WorldWideScience

Sample records for reduce target positioning

  1. Market segmentation, targeting and positioning

    OpenAIRE

    Camilleri, Mark Anthony

    2017-01-01

    Businesses may not be in a position to satisfy all of their customers, every time. It may prove difficult to meet the exact requirements of each individual customer. People do not have identical preferences, so rarely does one product completely satisfy everyone. Many companies may usually adopt a strategy that is known as target marketing. This strategy involves dividing the market into segments and developing products or services to these segments. A target marketing strategy is focused on ...

  2. 99mTc-labelled HYNIC-minigastrin with reduced kidney uptake for targeting of CCK-2 receptor-positive tumours

    International Nuclear Information System (INIS)

    Guggenberg, E. von; Gabriel, M.; Virgolini, I.J.; Decristoforo, C.; Dietrich, H.; Skvortsova, I.

    2007-01-01

    Different attempts have been made to develop a suitable radioligand for targeting CCK-2 receptors in vivo, for staging of medullary thyroid carcinoma (MTC) and other receptor-expressing tumours. After initial successful clinical studies with [DTPA 0 ,DGlu 1 ]minigastrin (DTPA-MG0) radiolabelled with 111 In and 90 Y, our group developed a 99m Tc-labelled radioligand, based on HYNIC-MG0. A major drawback observed with these derivatives is their high uptake by the kidneys. In this study we describe the preclinical evaluation of the optimised shortened peptide analogue, [HYNIC 0 ,DGlu 1 ,desGlu 2-6 ]minigastrin (HYNIC-MG11). 99m Tc labelling of HYNIC-MG11 was performed using tricine and EDDA as coligands. Stability experiments were carried out by reversed phase HPLC analysis in PBS, PBS/cysteine and plasma as well as rat liver and kidney homogenates. Receptor binding and cell uptake experiments were performed using AR4-2J rat pancreatic tumour cells. Animal biodistribution was studied in AR4-2J tumour-bearing nude mice. Radiolabelling was performed at high specific activities and radiochemical purity was >90%. 99m Tc-EDDA-HYNIC-MG11 showed high affinity for the CCK-2 receptor and cell internalisation comparable to that of 99m Tc-EDDA-HYNIC-MG0. Despite high stability in solution, a low metabolic stability in rat tissue homogenates was found. In a nude mouse tumour model, very low unspecific retention in most organs, rapid renal excretion with reduced renal retention and high tumour uptake were observed. 99m Tc-EDDA-HYNIC-MG11 shows advantages over 99m Tc-EDDA-HYNIC-MG0 in terms of lower kidney retention with unchanged uptake in tumours and CCK-2 receptor-positive tissue. However, the lower metabolic stability and impurities formed in the labelling process still leave room for further improvement. (orig.)

  3. Positive autobiographical memory retrieval reduces temporal discounting

    Science.gov (United States)

    Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R

    2017-01-01

    Abstract People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting—remembering the positive past—and have begun to characterize the psychological and neural mechanisms behind it. PMID:28655195

  4. Positive autobiographical memory retrieval reduces temporal discounting.

    Science.gov (United States)

    Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R; Phelps, Elizabeth A

    2017-10-01

    People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting-remembering the positive past-and have begun to characterize the psychological and neural mechanisms behind it. © The Author (2017). Published by Oxford University Press.

  5. Targets set to reduce Lake Erie algae

    Science.gov (United States)

    Evans, Mary

    2016-01-01

    In February 2016, the Great Lakes Executive Committee, which oversees the implementation of the Great Lakes Water Quality Agreement (GLWQA) between the U.S. and Canada, approved phosphorus loading targets for Lake Erie to reduce the size of harmful algal blooms (HABs), reduce the presence of the low oxygen zone in the central basin, and protect nearshore water quality. The targets are set with respect to the nutrient loads calculated for 2008. To reduce the impacts of HABs on Lake Erie a target was set of a 40 percent reduction in total and soluble reactive phosphorus loads in the spring from two Canadian rivers and several Michigan and Ohio rivers, especially the Maumee River (https://binational.net/2016/02/22/ finalptargets-ciblesfinalesdep/). States and the province of Ontario are already developing Domestic Action Plans to accomplish the reductions and scientists are developing research and monitoring plans to assess progress.

  6. Targeting incentives to reduce habitat fragmentation

    Science.gov (United States)

    David Lewis; Andrew Plantinga; Junjie Wu

    2009-01-01

    This article develops a theoretical model to analyze the spatial targeting of incentives for the restoration of forested landscapes when wildlife habitat can be enhanced by reducing fragmentation. The key theoretical result is that the marginal net benefits of increasing forest can be convex, in which case corner solutions--converting either none or all of the...

  7. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

    Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

  8. IFE Target Injection Tracking and Position Prediction Update

    International Nuclear Information System (INIS)

    Petzoldt, Ronald W.; Jonestrask, Kevin

    2005-01-01

    To achieve high gain in an inertial fusion energy power plant, driver beams must hit direct drive targets with ±20 μm accuracy (±100 μm for indirect drive). Targets will have to be tracked with even greater accuracy. The conceptual design for our tracking system, which predicts target arrival position and timing based on position measurements outside of the reaction chamber was previously described. The system has been built and has begun tracking targets at the first detector station. Additional detector stations are being modified for increased field of view. After three tracking stations are operational, position predictions at the final station will be compared to position measurements at that station as a measure of target position prediction accuracy.The as-installed design will be described together with initial target tracking and position prediction accuracy results. Design modifications that allow for improved accuracy and/or in-chamber target tracking will also be presented

  9. Methods for targetted mutagenesis in gram-positive bacteria

    Science.gov (United States)

    Yang, Yunfeng

    2014-05-27

    The present invention provides a method of targeted mutagenesis in Gram-positive bacteria. In particular, the present invention provides a method that effectively integrates a suicide integrative vector into a target gene in the chromosome of a Gram-positive bacterium, resulting in inactivation of the target gene.

  10. Online manual movement adjustments in response to target position changes and apparent target motion

    NARCIS (Netherlands)

    Oostwoud Wijdenes, L.; Brenner, E.; Smeets, J.B.J.

    2014-01-01

    This study set out to determine whether the fastest online hand movement corrections are only responses to changing judgments of the targets' position or whether they are also influenced by the apparent target motion. Introducing a gap between when a target disappears and when it reappears at a new

  11. Stereotactic Target point Verification in Actual Treatment Position of Radiosurgery

    International Nuclear Information System (INIS)

    Yun, Hyong Geun; Lee, Hyun Koo

    1995-01-01

    Purpose : Authors tried to enhance the safety and accuracy of radiosurgery by verifying stereotactic target point in actual treatment position prior to irradiation. Materials and Methods : Before the actual treatment, several sections of anthropomorphic head phantom were used to create a condition of unknown coordinated of the target point. A film was sand witched between the phantom sections and punctured by sharp needle tip. The tip of the needle represented the target point. The head phantom was fixed to the stereotactic ring and CT scan was done with CT localizer attached to the ring. After the CT scanning, the stereotactic coordinates of the target point were determined. The head phantom was secured to accelerator's treatment couch and the movement of laser isocenter to the stereotactic coordinates determined by CT scanning was performed using target positioner. Accelerator's anteroposterior and lateral portal films were taken using angiographic localizers. The stereotactic coordinates determined by analysis of portal films were compared with the stereotactic coordinates previously determined by CT scanning. Following the correction of discrepancy, the head phantom was irradiated using a stereotactic technique of several arcs. After the irradiation, the film which was sand witched between the phantom sections was developed and the degree of coincidence between the center of the radiation distribution with the target point represented by the hole in the film was measured. In the treatment of actual patients, the way of determining the stereotactic coordinates with CT localizers and angiographic localizers between two sets of coordinates, we proceeded to the irradiation of the actual patient. Results : In the phantom study, the agreement between the center of the radiation distribution and the localized target point was very good. By measuring optical density profiles of the sand witched film along axes that intersected the target point, authors could confirm

  12. Target Centroid Position Estimation of Phase-Path Volume Kalman Filtering

    Directory of Open Access Journals (Sweden)

    Fengjun Hu

    2016-01-01

    Full Text Available For the problem of easily losing track target when obstacles appear in intelligent robot target tracking, this paper proposes a target tracking algorithm integrating reduced dimension optimal Kalman filtering algorithm based on phase-path volume integral with Camshift algorithm. After analyzing the defects of Camshift algorithm, compare the performance with the SIFT algorithm and Mean Shift algorithm, and Kalman filtering algorithm is used for fusion optimization aiming at the defects. Then aiming at the increasing amount of calculation in integrated algorithm, reduce dimension with the phase-path volume integral instead of the Gaussian integral in Kalman algorithm and reduce the number of sampling points in the filtering process without influencing the operational precision of the original algorithm. Finally set the target centroid position from the Camshift algorithm iteration as the observation value of the improved Kalman filtering algorithm to fix predictive value; thus to make optimal estimation of target centroid position and keep the target tracking so that the robot can understand the environmental scene and react in time correctly according to the changes. The experiments show that the improved algorithm proposed in this paper shows good performance in target tracking with obstructions and reduces the computational complexity of the algorithm through the dimension reduction.

  13. Perceptual learning eases crowding by reducing recognition errors but not position errors.

    Science.gov (United States)

    Xiong, Ying-Zi; Yu, Cong; Zhang, Jun-Yun

    2015-08-01

    When an observer reports a letter flanked by additional letters in the visual periphery, the response errors (the crowding effect) may result from failure to recognize the target letter (recognition errors), from mislocating a correctly recognized target letter at a flanker location (target misplacement errors), or from reporting a flanker as the target letter (flanker substitution errors). Crowding can be reduced through perceptual learning. However, it is not known how perceptual learning operates to reduce crowding. In this study we trained observers with a partial-report task (Experiment 1), in which they reported the central target letter of a three-letter string presented in the visual periphery, or a whole-report task (Experiment 2), in which they reported all three letters in order. We then assessed the impact of training on recognition of both unflanked and flanked targets, with particular attention to how perceptual learning affected the types of errors. Our results show that training improved target recognition but not single-letter recognition, indicating that training indeed affected crowding. However, training did not reduce target misplacement errors or flanker substitution errors. This dissociation between target recognition and flanker substitution errors supports the view that flanker substitution may be more likely a by-product (due to response bias), rather than a cause, of crowding. Moreover, the dissociation is not consistent with hypothesized mechanisms of crowding that would predict reduced positional errors.

  14. Do Targeted Hiring Subsidies and Profiling Techniques Reduce Unemployment?

    DEFF Research Database (Denmark)

    Jahn, Elke; Wagner, Thomas

    To reduce unemployment targeted hiring subsidies for long-term unemployed are often recommended. To explore their effect on employment and wages, we devise a model with two types of unemployed and two methods of search, a public employment service (PES) and random search. The eligibility of a new......, which ad­vance the search effectiveness of the PES, crowd out the active jobseekers and reduce overall employment as well as social welfare. Nevertheless, reforms are a visible success for the PES and its target group, as they significantly increase the service's placement rate and lower the duration...

  15. Targeting HER2-positive cancer using multifunctional nanoparticles

    DEFF Research Database (Denmark)

    Juul, Christian Ammitzbøll

    Advanced delivery of chemotherapeutics to tumor tissue is an active field of research, as it offers several benefits over conventional cancer therapies. In the three introductory chapters of this thesis, the development of liposomes as drug carriers, including novel strategies to improve delivery...... efficiency, is thoroughly reviewed. Chapter 4 encompasses a comprehensive manuscript, which describes the in vitro and in vivo evaluation of a novel liposomal delivery platform designed to target the HER2 receptor on cancer cells and be activated by enzyme activity in the tumor. In Chapter 5, an alternative...... HER2-targeted liposome formulation was assessed in vitro. Rather than being enzyme-sensitive, these liposomes were responsive to reducing conditions. Such conditions are found in several cancers due to hypoxia as well as in endocytic compartments. The progressive in vitro optimization of a complex...

  16. Do Targeted Hiring Subsidies and Profiling Techniques Reduce Unemployment?

    DEFF Research Database (Denmark)

    Jahn, Elke; Wagner, Thomas

    , which advance the search effectiveness of the PES, crowd out the active jobseekers and reduce overall employment as well as social welfare. Nevertheless, reforms are a visible success for the PES and its target group, as they significantly increase the service's placement rate and lower the duration...

  17. Positive Child Rearing Practices: Parents training for reduce bullying

    OpenAIRE

    González, Brenda; Cabrera, Francisco; Martínez, Kalina

    2017-01-01

    The study aimed at assessing the effectiveness of a positive child rearing program with parents for reducing bullying and incrementing pro-social behavior of their children. Participants were eight couples and two single parents of 10 children identified as bullies. Half of the parents were assigned to a control group and the other half were trained to identify aggressive and pro-social behaviors of their children, as well as their antecedents and consequences. During eight weekly sessions pa...

  18. Lenses matching of compound eye for target positioning

    Science.gov (United States)

    Guo, Fang; Zheng, Yan Pei; Wang, Keyi

    2012-10-01

    Compound eye, as a new imaging method with multi-lens for a large field of view, could complete target positioning and detection fastly, especially at close range. Therefore it could be applicated in the fields of military and medical treatment and aviation with vast market potential and development prospect. Yet the compound eye imaging method designed use three layer construction of multiple lens array arranged in a curved surface and refractive lens and imaging sensor of CMOS. In order to simplify process structure and increase the imaging area of every sub-eye, the imaging area of every eye is coved with the whole CMOS. Therefore, for several imaging point of one target, the corresponding lens of every imaging point is unkonown, and thus to identify. So an algorithm was put forward. Firstly, according to the Regular Geometry relationship of several adjacent lenses, data organization of seven lenses with a main lens was built. Subsequently, by the data organization, when one target was caught by several unknown lenses, we search every combined type of the received lenses. And for every combined type, two lenses were selected to combine and were used to calculate one three-dimensional (3D) coordinate of the target. If the 3D coordinates are same to the some combine type of the lenses numbers, in theory, the lenses and the imaging points are matched. So according to error of the 3D coordinates is calculated by the different seven lenses numbers combines, the unknown lenses could be distinguished. The experimental results show that the presented algorithm is feasible and can complete matching task for imaging points and corresponding lenses.

  19. Positive-negative-selection-mediated gene targeting in rice

    Directory of Open Access Journals (Sweden)

    Zenpei eShimatani

    2015-01-01

    Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

  20. Predicting Drug-Target Interactions Based on Small Positive Samples.

    Science.gov (United States)

    Hu, Pengwei; Chan, Keith C C; Hu, Yanxing

    2018-01-01

    A basic task in drug discovery is to find new medication in the form of candidate compounds that act on a target protein. In other words, a drug has to interact with a target and such drug-target interaction (DTI) is not expected to be random. Significant and interesting patterns are expected to be hidden in them. If these patterns can be discovered, new drugs are expected to be more easily discoverable. Currently, a number of computational methods have been proposed to predict DTIs based on their similarity. However, such as approach does not allow biochemical features to be directly considered. As a result, some methods have been proposed to try to discover patterns in physicochemical interactions. Since the number of potential negative DTIs are very high both in absolute terms and in comparison to that of the known ones, these methods are rather computationally expensive and they can only rely on subsets, rather than the full set, of negative DTIs for training and validation. As there is always a relatively high chance for negative DTIs to be falsely identified and as only partial subset of such DTIs is considered, existing approaches can be further improved to better predict DTIs. In this paper, we present a novel approach, called ODT (one class drug target interaction prediction), for such purpose. One main task of ODT is to discover association patterns between interacting drugs and proteins from the chemical structure of the former and the protein sequence network of the latter. ODT does so in two phases. First, the DTI-network is transformed to a representation by structural properties. Second, it applies a oneclass classification algorithm to build a prediction model based only on known positive interactions. We compared the best AUROC scores of the ODT with several state-of-art approaches on Gold standard data. The prediction accuracy of the ODT is superior in comparison with all the other methods at GPCRs dataset and Ion channels dataset. Performance

  1. Reaching the global target to reduce stunting: an investment framework.

    Science.gov (United States)

    Shekar, Meera; Kakietek, Jakub; D'Alimonte, Mary R; Rogers, Hilary E; Eberwein, Julia Dayton; Akuoku, Jon Kweku; Pereira, Audrey; Soe-Lin, Shan; Hecht, Robert

    2017-06-01

    Childhood stunting, being short for one's age, has life-long consequences for health, human capital and economic growth. Being stunted in early childhood is associated with slower cognitive development, reduced schooling attainment and adult incomes decreased by 5-53%. The World Health Assembly has endorsed global nutrition targets including one to reduce the number of stunted children under five by 40% by 2025. The target has been included in the Sustainable Development Goals (SDG target 2.2). This paper estimates the cost of achieving this target and develops scenarios for generating the necessary financing. We focus on a key intervention package for stunting (KIPS) with strong evidence of effectiveness. Annual scale-up costs for the period of 2016-25 were estimated for a sample of 37 high burden countries and extrapolated to all low and middle income countries. The Lives Saved Tool was used to model the impact of the scale-up on stunting prevalence. We analysed data on KIPS budget allocations and expenditure by governments, donors and households to derive a global baseline financing estimate. We modelled two financing scenarios, a 'business as usual', which extends the current trends in domestic and international financing for nutrition through 2025, and another that proposes increases in financing from all sources under a set of burden-sharing rules. The 10-year financial need to scale up KIPS is US$49.5 billion. Under 'business as usual', this financial need is not met and the global stunting target is not reached. To reach the target, current financing will have to increase from US$2.6 billion to US$7.4 billion a year on average. Reaching the stunting target is feasible but will require large coordinated investments in KIPS and a supportive enabling environment. The example of HIV scale-up over 2001-11 is instructive in identifying the factors that could drive such a global response to childhood stunting. © The Author 2017. Published by Oxford University

  2. Do Targeted Hiring Subsidies and Profiling Techniques Reduce Unemployment?

    DEFF Research Database (Denmark)

    Jahn, Elke; Wagner, Thomas

    2008-01-01

    To reduce equilibrium unemployment targeted hiring subsidies and profiling techniques for long-term unemployed are often recommended. To analyze the effects of these two instruments, our model combines two search methods: the public employment service and random search, jobseekers choose between...... an active and a passive search strategy, while labour market policy has two options available. First, only the long-term unemployed placed by the public employment service are subsidized. Second, the subsidy is paid for each match with a long-term unemployed irrespective of the search method used. We show...

  3. Do Targeted Hiring Subsidies and Profiling Techniques Reduce Unemployment?

    DEFF Research Database (Denmark)

    Jahn, Elke; Wagner, Thomas

    To reduce equilibrium unemployment targeted hiring subsidies and profilin techniques for long-term unemployed are often recommended. To analyze the effects of these two instruments, our model combines two search methods: the public employment serviceand random search, jobseekers choose between...... an active and a passive search strategy, while labour market policy has two options available. First, only the long-term unemployed placed by the public employment service are subsidized. Second, the subsidy is paid for each match with a long-term unemployed irrespective of the search method used. We show...

  4. Characteristics of the positive ion source at reduced gas feed

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, S. K., E-mail: sksharma@ipr.res.in; Bharathi, P.; Prahlad, V.; Patel, P. J.; Choksi, B.; Jana, M. R.; Bansal, L. K.; Qureshi, K.; Sumod, C. B.; Vadher, V.; Thakkar, D.; Gupta, L. N.; Rambabu, S.; Parmar, S.; Contractor, N.; Sahu, A. K.; Pandya, B.; Sridhar, B.; Pandya, S.; Baruah, U. K. [Institute for Plasma Research, Bhat, Gandhinagar (India)

    2014-11-15

    The neutral beam injector of steady state superconducting tokamak (SST1-NBI) at IPR is designed for injecting upto 1.7 MW of neutral beam (Hº, 30–55 keV) power to the tokamak plasma for heating and current drive. Operations of the positive ion source (PINI or Plug-In-Neutral-Injector) of SST1-NBI were carried out on the NBI test stand. The PINI was operated at reduced gas feed rate of 2–3 Torr l/s, without using the high speed cryo pumps. Experiments were conducted to achieve a stable beam extraction by optimizing operational parameters namely, the arc current (120–300 A), acceleration voltage (16–40 kV), and a suitable control sequence. The beam divergence, power density profiles, and species fractions (H{sup +}:H{sub 2}{sup +}:H{sub 3}{sup +}) were measured by using the diagnostics such as thermal calorimetry, infrared thermography, and Doppler shift spectroscopy. The maximum extracted beam current was about 18 A. A further increase of beam current was found to be limited by the amount of gas feed rate to the ion source.

  5. Underwater target positioning with a single acoustic sensor

    Digital Repository Service at National Institute of Oceanography (India)

    David, M-S; Pascoal, A.M.; Joaquin, A.

    The availability of reliable underwater positioning systems to localize one or more vehicles simultaneously based on information received on-board a support ship or an autonomous surface vessel is key to the operation of some classes of AUVs...

  6. LH2 Target Design & Position Survey Techniques for the MUSE experiment for Precise Proton Radius Measurement

    Science.gov (United States)

    Le Pottier, Luc; Roy, Pryiashee; Lorenzon, Wolfgang; Raymond, Richard; Steinberg, Noah; Rossi de La Fuente, Erick; MUSE (MUon proton Scattering Experiment) Collaboration

    2017-09-01

    The proton radius puzzle is a currently unresolved problem which has intrigued the scientific community, dealing with a 7 σ discrepancy between the proton radii determined from muonic hydrogen spectroscopy and electron scattering measurements. The MUon Scattering Experiment (MUSE) aims to resolve this puzzle by performing the first simultaneous elastic scattering measurements of both electrons and muons on the proton, which will allow the comparison of the radii from the two interactions with reduced systematic uncertainties. The data from this experiment is expected to provide the best test of lepton universality to date. The experiment will take place at the Paul Scherrer Institute in Switzerland in 2018. An essential component of the experiment is a liquid hydrogen (LH2) cryotarget system. Our group at the University of Michigan is responsible for the design, fabrication and installation of this system. Here we present our LH2 target cell design and fabrication techniques for successful operation at 20 K and 1 atm, and our computer vision-based target position survey system which will determine the position of the target, installed inside a vacuum chamber, with 0.01 mm or better precision at the height of the liquid hydrogen target and along the beam direction during the experiment.

  7. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Peres, Elodie A.; Valable, Samuel; Guillamo, Jean-Sebastien; Marteau, Lena; Bernaudin, Jean-Francois; Roussel, Simon; Lechapt-Zalcman, Emmanuele; Bernaudin, Myriam; Petit, Edwige

    2011-01-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  8. Maintenance strategies to reduce downtime due to machine positional errors

    OpenAIRE

    Shagluf, Abubaker; Longstaff, A.P.; Fletcher, S.

    2014-01-01

    Proceedings of Maintenance Performance Measurement and Management (MPMM) Conference 2014 Manufacturing strives to reduce waste and increase Overall Equipment Effectiveness (OEE). When managing machine tool maintenance a manufacturer must apply an appropriate decision technique in order to reveal hidden costs associated with production losses, reduce equipment downtime competentely and similiarly identify the machines performance. Total productive maintenance (TPM) is a maintenance progr...

  9. Depression reduces perceptual sensitivity for positive words and pictures.

    Science.gov (United States)

    Atchley, Ruth Ann; Ilardi, Stephen S; Young, Keith M; Stroupe, Natalie N; O'Hare, Aminda J; Bistricky, Steven L; Collison, Elizabeth; Gibson, Linzi; Schuster, Jonathan; Lepping, Rebecca J

    2012-01-01

    There is evidence of maladaptive attentional biases for lexical information (e.g., Atchley, Ilardi, & Enloe, 2003; Atchley, Stringer, Mathias, Ilardi, & Minatrea, 2007) and for pictographic stimuli (e.g., Gotlib, Krasnoperova, Yue, & Joormann, 2004) among patients with depression. The current research looks for depressotypic processing biases among depressed out-patients and non-clinical controls, using both verbal and pictorial stimuli. A d' measure (sensitivity index) was used to examine each participant's perceptual sensitivity threshold. Never-depressed controls evidenced a detection bias for positive picture stimuli, while depressed participants had no such bias. With verbal stimuli, depressed individuals showed specific decrements in the detection of positive person-referent words (WINNER), but not with positive non-person-referent words (SUNSHINE) or with negative words. Never-depressed participants showed no such differences across word types. In the current study, depression is characterised both by an absence of the normal positivistic biases seen in individuals without mood disorders (consistent with McCabe & Gotlib, 1995), and by a specific reduction in sensitivity for person-referent positive information that might be inconsistent with depressotypic self-schemas.

  10. Techniques to control and position laser targets. Final report

    International Nuclear Information System (INIS)

    Jones, T.B.

    1978-06-01

    The purpose of the work was to investigate the potential role of various electrohydrodynamic phenomena in the fabrication of small spherical particles and shells for laser target applications. A number of topics were considered. These included charged droplet levitation, specifically the combined effects of the Rayleigh limit and droplet elongation in the presence of electric fields. Two new levitation schemes for uncharged dielectric particles were studied. A dynamic dielectrophoretic levitation scheme was proposed and unsuccessful attempts were made to observe levitation with it. Another static dielectrophoretic levitation scheme was studied and used extensively. A theory was developed for this type of levitation, and a dielectric constant measurement scheme proposed. A charged droplet generator for the production of single droplets ( 4 /O 2 bubbles in Viscasil silicone fluid were conducted to learn about the possibility of using silane to form SiO 2 microballons from bubbles

  11. Target Context Specification Can Reduce Costs in Nonfocal Prospective Memory

    Science.gov (United States)

    Lourenço, Joana S.; White, Katherine; Maylor, Elizabeth A.

    2013-01-01

    Performing a nonfocal prospective memory (PM) task results in a cost to ongoing task processing, but the precise nature of the monitoring processes involved remains unclear. We investigated whether target context specification (i.e., explicitly associating the PM target with a subset of ongoing stimuli) can trigger trial-by-trial changes in task…

  12. Prone positioning reduces severe pushing behavior: three case studies.

    Science.gov (United States)

    Fujino, Yuji; Amimoto, Kazu; Sugimoto, Satoshi; Fukata, Kazuhiro; Inoue, Masahide; Takahashi, Hidetoshi; Makita, Shigeru

    2016-09-01

    [Purpose] Pushing behavior is classically described as a disorder of body orientation in the coronal plane. Most interventions for pushing behavior have focused on correcting the deviation in vertical perception. However, pushing behavior seems to involve erroneous movements associated with excessive motor output by the non-paretic limbs and trunk. The present study aimed to inhibit muscular hyper-activity by placing the non-paretic limbs and trunk in the prone position. [Subjects and Methods] The subjects of the present study were 3 acute stroke patients with severe pushing behavior. The study consisted of the following 3 phases: baseline, intervention, and follow-up. In addition to conventional therapy, patients received relaxation therapy in the prone position for 10 minutes a day over 2 days. The severity of pushing behavior was assessed using the scale for contraversive pushing, and truncal balance was evaluated using the trunk control test. These assessments were performed before and after the baseline phase, and after the intervention and follow-up phases. [Results] At the baseline phase, both scores were poor. Both scores improved after the intervention and follow-up phases, and all the patients could sit independently. [Conclusion] Relaxation therapy in the prone position might ameliorate pushing behavior and impaired truncal balance.

  13. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    Energy Technology Data Exchange (ETDEWEB)

    Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

    2010-11-15

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  14. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    International Nuclear Information System (INIS)

    Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

    2010-01-01

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  15. Development of position measurement unit for flying inertial fusion energy target

    International Nuclear Information System (INIS)

    Tsuji, R; Endo, T; Yoshida, H; Norimatsu, T

    2016-01-01

    We have reported the present status in the development of a position measurement unit (PMU) for a flying inertial fusion energy (IFE) target. The PMU, which uses Arago spot phenomena, is designed to have a measurement accuracy smaller than 1 μm. By employing divergent, pulsed orthogonal laser beam illumination, we can measure the time and the target position at the pulsed illumination. The two-dimensional Arago spot image is compressed into one-dimensional image by a cylindrical lens for real-time processing. The PMU are set along the injection path of the flying target. The local positions of the target in each PMU are transferred to the controller and analysed to calculate the target trajectory. Two methods are presented to calculate the arrival time and the arrival position of the target at the reactor centre. (paper)

  16. Development of position measurement unit for flying inertial fusion energy target

    Science.gov (United States)

    Tsuji, R.; Endo, T.; Yoshida, H.; Norimatsu, T.

    2016-03-01

    We have reported the present status in the development of a position measurement unit (PMU) for a flying inertial fusion energy (IFE) target. The PMU, which uses Arago spot phenomena, is designed to have a measurement accuracy smaller than 1 μm. By employing divergent, pulsed orthogonal laser beam illumination, we can measure the time and the target position at the pulsed illumination. The two-dimensional Arago spot image is compressed into one-dimensional image by a cylindrical lens for real-time processing. The PMU are set along the injection path of the flying target. The local positions of the target in each PMU are transferred to the controller and analysed to calculate the target trajectory. Two methods are presented to calculate the arrival time and the arrival position of the target at the reactor centre.

  17. How to reduce turnover by creating a positive work climate.

    Science.gov (United States)

    Kushell, R E

    1979-08-01

    Despite company attempts to reduce employee turnover by offering attractive salaries and benefits, Kushell notes that attrition continues at an alarming rate. He states that more than one of every three employees will change jobs over the next five years, a transition that will take its toll on company morale and productivity. The underlying factor, according to the author, is the quality of the working environment. A 1969 University of Michigan survey of 1,533 workers, at every occupation level, reported that all respondents ranked interesting work and authority to get the job done far ahead of good pay and job security. Sources of employee frustration include a stifling bureaucracy, excessive job expectations, and unsuitable jobs. The author suggests that top managers ask themselves whether they are missing out on or losing talented employees. If this is the case, there are several guidelines management should follow: improve communication between employees and top management; define expectations of the employee; and promote candor in the job interview. Kushell concludes that top executives can have an impact on turnover by paying attention to what employees really want rather than what management thinks they want.

  18. MRO CRISM MAP-PROJECTED TARGETED REDUCED DATA RECORD V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — This volume contains the CRISM Map-projected Targeted Reduced Data Record (MTRDR) archive, a collection of multiband image cubes derived from targeted (gimbaled)...

  19. Synchronous Sounds Enhance Visual Sensitivity without Reducing Target Uncertainty

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Chen

    2011-10-01

    Full Text Available We examined the crossmodal effect of the presentation of a simultaneous sound on visual detection and discrimination sensitivity using the equivalent noise paradigm (Dosher & Lu, 1998. In each trial, a tilted Gabor patch was presented in either the first or second of two intervals consisting of dynamic 2D white noise with one of seven possible contrast levels. The results revealed that the sensitivity of participants' visual detection and discrimination performance were both enhanced by the presentation of a simultaneous sound, though only close to the noise level at which participants' target contrast thresholds started to increase with the increasing noise contrast. A further analysis of the psychometric function at this noise level revealed that the increase in sensitivity could not be explained by the reduction of participants' uncertainty regarding the onset time of the visual target. We suggest that this crossmodal facilitatory effect may be accounted for by perceptual enhancement elicited by a simultaneously-presented sound, and that the crossmodal facilitation was easier to observe when the visual system encountered a level of noise that happened to be close to the level of internal noise embedded within the system.

  20. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2015-10-01

    RHOB, RRAS, RHOA, PLAU, RHOF, ITGB5, ITGB3 Methylglyoxal degradation III 2.17Eþ00 1.30E01 AKR1C1/AKR1C2, AKR1C3, AKR1C4 Dopamine degradation...2007;25: 2921–7. 6. Bober SL, Recklitis CJ, Bakan J, Garber JE, Patenaude AF. Addressing sexual dysfunction after risk-reducing salpingo-oophorectomy

  1. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2017-12-01

    removed by Picard Tools, and base quality score recalibration and Indel (insert/deletion) realignment using the Genome Analysis Toolkit GATK (McKenna et...Analysis Toolkit : a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research 20, 1297-1303. McLean, C. Y., Bristor, D...CA151683), a Department of Defense Career Development award (CA130247), and grants from Gabrielle’s Angel Foundation and Concern Foundation. GGW is also

  2. STRATEGI SEGMENTING, TARGETING, POSITIONING SERTA STRATEGI HARGA PADA PERUSAHAAN KECAP BLEKOK DI CILACAP

    OpenAIRE

    Wijaya, Hari; Sirine, Hani

    2017-01-01

    To win the market competition, companies must have segmenting, targeting, positioning strategy and pricing strategy. This study aims to determine segmenting, targeting, positioning strategy as well as the company's pricing strategies on Kecap Blekok Company in Cilacap. Methods of data collection in this study using interviews and documentation. The analysis technique used is descriptive analysis techniques. The results showed market segment of Kecap Blekok Company is the lower middle class, t...

  3. Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus.

    Science.gov (United States)

    Cheung, N Wah; Conn, Jennifer J; d'Emden, Michael C; Gunton, Jenny E; Jenkins, Alicia J; Ross, Glynis P; Sinha, Ashim K; Andrikopoulos, Sofianos; Colagiuri, Stephen; Twigg, Stephen M

    2009-09-21

    Tight glycaemic control reduces the risk of development and progression of organ complications in people with type 1 or type 2 diabetes. In this position statement, the Australian Diabetes Society recommends a general target glycated haemoglobin (HbA(1c)) level of position statement also provides guidelines for the individualisation of glycaemic targets to a tighter or lesser degree, with a recommended target HbA(1c) level of diabetes and its duration, pregnancy, diabetes medication being taken, presence of cardiovascular disease, risk of and problems from hypoglycaemia, and comorbidities. Management of diabetes also includes: adequate control of other cardiovascular risk factors, including weight, blood pressure and lipid serum levels; antiplatelet therapy; and smoking cessation.

  4. Brand market positions estimation and defining the strategic targets of its development

    OpenAIRE

    S.M. Makhnusha

    2010-01-01

    In this article the author generalizes the concept of brand characteristics which influenceits profitability and market positions. An approach to brand market positions estimation anddefining the strategic targets of its development is proposed.Keywords: brand, brand expansion, brand extension, brand value, brand power, brandrelevance, brand awareness.

  5. Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells.

    Science.gov (United States)

    Schneider, Craig S; Perez, Jimena G; Cheng, Emily; Zhang, Clark; Mastorakos, Panagiotis; Hanes, Justin; Winkles, Jeffrey A; Woodworth, Graeme F; Kim, Anthony J

    2015-02-01

    A major limitation in the treatment of glioblastoma (GBM), the most common and deadly primary brain cancer, is delivery of therapeutics to invading tumor cells outside of the area that is safe for surgical removal. A promising way to target invading GBM cells is via drug-loaded nanoparticles that bind to fibroblast growth factor-inducible 14 (Fn14), thereby potentially improving efficacy and reducing toxicity. However, achieving broad particle distribution and nanoparticle targeting within the brain remains a significant challenge due to the adhesive extracellular matrix (ECM) and clearance mechanisms in the brain. In this work, we developed Fn14 monoclonal antibody-decorated nanoparticles that can efficiently penetrate brain tissue. We show these Fn14-targeted brain tissue penetrating nanoparticles are able to (i) selectively bind to recombinant Fn14 but not brain ECM proteins, (ii) associate with and be internalized by Fn14-positive GBM cells, and (iii) diffuse within brain tissue in a manner similar to non-targeted brain penetrating nanoparticles. In addition, when administered intracranially, Fn14-targeted nanoparticles showed improved tumor cell co-localization in mice bearing human GBM xenografts compared to non-targeted nanoparticles. Minimizing non-specific binding of targeted nanoparticles in the brain may greatly improve the access of particulate delivery systems to remote brain tumor cells and other brain targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Evaluation of accuracy in target positions of multmodality imaging using brain phantom

    Energy Technology Data Exchange (ETDEWEB)

    Juh, R. H.; Suh, T. S.; Chung, Y. A. [The Catholic University of Korea, Seoul (Korea, Republic of)

    2002-07-01

    Determination of target positions in radiation therapy or radiosurgery is critical to the successful treatment. It is often difficult to recognize the target position only from single image modality since each image modality has unique image pattern and image distortion problem. The purpose of this study is to evaluate the accuracy of target positions with multimodality brain phantom. We obtained CT, MR, and SPECT scan images with the specially designed brain phantom. Brain phantom consists of brain for images and frame for localization. The phantom was a water fillable cylinder containing 58 axial layers of 2.0 mm thickness. Each layer allows water to permeate various regions to match gray matter to white matter of 1:1 ratio. Localization frame with 5mm inner diameter and 150/160 mm length were attached to the outside of the brain slice and inside of the phantom cylinder. The phantom was filled with 0.16 M CuSO{sub 4} solution for MRI scan, and distilled water for CT and 15mCi (555 MBq) Tc-99m for SPECT. Axial slice images and volume images including the targets and localizer were obtained for each modality. To evaluate the errors in target positions, the position of localization and target balls measured in SPECT were compared with MR and CT. Transformation parameters for translation, rotation and scaling were determined by surface matching each SPECT with MR and CT images. Multimodality phantom was very useful to evaluate the accuracy of target positions among the different types of image modality such as CT, MR and SPECT.

  7. Timescale Halo: Average-Speed Targets Elicit More Positive and Less Negative Attributions than Slow or Fast Targets

    Science.gov (United States)

    Hernandez, Ivan; Preston, Jesse Lee; Hepler, Justin

    2014-01-01

    Research on the timescale bias has found that observers perceive more capacity for mind in targets moving at an average speed, relative to slow or fast moving targets. The present research revisited the timescale bias as a type of halo effect, where normal-speed people elicit positive evaluations and abnormal-speed (slow and fast) people elicit negative evaluations. In two studies, participants viewed videos of people walking at a slow, average, or fast speed. We find evidence for a timescale halo effect: people walking at an average-speed were attributed more positive mental traits, but fewer negative mental traits, relative to slow or fast moving people. These effects held across both cognitive and emotional dimensions of mind and were mediated by overall positive/negative ratings of the person. These results suggest that, rather than eliciting greater perceptions of general mind, the timescale bias may reflect a generalized positivity toward average speed people relative to slow or fast moving people. PMID:24421882

  8. A comparison of positive vicarious learning and verbal information for reducing vicariously learned fear

    OpenAIRE

    Reynolds, Gemma; Wasely, David; Dunne, Guler; Askew, Chris

    2017-01-01

    Research with children has demonstrated that both positive vicarious learning (modelling) and positive verbal information can reduce children’s acquired fear responses for a particular stimulus. However, this fear reduction appears to be more effective when the intervention pathway matches the initial fear learning pathway. That is, positive verbal information is a more effective intervention than positive modelling when fear is originally acquired via negative verbal information. Research ha...

  9. Turning lemonade into lemons: Dampening appraisals reduce positive affect and increase negative affect during positive activity scheduling.

    Science.gov (United States)

    Burr, Leigh-Anne; Javiad, Mahmood; Jell, Grace; Werner-Seidler, Aliza; Dunn, Barnaby D

    2017-04-01

    The way individuals appraise positive emotions may modulate affective experience during positive activity scheduling. Individuals may either engage in dampening appraisals (e.g., think "this is too good to last") or amplifying appraisals (e.g., think "I deserve this"). A cross-over randomized design was used to examine the consequences of these appraisal styles. Participants (N = 43) rated positive affect (PA) and negative affect (NA) during four daily walks in pleasant locations, whilst following dampening, emotion-focus amplifying (focusing on how good one feels), self-focus amplifying (focusing on positive self qualities), or control instructions. There was no difference between the two amplifying and control conditions, which all increased PA and reduced NA during the walks. However, the dampening condition significantly differed from all other conditions, reducing PA and increasing NA during the walk. Individual differences in anhedonia symptoms did not significantly moderate the pattern of findings. This evidence supports the view that dampening appraisals may be one mechanism driving anhedonia and may account for why positive activity scheduling can sometimes backfire when utilized in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Accuracy of position measurement method using Arago spot for inertial fusion energy target tracking system

    International Nuclear Information System (INIS)

    Saruta, Koichi; Tsuji, Ryusuke

    2007-01-01

    The accuracy of a position measurement method using the Arago spot is reported for an inertial fusion energy (IFE) target tracking system, where the position of the target is determined by the position of the Arago spot, which is a bright spot appearing in the central portion of the diffraction pattern of a spherical obstacle. We use a He-Ne laser as the light source and a charge-coupled device (CCD) camera with a microscope objective lens to magnify and record the diffraction pattern of a spherical target. We examine two different algorithms to determine the center of the Arago spot in order to compare the measurement performances. The experimental results show that the position of a 5-mm-diameter target can be obtained with a measurement resolution of 1 μm and an rms measurement error of less than 0.2μm for both algorithms when the distance between the target and the microscope objective lens is 5 cm. (author)

  11. Effects of Target Positioning Error on Motion Compensation for Airborne Interferometric SAR

    Directory of Open Access Journals (Sweden)

    Li Yin-wei

    2013-12-01

    Full Text Available The measurement inaccuracies of Inertial Measurement Unit/Global Positioning System (IMU/GPS as well as the positioning error of the target may contribute to the residual uncompensated motion errors in the MOtion COmpensation (MOCO approach based on the measurement of IMU/GPS. Aiming at the effects of target positioning error on MOCO for airborne interferometric SAR, the paper firstly deduces a mathematical model of residual motion error bring out by target positioning error under the condition of squint. And the paper analyzes the effects on the residual motion error caused by system sampling delay error, the Doppler center frequency error and reference DEM error which result in target positioning error based on the model. Then, the paper discusses the effects of the reference DEM error on the interferometric SAR image quality, the interferometric phase and the coherent coefficient. The research provides theoretical bases for the MOCO precision in signal processing of airborne high precision SAR and airborne repeat-pass interferometric SAR.

