observational study on a cohort of 283 patients diagnosed with COPD. We analyzed the demographic and lung function results. Patients were assessed by CAT and mMRC on the same day by the same interviewer, and divided into GOLD2011 categories according to the result of the evaluation. The degree of concordance and Spearman correlation were determined. We used ANOVA on the clinical and functional variables of the four GOLD2011 categories. Assessing the classification of patients according to the method used, an overall correlation ρ=0.613 and a degree of concordance κ=0.63 (moderate) were obtained. κ=0.44 was obtained for the 152 patients in categoriesA and B (moderate-low), and 0.38 for the 131 patients in categoriesC and D (low). Differences were observed between categories in terms of functional parameters. The classification of patients with COPD using the assessment proposed by GOLD2011 varies according to the method used (CAT or mMRC); more than 25% of patients were reclassified into different categories, implying differences in the recommended therapeutic strategy. Longitudinal studies are needed to appraise which method better classifies patients, according to its prognostic ability. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  1. How should individual participant data (IPD) from publicly funded clinical trials be shared?

    PubMed

    Tudur Smith, C; Hopkins, C; Sydes, M R; Woolfall, K; Clarke, M; Murray, G; Williamson, P

    2015-12-17

    Individual participant data (IPD) from completed clinical trials should be responsibly shared to support efficient clinical research, generate new knowledge and bring benefit to patients. The Medical Research Council (MRC) Hubs for Trials Methodology Research (HTMR) has developed guidance to facilitate the sharing of IPD from publicly funded clinical trials. Development of the guidance was completed over four phases which included a focussed review of policy documents, a web-based survey of the UK Clinical Research Collaboration (CRC) Registered Clinical Trials Units (CTU) Network, participation of an expert committee and an open consultation with the UKCRC Registered CTU Network. The project was funded by the MRC HTMR (MR/L004933/1-R39). Good practice principles include: (i) the use of a controlled access approach, using a transparent and robust system to review requests and provide secure data access; (ii) seeking consent for sharing IPD from trial participants in all future clinical trials with adequate assurance that patient privacy and confidentiality can be maintained; and (iii) establishing an approach to resource the sharing of IPD which would include support from trial funders, sponsor organisations and users of IPD. The guidance has been endorsed by Cancer Research UK, MRC Methodology Research Programme Advisory Group, Wellcome Trust and the Executive Group of the UKCRC Registered CTU Network. The National Institute for Health Research (NIHR) has confirmed it is supportive of the application of this guidance. Implementation of these principles will improve transparency, increase the coherent sharing of IPD from publicly funded trials, and help publicly funded trials to adhere to trial funder and journal requirements for data sharing.

  2. Exploring the role and function of trial steering committees: results of an expert panel meeting.

    PubMed

    Harman, Nicola L; Conroy, Elizabeth J; Lewis, Steff C; Murray, Gordon; Norrie, John; Sydes, Matt R; Lane, J Athene; Altman, Douglas G; Baigent, Colin; Bliss, Judith M; Campbell, Marion K; Elbourne, Diana; Evans, Stephen; Sandercock, Peter; Gamble, Carrol

    2015-12-30

    The independent oversight of clinical trials, which is recommended by the Medical Research Council (MRC) Guidelines for Good Clinical Practice, is typically provided by an independent advisory Data Monitoring Committee (DMC) and an independent executive committee, to whom the DMC makes recommendations. The detailed roles and function of this executive committee, known as the Trial Steering Committee (TSC), have not previously been studied or reviewed since those originally proposed by the MRC in 1998. An expert panel (n = 7) was convened comprising statisticians, clinicians and trial methodologists with prior TSC experience. Twelve questions about the role and responsibilities of the TSC were discussed by the panel at two full-day meetings. Each meeting was transcribed in full and the discussions were summarised. The expert panel reached agreement on the role of the TSC, to which it was accountable, the membership, the definition of independence, and the experience and training needed. The management of ethical issues, difficult/complex situations and issues the TSC should not ask the DMC to make recommendations on were more difficult to discuss without specific examples, but support existed for further work to help share issues and to provide appropriate training for TSC members. Additional topics discussed, which had not been identified by previous work relating to the DMCs but were pertinent to the role of the TSC, included the following: review of data sharing requests, indemnity, lifespan of the TSC, general TSC administration, and the roles of both the Funder and the Sponsor. This paper presents recommendations that will contribute to the revision and update of the MRC TSC terms of reference. Uncertainty remains in some areas due to the absence of real-life examples; future guidance on these issues would benefit from a repository of case studies. Notably, the role of a patient and public involvement (PPI) contributor was not discussed, and further work is

  3. Patterns of care of radiation therapy in patients with stage IV rectal cancer: a Surveillance, Epidemiology, and End Results analysis of patients from 2004 to 2009.

    PubMed

    Logan, Jennifer K; Huber, Kathryn E; Dipetrillo, Thomas A; Wazer, David E; Leonard, Kara L

    2014-03-01

    According to the 2013 National Comprehensive Cancer Network guidelines, pelvic radiation therapy (RT) is one of the preferred regimens for patients with metastatic rectal cancer (mRC). The objective of this study was to analyze patterns of care and outcomes data for the receipt of RT among patients with mRC using the Surveillance, Epidemiology, and End Results (SEER) database. Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (2004-2009). Patients were stratified according to their primary disease site (rectum vs rectosigmoid), tumor (T) classification, and lymph node (N) classification. Treatment regimens (with or without surgical resection, with or without RT) were recorded. The Fisher exact test was used to compare RT rates based on stratified factors. Two and five-year survival rates were compared among treatment groups. In total, 6873 patients with stage IV rectal cancer and 3417 patients with rectosigmoid cancer were identified. Overall, 20.5% of patients with rectal cancer underwent surgery alone, whereas 38.7% received RT with or without surgery. Within the rectosigmoid group, 51.4% of patients underwent surgery alone, and 15.1% received RT with or without surgery. The use of RT differed significantly between patients with in situ (Tis) through T2 tumors versus T3/T4 tumors (P < .001) and between those with N0 disease versus N1/N2 disease (P < .001). The 2-year and 5-year survival rates differed between treatment groups, with the highest survival rates observed among those who received combined surgery and RT. The primary treatments for patients with mRC include RT with or without surgery. RT is used more commonly in patients with primary rectal (vs rectosigmoid) tumors, N0 disease, or Tis-T2 tumors. Treatment with combination surgery and RT is associated with prolonged survival. © 2013 American Cancer Society.