  12. Methodological Approach to Company Cash Flows Target-Oriented Forecasting Based on Financial Position Analysis

    OpenAIRE

    Sergey Krylov

    2012-01-01

    The article treats a new methodological approach to the company cash flows target-oriented forecasting based on its financial position analysis. The approach is featured to be universal and presumes application of the following techniques developed by the author: financial ratio values correction techniques and correcting cash flows techniques. The financial ratio values correction technique assumes to analyze and forecast company financial position while the correcting cash flows technique i...

  13. Towards a European Position on Armed Drones and Targeted Killing: Surveying EU Counter-Terrorism Perspectives

    Directory of Open Access Journals (Sweden)

    Jessica Dorsey

    2015-04-01

    Full Text Available In this Research Paper, Jessica Dorsey and Dr. Christophe Paulussen gauge the extent to which European Union Member States share the position of the United States on armed drones and targeted killings. In doing so, it aims to assist in distilling a common EU position on the use of armed drones and a legal framework for counter-terrorism-related uses of force.

  14. Moving-Target Position Estimation Using GPU-Based Particle Filter for IoT Sensing Applications

    Directory of Open Access Journals (Sweden)

    Seongseop Kim

    2017-11-01

    Full Text Available A particle filter (PF has been introduced for effective position estimation of moving targets for non-Gaussian and nonlinear systems. The time difference of arrival (TDOA method using acoustic sensor array has normally been used to for estimation by concealing the location of a moving target, especially underwater. In this paper, we propose a GPU -based acceleration of target position estimation using a PF and propose an efficient system and software architecture. The proposed graphic processing unit (GPU-based algorithm has more advantages in applying PF signal processing to a target system, which consists of large-scale Internet of Things (IoT-driven sensors because of the parallelization which is scalable. For the TDOA measurement from the acoustic sensor array, we use the generalized cross correlation phase transform (GCC-PHAT method to obtain the correlation coefficient of the signal using Fast Fourier Transform (FFT, and we try to accelerate the calculations of GCC-PHAT based TDOA measurements using FFT with GPU compute unified device architecture (CUDA. The proposed approach utilizes a parallelization method in the target position estimation algorithm using GPU-based PF processing. In addition, it could efficiently estimate sudden movement change of the target using GPU-based parallel computing which also can be used for multiple target tracking. It also provides scalability in extending the detection algorithm according to the increase of the number of sensors. Therefore, the proposed architecture can be applied in IoT sensing applications with a large number of sensors. The target estimation algorithm was verified using MATLAB and implemented using GPU CUDA. We implemented the proposed signal processing acceleration system using target GPU to analyze in terms of execution time. The execution time of the algorithm is reduced by 55% from to the CPU standalone operation in target embedded board, NVIDIA Jetson TX1. Also, to apply large

  15. Reduced local immune response with continuous positive airway pressure during one-lung ventilation for oesophagectomy

    NARCIS (Netherlands)

    Verhage, R. J. J.; Boone, J.; Rijkers, G. T.; Cromheecke, G. J.; Kroese, A. C.; Weijs, T. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2014-01-01

    Background. Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This

  16. Development of a Simple Radioactive marker System to Reduce Positioning Errors in Radiation Treatment

    International Nuclear Information System (INIS)

    William H. Miller; Dr. Jatinder Palta

    2007-01-01

    The objective of this research is to implement an inexpensive, quick and simple monitor that provides an accurate indication of proper patient position during the treatment of cancer by external beam X-ray radiation and also checks for any significant changes in patient anatomy. It is believed that this system will significantly reduce the treatment margin, provide an additional, independent quality assurance check of positioning accuracy prior to all treatments and reduce the probability of misadministration of therapeutic dose

  17. Targeting Chromosomal Instability and Tumour Heterogeneity in HER2-Positive Breast Cancer

    DEFF Research Database (Denmark)

    Burrell, Rebecca A.; Birkbak, Nicolai Juul; Johnston, Stephen R.

    2010-01-01

    Chromosomal instability (CIN) is a common cause of tumour heterogeneity and poor prognosis in solid tumours and describes cell-cell variation in chromosome structure or number across a tumour population. In this article we consider evidence suggesting that CIN may be targeted and may influence...... response to distinct chemotherapy regimens, using HER2-positive breast cancer as an example. Pre-clinical models have indicated a role for HER2 signalling in initiating CIN and defective cell-cycle control, and evidence suggests that HER2-targeting may attenuate this process. Anthracyclines and platinum...... agents may target tumours with distinct patterns of karyotypic complexity, whereas taxanes may have preferential activity in tumours with relative chromosomal stability. A greater understanding of karyotypic complexity and identification of methods to directly examine and target CIN may support novel...

  18. Multi-target detection and positioning in crowds using multiple camera surveillance

    Science.gov (United States)

    Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

    2018-04-01

    In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

  19. A comparison of positive vicarious learning and verbal information for reducing vicariously learned fear.

    Science.gov (United States)

    Reynolds, Gemma; Wasely, David; Dunne, Güler; Askew, Chris

    2017-10-19

    Research with children has demonstrated that both positive vicarious learning (modelling) and positive verbal information can reduce children's acquired fear responses for a particular stimulus. However, this fear reduction appears to be more effective when the intervention pathway matches the initial fear learning pathway. That is, positive verbal information is a more effective intervention than positive modelling when fear is originally acquired via negative verbal information. Research has yet to explore whether fear reduction pathways are also important for fears acquired via vicarious learning. To test this, an experiment compared the effectiveness of positive verbal information and positive vicarious learning interventions for reducing vicariously acquired fears in children (7-9 years). Both vicarious and informational fear reduction interventions were found to be equally effective at reducing vicariously acquired fears, suggesting that acquisition and intervention pathways do not need to match for successful fear reduction. This has significant implications for parents and those working with children because it suggests that providing children with positive information or positive vicarious learning immediately after a negative modelling event may prevent more serious fears developing.

  20. Comparative Survey of Holding Positions for Reducing Vaccination Pain in Young Infants

    Directory of Open Access Journals (Sweden)

    Hui-Chu Yin

    2017-01-01

    Full Text Available Background. Infant holding position may reduce vaccination pain. However, the optimal position for young infants remains controversial. Objectives. To compare the effectiveness of holding infants in the supine position and the effectiveness of holding infants in upright position for relieving acute pain from vaccine injection. Methods. This prospective cohort study enrolled 6–12-week-old healthy infants. We examined infant pain responses by evaluating the following three categories: (1 crying, (2 irritability, and (3 facial expression. Results. In total, 282 infants were enrolled, with 103 and 179 held in the supine and upright positions, respectively. At 30 s after vaccination, the infants in the supine position showed a larger decrease in crying (p<0.001, irritability (p=0.002, and pained facial expression (p=0.001 than did those in the upright position. However, there was no significant difference in pain response between two groups at 180 s after intervention. Conclusion. In 2-month-old infants, the supine position may reduce acute pain more effectively than does the upright position. Our findings provide a clinical strategy for relieving vaccination pain in young infants.

  1. A systematic review of dual targeting in HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Tuxen, Malgorzata K; Nielsen, Dorte Lisbet

    2014-01-01

    BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15-20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both...... the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present...... of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. CONCLUSION: Dual blockade is likely to represent a substantial advance for patients...

  2. Analisis Segmentasi, Targeting Dan Positioning Pembiayaan Mobil Pada PT. Adira Dinamika Multifinance Tbk Cabang Manado

    OpenAIRE

    Soegoto, Agus Supandi; Mananeke, Lisbeth; Kembuan, Precylia Cyndi

    2014-01-01

    Persaingan yang semakin ketat saat ini, menuntut adanya keunggulan bersaing yang harus dimiliki oleh setiap Perusahaan, dan membutuhkan strategi pemasaran yang tepat. Jumlah pesaing yang semakin banyak membuat konsumen memiliki alternatif pilihan yang banyak untuk mendapatkan produk yang sesuai dengan harapannya. Untuk memenangkan persaingan tidak hanya sebatas menyusun bauran pemasaran sebagai taktik namun lebih dari itu juga untuk menyusun strategi segmenting, targeting marketing, dan posit...

  3. Analisis Strategi Segmenting, Targeting Dan Positioning Pada Perushaan Asuransi Pt.(persero) Jiwasraya, Pekanbaru

    OpenAIRE

    Sihotang, Jon Predianto; Karneli, Okta

    2017-01-01

    This research aims to identify and analyze the strategy of segmenting, targeting and positioning on the insurance company PT.(Persero) Asuransi Jiwasraya, Pekanbaru. In last 5 (five) years, the company experienced with unstable marketing. And the author believes that the trouble sits inside the marketing strategies that are not running well. The data had gained directly from the key informans by interviewing process in having accurate informations.The method of this research was used descript...

  4. Segmentation, Targeting, dan Positioning Studio Tato di Surabaya dalam Perkembangan Gaya Hidup

    OpenAIRE

    Anang Tri Wahyudi

    2013-01-01

    This study attempts to examine in depth the influence of lifestyle on the orientation of recipients (tattoo users) to the art of tattooing, which is independent of the value of a valuable commodity, and explore the extent to which the process of tattoo studios’ segmentation, targeting, and positioning in managing a tattoo studio. This study uses qualitative research methods with interpretive phenomenological foundation of thinking, which is oriented to truth that is subjective to informants, ...

  5. Prone versus supine positioning for whole and partial-breast radiotherapy: A comparison of non-target tissue dosimetry

    International Nuclear Information System (INIS)

    Kirby, Anna M.; Evans, Philip M.; Donovan, Ellen M.; Convery, Helen M.; Haviland, Joanna S.; Yarnold, John R.

    2010-01-01

    Purpose: To compare non-target tissue (including left-anterior-descending coronary-artery (LAD)) dosimetry of prone versus supine whole (WBI) and partial-breast irradiation (PBI). Methods and materials: Sixty-five post-lumpectomy breast cancer patients underwent CT-imaging supine and prone. On each dataset, the whole-breast clinical-target-volume (WB-CTV), partial-breast CTV (tumour-bed + 15 mm), ipsilateral-lung and chest-wall were outlined. Heart and LAD were outlined in left-sided cases (n = 30). Tangential-field WBI and PBI plans were generated for each position. Mean LAD, heart, and ipsilateral-lung doses (x mean ), maximum LAD (LAD max ) doses, and the volume of chest-wall receiving 50 Gy (V 50Gy ) were compared. Results: Two-hundred and sixty plans were generated. Prone positioning reduced heart and LAD doses in 19/30 WBI cases (median reduction in LAD mean = 6.2 Gy) and 7/30 PBI cases (median reduction in LAD max = 29.3 Gy) (no difference in 4/30 cases). However, prone positioning increased cardiac doses in 8/30 WBI (median increase in LAD mean = 9.5 Gy) and 19/30 PBI cases (median increase in LAD max = 22.9 Gy) (no difference in 3/30 cases). WB-CTV > 1000cm 3 was associated with improved cardiac dosimetry in the prone position for WBI (p = 0.04) and PBI (p = 0.04). Prone positioning reduced ipsilateral-lung mean in 65/65 WBI and 61/65 PBI cases, and chest-wall V 50Gy in all WBI cases. PBI reduced normal-tissue doses compared to WBI in all cases, regardless of the treatment position. Conclusions: In the context of tangential-field WBI and PBI, prone positioning is likely to benefit left-breast-affected women of larger breast volume, but to be detrimental in left-breast-affected women of smaller breast volume. Right-breast-affected women are likely to benefit from prone positioning regardless of breast volume.

  6. Shaft Position Influence on Technical Characteristics of Universal Two-Stages Helical Speed Reducers

    OpenAIRE

    Мilan Rackov; Zeljko Kanovic; Sinisa Kuzmanovic; Ruzica Trbojevic

    2005-01-01

    Purchasers of speed reducers decide on buying those reducers, that can the most approximately satisfy their demands with much smaller costs. Amount of used material, ie. mass and dimensions of gear unit influences on gear units price. Mass and dimensions of gear unit, besides output torque, gear unit ratio and efficiency, are the most important parameters of technical characteristics of gear units and their quality. Centre distance and position of shafts have significant influence on output t...

  7. Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine.

    Directory of Open Access Journals (Sweden)

    Sujatha P Koduvayur

    Full Text Available Cytotoxic drugs, such as nucleoside analogs and toxins, commonly suffer from off-target effects. One approach to mitigate this problem is to deliver the cytotoxic drug selectively to the intended site. While for toxins this can be achieved by conjugating the cell-killing moiety to a targeting moiety, it is not an option for nucleoside analogs, which rely on intracellular enzymes to convert them to their active triphosphorylated form. To overcome this limitation, and achieve site-targeted activation of nucleoside analogs, we fused the coding region of a prodrug-activating enzyme, deoxycytidine kinase (dCK, to affinity reagents that bind to the Her2 cell surface protein. We evaluated dCK fusions to an anti-Her2 affibody and Designed Ankyrin Repeat Protein (DARPin for their ability to kill cancer cells by promoting the activation of the nucleoside analog fludarabine. Cell staining and flow cytometry experiments with three Her2 positive cancer cell lines (BT-474-JB, JIMT-1 and SK-OV-3 indicate dCK fusions binding and cellular internalization. In contrast, these reagents bind only weakly to the Her2 negative cell line, MCF-7. Cell proliferation assays indicate that SK-OV-3 and BT-474-JB cell lines exhibit significantly reduced proliferation rates when treated with targeting-module fused dCK and fludarabine, compared to fludarabine alone. These findings demonstrate that we have succeeded in delivering active dCK into the Her2-positive cells, thereby increasing the activation of fludarabine, which ultimately reduces the dose of nucleoside analog needed for cell killing. This strategy may help establish the therapeutic index required to differentiate between healthy tissues and cancer cells.

  8. Radiation binary targeted therapy for HER-2 positive breast cancers: assumptions, theoretical assessment and future directions

    Energy Technology Data Exchange (ETDEWEB)

    Mundy, Daniel W [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States); Harb, Wael [Horizon Oncology, The Care Group, Unity Medical Center, Lafayette, IN 47901 (United States); Jevremovic, Tatjana [School of Nuclear Engineering, Purdue University, 400 Central Drive, West Lafayette, IN 47909 (United States)

    2006-03-21

    A novel radiation targeted therapy is investigated for HER-2 positive breast cancers. The proposed concept combines two known approaches, but never used together for the treatment of advanced, relapsed or metastasized HER-2 positive breast cancers. The proposed radiation binary targeted concept is based on the anti HER-2 monoclonal antibodies (MABs) that would be used as vehicles to transport the nontoxic agent to cancer cells. The anti HER-2 MABs have been successful in targeting HER-2 positive breast cancers with high affinity. The proposed concept would utilize a neutral nontoxic boron-10 predicting that anti HER-2 MABs would assure its selective delivery to cancer cells. MABs against HER-2 have been a widely researched strategy in the clinical setting. The most promising antibody is Trastuzumab (Herceptin (registered) ). Targeting HER-2 with the MAB Trastuzumab has been proven to be a successful strategy in inducing tumour regression and improving patient survival. Unfortunately, these tumours become resistant and afflicted women succumb to breast cancer. In the proposed concept, when the tumour region is loaded with boron-10 it is irradiated with neutrons (treatment used for head and neck cancers, melanoma and glioblastoma for over 40 years in Japan and Europe). The irradiation process takes less than an hour producing minimal side effects. This paper summarizes our recent theoretical assessments of radiation binary targeted therapy for HER-2 positive breast cancers on: the effective drug delivery mechanism, the numerical model to evaluate the targeted radiation delivery and the survey study to find the neutron facility in the world that might be capable of producing the radiation effect as needed. A novel method of drug delivery utilizing Trastuzumab is described, followed by the description of a computational Monte Carlo based breast model used to determine radiation dose distributions. The total flux and neutron energy spectra of five currently available

  9. Does the Brain Extrapolate the Position of a Transient Moving Target?

    Science.gov (United States)

    Quinet, Julie; Goffart, Laurent

    2015-08-26

    When an object moves in the visual field, its motion evokes a streak of activity on the retina and the incoming retinal signals lead to robust oculomotor commands because corrections are observed if the trajectory of the interceptive saccade is perturbed by a microstimulation in the superior colliculus. The present study complements a previous perturbation study by investigating, in the head-restrained monkey, the generation of saccades toward a transient moving target (100-200 ms). We tested whether the saccades land on the average of antecedent target positions or beyond the location where the target disappeared. Using target motions with different speed profiles, we also examined the sensitivity of the process that converts time-varying retinal signals into saccadic oculomotor commands. The results show that, for identical overall target displacements on the visual display, saccades toward a faster target land beyond the endpoint of saccades toward a target moving slower. The rate of change in speed matters in the visuomotor transformation. Indeed, in response to identical overall target displacements and durations, the saccades have smaller amplitude when they are made in response to an accelerating target than to a decelerating one. Moreover, the motion-related signals have different weights depending upon their timing relative to the target onset: early signals are more influential in the specification of saccade amplitude than later signals. We discuss the "predictive" properties of the visuo-saccadic system and the nature of this location where the saccades land, after providing some critical comments to the "hic-et-nunc" hypothesis (Fleuriet and Goffart, 2012). Complementing the work of Fleuriet and Goffart (2012), this study is a contribution to the more general scientific research aimed at understanding how ongoing action is dynamically and adaptively adjusted to the current spatiotemporal aspects of its goal. Using the saccadic eye movement as a probe

  10. Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    McGinniss, M.J.; Kazazian, H.H. Jr.; Bi, L.; Antonarakis, S.E. (John Hopkins Univ., Baltimore, MD (United States)); Hoyer, L.W. (American Red Cross Blood Services, Rockville, MD (United States)); Inaba, H. (Tokyo Medical College (Japan))

    1993-02-01

    Hemophilia A is due to the functional deficiency of factor VIII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients ([approximately]5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly ([approximately]45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM-reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five weree missense (Ser289Leu, Ser558Phe, Val634Ala, Val634Met, Asn1441Lys), and the sixth was a 3-bp deletion ([Delta]Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutation for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residue altered by mutation in these patients wer conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII. The results indicate a nonrandom distribution of mutations and suggest that mutations in a limited number of FVIII regions may cause CRM-positive and CRM-reduced heomphilia A. 48 refs., 1 fig., 1 tab.

  11. Toward Value Co-Creation: Increasing Women’s Presence in Management Positions through Competition against a Set Target

    Directory of Open Access Journals (Sweden)

    Irene Comeig

    2017-10-01

    Full Text Available Despite empirical evidence that women’s presence in management positions is a source of value co-creation for firms, these positions are still male-dominated. Some evidence from experimental economics suggests that one reason for this imbalance is that women shy away from competition. However, most of these studies have focused on competition systems that pit individuals against each other. We present an economic laboratory experiment that compares competition against others with competition against a set target. The crucial difference is that whereas the former involves competing against opponents, the latter does not. Our results show that significantly more women are willing to compete against a set target than against others. Furthermore, there is no reduction in men’s participation and no general efficiency reduction. Our findings suggest that firms that aim at value co-creation and sustainability through a gender-neutral promotion mechanism should introduce competition against a set target and reduce competition against others. This paper contributes to dispelling stereotypes about women’s reluctance to compete.

  12. Subliminal presentation of emotionally negative vs positive primes increases the perceived beauty of target stimuli.

    Science.gov (United States)

    Era, Vanessa; Candidi, Matteo; Aglioti, Salvatore Maria

    2015-11-01

    Emotions have a profound influence on aesthetic experiences. Studies using affective priming procedures demonstrate, for example, that inducing a conscious negative emotional state biases the perception of abstract stimuli towards the sublime (Eskine et al. Emotion 12:1071-1074, 2012. doi: 10.1037/a0027200). Moreover, subliminal happy facial expressions have a positive impact on the aesthetic evaluation of abstract art (Flexas et al. PLoS ONE 8:e80154, 2013). Little is known about how emotion influences aesthetic perception of non-abstract, representational stimuli, especially those that are particularly relevant for social behaviour, like human bodies. Here, we explore whether the subliminal presentation of emotionally charged visual primes modulates the explicit subjective aesthetic judgment of body images. Using a forward/backward masking procedure, we presented subliminally positive and negative, arousal-matched, emotional or neutral primes and measured their effect on the explicit evaluation of perceived beauty (high vs low) and emotion (positive vs negative) evoked by abstract and body images. We found that negative primes increased subjective aesthetic evaluations of target bodies or abstract images in comparison with positive primes. No influence of primes on the emotional dimension of the targets was found, thus ruling out an unspecific arousal effect and strengthening the link between emotional valence and aesthetic appreciation. More specifically, that subliminal negative primes increase beauty ratings compared to subliminal positive primes indicates a clear link between negative emotions and positive aesthetic evaluations and vice versa, suggesting a possible link between negative emotion and the experience of sublime in art. The study expands previous research by showing the effect of subliminal negative emotions on the subjective aesthetic evaluation not only of abstract but also of body images.

  13. Reducing Bedtime Disturbance and Night Waking Using Positive Bedtime Routines and Sleep Restriction

    Science.gov (United States)

    Christodulu, Kristin V.; Durand, V. Mark

    2004-01-01

    The purpose of this study was to investigate behavioral interventions designed to reduce sleep difficulties in four young children with developmental disorders. Positive bedtime routines and sleep restriction were successful in eliminating bedtime disturbances and nighttime awakenings in four children with significant sleep problems. Positive…

  14. Can Raters with Reduced Job Descriptive Information Provide Accurate Position Analysis Questionnaire (PAQ) Ratings?

    Science.gov (United States)

    Friedman, Lee; Harvey, Robert J.

    1986-01-01

    Job-naive raters provided with job descriptive information made Position Analysis Questionnaire (PAQ) ratings which were validated against ratings of job analysts who were also job content experts. None of the reduced job descriptive information conditions enabled job-naive raters to obtain either acceptable levels of convergent validity with…

  15. Algorithm of reducing the false positives in IDS based on correlation Analysis

    Science.gov (United States)

    Liu, Jianyi; Li, Sida; Zhang, Ru

    2018-03-01

    This paper proposes an algorithm of reducing the false positives in IDS based on correlation Analysis. Firstly, the algorithm analyzes the distinguishing characteristics of false positives and real alarms, and preliminary screen the false positives; then use the method of attribute similarity clustering to the alarms and further reduces the amount of alarms; finally, according to the characteristics of multi-step attack, associated it by the causal relationship. The paper also proposed a reverse causation algorithm based on the attack association method proposed by the predecessors, turning alarm information into a complete attack path. Experiments show that the algorithm simplifies the number of alarms, improve the efficiency of alarm processing, and contribute to attack purposes identification and alarm accuracy improvement.

  16. Segmentation, Targeting, dan Positioning Studio Tato di Surabaya dalam Perkembangan Gaya Hidup

    Directory of Open Access Journals (Sweden)

    Anang Tri Wahyudi

    2013-01-01

    Full Text Available This study attempts to examine in depth the influence of lifestyle on the orientation of recipients (tattoo users to the art of tattooing, which is independent of the value of a valuable commodity, and explore the extent to which the process of tattoo studios’ segmentation, targeting, and positioning in managing a tattoo studio. This study uses qualitative research methods with interpretive phenomenological foundation of thinking, which is oriented to truth that is subjective to informants, which consists of a tattoo studio tattooist and managers who have more than five years of experience, and the recipient women and men under the age of 30. The development of post-modern lifestyle is synonymous with consumer culture, which affects the orientation of recipients towards tattoos as works of art, a medium of expression, search for identity, and part of fashion accessories, therefore tattoos become works of art that have commodity value. The existing tattoo studios already have market segments, target markets, positioning, and clear marketing strategy, however there are some tattoo studios that do not determine their market segments and target goals. They tend to flow and follow the situation and market conditions. Several factors that affect the condition and management of tattoo studios today are environmental factors, resource constraints, and tattoos as art products that are homogeneous.

  17. Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods.

    Science.gov (United States)

    Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choe, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B; Gupta, Neha; Kohane, Isaac S; Green, Robert C; Kong, Sek Won

    2014-08-01

    As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false-positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here, we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false-negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous single nucleotide variants (SNVs); 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery in NA12878, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and an ensemble genotyping would be essential to minimize false-positive DNM candidates. © 2014 WILEY PERIODICALS, INC.

  18. Reducing emissions from agriculture to meet the 2 °C target

    DEFF Research Database (Denmark)

    Wollenberg, Eva; Richards, Meryl; Smith, Pete

    2016-01-01

    identify a preliminary global target for reducing emissions from agriculture of ~1 GtCO2e yr−1 by 2030 to limit warming in 2100 to 2 °C above pre-industrial levels. Yet plausible agricultural development pathways with mitigation cobenefits deliver only 21–40% of needed mitigation. The target indicates...... that more transformative technical and policy options will be needed, such as methane inhibitors and finance for new practices. A more comprehensive target for the 2 °C limit should be developed to include soil carbon and agriculture-related mitigation options. Excluding agricultural emissions from......More than 100 countries pledged to reduce agricultural greenhouse gas (GHG) emissions in the 2015 Paris Agreement of the United Nations Framework Convention on Climate Change. Yet technical information about how much mitigation is needed in the sector vs. how much is feasible remains poor. We...

  19. Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine

    International Nuclear Information System (INIS)

    Recondo, Gonzalo Jr; Vega, Maximo de la; Galanternik, Fernando; Díaz-Cantón, Enrique; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer

  20. Importance of Lorentz structure in the parton model: Target mass corrections, transverse momentum dependence, positivity bounds

    International Nuclear Information System (INIS)

    D'Alesio, U.; Leader, E.; Murgia, F.

    2010-01-01

    We show that respecting the underlying Lorentz structure in the parton model has very strong consequences. Failure to insist on the correct Lorentz covariance is responsible for the existence of contradictory results in the literature for the polarized structure function g 2 (x), whereas with the correct imposition we are able to derive the Wandzura-Wilczek relation for g 2 (x) and the target-mass corrections for polarized deep inelastic scattering without recourse to the operator product expansion. We comment briefly on the problem of threshold behavior in the presence of target-mass corrections. Careful attention to the Lorentz structure has also profound implications for the structure of the transverse momentum dependent parton densities often used in parton model treatments of hadron production, allowing the k T dependence to be derived explicitly. It also leads to stronger positivity and Soffer-type bounds than usually utilized for the collinear densities.

  1. Targets and timelines for reducing salt in processed food in the Americas.

    Science.gov (United States)

    Campbell, Norm; Legowski, Barbara; Legetic, Branka; Ferrante, Daniel; Nilson, Eduardo; Campbell, Christine; L'Abbé, Mary

    2014-09-01

    Reducing dietary salt is one of the most effective interventions to lessen the burden of premature death and disability. In high-income countries and those in nutrition transition, processed foods are a significant if not the main source of dietary salt. Reformulating these products to reduce their salt content is recommended as a best buy to prevent chronic diseases across populations. In the Americas, there are targets and timelines for reduced salt content of processed foods in 8 countries--Argentina, Brazil, Canada, Chile, Ecuador, Mexico, and the National Salt Reduction Initiative in the United States and Paraguay. While there are common elements across the countries, there are notable differences in their approaches: 4 countries have exclusively voluntary targets, 2 countries have combined voluntary and regulated components, and 1 country has only regulations. The countries have set different types of targets and in some cases combined them: averages, sales-weighted averages, upper limits, and percentage reductions. The foods to which the targets apply vary from single categories to comprehensive categories accounting for all processed products. The most accessible and transparent targets are upper limits per food category. Most likely to have a substantive and sustained impact on salt intake across whole populations is the combination of sales-weighted averages and upper limits. To assist all countries with policies to improve the overall nutritional value of processed foods, the authors call for food companies to supply food composition data and product sales volume data to transparent and open-access platforms and for global companies to supply the products that meet the strictest targets to all markets. Countries participating in common markets at the subregional level can consider harmonizing targets, nutrition labels, and warning labels. ©2014 Wiley Periodicals, Inc.

  2. Isochoric heating of reduced mass targets by ultra-intense laser produced relativistic electrons

    Energy Technology Data Exchange (ETDEWEB)

    Neumayer, P; Lee, H J; Offerman, D; Shipton, E; Kemp, A; Kritcher, A L; Doppner, T; Back, C A; Glenzer, S H

    2009-02-04

    We present measurements of the chlorine K-alpha emission from reduced mass targets, irradiated with ultra-high intensity laser pulses. Chlorinated plastic targets with diameters down to 50 micrometers and mass of a few 10{sup -8} g were irradiated with up to 7 J of laser energy focused to intensities of several 10{sup 19} W/cm{sup 2}. The conversion of laser energy to K-alpha radiation is measured, as well as high resolution spectra that allow observation of line shifts, indicating isochoric heating of the target up to 18 eV. A zero-dimensional 2-temperature equilibration model, combined with electron impact K-shell ionization and post processed spectra from collisional radiative calculations reproduces the observed K-alpha yields and line shifts, and shows the importance of target expansion due to the hot electron pressure.

  3. Evaluation of Target Position's Accuracy in 2D-3D Matching using Rando Phantom

    International Nuclear Information System (INIS)

    Jang, Eun Sung; Kang, Soo Man; Lee, Chul Soo

    2009-01-01

    The aim of this study is to compare patient's body posture and its position at the time of simulation with one at the treatment room using On-board Imaging (OBI) and CT (CBCT). The detected offsets are compared with position errors of Rando Phantom that are practically applied. After that, Rando Phantom's position is selected by moving couch based on detected deviations. In addition, the errors between real measured values of Rando Phantom position and theoretical ones is compared. And we will evaluate target position's accuracy of KV X-ray imaging's 2D and CBCT's 3D one. Using the Rando Phantom (Alderson Research Laboratories Inc. Stanford. CT, USA) which simulated human body's internal structure, we will set up Rando Phantom on the treatment couch after implementing simulation and RTP according to the same ways as the real radioactive treatment. We tested Rando Phantom that are assumed to have accurate position with different 3 methods. We measured setup errors on the axis of X, Y and Z, and got mean standard deviation errors by repeating tests 10 times on each tests. The difference between mean detection error and standard deviation are as follows; lateral 0.4±0.3 mm, longitudinal 0.6±0.5 mm, vertical 0.4±0.2 mm which all within 0-10 mm. The couch shift variable after positioning that are comparable to residual errors are 0.3±0.1, 0.5±0.1, and 0.3±0.1 mm. The mean detection errors by longitudinal shift between 20-40 mm are 0.4±0.3 in lateral, 0.6±0.5 in longitudinal, 0.5±0.3 in vertical direction. The detection errors are all within range of 0.3-0.5 mm. Residual errors are within 0.2-0.5 mm. Each values are mean values based on 3 tests. Phantom is based on treatment couch shift and error within the average 5 mm can be gained by the diminution detected by image registration based on OBI and CBCT. Therefore, the selection of target position which depends on OBI and CBCT could be considered as useful.

  4. IMPACT OF REDUCING THE 100 C LIQUIDUS TEMPERATURE OFFSET ON WASTE LOADING TARGETS

    Energy Technology Data Exchange (ETDEWEB)

    Peeler, D.; Edwards, T.

    2010-11-11

    The objective of this report is to assess the potential impact of reducing conservatism in the implementation of the current liquidus temperature (TL) model in the Product Composition Control System (PCCS) on the ability to target higher waste loadings (WLs) for future sludge batches. No changes to the TL model or the associated uncertainties (model or measurement) are proposed, rather only changes in the magnitude of the offset used between the nominal melt pool temperature (1150 C) and the Property Acceptance Region (PAR) value (1050 C). This strategy is consistent with that outlined and initially assessed by Brown et al. (2001). In that report, the authors stated even a fairly conservative change in this safety factor could have a significant impact on waste loading. The results of this study clearly indicate that the implementation of an 1100 C TL PAR criterion (which translates into a reduction in the TL offset from 100 C to 50 C) can have significantly positive impacts on the ability to gain access to WLs exceeding 45%. This is especially true for those frit and sludge systems that are TL limited using the current 1050 C TL criterion, and are not limited by a second constraint (such as viscosity, nepheline, or durability) until much higher WLs. Examples of various glass forming systems are provided that are currently limited to maximum WLs in the mid-40s, but could be processed in the lower 50s through implementation of this new strategy. One example is in the Sludge Batch 10 (SB10) system, where for a specific glass forming system the projected operating window of 38-41% WL (using the current constraints) became 38-52% WL with the use of an 1100 C TL PAR value. This change both provided access to significantly higher WLs, and transitioned a once infeasible flowsheet to a system that could potentially be processed in the Defense Waste Processing Facility (DWPF). This potential change in the TL constraint also provides access to frit compositions (or glass

  5. Fuzzy adaptive Kalman filter for indoor mobile target positioning with INS/WSN integrated method

    Institute of Scientific and Technical Information of China (English)

    杨海; 李威; 罗成名

    2015-01-01

    Pure inertial navigation system (INS) has divergent localization errors after a long time. In order to compensate the disadvantage, wireless sensor network (WSN) associated with the INS was applied to estimate the mobile target positioning. Taking traditional Kalman filter (KF) as the framework, the system equation of KF was established by the INS and the observation equation of position errors was built by the WSN. Meanwhile, the observation equation of velocity errors was established by the velocity difference between the INS and WSN, then the covariance matrix of Kalman filter measurement noise was adjusted with fuzzy inference system (FIS), and the fuzzy adaptive Kalman filter (FAKF) based on the INS/WSN was proposed. The simulation results show that the FAKF method has better accuracy and robustness than KF and EKF methods and shows good adaptive capacity with time-varying system noise. Finally, experimental results further prove that FAKF has the fast convergence error, in comparison with KF and EKF methods.

  6. Stereographic Targeting in Prostate Radiotherapy: Speed and Precision by Daily Automatic Positioning Corrections Using Kilovoltage/Megavoltage Image Pairs

    International Nuclear Information System (INIS)

    Mutanga, Theodore F.; Boer, Hans C.J. de; Wielen, Gerard J. van der; Wentzler, Davy; Barnhoorn, Jaco; Incrocci, Luca; Heijmen, Ben J.M.

    2008-01-01

    Purpose: A fully automated, fast, on-line prostate repositioning scheme using implanted markers, kilovoltage/megavoltage imaging, and remote couch movements has been developed and clinically applied. The initial clinical results of this stereographic targeting (SGT) method, as well as phantom evaluations, are presented. Methods and Materials: Using the SGT method, portal megavoltage images are acquired with the first two to six monitor units of a treatment beam, immediately followed by acquisition of an orthogonal kilovoltage image without gantry motion. The image pair is automatically analyzed to obtain the marker positions and three-dimensional prostate displacement and rotation. Remote control couch shifts are applied to correct for the displacement. The SGT performance was measured using both phantom images and images from 10 prostate cancer patients treated using SGT. Results: With phantom measurements, the accuracy of SGT was 0.5, 0.2, and 0.3 mm (standard deviation [SD]) for the left-right, craniocaudal, and anteroposterior directions, respectively, for translations and 0.5 o (SD) for the rotations around all axes. Clinically, the success rate for automatic marker detection was 99.5%, and the accuracy was 0.3, 0.5 and 0.8 mm (SD) in the left-right, craniocaudal, and anteroposterior axes. The SDs of the systematic center-of-mass positioning errors (Σ) were reduced from 4.0 mm to <0.5 mm for all axes. The corresponding SD of the random (σ) errors was reduced from 3.0 to <0.8 mm. These small residual errors were achieved with a treatment time extension of <1 min. Conclusion: Stereographic targeting yields systematic and random prostate positioning errors of <1 mm with <1 min of added treatment time

  7. Shaft Position Influence on Technical Characteristics of Universal Two-Stages Helical Speed Reducers

    Directory of Open Access Journals (Sweden)

    Мilan Rackov

    2005-10-01

    Full Text Available Purchasers of speed reducers decide on buying those reducers, that can the most approximately satisfy their demands with much smaller costs. Amount of used material, ie. mass and dimensions of gear unit influences on gear units price. Mass and dimensions of gear unit, besides output torque, gear unit ratio and efficiency, are the most important parameters of technical characteristics of gear units and their quality. Centre distance and position of shafts have significant influence on output torque, gear unit ratio and mass of gear unit through overall dimension of gear unit housing. Thus these characteristics are dependent on each other. This paper deals with analyzing of centre distance and shaft position influence on output torque and ratio of universal two stages gear units.

  8. Novel treatment option for MUC16-positive malignancies with the targeted TRAIL-based fusion protein Meso-TR3

    International Nuclear Information System (INIS)

    Garg, Gunjal; Spitzer, Dirk; Gibbs, Jesse; Belt, Brian; Powell, Matthew A; Mutch, David G; Goedegebuure, Peter; Collins, Lynne; Piwnica-Worms, David; Hawkins, William G

    2014-01-01

    The targeted delivery of cancer therapeutics represents an ongoing challenge in the field of drug development. TRAIL is a promising cancer drug but its activity profile could benefit from a cancer-selective delivery mechanism, which would reduce potential side effects and increase treatment efficiencies. We recently developed the novel TRAIL-based drug platform TR3, a genetically fused trimer with the capacity for further molecular modifications such as the addition of tumor-directed targeting moieties. MUC16 (CA125) is a well characterized biomarker in several human malignancies including ovarian, pancreatic and breast cancer. Mesothelin is known to interact with MUC16 with high affinity. In order to deliver TR3 selectively to MUC16-expressing cancers, we investigated the possibility of targeted TR3 delivery employing the high affinity mesothelin/MUC16 ligand/receptor interaction. Using genetic engineering, we designed the novel cancer drug Meso-TR3, a fusion protein between native mesothelin and TR3. The recombinant proteins were produced with mammalian HEK293T cells. Meso-TR3 was characterized for binding selectivity and killing efficacy against MUC16-positive cancer cells and controls that lack MUC16 expression. Drug efficacy experiments were performed in vitro and in vivo employing an intraperitoneal xenograft mouse model of ovarian cancer. Similar to soluble mesothelin itself, the strong MUC16 binding property was retained in the Meso-TR3 fusion protein. The high affinity ligand/receptor interaction was associated with a selective accumulation of the cancer drug on MUC16-expressing cancer targets and directly correlated with increased killing activity in vitro and in a xenograft mouse model of ovarian cancer. The relevance of the mesothelin/MUC16 interaction for attaching Meso-TR3 to the cancer cells was verified by competitive blocking experiments using soluble mesothelin. Mechanistic studies using soluble DR5-Fc and caspase blocking assays confirmed

  9. The positive deviance/hearth approach to reducing child malnutrition: systematic review.

    Science.gov (United States)

    Bisits Bullen, Piroska A

    2011-11-01

    The Positive Deviance/Hearth approach aims to rehabilitate malnourished children using practices from mothers in the community who have well-nourished children despite living in poverty. This study assesses its effectiveness in a range of settings. Systematic review of peer reviewed intervention trials and grey literature evaluation reports of child malnutrition programs using the Positive Deviance/Hearth approach. Ten peer reviewed studies and 14 grey literature reports met the inclusion criteria. These described results for 17 unique Positive Deviance/Hearth programs in 12 countries. Nine programs used a pre- and post-test design without a control, which limited the conclusions that could be drawn. Eight used more robust designs such as non-randomized trials, non-randomized cross-sectional sibling studies and randomized controlled trials (RCTs). Of the eight programs that reported nutritional outcomes, five reported some type of positive result in terms of nutritional status - although the improvement was not always as large as predicted, or across the entire target population. Both the two RCTs demonstrated improvements in carer feeding practices. Qualitative results unanimously reported high levels of satisfaction from participants and recipient communities. Overall this study shows mixed results in terms of program effectiveness, although some Positive Deviance/Hearth programs have clearly been successful in particular settings. Sibling studies suggest that the Positive Deviance/Hearth approach may have a role in preventing malnutrition, not just rehabilitation. Further research is needed using more robust study designs and larger sample sizes. Issues related to community participation and consistency in reporting results need to be addressed. © 2011 Blackwell Publishing Ltd.