  4. Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes

    PubMed Central

    Maneiro, E; Lopez-Armada, M; de Andres, M C; Carames, B; Martin, M; Bonilla, A; del Hoyo, P; Galdo, F; Arenas, J; Blanco, F

    2005-01-01

    Objective: To investigate the effect of nitric oxide (NO) on mitochondrial activity and its relation with the apoptosis of human articular chondrocytes. Materials and methods: Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities, and mitochondrial membrane potential (Δψm). The activities of the mitochondrial respiratory chain (MRC) complexes (complex I: NADH CoQ1 reductase, complex II: succinate dehydrogenase, complex III: ubiquinol cytochrome c reductase, complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from normal cartilage. The Δψm was measured by 5,5',6,6'-tetracholoro-1,1',3,3'-tetraethylbenzimidazole carbocyanide iodide (JC-1) using flow cytometry. Apoptosis was analysed by flow cytometry. The mRNA expression of caspases was analysed by ribonuclease protection analysis and the detection of protein synthesis by western blotting. Sodium nitroprusside (SNP) was used as an NO compound donor. Results: SNP at concentrations higher than 0.5 mmol/l for 24 hours induced cellular changes characteristic of apoptosis. SNP elicited mRNA expression of caspase-3 and caspase-7 and down regulated bcl-2 synthesis in a dose and time dependent manner. Furthermore, 0.5 mM SNP induced depolarisation of the mitochondrial membrane at 5, 12, and 24 hours. Analysis of the MRC showed that at 5 hours, 0.5 mM SNP reduced the activity of complex IV by 33%. The individual inhibition of mitochondrial complex IV with azide modified the Δψm and induced apoptosis. Conclusions: This study suggests that the effect of NO on chondrocyte survival is mediated by its effect on complex IV of the MRC. PMID:15708893

  5. Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison.

    PubMed

    Vanhoutte, Els K; Draak, Thomas H P; Gorson, Kenneth C; van Nes, Sonja I; Hoeijmakers, Janneke G J; Van der Pol, W-Ludo; Notermans, Nicolette C; Lewis, Richard A; Nobile-Orazio, Eduardo; Léger, Jean-Marc; Van den Bergh, Peter Y K; Lauria, Giuseppe; Bril, Vera; Katzberg, Hans; Lunn, Michael P T; Pouget, Jean; van der Kooi, Anneke J; Hahn, Angelika F; van Doorn, Pieter A; Cornblath, David R; van den Berg, Leonard H; Faber, Catharina G; Merkies, Ingemar S J

    2015-09-01

    This study aimed to 'define responder' through the concept of minimum clinically important differences using the individually obtained standard errors (MCID-SE) and a heuristic 'external criterion' responsiveness method in patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). One hundred and fourteen newly diagnosed or relapsing patients (GBS: 55, CIDP: 59) were serially examined (1-year follow-up). The inflammatory Rasch-built overall disability scale (I-RODS), Rasch-transformed MRC sum score (RT-MRC), and Rasch-transformed modified-INCAT-sensory scale (RT-mISS) were assessed. Being-a-responder was defined as having a MCID-SE cut-off ≥1.96. Also, the correlations between patients' scores on each scale and the EuroQoL health-status 'thermometer' (external criterion) were determined (higher correlation indicated better responsiveness). In both diseases, the SEs showed a characteristic 'U'-shaped dynamic pattern across each scales' continuum. The number of patients showing a meaningful change were higher for the I-RODS > RT-MRC > RT-mISS and were in GBS higher than CIDP patients. The MCID-SE concept using Rasch-transformed data demonstrated an individual pattern of 'being-a-responder' in patients with immune-mediated neuropathies, and the findings were validated by the external criterion responsiveness method. The I-RODS showed greater responsiveness compared with the MRC and INCAT-sensory scales, and its use is therefore recommended in future trials in GBS and CIDP. © 2015 Peripheral Nerve Society.

  6. Magnetic MIMO Signal Processing and Optimization for Wireless Power Transfer

    NASA Astrophysics Data System (ADS)

    Yang, Gang; Moghadam, Mohammad R. Vedady; Zhang, Rui

    2017-06-01

    In magnetic resonant coupling (MRC) enabled multiple-input multiple-output (MIMO) wireless power transfer (WPT) systems, multiple transmitters (TXs) each with one single coil are used to enhance the efficiency of simultaneous power transfer to multiple single-coil receivers (RXs) by constructively combining their induced magnetic fields at the RXs, a technique termed "magnetic beamforming". In this paper, we study the optimal magnetic beamforming design in a multi-user MIMO MRC-WPT system. We introduce the multi-user power region that constitutes all the achievable power tuples for all RXs, subject to the given total power constraint over all TXs as well as their individual peak voltage and current constraints. We characterize each boundary point of the power region by maximizing the sum-power deliverable to all RXs subject to their minimum harvested power constraints. For the special case without the TX peak voltage and current constraints, we derive the optimal TX current allocation for the single-RX setup in closed-form as well as that for the multi-RX setup. In general, the problem is a non-convex quadratically constrained quadratic programming (QCQP), which is difficult to solve. For the case of one single RX, we show that the semidefinite relaxation (SDR) of the problem is tight. For the general case with multiple RXs, based on SDR we obtain two approximate solutions by applying time-sharing and randomization, respectively. Moreover, for practical implementation of magnetic beamforming, we propose a novel signal processing method to estimate the magnetic MIMO channel due to the mutual inductances between TXs and RXs. Numerical results show that our proposed magnetic channel estimation and adaptive beamforming schemes are practically effective, and can significantly improve the power transfer efficiency and multi-user performance trade-off in MIMO MRC-WPT systems.