  10. Metformin Targets Brown Adipose Tissue in vivo and Reduces Oxygen Consumption in vitro

    DEFF Research Database (Denmark)

    Breining, Peter; Jensen, Jonas B; Sundelin, Elias I

    2018-01-01

    basic metabolic rate, making BAT an attractive target for treatment of type 2 diabetes. Under the hypothesis that BAT is a metformin target tissue, we investigated in vivo uptake of [11 C]-metformin tracer in mice and studied in vitro effects of metformin on cultured human brown adipocytes. Injected [11......Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well-documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence...... uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose dependent manner. Collectively, these results support BAT as a putative metformin...

  11. Laser coupling to reduced-scale targets at Nif Early Light

    Energy Technology Data Exchange (ETDEWEB)

    Hinkel, D.E.; Schneider, M.B.; Young, B.K.; Holder, J.P.; Langdon, A.B.; Bonanno, G.; Bower, D.E.; Bruns, H.C.; Campbell, K.M.; Celeste, J.R.; Compton, S.; Costa, R.L.; Dewald, E.L.; Dixit, S.N.; Eckart, M.J.; Eder, D.C.; Edwards, M.J.; Ellis, A.D.; Emig, J.A.; Froula, D.H.; Glenzer, S.H.; Hargrove, D.; Haynam, C.A.; Heeter, R.F.; Henesian, M.A.; Holtmeier, G.; James, D.L.; Jancaitis, K.S.; Kalantar, K.H.; Kamperschroer, J.H.; Kauffman, R.L.; Kimbrough, J.; Kirkwood, R.K.; Koniges, A.E.; Landen, O.L.; Landon, M.; Lee, F.D.; MacGowan, B.J.; Mackinnon, A.J.; Manes, K.R.; Marshall, C.; May, M.J.; McDonald, J.W.; Menapace, J.; Moses, S.E.I.; Munro, D.H.; Murray, J.R.; Niemann, C.; Power, G.D.; Rekow, V.; Ruppe, J.A.; Schein, J.; Shepherd, R.; Singh, M.S.; Springer, P.T.; Still, C.H.; Suter, L.J.; Tietbohl, G.L.; Turner, R.E.; VanWonterghem, B.M.; Wallace, R.J.; Warrick, A.; Weber, F.; Wegner, P.J.; Williams, E.A.; Young, P.E. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Baldis, H.A. [California at Davis Univ., CA (United States); Pellinen, D.; Watts, P. [Bechtel Nevada Corporation, Livermore, CA (United States)

    2006-06-15

    Deposition of maximum laser energy into a small, high-Z enclosure in a short laser pulse creates a hot environment. Such targets were recently included in an experimental campaign using the first four of the 192 beams of the National Ignition Facility (NIF) under construction at the University of California Lawrence Livermore National Laboratory. These targets demonstrate good laser coupling, reaching a radiation temperature of 340 eV. In addition, the Raman backscatter spectrum contains features consistent with Brillouin backscatter of Raman forward scatter. Also, NIF Early Light diagnostics indicate that 20% of the direct backscatter from these reduced-scale targets is in the polarization orthogonal to that of the incident light. (authors)

  12. Laser coupling to reduced-scale targets at NIF Early Light

    International Nuclear Information System (INIS)

    Hinkel, D E; Schneider, M B; Young, B K; Holder, J P; Langdon, A B; Baldis, H A; Bonanno, G; Bower, D E; Bruns, H C; Campbell, K M; Celeste, J R; Compton, S; Costa, R L; Dewald, E L; Dixit, S N; Eckart, M J; Eder, D C; Edwards, M J; Ellis, A D; Emig, J A; Froula, D H; Glenzer, S H; Hargrove, D; Haynam, C A; Heeter, R F; Henesian, M A; Holtmeier, G; James, D L; Jancaitis, K S; Kalantar, D H; Kamperschroer, J H; Kauffman, R L; Kimbrough, J; Kirkwood, R K; Koniges, A E; Landen, O L; Landon, M; Lee, F D; MacGowan, B J; Mackinnon, A J; Manes, K R; Marshall, C; May, M J; McDonald, J W; Menapace, J; Moses, S I; Munro, D H; Murray, J R; Niemann, C; Pellinen, D; Power, G D; Rekow, V; Ruppe, J A; Schein, J; Shepherd, R; Singh, M S; Springer, P; Still, C H; Suter, L J; Tietbohl, G L; Turner, R E; VanWonterghem, B M; Wallace, R J; Warrick, A; Watts, P; Weber, F; Wegner, P J; Williams, E A; Young, P E

    2005-01-01

    Deposition of maximum laser energy into a small, high-Z enclosure in a short laser pulse creates a hot environment. Such targets were recently included in an experimental campaign using the first four of the 192 beams of the National Ignition Facility [J. A. Paisner, E. M. Campbell, and W. J. Hogan, Fusion Technology 26 26, 755 (1994)], under construction at the University of California Lawrence Livermore National Laboratory. These targets demonstrate good laser coupling, reaching a radiation temperature of 340 eV. In addition, the Raman backscatter spectrum contains features consistent with Brillouin backscatter of Raman forward scatter [A. B. Langdon and D. E. Hinkel, Physical Review Letters 89, 015003 (2002)]. Also, NIF Early Light diagnostics indicate that 20% of the direct backscatter from these reduced-scale targets is in the polarization orthogonal to that of the incident light

  13. The Universal Patient Centredness Questionnaire: scaling approaches to reduce positive skew

    Directory of Open Access Journals (Sweden)

    Bjertnaes O

    2016-11-01

    Full Text Available Oyvind Bjertnaes, Hilde Hestad Iversen, Andrew M Garratt Unit for Patient-Reported Quality, Norwegian Institute of Public Health, Oslo, Norway Purpose: Surveys of patients’ experiences typically show results that are indicative of positive experiences. Unbalanced response scales have reduced positive skew for responses to items within the Universal Patient Centeredness Questionnaire (UPC-Q. The objective of this study was to compare the unbalanced response scale with another unbalanced approach to scaling to assess whether the positive skew might be further reduced. Patients and methods: The UPC-Q was included in a patient experience survey conducted at the ward level at six hospitals in Norway in 2015. The postal survey included two reminders to nonrespondents. For patients in the first month of inclusion, UPC-Q items had standard scaling: poor, fairly good, good, very good, and excellent. For patients in the second month, the scaling was more positive: poor, good, very good, exceptionally good, and excellent. The effect of scaling on UPC-Q scores was tested with independent samples t-tests and multilevel linear regression analysis, the latter controlling for the hierarchical structure of data and known predictors of patient-reported experiences. Results: The response rate was 54.6% (n=4,970. Significantly lower scores were found for all items of the more positively worded scale: UPC-Q total score difference was 7.9 (P<0.001, on a scale from 0 to 100 where 100 is the best possible score. Differences between the four items of the UPC-Q ranged from 7.1 (P<0.001 to 10.4 (P<0.001. Multivariate multilevel regression analysis confirmed the difference between the response groups, after controlling for other background variables; UPC-Q total score difference estimate was 8.3 (P<0.001. Conclusion: The more positively worded scaling significantly lowered the mean scores, potentially increasing the sensitivity of the UPC-Q to identify differences over

  14. Target position uncertainty during visually guided deep-inspiration breath-hold radiotherapy in locally advanced lung cancer

    DEFF Research Database (Denmark)

    Rydhog, Jonas Scherman; de Blanck, Steen Riisgaard; Josipovic, Mirjana

    2017-01-01

    Purpose: The purpose of this study was to estimate the uncertainty in voluntary deep-inspiration breath hold (DISH) radiotherapy for locally advanced non-small cell lung cancer (NSCLC) patients.Methods: Perpendicular fluoroscopic movies were acquired in free breathing (FB) and DIBH during a course...... of visually guided DIBH radiotherapy of nine patients with NSCLC. Patients had liquid markers injected in mediastinal lymph nodes and primary tumours. Excursion, systematic- and random errors, and inter-breath-hold position uncertainty were investigated using an image based tracking algorithm.Results: A mean...... small in visually guided breath-hold radiotherapy of NSCLC. Target motion could be substantially reduced, but not eliminated, using visually guided DIBH. (C) 2017 Elsevier B.V. All rights reserved....

  15. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications.

    Science.gov (United States)

    Mordang, Jan-Jurre; Gubern-Mérida, Albert; den Heeten, Gerard; Karssemeijer, Nico

    2016-04-01

    significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (psystem with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.

  16. Toward Reducing Ageism: PEACE (Positive Education about Aging and Contact Experiences) Model.

    Science.gov (United States)

    Levy, Sheri R

    2018-03-19

    The population of older adults is growing worldwide. Negative ageism (negative attitudes and behavior toward older adults) is a serious international concern that negatively influences not only older adults but also individuals across the age continuum. This article proposes and examines the application of an integrative theoretical model across empirical evidence in the literature on ageism in psychology, medicine, social work, and sociology. The proposed Positive Education about Aging and Contact Experiences (PEACE) model focuses on 2 key contributing factors expected to reduce negative ageism: (a) education about aging including facts on aging along with positive older role models that dispel negative and inaccurate images of older adulthood; and (b) positive contact experiences with older adults that are individualized, provide or promote equal status, are cooperative, involve sharing of personal information, and are sanctioned within the setting. These 2 key contributing factors have the potential to be interconnected and work together to reduce negative stereotypes, aging anxiety, prejudice, and discrimination associated with older adults and aging. This model has implications for policies and programs that can improve the health and well-being of individuals, as well as expand the residential, educational, and career options of individuals across the age continuum.

  17. Anisotropic depth migration: reducing lateral-position uncertainty of subsurface structures in the Alberta foothills

    Energy Technology Data Exchange (ETDEWEB)

    Vestrum, R.W.; Lawton, D.C.

    1999-01-01

    Seismic velocity anisotropy causes lateral-positioning errors on seismic images, and the use of anisotropic depth migration corrects this lateral mispositioning of subsurface targets. The assumption of isotropic seismic velocities implies that traditional depth migration corrects only for positioning errors caused by lateral velocity heterogeneity, and mispositioning due to seismic anisotropy remained uncorrected on depth-migrated sections. Also, isotropic depth migration was only applied in cases in which significant lateral velocity changes occurred, and lateral mispositioning due to seismic anisotropy remained uncorrected on time-migrated sections. If seismic is to accurately image the subsurface, then there is a need for reconsidering the assumptions made in depth imaging as well as a need to reconsider at what point depth migration applies to seismic data. Now that it is possible to correct for seismic anisotropy as well as lateral velocity heterogeneity, anisotropic depth migration potentially can be used to improve seismic imaging and positioning in areas in which traditional depth migration did not apply. 5 refs.

  18. Anisotropic depth migration: reducing lateral-position uncertainty of subsurface structures in the Alberta foothills

    Energy Technology Data Exchange (ETDEWEB)

    Vestrum, R.W.; Lawton, D.C.

    1999-11-01

    Seismic velocity anisotropy causes lateral-positioning errors on seismic images, and the use of anisotropic depth migration corrects this lateral mispositioning of subsurface targets. The assumption of isotropic seismic velocities implies that traditional depth migration corrects only for positioning errors caused by lateral velocity heterogeneity, and mispositioning due to seismic anisotropy remained uncorrected on depth-migrated sections. Also, isotropic depth migration was only applied in cases in which significant lateral velocity changes occurred, and lateral mispositioning due to seismic anisotropy remained uncorrected on time-migrated sections. If seismic is to accurately image the subsurface, then there is a need for reconsidering the assumptions made in depth imaging as well as a need to reconsider at what point depth migration applies to seismic data. Now that it is possible to correct for seismic anisotropy as well as lateral velocity heterogeneity, anisotropic depth migration potentially can be used to improve seismic imaging and positioning in areas in which traditional depth migration did not apply. 5 refs.

  19. Interrogating Key Positions of Size-Reduced TALE Repeats Reveals a Programmable Sensor of 5-Carboxylcytosine.

    Science.gov (United States)

    Maurer, Sara; Giess, Mario; Koch, Oliver; Summerer, Daniel

    2016-12-16

    Transcription-activator-like effector (TALE) proteins consist of concatenated repeats that recognize consecutive canonical nucleobases of DNA via the major groove in a programmable fashion. Since this groove displays unique chemical information for the four human epigenetic cytosine nucleobases, TALE repeats with epigenetic selectivity can be engineered, with potential to establish receptors for the programmable decoding of all human nucleobases. TALE repeats recognize nucleobases via key amino acids in a structurally conserved loop whose backbone is positioned very close to the cytosine 5-carbon. This complicates the engineering of selectivities for large 5-substituents. To interrogate a more promising structural space, we engineered size-reduced repeat loops, performed saturation mutagenesis of key positions, and screened a total of 200 repeat-nucleobase interactions for new selectivities. This provided insight into the structural requirements of TALE repeats for affinity and selectivity, revealed repeats with improved or relaxed selectivity, and resulted in the first selective sensor of 5-carboxylcytosine.

  20. Reduced complexity FFT-based DOA and DOD estimation for moving target in bistatic MIMO radar

    KAUST Repository

    Ali, Hussain

    2016-06-24

    In this paper, we consider a bistatic multiple-input multiple-output (MIMO) radar. We propose a reduced complexity algorithm to estimate the direction-of-arrival (DOA) and direction-of-departure (DOD) for moving target. We show that the calculation of parameter estimation can be expressed in terms of one-dimensional fast-Fourier-transforms which drastically reduces the complexity of the optimization algorithm. The performance of the proposed algorithm is compared with the two-dimension multiple signal classification (2D-MUSIC) and reduced-dimension MUSIC (RD-MUSIC) algorithms. It is shown by simulations, our proposed algorithm has better estimation performance and lower computational complexity compared to the 2D-MUSIC and RD-MUSIC algorithms. Moreover, simulation results also show that the proposed algorithm achieves the Cramer-Rao lower bound. © 2016 IEEE.

  1. Desulfotomaculum spp. and related Gram-positive sulfate-reducing bacteria in deep subsurface environments.

    Directory of Open Access Journals (Sweden)

    Thomas eAullo

    2013-12-01

    Full Text Available Gram-positive spore-forming sulfate reducers and particularly members of the genus Desulfotomaculum are commonly found in the subsurface biosphere by culture based and molecular approaches. Due to their metabolic versatility and their ability to persist as endospores. Desulfotomaculum spp. are well adapted for colonizing environments through a slow sedimentation process. Because of their ability to grow autotrophically (H2/CO2 and produce sulfide or acetate, these microorganisms may play key roles in deep lithoautotrophic microbial communities. Available data about Desulfotomaculum spp. and related species from studies carried out from deep freshwater lakes, marine sediments, oligotrophic and organic rich deep geological settings are discussed in this review.

  2. Reduced cost design of liquid lithium target for international fusion material irradiation facility (IFMIF)

    International Nuclear Information System (INIS)

    Nakamura, Hiroo; Ida, Mizuho; Sugimoto, Masayoshi; Takeuchi, Hiroshi; Yutani, Toshiaki

    2001-01-01

    The International Fusion Materials Irradiation Facility (IFMIF) is being jointly planned to provide an accelerator-based D-Li neutron source to produce intense high energy neutrons (2 MW/m 2 ) up to 200 dpa and a sufficient irradiation volume (500 cm 3 ) for testing the candidate materials and components up to about a full lifetime of their anticipated use in ITER and DEMO. To realize such a condition, 40 MeV deuteron beam with a current of 250 mA is injected into high speed liquid lithium flow with a speed of 20 m/s. Following Conceptual Design Activity (1995-1998), a design study with focus on cost reduction without changing its original mission has been done in 1999. The following major changes to the CAD target design have been considered in the study and included in the new design: i) number of the Li target has been changed from 2 to 1, ii) spare of impurity traps of the Li loop was removed although the spare will be stored in a laboratory for quick exchange, iii) building volume was reduced via design changes in lithium loop length. This paper describes the reduced cost design of the lithium target system and recent status of Key Element Technology activities. (author)

  3. GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

    Science.gov (United States)

    Duann, Pu; Lianos, Elias A

    2009-09-01

    Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

  4. Reducing US cardiovascular disease burden and disparities through national and targeted dietary policies: A modelling study.

    Directory of Open Access Journals (Sweden)

    Jonathan Pearson-Stuttard

    2017-06-01

    Full Text Available Large socio-economic disparities exist in US dietary habits and cardiovascular disease (CVD mortality. While economic incentives have demonstrated success in improving dietary choices, the quantitative impact of different dietary policies on CVD disparities is not well established. We aimed to quantify and compare the potential effects on total CVD mortality and disparities of specific dietary policies to increase fruit and vegetable (F&V consumption and reduce sugar-sweetened beverage (SSB consumption in the US.Using the US IMPACT Food Policy Model and probabilistic sensitivity analyses, we estimated and compared the reductions in CVD mortality and socio-economic disparities in the US population potentially achievable from 2015 to 2030 with specific dietary policy scenarios: (a a national mass media campaign (MMC aimed to increase consumption of F&Vs and reduce consumption of SSBs, (b a national fiscal policy to tax SSBs to increase prices by 10%, (c a national fiscal policy to subsidise F&Vs to reduce prices by 10%, and (d a targeted policy to subsidise F&Vs to reduce prices by 30% among Supplemental Nutrition Assistance Program (SNAP participants only. We also evaluated a combined policy approach, combining all of the above policies. Data sources included the Surveillance, Epidemiology, and End Results Program, National Vital Statistics System, National Health and Nutrition Examination Survey, and published meta-analyses. Among the individual policy scenarios, a national 10% F&V subsidy was projected to be most beneficial, potentially resulting in approximately 150,500 (95% uncertainty interval [UI] 141,400-158,500 CVD deaths prevented or postponed (DPPs by 2030 in the US. This far exceeds the approximately 35,100 (95% UI 31,700-37,500 DPPs potentially attributable to a 30% F&V subsidy targeting SNAP participants, the approximately 25,800 (95% UI 24,300-28,500 DPPs for a 1-y MMC, or the approximately 31,000 (95% UI 26,800-35,300 DPPs for a 10

  5. A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups

    Directory of Open Access Journals (Sweden)

    Julie Lao

    2017-03-01

    Full Text Available The pathogenicity of the different flu species is a real public health problem worldwide. To combat this scourge, we established a method to detect drug targets, reducing the possibility of escape. Besides being able to attach a drug candidate, these targets should have the main characteristic of being part of an essential viral function. The invariance groups that are sets of residues bearing an essential function can be detected genetically. They consist of invariant and synthetic lethal residues (interdependent residues not varying or slightly varying when together. We analyzed an alignment of more than 10,000 hemagglutinin sequences of influenza to detect six invariance groups, close in space, and on the protein surface. In parallel we identified five potential pockets on the surface of hemagglutinin. By combining these results, three potential binding sites were determined that are composed of invariance groups located respectively in the vestigial esterase domain, in the bottom of the stem and in the fusion area. The latter target is constituted of residues involved in the spring-loaded mechanism, an essential step in the fusion process. We propose a model describing how this potential target could block the reorganization of the hemagglutinin HA2 secondary structure and prevent viral entry into the host cell.

  6. Investigation on fabrication and positioning of cryogenic shell laser fusion targets. Annual report, October 1, 1977--November 30, 1978

    International Nuclear Information System (INIS)

    Kim, K.

    1978-01-01

    The research has been directed toward fabrication and positioning of cryogenic shell laser fusion targets, with particular emphasis on the development of a scheme which would allow for continuous fabrication, inspection, and delivery of the targets. Specifically, progress has been made in each of the following areas: (1) fabrication of a uniform layer of solid DT inside a glass microshell using a combination of helium gas jets and a heater wire; (2) levitation-freezing of a DT-filled glass microshell as a method for fabricating and positioning a cryogenic shell target; (3) a target fabrication system intended for continuous fabrication, inspection, and delivery of cryogenic targets; and (4) development of diagnostics for inspection, recording, and analysis of a solid DT layer inside a glass microshell, and for observing the parameters controlling the target freezing process

  7. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications

    International Nuclear Information System (INIS)

    Mordang, Jan-Jurre; Gubern-Mérida, Albert; Karssemeijer, Nico; Heeten, Gerard den

    2016-01-01

    range of 0.8–1.0 were significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (p<0.05), respectively. Additionally, the sensitivity at one false positive per 50 cases and one false positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus 67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. Conclusions: By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.

  8. Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications

    Energy Technology Data Exchange (ETDEWEB)

    Mordang, Jan-Jurre, E-mail: Jan-Jurre.Mordang@radboudumc.nl; Gubern-Mérida, Albert; Karssemeijer, Nico [Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen 6525 GA (Netherlands); Heeten, Gerard den [The National Training Centre for Breast Cancer Screening, Nijmegen 6503 GJ, The Netherlands and Department of Radiology, Amsterdam Medical Center, Amsterdam 1100 DD (Netherlands)

    2016-04-15

    range of 0.8–1.0 were significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (p<0.05), respectively. Additionally, the sensitivity at one false positive per 50 cases and one false positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus 67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. Conclusions: By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.

  9. MRI target delineation may reduce long-term toxicity after prostate radiotherapy.

    Science.gov (United States)

    Sander, Lotte; Langkilde, Niels Christian; Holmberg, Mats; Carl, Jesper

    2014-06-01

    Aiming for minimal toxicity after radical prostate cancer (PC) radiotherapy (RT), magnetic resonance imaging (MRI) target delineation could be a possible benefit knowing that clinical target volumes (CTV) are up to 30% smaller, when CTV delineation on MRI is compared to standard computed tomography (CT). This study compares long-term toxicity using CT or MRI delineation before PC RT. Urinary and rectal toxicity assessments 36 months after image-guided RT (78 Gy) using CTC-AE scores in two groups of PC patients. Peak symptom score values were registered. One group of patients (n=72) had standard CT target delineation and gold markers as fiducials. Another group of patients (n=73) had MRI target delineation and a nickel-titanium stent as fiducial. At 36 months no difference in overall survival (92% in both groups, p=0.29) or in PSA-relapse free survival was found between the groups (MRI=89% and CT=94%, p=0.67). A significantly smaller CTV was found in the MRI group (p=0.02). Urinary retention and frequency were significantly reduced in the MRI group (p=0.03 in the matter of both). The overall urinary and rectal toxicity did not differ between the two groups. MRI delineation leads to a significantly reduced CTV. Significantly lower urinary frequency and urinary retention toxicity scores were observed following MRI delineation. The study did not find significant differences in overall urinary or rectal toxicity between the two groups. PSA-relapse survival did not differ between the two groups at 36 months.

  10. Target volume shape variation during irradiation of rectal cancer patients in supine position: Comparison with prone position

    International Nuclear Information System (INIS)

    Nijkamp, Jasper; Jong, Rianne de; Sonke, Jan-Jakob; Vliet, Corine van; Marijnen, Corrie

    2009-01-01

    Purpose: To quantify the inter-fraction shape variation of the mesorectum for rectal cancer patients treated with 5 x 5 Gy in supine position and compare it to variation in prone position. Methods and materials: For 28 patients a planning CT (pCT) and five daily cone-beam-CT (CBCT) scans were acquired in supine position. The mesorectal part of the CTV (MesoRect) was delineated on all scans. The shape variation was quantified by the distance between the pCT- and the CBCT delineations and stored in surface maps after online setup correction. Data were analyzed for male and female patients separately and compared to prone data. Results: A large range of systematic, 1-8 mm (1SD), and random, 1-5 mm, shape variation was found, comparable to prone patients. Random-shape variation was comparable for male and female patients, while systematic variation was 3 mm larger for female patients. Conclusions: Shape variation of the MesoRect is substantial, heterogeneous and different between male and female patients. Differences between supine and prone orientation, however, are small. Clinical margins should be differentiated in position along the cranio-caudal axis, in anterior-posterior direction and for gender. Margins should also be increased, even when online setup correction is used. Due to the small margin differences between prone and supine treatments, the setup choice should be determined on dose to the organs at risk.

  11. Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes.

    Directory of Open Access Journals (Sweden)

    Yunwon Moon

    Full Text Available This study evaluated HIF-1α inhibitors under different hypoxic conditions, physiological hypoxia (5% O2 and severe hypoxia (0.1% O2. We found that chenodeoxy cholic acid (CDCA reduced the amount of HIF-1α protein only under physiological hypoxia but not under severe hypoxia without decreasing its mRNA level. By using a proteasome inhibitor MG132 and a translation inhibitor cyclohexamide, we showed that CDCA reduced HIF-1α protein by decreasing its translation but not by enhancing its degradation. The following findings indicated that farnesoid X receptor (FXR, a CDCA receptor and its target gene, Small heterodimer partner (SHP are not involved in this effect of CDCA. Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1α protein. Furthermore a FXR antagonist, guggulsterone failed to prevent CDCA from decreasing HIF-1α protein. Furthermore, guggulsterone by itself reduced HIF-1α protein even in the presence of MG132. These findings suggested that CDCA and guggulsterone reduced the translation of HIF-1α in a mechanism which FXR and SHP are not involved. This study reveals novel therapeutic functions of traditional nontoxic drugs, CDCA and guggulsterone, as inhibitors of HIF-1α protein.

  12. The efficacy and safety of the targeted drug combined with adriamycin liposome solution for HER-2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Zi-Ping Zhou

    2017-05-01

    Full Text Available Objective: To study the efficacy and safety of the targeted drug trastuzumab combined with adriamycin liposome solution for HER-2-positive breast cancer. Methods: A total of 112 patients with breast cancer who received chemotherapy in Department of Cardiothoracic Breast Surgery, Guangdong TongJiang Hospital between May 2014 and April 2016 were selected as the research subjects and divided into two groups by random number table, liposome group received trastuzumab + adriamycin liposome chemotherapy, and the control group received trastuzumab + adriamycin chemotherapy. Before chemotherapy as well as 4 weeks and 8 weeks after chemotherapy, serum levels of tumor markers, cytokines and myocardial injury indexes were detected, the electrocardiography was conducted and the degree of myocardial injury was determined. Results: 4 weeks and 8 weeks after chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF and MK levels of both groups were significantly lower than those before chemotherapy, serum CK-MB and cTnI levels were significantly higher than those before chemotherapy, limb leads QRS amplitudes and chest leads QRS amplitudes were significantly lower than those before chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF, MK, CK-MB and cTnI levels of liposome group were significantly lower than those of control group, and the limb leads QRS amplitudes and chest lead QRS amplitudes were significantly higher than those of control group. Conclusion: Targeted drug combined with adriamycin liposome therapy for HER-2-positive breast cancer can improve the curative effect and reduce the cardiotoxicity.

  13. Motivational Interviewing Targeting Risky Sex in HIV-Positive Young Thai Men Who Have Sex with Men

    Science.gov (United States)

    Rongkavilit, Chokechai; Wang, Bo; Naar-King, Sylvie; Bunupuradah, Torsak; Parsons, Jeffrey T.; Panthong, Apirudee; Koken, Juline A.; Saengcharnchai, Pichai; Phanuphak, Praphan

    2014-01-01

    Motivational interviewing (MI) has been shown to reduce sexual risks among HIV-positive men who have sex with men (HMSM) in the U.S. We conducted a randomized trial of Healthy Choices, a 4-session MI intervention, targeting sexual risks among 110 HIV-positive youth ages 16–25 years in Thailand. Risk assessments were conducted at baseline, 1 month, and 6 months post-intervention. This report presents the analysis of 74 HMSM in the study. There were 37 HMSM in the Intervention group and 37 in the control group. The proportions of participants having anal sex and having sex with either HIV-uninfected or unknown partners in past 30 days were significantly lower in Intervention group than in control group at 6 months post-intervention (38% vs. 65%, p = .04; and 27% vs. 62%, p Thai HMSM was associated with sexual risk reduction. Improvements in mental health and HIV stigma were noted in Intervention group. Healthy Choices is a promising behavioral intervention and should be further developed to serve the needs of young HMSM in resource-limited countries. PMID:24668304

  14. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer

    Directory of Open Access Journals (Sweden)

    Iniesta Pilar

    2011-08-01

    Full Text Available Abstract Background Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312. Results The aldehyde dehydrogenase (ALDH positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect and through decrease in telomere length (long-term effect. Administration of this telomerase inhibitor (40 mg/kg in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls. Combination therapy consisting of irradiation (10Gy plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length in vivo. Conclusions We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer.

  15. National Ignition Facility subsystem design requirements target positioning subsystem SSDR 1.8.2

    International Nuclear Information System (INIS)

    Pittenger, L.

    1996-01-01

    This Subsystem Design Requirement document is a development specification that establishes the performance, design, development and test requirements for the target positioner subsystem (WBS 1.8.2) of the NIF Target Experimental System (WBS 1.8)

  16. Intratracheal Administration of Small Interfering RNA Targeting Fas Reduces Lung Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Del Sorbo, Lorenzo; Costamagna, Andrea; Muraca, Giuseppe; Rotondo, Giuseppe; Civiletti, Federica; Vizio, Barbara; Bosco, Ornella; Martin Conte, Erica L; Frati, Giacomo; Delsedime, Luisa; Lupia, Enrico; Fanelli, Vito; Ranieri, V Marco

    2016-08-01

    Lung ischemia-reperfusion injury is the main cause of primary graft dysfunction after lung transplantation and results in increased morbidity and mortality. Fas-mediated apoptosis is one of the pathologic mechanisms involved in the development of ischemia-reperfusion injury. We hypothesized that the inhibition of Fas gene expression in lungs by intratracheal administration of small interfering RNA could reduce lung ischemia-reperfusion injury in an ex vivo model reproducing the procedural sequence of lung transplantation. Prospective, randomized, controlled experimental study. University research laboratory. C57/BL6 mice weighing 28-30 g. Ischemia-reperfusion injury was induced in lungs isolated from mice, 48 hours after treatment with intratracheal small interfering RNA targeting Fas, control small interfering RNA, or vehicle. Isolated lungs were exposed to 6 hours of cold ischemia (4°C), followed by 2 hours of warm (37°C) reperfusion with a solution containing 10% of fresh whole blood and mechanical ventilation with constant low driving pressure. Fas gene expression was significantly silenced at the level of messenger RNA and protein after ischemia-reperfusion in lungs treated with small interfering RNA targeting Fas compared with lungs treated with control small interfering RNA or vehicle. Silencing of Fas gene expression resulted in reduced edema formation (bronchoalveolar lavage protein concentration and lung histology) and improvement in lung compliance. These effects were associated with a significant reduction of pulmonary cell apoptosis of lungs treated with small interfering RNA targeting Fas, which did not affect cytokine release and neutrophil infiltration. Fas expression silencing in the lung by small interfering RNA is effective against ischemia-reperfusion injury. This approach represents a potential innovative strategy of organ preservation before lung transplantation.

  17. Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy.

    Science.gov (United States)

    Choi, Joung-Woo; Kim, Hyun Ah; Nam, Kihoon; Na, Youjin; Yun, Chae-Ok; Kim, SungWan

    2015-12-28

    Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP-PEG-HCBP1 can protect biological activity of Ad against serum, and considerably reduced both innate and adaptive immune response against Ad. shMet-expressing oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated enhanced cancer cell killing efficacy in comparison to oAd/ABP complex. Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1 complex had significantly decreased Met and VEGF expression in hepatoma cancer, but not in non-hepatoma cancer. In sum, these results suggest that HCBP1-conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and efficiently to treat hepatoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Isotopically tailored lead target with reduced polonium and bismuth radio-waste

    International Nuclear Information System (INIS)

    Khorasanov, G.L.; Ivanov, A.P.; Lunev, V.P.; Blokhin, A.I.

    2002-01-01

    Residual activity of a lead target after 1 year irradiation with a high power, 0.8 GeV*30 mA, proton beam is studied. It is concluded that the main radiotoxicity of irradiated lead is connected with bismuth isotope, Bi-207, which is produced in natural lead, mix of several stable isotopes, via (p,2n) reaction with Pb-208 nuclei. It is proposed to use, as a target material, lead enriched with another stable isotope, Pb-206, in order to reduce producing Bi-207 and Po-210. Estimation of charges for obtaining large quantities of lead-206 is also given. Accumulation of hazardous radionuclides, Bi-207, Bi-208, and Po-210, in natural lead to be used as a coolant in future fast reactors and accelerator driven reactors is predicted. In accelerator driven systems a large portion of Bi-207 can be produced via Pb-208(p,2n)Bi-207 reaction in a target of natural lead (Pb-208/Pb-207/Pb-206/Pb-204=52.35/22.08/24.14/1.42 %). A new isotopically tailored coolant-converter for ADS consisting of lead isotope, Pb-206, is proposed. By using this material, it is possible to reduce essentially the production of the most radio-toxic isotopes of Bi and Po and to avoid disposing the large amounts of lead. To provide the future fast reactors and accelerator driven systems with low-activation coolant - converter, the new technology of obtaining the large amounts of natural lead enriched with lead isotope, Pb-206, should be developed. (authors)

  19. Feedback enhances the positive effects and reduces the negative effects of multiple-choice testing.

    Science.gov (United States)

    Butler, Andrew C; Roediger, Henry L

    2008-04-01

    Multiple-choice tests are used frequently in higher education without much consideration of the impact this form of assessment has on learning. Multiple-choice testing enhances retention of the material tested (the testing effect); however, unlike other tests, multiple-choice can also be detrimental because it exposes students to misinformation in the form of lures. The selection of lures can lead students to acquire false knowledge (Roediger & Marsh, 2005). The present research investigated whether feedback could be used to boost the positive effects and reduce the negative effects of multiple-choice testing. Subjects studied passages and then received a multiple-choice test with immediate feedback, delayed feedback, or no feedback. In comparison with the no-feedback condition, both immediate and delayed feedback increased the proportion of correct responses and reduced the proportion of intrusions (i.e., lure responses from the initial multiple-choice test) on a delayed cued recall test. Educators should provide feedback when using multiple-choice tests.

  20. [How to reduce health inequities by targeting social determinants: the role of the health sector in Mexico].

    Science.gov (United States)

    Martínez Valle, Adolfo; Terrazas, Paulina; Alvarez, Fernando

    2014-04-01

    To study lines of action implemented in Mexico by the health sector from 2007 to 2012 in order to combat health inequities by targeting social determinants. To contribute to better understanding and knowledge of how health system inequalities in the Region of the Americas can be reduced. To formulate recommendations for designing a future public policy agenda to address the social determinants associated with health inequities in Mexico. The policies and programs established in the National Health Program (PRONASA) 2007 - 2012 were reviewed, and those that met four criteria were selected: i) they affected the social determinants of health (SDH); ii) they developed specific lines of action aimed at reducing health inequities; iii) they set concrete goals; and iv) they had been evaluated to determine whether those goals had been met. Three programs were selected: Seguro Popular, Programa de Desarrollo Humano Oportunidades (PDHO), and Caravanas de la Salud. Once each program's specific lines of action targeting SDH had been identified, the monitoring and evaluation indicators established in PRONASA 2007 - 2012, along with other available evaluations and empirical evidence, were used to measure the extent to which the goals were met. The findings showed that Seguro Popular had had a positive impact in terms of the financial protection of lower-income households. Moreover, the reduction in the gap between workers covered by the social security system and those who were not was more evident. By reducing poverty among its beneficiaries, the PDHO also managed to reduce health inequities. The indicators for Caravanas de la Salud, on the other hand, did not show statistically significant differences between the control localities and the localities covered by the program, except in the case of Pap tests. These findings have important public policy implications for designing an agenda that promotes continued targeting of SDH and heightening its impact in terms of reducing

  1. Gabor Deconvolution as Preliminary Method to Reduce Pitfall in Deeper Target Seismic Data

    Science.gov (United States)

    Oktariena, M.; Triyoso, W.

    2018-03-01

    pitfall area is reduced and some morphed as background lithology. Gabor Deconvolution removes the attenuation by performing Gabor Domain spectral division, which in extension also reduces interpretation pitfall in deeper target seismic.

  2. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

    2014-01-01

    Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...

  3. DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

    Science.gov (United States)

    Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

    2014-09-17

    DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

  4. Targeted biomarker profiling of matched primary and metastatic estrogen receptor positive breast cancers.

    Directory of Open Access Journals (Sweden)

    Erica B Schleifman

    Full Text Available Patients with newly diagnosed, early stage estrogen receptor positive (ER+ breast cancer often show disease free survival in excess of five years following surgery and systemic adjuvant therapy. An important question is whether diagnostic tumor tissue from the primary lesion offers an accurate molecular portrait of the cancer post recurrence and thus may be used for predictive diagnostic purposes for patients with relapsed, metastatic disease. As the class I phosphatidylinositol 3' kinase (PI3K pathway is frequently activated in ER+ breast cancer and has been linked to acquired resistance to hormonal therapy, we hypothesized pathway status could evolve over time and treatment. Biomarker analyses were conducted on matched, asynchronous primary and metastatic tumors from 77 patients with ER+ breast cancer. We examined whether PIK3CA and AKT1 alterations or PTEN and Ki67 levels showed differences between primary and metastatic samples. We also sought to look more broadly at gene expression markers reflective of proliferation, molecular subtype, and key receptors and signaling pathways using an mRNA analysis platform developed on the Fluidigm BioMark™ microfluidics system to measure the relative expression of 90 breast cancer related genes in formalin-fixed paraffin-embedded (FFPE tissue. Application of this panel of biomarker assays to matched tumor pairs showed a high concordance between primary and metastatic tissue, with generally few changes in mutation status, proliferative markers, or gene expression between matched samples. The collection of assays described here has been optimized for FFPE tissue and may have utility in exploratory analyses to identify patient subsets responsive to targeted therapies.

  5. Reducing mortality risk by targeting specific air pollution sources: Suva, Fiji.

    Science.gov (United States)

    Isley, C F; Nelson, P F; Taylor, M P; Stelcer, E; Atanacio, A J; Cohen, D D; Mani, F S; Maata, M

    2018-01-15

    Health implications of air pollution vary dependent upon pollutant sources. This work determines the value, in terms of reduced mortality, of reducing ambient particulate matter (PM 2.5 : effective aerodynamic diameter 2.5μm or less) concentration due to different emission sources. Suva, a Pacific Island city with substantial input from combustion sources, is used as a case-study. Elemental concentration was determined, by ion beam analysis, for PM 2.5 samples from Suva, spanning one year. Sources of PM 2.5 have been quantified by positive matrix factorisation. A review of recent literature has been carried out to delineate the mortality risk associated with these sources. Risk factors have then been applied for Suva, to calculate the possible mortality reduction that may be achieved through reduction in pollutant levels. Higher risk ratios for black carbon and sulphur resulted in mortality predictions for PM 2.5 from fossil fuel combustion, road vehicle emissions and waste burning that surpass predictions for these sources based on health risk of PM 2.5 mass alone. Predicted mortality for Suva from fossil fuel smoke exceeds the national toll from road accidents in Fiji. The greatest benefit for Suva, in terms of reduced mortality, is likely to be accomplished by reducing emissions from fossil fuel combustion (diesel), vehicles and waste burning. Copyright © 2017. Published by Elsevier B.V.

  6. Strategi Segmenting, Targeting dan Positioning Pengaruhnya terhadap Keputusan Konsumen Menggunakan Produk Kpr Bni Griya

    OpenAIRE

    Karamoy, Sandy Wulan

    2013-01-01

    Penentuan segmen pasar sangat penting dalam mengenali calon nasabah dan memastikan siapa yang potensial menjadi nasabah. Segmentasi ini dapat dibagi berdasar lokasi, usia, jenis kelamin, tingkat penghasilan, kebiasaan dan sebagainya. Penentuan targeting sangat tergantung dari hal-hal seperti karakter produk, karakter segmentasi, dan tingkat persaingan pada segmen yang sudah dipilih. Targeting ini menentukan kepada siapa target market dari suatu produk, apakah kepada semua orang, sebagian ora...

  7. Targeting of alpha-v integrins reduces malignancy of bladder carcinoma.

    Directory of Open Access Journals (Sweden)

    Geertje van der Horst

    Full Text Available Low survival rates of metastatic cancers emphasize the need for a drug that can prevent and/or treat metastatic cancer. αv integrins are involved in essential processes for tumor growth and metastasis and targeting of αv integrins has been shown to decrease angiogenesis, tumor growth and metastasis. In this study, the role of αv integrin and its potential as a drug target in bladder cancer was investigated. Treatment with an αv integrin antagonist as well as knockdown of αv integrin in the bladder carcinoma cell lines, resulted in reduced malignancy in vitro, as illustrated by decreased proliferative, migratory and clonogenic capacity. The CDH1/CDH2 ratio increased, indicating a shift towards a more epithelial phenotype. This shift appeared to be associated with downregulation of EMT-inducing transcription factors including SNAI2. The expression levels of the self-renewal genes NANOG and BMI1 decreased as well as the number of cells with high Aldehyde Dehydrogenase activity. In addition, self-renewal ability decreased as measured with the urosphere assay. In line with these observations, knockdown or treatment of αv integrins resulted in decreased metastatic growth in preclinical in vivo models as assessed by bioluminescence imaging. In conclusion, we show that αv integrins are involved in migration, EMT and maintenance of Aldehyde Dehydrogenase activity in bladder cancer cells. Targeting of αv integrins might be a promising approach for treatment and/or prevention of metastatic bladder cancer.