  7. Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation.

    PubMed

    Liu, Xinyi; Feng, Dongfei; Liu, Dianming; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Wang, Jing; Wang, Lihong; Jiang, Wei

    2016-01-01

    Breast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate. We identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM. The results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC. Our study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer.

  8. Active urea transport independent of H+ and Na+ transport in frog skin epithelium.

    PubMed

    Lacoste, I; Dunel-Erb, S; Harvey, B J; Laurent, P; Ehrenfeld, J

    1991-10-01

    We investigated the relationship between H+ secretion (JH), Na+ absorption (JNa), and urea transport (Ju) in skin of frogs (Rana esculenta) adapted to running tap water, NaCl (100 mM), and KCl (100 mM). In addition, cell morphological changes, particularly in the mitochondria-rich cells (MRC), were followed. NaCl adaptation stimulated an active Ju, reduced JNa and JH, and caused a decrease in the apical surface of MRC. After KCl adaptation, JNa and JH were increased and highly correlated, with a twofold increase in Ju, whereas the numerous MRC developed infoldings on their apical membranes. No correlation was found between JH and Ju. Clamping the skins in a range of +/- 50 mV or changing the external pH from 7.4 to 5.4 (at high cellular buffering power) had no effect on Ju. Depolarization of the basolateral membranes (serosal KCl-Ringer) had no effect on Ju. Ju was reversibly blocked by acidification of the cells by oxygen-free solution and sulfhydryl reagents (Hg2+, p-chloromercuribenzenesulfonic acid, and N-ethylmaleimide). Diethylstilbestrol, a proton transport blocker, had no effect on Ju. Apical addition of amiloride and derivatives (phenamil and ethylisopropyl amiloride) reversibly blocked Ju, whereas ouabain had no effect. We conclude that a cation (Na+ or H+)-dependent process is unlikely to exist in R. esculenta skin. A primary active transport in a two-step process is the simplest hypothesis to account for the energy-dependent Ju that develops in NaCl-adapted frogs.

  9. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    PubMed

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development.

  10. Impact of COPD severity on physical disability and daily living activities: EDIP-EPOC I and EDIP-EPOC II studies.

    PubMed

    Rodriguez Gonzalez-Moro, J M; de Lucas Ramos, P; Izquierdo Alonso, J L; López-Muñiz Ballesteros, B; Antón Díaz, E; Ribera, X; Martín, A

    2009-05-01

    The severity of chronic obstructive pulmonary disease (COPD) is associated to patients' health-related quality of life (HRQL). Physical impairment increasingly affects daily activities creating economic, social and personal burden for patients and their families. This burden should be considered in the management of COPD patients; therefore, we intended to assess the impact of the disease severity on physical disability and daily activities. Two epidemiological observational cross-sectional descriptive studies were carried out in 1596 patients with moderate COPD and 2012 patients with severe or very severe COPD in the routine clinical practice. Demographic and basic clinical-epidemiological data were collected and patients completed questionnaires to assess their physical disability because of COPD [Medical Research Council (MRC)], COPD repercussion on daily activities [London Chest Activity of Daily Living (LCADL)], job, economy and family habits and their health status [EQ-5D visual analogue scale (VAS)]. In all, 37% of severe/very severe COPD patients and 10% of moderate (p < 0.0001) had MRC grades 4 and 5. Mean global LCADL was significantly higher in severe/very severe than in moderate patients [29.6 (CI 95%: 28.91-30.25) vs. 21.4 (CI 95%: 20.8-21.9); p < 0.0001]. COPD job impact and economic and family habits repercussions were significantly higher and health status significantly worse in severe/very severe cases than in patients with moderate COPD. COPD severity is highly associated with physical disability by MRC grading, with functionality on daily activities and with impairment of other social and clinical activities. Moderate COPD patients show already a significant degree of impairment in all these parameters.

  11. Tethering of SCFDia2 to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase

    PubMed Central

    Maculins, Timurs; Nkosi, Pedro Junior; Nishikawa, Hiroko; Labib, Karim

    2015-01-01

    Summary Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood [1, 2]. In budding yeast, the F-box protein Dia2 drives ubiquitylation of the CMG helicase at the end of replication, leading to a disassembly pathway that requires the Cdc48 segregase [3]. The substrate-binding domain of Dia2 comprises leucine-rich repeats, but Dia2 also has a TPR domain at its amino terminus that interacts with the Ctf4 and Mrc1 subunits of the replisome progression complex [4, 5], which assembles around the CMG helicase at replication forks [6]. Previous studies suggested two disparate roles for the TPR domain of Dia2, either mediating replisome-specific degradation of Mrc1 and Ctf4 [4] or else tethering SCFDia2 (SCF [Skp1/cullin/F-box protein]) to the replisome to increase its local concentration at replication forks [5]. Here, we show that SCFDia2 does not mediate replisome-specific degradation of Mrc1 and Ctf4, either during normal S phase or in response to replication stress. Instead, the tethering of SCFDia2 to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG, both in vitro and in vivo. Correspondingly, loss of tethering reduces the efficiency of CMG disassembly in vivo and is synthetic lethal in combination with a disassembly-defective allele of CDC48. Residual ubiquitylation of Mcm7 in dia2-ΔTPR cells is still CMG specific, highlighting the complex regulation of the final stages of chromosome replication, about which much still remains to be learned. PMID:26255844

  12. Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells.

    PubMed

    Jiang, Ying; Rao, Kaimin; Yang, Guangtao; Chen, Xi; Wang, Qian; Liu, Ailin; Zheng, Hongyan; Yuan, Jing

    2012-03-01

    p53 can mediate DNA damage-induced apoptosis in various cell lines treated with Benzo(a)pyrene (BaP). However, the potential role of p73, one of the p53 family members, in BaP-induced apoptotic cell death remains to be determined. In this study, normal fetal lung fibroblasts (MRC-5) and human lung adenocarcinoma cells (H1299, p53-null) were treated with BaP at concentrations of 8, 16, 32, 64, and 128 μM for 4 and 12 h. The oxidative stress status, extent of DNA damage, expression of p53, p73, mdm2, bcl-2, and bax at the mRNA and protein levels, and the percentages of apoptosis and/or necrosis were assessed. In the two BaP-treated cell lines, we observed increased malondialdehyde (MDA) formation and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity at 4 h after the treatment; furthermore, at the time points of 4 and 12 h, we observed extremely high levels of DNA damage. In addition, at 4 h after the treatment, BaP had induced necrosis in MRC-5 and H1299 cells, but it had inhibited apoptosis in MRC-5 cells (P < 0.01 for all). Furthermore, in BaP-treated H1299 cells, only the p73 mRNA level was up-regulated. The results suggested that BaP-induced DNA damage could trigger a shift from apoptotic cell death toward necrotic cell death and that necrotic cell death is independent of p53 and p73 in these cell lines. Future studies are needed to investigate the time course of changes in the type of BaP-induced cell death in more cell lines.

  13. Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of β-Lactamase-Producing Escherichia coli.

    PubMed

    Baker, Kristin R; Sigurðardóttir, Helga Høeg; Jana, Bimal; Guardabassi, Luca

    2017-03-01

    Reversal of antimicrobial resistance is an appealing and largely unexplored strategy in drug discovery. The objective of this study was to identify potential targets for "helper" drugs reversing cephem resistance in Escherichia coli strains producing β-lactamases. A CMY-2-encoding plasmid was transferred by conjugation to seven isogenic deletion mutants exhibiting cephem hypersusceptibility. The effect of each mutation was evaluated by comparing the MICs in the wild type and the mutant harboring the same plasmid. Mutation of two genes encoding proteins involved in cell wall biosynthesis, dapF and mrcB, restored susceptibility to cefoxitin (FOX) and reduced the MICs of cefotaxime and ceftazidime, respectively, from the resistant to the intermediate category according to clinical breakpoints. The same mutants harboring a CTX-M-1-encoding plasmid fell into the intermediate or susceptible category for all three drugs. Individual deletion of dapF and mrcB in a clinical isolate of CTX-M-15-producing E. coli sequence type 131 (ST131) resulted in partial reversal of ceftazidime and cefepime resistance but did not reduce MICs below susceptibility breakpoints. Growth curve analysis indicated no fitness cost in a ΔmrcB mutant, whereas a ΔdapF mutant had a 3-fold longer lag phase than the wild type, suggesting that drugs targeting DapF may display antimicrobial activity, in addition to synergizing with selected cephems. DapF appeared to be a potential FOX helper drug target candidate, since dapF inactivation resulted in synergistic potentiation of FOX in the genetic backgrounds tested. The study showed that individual inactivation of two nonessential genes involved in cell wall biogenesis potentiates cephem activity according to drug- and strain-specific patterns.

  14. Microbial reverse electrodialysis cells for synergistically enhanced power production.

    PubMed

    Kim, Younggy; Logan, Bruce E

    2011-07-01

    A new type of bioelectrochemical system for producing electrical power, called a microbial reverse-electrodialysis cell (MRC), was developed to increase voltages and power densities compared to those generated individually by microbial fuel cells (MFCs) or reverse electrodialysis (RED) systems. In RED systems, electrode overpotentials create significant energy losses due to thermodynamically unfavorable electrode reactions, and therefore a large number of stacked cells must be used to have significant energy recovery. This results in high capital costs for the large number of membranes, and increases energy losses from pumping water through a large number of cells. In an MRC, high overpotentials are avoided through oxidation of organic matter by exoelectrogenic bacteria on the anode and oxygen reduction on the cathode. An MRC containing only five pairs of RED cells, fed solutions typical of seawater (600 mM NaCl) and river water (12 mM NaCl) at 0.85 mL/min, produced up to 3.6 W/m(2) (cathode surface area) and 1.2-1.3 V with acetate as a substrate. Pumping accounted for <2% of the produced power. A higher flow rate (1.55 mL/min) increased power densities up to 4.3 W/m(2). COD removal was 98% with a Coulombic efficiency of 64%. Power production by the individual components was substantially lower with 0.7 W/m(2) without salinity driven energy, and <0.015 W/m(2) with reduced exoelectrogenic activity due to substrate depletion. These results show that the combination of an MFC and a RED stack synergistically increases performance relative to the individual systems, producing a new type of system that can be used to more efficiently capture salinity driven energy from seawater and river water.

  15. Differentiation syndrome in acute myeloid leukemia after treatment with azacitidine.

    PubMed

    Laufer, Christin B; Roberts, Owen

    2015-11-01

    We report a case report of hyperleukocytosis, fever, hypotension, pulmonary and pericardial effusions, and acute kidney injury during initial treatment with azacitidine in a patient with AML-MRC. Collectively, the symptomatology resembled differentiation syndrome. Azacitidine has been previously associated with fever, peripheral edema, and hyperleukocytosis, but its side effect profile has never been described as similar to differentiation syndrome. The patient's deteriorating course quickly turned around after treatment with dexamethasone. This potential reaction, and potential treatment, is important for clinicians to be aware of.