  8. Working memory load reduces the late positive potential and this effect is attenuated with increasing anxiety.

    Science.gov (United States)

    MacNamara, Annmarie; Ferri, Jamie; Hajcak, Greg

    2011-09-01

    Emotion regulation decreases the processing of arousing stimuli, as indexed by the late positive potential (LPP), an electrocortical component that varies in amplitude with emotional arousal. Emotion regulation increases activity in the prefrontal areas associated with cognitive control, including the dosolateral prefrontal cortex (DLPFC). The present study manipulated working memory load, known to activate the DLPFC, and recorded the LPP elicited by aversive and neutral IAPS pictures presented during the retention interval. The LPP was larger on low-load compared to high-load trials, and on trials with aversive compared to neutral pictures. These LPP data suggest that emotional content and working memory load have opposing effects on attention to distracting stimuli. State anxiety was associated with reduced modulation of the LPP by working memory load. Results are discussed in terms of competition for attention between emotion and cognition and suggest a relationship between DLPFC activation and the allocation of attentional resources to distracting visual stimuli-a relationship that may be disrupted with increasing anxiety.

  9. Reduced Osteogenesis of Human Osteogenic Precursors' Cells Cultured in the Random Positioning Machine

    Science.gov (United States)

    Gershovich, J. G.; Buravkova, L. B.

    2008-06-01

    Recent studies have shown that simulated microgravity (SMG) results in altered proliferation and differentiation not only osteoblasts but also affects on osteogenic capacity of mesenchymal stem cells (MSCs) from various sources. For present study we used system that simulates effects of microgravity produced by the Random Positioning Machine (RPM). Cultured MCSs from human bone marrow and human osteoblasts (OBs) were exposed to SMG at RPM for 10-40 days. Induced osteogenesis of these progenitor cells was compared with the appropriate static (1g) and dynamic (horizontal shaker) controls. Clinorotated OBs and MSCs showed proliferation rate lower than static and dynamic control groups of cells in the early terms of SMG. Significant reduction of ALP activity was detected after 10 days of clinorotation of MSCs. There was no such dramatic difference in ALP activity of MSCs derived cells between SMG and control groups after 20 days of clinorotation but the expression of ALP was still reduced. However, virtually no matrix mineralization was found in OBs cultured under SMG conditions in the presence of differentiation stimuli. The similar effect was observed when we assayed matrix calcification of MSCs derived cultures. Thus, our results confirm low gravity mediated reduction of osteogenesis of different osteogenic precursors' cells and can clarify the mechanisms of bone loss during spaceflight.

  10. Reduced Treatment-Emergent Sexual Dysfunction as a Potential Target in the Development of New Antidepressants

    Directory of Open Access Journals (Sweden)

    David S. Baldwin

    2013-01-01

    Full Text Available Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered “ideal.” As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.

  11. Positioning accuracy analysis of adjusting target mechanism of three-dimensional attitude

    International Nuclear Information System (INIS)

    Ma Li; Wang Kun; Sun Linzhi; Zhou Shasha

    2012-01-01

    A novel adjusting target mechanism of three-dimensional attitude is presented according to the characteristics of the target transport subsystem in inertial confinement fusion (ICF). The mechanism consists of a tangent mechanism adjusting rotation angle and a set of orthogonal tangent mechanism adjusting two-dimensional deflection angles. The structural parameters of the adjusting target mechanism are analyzed according to principle errors, structure errors and motion errors of following. The analysis results indicate that the system error of the adjusting target mechanism is influenced by the displacement of the linear actuators, the actuator ball radius, the working radius of the tangent mechanism, the angle error of the inclined installation hole, the centralization error of the actuators, the orthogonal error of the two tangent mechanism, and the angle errors of the inclined target rod inclined rotation shaft. The errors of the inclined target rod and inclined rotation shaft are the two greatest impact factors, the spherical contact error is the next. By means of precise assembly and control system compensation, the accuracy of the adjusting target mechanism can be less than 0.1 mrad. (authors)

  12. Nanovectors for Targeting and Delivery of Therapeutics to HER-2 NEU Positive Breast Cancer Cells

    National Research Council Canada - National Science Library

    Serda, Rita E

    2008-01-01

    Nanofabricated devices designed to carry drug and contrast agents to breast cancer cells are surface modified with targeting moieties that recognize unique or abundantly expressed molecules on the surface of tumor cells...

  13. Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

    Science.gov (United States)

    Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

    2017-07-05

    Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  14. Asymmetric Supercapacitors Based on Reduced Graphene Oxide with Different Polyoxometalates as Positive and Negative Electrodes.

    Science.gov (United States)

    Dubal, Deepak P; Chodankar, Nilesh R; Vinu, Ajayan; Kim, Do-Heyoung; Gomez-Romero, Pedro

    2017-07-10

    Nanofabrication using a "bottom-up" approach of hybrid electrode materials into a well-defined architecture is essential for next-generation miniaturized energy storage devices. This paper describes the design and fabrication of reduced graphene oxide (rGO)/polyoxometalate (POM)-based hybrid electrode materials and their successful exploitation for asymmetric supercapacitors. First, redox active nanoclusters of POMs [phosphomolybdic acid (PMo 12 ) and phosphotungstic acid (PW 12 )] were uniformly decorated on the surface of rGO nanosheets to take full advantage of both charge-storing mechanisms (faradaic from POMs and electric double layer from rGO). The as-synthesized rGO-PMo 12 and rGO-PW 12 hybrid electrodes exhibited impressive electrochemical performances with specific capacitances of 299 (269 mF cm -2 ) and 370 F g -1 (369 mF cm -2 ) in 1 m H 2 SO 4 as electrolyte at 5 mA cm -2 . An asymmetric supercapacitor was then fabricated using rGO-PMo 12 as the positive and rGO-PW 12 as the negative electrode. This rGO-PMo 12 ∥rGO-PW 12 asymmetric cell could be successfully cycled in a wide voltage window up to 1.6 V and hence exhibited an excellent energy density of 39 Wh kg -1 (1.3 mWh cm -3 ) at a power density of 658 W kg -1 (23 mW cm -3 ). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. False-Positive Rate Determination of Protein Target Discovery using a Covalent Modification- and Mass Spectrometry-Based Proteomics Platform

    Science.gov (United States)

    Strickland, Erin C.; Geer, M. Ariel; Hong, Jiyong; Fitzgerald, Michael C.

    2014-01-01

    Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2 % and analysis of the isobaric mass tag (e.g., iTRAQ®) reporter ions used for peptide quantitation. Our results also suggest that technical replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

  16. MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Wald, Abigail I.; Akhtar, Parvez; Munko, Ana C.; Xu, Jingjing; Gibson, Sandra P.; Grandis, Jennifer R.; Ferris, Robert L.; Khan, Saleem A.

    2015-01-01

    Squamous cell carcinoma of the head and neck (SCCHN) remains a prevalent and devastating disease. Recently, there has been an increase in SCCHN cases that are associated with high-risk human papillomavirus (HPV) infection. The clinical characteristics of HPV-positive and HPV-negative SCCHN are known to be different but their molecular features are only recently beginning to emerge. MicroRNAs (miRNAs, miRs) are small, non-coding RNAs that are likely to play significant roles in cancer initiation and progression where they may act as oncogenes or tumor suppressors. Previous studies in our laboratory showed that miR-363 is overexpressed in HPV-positive compared to HPV-negative SCCHN cell lines, and the HPV type 16-E6 oncoprotein upregulates miR-363 in SCCHN cell lines. However, the functional role of miR-363 in SCCHN in the context of HPV infection remains to be elucidated. We analyzed miR-363 levels in SCCHN tumors with known HPV-status from The Cancer Genome Atlas (TCGA) and an independent cohort from our institution. Cell migration studies were conducted following the overexpression of miR-363 in HPV-negative cell lines. Bioinformatic tools and a luciferase reporter assay were utilized to confirm that miR-363 targets the 3’-UTR of myosin 1B (MYO1B). MYO1B mRNA and protein expression levels were evaluated following miR-363 overexpression in HPV-negative SCCHN cell lines. Small interfering RNA (siRNA) knockdown of MYO1B was performed to assess the phenotypic implication of reduced MYO1B expression in SCCHN cell lines. MiR-363 was found to be overexpressed in HPV-16-positive compared to the HPV-negative SCCHN tumors. Luciferase reporter assays performed in HPV-negative JHU028 cells confirmed that miR-363 targets one of its two potential binding sites in the 3’UTR of MYO1B. MYO1B mRNA and protein levels were reduced upon miR-363 overexpression in four HPV-negative SCCHN cell lines. Increased miR-363 expression or siRNA knockdown of MYO1B expression reduced

  17. Positioning bedridden patients to reduce interface pressures over the sacrum and great trochanter.

    Science.gov (United States)

    Yoshikawa, Y; Maeshige, N; Sugimoto, M; Uemura, M; Noguchi, M; Terashi, H

    2015-07-01

    In this study, we evaluated the effect of hip-joint rotation on the interface pressure over the sacrum and greater trochanter with a new protocol for positioning of bedridden elderly patients. The interface pressure values over the sacrum and greater trochanter in bedridden patients were evaluated. These were collected in the supine position, 90° lateral position, and 30° and 40° laterally inclined positions with external rotation or neutral positioning of the hip joint. Each interface pressure was assessed with a device measuring pressure distribution, after which, the peak pressure index (PPI) was calculated. In the 17 patients examined, the PPI over the sacrum in the supine position was significantly greater than that in other positions. In the 30° and 40° laterally inclined positions, the PPIs over the greater trochanter were significantly lower in the neutral position of the hip joint compared with those in the external rotation position. Our findings revealed the effects of hip-joint rotation on the interface pressure for the greater trochanter, possibly due to the increased distance between the greater trochanter and the sacrum caused by neutral position of the hip joint. The results demonstrate that it is to best place the hip joint in a neutral position when the legs are in contact with the bed in order to distribute the pressure over the greater trochanter in the 30° and 40° laterally inclined positions. These results can be applied to the clinical setting to improve patient positioning and decrease pressure ulcers. The authors declare that they have no competing financial interests.

  18. Reduced positive affect (anhedonia) is independently associated with 7-year mortality in patients treated with percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Damen, Nikki L; Pelle, Aline J; Boersma, Eric

    2013-01-01

    Negative mood states (e.g., anxiety and depression) have been associated with increased cardiovascular morbidity and mortality in coronary artery disease (CAD), but little is known about the impact of positive emotions on these health outcomes. We examined whether anhedonia (i.e., reduced positive...

  19. SU-F-T-644: Reproducibility of Target Position Using Moderate Voluntary Breath- Hold During Liver Stereotactic Ablative Radiotherapy

    International Nuclear Information System (INIS)

    Cui, G; Trakul, N; Chang, E; Shiu, A

    2016-01-01

    Purpose: To evaluate the reproducibility of target position using moderate voluntary breath-hold during liver stereotactic ablative radiotherapy (SABR). Methods: Two patients who underwent liver SABR on a Varian TrueBeam STx linac were used for this study. Fiducial markers were placed in and around the target in the liver as surrogates for the target position and motion. GTVs were contoured by assessing tumor extent on contrast enhanced CT. The PTV was created from the GTV by adding 2 mm margins to account for the residual motion during breath-holds. A portable biofeedback system was used to facilitate the breath-hold to a reproducible position. The Varian RPM system was used for gating the linac. Proceeding each treatment, orthogonal kV pairs were taken, and alignment to nearby bony anatomy was performed. Then the breath-hold CBCT was acquired to align the fiducial markers. On-line fluoroscopy was used to fine-tune the breath-hold gating thresholds to correlate with the positions of the fiducial markers. The inter-fraction reproducibility of the target was evaluated by the offsets of the daily breath-hold CBCTs from the paired kV matches as a direct measure of the target position relative to the bony anatomy. The intra-fraction reproducibility of the target position was assessed by the gated window of the RPM marker block for each fraction. Results: The absolute mean offsets between the CBCT and paired kV matches in the vertical, longitudinal, and lateral directions were 0.06 cm, 0.10 cm, and 0.06 cm for patient 1, and 0.37 cm, 0.62 cm, and 0.09 cm for patient 2. The gated window of the RPM marker block for the breath-hold for each fraction was within 0.63 ± 0.16 cm and 0.59 ± 0.12 cm for patients 1 and 2, respectively. Conclusion: Moderate voluntary breath-hold showed good inter- and intra-fraction reproducibility of target position during liver SABR.

  20. SU-F-T-644: Reproducibility of Target Position Using Moderate Voluntary Breath- Hold During Liver Stereotactic Ablative Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Cui, G; Trakul, N; Chang, E; Shiu, A [University Southern California, Los Angeles, CA (United States)

    2016-06-15

    Purpose: To evaluate the reproducibility of target position using moderate voluntary breath-hold during liver stereotactic ablative radiotherapy (SABR). Methods: Two patients who underwent liver SABR on a Varian TrueBeam STx linac were used for this study. Fiducial markers were placed in and around the target in the liver as surrogates for the target position and motion. GTVs were contoured by assessing tumor extent on contrast enhanced CT. The PTV was created from the GTV by adding 2 mm margins to account for the residual motion during breath-holds. A portable biofeedback system was used to facilitate the breath-hold to a reproducible position. The Varian RPM system was used for gating the linac. Proceeding each treatment, orthogonal kV pairs were taken, and alignment to nearby bony anatomy was performed. Then the breath-hold CBCT was acquired to align the fiducial markers. On-line fluoroscopy was used to fine-tune the breath-hold gating thresholds to correlate with the positions of the fiducial markers. The inter-fraction reproducibility of the target was evaluated by the offsets of the daily breath-hold CBCTs from the paired kV matches as a direct measure of the target position relative to the bony anatomy. The intra-fraction reproducibility of the target position was assessed by the gated window of the RPM marker block for each fraction. Results: The absolute mean offsets between the CBCT and paired kV matches in the vertical, longitudinal, and lateral directions were 0.06 cm, 0.10 cm, and 0.06 cm for patient 1, and 0.37 cm, 0.62 cm, and 0.09 cm for patient 2. The gated window of the RPM marker block for the breath-hold for each fraction was within 0.63 ± 0.16 cm and 0.59 ± 0.12 cm for patients 1 and 2, respectively. Conclusion: Moderate voluntary breath-hold showed good inter- and intra-fraction reproducibility of target position during liver SABR.

  1. Interactive "Video doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings

    OpenAIRE

    Gilbert, P; Ciccarone, D; Gansky, SA; Bangsberg, DR; Clanon, K; McPhee, SJ; Calderón, SH; Bogetz, A; Gerbert, B

    2008-01-01

    Background Reducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission. Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks, it is unknown how to best provide “prevention with positives” in clinical settings. Positive Choice, an interactive, patient-tailored computer program, was developed in the United States to improve clinic-based...

  2. CAR T Cells Targeting Podoplanin Reduce Orthotopic Glioblastomas in Mouse Brains.

    Science.gov (United States)

    Shiina, Satoshi; Ohno, Masasuke; Ohka, Fumiharu; Kuramitsu, Shunichiro; Yamamichi, Akane; Kato, Akira; Motomura, Kazuya; Tanahashi, Kuniaki; Yamamoto, Takashi; Watanabe, Reiko; Ito, Ichiro; Senga, Takeshi; Hamaguchi, Michinari; Wakabayashi, Toshihiko; Kaneko, Mika K; Kato, Yukinari; Chandramohan, Vidyalakshmi; Bigner, Darell D; Natsume, Atsushi

    2016-03-01

    Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults with a 5-year overall survival rate of less than 10%. Podoplanin (PDPN) is a type I transmembrane mucin-like glycoprotein, expressed in the lymphatic endothelium. Several solid tumors overexpress PDPN, including the mesenchymal type of GBM, which has been reported to present the worst prognosis among GBM subtypes. Chimeric antigen receptor (CAR)-transduced T cells can recognize predefined tumor surface antigens independent of MHC restriction, which is often downregulated in gliomas. We constructed a lentiviral vector expressing a third-generation CAR comprising a PDPN-specific antibody (NZ-1-based single-chain variable fragment) with CD28, 4-1BB, and CD3ζ intracellular domains. CAR-transduced peripheral blood monocytes were immunologically evaluated by calcein-mediated cytotoxic assay, ELISA, tumor size, and overall survival. The generated CAR T cells were specific and effective against PDPN-positive GBM cells in vitro. Systemic injection of the CAR T cells into an immunodeficient mouse model inhibited the growth of intracranial glioma xenografts in vivo. CAR T-cell therapy that targets PDPN would be a promising adoptive immunotherapy to treat mesenchymal GBM. ©2016 American Association for Cancer Research.

  3. MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.

    Science.gov (United States)

    Lu, Yunqi; Hu, Zhongyi; Mangala, Lingegowda S; Stine, Zachary E; Hu, Xiaowen; Jiang, Dahai; Xiang, Yan; Zhang, Youyou; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; DeMarzo, Angelo M; Sood, Anil K; Zhang, Lin; Dang, Chi V

    2018-01-01

    The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers. Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Reducing HIV infection in people who inject drugs is impossible without targeting recently-infected subjects.

    Science.gov (United States)

    Vasylyeva, Tetyana I; Friedman, Samuel R; Lourenco, Jose; Gupta, Sunetra; Hatzakis, Angelos; Pybus, Oliver G; Katzourakis, Aris; Smyrnov, Pavlo; Karamitros, Timokratis; Paraskevis, Dimitrios; Magiorkinis, Gkikas

    2016-11-28

    Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

  5. Methane - quick fix or tough target? New methods to reduce emissions.

    Science.gov (United States)

    Nisbet, E. G.; Lowry, D.; Fisher, R. E.; Brownlow, R.

    2016-12-01

    Methane is a cost-effective target for greenhouse gas reduction efforts. The UK's MOYA project is designed to improve understanding of the global methane budget and to point to new methods to reduce future emissions. Since 2007, methane has been increasing rapidly: in 2014 and 2015 growth was at rates last seen in the 1980s. Unlike 20thcentury growth, primarily driven by fossil fuel emissions in northern industrial nations, isotopic evidence implies present growth is driven by tropical biogenic sources such as wetlands and agriculture. Discovering why methane is rising is important. Schaefer et al. (Science, 2016) pointed out the potential clash between methane reduction efforts and food needs of a rising, better-fed (physically larger) human population. Our own work suggests tropical wetlands are major drivers of growth, responding to weather changes since 2007, but there is no acceptable way to reduce wetland emission. Just as sea ice decline indicates Arctic warming, methane may be the most obvious tracker of climate change in the wet tropics. Technical advances in instrumentation can do much in helping cut urban and industrial methane emissions. Mobile systems can be mounted on vehicles, while drone sampling can provide a 3D view to locate sources. Urban land planning often means large but different point sources are typically clustered (e.g. landfill or sewage plant near incinerator; gas wells next to cattle). High-precision grab-sample isotopic characterisation, using Keeling plots, can separate source signals, to identify specific emitters, even where they are closely juxtaposed. Our mobile campaigns in the UK, Kuwait, Hong Kong and E. Australia show the importance of major single sources, such as abandoned old wells, pipe leaks, or unregulated landfills. If such point sources can be individually identified, even when clustered, they will allow effective reduction efforts to occur: these can be profitable and/or improve industrial safety, for example in the

  6. Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells

    Czech Academy of Sciences Publication Activity Database

    Ohradanova-Repic, A.; Nogueira, E.; Hartl, I.; Gomes, A.C.; Preto, A.; Steinhuber, E.; Muehlgrabner, V.; Repic, M.; Kuttke, M.; Zwirzitz, A.; Prouza, M.; Suchánek, M.; Wozniak-Knopp, G.; Hořejší, Václav; Schabbauer, G.; Cavaco-Paulo, A.; Stockinger, H.

    2018-01-01

    Roč. 14, č. 1 (2018), s. 123-130 ISSN 1549-9634 Institutional support: RVO:68378050 Keywords : Active targeting * Liposome functionalization * Immunoliposome * Antibody engineering * Recombinant Fab antibody fragment Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 5.720, year: 2016

  7. Structural biology. Structures of the CRISPR-Cmr complex reveal mode of RNA target positioning

    NARCIS (Netherlands)

    Taylor, D.W.; Zhu, Y.; Staals, R.H.J.; Kornfeld, J.E.; Shinkai, A.; Oost, van der J.; Nogales, E.; Doudna, J.A.

    2015-01-01

    Adaptive immunity in bacteria involves RNA-guided surveillance complexes that use CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR RNAs (crRNAs) to target invasive nucleic acids for degradation. Whereas type I and type II CRISPR-Cas

  8. [{sup 177}Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Mikael; Gedda, Lars [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Experimental Urology, Rudbeck Laboratory, Uppsala (Sweden); Tolmachev, Vladimir; Andersson, Karl; Carlsson, Joergen [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University, Medical Radiation Physics, Uppsala University Hospital, Uppsala (Sweden)

    2005-12-01

    The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter {sup 177}Lu and to make initial characterisations in vitro and in vivo. Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A{sup ''}-DTPA and chelated to {sup 177}Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of {sup 177}Lu was determined 1, 3 and 7 days after [{sup 177}Lu]pertuzumab administration. Gamma camera images were taken after 3 days. The immunoreactivity of [{sup 177}Lu]pertuzumab was 85.8{+-}1.3%. The affinity of non-radioactive pertuzumab was 1.8{+-}1.1 nM, and that of [{sup 177}Lu]pertuzumab, 4.1{+-}0.7 nM. The cellular retention after 5 h pre-incubation was 90{+-}2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of {sup 177}Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. Pertuzumab was efficiently labelled with {sup 177}Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [{sup 177}Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy. (orig.)

  9. Resonant leadership and workplace empowerment: the value of positive organizational cultures in reducing workplace incivility.

    Science.gov (United States)

    Laschinger, Heather K Spence; Wong, Carol A; Cummings, Greta G; Grau, Ashley L

    2014-01-01

    Nursing leaders are indispensable in creating positive nursing work environments that retain an empowered and satisfied nursing workforce. Positive and supportive leadership styles can lower patient mortality and improve nurses' health, job satisfaction, organizational commitment, emotional exhaustion, and intent to stay in their position. The results of this study support the role of positive leadership approaches that empower nurses and discourage workplace incivility and burnout in nursing work environments. The findings also provide empirical support for the notion of resonant leadership, a relatively new theory of relationship-focused leadership approaches. This research adds to the growing body of knowledge documenting the key role of positive leadership practices in creating healthy work environments that promote retention of nurses in a time of a severe nursing shortage.

  10. Positive Affect Is Associated With Reduced Fixation in a Realistic Medical Simulation.

    Science.gov (United States)

    Crane, Monique F; Brouwers, Sue; Forrest, Kirsty; Tan, Suyin; Loveday, Thomas; Wiggins, Mark W; Munday, Chris; David, Leila

    2017-08-01

    This study extends previous research by exploring the association between mood states (i.e., positive and negative affect) and fixation in practicing anesthetists using a realistic medical simulation. The impact of practitioner emotional states on fixation is a neglected area of research. Emerging evidence is demonstrating the role of positive affect in facilitating problem solving and innovation, with demonstrated implications for practitioner fixation. Twelve practicing anesthetists (4 females; M age = 39 years; SD = 6.71) were involved in a medical simulation. Prior to the simulation, practitioners rated the frequency they had experienced various positive and negative emotions in the previous three days. During the simulation, the patient deteriorated rapidly, and anesthetists were observed for their degree of fixation. After the simulation, practitioners indicated the frequency of these same emotions during the simulation. Nonparametric correlations were used to explore the independent relationships between positive and negative affect and the behavioral measures. Only positive affect impacted the likelihood of fixation. Anesthetists who reported more frequent recent positive affect in the three days prior to the simulation and during the simulation tended to be less fixated as judged by independent raters, identified a decline in patient oxygen saturation more quickly, and more rapidly implemented the necessary intervention (surgical cricothyroidotomy). These findings have some real-world implications for positive affect in patient safety. This research has broad implications for professions where fixation may impair practice. This research suggests that professional training should teach practitioners to identify their emotions and understand the role of these emotions in fixation.

  11. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-04-17

    Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

  12. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

    International Nuclear Information System (INIS)

    Liu, Shikai; Song, Lili; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-01-01

    Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1

  13. Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

    Science.gov (United States)

    Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

    2017-11-01

    It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  14. Analisis Segmenting, Targeting, Positioning dan Marketing Mix pada Pt.murni Jaya

    OpenAIRE

    Widjaya, Pieter Gunawan

    2017-01-01

    Persaingan bisnis kecap di pasar domestik yang semakin kompetitif merupakan dampak dari banyaknya pemain baru yang sudah ikut ambil bagian di industri ini. Dalam penelitian ini, objek yang diteliti adalah PT.Murni Jaya, yaitu salah satu Perusahaan keluarga penghasil kecap di Kediri. Tujuan dari penelitian ini adalah untuk menganalisis mengenai segmen, target, dan posisi pasar serta bauran pemasaran PT.Murni Jaya. Metode penelitian ini adalah kualitatif, dengan menggunakan metode studi kasus d...

  15. Polymer–lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells

    Directory of Open Access Journals (Sweden)

    Li J

    2017-09-01

    Full Text Available Jun Li,1,* Wenqing Xu,2,* Xiaoli Yuan,3,* Huaiwen Chen,3 Hao Song,1,4 Bingquan Wang,5 Jun Han5 1College of Pharmacy, Liaocheng University, Liaocheng, Shandong, 2Railway Police College, Zhengzhou, 3Department of Cadre Health Care, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, 4Centre for Stem Cell & Regenerative Medicine, Liaocheng People’s Hospital, 5Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong, China *These authors contributed equally to this work Purpose: Breast cancer stem cells (CSCs are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer–lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2 to target both HER2-positive breast CSCs and cancer cells.Methods: The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer–lipid salinomycin nanoparticles was evaluated in vitro and in vivo.Results: Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.Conclusion: Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells. Keywords: nanoparticles, breast cancer, cancer stem cells, salinomycin, HER2

  16. Glycopolymer micelles with reducible ionic cores for hepatocytes-targeting delivery of DOX.

    Science.gov (United States)

    Wang, Yanxia; Zhang, Xinge; Yu, Peien; Li, Chaoxing

    2013-01-30

    A novel galactose-decorated cross-linked micelles (cl-micelles) with ionic cores using cystamine (Cys) as a biodegradable cross-linker was prepared by using block ionomer complexes of poly(ethylene glycol)-b-poly(2-acryloxyethyl-galactose)-b-poly(acrylic acid) (PEG-b-PAEG-b-PAA) and Ca(2+) (PEG-b-PAEG-b-PAA cl-micelles/Cys). Doxorubicin (DOX) was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. Proton nuclear magnetic resonance spectrum and Fourier transform infrared spectrometer indicated galactose ligands were exposed at the micellar surface. The micelles were spherical in shape, with an average size of 100nm. The in vitro release studies confirmed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys accomplished rapid drug release under reducing condition. Remarkably, PEG-b-PAEG-b-PAA cl-micelles/Cys efficiently delivered and released DOX into the cell nucleus of HepG2 cells, and the intensity of fluorescence observed in HepG2 cells was stronger than that incubated with the micelles without galactose ligands. In contrast, little fluorescence was observed in NIH3T3 cells after incubation with PEG-b-PAEG-b-PAA cl-micelles/Cys. Interestingly, cytotoxicity assays showed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys retained higher cell inhibition efficiency in HepG2 cells as compared with NIH3T3 cells, and were more potent than the micelles without galactose ligands and the micelles with non degradable cross-links. These results indicate that PEG-b-PAEG-b-PAA cl-micelles/Cys have great potential in liver tumor-targeted chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. The positive effect of targeted marketing on an existing uterine fibroid embolization practice.

    Science.gov (United States)

    Chrisman, Howard B; Basu, Pat Auveek; Omary, Reed A

    2006-03-01

    Although uterine fibroid embolization is an effective treatment option for symptomatic women, it is unclear what methods can be used to expand referrals in an already established practice. The authors tested the hypothesis that an advertising strategy focused on a defined target market can expand an existing uterine fibroid embolization practice. A market-driven planning sequence was employed. This included a determination of goals, an examination of current competition, determination of target market based on local environment and previous consumer use, pretest of product sample, and implementation of advertisement. Based on the analysis the authors determined that the target audience was professional black women aged 35 to 45. A specific weekly magazine was selected due to readership demographics. An advertisement was run for 8 consecutive weeks. The authors prospectively tracked patient inquiries, clinic visits, cases performed, and revenues generated for 3 months following the initial advertisement. All patients were seen in a fully staffed, preexisting fibroid clinic located within an urban, university-based academic practice performing 250 uterine fibroid embolizations annually. Ninety calls were received directly related to the advertisement. There were 35 clinic visits, which resulted in 17 uterine fibroid embolizations and 52 total MR imaging procedures. Eighteen patients were not considered candidates based on established protocols. The 17 extra cases performed over 3 months represented a 27% increase in case volume. Total professional cash collections for these cases (including MR imaging) were 58,317 US dollars. The cost of advertising was 8,000 US dollars. As a result of existing infrastructure, no additional costs were necessary. This resulted in a net revenue gain 50,317 US dollars and a nonannualized rate of return of approximately 625%. As Interventional Radiologists look to develop and expand existing practices, traditional marketing tools such as

  18. A novel respiratory motion compensation strategy combining gated beam delivery and mean target position concept - A compromise between small safety margins and long duty cycles

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Kavanagh, Anthony; Webb, Steve; Brada, Michael

    2011-01-01

    Purpose: To evaluate a novel respiratory motion compensation strategy combining gated beam delivery with the mean target position (MTP) concept for pulmonary stereotactic body radiotherapy (SBRT). Materials and methods: Four motion compensation strategies were compared for 10 targets with motion amplitudes between 6 mm and 31 mm: the internal target volume concept (plan ITV ); the MTP concept where safety margins were adapted based on 4D dose accumulation (plan MTP ); gated beam delivery without margins for motion compensation (plan gated ); a novel approach combining gating and the MTP concept (plan gated and MTP ). Results: For 5/10 targets with an average motion amplitude of 9 mm, the differences in the mean lung dose (MLD) between plan gated and plan MTP were gated and MTP . Despite significantly shorter duty cycles, plan gated reduced the MLD by gated and MTP . The MLD was increased by 18% in plan MTP compared to that of plan gated and MTP . Conclusions: For pulmonary targets with motion amplitudes >10-15 mm, the combination of gating and the MTP concept allowed small safety margins with simultaneous long duty cycles.

  19. Mirror position display equipment for the target chamber mirror mounts of the LASL HELIOS laser fusion facility

    International Nuclear Information System (INIS)

    Wells, F.D.; Remington, D.A.

    1979-01-01

    Equipment has been fabricated which records the absolute positions of sixteen mirror mounts used to direct and focus eight high-energy laser beams for research in laser induced fusion. Each mirror mount is driven by three stepping motors, controlled to produce the motions of Focus, Tilt, and Rotate relative to the target. Stepping of the motors is sensed by incremental optical encoders coupled to the motor drive shafts. Outputs from the encoder tracks are multiplexed to a microprocessor which transmits motor step information via a fiber optical data link to a Mirror Position Display chassis. This unit accumulates the steps, stores the motor positions, displays mirror position data to the operator, and provides the equipment control functions. Standby battery power is included to retain the motor step data in the event of power failure

  20. Branding MBA Programs: The Use of Target Market Desired Outcomes for Effective Brand Positioning

    Science.gov (United States)

    Heslop, Louise A.; Nadeau, John

    2010-01-01

    Branding is about delivering on desired outcomes. The importance of positioning program offerings on the basis of outcomes sought in the education market is illustrated in this study of choice of an MBA program by prospective students. MBA fair attendees were surveyed and multiple methods were employed to determine the importance of desired…

  1. Maintenance Strategies to Reduce Downtime Due to\\ud Machine Positional Errors

    OpenAIRE

    Shagluf, Abubaker; Longstaff, Andrew P.; Fletcher, Simon

    2014-01-01

    Manufacturing strives to reduce waste and increase\\ud Overall Equipment Effectiveness (OEE). When managing machine tool maintenance a manufacturer must apply an appropriate decision technique in order to reveal hidden costs associated with production losses, reduce equipment downtime\\ud competently and similarly identify the machines’ performance.\\ud Total productive maintenance (TPM) is a maintenance program that involves concepts for maintaining plant and equipment effectively. OEE is a pow...

  2. Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists.

    Science.gov (United States)

    Fevre, Marie-Cécile; Vincent, Caroline; Picard, Julien; Vighetti, Arnaud; Chapuis, Claire; Detavernier, Maxime; Allenet, Benoît; Payen, Jean-François; Bosson, Jean-Luc; Albaladejo, Pierre

    2018-02-01

    Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professional's ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety. Three groups of healthcare professionals (41 anaesthesiologists and intensivists, 41 residents in anaesthesiology and intensive care, 39 nurse anaesthetists) were included and required to perform 3 tasks (positioning the tip of a needle in three different targets in a silicon phantom) by using successively a conventional US-guided needle positioning and a needle GPS. We measured execution times to perform the tasks, hand-eye coordination and the number of repositioning occurrences or errors in handling the needle or the probe. Without the GPS system, we observed a significant inter-individual difference for execution time (Pgaming were found to be independent factors associated with a shorter execution time. Use of GPS attenuated the inter-individual and group variability. We observed a reduced execution time and improved hand-eye coordination in all groups as compared to US without GPS. Neither US training, video gaming nor demographic personal or professional factors were found to be significantly associated with reduced execution time when GPS was used. US associated with GPS systems may improve safety and decrease execution time by reducing inter-individual variability between professionals for needle-handling procedures. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  3. Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective Matrix Metalloproteinase Inhibitor.

    Science.gov (United States)

    Fischer, Thomas; Riedl, Rainer

    2017-04-01

    Invited for this month's cover picture is the group of Professor Rainer Riedl from the Institute of Chemistry and Biotechnology at the Zurich University of Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure-based design of a drug-like small molecule inhibitor of matrix metalloproteinase-13 (MMP-13) with a combined dual binding motif. The targeted introduction of a single fluoro atom was of vital importance for the optimization of the inhibitor. For more details, read the full text of the Communication at 10.1002/open.201600158.

  4. Trait anxiety reduces affective fading for both positive and negative autobiographical memories.

    Science.gov (United States)

    Walker, W Richard; Yancu, Cecile N; Skowronski, John J

    2014-01-01

    The affect associated with negative events fades faster than the affect associated with positive events (the Fading Affect Bias; the FAB). The research that we report examined the relation between trait anxiety and the FAB. Study 1 assessed anxiety using the Depression, Anxiety, and Stress Scale; Studies 2 and 3 used the Beck Anxiety Inventory. Studies 1 and 2 used retrospective procedures to probe positive event memories and negative event memories while Study 3 used a diary procedure. The results of all 3 studies showed that increased anxiety was associated with both a lowered FAB and lower overall affect fading for both positive events and negative events. These results suggest that for people free of trait anxiety, the FAB reflects the operation of a healthy coping mechanism in autobiographical memory that is disrupted by trait anxiety.

  5. The position of the targets of the public health policy of maternal and child in Bandung

    Science.gov (United States)

    Sugyati, C.; Mariana, D.; Sjoraida, D. F.

    2018-03-01

    This study seeks to make a deep, systematic analysis of the urgency of implementing elements in the implementation of public health policies, especially in the field of mother and child in Bandung City, West Java. This study is important to evaluate whether the government services on maternal and child health is sufficient or not. With the descriptive-qualitative method, this study presents a discussion of how the implementers interact with the community as their targets in implementing public health programs in Bandung City so that their presence is indispensable. With theories of implementation of policies and health campaign, the data was obtained and showed that (a) the unity of the coordination and uniformity of information services, and a network of cooperation in public health institutions, in the Government of Bandung City, have been performed well; (b) in getting their rights the targets are highly motivated for the services of public health and some of them function to be the volunteers to assist local health policy implementers. However, the lack of health care workers who were directly addressing maternal and child health was perceived by the public so well that this study recommends the convening of additional formal health workers in the community.

  6. Simulations of beam trajectory for position target optimization of extraction system output beams cyclotron proton Decy-13

    International Nuclear Information System (INIS)

    Idrus Abdul Kudus; Taufik

    2015-01-01

    Positioning and track simulation beam the cyclotron Decy-13 for laying optimization the target system have been done using lorentz force function and scilab 5.4.1 simulation. Magnetic field and electric field is calculated using Opera3D/Tosca as a simulation input. Used radio frequency is 77.66 MHz with the amplitude voltage is 40 kV is obtained energy 13 MeV. The result showed that the coordinates of the laying of the target system in a vacuum chamber is located at x = -389 mm and y = 445 mm with the width of the output beam is 10 mm. The laying stripper position for the output in center target is located at x = -76 mm and y =416 mm from the center coordinate on the center of dee with the energy of proton is 13 MeV at the point of beam extraction carbon foil. The changes position laying is carried out on range x = -70; y = 424 mm until x = - 118; y = 374 mm result for shifting area stripper which is still capable of deflection the electron beam. (author)

  7. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure.

    Science.gov (United States)

    Nutt, David; Demyttenaere, Koen; Janka, Zoltan; Aarre, Trond; Bourin, Michel; Canonico, Pier Luigi; Carrasco, Jose Luis; Stahl, Steven

    2007-07-01

    Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.

  8. [A project to reduce the incidence of facial pressure ulcers caused by prolonged surgery with prone positioning].

    Science.gov (United States)

    Lee, Wen-Yi; Lin, Pao-Chen; Weng, Chia-Hsing; Lin, Yi-Lin; Tsai, Wen-Lin

    2012-06-01

    We observed in our institute a 13.6% incidence of prolonged surgery (>4 hours) induced facial pressure ulcers that required prone positioning. Causes identified included: (1) customized silicon face pillows used were not suited for every patient; (2) our institute lacked a standard operating procedure for prone positioning; (3) our institute lacked a postoperative evaluation and audit procedure for facial pressure ulcers. We designed a strategy to reduce post-prolonged surgery facial pressure ulcer incidence requiring prone positioning by 50% (i.e., from 13.6% to 6.8%). We implemented the following: (1) Created a new water pillow to relieve facial pressure; (2) Implemented continuing education pressure ulcer prevention and evaluation; (3) Established protocols on standard care for prone-position patients and proper facial pressure ulcer identification; (4) Established a face pressure ulcers accident reporting mechanism; and (5) Established an audit mechanism facial pressure ulcer cases. After implementing the resolution measures, 116 patients underwent prolonged surgery in a prone position (mean operating time: 298 mins). None suffered from facial pressure ulcers. The measures effectively reduced the incidence of facial pressure ulcers from 13.6% to 0.0%. The project used a water pillow to relieve facial pressure and educated staff to recognize and evaluate pressure ulcers. These measures were demonstrated effective in reducing the incidence of facial pressure ulcers caused by prolonged prone positioning.

  9. Understanding Antipsychotic Drug Treatment Effects: A Novel Method to Reduce Pseudospecificity of the Positive and Negative Syndrome Scale (PANSS) Factors.