  16. Does Adolescent Affect Impact Adult Social Integration? Evidence from the British 1946 Birth Cohort

    PubMed Central

    Hatch, Stephani L.; Wadsworth, Michael EJ

    2012-01-01

    Using data from the MRC National Survey of Health and Development (the British 1946 birth cohort), we take a life course approach with a sociology of mental health framework to examine the relationship between adolescent affect and adult social integration. The results suggest that being observed as anxious or sad in adolescence has long-term effect on adult social integration. These associations are not explained by adult mental health or socioeconomic status, for the most part. The results demonstrate support for social selection processes between adolescent mental health and adult social outcomes and suggest a disparate effect of type of adolescent affect on adult social outcomes. PMID:22723717

  17. JPRS Report Science & Technology Japan.

    DTIC Science & Technology

    2007-11-02

    34Ceramics Machining Handbook ," Nikkan Kogyo Shinbunsha (1987) p 211. 7. N. Yasunaga, "Ceramics Machining Handbook ," Nikkan Kogyo Shinbunsha (1987) p...a DNA library at the Clinical Research Center ( CRC ) of the Medical Research Council (MRC) to use the database and library as the core of technical...right track at last. It may be said that it started by the top-down method, but it is flowering from the bottom up. JPRS-JST-89-028 15 December 1989

  18. The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of MtDNA Deficient Prostate Cancer

    DTIC Science & Technology

    2012-03-01

    mitochondrial respiration, LNCaP cells were cultured in the absence or presence of inhibitors of various complexes of the MRC: rotenone inhibits complex I...antimycin A inhibits complex III; oligomycin inhibits Fo-ATPase of complex V. Rotenone , antimycin A and oligomycin at the concentration used inhibited the...or absence of rotenone (400 nM), antimycin A (160 ng/ml) and oligomycin (8 mg/ml). (b) HMGR in total-protein lysates of LNCaP cultured 6 h in the

  19. Selective and potent in vitro antitrypanosomal activities of ten microbial metabolites.

    PubMed

    Otoguro, Kazuhiko; Ishiyama, Aki; Namatame, Miyuki; Nishihara, Aki; Furusawa, Toshiaki; Masuma, Rokuro; Shiomi, Kazuro; Takahashi, Yoko; Yamada, Haruki; Omura, Satoshi

    2008-06-01

    More than 400 compounds isolated from soil microorganisms, and catalogued in the antibiotic library of the Kitasato Institute for Life Sciences, were screened against African trypanosomes. Ten compounds were found to have selective and potent antitrypanosomal activity in vitro: aureothin, cellocidin, destomycin A, echinomycin, hedamycin, irumamycin, LL-Z 1272beta, O-methylnanaomycin A, venturicidin A and virustomycin A. Results of the in vitro assays using the GUTat 3.1 strain of Trypanosomal brucei brucei and the STIB900 strain of T. b. rhodesiense are presented. Cytotoxicity was determined using a human MRC-5 cell line. This is the first report of antitrypanosomal activities of the 10 microbial metabolites listed above.

  20. 'Incongruous juxtapositions': the chimaera and Mrs McK.

    PubMed

    Martin, Aryn

    2007-09-01

    A century ago, the German botanist Hans Winkler (best known for coining the term 'genome') accomplished two novel transplantations. First, he produced a single plant that grafted together two completely disparate species: tomato and nightshade. Second, he chose the descriptive word 'chimaera' to name his innovation, transplanting the term from mythology to biology. This paper features Mrs McK, the first human chimera, and thus follows the term from botany to clinical medicine. Her remarkable story, pieced together from the notes, drafts and correspondence of Robert Race and his colleagues at the MRC Blood Group Unit, draws attention to the significance of names and naming.

  1. Techniques for Remote Sensing of Ionospheric Electron Density from a Spacecraft.

    DTIC Science & Technology

    1981-08-05

    J FULKS . T E OLD F19628-BO-C-O169 UNCLASSIFIED MRC-R-66B AFGL-TR-81-0331 t4. IIIIIIIIIIIIIIfflfflf II l lllhh~lflfll IIIEIIEEEEEEEEI 11111Al L~12 im...SPACECRAFT Joseph A. Ball Gordon J. Fulks Thomas E. Old William R. Wortman Mission Research Corporation 735 State Street P.O. Drawer 719 Santa Barbara...TECHNIQUES FOR REMOTE SENSING OF IONOSPHERIC ELECTRON DENSITY F-ETC(U) AUG 81 J5 A BALL, 6 J FULKS , T E OLD F19628-60-C-0169 UNCLASSIFIED NRC-R-GAB AFGL-TR

  2. Decision Support for Attack Submarine Commanders.

    DTIC Science & Technology

    1980-10-01

    AD-AO95 892 DECISION SCIENCE CONSORTIUM INC FALLS CHURCH VA F./e 12/2 DECISION SUPPORT FOR ATTACK SUBMARINE COMMANDERS. (U) OCT 80 M S COHEN, R V...BROWN N00014-80-C-0046 UNCLASSIFIED TR-8S-11 ML DECISIN IEN$CE CUIVSURTiUM, MrC. DECISION SUPPORT FOR A TTA CK SUBMARINE COMMANDERS Marvin S . Cohen and...on reverse) DDI ,o..ŕ 1473 EDITION OF I NOV 65 IS OISOLCTZ Unclassified S /N 0102-014-6601 1 SECURITY CLASIFICATION OF TNIS PAGE (10bon DW& tateo* 01

  3. Spatial-Temporal Combining-Based ZF Detection in Ultra-Wideband Communications

    NASA Astrophysics Data System (ADS)

    An, Jinyoung; Kim, Sangchoon

    The performance of ultra-wideband (UWB) multiple input multiple output (MIMO) receiver based on the RAKE maximal ratio combiner (MRC) followed by a zero forcing (ZF) detector is analytically examined. For a UWB MIMO system with NT transmit antennas, NR receive antennas, and L resolvable multipath components, the proposed MIMO detection scheme is shown to have the diversity order of LNR-NT+1 and its analytical error rate expression is presented in a log-normal fading channel. We also compare the analytical BERs with the simulated results.

  4. Cytotoxic activity of antioxidant constituents from Hypericum triquetrifolium Turra.

    PubMed

    Conforti, F; Loizzo, M R; Statti, A G; Menichini, F

    2007-01-01

    The Sulforodamine B (SRB) assay was used to test cytotoxicity against four human cancer cell lines and one normal cell line of antioxidant constituents isolated from Hypericum triquetrifolium Turra. Methanolic extract and pure compounds were tested against the large cell lung carcinoma cell line COR-L23, the hepatocellular carcinoma cell line HepG-2, renal cell adenocarcinoma ACHN, the amelanotic melanoma cell line C32 and normal human foetal lung MRC5. The results showed that I3-II8-biapigenin exhibited strong cytotoxic activity (IC50 = 5.73 micro g mL(-1)) showing a certain degree of selectivity against the different cell types.

  5. Single-walled carbon nanotubes (SWCNTs) inhibit heat shock protein 90 (HSP90) signaling in human lung fibroblasts and keratinocytes.

    PubMed

    Ong, Li-Chu; Tan, Yuen-Fen; Tan, Boon Shing; Chung, Felicia Fei-Lei; Cheong, Soon-Keng; Leong, Chee-Onn

    2017-08-15

    Single-walled carbon nanotubes (SWCNTs) are carbon-based nanomaterials that possess immense industrial potential. Despite accumulating evidence that exposure to SWCNTs might be toxic to humans, our understanding of the mechanisms for cellular toxicity of SWCNTs remain limited. Here, we demonstrated that acute exposure of short (1-3μm) and regular-length (5-30μm) pristine, carboxylated or hydroxylated SWCNTs inhibited cell proliferation in human somatic and human stem cells in a cell type-dependent manner. The toxicity of regular-length pristine SWCNT was most evidenced in NP69>CYT00086>MCF-10A>MRC-5>HaCaT > HEK-293T>HepG2. In contrast, the short pristine SWCNTs were relatively less toxic in most of the cells being tested, except for NP69 which is more sensitive to short pristine SWCNTs as compared to regular-length pristine SWCNTs. Interestingly, carboxylation and hydroxylation of regular-length SWCNTs, but not the short SWCNTs, significantly reduced the cytotoxicity. Exposure of SWCNTs also induced caspase 3 and 9 activities, mitochondrial membrane depolarization, and significant apoptosis and necrosis in MRC-5 embryonic lung fibroblasts. In contrast, SWCNTs inhibited the proliferation of HaCaT human keratinocytes without inducing cell death. Further analyses by gene expression profiling and Connectivity Map analysis showed that SWCNTs induced a gene expression signature characteristic of heat shock protein 90 (HSP90) inhibition in MRC-5 cells, suggesting that SWCNTs may inhibit the HSP90 signaling pathway. Indeed, exposure of MRC-5 cells to SWCNTs results in a dose-dependent decrease in HSP90 client proteins (AKT, CDK4 and BCL2) and a concomitant increase in HSP70 expression. In addition, SWCNTs also significantly inhibited HSP90-dependent protein refolding. Finally, we showed that ectopic expression of HSP90, but not HSP40 or HSP70, completely abrogated the cytotoxic effects of SWCNTs, suggesting that SWCNT-induced cellular toxicity is HSP90 dependent. In

  6. Efficacy of indacaterol on quality of life and pulmonary function in patients with COPD and inhaler device preferences

    PubMed Central

    Ohno, Takeshi; Wada, Shota; Hanada, Souichirou; Sawaguchi, Hirochiyo; Muraki, Masato; Tohda, Yuji

    2014-01-01

    Background Indacaterol is a novel, once-daily, inhaled, long-acting b2-agonist for patients with chronic obstructive pulmonary disease (COPD). The study objective was to evaluate the efficacy of indacaterol on quality of life and pulmonary function in patients with COPD in a real-world setting, and also to evaluate its inhaler device (Breezhaler®), which is important for both adherence and management. Methods Twenty-eight outpatients with COPD were treated with indacaterol (150 μg once daily for 8 weeks), and the effects on pulmonary function were evaluated using a questionnaire survey with the modified Medical Research Council (mMRC) dyspnea scale and COPD assessment test (CAT) before and after treatment. Similar investigations were also performed separately among different baseline medications. Moreover, original questionnaire surveys for indacaterol and its device were performed. Results Overall, mMRC dyspnea scale and CAT scores significantly improved (1.96±1.04 to 1.57±1.07 and 17.39±8.23 to 12.82±8.42, respectively; P<0.05). Significant improvements in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were also observed on pulmonary function tests (2.91±0.66 L to 3.07±0.65 L and 1.46±0.60 L to 1.58±0.59 L, respectively; P<0.05). Replacement therapy from salmeterol to indacaterol significantly improved mMRC and FVC values, but did not significantly improve CAT scores or other pulmonary functions. Add-on therapy with indacaterol significantly improved mMRC score, CAT score, FVC, and FEV1, regardless of whether tiotropium was used as a baseline treatment. All subjects in a questionnaire survey found the inhaler device easy to use. There were no serious adverse events leading to treatment discontinuation. Conclusion Indacaterol is thought to be effective and well tolerated as a bronchodilator for the management of COPD. Treatment with indacaterol in addition to a long-acting muscarinic antagonist was also useful. PMID:24489464

  7. Efficacy of indacaterol on quality of life and pulmonary function in patients with COPD and inhaler device preferences.