    Science.gov (United States)

    Hopkins, Seth C; Ogirala, Ajay; Loebel, Antony; Koblan, Kenneth S

    2017-12-01

    The Positive and Negative Syndrome Scale (PANSS) is the most widely used efficacy measure in acute treatment studies of schizophrenia. However, interpretation of the efficacy of antipsychotics in improving specific symptom domains is confounded by moderate-to-high correlations among standard (Marder) PANSS factors. The authors review the results of an uncorrelated PANSS score matrix (UPSM) transform designed to reduce pseudospecificity in assessment of symptom change in patients with schizophrenia. Based on a factor analysis of five pooled, placebo-controlled lurasidone clinical trials (N=1,710 patients), a UPSM transform was identified that generated PANSS factors with high face validity (good correlation with standard Marder PANSS factors), and high specificity/orthogonality (low levels of between-factor correlation measuring change during treatment). Between-factor correlations were low at baseline for both standard (Marder) PANSS factors and transformed PANSS factors. However, when measured change in symptom severity was measured during treatment (in a pooled 5-study analysis), there was a notable difference for standard PANSS factors, where changes across factors were found to be highly correlated (factors exhibited pseudospecificity), compared to transformed PANSS factors, where factor change scores exhibited the same low levels of between-factor correlation observed at baseline. At Week 6-endpoint, correlations among PANSS factor severity scores were moderate-to-high for standard factors (0.34-0.68), but continued to be low for the transformed factors (-0.22-0.20). As an additional validity check, we analyzed data from one of the original five pooled clinical trials that included other well-validated assessment scales (MADRS, Negative Symptom Assessment scale [NSA]). In this baseline analysis, UPSM-transformed PANSS factor severity scores (negative and depression factors) were found to correlate well with the MADRS and NSA. The availability of transformed

  10. Improved laser-to-proton conversion efficiency in isolated reduced mass targets

    Energy Technology Data Exchange (ETDEWEB)

    Morace, A. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Bellei, C.; Patel, P. K. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (United States); Bartal, T.; Kim, J.; Beg, F. N. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); Willingale, L.; Maksimchuk, A.; Krushelnick, K. [University of Michigan, 2200 Bonisteel Blvd. Ann Arbor, Michigan 48109 (United States); Wei, M. S. [Center for Energy Research, University of California, 9500 Gilman Drive, La Jolla, California 92093 (United States); General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States); Batani, D. [Univ. Bordeaux, CNRS, CEA, CELIA (Centre Lasers Intenses et Applications), UMR 5107, F-33405 Talence (France); Piovella, N. [Dipartimento di Fisica, Università degli Studi di Milano, via Celoria 16, 20133 Milano (Italy); Stephens, R. B. [General Atomics, 3550 General Atomics Court, San Diego, California 92121 (United States)

    2013-07-29

    We present experimental results of laser-to-proton conversion efficiency as a function of lateral confinement of the refluxing electrons. Experiments were carried out using the T-Cubed laser at the Center for Ultrafast Optical Science, University of Michigan. We demonstrate that the laser-to-proton conversion efficiency increases by 50% with increased confinement of the target from surroundings with respect to a flat target of the same thickness. Three-dimensional hybrid particle-in-cell simulations using LSP code agree with the experimental data. The adopted target design is suitable for high repetition rate operation as well as for Inertial Confinement Fusion applications.

  11. A Positive Model for Reducing and Preventing School Burnout in High School Students

    Science.gov (United States)

    Aypay, Ayse

    2017-01-01

    This study aims to develop and test the validity of a model limited to attitude towards the future and subjective well-being for reducing and preventing the school burnout that high school students can experience. The study is designed as a relational screening model conducted over 389 high school students. The data in this study are analyzed…

  12. Reducing threats in conversations about environmental behavior change: The positive impact of Motivational Interviewing

    NARCIS (Netherlands)

    Klonek, F.E.; Güntner, A.V.; Lehmann-Willenbrock, N.K.; Kauffeld, S.

    2015-01-01

    Human behavior contributes to a waste of environmental resources and our society is looking for ways to reduce this problem. However, humans may perceive feedback about their environmental behavior as threatening. According to self-determination theory (SDT), threats decrease intrinsic motivation

  13.   Antibiotica Impregnated Shunts effectively reduces positive cultures from External Ventricular Drainage

    DEFF Research Database (Denmark)

    Sørensen, Preben; Gulisano, Helga Angela; Ejlertsen, Tove

    -samples were collected every day. Samples was obtained from the line away from the patient and cultered on agar plates for six days in both aerobic and aerobic environment. VAI was defined as positive cultures in CSF.   Results A total of 485 patients were included. No significant differences in gender, age....... The frequency of VAI differs in the literature between x and 21.1 % depending mainly on methods of diagnosis.     Methods A prospective study with historical controls. From 1.1.2001 to 31.9.2007 patients was treated with standard EVD, and from 1.10.2007 -to 31.9.2008 AIS (Bactiseal, Codman ) was used. CSF...... or diagnosis.   Standard drain: 417 patients. 97 patients had positive CFS-cultures (23.3 %). 10 patients had more than one infection. Most frequent findings was Propionibacterium Acnes, Coagulasenegative Staffyllococci and Staffylococcus Epidermidis accounting for 70,1 % of species.   AIS-drain: 68 patients...

  14. Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer's disease.

    Science.gov (United States)

    Mistridis, Panagiota; Taylor, Kirsten I; Kissler, Johanna M; Monsch, Andreas U; Kressig, Reto W; Kivisaari, Sasa L

    2013-01-01

    Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g., autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer's disease (AD), which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14), patients with AD (n = 15) and its putative prodrome amnestic mild cognitive impairment (n = 11) completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies.

  15. Promoting Social Nurturance and Positive Social Environments to Reduce Obesity in High-Risk Youth.

    Science.gov (United States)

    Wilson, Dawn K; Sweeney, Allison M; Kitzman-Ulrich, Heather; Gause, Haylee; St George, Sara M

    2017-03-01

    Nurturing environments within the context of families, schools, and communities all play an important role in enhancing youth's behavioral choices and health outcomes. The increasing prevalence rates of obesity among youth, especially among low income and ethnic minorities, highlight the need to develop effective and innovative intervention approaches that promote positive supportive environments across different contexts for at-risk youth. We propose that the integration of Social Cognitive Theory, Family Systems Theory, and Self-Determination Theory offers a useful framework for understanding how individual, family, and social-environmental-level factors contribute to the development of nurturing environments. In this paper, we summarize evidence-based randomized controlled trials that integrate positive parenting, motivational, and behavioral skills strategies in different contexts, including primary care, home, community, and school-based settings. Taken together, these studies suggest that youth and parents are most likely to benefit when youth receive individual-level behavioral skills, family-level support and communication, and autonomous motivational support from the broader social environment. Future investigators and healthcare providers should consider integrating these evidence-based approaches that support the effects of positive social climate-based interventions on promoting healthy eating, physical activity, and weight management in youth.

  16. Respiratory gating during stereotactic body radiotherapy for lung cancer reduces tumor position variability.

    Science.gov (United States)

    Saito, Tetsuo; Matsuyama, Tomohiko; Toya, Ryo; Fukugawa, Yoshiyuki; Toyofuku, Takamasa; Semba, Akiko; Oya, Natsuo

    2014-01-01

    We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images. Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test. The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3-30 mm vs. 2 mm, range 0-4 mm; psimulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.

  17. Promoting Social Nurturance and Positive Social Environments to Reduce Obesity in High Risk Youth

    Science.gov (United States)

    Wilson, Dawn K.; Sweeney, Allison M.; Kitzman-Ulrich, Heather; Gause, Haylee; St. George, Sara M.

    2017-01-01

    Nurturing environments within the context of families, schools, and communities all play an important role in enhancing youth’s behavioral choices and health outcomes. The increasing prevalence rates of obesity among youth, especially among low income and ethnic minorities, highlight the need to develop effective and innovative intervention approaches that promote positive supportive environments across different contexts for at risk youth. We propose that the integration of Social Cognitive Theory, Family Systems Theory, and Self-Determination Theory offers a useful framework for understanding how individual, family and social-environmental level factors contribute to the development of nurturing environments. In this paper, we summarize evidence-based randomized controlled trials that integrate positive parenting, motivational, and behavioral skills strategies in different contexts, including primary care, home, community, and school-based settings. Taken together, these studies suggest that youth and parents are most likely to benefit when youth receive individual-level behavioral skills, family-level support and communication, and autonomous motivational support from the broader social environment. Future investigators and health care providers should consider integrating these evidence-based approaches that support the effects of positive social climate-based interventions on promoting healthy eating, physical activity, and weight management in youth. PMID:28229248

  18. Potential for reducing air-pollutants while achieving 2 °C global temperature change limit target.

    Science.gov (United States)

    Hanaoka, Tatsuya; Akashi, Osamu; Fujiwara, Kazuya; Motoki, Yuko; Hibino, Go

    2014-12-01

    This study analyzes the potential to reduce air pollutants while achieving the 2 °C global temperature change limit target above pre-industrial levels, by using the bottom-up optimization model, AIM/Enduse[Global]. This study focuses on; 1) estimating mitigation potentials and costs for achieving 2 °C, 2.5 °C, and 3 °C target scenarios, 2) assessing co-benefits of reducing air pollutants such as NOx, SO2, BC, PM, and 3) analyzing features of sectoral attributions in Annex I and Non-Annex I groups of countries. The carbon tax scenario at 50 US$/tCO2-eq in 2050 can reduce GHG emissions more than the 3 °C target scenario, but a higher carbon price around 400 US$/tCO2-eq in 2050 is required to achieve the 2 °C target scenario. However, there is also a co-benefit of large reduction potential of air pollutants, in the range of 60-80% reductions in 2050 from the reference scenario while achieving the 2 °C target. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Reducing threats in conversations about environmental behavior change: The positive impact of Motivational Interviewing

    OpenAIRE

    Klonek, F.E.; Güntner, A.V.; Lehmann-Willenbrock, N.K.; Kauffeld, S.

    2015-01-01

    Human behavior contributes to a waste of environmental resources and our society is looking for ways to reduce this problem. However, humans may perceive feedback about their environmental behavior as threatening. According to self-determination theory (SDT), threats decrease intrinsic motivation for behavior change. According to self-affirmation theory (SAT), threats can harm individuals’ self-integrity. Therefore, individuals should show self-defensive biases, e.g., in terms of presenting c...

  20. Wireless Positioning Based on a Segment-Wise Linear Approach for Modeling the Target Trajectory

    DEFF Research Database (Denmark)

    Figueiras, Joao; Pedersen, Troels; Schwefel, Hans-Peter

    2008-01-01

    Positioning solutions in infrastructure-based wireless networks generally operate by exploiting the channel information of the links between the Wireless Devices and fixed networking Access Points. The major challenge of such solutions is the modeling of both the noise properties of the channel...... measurements and the user mobility patterns. One class of typical human being movement patterns is the segment-wise linear approach, which is studied in this paper. Current tracking solutions, such as the Constant Velocity model, hardly handle such segment-wise linear patterns. In this paper we propose...... a segment-wise linear model, called the Drifting Points model. The model results in an increased performance when compared with traditional solutions....

  1. Targeted Radiosensitization of ETS Fusion-Positive Prostate Cancer through PARP1 Inhibition

    Directory of Open Access Journals (Sweden)

    Sumin Han

    2013-10-01

    Full Text Available ETS gene fusions, which result in overexpression of an ETS transcription factor, are considered driving mutations in approximately half of all prostate cancers. Dysregulation of ETS transcription factors is also known to exist in Ewing's sarcoma, breast cancer, and acute lymphoblastic leukemia. We previously discovered that ERG, the predominant ETS family member in prostate cancer, interacts with the DNA damage response protein poly (ADP-ribose polymerase 1 (PARP1 in human prostate cancer specimens. Therefore, we hypothesized that the ERG-PARP1 interaction may confer radiation resistance by increasing DNA repair efficiency and that this radio-resistance could be reversed through PARP1 inhibition. Using lentiviral approaches, we established isogenic models of ERG overexpression in PC3 and DU145 prostate cancer cell lines. In both cell lines, ERG overexpression increased clonogenic survival following radiation by 1.25 (±0.07 fold (mean ± SEM and also resulted in increased PARP1 activity. PARP1 inhibition with olaparib preferentially radiosensitized ERG-positive cells by a factor of 1.52 (±0.03 relative to ERG-negative cells (P < .05. Neutral and alkaline COMET assays and immunofluorescence microscopy assessing γ-H2AX foci showed increased short- and long-term efficiencies of DNA repair, respectively, following radiation that was preferentially reversed by PARP1 inhibition. These findings were verified in an in vivo xenograft model. Our findings demonstrate that ERG overexpression confers radiation resistance through increased efficiency of DNA repair following radiation that can be reversed through inhibition of PARP1. These results motivate the use of PARP1 inhibitors as radiosensitizers in patients with localized ETS fusion-positive cancers.

  2. Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

    Science.gov (United States)

    Busam, Klaus J; Pulitzer, Melissa P; Coit, Daniel C; Arcila, Maria; Leng, Danielle; Jungbluth, Achim A; Wiesner, Thomas

    2017-06-01

    Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.

  3. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    Science.gov (United States)

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  4. Reducing time to identification of positive blood cultures with MALDI-TOF MS analysis after a 5-h subculture.

    Science.gov (United States)

    Verroken, A; Defourny, L; Lechgar, L; Magnette, A; Delmée, M; Glupczynski, Y

    2015-02-01

    Speeding up the turn-around time of positive blood culture identifications is essential in order to optimize the treatment of septic patients. Several sample preparation techniques have been developed allowing direct matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) identification of positive blood cultures. Yet, the hands-on time restrains their routine workflow. In this study, we evaluated an approach whereby MALDI-TOF MS identification without any additional steps was carried out on short subcultured colonies from positive blood bottles with the objective of allowing results reporting on the day of positivity detection. Over a 7-month period in 2012, positive blood cultures detected by 9 am with an automated system were inoculated onto a Columbia blood agar and processed after a 5-h incubation on a MALDI-TOF MicroFlex platform (Bruker Daltonik GmbH). Single-spotted colonies were covered with 1 μl formic acid and 1 μl matrix solution. The results were compared to the validated identification techniques. A total of 925 positive blood culture bottles (representing 470 bacteremic episodes) were included. Concordant identification was obtained in 727 (81.1 %) of the 896 monomicrobial blood cultures, with failure being mostly observed with anaerobes and yeasts. In 17 episodes of polymicrobic bacteremia, the identification of one of the two isolates was achieved in 24/29 (82.7 %) positive cultures. Routine implementation of MALDI-TOF MS identification on young positive blood subcultures provides correct results to the clinician in more than 80 % of the bacteremic episodes and allows access to identification results on the day of blood culture positivity detection, potentially accelerating the implementation of targeted clinical treatments.

  5. Early Pancreatic Ductal Adenocarcinoma Survival Is Dependent on Size: Positive Implications for Future Targeted Screening.

    Science.gov (United States)

    Hur, Chin; Tramontano, Angela C; Dowling, Emily C; Brooks, Gabriel A; Jeon, Alvin; Brugge, William R; Gazelle, G Scott; Kong, Chung Yin; Pandharipande, Pari V

    2016-08-01

    Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies. Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated. A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy. For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

  6. Reducing WI-FI handover delay using a new positioning process

    International Nuclear Information System (INIS)

    Zaidi, M.; Bhar, J.; Tourki, R.

    2011-01-01

    Mobility has now a crucial requirement for wireless communication. Handover is one of the major tasks that are used to support continuous transmission for a mobile terminal into different radio coverage area. Optimizing the existing handover protocol requires integrating new functionalities. This work focuses on presenting and optimizing handover algorithm. We analyze handover time in wireless local area networks based on the IEEE 802.11b MAC protocol. In fact, scan phase is the main contributor to the handover time. Then, we propose a handover model which replaces a scan phase by a positioning process. This model is able to select the suitable access point (AP) based on the shortest distance far from the mobile terminal (MT). Proposed Handover allows a mobile user to reacting quickly to decide about to which access point to connect. Simulation results show that the proposed model provides gains in term of delays and Handover success in various scenarios.

  7. Reducing the environmental impact of hydraulic fracturing through design optimisation of positive displacement pumps

    International Nuclear Information System (INIS)

    Josifovic, Aleksandar; Roberts, Jennifer J.; Corney, Jonathan; Davies, Bruce; Shipton, Zoe K.

    2016-01-01

    The current approach to hydraulic fracturing requires large amounts of industrial hardware to be transported, installed and operated in temporary locations. A significant proportion of this equipment is comprised of the fleet of pumps required to provide the high pressures and flows necessary for well stimulation. Studies have shown that over 90% of the emissions of CO_2 and other pollutants that occur during a hydraulic fracturing operation are associated with these pumps. Pollution and transport concerns are of paramount importance for the emerging hydraulic fracturing industry in Europe, and so it is timely to consider these factors when assessing the design of high pressure pumps for the European resources. This paper gives an overview of the industrial plant required to carry out a hydraulic fracturing operation. This is followed by an analysis of the pump's design space that could result in improved pump efficiency. We find that reducing the plunger diameter and running the pump at higher speeds can increase the overall pump efficiency by up to 4.6%. Such changes to the pump's parameters would results in several environmental benefits beyond the obvious economic gains of lower fuel consumption. The paper concludes with a case study that quantifies these benefits. - Highlights: • We develop a parameterized model of hydraulic fracturing pumps. • We explore performance variation to optimise pump efficiency and performance. • New design could increase pump energy efficiency up to 4.6% and improve reliability. • The new design could also reduce environmental and social impacts of pumping. • This illustrates how optimised mechanical design can lower impacts and cost.

  8. Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients.

    Science.gov (United States)

    Mounier, R; Adrie, C; Français, A; Garrouste-Orgeas, M; Cheval, C; Allaouchiche, B; Jamali, S; Dinh-Xuan, A T; Goldgran-Toledano, D; Cohen, Y; Azoulay, E; Timsit, J-F; Ricard, J-D

    2010-04-01

    The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome. 2,409 prospectively included patients were admitted over 9 yrs (2000-2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios patients on the PP propensity score (+/-10%), MV duration longer than that in PP patients before the first turn prone, and centre. VAP incidence was similar in the PP and control groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39-0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.

  9. Are vehicle travel reduction targets justified? Evaluating mobility management policy objectives such as targets to reduce VMT and increase use of alternative modes

    Energy Technology Data Exchange (ETDEWEB)

    Litman, T.

    2009-09-17

    This article presented several reasons for reforming current transportation policies to include targets to reduce vehicle miles of travel (VMT) and encourage use of alternative modes such as walking, cycling or public transit. Demographic and economic trends are increasing the demand for alternative modes, and economic competitiveness will require increased efficiency. As such, a variety of integrated transportation and land use policy reforms are needed to prepare for the future. Mobility management strategies that reduce vehicle travel include efficient road and parking pricing; more flexible zoning codes; and ridesharing incentives. Most mobility management strategies help solve a variety of problems and provide many benefits, including congestion reduction, road and parking cost savings, consumer savings, traffic safety, improved mobility for non-drivers, energy conservation, emission reductions, efficient land development, and improved public fitness and health. Improvements to public transit, road and parking pricing, and commute trip reduction programs also tend to reduce urban-peak traffic. The article suggested that VMT reduction targets are the first step in implementing mobility management policies. Although automobile travel will not disappear, it will decrease compared with current planning practices. 55 refs., 8 tabs., 6 figs.

  10. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    International Nuclear Information System (INIS)

    Azuma, Koichi; Tsurutani, Junji; Sakai, Kazuko; Kaneda, Hiroyasu; Fujisaka, Yasuhito; Takeda, Masayuki; Watatani, Masahiro; Arao, Tokuzo; Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu; Nishio, Kazuto; Nakagawa, Kazuhiko

    2011-01-01

    Highlights: → A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. → Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. → Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC 50 of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  11. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Koichi [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Tsurutani, Junji, E-mail: tsurutani_j@dotd.med.kindai.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Sakai, Kazuko; Kaneda, Hiroyasu [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Fujisaka, Yasuhito; Takeda, Masayuki [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Watatani, Masahiro [Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Arao, Tokuzo [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan)

    2011-04-01

    Highlights: {yields} A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. {yields} Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. {yields} Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC{sub 50} of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  12. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    International Nuclear Information System (INIS)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A.; Schoot, Agustinus J.A.J. van de; Buist, Marrije R.

    2018-01-01

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V 15Gy , V 30Gy , V 45Gy and D mean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V 15Gy , V 30Gy , V 45Gy and D mean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V 45Gy for bowel bag was >275 cm 3 and >200 cm 3 , respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [de

  13. Predicting residue contacts using pragmatic correlated mutations method: reducing the false positives

    Directory of Open Access Journals (Sweden)

    Alexov Emil G

    2006-11-01

    Full Text Available Abstract Background Predicting residues' contacts using primary amino acid sequence alone is an important task that can guide 3D structure modeling and can verify the quality of the predicted 3D structures. The correlated mutations (CM method serves as the most promising approach and it has been used to predict amino acids pairs that are distant in the primary sequence but form contacts in the native 3D structure of homologous proteins. Results Here we report a new implementation of the CM method with an added set of selection rules (filters. The parameters of the algorithm were optimized against fifteen high resolution crystal structures with optimization criterion that maximized the confidentiality of the predictions. The optimization resulted in a true positive ratio (TPR of 0.08 for the CM without filters and a TPR of 0.14 for the CM with filters. The protocol was further benchmarked against 65 high resolution structures that were not included in the optimization test. The benchmarking resulted in a TPR of 0.07 for the CM without filters and to a TPR of 0.09 for the CM with filters. Conclusion Thus, the inclusion of selection rules resulted to an overall improvement of 30%. In addition, the pair-wise comparison of TPR for each protein without and with filters resulted in an average improvement of 1.7. The methodology was implemented into a web server http://www.ces.clemson.edu/compbio/recon that is freely available to the public. The purpose of this implementation is to provide the 3D structure predictors with a tool that can help with ranking alternative models by satisfying the largest number of predicted contacts, as well as it can provide a confidence score for contacts in cases where structure is known.

  14. Familial hypercholesterolaemia reduces the quality of life of patients not reaching treatment targets

    DEFF Research Database (Denmark)

    Mortensen, Gitte Lee; Madsen, Ivan Bredbjerg; Kruse, Charlotte

    2016-01-01

    are only met in approximately 50% of patients. This comparative study examined the quality of life (QoL) impact of FH in patients who had and had not reached the target of treatment. METHODS: Two qualitative focus group interviews were carried out with a total of ten FH patients. A semi...... of treatment. FUNDING: The study was funded by a research grant from Amgen. TRIAL REGISTRATION: not relevant....

  15. Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods.

    Science.gov (United States)

    Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna

    2014-08-21

    Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

  16. ANALISIS SEGMENTASI, TARGETING, POSITIONING (STP TERHADAP PENINGKATAN VOLUME PENJUALAN PADA RUMAH GRIYA MULYA ASRI DI KOTA MAKASSAR

    Directory of Open Access Journals (Sweden)

    Fitri _

    2017-08-01

    Full Text Available Volume at Griya Mulya Asri House In Makassar City. Guided by DR.Hj.Herminawati Abubakar., S.E., M.M and DR.Haeruddin Saleh., S.E., M.SiHome is a basic human need other than clothing and food. The increasing housing demand for Makassar residents encourages housing developers to provide more viable alternative housing solutions. Griya Mulya Asri Housing Estate is one of the best alternative choice for people who want a relaxed atmosphere amidst the urban bustle. Griya Mulya Asri Housing is very good for the habitable area in terms of price, facilities, comfort and location.This study aims to analyze the strategy of segmentation, targeting, positioning (STP applied by PT Hinda Assalam Brother to increase the sales volume of the house at Griya Mulya Asri. Analyzer used is multiple linear regression. Respondents of this research are Griya Mulya Asri resident. The result of analysis shows that segmentation, targeting, positioning strategy influence to the increase of sales volume.

  17. Guidance and Control of Position and Attitude for Rendezvous and Dock/Berthing with a Noncooperative/Target Spacecraft

    Directory of Open Access Journals (Sweden)

    Gilberto Arantes

    2014-01-01

    Full Text Available Noncooperative target spacecrafts are those assets in orbit that cannot convey any information about their states (position, attitude, and velocities or facilitate rendezvous and docking/berthing (RVD/B process. Designing a guidance, navigation, and control (GNC module for the chaser in a RVD/B mission with noncooperative target should be inevitably solved for on-orbit servicing technologies. The proximity operations and the guidance for achieving rendezvous problems are addressed in this paper. The out-of-plane maneuvers of proximity operations are explored with distinct subphases, including a chaser far approach in the target’s orbit to the first hold point and a closer approach to the final berthing location. Accordingly, guidance solutions are chosen for each subphase from the standard Hill based Closhessy-Willtshire (CW solution, elliptical fly-around, and Glideslope algorithms. The control is based on a linear quadratic regulator approach (LQR. At the final berthing location, attitude tracker based on a proportional derivative (PD form is tested to synchronize the chaser and target attitudes. The paper analyzes the performance of both controllers in terms of the tracking ability and the robustness. Finally, it prescribes any restrictions that may be imposed on the guidance during any subphase which can help to improve the controllers tracking ability.

  18. Nanoparticle targeting of Gram-positive and Gram-negative bacteria for magnetic-based separations of bacterial pathogens

    Science.gov (United States)

    Lu, Hoang D.; Yang, Shirley S.; Wilson, Brian K.; McManus, Simon A.; Chen, Christopher V. H.-H.; Prud'homme, Robert K.

    2017-04-01

    Antimicrobial resistance is a healthcare problem of increasing significance, and there is increasing interest in developing new tools to address bacterial infections. Bacteria-targeting nanoparticles hold promise to improve drug efficacy, compliance, and safety. In addition, nanoparticles can also be used for novel applications, such as bacterial imaging or bioseperations. We here present the use of a scalable block-copolymer-directed self-assembly process, Flash NanoPrecipitation, to form zinc(II)-bis(dipicolylamine) modified nanoparticles that bind to both Gram-positive and Gram-negative bacteria with specificity. Particles have tunable surface ligand densities that change particle avidity and binding efficacy. A variety of materials can be encapsulated into the core of the particles, such as optical dyes or iron oxide colloids, to produce imageable and magnetically active bacterial targeting constructs. As a proof-of-concept, these particles are used to bind and separate bacteria from solution in a magnetic column. Magnetic manipulation and separation would translate to a platform for pathogen identification or removal. These magnetic and targeted nanoparticles enable new methods to address bacterial infections.

  19. Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells

    NARCIS (Netherlands)

    Song, Juan; Cano-Rodriquez, David; Winkle, Melanie; Gjaltema, Rutger A. F.; Goubert, Desiree; Jurkowski, Tomasz P.; Heijink, Irene H.; Rots, Marianne G.; Hylkema, Machteld N.

    2017-01-01

    Airway mucus hypersecretion contributes to the morbidity and mortality in patients with chronic inflammatory lung diseases. Reducing mucus production is crucial for improving patients' quality of life. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical

  20. Travel demand management targeting reduced private car use : Effectiveness, public acceptability and political feasibility

    NARCIS (Netherlands)

    Garling, Tommy; Schuitema, Geertje

    2007-01-01

    The private car is fast, comfortable, and convenient. However, worldwide massive car use causes serious environmental problems. Although breakthroughs in clean automobile technology may be under way, reducing car use seems necessary in order to achieve a sustainable transportation system. Several

  1. Reduced complexity FFT-based DOA and DOD estimation for moving target in bistatic MIMO radar

    KAUST Repository

    Ali, Hussain; Ahmed, Sajid; Al-Naffouri, Tareq Y.; Alouini, Mohamed-Slim

    2016-01-01

    classification (2D-MUSIC) and reduced-dimension MUSIC (RD-MUSIC) algorithms. It is shown by simulations, our proposed algorithm has better estimation performance and lower computational complexity compared to the 2D-MUSIC and RD-MUSIC algorithms. Moreover

  2. Mobile operators have set ambitious targets – Is it possible to boost network capacity while reducing its energy consumption?

    DEFF Research Database (Denmark)

    Micallef, Gilbert; Mogensen, Preben; Scheck, Hans-Otto

    2012-01-01

    While operators have to upgrade the capacity of their networks, they have committed themselves to reduce their CO2 emissions, partly by reducing their energy consumption. This article investigates the challenges faced by operators and quantifies, through a number of case studies, the impact...... the possible savings by adopting an energy-efficient capacity evolution together with an equipment replacement and site upgrade strategy. Results show that network operators can get relatively close to their targets, with energy reductions of up to 40% noted. While this can be improved further through software...... based energy saving features, further CO2 emissions can be offset through carbon-neutral energy sources....

  3. Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

    Science.gov (United States)

    Chaparro, María Jesús; Calderón, Félix; Castañeda, Pablo; Fernández-Alvaro, Elena; Gabarró, Raquel; Gamo, Francisco Javier; Gómez-Lorenzo, María G; Martín, Julio; Fernández, Esther

    2018-04-13

    Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits. Optimization efforts on several chemical series have been successful, and clinical candidates have been identified. In addition, recent advances in genetics and proteomics have led to the target deconvolution of phenotypic clinical candidates. New mechanisms of action will also be critical to overcome resistance and reduce attrition. Therefore, a complementary strategy focused on identifying well-validated targets to start hit identification programs is essential to reinforce the clinical pipeline. Leveraging published data, we have assessed the status quo of the current antimalarial target portfolio with a focus on the blood stage clinical disease. From an extensive list of reported Plasmodium targets, we have defined triage criteria. These criteria consider genetic, pharmacological, and chemical validation, as well as tractability/doability, and safety implications. These criteria have provided a quantitative score that has led us to prioritize those targets with the highest probability to deliver successful and differentiated new drugs.

  4. Paralog-divergent Features May Help Reduce Off-target Effects of Drugs: Hints from Glucagon Subfamily Analysis

    Directory of Open Access Journals (Sweden)

    Zhining Sa

    2017-08-01

    Full Text Available Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR and glucagon-like peptide-1 receptor (GLP-1R, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-II amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR, which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-1R. The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.

  5. Lateral view dissection of the prostato-urethral junction to reduce positive apical margin in laparoscopic radical prostatectomy.

    Science.gov (United States)

    Sasaki, Hiroshi; Miki, Jun; Kimura, Takahiro; Sanuki, Kunitaro; Miki, Kenta; Takahashi, Hiroyuki; Egawa, Shin

    2009-08-01

    To assess the impact of lateral view apical dissection in laparoscopic radical prostatectomy (LRP) on the reduction of positive surgical margin rates and recovery of postoperative continence. One hundred and forty-four consecutive patients underwent LRP from October 2004 to March 2008. Lateral view dissection of the prostato-urethral junction was conducted in 76 of them (Group 2). Standard dissection was used in the remaining patients (Group 1). The effect of this technical modification on the reduction of positive surgical margin rates and postoperative recovery of urinary continence was assessed in the two groups. Overall, the incidence of positive margins decreased from 23 (35.9%) in Group 1 to 16 cases (21.9%) in Group 2 (P = 0.07). Positive margin rates in pT2 decreased from 30.6% to 6.5% (P = 0.006). Apical and dorso-apical margins were reduced from 26.5% to 4.3% (P = 0.009) and from 10.2% to 0% (P Lateral view dissection of the prostato-urethral junction is an easily applicable technical modification. It provides better visualization of apical anatomy substantially contributing to the reduction of positive surgical margin rates, especially at the level of prostatic apex.

  6. Muscle mass as a target to reduce fatigue in patients with advanced cancer.

    Science.gov (United States)

    Neefjes, Elisabeth C W; van den Hurk, Renske M; Blauwhoff-Buskermolen, Susanne; van der Vorst, Maurice J D L; Becker-Commissaris, Annemarie; de van der Schueren, Marian A E; Buffart, Laurien M; Verheul, Henk M W

    2017-08-01

    Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82). The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  7. PET imaging for the quantification of biologically heterogeneous tumours: measuring the effect of relative position on image-based quantification of dose-painting targets

    International Nuclear Information System (INIS)

    McCall, Keisha C; Barbee, David L; Kissick, Michael W; Jeraj, Robert

    2010-01-01

    measurement of contrast recovery values which were larger than 30%. However, the magnitudes of the errors were found to depend on the size of the sphere and method of image reconstruction. The error values from standard OSEM images of the 5 mm diameter sphere were 20-35%, and for the 10 mm diameter sphere were 5-10%. The position-dependent variation of contrast recovery can result in changes in spatial distribution within images of heterogeneous tumours. In experiments simulating random set-up errors during imaging of two HN patients, the expectation value of the correlation was ∼1.0 for these tumours; however, Pearson correlation coefficient values as low as 0.8 were observed. Moreover, variations within the images can drastically change the delineation of biological target volumes. The errors in target delineation were more prominent in very heterogeneous tumours. As an example, in a pair of images with a correlation of 0.8, there was a 36% change in the volume of the dose-painting target delineated at 50%-of-max-SUV (ROI 50% ). The results of these studies indicate that the contrast recovery and spatial distributions of tracer within PET images are susceptible to changes in the position of the patient/tumour at the time of imaging. As such, random set-up errors in HN patients can result in reduced correlation between subsequent image-studies of the same tumour.

  8. Effect of reducing abdominal compression during prone CT colonography on ascending colonic rotation during supine-to-prone positional change

    International Nuclear Information System (INIS)

    Jang, Jong eon; Park, Seong Ho; Lee, Jong Seok; Kim, Hyun Jin; KIm, Ah Young; Ha, Hyun Kwon

    2016-01-01

    To determine the effect of reduced abdominal compression in prone position on ascending colonic movement during supine-to-prone positional change during CT colonography (CTC). Eighteen consecutive patients who had undergone prone CTC scanning with cushion blocks placed under the chest and hip/thigh to reduce abdominal compression and had confirmed sessile polyps ≥ 6 mm in the well-distended, straight, mid-ascending colon, were included. Radial location along the ascending colonic luminal circumference (°) was measured for 24 polyps and 54 colonic teniae on supine and prone CTC images. The supine-to-prone change ranging between -180° and +180° (- and + for internal and external colonic rotations, respectively), was determined. In addition, possible causes of any ascending colonic rotations were explored. Abdominal compression during prone CTC scanning completely disappeared with the use of cushion blocks in 17 of 18 patients. However, some degrees of ascending colonic rotation were still observed, with the radial location changes of -22° to 61° (median, 13.9°) for the polyps and similar degrees for teniae. Fifty-four percent and 56% of polyps and teniae, respectively, showed changes > 10°. The radial location change of the polyps was significantly associated with the degree of anterior shift of the small bowel and mesentery (r = 0.722, p < 0.001) and the degree of posterior displacement of the ascending colon (r = 0.566, p = 0.004) during supine-to-prone positional change. Ascending colonic rotation upon supine-to-prone positional change during CTC, mostly in the form of external rotation, is not eliminated by removing abdominal compression in prone position

  9. Effect of positively charged particles on sputtering damage of organic electro-luminescent diodes with Mg:Ag alloy electrodes fabricated by facing target sputtering

    Directory of Open Access Journals (Sweden)

    Kouji Suemori

    2017-04-01

    Full Text Available We investigated the influence of the positively charged particles generated during sputtering on the performances of organic light-emitting diodes (OLEDs with Mg:Ag alloy electrodes fabricated by sputtering. The number of positively charged particles increased by several orders of magnitude when the target current was increased from 0.1 A to 2.5 A. When a high target current was used, many positively charged particles with energies higher than the bond energy of single C–C bonds, which are typically found in organic molecules, were generated. In this situation, we observed serious OLED performance degradation. On the other hand, when a low target current was used, OLED performance degradation was not observed when the number of positively charged particles colliding with the organic underlayer increased. We concluded that sputtering damage caused by positively charged particles can be avoided by using a low target current.

  10. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

    Science.gov (United States)

    Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

    2009-01-01

    Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

  11. Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis.

    Directory of Open Access Journals (Sweden)

    Vitor Coutinho Carneiro

    2014-05-01

    Full Text Available Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosomiasis and females of S. mansoni lay 300 eggs daily. A large fraction of the total mRNA in the mature female worm encodes one eggshell protein, Smp14. We report that the nuclear receptors SmRXR1 and SmNR1 regulate Smp14 transcription through the recruitment of two histone acetyltransferases (HATs, SmGCN5 and SmCBP1. The treatment of HEK293 cells with histone deacetylase (HDAC inhibitors (NaB or TSA produced an 8-fold activation of the SmRXR1/SmNR1-mediated Smp14 promoter activity. Incubation with synthetic HAT inhibitors, including PU139, significantly impaired the Smp14 promoter activity in these cells. Worm pairs cultivated in the presence of PU139 exhibited limited expression of Smp14 mRNA and protein. ChIP analysis demonstrated chromatin condensation at the Smp14 promoter site in worms treated with PU139. ChIP also revealed the presence of H3K27me3 and the absence of RNA Pol II at the Smp14 promoter region in the PU139-treated worms. Most significantly, the PU139-mediated inhibition of Smp14 expression resulted in a significant number of abnormal eggs as well as defective eggs within the ootype. In addition, scanning electron microscopy revealed structural defects and unformed eggshells, and vitelline cell leakage was apparent. The dsRNAi-targeting of SmGCN5 or SmCBP1 significantly decreased Smp14 transcription and protein synthesis, which compromised the reproductive system of mature female worms, egg-laying and egg morphology. Our data strongly suggest that the inhibition of Smp14 expression targeting SmGCN5 and/or SmCBP1 represents a novel and effective strategy to control S. mansoni egg development.

  12. Reduced nighttime transpiration is a relevant breeding target for high water-use efficiency in grapevine.

    Science.gov (United States)

    Coupel-Ledru, Aude; Lebon, Eric; Christophe, Angélique; Gallo, Agustina; Gago, Pilar; Pantin, Florent; Doligez, Agnès; Simonneau, Thierry

    2016-08-09

    Increasing water scarcity challenges crop sustainability in many regions. As a consequence, the enhancement of transpiration efficiency (TE)-that is, the biomass produced per unit of water transpired-has become crucial in breeding programs. This could be achieved by reducing plant transpiration through a better closure of the stomatal pores at the leaf surface. However, this strategy generally also lowers growth, as stomatal opening is necessary for the capture of atmospheric CO2 that feeds daytime photosynthesis. Here, we considered the reduction in transpiration rate at night (En) as a possible strategy to limit water use without altering growth. For this purpose, we carried out a genetic analysis for En and TE in grapevine, a major crop in drought-prone areas. Using recently developed phenotyping facilities, potted plants of a cross between Syrah and Grenache cultivars were screened for 2 y under well-watered and moderate soil water deficit scenarios. High genetic variability was found for En under both scenarios and was primarily associated with residual diffusion through the stomata. Five quantitative trait loci (QTLs) were detected that underlay genetic variability in En Interestingly, four of them colocalized with QTLs for TE. Moreover, genotypes with favorable alleles on these common QTLs exhibited reduced En without altered growth. These results demonstrate the interest of breeding grapevine for lower water loss at night and pave the way to breeding other crops with this underexploited trait for higher TE.

  13. [Acupuncture Intervention Reduced Weight Gain Induced by Hypoglycemic Agents through Food Intake-related Targets in Central Nervous System].

    Science.gov (United States)

    Jing, Xin-yue; Ou, Chen; Lu, Sheng-feng; Zhu, Bing-mei

    2015-12-01

    Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses.

  14. Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

    Science.gov (United States)

    Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

    2015-07-01

    Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  15. A Connection Model between the Positioning Mechanism and Ultrasonic Measurement System via a Web Browser to Assess Acoustic Target Strength

    Science.gov (United States)

    Ishii, Ken; Imaizumi, Tomohito; Abe, Koki; Takao, Yoshimi; Tamura, Shuko

    This paper details a network-controlled measurement system for use in fisheries engineering. The target strength (TS) of fish is important in order to convert acoustic integration values obtained during acoustic surveys into estimates of fish abundance. The target strength pattern is measured with the combination of the rotation system for the aspect of the sample and the echo data acquisition system using the underwater supersonic wave. The user interface of the network architecture is designed for collaborative use with researchers in other organizations. The flexible network architecture is based on the web direct-access model for the rotation mechanism. The user interface is available for monitoring and controlling via a web browser that is installed in any terminal PC (personal computer). Previously the combination of two applications was performed not by a web browser but by the exclusive interface program. So a connection model is proposed between two applications by indirect communication via the DCOM (Distributed Component Object Model) server and added in the web direct-access model. A prompt report system in the TS measurement system and a positioning and measurement system using an electric flatcar via a web browser are developed. By a secure network architecture, DCOM communications via both Intranet and LAN are successfully certificated.

  16. Interventions targeting absences increase adherence and reduce abandonment of childhood cancer treatment in El Salvador.

    Science.gov (United States)

    Salaverria, Carmen; Rossell, Nuria; Hernandez, Angelica; Fuentes Alabi, Soad; Vasquez, Roberto; Bonilla, Miguel; Lam, Catherine G; Ribeiro, Raul C

    2015-09-01

    In El Salvador, about 200 new cases of pediatric cancer are diagnosed each year, and survival rates approach 70%. Although treatment is available at no cost, abandonment of therapy has remained at a steady yearly rate of 13% during the past decade. A time sensitive adherence tracking procedure (TS-ATP) was recently implemented to detect missed appointments, identify their causes, and intervene promptly. Procedure The study team was informed daily of patient/family failure to attend medical appointments in the pediatric oncology unit; the families were contacted and interviewed to ascertain and address the reasons. Patients who did not return after this initial contact were contacted again through local health clinics and municipalities. Law enforcement was a last resort for patients undergoing frontline treatment with a good prognosis., The system was adapted to clinical urgency: families of patients undergoing induction therapy were contacted within 24 hr, those in other therapy phases, within 48 hr, and those who had completed treatment, within one week. Reasons for absence were obtained by telephone or in person. The annual rate of abandonment was reduced from 13-3% during the 2 years period. There were 1,111 absences reported and 1,472 contacts with caregivers and institutions. The three main reasons for absences were financial needs (165, 23%), unforeseen barriers (116, 16%), and domestic needs (86, 12%). Use of the treatment adherence tracking system to locate and communicate with patients/families after missed appointments and the allocated aid stemming from these interviews substantially reduced abandonment and non-adherence. © 2015 Wiley Periodicals, Inc.

  17. Health outcomes in acromegaly: depression and anxiety are promising targets for improving reduced quality of life

    Directory of Open Access Journals (Sweden)

    Victor Jacobus Geraedts

    2015-01-01

    Full Text Available IINTRODUCTION. Remission criteria of acromegaly are based on biochemical variables, i.e. normalization of increased hormone levels. However, the established reduction in Quality of Life (QoL is suggested to be independent of biochemical control. The aim of this study was to test which aspects predict Qol best in acromegaly. METHODS/Design. This is a prospective cohort study in 80 acromegalic patients, with a cross-sectional and longitudinal part. The main outcome measure was health-related quality of life (QoL, measured by a generic and a disease-specific questionnaire (the SF-36 and AcroQol. Main predictors were age, gender, biochemical control, disease characteristics, treatment modalities and psychopathology. RESULTS. Our cohort of 80 acromegalics had a mean age 54.7 ± 12.3 years with an average disease duration of 10.8 ± 10.0 years. Ratio macro-/microadenoma was 54/26. In adjusted mixed method models, we found that psychopathology significantly predicts QoL in acromegaly (in models including the variables age, gender, disease duration, tumor size, basal hormone levels, relevant treatment modalities and relevant comorbidities, with a higher degree of psychopathology indicating a lower QoL (depression vs. AcroQoL: B=-1.175, p<0.001, depression vs. SF36: B=-1.648, p<0.001, anxiety vs. AcroQoL: B=-0.399, p<0.001, anxiety vs. SF36: B=-0.661, p<0.001. The explained variances demonstrate superiority of psychopathology over biochemical control and other variables in predicting QoL in our models. DISCUSSION. Superiority of psychopathology over biochemical control calls for a more extensive approach regarding diagnosing depression and anxiety in pituitary adenomas to improve QoL. Depressive symptoms and anxiety are modifiable factors that might provide valuable targets for possible future treatment interventions.

  18. Methodology to reduce 6D patient positional shifts into a 3D linear shift and its verification in frameless stereotactic radiotherapy

    Science.gov (United States)

    Sarkar, Biplab; Ray, Jyotirmoy; Ganesh, Tharmarnadar; Manikandan, Arjunan; Munshi, Anusheel; Rathinamuthu, Sasikumar; Kaur, Harpreet; Anbazhagan, Satheeshkumar; Giri, Upendra K.; Roy, Soumya; Jassal, Kanan; Kalyan Mohanti, Bidhu

    2018-04-01

    The aim of this article is to derive and verify a mathematical formulation for the reduction of the six-dimensional (6D) positional inaccuracies of patients (lateral, longitudinal, vertical, pitch, roll and yaw) to three-dimensional (3D) linear shifts. The formulation was mathematically and experimentally tested and verified for 169 stereotactic radiotherapy patients. The mathematical verification involves the comparison of any (one) of the calculated rotational coordinates with the corresponding value from the 6D shifts obtained by cone beam computed tomography (CBCT). The experimental verification involves three sets of measurements using an ArcCHECK phantom, when (i) the phantom was not moved (neutral position: 0MES), (ii) the position of the phantom shifted by 6D shifts obtained from CBCT (6DMES) from neutral position and (iii) the phantom shifted from its neutral position by 3D shifts reduced from 6D shifts (3DMES). Dose volume histogram and statistical comparisons were made between ≤ft and ≤ft . The mathematical verification was performed by a comparison of the calculated and measured yaw (γ°) rotation values, which gave a straight line, Y  =  1X with a goodness of fit as R 2  =  0.9982. The verification, based on measurements, gave a planning target volume receiving 100% of the dose (V100%) as 99.1  ±  1.9%, 96.3  ±  1.8%, 74.3  ±  1.9% and 72.6  ±  2.8% for the calculated treatment planning system values TPSCAL, 0MES, 3DMES and 6DMES, respectively. The statistical significance (p-values: paired sample t-test) of V100% were found to be 0.03 for the paired sample ≤ft and 0.01 for ≤ft . In this paper, a mathematical method to reduce 6D shifts to 3D shifts is presented. The mathematical method is verified by using well-matched values between the measured and calculated γ°. Measurements done on the ArcCHECK phantom also proved that the proposed methodology is correct. The post-correction of the

  19. Targeted mass media interventions promoting healthy behaviours to reduce risk of non-communicable diseases in adult, ethnic minorities.

    Science.gov (United States)

    Mosdøl, Annhild; Lidal, Ingeborg B; Straumann, Gyri H; Vist, Gunn E

    2017-02-17

    Physical activity, a balanced diet, avoidance of tobacco exposure, and limited alcohol consumption may reduce morbidity and mortality from non-communicable diseases (NCDs). Mass media interventions are commonly used to encourage healthier behaviours in population groups. It is unclear whether targeted mass media interventions for ethnic minority groups are more or less effective in changing behaviours than those developed for the general population. To determine the effects of mass media interventions targeting adult ethnic minorities with messages about physical activity, dietary patterns, tobacco use or alcohol consumption to reduce the risk of NCDs. We searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, ERIC, SweMed+, and ISI Web of Science until August 2016. We also searched for grey literature in OpenGrey, Grey Literature Report, Eldis, and two relevant websites until October 2016. The searches were not restricted by language. We searched for individual and cluster-randomised controlled trials, controlled before-and-after studies (CBA) and interrupted time series studies (ITS). Relevant interventions promoted healthier behaviours related to physical activity, dietary patterns, tobacco use or alcohol consumption; were disseminated via mass media channels; and targeted ethnic minority groups. The population of interest comprised adults (≥ 18 years) from ethnic minority groups in the focal countries. Primary outcomes included indicators of behavioural change, self-reported behavioural change and knowledge and attitudes towards change. Secondary outcomes were the use of health promotion services and costs related to the project. Two authors independently reviewed the references to identify studies for inclusion. We extracted data and assessed the risk of bias in all included studies. We did not pool the results due to heterogeneity in comparisons made, outcomes, and study designs. We describe the results narratively and present them in 'Summary of findings

  20. Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs.

    Science.gov (United States)

    Tate, Alan D; Antonelli, Patrick J; Hannabass, Kyle R; Dirain, Carolyn O

    2017-03-01

    Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

  1. Alternative pathways to the 1.5 °C target reduce the need for negative emission technologies

    Science.gov (United States)

    van Vuuren, Detlef P.; Stehfest, Elke; Gernaat, David E. H. J.; van den Berg, Maarten; Bijl, David L.; de Boer, Harmen Sytze; Daioglou, Vassilis; Doelman, Jonathan C.; Edelenbosch, Oreane Y.; Harmsen, Mathijs; Hof, Andries F.; van Sluisveld, Mariësse A. E.

    2018-05-01

    Mitigation scenarios that achieve the ambitious targets included in the Paris Agreement typically rely on greenhouse gas emission reductions combined with net carbon dioxide removal (CDR) from the atmosphere, mostly accomplished through large-scale application of bioenergy with carbon capture and storage, and afforestation. However, CDR strategies face several difficulties such as reliance on underground CO2 storage and competition for land with food production and biodiversity protection. The question arises whether alternative deep mitigation pathways exist. Here, using an integrated assessment model, we explore the impact of alternative pathways that include lifestyle change, additional reduction of non-CO2 greenhouse gases and more rapid electrification of energy demand based on renewable energy. Although these alternatives also face specific difficulties, they are found to significantly reduce the need for CDR, but not fully eliminate it. The alternatives offer a means to diversify transition pathways to meet the Paris Agreement targets, while simultaneously benefiting other sustainability goals.

  2. Effects of respiration on target and critical structure positions during treatment assessed with movie-loop electronic portal imaging

    International Nuclear Information System (INIS)

    Herman, Michael G.; Khadivi, Kevin O.; Kleinberg, Lawrence; Gage, Irene; Abrams, Ross A.

    1997-01-01

    excursions occurred, some portion (exceeding 10%) of the GTV was noted to move beyond the treatment field during the treatment. During tangential breast treatments, increases of up to 20% in treated lung volumes were observed. Conclusions: Diagnostic, simulation and verification images used in radiation therapy are snapshots of dynamic patient anatomy. The magnitude of physiologic motion due to respiration may significantly impact on target volume coverage during the treatment fraction. Movie-loop EPID data recorded during treatments of breast and lung treatments show that while the mean displacements are small, large >3cm displacements and broad standard deviations in target or normal anatomy position exist. The implied effects on decreasing target volume treated or increased normal tissue irradiated will compromise our efforts to deliver dose-escalated, three-dimensional and dynamic radiation therapy

  3. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Alison K Bauer

    Full Text Available Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+ and Nrf2(-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/- mice compared to Nrf2(+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/- mice than in Nrf2(+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+ mice relative to Nrf2(-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy.

  4. Evaluation of modified stainless steel surfaces targeted to reduce biofilm formation by common milk sporeformers.

    Science.gov (United States)

    Jindal, Shivali; Anand, Sanjeev; Huang, Kang; Goddard, Julie; Metzger, Lloyd; Amamcharla, Jayendra

    2016-12-01

    The development of bacterial biofilms on stainless steel (SS) surfaces poses a great threat to the quality of milk and other dairy products as the biofilm-embedded bacteria can survive thermal processing. Established biofilms offer cleaning challenges because they are resistant to most of the regular cleaning protocols. Sporeforming thermoduric organisms entrapped within biofilm matrix can also form heat-resistant spores, and may result in a long-term persistent contamination. The main objective of this study was to evaluate the efficacy of different nonfouling coatings [AMC 18 (Advanced Materials Components Express, Lemont, PA), Dursan (SilcoTek Corporation, Bellefonte, PA), Ni-P-polytetrafluoroethylene (PTFE, Avtec Finishing Systems, New Hope, MN), and Lectrofluor 641 (General Magnaplate Corporation, Linden, NJ)] on SS plate heat exchanger surfaces, to resist the formation of bacterial biofilms. It was hypothesized that modified SS surfaces would promote a lesser amount of deposit buildup and bacterial adhesion as compared with the native SS surface. Vegetative cells of aerobic sporeformers, Geobacillus stearothermophilus (ATCC 15952), Bacillus licheniformis (ATCC 6634), and Bacillus sporothermodurans (DSM 10599), were used to study biofilm development on the modified and native SS surfaces. The adherence of these organisms, though influenced by surface energy and hydrophobicity, exhibited no apparent relation with surface roughness. The Ni-P-PTFE coating exhibited the least bacterial attachment and milk solid deposition, and hence, was the most resistant to biofilm formation. Scanning electron microscopy, which was used to visualize the extent of biofilm formation on modified and native SS surfaces, also revealed lower bacterial attachment on the Ni-P-PTFE as compared with the native SS surface. This study thus provides evidence of reduced biofilm formation on the modified SS surfaces. Copyright © 2016 American Dairy Science Association. Published by Elsevier

  5. Reduced number and morphofunctional change of alveolar macrophages in MafB gene-targeted mice.

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    Michiko Sato-Nishiwaki

    Full Text Available Alveolar macrophages (AMs play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD. We previously demonstrated that the transcription factor, MafB, increased in the AMs of mice exposed to cigarette smoke, and in those of human patients with COPD. The aim of this study was to evaluate the role of MafB in AMs using newly established transgenic (TG mice that specifically express dominant negative (DN MafB in macrophages under the control of macrophage scavenger receptor (MSR enhancer-promoter. We performed cell differential analyses in bronchoalveolar lavage cells, morphological analyses with electron microscopy, and flow cytometry-based analyses of surface markers and a phagocytic capacity assay in macrophages. AM number in the TG mice was significantly decreased compared with wild-type (WT mice. Morphologically, the high electron density area in the nucleus increased, the shape of pseudopods on the AMs was altered, and actin filament was less localized in the pseudopods of AMs of TG mice, compared with WT mice. The expression of surface markers, F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the phenotype of macrophages with respect to the number of alveolar macrophages, the nuclear compartment, cellular shape, surface marker expression, and phagocytic function. MSR-DN MafB TG mice may present a useful model to clarify the precise role of MafB in macrophages.

  6. Preventing, Reducing and Ending LGBTQ2S Youth Homelessness: The Need for Targeted Strategies

    Directory of Open Access Journals (Sweden)

    Alex Abramovich

    2016-10-01

    Full Text Available Gender non-conforming and sexual minority youth are overrepresented in the homeless youth population and are frequently discriminated against in shelters and youth serving organizations. This paper provides a contextual understanding of the ways that institutional and governmental policies and standards often perpetuate the social exclusion of lesbian, gay, bisexual, transgender, queer, and 2-Spirit (LGBTQ2S youth, by further oppression and marginalization. Factors, including institutional erasure, homophobic and transphobic violence, and discrimination that is rarely dealt with, addressed, or even noticed by shelter workers, make it especially difficult for LGBTQ2S youth experiencing homelessness to access support services, resulting in a situation where they feel safer on the streets than in shelters and housing programs. This paper draws on data from a qualitative Critical Action Research study that investigated the experiences of a group of LGBTQ2S homeless youth and the perspectives of staff in shelters through one-on-one interviews in Toronto, Canada. One of the main recommendations of the study included the need for governmental policy to address LGBTQ2S youth homelessness. A case study is shared to illustrate how the Government of Alberta has put this recommendation into practice by prioritizing LGBTQ2S youth homelessness in their provincial plan to end youth homelessness. The case study draws on informal and formal data, including group activities, questions, and surveys that were collected during a symposium on LGBTQ2S youth homelessness. This paper provides an overview of a current political, social justice, and public health concern, and contributes knowledge to an under researched field of study by highlighting concrete ways to prevent, reduce, and end LGBTQ2S youth homelessness.

  7. Dual actions of albumin packaging and tumor targeting enhance the antitumor efficacy and reduce the cardiotoxicity of doxorubicin in vivo

    Directory of Open Access Journals (Sweden)

    Zheng K

    2015-08-01

    Full Text Available Ke Zheng,1 Rui Li,2 Xiaolei Zhou,2 Ping Hu,2 Yaxin Zhang,2 Yunmei Huang,3 Zhuo Chen,2 Mingdong Huang2 1College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China; 2State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, People’s Republic of China; 3Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Abstract: Doxorubicin (DOX is an effective chemotherapy drug used to treat different types of cancers. However, DOX has severe side effects, especially life-threatening cardiotoxicity. We herein report a new approach to reduce the toxicity of DOX by embedding DOX inside human serum albumin (HSA. HSA is further fused by a molecular biology technique with a tumor-targeting agent, amino-terminal fragment of urokinase (ATF. ATF binds with a high affinity to urokinase receptor, which is a cell-surface receptor overexpressed in many types of tumors. The as-prepared macromolecule complex (ATF–HSA:DOX was not as cytotoxic as free DOX to cells in vitro, and was mainly localized in cell cytosol in contrast to DOX that was localized in cell nuclei. However, in tumor-bearing mice, ATF–HSA:DOX was demonstrated to have an enhanced tumor-targeting and antitumor efficacy compared with free DOX. More importantly, histopathological examinations of the hearts from the mice treated with ATF–HSA:DOX showed a significantly reduced cardiotoxicity compared with hearts from mice treated with free DOX. These results demonstrate the feasibility of this approach in reducing the cardiotoxicity of DOX while strengthening its antitumor efficacy. Such a tumor-targeted albumin packaging strategy can also be applied to other antitumor drugs. Keywords: amino-terminal fragment of urokinase, urokinase receptor, drug carrier, human serum albumin, doxorubicin, cytotoxicity

  8. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings.

    Directory of Open Access Journals (Sweden)

    Paul Gilbert

    2008-04-01

    Full Text Available Reducing substance use and unprotected sex by HIV-positive persons improves individual health status while decreasing the risk of HIV transmission. Despite recommendations that health care providers screen and counsel their HIV-positive patients for ongoing behavioral risks, it is unknown how to best provide "prevention with positives" in clinical settings. Positive Choice, an interactive, patient-tailored computer program, was developed in the United States to improve clinic-based assessment and counseling for risky behaviors.We conducted a parallel groups randomized controlled trial (December 2003-September 2006 at 5 San Francisco area outpatient HIV clinics. Eligible patients (HIV-positive English-speaking adults completed an in-depth computerized risk assessment. Participants reporting substance use or sexual risks (n = 476 were randomized in stratified blocks. The intervention group received tailored risk-reduction counseling from a "Video Doctor" via laptop computer and a printed Educational Worksheet; providers received a Cueing Sheet on reported risks. Compared with control, fewer intervention participants reported continuing illicit drug use (RR 0.81, 95% CI: 0.689, 0.957, p = 0.014 at 3 months; and RR 0.65, 95% CI: 0.540, 0.785, p<0.001 at 6 months and unprotected sex (RR 0.88, 95% CI: 0.773, 0.993, p = 0.039 at 3 months; and RR 0.80, 95% CI: 0.686, 0.941, p = 0.007 at 6 months. Intervention participants reported fewer mean days of ongoing illicit drug use (-4.0 days vs. -1.3 days, p = 0.346, at 3 months; and -4.7 days vs. -0.7 days, p = 0.130, at 6 months than did controls, and had fewer casual sex partners at (-2.3 vs. -1.4, p = 0.461, at 3 months; and -2.7 vs. -0.6, p = 0.042, at 6 months.The Positive Choice intervention achieved significant cessation of illicit drug use and unprotected sex at the group-level, and modest individual-level reductions in days of ongoing drug use and number of casual sex partners compared with the

  9. Comparison of Magnetic Resonance Imaging and Computed Tomography for Breast Target Volume Delineation in Prone and Supine Positions

    Energy Technology Data Exchange (ETDEWEB)

    Pogson, Elise M. [Centre for Medical Radiation Physics, Faculty of Engineering and Information Sciences, University of Wollongong, Wollongong (Australia); Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); Ingham Institute for Applied Medical Research, Liverpool (Australia); Delaney, Geoff P. [Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); Ingham Institute for Applied Medical Research, Liverpool (Australia); South Western Sydney Clinical School, University of New South Wales, Sydney (Australia); School of Medicine, University of Western Sydney, Sydney (Australia); Ahern, Verity [Crown Princess Mary Cancer Care Centre, Westmead Hospital, Westmead (Australia); Boxer, Miriam M. [Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); South Western Sydney Clinical School, University of New South Wales, Sydney (Australia); Chan, Christine [Department of Radiology, Liverpool Hospital, Liverpool (Australia); David, Steven [Peter MacCallum Cancer Centre, Melbourne (Australia); Dimigen, Marion [Department of Radiology, Liverpool Hospital, Liverpool (Australia); Harvey, Jennifer A. [School of Medicine, University of Queensland, Herston (Australia); Princess Alexandra Hospital, Woolloongabba (Australia); Koh, Eng-Siew [Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); Ingham Institute for Applied Medical Research, Liverpool (Australia); South Western Sydney Clinical School, University of New South Wales, Sydney (Australia); Lim, Karen [Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); South Western Sydney Clinical School, University of New South Wales, Sydney (Australia); Papadatos, George [Liverpool and Macarthur Cancer Therapy Centres, Liverpool (Australia); and others

    2016-11-15

    Purpose: To determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials: Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results: Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57 (95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52 (95% CI 0.48-0.56) for MRI supine, 0.56 (95% CI 0.53-0.59) for CT prone and 0.55 (95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41 (95% CI 0.36-0.46) for supine and 0.38 (0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions: Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images.

  10. A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

    International Nuclear Information System (INIS)

    Garcia-Garayoa, Elisa; Blaeuenstein, Peter; Blanc, Alain; Maes, Veronique; Tourwe, Dirk; Schubiger, P.A.

    2009-01-01

    Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with 99m Tc/ 188 Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at all p.i. times. In vivo uptake was specific, and accumulation of activity in the kidneys was low. Radioactivity clearance from healthy organs was faster than that from the tumour, resulting in improved tumour-to-tissue ratios and good SPECT/CT imaging. Treatment with 188 Re-NT-XIX (30 MBq, in three or four fractions) decreased tumour growth by 50% after 3 weeks. The high in vivo stability and the favourable in vivo behaviour makes NT-XIX an excellent candidate for the imaging and therapy of NTR1-positive tumours. (orig.)

  11. Contribution of the residue at position 4 within classical nuclear localization signals to modulating interaction with importins and nuclear targeting.

    Science.gov (United States)

    Smith, Kate M; Di Antonio, Veronica; Bellucci, Luca; Thomas, David R; Caporuscio, Fabiana; Ciccarese, Francesco; Ghassabian, Hanieh; Wagstaff, Kylie M; Forwood, Jade K; Jans, David A; Palù, Giorgio; Alvisi, Gualtiero

    2018-08-01

    Nuclear import involves the recognition by importin (IMP) superfamily members of nuclear localization signals (NLSs) within protein cargoes destined for the nucleus, the best understood being recognition of classical NLSs (cNLSs) by the IMPα/β1 heterodimer. Although the cNLS consensus [K-(K/R)-X-(K/R) for positions P2-P5] is generally accepted, recent studies indicated that the contribution made by different residues at the P4 position can vary. Here, we apply a combination of microscopy, molecular dynamics, crystallography, in vitro binding, and bioinformatics approaches to show that the nature of residues at P4 indeed modulates cNLS function in the context of a prototypical Simian Virus 40 large tumor antigen-derived cNLS (KKRK, P2-5). Indeed, all hydrophobic substitutions in place of R impaired binding to IMPα and nuclear targeting, with the largest effect exerted by a G residue at P4. Substitution of R with neutral hydrophobic residues caused the loss of electrostatic and van der Waals interactions between the P4 residue side chains and IMPα. Detailed bioinformatics analysis confirmed the importance of the P4 residue for cNLS function across the human proteome, with specific residues such as G being associated with low activity. Furthermore, we validate our findings for two additional cNLSs from human cytomegalovirus (HCMV) DNA polymerase catalytic subunit UL54 and processivity factor UL44, where a G residue at P4 results in a 2-3-fold decrease in NLS activity. Our results thus showed that the P4 residue makes a hitherto poorly appreciated contribution to nuclear import efficiency, which is essential to determining the precise nuclear levels of cargoes. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Therapeutic mechanisms of Mindfulness-Oriented Recovery Enhancement for internet gaming disorder: Reducing craving and addictive behavior by targeting cognitive processes.

    Science.gov (United States)

    Li, Wen; Garland, Eric L; Howard, Matthew O

    2018-03-22

    Internet gaming disorder (IGD) is characterized by signs and symptoms similar to substance use and gambling disorders, and associated with psychosocial impairments. Research suggests that maladaptive gaming-related cognitions and coping may be implicated in IGD; therefore, interventions for IGD need to target these underlying mechanisms. Mindfulness-based treatment is effective in changing maladaptive cognitive processes and increasing adaptive coping among people with addictions. This study used data from an RCT of Mindfulness-Oriented Recovery Enhancement (MORE) for IGD to further examine changes in maladaptive gaming-related cognitions and positive reappraisal as mediators of the effects of MORE on IGD signs/symptoms. Participants (N = 30, Age M = 25.0, SD  = 5.4) were randomized to 8-weekly sessions of MORE or a support group (SG) control condition. IGD severity, levels of craving for video game playing, maladaptive gaming-related cognitions, and positive reappraisal were measured at pre-and posttreatment, and 3-month follow-up. Multivariate path analyses revealed that effects of MORE in reducing IGD and craving were statistically mediated by changes in maladaptive gaming-related cognitions. Though changes in positive reappraisal did not significantly mediate effects of MORE on IGD or craving, MORE enhanced positive reappraisal to a significantly greater extent than the SG at posttreatment. Findings suggest that effects of mindfulness treatment in reducing maladaptive gaming-related cognitions might lead to reductions in IGD severity and cravings for video game playing. This cognitive mechanism should be evaluated in a future, full-scale RCT.

  13. Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway.

    Science.gov (United States)

    Murtaza, Munazza; Khan, Gulnaz; Aftab, Meha Fatima; Afridi, Shabbir Khan; Ghaffar, Safina; Ahmed, Ayaz; Hafizur, Rahman M; Waraich, Rizwana Sanaullah

    2017-01-01

    Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases.

  14. Simulation study on discrete charge effects of SiNW biosensors according to bound target position using a 3D TCAD simulator.

    Science.gov (United States)

    Chung, In-Young; Jang, Hyeri; Lee, Jieun; Moon, Hyunggeun; Seo, Sung Min; Kim, Dae Hwan

    2012-02-17

    We introduce a simulation method for the biosensor environment which treats the semiconductor and the electrolyte region together, using the well-established semiconductor 3D TCAD simulator tool. Using this simulation method, we conduct electrostatic simulations of SiNW biosensors with a more realistic target charge model where the target is described as a charged cube, randomly located across the nanowire surface, and analyze the Coulomb effect on the SiNW FET according to the position and distribution of the target charges. The simulation results show the considerable variation in the SiNW current according to the bound target positions, and also the dependence of conductance modulation on the polarity of target charges. This simulation method and the results can be utilized for analysis of the properties and behavior of the biosensor device, such as the sensing limit or the sensing resolution.

  15. Simulation study on discrete charge effects of SiNW biosensors according to bound target position using a 3D TCAD simulator

    International Nuclear Information System (INIS)

    Chung, In-Young; Moon, Hyunggeun; Jang, Hyeri; Lee, Jieun; Kim, Dae Hwan; Seo, Sung Min

    2012-01-01

    We introduce a simulation method for the biosensor environment which treats the semiconductor and the electrolyte region together, using the well-established semiconductor 3D TCAD simulator tool. Using this simulation method, we conduct electrostatic simulations of SiNW biosensors with a more realistic target charge model where the target is described as a charged cube, randomly located across the nanowire surface, and analyze the Coulomb effect on the SiNW FET according to the position and distribution of the target charges. The simulation results show the considerable variation in the SiNW current according to the bound target positions, and also the dependence of conductance modulation on the polarity of target charges. This simulation method and the results can be utilized for analysis of the properties and behavior of the biosensor device, such as the sensing limit or the sensing resolution. (paper)

  16. In vivo imaging of chromogranin A-positive endocrine tumours by three-step monoclonal antibody targeting

    International Nuclear Information System (INIS)

    Siccardi, A.G.; Paganelli, G.; Pontiroli, A.E.; Pelagi, M.; Magnani, P.; Viale, G.; Faglia, G.; Fazio, F.

    1996-01-01

    The detection of chromogranins (Cg) by immunohistochemistry and serology represents a new in vitro diagnostic tool for endocrine tumours. We have recently reported on the feasibility of targeting chromogranin A (CgA) for in vivo detection of pituitary adenomas by immunoscintigraphy (ISG). The scintigraphic procedure, based on an anti-CgA monoclonal antibody and on the avidin-biotin three-step method (Cg-3S-ISG), was evaluated on a group of 29 consecutive patients with known or suspected endocrine tumours other than pituitary adenomas, i.e. medullary thyroid carcinoma, carcinoid, insulinoma and parathormone- or ACTH-producing tumours. Primary tumours (10) and recurrences (16) were visualised in 26 patients, whereas conventional imaging techniques (planar radiography, computerised tomography, magnetic resonance imaging and ultrasonography) failed to detect the tumour sites in ten of the same (Cg-3S-ISG-positive) patients. Therefore, these preliminary results indicate that Cg-3S-ISG, the first immunological method able to detect endocrine tumours in vivo, has a higher diagnostic accuracy than conventional imaging techniques (93.1% compared with 65.5%). (orig.). With 3 figs., 1 tab

  17. Experimental investigation of the formation of negative hydrogen ions in collisions between positive ions and atomic or molecular targets

    International Nuclear Information System (INIS)

    Lattouf, Elie

    2013-01-01

    The formation of the negative hydrogen ion (H - ) in collisions between a positive ion and a neutral atomic or molecular target is studied experimentally at impact energies of a few keV. The doubly-differential cross sections for H - formation are measured as a function of the kinetic energy and emission angle for the collision systems OH + + Ar and O + + H 2 O at 412 eV/a.m.u. These H - ions can be emitted at high energies (keV) in hard quasi-elastic two-body collisions involving a large momentum transfer to the H center. However, H - anions are preferentially emitted at low energy (eV) due to soft many-body (≥ 2) collisions resulting in a low momentum transfer. The formation of H - ions by electron capture follows excitation or ionization of the molecule. The molecular fragmentation dynamics is modeled to simulate the emission of H - ions. The overall good agreement between the simulation and the experiment leads to the understanding of most of the experimental observations. (author) [fr

  18. Systematic hybrid LOH: a new method to reduce false positives and negatives during screening of yeast gene deletion libraries

    DEFF Research Database (Denmark)

    Alvaro, D.; Sunjevaric, I.; Reid, R. J.

    2006-01-01

    We have developed a new method, systematic hybrid loss of heterozygosity, to facilitate genomic screens utilizing the yeast gene deletion library. Screening is performed using hybrid diploid strains produced through mating the library haploids with strains from a different genetic background......, to minimize the contribution of unpredicted recessive genetic factors present in the individual library strains. We utilize a set of strains where each contains a conditional centromere construct on one of the 16 yeast chromosomes that allows the destabilization and selectable loss of that chromosome. After...... complementation of any spurious recessive mutations in the library strain, facilitating attribution of the observed phenotype to the documented gene deletion and dramatically reducing false positive results commonly obtained in library screens. The systematic hybrid LOH method can be applied to virtually any...

  19. Kinetic Targeting of pegylated liposomal Doxorubicin: a new Approach to Reduce Toxicity during Chemotherapy (CARL-trial

    Directory of Open Access Journals (Sweden)

    Jansen Martin

    2011-08-01

    Full Text Available Abstract Background The therapeutic success of chemotherapeutic agents is often limited by severe adverse effects. To reduce toxicity of these drugs, nanoscale particle-based drug delivery systems (DDS are used. DDS accumulate to some extent in tumor tissues, but only a very small portion of a given dose reaches this target. Accumulation of DDS in tumor tissues is supposed to be much faster than in certain other tissues in which side effects occur ("Kinetic Targeting". Once saturation in tumor tissue is achieved, most of the administered DDS still circulate in the plasma. The extracorporeal elimination of these circulating nanoparticles would probably reduce toxicity. Methods For the CARL-trial (Controlled Application and Removal of Liposomal chemotherapeutics, pegylated liposomal doxorubicin (PLD was used as chemotherapeutic agent and double filtration plasmapheresis (DFPP was performed for extracorporeal elimination of liposomes. PLD was given as 40 mg/m2 every 3 weeks in combination with vinorelbine 2 × 25 mg/m2 (neoadjuvant treatment of breast cancer, 12 patients, or as 40 mg/m2 every 4 weeks (recurrent ovarian cancer, 3 patients. Primary endpoints were the efficiency and safety profile of DFPP, and secondary endpoints were side effects and tumor response. Results DFPP eliminated ~62% of circulating PLD, corresponding to ~45% of the total dose (n = 57 cycles. AUC of doxorubicin was reduced by 50%. No leakage of doxorubicin was detected during elimination, and no relevant DFPP-related side effects occurred. Reduction in tumor size > 30% occurred in 10/12 (neoadjuvant and in 1/3 patients (recurrent. Only five grade 2 events and one grade 3 event (mucositis, neutropenia or leucopenia and a single palmar-plantar erythrodysesthesia grade 2 were reported. Conclusion Extracorporeal elimination of PLD by DFPP is safe and efficient. CARL can diminish the main dose-limiting side effects of PLD, and probably many different DDS alike. Trial

  20. The Effectiveness of “Couple’s Dialogue with Third Position/Person” Training to Reduce Marital Dissatisfaction

    Directory of Open Access Journals (Sweden)

    حسين پورشهريار

    2015-12-01

    Full Text Available Studies have shown that marital dissatis factionis correlated with a broadet of personal and interpersonal issues and problems. So, interventional proceedings have designed and evaluated mainly based on the results of such studies. The aim of the present study was to evaluate the effectiveness of “pattern of couple’s dialogue with third position/person” training to reduce marital dissatisfaction. A sample of 28 couples (56 subjects were selected regarding their main complain, diagnostic in terview and marital satisfaction question naire (ENRICH scores and were assigned in control and experimental groups randomly. The subjects on experimental group participated in couple’s dialogue with third position\\person program in 8 weekly sessions. Multivariate analysis of variance (MANOVA showed that although the linear combinations of dimensions of marital satis  faction differentiated the levels of groups, the three components of marital communication, family and friends and marriage and children received more statistical power than other six components. Accordingly, we can consider that correction of the pattern of couple’s dialogue via modification of cognitive distortions and emotional control and regulation can sign ificantly in crease the level of marital satis faction.

  1. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A. [Academic Medical Center, University of Amsterdam, Department of Radiation Oncology, Amsterdam (Netherlands); Schoot, Agustinus J.A.J. van de [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiation Oncology, Amsterdam (Netherlands); Buist, Marrije R. [Academic Medical Center, University of Amsterdam, Department of Gynaecology and Obstetrics, Amsterdam (Netherlands)

    2018-03-15

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V{sub 45Gy} for bowel bag was >275 cm{sup 3} and >200 cm{sup 3}, respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [German] In der vorliegenden Studie wurden die moeglichen klinischen Vorteile einer Zielvolumenpraezisierung durch Ausschluss des tumorfreien proximalen Gebaermutteranteils bei der ''image-guided adaptive radiotherapy

  2. Sputum, sex and scanty smears: new case definition may reduce sex disparities in smear-positive tuberculosis.

    Science.gov (United States)

    Ramsay, A; Bonnet, M; Gagnidze, L; Githui, W; Varaine, F; Guérin, P J

    2009-05-01

    Urban clinic, Nairobi. To evaluate the impact of specimen quality and different smear-positive tuberculosis (TB) case (SPC) definitions on SPC detection by sex. Prospective study among TB suspects. A total of 695 patients were recruited: 644 produced > or =1 specimen for microscopy. The male/female sex ratio was 0.8. There were no significant differences in numbers of men and women submitting three specimens (274/314 vs. 339/380, P = 0.43). Significantly more men than women produced a set of three 'good' quality specimens (175/274 vs. 182/339, P = 0.01). Lowering thresholds for definitions to include scanty smears resulted in increases in SPC detection in both sexes; the increase was significantly higher for women. The revised World Health Organization (WHO) case definition was associated with the highest detection rates in women. When analysis was restricted only to patients submitting 'good' quality specimen sets, the difference in detection between sexes was on the threshold for significance (P = 0.05). Higher SPC notification rates in men are commonly reported by TB control programmes. The revised WHO SPC definition may reduce sex disparities in notification. This should be considered when evaluating other interventions aimed at reducing these. Further study is required on the effects of the human immuno-deficiency virus and instructed specimen collection on sex-specific impact of new SPC definition.

  3. Unsweetened ice popsicles impart a positive feeling and reduce self-mutilation after paediatric dental treatment with local anaesthesia.

    Science.gov (United States)

    Ram, Diana; Berson, Tamar; Moskovitz, Moti; Efrat, Jacob

    2010-09-01

    The purpose of the current study was to assess whether an unsweetened ice-popsicle imparts a positive feeling to children after dental treatment in which local anaesthesia is administered, and whether it reduces the tendency of children to self-mutilate (bite the lip, cheek or tongue) after the administration of local anaesthesia. Crossover study of 31 children aged 4-11 years old who needed similar dental treatments on both sides of the mandible or maxilla under local anaesthesia. At the end of each appointment the child received a toy or an ice-popsicle especially made for this study. Patients and parents answered a questionnaire regarding the children's behaviour and feeling immediately after the treatment, and 10 and 30 min after receiving the ice-popsicle or toy. Children who received ice-popsicles after dental treatment under local anaesthesia felt less discomfort and suffered less soft tissue trauma than they did when they received a toy. Reduction in soft tissue trauma was evident 10 min after receiving the ice-popsicles. Licking of an ice-popsicle after dental treatment with local anaesthesia reduces the feeling of discomfort and the biting of soft tissue and self- mutilation.

  4. Optimal reduced-rank quadratic classifiers using the Fukunaga-Koontz transform with applications to automated target recognition

    Science.gov (United States)

    Huo, Xiaoming; Elad, Michael; Flesia, Ana G.; Muise, Robert R.; Stanfill, S. Robert; Friedman, Jerome; Popescu, Bogdan; Chen, Jihong; Mahalanobis, Abhijit; Donoho, David L.

    2003-09-01

    In target recognition applications of discriminant of classification analysis, each 'feature' is a result of a convolution of an imagery with a filter, which may be derived from a feature vector. It is important to use relatively few features. We analyze an optimal reduced-rank classifier under the two-class situation. Assuming each population is Gaussian and has zero mean, and the classes differ through the covariance matrices: ∑1 and ∑2. The following matrix is considered: Λ=(∑1+∑2)-1/2∑1(∑1+∑2)-1/2. We show that the k eigenvectors of this matrix whose eigenvalues are most different from 1/2 offer the best rank k approximation to the maximum likelihood classifier. The matrix Λ and its eigenvectors have been introduced by Fukunaga and Koontz; hence this analysis gives a new interpretation of the well known Fukunaga-Koontz transform. The optimality that is promised in this method hold if the two populations are exactly Guassian with the same means. To check the applicability of this approach to real data, an experiment is performed, in which several 'modern' classifiers were used on an Infrared ATR data. In these experiments, a reduced-rank classifier-Tuned Basis Functions-outperforms others. The competitive performance of the optimal reduced-rank quadratic classifier suggests that, at least for classification purposes, the imagery data behaves in a nearly-Gaussian fashion.

  5. Test and implementation of position sensors on load and unload [18O]H2O control valve of the target used in 18F - production by proton irradiation

    International Nuclear Information System (INIS)

    Costa, Osvaldo L. da; Sciani, Valdir

    2009-01-01

    The radionuclide 18 F used to produce the radiopharmaceutical [ 18 F]FDG has 109.7 min of half-life, becoming your productive chain so peculiar, because since the beginning of [ 18 O]H 2 O irradiation until the PET-CT exam there is a period about six hours, and any procedure fail in the productive chain will result in a delay to the PET CT exam. The absence of the position signs from [ 18 O]H 2 O load and unload valve of the target may result in 18 F production loss and even area contamination around the target. In this paper, three types of position sensors, into cyclotron radionuclides production environment in Cyclotron Accelerator Center from IPEN-CNEN/SP were tested. The tests were an indicative to discover the fitter sensor to the [ 18 O]H 2 O load and unload valve from target used in [ 18 F]fluoride production. After finding the fitter sensor, it was implemented in 18 F- target, supplying the correct position from [ 18 O]H 2 O load and unload valve to programmable logic controller, that had the software modified, respecting in this way the valve position. By this way, it was possible to reduce the incidence of fails, increasing the reliability in [ 18 F]FDG productive chain. (author)

  6. Open table-top device positioning technique to reduce small bowel obstruction. Positioning accuracy and impact on conformal radiation therapy techniques

    International Nuclear Information System (INIS)

    Rudat, V.; Flentje, M.; Engenhart, R.; Metzger, M.; Wannenmacher, M.

    1995-01-01

    The immobilization error of patients positioned on the opern table-top device in prone prosition as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformal radiotherapy. The positioning error was determined by superposing 106 portal films with the corresponding simultor films from 21 patients with carcinoma of the rectum who received 3D-planned conformal radiotherapy (o-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. The positioning error along the medio-lateral, dorso-ventral und cranio-caudal axis was 1.4/-0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a media of 5.1 . Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the tratment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top decive. (orig.) [de

  7. Abundant off-target edits from site-directed RNA editing can be reduced by nuclear localization of the editing enzyme.

    Science.gov (United States)

    Vallecillo-Viejo, Isabel C; Liscovitch-Brauer, Noa; Montiel-Gonzalez, Maria Fernanda; Eisenberg, Eli; Rosenthal, Joshua J C

    2018-01-02

    Site-directed RNA editing (SDRE) is a general strategy for making targeted base changes in RNA molecules. Although the approach is relatively new, several groups, including our own, have been working on its development. The basic strategy has been to couple the catalytic domain of an adenosine (A) to inosine (I) RNA editing enzyme to a guide RNA that is used for targeting. Although highly efficient on-target editing has been reported, off-target events have not been rigorously quantified. In this report we target premature termination codons (PTCs) in messages encoding both a fluorescent reporter protein and the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein transiently transfected into human epithelial cells. We demonstrate that while on-target editing is efficient, off-target editing is extensive, both within the targeted message and across the entire transcriptome of the transfected cells. By redirecting the editing enzymes from the cytoplasm to the nucleus, off-target editing is reduced without compromising the on-target editing efficiency. The addition of the E488Q mutation to the editing enzymes, a common strategy for increasing on-target editing efficiency, causes a tremendous increase in off-target editing. These results underscore the need to reduce promiscuity in current approaches to SDRE.