    PubMed

    Ohno, Takeshi; Wada, Shota; Hanada, Souichirou; Sawaguchi, Hirochiyo; Muraki, Masato; Tohda, Yuji

    2014-01-01

    Indacaterol is a novel, once-daily, inhaled, long-acting b2-agonist for patients with chronic obstructive pulmonary disease (COPD). The study objective was to evaluate the efficacy of indacaterol on quality of life and pulmonary function in patients with COPD in a real-world setting, and also to evaluate its inhaler device (Breezhaler®), which is important for both adherence and management. Twenty-eight outpatients with COPD were treated with indacaterol (150 μg once daily for 8 weeks), and the effects on pulmonary function were evaluated using a questionnaire survey with the modified Medical Research Council (mMRC) dyspnea scale and COPD assessment test (CAT) before and after treatment. Similar investigations were also performed separately among different baseline medications. Moreover, original questionnaire surveys for indacaterol and its device were performed. Overall, mMRC dyspnea scale and CAT scores significantly improved (1.96±1.04 to 1.57±1.07 and 17.39±8.23 to 12.82±8.42, respectively; P<0.05). Significant improvements in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were also observed on pulmonary function tests (2.91±0.66 L to 3.07±0.65 L and 1.46±0.60 L to 1.58±0.59 L, respectively; P<0.05). Replacement therapy from salmeterol to indacaterol significantly improved mMRC and FVC values, but did not significantly improve CAT scores or other pulmonary functions. Add-on therapy with indacaterol significantly improved mMRC score, CAT score, FVC, and FEV1, regardless of whether tiotropium was used as a baseline treatment. All subjects in a questionnaire survey found the inhaler device easy to use. There were no serious adverse events leading to treatment discontinuation. Indacaterol is thought to be effective and well tolerated as a bronchodilator for the management of COPD. Treatment with indacaterol in addition to a long-acting muscarinic antagonist was also useful.

  8. Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment

    PubMed Central

    Zhong, Ting; Zhang, Li-ying; Wang, Zeng-yan; Wang, Yue; Song, Feng-mei; Zhang, Ya-hong; Yu, Jing-hua

    2017-01-01

    Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

  9. Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1.

    PubMed

    Salah, R; Michaud, P; Mati, F; Harrat, Z; Lounici, H; Abdi, N; Drouiche, N; Mameri, N

    2013-01-01

    In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight-activity relationship and an electrostatic interaction-activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

  10. Erectile dysfunction in COPD patients.

    PubMed

    Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

    2016-02-01

    Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

  11. Designing the Bayous: The Control of Water in the Atchafalaya Basin 1800-1995

    DTIC Science & Technology

    1998-01-01

    Colonel Ernest Graves, the MRC’s resident member in the office of the Chief of Engineers, sent his chief engineering assistant, H . Velpeau "Val" Darling...sensitivity was "absolute and total." After his trip, Veysey told Major General Ernest Graves, Jr., director of civil works, that he wanted the £IS to...100, 20 (17 May 1928): 790. 30. Michael Barone , Our Country: The Shaping of America from Roosevelt to Reagan (New York City: The Free Press, 1990), p

  12. Impact Assessment on Teachers of Student-led, Inquiry-based Planetary Science Instruction in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, E. A., III; Slagle, E. M.; Carlson, C.; Nieser, K.

    2015-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. A total of 1300 students from the 2013-2014 and 2014-2015 cohort wereinvited to submit self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased "Quite a bit" as a result of their participation in the MRC program in the following areas: "Getting

  13. Synthesis, characterization and biological activities of copper(II) complex of 2-Benzimidazolyl-urea and the nitrate salt of 2-Benzimidazolyl-urea

    NASA Astrophysics Data System (ADS)

    Poyraz, Mehmet; Sari, Musa; Banti, Christina N.; Hadjikakou, Sotiris K.

    2017-10-01

    The synthesis of the complex {[Cu(BZIMU)2](NO3)2} (1) (BZIMU = 2-Benzimidazolyl-urea) is reported here. The complex 1 was characterized by elemental analysis, FT-IR, magnetic susceptibility and molar conductance measurements. The crystal structures of 1 and of the nitrate salt of [(BZIMUH+)(NO3)-] (2) were determined by X-ray diffraction analysis. The copper complex 1 and [(BZIMUH+)(NO3)-] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cervix adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cell line and normal human fetal lung fibroblast cells (MRC-5) with SRB assay.

  14. Consultation performance of general practitioners when supported by an asthma/COPDC-service

    PubMed Central

    2012-01-01

    Background General practitioners (GPs) can refer patients to an asthma/COPD service (AC-service) for diagnostic assessment of spirometry and medical history and for asthma or COPD monitoring. The AC-service reports diagnostic results and additional information about disease burden (BORG-score for complaints, MRC-dyspnoea score, exacerbation rate), life style, medication and compliance, to the patient’s GP. This study explores how GPs use this additional information when discussing the patient’s disease burden and how this influences GPs’ information and education provision during consultations with asthma/COPD patients. Method Patients with (a suspicion of) asthma or COPD were referred to an AC-service and consulted their GPs after they had received a report from the AC-service. Retrospectively patients answered questions about their GPs’ performance during these consultations. Performances were compared with performances of the same GPs during consultations without support of the AC-service (usual care), earlier that year. Results Of consultations not initiated by an AC-service check-up, 91% focussed on complaints, the initial reason for the consultation. In AC-service supported follow-up consultations, GPs explored disease burden when the (BORG-)score for complaints was high - as reported by the AC-service - even when patients themselves thought it was irrelevant. GPs put significantly less effort in exploring disease burden when the Borg-score was low (BORG 3–4: 69%; BORG1-2: 51%, p = 0,01). GPs mostly ignored MRC-dyspnoea scores: attention to dyspnoea was 18% for MRC-score <3 and 25% for MRC-score ≥3 (p = 0,63). GPs encouraged physical fitness in 13% of patients. Smoking behaviour was discussed with 66% of the actual smokers but only 14% remembered a stop smoking advice. Furthermore, pharmacotherapeutic management education in AC-service supported consultations did not differ from performance in usual care according to patient evaluations