  8. A new approach to treatment of resistant gram-positive infections: potential impact of targeted IV to oral switch on length of stay

    Directory of Open Access Journals (Sweden)

    Trust Sarah

    2006-06-01

    Full Text Available Abstract Background Patients prescribed intravenous (IV glycopeptides usually remain in hospital until completion of this treatment. Some of these patients could be discharged earlier if a switch to an oral antibiotic was made. This study was designed to identify the percentage of inpatients currently prescribed IV glycopeptides who could be discharged earlier if a switch to an oral agent was used, and to estimate the number of bed days that could be saved. We also aimed to identify the patient group(s most likely to benefit, and to estimate the number of days of IV therapy that could be prevented in patients who remained in hospital. Methods Patients were included if they were prescribed an IV glycopeptide for 5 days or more. Predetermined IV to oral antibiotic switch criteria and discharge criteria were applied. A multiple logistic regression model was used to identify the characteristics of the patients most likely to be suitable for earlier discharge. Results Of 211 patients, 62 (29% could have had a reduced length of stay if they were treated with a suitable oral antibiotic. This would have saved a total of 649 inpatient days (median 5 per patient; range 1–54. A further 31 patients (15% could have switched to oral therapy as an inpatient thus avoiding IV line use. The patients most likely to be suitable for early discharge were those with skin and soft tissue infection, under the cardiology, cardiothoracic surgery, orthopaedics, general medical, plastic surgery and vascular specialities, with no high risk comorbidity and less than five other regularly prescribed drugs. Conclusion The need for glycopeptide therapy has a significant impact on length of stay. Effective targeting of oral antimicrobials could reduce the need for IV access, allow outpatient treatment and thus reduce the length of stay in patients with infections caused by antibiotic resistant gram-positive bacteria.

  9. The tick biocontrol agent Metarhizium brunneum (= M. anisopliae) (strain F52) does not reduce non-target arthropods.

    Science.gov (United States)

    Fischhoff, Ilya R; Keesing, Felicia; Ostfeld, Richard S

    2017-01-01

    Previous studies have found that Met52®, which contains the entomopathogenic fungus Metarhizium brunneum, is effective in reducing the abundance of Ixodes scapularis, the tick vector for the bacterium causing Lyme disease and for other tick-borne pathogens. Given widespread interest in effective, safe methods for controlling ticks, Met52 has the potential to be used at increasing scales. The non-target impacts of Met52, as applied for tick control, have not yet been assessed. A Before-After-Control-Impact experiment was conducted to assess the effects of Met52 on non-target arthropods in lawn and forest habitats typical of residential yards. Ground-dwelling arthropods were collected using bulk sampling of soil and litter, and pitfall sampling. Arthropods were sampled once before and twice after treatment of plots with either Met52 or water (control). Multivariate general linear models were used to jointly model the abundance of arthropod orders. For each sampling method and post-spray sampling occasion, Akaike Information Criterion values were used to compare the fits of two alternative models: one that included effects of period (before vs. after spray), habitat (lawn vs. forest), and treatment (Met52 vs. control), versus a nested null model that included effects of period, and habitat, but no treatment effect. The null model was consistently better supported by the data. Significant effects were found of period and habitat but not treatment. Retrospective power analysis indicated the study had 80% power to detect a 50% reduction in arthropod abundance, as measured by bulk samples taken before versus one week after treatment. The deployment of Met52 in suburban settings is unlikely to cause meaningful reductions in the abundance of non-target arthropods.

  10. The tick biocontrol agent Metarhizium brunneum (= M. anisopliae (strain F52 does not reduce non-target arthropods.

    Directory of Open Access Journals (Sweden)

    Ilya R Fischhoff

    Full Text Available Previous studies have found that Met52®, which contains the entomopathogenic fungus Metarhizium brunneum, is effective in reducing the abundance of Ixodes scapularis, the tick vector for the bacterium causing Lyme disease and for other tick-borne pathogens. Given widespread interest in effective, safe methods for controlling ticks, Met52 has the potential to be used at increasing scales. The non-target impacts of Met52, as applied for tick control, have not yet been assessed. A Before-After-Control-Impact experiment was conducted to assess the effects of Met52 on non-target arthropods in lawn and forest habitats typical of residential yards. Ground-dwelling arthropods were collected using bulk sampling of soil and litter, and pitfall sampling. Arthropods were sampled once before and twice after treatment of plots with either Met52 or water (control. Multivariate general linear models were used to jointly model the abundance of arthropod orders. For each sampling method and post-spray sampling occasion, Akaike Information Criterion values were used to compare the fits of two alternative models: one that included effects of period (before vs. after spray, habitat (lawn vs. forest, and treatment (Met52 vs. control, versus a nested null model that included effects of period, and habitat, but no treatment effect. The null model was consistently better supported by the data. Significant effects were found of period and habitat but not treatment. Retrospective power analysis indicated the study had 80% power to detect a 50% reduction in arthropod abundance, as measured by bulk samples taken before versus one week after treatment. The deployment of Met52 in suburban settings is unlikely to cause meaningful reductions in the abundance of non-target arthropods.

  11. Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization

    International Nuclear Information System (INIS)

    Rath, Barbara H; Wahba, Amy; Camphausen, Kevin; Tofilon, Philip J

    2015-01-01

    Toward developing a model system for investigating the role of the microenvironment in the radioresistance of glioblastoma (GBM), human glioblastoma stem-like cells (GSCs) were grown in coculture with human astrocytes. Using a trans-well assay, survival analyses showed that astrocytes significantly decreased the radiosensitivity of GSCs compared to standard culture conditions. In addition, when irradiated in coculture, the initial level of radiation-induced γH2AX foci in GSCs was reduced and foci dispersal was enhanced suggesting that the presence of astrocytes influenced the induction and repair of DNA double-strand breaks. These data indicate that astrocytes can decrease the radiosensitivity of GSCs in vitro via a paracrine-based mechanism and further support a role for the microenvironment as a determinant of GBM radioresponse. Chemokine profiling of coculture media identified a number of bioactive molecules not present under standard culture conditions. The gene expression profiles of GSCs grown in coculture were significantly different as compared to GSCs grown alone. These analyses were consistent with an astrocyte-mediated modification in GSC phenotype and, moreover, suggested a number of potential targets for GSC radiosensitization that were unique to coculture conditions. Along these lines, STAT3 was activated in GSCs grown with astrocytes; the JAK/STAT3 inhibitor WP1066 enhanced the radiosensitivity of GSCs under coculture conditions and when grown as orthotopic xenografts. Further, this coculture system may also provide an approach for identifying additional targets for GBM radiosensitization

  12. Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

    Science.gov (United States)

    Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

    2009-01-01

    Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

  13. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection.

    Science.gov (United States)

    Troupin, Andrea; Londono-Renteria, Berlin; Conway, Michael J; Cloherty, Erin; Jameson, Samuel; Higgs, Stephen; Vanlandingham, Dana L; Fikrig, Erol; Colpitts, Tonya M

    2016-09-01

    Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Aedes aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Nasal continuous positive airway pressure therapy in a non-tertiary neonatal unit: reduced need for up-transfers.

    Science.gov (United States)

    Kiran, Sai; Murki, Srinivas; Pratap, Oleti Tejo; Kandraju, Hemasree; Reddy, Anupama

    2015-02-01

    To evaluate the need for up-transfer after starting of nasal continuous positive airway pressure (n-CPAP) services in a Level II special newborn care unit (SNCU). Five hundred fifty infants admitted to Level II SNCU, 252 infants during one year prior to introduction of n-CPAP (retrospective data from case records and electronic data base) and 298 infants during one year after introduction of n-CPAP services (prospective data in predefined case reporting form) were evaluated in this before and after intervention trial. The primary outcome was proportion of infants needing up-transfers from Level II SNCU for any indication. Baseline demographic data like birth weight, gestation and other perinatal factors were similar between the two epochs. Among the infants admitted to Level II SNCU, up-transfer for any reason was significantly higher in the pre-CPAP epoch compared with CPAP epoch (n = 93, 36 % vs. n = 74, 24.8 %, p = 0.002, OR 0.56, 95 % CI 0.38 to 0.83). However parent desired up-transfers were similar between the two epochs (n = 9, 3 % vs. n = 16, 5 %, p = 0.40). Introduction of n-CPAP treatment modality reduced up-transfers in subgroups of very low birth weight infants (VLBW) (n = 20, 74 % vs. n = 15, 37 %, p = 0.003) and also in preterm infants (n = 50, 54 % vs. n = 34, 32 %, p = 0.002). Introduction of n-CPAP services in a non-tertiary care neonatal unit, significantly reduced the need for up-transfers, especially in VLBW and preterm infants.

  15. Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

    Science.gov (United States)

    Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

    2016-04-01

    Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Ensemble clustering in visual working memory biases location memories and reduces the Weber noise of relative positions.

    Science.gov (United States)

    Lew, Timothy F; Vul, Edward

    2015-01-01

    People seem to compute the ensemble statistics of objects and use this information to support the recall of individual objects in visual working memory. However, there are many different ways that hierarchical structure might be encoded. We examined the format of structured memories by asking subjects to recall the locations of objects arranged in different spatial clustering structures. Consistent with previous investigations of structured visual memory, subjects recalled objects biased toward the center of their clusters. Subjects also recalled locations more accurately when they were arranged in fewer clusters containing more objects, suggesting that subjects used the clustering structure of objects to aid recall. Furthermore, subjects had more difficulty recalling larger relative distances, consistent with subjects encoding the positions of objects relative to clusters and recalling them with magnitude-proportional (Weber) noise. Our results suggest that clustering improved the fidelity of recall by biasing the recall of locations toward cluster centers to compensate for uncertainty and by reducing the magnitude of encoded relative distances.

  17. High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice

    DEFF Research Database (Denmark)

    Thieme, V; Jolly, N; Madsen, A N

    2016-01-01

    BACKGROUND AND PURPOSE: Human pancreatic polypeptide (hPP) is known to suppress appetite and food intake, thereby representing a potential therapeutic approach against obesity and associated metabolic disorders. The aim of this study was to improve hPP stability by covalent PEGylation with diverse...... fasting-induced food intake and bioavailability. KEY RESULTS: In human epithelia and colonic mucosal preparations, activity of the modified hPP peptides depended on the core sequence and latency of the peptides was related to PEG size. Peptides modified with a 22 kDa PEG (PEG22) remained intact in blood...... plasma and on incubation with liver homogenates for more than 96 h. Finally, hPP2-36 , [K(22) (PEG22)]hPP2-36 and [K(22) (PEG22),Q(34) ]hPP significantly reduced cumulative food intake in mice over 16 h after s.c. administration. CONCLUSIONS AND IMPLICATIONS: Modification with PEG22 at position 22...

  18. Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.

    Science.gov (United States)

    Vilaseca, Marina; García-Calderó, Héctor; Lafoz, Erica; Ruart, Maria; López-Sanjurjo, Cristina Isabel; Murphy, Michael P; Deulofeu, Ramon; Bosch, Jaume; Hernández-Gea, Virginia; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2017-07-01

    In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl 4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl 4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets.

    Science.gov (United States)

    Bieszk, Nella; Grabner, Michael; Wei, Wenhui; Bonine, Nicole G; Stephenson, Judith J

    2016-01-01

    To evaluate awareness of the 2012 American Diabetes Association (ADA) Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C) goals in the management of type 2 diabetes (T2D). The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS) study used the HealthCore claims database to identify T2D patients, stratified by risk, and their treating physicians to assess primary care physician and endocrinologist awareness of the 2012 ADA Position Statement. Physicians completed online surveys on A1C targets before and after receiving an educational intervention to review the position statement. Of 125 responding physicians (mean age 50.3 years, 12.8% endocrinologists) who were linked to 125 patient profiles (mean age 56.9 years, 42% female, mean A1C 7.2%), 92% were at least somewhat aware of the position statement prior to the intervention and 59% believed that the statement would impact how they set A1C targets. The educational intervention resulted in mostly less stringent goal setting for both lower and higher risk patients, but changes were not significant. The proportion of physician-assigned A1C targets within ADA-recommended ranges increased from 56% to 66% post-intervention ( P ADA Position Statement and believe that it may influence treatment goals. While patient-specific A1C targets were not significantly impacted, physicians indicated that they would make targets more or less stringent for lower and higher risk patients, respectively, across their practice. Further research into optimizing physician education regarding individualized A1C targets is warranted.

  20. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

  1. Sleep Apnea Related Risk of Motor Vehicle Accidents is Reduced by Continuous Positive Airway Pressure: Swedish Traffic Accident Registry Data

    Science.gov (United States)

    Karimi, Mahssa; Hedner, Jan; Häbel, Henrike; Nerman, Olle; Grote, Ludger

    2015-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle accidents (MVAs). The rate of MVAs in patients suspected of having OSA was determined and the effect of continuous positive airway pressure (CPAP) was investigated. Design: MVA rate in patients referred for OSA was compared to the rate in the general population using data from the Swedish Traffic Accident Registry (STRADA), stratified for age and calendar year. The risk factors for MVAs, using demographic and polygraphy data, and MVA rate before and after CPAP were evaluated in the patient group. Setting: Clinical sleep laboratory and population based control (n = 635,786). Patients: There were 1,478 patients, male sex 70.4%, mean age 53.6 (12.8) y. Interventions: CPAP. Measurements and Results: The number of accidents (n = 74) among patients was compared with the expected number (n = 30) from a control population (STRADA). An increased MVA risk ratio of 2.45 was found among patients compared with controls (P accident risk was most prominent in the elderly patients (65–80 y, seven versus two MVAs). In patients, driving distance (km/y), EDS (Epworth Sleepiness score ≥ 16), short habitual sleep time (≤ 5 h/night), and use of hypnotics were associated with increased MVA risk (odds ratios 1.2, 2.1, 2.7 and 2.1, all P ≤ 0.03). CPAP use ≥ 4 h/night was associated with a reduction of MVA incidence (7.6 to 2.5 accidents/1,000 drivers/y). Conclusions: The motor vehicle accident risk in this large cohort of unselected patients with obstructive sleep apnea suggests a need for accurate tools to identify individuals at risk. Sleep apnea severity (e.g., apnea-hypopnea index) failed to identify patients at risk. Citation: Karimi M, Hedner J, Häbel H, Nerman O, Grote L. Sleep apnea related risk of motor vehicle accidents is reduced by continuous positive airway pressure: Swedish traffic accident registry data. SLEEP 2015;38(3):341–349. PMID:25325460

  2. C'mon get happy: reduced magnitude and duration of response during a positive-affect induction in depression.

    Science.gov (United States)

    Horner, Michelle S; Siegle, Greg J; Schwartz, Robert M; Price, Rebecca B; Haggerty, Agnes E; Collier, Amanda; Friedman, Edward S

    2014-11-01

    Depression involves decreased positive affect. Whether this is due to a failure to achieve or maintain positive emotion in response to discrete stimuli is unclear. Understanding the nature of decreased positive affect could help to address how to intervene in the phenomenon, for example, how to structure interventions using positive and rewarding stimuli in depression. Thus, we examined the time course of affect following exposure to positive stimuli in depressed and healthy individuals. Seventy-one adults with major depressive disorder and thirty-four never-depressed controls read a self-generated highly positive script and continuously rated their affect for 7 min. Both groups quickly achieved increased positive affect, however, compared to controls, depressed participants did not achieve the same level of positive affect, did not maintain their positive affect, spent less time rating their affect as happy, and demonstrated larger drops in mood. These data indicate that depressed and nondepressed individuals can generate positive reactions to happy scripts, but depressed individuals cannot achieve or sustain equivalent levels of positive affect. Interventions for depression might fruitfully focus on increasing depressed individuals' ability to maintain initial engagement with positive stimuli over a sustained period of time. © 2014 Wiley Periodicals, Inc.

  3. Improving positive parenting skills and reducing harsh and abusive parenting in low- and middle-income countries: a systematic review.

    Science.gov (United States)

    Knerr, Wendy; Gardner, Frances; Cluver, Lucie

    2013-08-01

    Family and youth violence are increasingly recognized as key public health issues in developing countries. Parenting interventions form an important evidence-based strategy for preventing violence, both against and by children, yet most rigorous trials of parenting interventions have been conducted in high-income countries, with far fewer in low- and middle-income countries (LMICs). This systematic review, conducted in line with Cochrane Handbook guidelines, investigated the effectiveness of parenting interventions for reducing harsh/abusive parenting, increasing positive parenting practices, and improving parent-child relationships in LMICs. Attitudes and knowledge were examined as secondary outcomes. A range of databases were systematically searched, and randomized trials included. High heterogeneity precluded meta-analysis, but characteristics of included studies were described according to type of delivery mode and outcome. Twelve studies with 1580 parents in nine countries reported results favoring intervention on a range of parenting measures. The validity of results for most studies is unclear due to substantial or unclear risks of bias. However, findings from the two largest, highest-quality trials suggest parenting interventions may be feasible and effective in improving parent-child interaction and parental knowledge in relation to child development in LMICs, and therefore may be instrumental in addressing prevention of child maltreatment in these settings. Given the well-established evidence base for parenting interventions in high-income countries, and increasingly good evidence for their applicability across cultures and countries, there is now an urgent need for more rigorously evaluated and reported studies, focusing on youth outcomes as well as parenting, adapted for contexts of considerable resource constraints.

  4. Targeting Germinal Matrix Hemorrhage-Induced Overexpression of Sodium-Coupled Bicarbonate Exchanger Reduces Posthemorrhagic Hydrocephalus Formation in Neonatal Rats.

    Science.gov (United States)

    Li, Qian; Ding, Yan; Krafft, Paul; Wan, Weifeng; Yan, Feng; Wu, Guangyong; Zhang, Yixin; Zhan, Qunling; Zhang, John H

    2018-01-31

    Germinal matrix hemorrhage (GMH) is a leading cause of mortality and lifelong morbidity in preterm infants. Posthemorrhagic hydrocephalus (PHH) is a common complication of GMH. A sodium-coupled bicarbonate exchanger (NCBE) encoded by solute carrier family 4 member 10 gene is expressed on the choroid plexus basolateral membrane and may play a role in cerebrospinal fluid production and the development of PHH. Following GMH, iron degraded from hemoglobin has been linked to PHH. Choroid plexus epithelial cells also contain iron-responsive element-binding proteins (IRPs), IRP1, and IRP2 that bind to mRNA iron-responsive elements. The present study aims to resolve the following issues: (1) whether the expression of NCBE is regulated by IRPs; (2) whether NCBE regulates the formation of GMH-induced hydrocephalus; and (3) whether inhibition of NCBE reduces PHH development. GMH model was established in P7 rat pups by injecting bacterial collagenase into the right ganglionic eminence. Another group received iron trichloride injections instead of collagenase. Deferoxamine was administered intraperitoneally for 3 consecutive days after GMH/iron trichloride. Solute carrier family 4 member 10 small interfering RNA or scrambled small interfering RNA was administered by intracerebroventricular injection 24 hours before GMH and followed with an injection every 7 days over 21 days. NCBE expression increased while IRP2 expression decreased after GMH/iron trichloride. Deferoxamine ameliorated both the GMH-induced and iron trichloride-induced decrease of IRP2 and decreased NCBE expressions. Deferoxamine and solute carrier family 4 member 10 small interfering RNA improved cognitive and motor functions at 21 to 28 days post GMH and reduced cerebrospinal fluid production as well as the degree of hydrocephalus at 28 days after GMH. Targeting iron-induced overexpression of NCBE may be a translatable therapeutic strategy for the treatment of PHH following GMH. © 2018 The Authors

  5. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

    Science.gov (United States)

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

    2014-01-17

    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

  6. Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

    Science.gov (United States)

    Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

    2018-03-30

    High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

  7. Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

    Energy Technology Data Exchange (ETDEWEB)

    Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen; Lee, Jae; Lee, Choonik; Matuszak, Martha M.; Ten Haken, Randall K.; Brock, Kristy K., E-mail: kbrock@med.umich.edu

    2016-11-01

    Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the

  8. Technical Note: Using k-means clustering to determine the number and position of isocenters in MLC-based multiple target intracranial radiosurgery.

    Science.gov (United States)

    Yock, Adam D; Kim, Gwe-Ya

    2017-09-01

    To present the k-means clustering algorithm as a tool to address treatment planning considerations characteristic of stereotactic radiosurgery using a single isocenter for multiple targets. For 30 patients treated with stereotactic radiosurgery for multiple brain metastases, the geometric centroids and radii of each met were determined from the treatment planning system. In-house software used this as well as weighted and unweighted versions of the k-means clustering algorithm to group the targets to be treated with a single isocenter, and to position each isocenter. The algorithm results were evaluated using within-cluster sum of squares as well as a minimum target coverage metric that considered the effect of target size. Both versions of the algorithm were applied to an example patient to demonstrate the prospective determination of the appropriate number and location of isocenters. Both weighted and unweighted versions of the k-means algorithm were applied successfully to determine the number and position of isocenters. Comparing the two, both the within-cluster sum of squares metric and the minimum target coverage metric resulting from the unweighted version were less than those from the weighted version. The average magnitudes of the differences were small (-0.2 cm 2 and 0.1% for the within cluster sum of squares and minimum target coverage, respectively) but statistically significant (Wilcoxon signed-rank test, P k-means clustering algorithm represented an advantage of the unweighted version for the within-cluster sum of squares metric, and an advantage of the weighted version for the minimum target coverage metric. While additional treatment planning considerations have a large influence on the final treatment plan quality, both versions of the k-means algorithm provide automatic, consistent, quantitative, and objective solutions to the tasks associated with SRS treatment planning using a single isocenter for multiple targets. © 2017 The Authors. Journal

  9. Parental knowledge reduces long term anxiety induced by false-positive test results after newborn screening for cystic fibrosis

    NARCIS (Netherlands)

    Vernooij-van Langen, A.M.M.; Pal, S.M. van der; Reijntjens, A.J.T.; Loeber, J.G.; Dompeling, E.; Dankert-Roelse, J.E.

    2014-01-01

    Background: False-positive screening results in newborn screening for cystic fibrosis may lead to parental stress, family relationship problems and a changed perception of the child's health. Aim of the study: To evaluate whether parental anxiety induced by a false positive screening result

  10. Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial

    Directory of Open Access Journals (Sweden)

    Lindh Magnus

    2011-04-01

    Full Text Available Abstract Background Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs would have an impact on antibiotic prescription rate in primary care clinical settings. Methods Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit and after 10 days (follow-up visit. Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days. The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. Results A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202 of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204 (P = 0.005 of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202 in the rapid result group and 17.2% (35 of 204 in the delayed result group (P

  11. The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets

    Directory of Open Access Journals (Sweden)

    Bieszk N

    2016-11-01

    Full Text Available Nella Bieszk,1 Michael Grabner,2 Wenhui Wei,1 Nicole G Bonine,2 Judith J Stephenson,2 1Sanofi US, Inc., Bridgewater, NJ, 2HealthCore, Inc., Wilmington, DE, USA Objective: To evaluate awareness of the 2012 American Diabetes Association (ADA Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C goals in the management of type 2 diabetes (T2D. Research design and methods: The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS study used the HealthCore claims database to identify T2D patients, stratified by risk, and their treating physicians to assess primary care physician and endocrinologist awareness of the 2012 ADA Position Statement. Physicians completed online surveys on A1C targets before and after receiving an educational intervention to review the position statement. Results: Of 125 responding physicians (mean age 50.3 years, 12.8% endocrinologists who were linked to 125 patient profiles (mean age 56.9 years, 42% female, mean A1C 7.2%, 92% were at least somewhat aware of the position statement prior to the intervention and 59% believed that the statement would impact how they set A1C targets. The educational intervention resulted in mostly less stringent goal setting for both lower and higher risk patients, but changes were not significant. The proportion of physician-assigned A1C targets within ADA-recommended ranges increased from 56% to 66% post-intervention (P<0.0001. Conclusion: Physicians treating T2D are aware of the 2012 ADA Position Statement and believe that it may influence treatment goals. While patient-specific A1C targets were not significantly impacted, physicians indicated that they would make targets more or less stringent for lower and higher risk patients, respectively, across their practice. Further research into optimizing physician education regarding individualized A1C targets is warranted. Keywords

  12. Mixed Lineage Kinases as Novel Targets for the Treatment of Endocrine-Resistant, ER-Positive Breast Cancer

    Science.gov (United States)

    2016-06-01

    were analyzed by High Performance Liquid Chromatography (HPLC) and both targeted and untargeted Mass Spectrometry (MS). As shown in Figure 1...metastasizes to lung and lymph node. HCl-011: Derived from a pleural effusion (metastatic) of an IDC. This line was derived from a patient who was...metastasizes to lung and lymph node. HCl-013: Derived from a pleural effusion of an Invasive Lobular Carcinoma. The patient from whom this line was

  13. Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576.

    Science.gov (United States)

    Bursi, Roberta; Erdemli, Gul; Campbell, Robert; Hutmacher, Matthew M; Kerbusch, Thomas; Spanswick, David; Jeggo, Ross; Nations, Kari R; Dogterom, Peter; Schipper, Jacques; Shahid, Mohammed

    2011-12-01

    The α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor potentiator Org 26576 represents an interesting pharmacological tool to evaluate the utility of glutamatergic enhancement towards the treatment of psychiatric disorders. In this study, a rat-human translational pharmacokinetic-pharmacodynamic (PK-PD) model of AMPA receptor modulation was used to predict human target engagement and inform dose selection in efficacy clinical trials. Modelling and simulation was applied to rat plasma and cerebrospinal fluid (CSF) pharmacokinetic and pharmacodynamic measurements to identify a target concentration (EC(80)) for AMPA receptor modulation. Human plasma pharmacokinetics was determined from 33 healthy volunteers and eight major depressive disorder patients. From four out of these eight patients, CSF PK was also determined. Simulations of human CSF levels were performed for several doses of Org 26576. Org 26576 (0.1-10 mg/kg, i.v.) potentiated rat hippocampal AMPA receptor responses in an exposure-dependant manner. The rat plasma and CSF PK data were fitted by one-compartment model each. The rat CSF PK-PD model yielded an EC(80) value of 593 ng/ml (90% confidence interval 406.8, 1,264.1). The human plasma and CSF PK data were simultaneously well described by a two-compartment model. Simulations showed that in humans at 100 mg QD, CSF levels of Org 26576 would exceed the EC(80) target concentration for about 2 h and that 400 mg BID would engage AMPA receptors for 24 h. The modelling approach provided useful insight on the likely human dose-molecular target engagement relationship for Org 26576. Based on the current analysis, 100 and 400 mg BID would be suitable to provide 'phasic' and 'continuous' AMPA receptor engagement, respectively.

  14. Feeling worse to feel better: pain-offset relief simultaneously stimulates positive affect and reduces negative affect.

    Science.gov (United States)

    Franklin, Joseph C; Lee, Kent M; Hanna, Eleanor K; Prinstein, Mitchell J

    2013-04-01

    Although pain itself induces negative affect, the removal (or offset) of pain induces a powerful state of relief. Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains a poorly understood emotion. In particular, some theorists associate relief with increased positive affect, whereas others associate relief with diminished negative affect. In the present study, we examined the affective nature of relief in a pain-offset paradigm with psychophysiological measures that were specific to negative valence (startle eyeblink reactivity) and positive valence (startle postauricular reactivity). Results revealed that pain offset simultaneously stimulates positive affect and diminishes negative affect for at least several seconds. Results also indicated that pain intensity differentially affects the positive and negative valence aspects of relief. These findings clarify the affective nature of relief and provide insight into why people engage in both normal and abnormal behaviors associated with relief.

  15. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    Science.gov (United States)

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  16. Modelling small groundwater systems - the role of targeted field investigations and observational data in reducing model uncertainty

    Science.gov (United States)

    Abesser, Corinna; Hughes, Andrew; Boon, David

    2017-04-01

    Coastal dunes are delicate systems that are under threat from a variety of human and natural influences. Groundwater modelling can provide a better understanding of how these systems operate and can be a useful tool towards the effective management of a coastal dune system, e.g. through predicting impacts from climatic change, sea level rise and land use management. Because of their small size, typically 10 - 100 km2, models representing small dune aquifer systems are more sensitive to uncertainties in input data, model geometry and model parameterisation as well as to the availability of observational data. This study describes the development of a groundwater flow model for a small (8 km2) spit dune system, Braunton Burrows, on the Southwest coast of England, UK. The system has been extensively studied and its hydrology is thought to be well understood. However, model development revealed a high degree of uncertainty relating to model structure (definition of model boundary conditions) and parameterisation (e.g., transmissivity distributions within the model domain). An iterative approach was employed, integrating (1) sensitivity analyses, (2) targeted field investigations and (3) Monte Carlo simulations within a cycle of repeated interrogation of the model outputs, observed data and conceptual understanding. Assessment of "soft information" and targeted field investigations were an important part of this iterative modelling process. For example, a passive seismic survey (TROMINO®) provided valuable new data for the characterisation of concealed bedrock topography and thickness of superficial deposits. The data confirmed a generally inclined underlying wave cut rock shelf platform (as suggested by literature sources), revealed a buried valley, and led to a more detailed delineation of transmissivity zones within the model domain. Constructing models with increasingly more complex spatial distributions of transmissivity, resulted in considerable improvements in

  17. Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

    Science.gov (United States)

    Romeo, Stefania; Viaggi, Cristina; Di Camillo, Daniela; Willis, Allison W; Lozzi, Luca; Rocchi, Cristina; Capannolo, Marta; Aloisi, Gabriella; Vaglini, Francesca; Maccarone, Rita; Caleo, Matteo; Missale, Cristina; Racette, Brad A; Corsini, Giovanni U; Maggio, Roberto

    2013-01-01

    This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

  18. A comparison of different methods for reducing the unintended positional drift accompanying walking-in-place locomotion

    DEFF Research Database (Denmark)

    Nilsson, Niels Christian; Serafin, Stefania; Nordahl, Rolf

    2014-01-01

    If Walking-in-place (WIP) techniques are to be considered a useful way of facilitating virtual locomotion, it is crucial that the user remains stationary with respect to the physical environment. However, it has recently been documented that WIP locmotion may lead to Unintended Positional Drift...

  19. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Erichsen, Helle K; Brown, David T

    2012-01-01

    GABA-A receptor positive allosteric modulators (PAMs) mediate robust analgesia in animal models of pathological pain, in part via enhancing injury-induced loss of GABA-A-α2 and -α3 receptor function within the spinal cord. As yet, a lack of clinically suitable tool compounds has prevented this co...

  20. Reducing uncertainty of estimated nitrogen load reductions to aquatic systems through spatially targeting agricultural mitigation measures using groundwater nitrogen reduction

    DEFF Research Database (Denmark)

    Hashemi, Fatemeh; Olesen, Jørgen Eivind; Jabloun, Mohamed

    2018-01-01

    variation across the landscape in natural N-reduction (denitrification) of leached nitrate in the groundwater and surface water systems. A critical basis for including spatial targeting in regulation of N-load in Denmark is the uncertainty associated with the effect of spatially targeting measures, since......The need to further abate agricultural nitrate (N)-loadings to coastal waters in Denmark represents the main driver for development of a new spatially targeted regulation that focus on locating N-mitigation measures in agricultural areas with high N-load. This targeting makes use of the spatial...... the effect will be critically affected by uncertainty in the quantification of the spatial variation in N-reduction. In this study, we used 30 equally plausible N-reduction maps, at 100 m grid and sub-catchment resolutions, for the 85-km2 groundwater dominated Norsminde catchment in Denmark, applying set...

  1. Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

    Science.gov (United States)

    Denlinger-Apte, Rachel L; Joel, Danielle L; Strasser, Andrew A; Donny, Eric C

    2017-10-01

    Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers

  2. Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention.

    Science.gov (United States)

    Lajoie, Julie; Mwangi, Lucy; Fowke, Keith R

    2017-09-12

    For over three decades, HIV infection has had a tremendous impact on the lives of individuals and public health. Microbicides and vaccines studies have shown that immune activation at the genital tract is a risk factor for HIV infection. Furthermore, lower level of immune activation, or what we call immune quiescence, has been associated with a lower risk of HIV acquisition. This unique phenotype is observed in highly-exposed seronegative individuals from different populations including female sex workers from the Pumwani cohort in Nairobi, Kenya. Here, we review the link between immune activation and susceptibility to HIV infection. We also describe a new concept in prevention where, instead of targeting the virus, we modulate the host immune system to resist HIV infection. Mimicking the immune quiescence phenotype might become a new strategy in the toolbox of biomedical methods to prevent HIV infection. Clinical trial registration on clinicaltrial.gov: #NCT02079077.

  3. Building Assets Reducing Risks: Academic Success for All Students through Positive Relationships and Use of Real-Time Data

    Science.gov (United States)

    Corsello, Maryann; Sharma, Anu; Jerabek, Angela

    2015-01-01

    Building Assets Reducing Risks (BARR) is a social emotional model that achieves academic outcomes through combining use of real-time student data with proven relationship-building strategies and intensive teacher collaboration to prevent course failure. BARR is a recipient of US Department of Education "Investing in Innovation (i3)"…

  4. The effect of reduced air density on streamer-to-leader transition and on properties of long positive leader

    International Nuclear Information System (INIS)

    Bazelyan, E M; Raizer, Yu P; Aleksandrov, N L

    2007-01-01

    New results of observations of the leader process in a pressure chamber are presented for reduced air pressures. The analysis of these data and observations of the leader discharge in peak regions shows that the length of the leader tip and some other characteristics vary by several times as pressure decreases from 1 to 0.3 atm, whereas, under the conditions considered, the leader velocity remains almost independent of air density, the leader current being the same. These data are used to extract relationships between discharge parameters. It is shown that, at reduced air densities, electric field in a 'young' section of the leader channel exceeds electric field in the streamer zone. Therefore, transition of the leader process to the final-jump phase is not inevitably followed by a breakdown of the gap for reduced pressures, as opposed to the discharge in atmospheric pressure air. The model suggested previously by the authors for the streamer-to- leader transition at atmospheric pressure is amended to take into account hydrodynamic expansion of the channel and used to simulate the process at a relative air density of 0.3. The calculated results are used to interpret the observations of the leader process at reduced air pressures

  5. TargetM6A: Identifying N6-Methyladenosine Sites From RNA Sequences via Position-Specific Nucleotide Propensities and a Support Vector Machine.

    Science.gov (United States)

    Li, Guang-Qing; Liu, Zi; Shen, Hong-Bin; Yu, Dong-Jun

    2016-10-01

    As one of the most ubiquitous post-transcriptional modifications of RNA, N 6 -methyladenosine ( [Formula: see text]) plays an essential role in many vital biological processes. The identification of [Formula: see text] sites in RNAs is significantly important for both basic biomedical research and practical drug development. In this study, we designed a computational-based method, called TargetM6A, to rapidly and accurately target [Formula: see text] sites solely from the primary RNA sequences. Two new features, i.e., position-specific nucleotide/dinucleotide propensities (PSNP/PSDP), are introduced and combined with the traditional nucleotide composition (NC) feature to formulate RNA sequences. The extracted features are further optimized to obtain a much more compact and discriminative feature subset by applying an incremental feature selection (IFS) procedure. Based on the optimized feature subset, we trained TargetM6A on the training dataset with a support vector machine (SVM) as the prediction engine. We compared the proposed TargetM6A method with existing methods for predicting [Formula: see text] sites by performing stringent jackknife tests and independent validation tests on benchmark datasets. The experimental results show that the proposed TargetM6A method outperformed the existing methods for predicting [Formula: see text] sites and remarkably improved the prediction performances, with MCC = 0.526 and AUC = 0.818. We also provided a user-friendly web server for TargetM6A, which is publicly accessible for academic use at http://csbio.njust.edu.cn/bioinf/TargetM6A.

  6. A preliminary study of spiritual self-schema (3-S(+)) therapy for reducing impulsivity in HIV-positive drug users.

    Science.gov (United States)

    Margolin, Arthur; Schuman-Olivier, Zev; Beitel, Mark; Arnold, Ruth M; Fulwiler, Carl E; Avants, S Kelly

    2007-10-01

    The purpose of this study was twofold. First, pretreatment correlations are presented among impulsivity, intoxicant use, HIV risk behavior, spirituality, and motivation in a sample of 38 HIV-positive drug users. Second, treatment outcomes are presented from a preliminary study of spiritual self-schema (3-S(+)) therapy - a manual-guided psychotherapy integrating cognitive and Buddhist psychologies - for increasing motivation for abstinence, HIV prevention, and medication adherence. Impulsivity was negatively correlated with spiritual practices and motivation for recovery, and was positively related to intoxicant use and HIV risk behavior. Relative to a standard care comparison condition, patients completing 3-S(+) therapy reported greater decreases in impulsivity and intoxicant use, and greater increases in spiritual practices and motivation for abstinence, HIV prevention, and medication adherence. (c) 2007 Wiley Periodicals, Inc.

  7. Distinct neural systems underlying reduced emotional enhancement for positive and negative stimuli in early Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Panagiota eMistridis

    2014-01-01

    Full Text Available Emotional information is typically better remembered than neutral content, and previous studies suggest that this effect is subserved particularly by the amygdala together with its interactions with the hippocampus. However, it is not known whether amygdala damage affects emotional memory performance at immediate and delayed recall, and whether its involvement is modulated by stimulus valence. Moreover, it is unclear to what extent more distributed neocortical regions involved in e.g. autobiographical memory, also contribute to emotional processing. We investigated these questions in a group of patients with Alzheimer’s disease (AD, which affects the amygdala, hippocampus and neocortical regions. Healthy controls (n = 14, patients with AD (n = 15 and its putative prodrome amnestic mild cognitive impairment (n = 11 completed a memory task consisting of immediate and delayed free recall of a list of positive, negative and neutral words. Memory performance was related to brain integrity in region of interest and whole-brain voxel-based morphometry analyses. In the brain-behavioral analyses, the left amygdala volume predicted the immediate recall of both positive and negative material, whereas at delay, left and right amygdala volumes were associated with performance with positive and negative words, respectively. Whole-brain analyses revealed additional associations between left angular gyrus integrity and the immediate recall of positive words as well as between the orbitofrontal cortex and the delayed recall of negative words. These results indicate that emotional memory impairments in AD may be underpinned by damage to regions implicated in emotional processing as well as frontoparietal regions, which may exert their influence via autobiographical memories and organizational strategies.

  8. Positive Catch & Economic Benefits of Periodic Octopus Fishery Closures: Do Effective, Narrowly Targeted Actions ‘Catalyze’ Broader Management?

    Science.gov (United States)

    Oliver, Thomas A.; Oleson, Kirsten L. L.; Ratsimbazafy, Hajanaina; Raberinary, Daniel; Benbow, Sophie; Harris, Alasdair

    2015-01-01

    Overview Eight years of octopus fishery records from southwest Madagascar reveal significant positive impacts from 36 periodic closures on: (a) fishery catches and (b) village fishery income, such that (c) economic benefits from increased landings outweigh costs of foregone catch. Closures covered ~20% of a village’s fished area and lasted 2-7 months. Fishery Catches from Each Closed Site Octopus landings and catch per unit effort (CPUE) significantly increased in the 30 days following a closure’s reopening, relative to the 30 days before a closure (landings: +718%, poctopus fishery income doubled in the 30 days after a closure, relative to 30 days before (+132%, p<0.001, n = 28). Control villages not implementing a closure showed no increase in income after “no ban” closures and modest increases after “ban” closures. Villages did not show a significant decline in income during closure events. Net Economic Benefits from Each Closed Site Landings in closure sites generated more revenue than simulated landings assuming continued open-access fishing at that site (27/36 show positive net earnings; mean +$305/closure; mean +57.7% monthly). Benefits accrued faster than local fishers’ time preferences during 17-27 of the 36 closures. High reported rates of illegal fishing during closures correlated with poor economic performance. Broader Co-Management We discuss the implications of our findings for broader co-management arrangements, particularly for catalyzing more comprehensive management. PMID:26083862

  9. Positive Catch & Economic Benefits of Periodic Octopus Fishery Closures: Do Effective, Narrowly Targeted Actions 'Catalyze' Broader Management?