  15. Folic before frolic.

    PubMed

    Austin, Martine

    2012-10-01

    In 1991 studies confirmed that taking folic acid both prior to conception and during the early stages of pregnancy could help reduce the risk of neural tube defects (NTDs) like spina bifida by up to 72 per cent (Medical Research Council (MRC) 1991). Yet despite this knowledge, very little has been done to promote awareness of this in the UK since the mid 1990s, and recent studies show that awareness and intake of folic acid are low. This article introduces a new initiative which aims to boost women's awareness (and most importantly uptake) of folic acid, and highlights the important role midwives can play in creating and maintaining this awareness.

  16. Relationship between Breathlessness and Anxiety in Asthma and Bronchitis: A Comparative Study

    PubMed Central

    Oswald, N. C.; Waller, R. E.; Drinkwater, J.

    1970-01-01

    Two personality testing forms, the Eysenck Personality Inventory Form A and the Cattell Self Analysis Form, were completed on 471 hospital patients who fell within the general diagnostic range of asthma, bronchitis, or both. Respiratory diagnoses were based on the standard M.R.C. questionary. All categories of patients showed a tendency towards neuroticism, anxiety, and introversion, and the scores were slightly higher for bronchitics than for asthmatics. Neuroticism and anxiety increased with increasing respiratory disability. Variations in these scores with age of onset of symptoms and length of history were small. PMID:5440566

  17. Women's choices for fetal chromosome analysis.

    PubMed

    Abramsky, L; Rodeck, C H

    1991-01-01

    Five hundred and eighty women aged 35 or more at the expected date of delivery were offered the chance to join the MRC trial comparing CVS and amniocentesis at Queen Charlotte's Hospital. After a 1 h non-directive counselling session, they were asked to choose between having no test, having amniocentesis, or joining the trial in the hopes of having CVS (or in some cases having CVS outside the trial). The majority of women chose to have some test, and CVS was a more popular choice than amniocentesis.

  18. On Shape Normalization for Non-Uniformly Active Catalyst Pellets. III.

    DTIC Science & Technology

    1981-10-01

    ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLET--ETC(U) OCT Al M4 MORBIDELLI . A VARMA DAA629 RI C 001 UNCLASSIFIED MRC-TSR-2289 NL 7...RESEARCH CENTRR ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLETS - III M. Morbidelli and A. Varma Technical Summary Report #2289 October...lies with N4RC, and not with the authors of this report. ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLETS - III M. Morbidelli and A

  19. Efficient Multipath Diversity Receiver for STBC Block Transmission System

    NASA Astrophysics Data System (ADS)

    Wang, Jieling; Yang, Hong; Yi, Kechu

    A space-time and multipath diversity combining algorithm is presented for STBC single carrier block transmission system with two transmit and one receive antennas. The initial solution is achieved by an STBC-based frequency domain equalizer, and the multipath components in the received signal are decoupled by this initial solution and channel state information. Finally, STBC combining is carried out on each decoupled multipath component separately, and then the single carrier output branches are combined further using the maximal ratio combining (MRC) algorithm.

  20. Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents.

    PubMed

    Gnoatto, Simone C B; Susplugas, Sophie; Dalla Vechia, Luciana; Ferreira, Thais B; Dassonville-Klimpt, Alexandra; Zimmer, Karine R; Demailly, Catherine; Da Nascimento, Sophie; Guillon, Jean; Grellier, Philippe; Verli, Hugo; Gosmann, Grace; Sonnet, Pascal

    2008-01-15

    A series of new piperazine derivatives of ursolic acid was synthesized and tested against Plasmodium falciparum strains. They were also tested on their cytotoxicity effects upon MRC-5 cells. Seven new piperazinyl analogues showed significant activity in the nanomolar range (IC(50)=78-167nM) against Plasmodium falciparum CQ-resistant strain FcB1. A possible mechanism of interaction implicating binding of these compounds to beta-hematin was supported by in vitro tests. Moreover, the importance of the hydrophilic framework attached at the terminal nitrogen atom of the bis-(3-aminopropyl)piperazine joined to the triterpene ring was also explored through molecular dynamic simulations.

  1. Spread Spectrum Mobile Radio Communications

    DTIC Science & Technology

    1987-10-30

    obtain 1 M I j-’/ (2.9)2m --- I-- +d d2r/2 From (2.9) one can evaluate the bit-error probability over a Rayleigh fading channel for CPM schemes. Figure...k interferers. The error probability for the interfering case is m j-1 where Q is the Gaussian error function and m is the total number of sequences...into 5.16, hence f(e)_ M 1 (2.22)( M -J)(NI-i)! for M -branch MRC, assuming independent Rayleigh fading in each branch. The average receiver output SNR

  2. Mars Rover Curriculum: Impact Assessment and Evaluation

    NASA Astrophysics Data System (ADS)

    Bering, E. A., III; Carlson, C.; Nieser, K.; Slagle, E. M.; Jacobs, L. T.; Kapral, A. J.

    2014-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover: the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 140 Mars Rover teachers from the 2012-2013 and 2013-2014 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~40 teachers have participated with responses still coming in. A total of 675 students from the 2013-2014 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-