    Science.gov (United States)

    Oliver, Thomas A; Oleson, Kirsten L L; Ratsimbazafy, Hajanaina; Raberinary, Daniel; Benbow, Sophie; Harris, Alasdair

    2015-01-01

    Eight years of octopus fishery records from southwest Madagascar reveal significant positive impacts from 36 periodic closures on: (a) fishery catches and (b) village fishery income, such that (c) economic benefits from increased landings outweigh costs of foregone catch. Closures covered ~20% of a village's fished area and lasted 2-7 months. Octopus landings and catch per unit effort (CPUE) significantly increased in the 30 days following a closure's reopening, relative to the 30 days before a closure (landings: +718%, poctopus fishery income doubled in the 30 days after a closure, relative to 30 days before (+132%, p<0.001, n = 28). Control villages not implementing a closure showed no increase in income after "no ban" closures and modest increases after "ban" closures. Villages did not show a significant decline in income during closure events. Landings in closure sites generated more revenue than simulated landings assuming continued open-access fishing at that site (27/36 show positive net earnings; mean +$305/closure; mean +57.7% monthly). Benefits accrued faster than local fishers' time preferences during 17-27 of the 36 closures. High reported rates of illegal fishing during closures correlated with poor economic performance. We discuss the implications of our findings for broader co-management arrangements, particularly for catalyzing more comprehensive management.

  10. The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

    Science.gov (United States)

    Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

    2016-01-01

    Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

  11. Translational and rotational intra- and inter-fractional errors in patient and target position during a short course of frameless stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Josipovic, Mirjana; Fredberg Persson, Gitte; Logadottir, Aashildur; Smulders, Bob; Westmann, Gunnar; Bangsgaard, Jens Peter

    2012-01-01

    Background. Implementation of cone beam computed tomography (CBCT) in frameless stereotactic body radiotherapy (SBRT) of lung tumours enables setup correction based on tumour position. The aim of this study was to compare setup accuracy with daily soft tissue matching to bony anatomy matching and evaluate intra- and inter-fractional translational and rotational errors in patient and target positions. Material and methods. Fifteen consecutive SBRT patients were included in the study. Vacuum cushions were used for immobilisation. SBRT plans were based on midventilation phase of four-dimensional (4D)-CT or three-dimensional (3D)-CT from PET/CT. Margins of 5 mm in the transversal plane and 10 mm in the cranio-caudal (CC) direction were applied. SBRT was delivered in three fractions within a week. At each fraction, CBCT was performed before and after the treatment. Setup accuracy comparison between soft tissue matching and bony anatomy matching was evaluated on pretreatment CBCTs. From differences in pre- and post-treatment CBCTs, we evaluated the extent of translational and rotational intra-fractional changes in patient position, tumour position and tumour baseline shift. All image registration was rigid with six degrees of freedom. Results. The median 3D difference between patient position based on bony anatomy matching and soft tissue matching was 3.0 mm (0-8.3 mm). The median 3D intra-fractional change in patient position was 1.4 mm (0-12.2 mm) and 2.2 mm (0-13.2 mm) in tumour position. The median 3D intra-fractional baseline shift was 2.2 mm (0-4.7 mm). With correction of translational errors, the remaining systematic and random errors were approximately 1deg. Conclusion. Soft tissue tumour matching improved precision of treatment delivery in frameless SBRT of lung tumours compared to image guidance using bone matching. The intra-fractional displacement of the target position was affected by both translational and rotational changes in tumour baseline position

  12. Infrastructure and automobile shifts: positioning transit to reduce life-cycle environmental impacts for urban sustainability goals

    International Nuclear Information System (INIS)

    Chester, Mikhail; Pincetl, Stephanie; Elizabeth, Zoe; Eisenstein, William; Matute, Juan

    2013-01-01

    Public transportation systems are often part of strategies to reduce urban environmental impacts from passenger transportation, yet comprehensive energy and environmental life-cycle measures, including upfront infrastructure effects and indirect and supply chain processes, are rarely considered. Using the new bus rapid transit and light rail lines in Los Angeles, near-term and long-term life-cycle impact assessments are developed, including consideration of reduced automobile travel. Energy consumption and emissions of greenhouse gases and criteria pollutants are assessed, as well the potential for smog and respiratory impacts. Results show that life-cycle infrastructure, vehicle, and energy production components significantly increase the footprint of each mode (by 48–100% for energy and greenhouse gases, and up to 6200% for environmental impacts), and emerging technologies and renewable electricity standards will significantly reduce impacts. Life-cycle results are identified as either local (in Los Angeles) or remote, and show how the decision to build and operate a transit system in a city produces environmental impacts far outside of geopolitical boundaries. Ensuring shifts of between 20–30% of transit riders from automobiles will result in passenger transportation greenhouse gas reductions for the city, and the larger the shift, the quicker the payback, which should be considered for time-specific environmental goals. (letter)

  13. Infrastructure and automobile shifts: positioning transit to reduce life-cycle environmental impacts for urban sustainability goals

    Science.gov (United States)

    Chester, Mikhail; Pincetl, Stephanie; Elizabeth, Zoe; Eisenstein, William; Matute, Juan

    2013-03-01

    Public transportation systems are often part of strategies to reduce urban environmental impacts from passenger transportation, yet comprehensive energy and environmental life-cycle measures, including upfront infrastructure effects and indirect and supply chain processes, are rarely considered. Using the new bus rapid transit and light rail lines in Los Angeles, near-term and long-term life-cycle impact assessments are developed, including consideration of reduced automobile travel. Energy consumption and emissions of greenhouse gases and criteria pollutants are assessed, as well the potential for smog and respiratory impacts. Results show that life-cycle infrastructure, vehicle, and energy production components significantly increase the footprint of each mode (by 48-100% for energy and greenhouse gases, and up to 6200% for environmental impacts), and emerging technologies and renewable electricity standards will significantly reduce impacts. Life-cycle results are identified as either local (in Los Angeles) or remote, and show how the decision to build and operate a transit system in a city produces environmental impacts far outside of geopolitical boundaries. Ensuring shifts of between 20-30% of transit riders from automobiles will result in passenger transportation greenhouse gas reductions for the city, and the larger the shift, the quicker the payback, which should be considered for time-specific environmental goals.

  14. Reduce in Variation and Improve Efficiency of Target Volume Delineation by a Computer-Assisted System Using a Deformable Image Registration Approach

    International Nuclear Information System (INIS)

    Chao, K.S. Clifford; Bhide, Shreerang FRCR; Chen, Hansen; Asper, Joshua PAC; Bush, Steven; Franklin, Gregg; Kavadi, Vivek; Liengswangwong, Vichaivood; Gordon, William; Raben, Adam; Strasser, Jon; Koprowski, Christopher; Frank, Steven; Chronowski, Gregory; Ahamad, Anesa; Malyapa, Robert; Zhang Lifei; Dong Lei

    2007-01-01

    Purpose: To determine whether a computer-assisted target volume delineation (CAT) system using a deformable image registration approach can reduce the variation of target delineation among physicians with different head and neck (HN) IMRT experiences and reduce the time spent on the contouring process. Materials and Methods: We developed a deformable image registration method for mapping contours from a template case to a patient case with a similar tumor manifestation but different body configuration. Eight radiation oncologists with varying levels of clinical experience in HN IMRT performed target delineation on two HN cases, one with base-of-tongue (BOT) cancer and another with nasopharyngeal cancer (NPC), by first contouring from scratch and then by modifying the contours deformed by the CAT system. The gross target volumes were provided. Regions of interest for comparison included the clinical target volumes (CTVs) and normal organs. The volumetric and geometric variation of these regions of interest and the time spent on contouring were analyzed. Results: We found that the variation in delineating CTVs from scratch among the physicians was significant, and that using the CAT system reduced volumetric variation and improved geometric consistency in both BOT and NPC cases. The average timesaving when using the CAT system was 26% to 29% for more experienced physicians and 38% to 47% for the less experienced ones. Conclusions: A computer-assisted target volume delineation approach, using a deformable image-registration method with template contours, was able to reduce the variation among physicians with different experiences in HN IMRT while saving contouring time

  15. Signal Processing of Ground Penetrating Radar Using Spectral Estimation Techniques to Estimate the Position of Buried Targets

    Directory of Open Access Journals (Sweden)

    Shanker Man Shrestha

    2003-11-01

    Full Text Available Super-resolution is very important for the signal processing of GPR (ground penetration radar to resolve closely buried targets. However, it is not easy to get high resolution as GPR signals are very weak and enveloped by the noise. The MUSIC (multiple signal classification algorithm, which is well known for its super-resolution capacity, has been implemented for signal and image processing of GPR. In addition, conventional spectral estimation technique, FFT (fast Fourier transform, has also been implemented for high-precision receiving signal level. In this paper, we propose CPM (combined processing method, which combines time domain response of MUSIC algorithm and conventional IFFT (inverse fast Fourier transform to obtain a super-resolution and high-precision signal level. In order to support the proposal, detailed simulation was performed analyzing SNR (signal-to-noise ratio. Moreover, a field experiment at a research field and a laboratory experiment at the University of Electro-Communications, Tokyo, were also performed for thorough investigation and supported the proposed method. All the simulation and experimental results are presented.

  16. Receptor-mediated targeting of 67Ga-Deferoxamine-Folate to folate-receptor-positive human kb tumor xenografts

    International Nuclear Information System (INIS)

    Mathias, Carla J.; Wang, Susan; Low, Philip S.; Waters, David J.; Green, Mark A.

    1999-01-01

    The radiochemical synthesis and stability of 67 Ga-deferoxamine-folate ([ 67 Ga]Ga-DF-Folate) were examined as a function of DF-Folate concentration. Optimal labeling occurred at DF-Folate concentrations ≥2.5 μg/mL. To define the possible biological significance of variations in product formulation, the biodistribution of [ 67 Ga]Ga-DF-Folate was examined as a function of administered deferoxamine-folate dose in an athymic mouse KB tumor model. The folate-receptor-positive KB tumors were found to concentrate the 67 Ga radiolabel in a dose-dependent fashion, consistent with saturable involvement of the folate receptor in mediating tumor accumulation of the radiopharmaceutical

  17. In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA.

    Directory of Open Access Journals (Sweden)

    David Sychantha

    2017-10-01

    Full Text Available The O-acetylation of the essential cell wall polymer peptidoglycan occurs in most Gram-positive bacterial pathogens, including species of Staphylococcus, Streptococcus and Enterococcus. This modification to peptidoglycan protects these pathogens from the lytic action of the lysozymes of innate immunity systems and, as such, is recognized as a virulence factor. The key enzyme involved, peptidoglycan O-acetyltransferase A (OatA represents a particular challenge to biochemical study since it is a membrane associated protein whose substrate is the insoluble peptidoglycan cell wall polymer. OatA is predicted to be bimodular, being comprised of an N-terminal integral membrane domain linked to a C-terminal extracytoplasmic domain. We present herein the first biochemical and kinetic characterization of the C-terminal catalytic domain of OatA from two important human pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Using both pseudosubstrates and novel biosynthetically-prepared peptidoglycan polymers, we characterized distinct substrate specificities for the two enzymes. In addition, the high resolution crystal structure of the C-terminal domain reveals an SGNH/GDSL-like hydrolase fold with a catalytic triad of amino acids but with a non-canonical oxyanion hole structure. Site-specific replacements confirmed the identity of the catalytic and oxyanion hole residues. A model is presented for the O-acetylation of peptidoglycan whereby the translocation of acetyl groups from a cytoplasmic source across the cytoplasmic membrane is catalyzed by the N-terminal domain of OatA for their transfer to peptidoglycan by its C-terminal domain. This study on the structure-function relationship of OatA provides a molecular and mechanistic understanding of this bacterial resistance mechanism opening the prospect for novel chemotherapeutic exploration to enhance innate immunity protection against Gram-positive pathogens.

  18. Sputum, sex and scanty smears: new case definition may reduce sex disparities in smear-positive tuberculosis

    OpenAIRE

    Ramsay, A; Bonnet, M; Gagnidze, L; Githui, W; Varaine, F; Guérin, P J

    2009-01-01

    SETTING: Urban clinic, Nairobi. OBJECTIVES: To evaluate the impact of specimen quality and different smear-positive tuberculosis (TB) case (SPC) definitions on SPC detection by sex. DESIGN: Prospective study among TB suspects. RESULTS: A total of 695 patients were recruited: 644 produced > or =1 specimen for microscopy. The male/female sex ratio was 0.8. There were no significant differences in numbers of men and women submitting three specimens (274/314 vs. 339/380, P = 0.43). Significantly ...

  19. Method for reducing x-ray background signals from insertion device x-ray beam position monitors

    Directory of Open Access Journals (Sweden)

    Glenn Decker

    1999-11-01

    Full Text Available A method is described that provides a solution to the long-standing problem of stray radiation-induced signals on photoemission-based x-ray beam position monitors (BPMs located on insertion device x-ray beam lines. The method involves the introduction of a chicane into the accelerator lattice that directs unwanted x radiation away from the photosensitive x-ray BPM blades. This technique has been implemented at the Advanced Photon Source, and experimental confirmation of the technique is provided.

  20. Transient overexpression of DNA adenine methylase enables efficient and mobile genome engineering with reduced off-target effects

    DEFF Research Database (Denmark)

    Lennen, Rebecca; Nilsson Wallin, Annika; Pedersen, Margit

    2016-01-01

    Homologous recombination of single-stranded oligonucleotides is a highly efficient process for introducing precise mutations into the genome of E. coli and other organisms when mismatch repair (MMR) is disabled. This can result in the rapid accumulation of off-target mutations that can mask desir...

  1. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

    NARCIS (Netherlands)

    Willemsen, A.E.C.A.B.; Lubberman, F.J.E.; Tol, J.; Gerritsen, W.R.; Herpen, C.M.L. van; Erp, N. van

    2016-01-01

    Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and

  2. American Society of Clinical Oncology Position Statement: Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations.

    Science.gov (United States)

    Griggs, Jennifer; Maingi, Shail; Blinder, Victoria; Denduluri, Neelima; Khorana, Alok A; Norton, Larry; Francisco, Michael; Wollins, Dana S; Rowland, Julia H

    2017-07-01

    ASCO is committed to addressing the needs of sexual and gender minority (SGM) populations as a diverse group at risk for receiving disparate care and having suboptimal experiences, including discrimination, throughout the cancer care continuum. This position statement outlines five areas of recommendations to address the needs of both SGM populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In making these recommendations, the Society calls for increased outreach and educational support for SGM patients; increased SGM cultural competency training for providers; improvement of quality-of-care metrics that include sexual orientation and gender information variables; and increased data collection to inform future work addressing the needs of SGM communities.

  3. Contribution of ICT to Climate Targets of Cities. Exploring the potential of Information and Communication Technologies in reducing emissions and energy use from buildings and travel

    Energy Technology Data Exchange (ETDEWEB)

    Kramers, Anna

    2012-07-01

    This thesis examines how ICT solutions can assist in lowering energy use and greenhouse gas (GHG) emissions from buildings and travel in order to help cities meet their climate targets. It also provides an overview of relevant research intended to furnish new knowledge about the issues involved and to find solutions to social problems. The first part of the thesis provides an analysis and compilation of critical system boundaries that need to be used for cities to set targets for energy use and GHG emissions. The climate targets of cities are dependent on setting system boundaries and establishing methods of calculations for monitoring whether the targets have been achieved. Today, there is no official standard for how the system boundaries must be set or what calculation methodologies to apply to evaluate the climate targets. Four main categories of system boundaries were identified: the temporal scope, the object of target setting, the unit of target setting, and the target range (e.g. consumer-producer and lifecycle perspective). Eight European cities were examined in relation to how they set climate targets. The examination showed that awareness of what is included in the targets is limited and that there is a need for standardised and consistent protocols and methods of setting climate targets for cities. In the second part of the thesis, leading Advanced Traveller Information Systems (ATIS) and their functionalities were investigated. The relationship between individual decisions on different travel modes and functionalities of ATIS was investigated through a systematic investigation of the functionality of nine ATIS, mainly from Sweden, Germany, UK and USA. This allowed decisions that could lead to lower energy use and emissions of GHG to be identified. It also resulted in a proposal on requirements for new and improved functionality that could support a reduction in energy use and GHG emissions and a shift to renewable energy sources if implemented in next

  4. Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion.

    Science.gov (United States)

    Triplett, Brandon M; Muller, Brad; Kang, Guolian; Li, Ying; Cross, Shane J; Moen, Joseph; Cunningham, Lea; Janssen, William; Mamcarz, Ewelina; Shook, David R; Srinivasan, Ashok; Choi, John; Hayden, Randall T; Leung, Wing

    2018-02-01

    T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02). CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Picornaviruses and nuclear functions: targeting a cellular compartment distinct from the replication site of a positive-strand RNA virus

    Directory of Open Access Journals (Sweden)

    Dylan eFlather

    2015-06-01

    Full Text Available The compartmentalization of DNA replication and gene transcription in the nucleus and protein production in the cytoplasm is a defining feature of eukaryotic cells. The nucleus functions to maintain the integrity of the nuclear genome of the cell and to control gene expression based on intracellular and environmental signals received through the cytoplasm. The spatial separation of the major processes that lead to the expression of protein-coding genes establishes the necessity of a transport network to allow biomolecules to translocate between these two regions of the cell. The nucleocytoplasmic transport network is therefore essential for regulating normal cellular functioning. The Picornaviridae virus family is one of many viral families that disrupt the nucleocytoplasmic trafficking of cells to promote viral replication. Picornaviruses contain positive-sense, single-stranded RNA genomes and replicate in the cytoplasm of infected cells. As a result of the limited coding capacity of these viruses, cellular proteins are required by these intracellular parasites for both translation and genomic RNA replication. Being of messenger RNA polarity, a picornavirus genome can immediately be translated upon entering the cell cytoplasm. However, the replication of viral RNA requires the activity of RNA-binding proteins, many of which function in host gene expression, and are consequently localized to the nucleus. As a result, picornaviruses disrupt nucleocytoplasmic trafficking to exploit protein functions normally localized to a different cellular compartment from which they translate their genome to facilitate efficient replication. Furthermore, picornavirus proteins are also known to enter the nucleus of infected cells to limit host-cell transcription and down-regulate innate antiviral responses. The interactions of picornavirus proteins and host-cell nuclei are extensive, required for a productive infection, and are the focus of this review.

  6. Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway

    OpenAIRE

    Murtaza, Munazza; Khan, Gulnaz; Aftab, Meha Fatima; Afridi, Shabbir Khan; Ghaffar, Safina; Ahmed, Ayaz; Hafizur, Rahman M.; Waraich, Rizwana Sanaullah

    2017-01-01

    Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic s...

  7. LiF Reduces MICs of Antibiotics against Clinical Isolates of Gram-Positive and Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    H. C. Syed

    2012-01-01

    Full Text Available Antibiotic resistance is an ever-growing problem yet the development of new antibiotics has slowed to a trickle, giving rise to the use of combination therapy to eradicate infections. The purpose of this study was to evaluate the combined inhibitory effect of lithium fluoride (LiF and commonly used antimicrobials on the growth of the following bacteria: Enterococcus faecalis, Staphyloccoccus aureus, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, and Streptococcus pneumoniae. The in vitro activities of ceftazidime, sulfamethoxazole-trimethoprim, streptomycin, erythromycin, amoxicillin, and ciprofloxacin, doxycycline, alone or combined with LiF were performed by microdilution method. MICs were determined visually following 18–20 h of incubation at 37°C. We observed reduced MICs of antibiotics associated with LiF ranging from two-fold to sixteen-fold. The strongest decreases of MICs observed were for streptomycin and erythromycin associated with LiF against Acinetobacter baumannii and Streptococcus pneumoniae. An eight-fold reduction was recorded for streptomycin against S. pneumoniae whereas an eight-fold and a sixteen-fold reduction were obtained for erythromycin against A. baumannii and S. pneumoniae. This suggests that LiF exhibits a synergistic effect with a wide range of antibiotics and is indicative of its potential as an adjuvant in antibiotic therapy.

  8. Ion-driver fast ignition: Reducing heavy-ion fusion driver energy and cost, simplifying chamber design, target fab, tritium fueling and power conversion

    Energy Technology Data Exchange (ETDEWEB)

    Logan, G.; Callahan-Miller, D.; Perkins, J.; Caporaso, G.; Tabak, M.; Moir, R.; Meier, W.; Bangerter, Roger; Lee, Ed

    1998-04-01

    Ion fast ignition, like laser fast ignition, can potentially reduce driver energy for high target gain by an order of magnitude, while reducing fuel capsule implosion velocity, convergence ratio, and required precisions in target fabrication and illumination symmetry, all of which should further improve and simplify IFE power plants. From fast-ignition target requirements, we determine requirements for ion beam acceleration, pulse-compression, and final focus for advanced accelerators that must be developed for much shorter pulses and higher voltage gradients than today's accelerators, to deliver the petawatt peak powers and small focal spots ({approx}100 {micro}m) required. Although such peak powers and small focal spots are available today with lasers, development of such advanced accelerators is motivated by the greater likely efficiency of deep ion penetration and deposition into pre-compressed 1000x liquid density DT cores. Ion ignitor beam parameters for acceleration, pulse compression, and final focus are estimated for two examples based on a Dielectric Wall Accelerator; (1) a small target with {rho}r {approx} 2 g/cm{sup 2} for a small demo/pilot plant producing {approx}40 MJ of fusion yield per target, and (2) a large target with {rho}r {approx} 10 g/cm{sup 2} producing {approx}1 GJ yield for multi-unit electricity/hydrogen plants, allowing internal T-breeding with low T/D ratios, >75 % of the total fusion yield captured for plasma direct conversion, and simple liquid-protected chambers with gravity clearing. Key enabling development needs for ion fast ignition are found to be (1) ''Close-coupled'' target designs for single-ended illumination of both compressor and ignitor beams; (2) Development of high gradient (>25 MV/m) linacs with high charge-state (q {approx} 26) ion sources for short ({approx}5 ns) accelerator output pulses; (3) Small mm-scale laser-driven plasma lens of {approx}10 MG fields to provide steep focusing angles

  9. Ion-driver fast ignition: Reducing heavy-ion fusion driver energy and cost, simplifying chamber design, target fab, tritium fueling and power conversion

    International Nuclear Information System (INIS)

    Logan, G.; Callahan-Miller, D.; Perkins, J.; Caporaso, G.; Tabak, M.; Moir, R.; Meier, W.; Bangerter, Roger; Lee, Ed

    1998-01-01

    Ion fast ignition, like laser fast ignition, can potentially reduce driver energy for high target gain by an order of magnitude, while reducing fuel capsule implosion velocity, convergence ratio, and required precisions in target fabrication and illumination symmetry, all of which should further improve and simplify IFE power plants. From fast-ignition target requirements, we determine requirements for ion beam acceleration, pulse-compression, and final focus for advanced accelerators that must be developed for much shorter pulses and higher voltage gradients than today's accelerators, to deliver the petawatt peak powers and small focal spots (∼100 (micro)m) required. Although such peak powers and small focal spots are available today with lasers, development of such advanced accelerators is motivated by the greater likely efficiency of deep ion penetration and deposition into pre-compressed 1000x liquid density DT cores. Ion ignitor beam parameters for acceleration, pulse compression, and final focus are estimated for two examples based on a Dielectric Wall Accelerator; (1) a small target with ρr ∼ 2 g/cm 2 for a small demo/pilot plant producing ∼40 MJ of fusion yield per target, and (2) a large target with ρr ∼ 10 g/cm 2 producing ∼1 GJ yield for multi-unit electricity/hydrogen plants, allowing internal T-breeding with low T/D ratios, >75 % of the total fusion yield captured for plasma direct conversion, and simple liquid-protected chambers with gravity clearing. Key enabling development needs for ion fast ignition are found to be (1) ''Close-coupled'' target designs for single-ended illumination of both compressor and ignitor beams; (2) Development of high gradient (>25 MV/m) linacs with high charge-state (q ∼ 26) ion sources for short (∼5 ns) accelerator output pulses; (3) Small mm-scale laser-driven plasma lens of ∼10 MG fields to provide steep focusing angles close-in to the target (built-in as part of each target); (4) beam space charge

  10. A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

    Science.gov (United States)

    Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

    2015-11-01

    One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Wake Shield Target Protection

    International Nuclear Information System (INIS)

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-01-01

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed

  12. Reducing turnover is not enough: The need for proficient organizational cultures to support positive youth outcomes in child welfare.

    Science.gov (United States)

    Williams, Nathaniel J; Glisson, Charles

    2013-11-01

    High caseworker turnover has been identified as a factor in the poor outcomes of child welfare services. However, almost no empirical research has examined the relationship between caseworker turnover and youth outcomes in child welfare systems and there is an important knowledge gap regarding whether, and how, caseworker turnover relates to outcomes for youth. We hypothesized that the effects of caseworker turnover are moderated by organizational culture such that reduced caseworker turnover is only associated with improved youth outcomes in organizations with proficient cultures. The study applied hierarchical linear models (HLM) analysis to the second National Survey of Child and Adolescent Well-being (NSCAW II) with a U.S. nationwide sample of 2,346 youth aged 1.5- to 18-years-old and 1,544 caseworkers in 73 child welfare agencies. Proficient organizational culture was measured by caseworkers' responses to the Organizational Social Context (OSC) measure; staff turnover was reported by the agencies' directors; and youth outcomes were measured as total problems in psychosocial functioning with the Child Behavior Checklist (CBCL) completed by the youths' caregivers at intake and at 18 month follow-up. The association between caseworker turnover and youth outcomes was moderated by organizational culture. Youth outcomes were improved with lower staff turnover in proficient organizational cultures and the best outcomes occurred in organizations with low turnover and high proficiency. To be successful, efforts to improve child welfare services by lowering staff turnover must also create proficient cultures that expect caseworkers to be competent and responsive to the needs of the youth and families they serve.

  13. The efficacy of targeted health agents education to reduce the duration of untreated psychosis in a rural population.

    Science.gov (United States)

    Padilla, Eduardo; Molina, Juan; Kamis, Danielle; Calvo, Maria; Stratton, Lee; Strejilevich, Sergio; Aleman, Gabriela Gonzalez; Guerrero, Gonzalo; Bourdieu, Mercedes; Conesa, Horacio A; Escobar, Javier I; de Erausquin, Gabriel A

    2015-02-01

    The duration of untreated psychosis (DUP) is a key determinant in the severity of symptoms in patients with schizophrenia. DUP is a modifiable factor that if reduced can improve patient outcome and treatment response. We sought to decrease DUP in rural Argentina by instituting annual training of local health agents to better identify signs of mental illness and offer earlier intervention. DUP was estimated using Schedules of Clinical Assessment in Neuropsychiatry (SCAN). Ongoing training was correlated with a reduction in DUP. Reducing DUP through better screening can decrease the psychosocial burden of disease and improve the trajectory of psychosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

    Science.gov (United States)

    Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

    2018-05-01

    Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer

  15. Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice.

    Science.gov (United States)

    Nasr, Magda; Nafee, Noha; Saad, Hoda; Kazem, Amani

    2014-09-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Epirubicin (EPI), an anthracycline derivative, is one of the main line treatments for HCC. However, serious side effects including cardiomyopathy and congestive heart failure limit its long term administration. Our main goal is to develop a delivery strategy that ensures improved efficacy of the chemotherapeutic agent together with reduced cardiotoxicity. In this context, EPI was loaded in chitosan-PLGA nanoparticles linked with asialofetuin (EPI-NPs) selectively targeting hepatocytes. In an attempt to reduce cardiotoxicity, targeted EPI-NPs were coadministered with tocotrienols. EPI-NPs significantly enhanced the antiproliferative effect compared to free EPI as studied on Hep G2 cell line. Nanoencapsulated EPI injected in HCC mouse model revealed higher p53-mediated apoptosis and reduced angiogenesis in the tumor. Combined therapy of EPI-NPs with tocotrienols further enhanced apoptosis and reduced VEGF level in a dose dependent manner. Assessment of cardiotoxicity indicated that EPI-NPs diminished the high level of proinflammatory cytokine tumor necrosis factor-α (TNF-α) as well as oxidative stress-induced cardiotoxicity as manifested by reduced level of lipid peroxidation products (TBARS) and nitric oxide (NO). EPI-NPs additionally restored the diminished level of superoxide dismutase (SOD) and reduced glutathione (GSH) in the heart. Interestingly, tocotrienols provided both antitumor activity and higher protection against oxidative stress and inflammation induced by EPI in the heart. This hepatocyte-targeted biodegradable nanoparticle/tocotrienol combined therapy represents intriguing therapeutic strategy for EPI providing not only superior efficacy but also higher safety levels. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Multifactorial assessment and targeted intervention to reduce falls among the oldest-old: a randomized controlled trial

    NARCIS (Netherlands)

    Ferrer, A.; Formiga, F.; Sanz, H.; de Vries, O.J.; Badia, T.; Pujol, R.

    2014-01-01

    Background: The purpose of this study was to assess the effectiveness of a multifactorial intervention to reduce falls among the oldest-old people, including individuals with cognitive impairment or comorbidities. Methods: A randomized, single-blind, parallel-group clinical trial was conducted from

  17. Modeling predicted that tobacco control policies targeted at lower educated will reduce the differences in life expectancy

    NARCIS (Netherlands)

    Bemelmans, W.J.E.; Lenthe, F. van; Hoogenveen, R.; Kunst, A.; Deeg, D.J.H.; Brandt, P.A. van den; Goldbohm, R.A.; Verschuren, W.M.M.

    2006-01-01

    Background and Objective: To estimate the effects of reducing the prevalence of smoking in lower educated groups on educational differences in life expectancy. Methods: A dynamic Markov-type multistate transition model estimated the effects on life expectancy of two scenarios. A "maximum scenario"

  18. Targeting N-acyl-homoserine-lactones to mitigate membrane biofouling based on quorum sensing using a biofouling reducer.

    Science.gov (United States)

    Siddiqui, Muhammad Faisal; Sakinah, Mimi; Singh, Lakhveer; Zularisam, A W

    2012-10-31

    Exploring novel biological anti-quorum sensing (QS) agents to control membrane biofouling is of great worth in order to allow sustainable performance of membrane bioreactors (MBRs) for wastewater treatment. In recent studies, QS inhibitors have provided evidence of alternative route to control membrane biofouling. This study investigated the role of Piper betle extract (PBE) as an anti-QS agent to mitigate membrane biofouling. Results demonstrated the occurrence of the N-acyl-homoserine-lactone (AHL) autoinducers (AIs), correlate QS activity and membrane biofouling mitigation. The AIs production in bioreactor was confirmed using an indicator strain Agrobacterium tumefaciens (NTL4) harboring plasmid pZLR4. Moreover, three different AHLs were found in biocake using thin layer chromatographic analysis. An increase in extracellular polymeric substances (EPS) and transmembrane pressure (TMP) was observed with AHL activity of the biocake during continuous MBR operation, which shows that membrane biofouling was in close relationship with QS activity. PBE was verified to mitigate membrane biofouling via inhibiting AIs production. SEM analysis further confirmed the effect of PBE on EPS and biofilm formation. These results exhibited that PBE could be a novel agent to target AIs for mitigation of membrane biofouling. Further work can be carried out to purify the active compound of Piper betle extract to target the QS to mitigate membrane biofouling. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Review of interventions to reduce ultraviolet tanning: Need for treatments targeting excessive tanning, an emerging addictive behavior.

    Science.gov (United States)

    Stapleton, Jerod L; Hillhouse, Joel; Levonyan-Radloff, Kristine; Manne, Sharon L

    2017-12-01

    Millions of Americans engage in tanning each year, defined as intentional ultraviolet radiation (UVR) exposure in the form of sunbathing or the use of indoor tanning beds. An emerging body of research suggests that UVR has addictive properties and some tanners engage in excessive tanning. This article provides an overview of the evidence of tanning addiction and a systematic review of existing tanning interventions with the goal of evaluating their potential to impact addicted tanners. Our search identified 24 intervention studies that were summarized and discussed according to 3 primary themes. First, there is a dearth of tanning interventions that target excessive tanning or are designed as treatments for tanning addiction. Second, tanning interventions are primarily educational interventions designed to increase knowledge of the risks of tanning. Third, there are notable aspects of existing tanning interventions that are relevant to addiction science, including the use of brief motivational and cognitive-behavioral-based interventions. Future directions are considered including recommendations for utilizing the existing evidence base to formulate interventions targeting excessive tanners. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Robot-assisted radical prostatectomy: Multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins.

    Science.gov (United States)

    Petralia, Giuseppe; Musi, Gennaro; Padhani, Anwar R; Summers, Paul; Renne, Giuseppe; Alessi, Sarah; Raimondi, Sara; Matei, Deliu V; Renne, Salvatore L; Jereczek-Fossa, Barbara A; De Cobelli, Ottavio; Bellomi, Massimo

    2015-02-01

    To investigate whether use of multiparametric magnetic resonance (MR) imaging-directed intraoperative frozen-section (IFS) analysis during nerve-sparing robot-assisted radical prostatectomy reduces the rate of positive surgical margins. This retrospective analysis of prospectively acquired data was approved by an institutional ethics committee, and the requirement for informed consent was waived. Data were reviewed for 134 patients who underwent preoperative multiparametric MR imaging (T2 weighted, diffusion weighted, and dynamic contrast-material enhanced) and nerve-sparing robot-assisted radical prostatectomy, during which IFS analysis was used, and secondary resections were performed when IFS results were positive for cancer. Control patients (n = 134) matched for age, prostate-specific antigen level, and stage were selected from a pool of 322 patients who underwent nerve-sparing robot-assisted radical prostatectomy without multiparametric MR imaging and IFS analysis. Rates of positive surgical margins were compared by means of the McNemar test, and a multivariate conditional logistic regression model was used to estimate the odds ratio of positive surgical margins for patients who underwent MR imaging and IFS analysis compared with control subjects. Eighteen patients who underwent MR imaging and IFS analysis underwent secondary resections, and 13 of these patients were found to have negative surgical margins at final pathologic examination. Positive surgical margins were found less frequently in the patients who underwent MR imaging and IFS analysis than in control patients (7.5% vs 18.7%, P = .01). When the differences in risk factors are taken into account, patients who underwent MR imaging and IFS had one-seventh the risk of having positive surgical margins relative to control patients (adjusted odds ratio: 0.15; 95% confidence interval: 0.04, 0.61). The significantly lower rate of positive surgical margins compared with that in control patients provides

  1. Small interfering RNA targeting HIF-1{alpha} reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Staab, Adrian [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Paul Scherrer Institute (PSI), Villigen (Switzerland); Fleischer, Markus [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Wuerzburg Univ. (Germany). Medical Clinic II; Loeffler, Juergen; Einsele, Herrmann [Wuerzburg Univ. (Germany). Medical Clinic II; Said, Harun M.; Katzer, Astrid; Flentje, Michael [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Plathow, Christian [Freiburg Univ. (Germany). Dept. of Nuclear Medicine; Vordermark, Dirk [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Halle-Wittenberg Univ. (Germany). Dept. of Radiation Oncology

    2011-04-15

    Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1{alpha} expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1{alpha} siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1{alpha}. HIF-1{alpha} protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O{sub 2} (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1{alpha}-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER') was calculated as the ratio of the doses to achieve the same survival at 0.1% O{sub 2} as at ambient oxygen tensions. OER' was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1{alpha}-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1{alpha}-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. (orig.)

  2. Small interfering RNA targeting HIF-1α reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

    International Nuclear Information System (INIS)

    Staab, Adrian; Fleischer, Markus; Wuerzburg Univ.; Loeffler, Juergen; Einsele, Herrmann; Said, Harun M.; Katzer, Astrid; Flentje, Michael; Plathow, Christian; Vordermark, Dirk; Halle-Wittenberg Univ.

    2011-01-01

    Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1α. HIF-1α protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O 2 (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1α-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER') was calculated as the ratio of the doses to achieve the same survival at 0.1% O 2 as at ambient oxygen tensions. OER' was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1α-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1α-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1α-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1α-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. (orig.)

  3. Positive performance and health effects of a football training program over 12 weeks can be maintained over a 1-year period with reduced training frequency

    DEFF Research Database (Denmark)

    Randers, Morten Bredsgaard; Nielsen, Jens Jung; Krustrup, Birgitte Rejkjær

    2010-01-01

    We examined whether improvements in the performance and health profile of an intensive 12-week football intervention could be maintained with a reduced training frequency. Seventeen healthy untrained males completed the study. Ten subjects trained 2.4 times/week for 12 weeks and another 52 weeks ...... unaltered for CG. In conclusion, positive adaptations in cardiovascular fitness obtained over 12 weeks of regular recreational football training can be maintained over a 1-year period with a reduced training frequency, with further development in musculo-skeletal fitness.......We examined whether improvements in the performance and health profile of an intensive 12-week football intervention could be maintained with a reduced training frequency. Seventeen healthy untrained males completed the study. Ten subjects trained 2.4 times/week for 12 weeks and another 52 weeks...... (P12 weeks. After 64 weeks, quadriceps muscle mass (11%), mean fiber area (10%) and citrate synthase activity (18%) were higher (P

  4. Posture Used in fMRI-PET Elicits Reduced Cortical Activity and Altered Hemispheric Asymmetry with Respect to Sitting Position: An EEG Resting State Study

    Directory of Open Access Journals (Sweden)

    Chiara Spironelli

    2017-12-01

    Full Text Available Horizontal body position is a posture typically adopted for sleeping or during brain imaging recording in both neuroscience experiments and diagnostic situations. Recent literature showed how this position and similar ones with head down are associated to reduced plasticity, impaired pain and emotional responses. The present study aimed at further understanding the decrease of cortical activity associated with horizontal body position by measuring high-frequency EEG bands – typically associated with high-level cognitive activation – in a resting state experimental condition. To this end, two groups of 16 female students were randomly assigned to either sitting control (SC or 2-h horizontal Bed Rest condition (hBR while EEG was recorded from 38 scalp recording sites. The hBR group underwent several body transitions, from sitting to supine, and from supine to sitting. Results revealed a clear effect of horizontal posture: the hBR group showed, compared to its baseline and to SC, reduced High-Beta and Gamma EEG band amplitudes throughout the 2-h of hBR condition. In addition, before and after the supine condition, hBR group as well as SC exhibited a greater left vs. right frontal activation in both EEG bands while, on the contrary, the supine position induced a bilateral and reduced activation in hBR participants. The cortical sources significantly more active in SC compared with hBR participants included the left Inferior Frontal Gyrus and left Insula. Results are discussed in relation to the differences among neuroimaging methods (e.g., fMRI, EEG, NIRS, which can be partially explained by posture-induced neural network changes.

  5. p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

    Science.gov (United States)

    Menon, Ramkumar; Papaconstantinou, John

    2016-01-01

    Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

  6. Positive criminology in practice.

    Science.gov (United States)

    Ronel, Natti; Segev, Dana

    2014-11-01

    The discourse regarding offender rehabilitation has been criticized by various scholars who have claimed that reducing negative causes and managing risk will not automatically prompt positive human development and elements that are associated with desistance. Positive criminology is an innovative concept that challenges the common preoccupation with negative elements, by placing emphasis on human encounters and forces of inclusion that are experienced positively by target individuals and that can promote crime desistance. However, as the concept is relatively new, there are still no guiding principles for the practice of positive criminology that could direct research and the criminal justice system. This article attempts to fill that gap by providing principles that could be practiced by criminal justice personnel and examples of different interventions that reflect positive criminology. The article also provides ideological explanations for adopting the concept of positive criminology in practice. © The Author(s) 2013.

  7. School, Supervision and Adolescent-Sensitive Clinic Care: Combination Social Protection and Reduced Unprotected Sex Among HIV-Positive Adolescents in South Africa.

    Science.gov (United States)

    Toska, Elona; Cluver, Lucie D; Boyes, Mark E; Isaacsohn, Maya; Hodes, Rebecca; Sherr, Lorraine

    2017-09-01

    Social protection can reduce HIV-risk behavior in general adolescent populations, but evidence among HIV-positive adolescents is limited. This study quantitatively tests whether social protection is associated with reduced unprotected sex among 1060 ART-eligible adolescents from 53 government facilities in South Africa. Potential social protection included nine 'cash/cash-in-kind' and 'care' provisions. Analyses tested interactive/additive effects using logistic regressions and marginal effects models, controlling for covariates. 18 % of all HIV-positive adolescents and 28 % of girls reported unprotected sex. Lower rates of unprotected sex were associated with access to school (OR 0.52 95 % CI 0.33-0.82 p = 0.005), parental supervision (OR 0.54 95 % CI 0.33-0.90 p = 0.019), and adolescent-sensitive clinic care (OR 0.43 95 % CI 0.25-0.73 p = 0.002). Gender moderated the effect of adolescent-sensitive clinic care. Combination social protection had additive effects amongst girls: without any provisions 49 % reported unprotected sex; with 1-2 provisions 13-38 %; and with all provisions 9 %. Combination social protection has the potential to promote safer sex among HIV-positive adolescents, particularly girls.

  8. Development of a Targeted anti-HER2 scFv Chimeric Peptide for Gene Delivery into HER2-Positive Breast Cancer Cells.

    Science.gov (United States)

    Cheraghi, Roya; Nazari, Mahboobeh; Alipour, Mohsen; Majidi, Asia; Hosseinkhani, Saman

    2016-12-30

    Chimeric polymers are known as suitable carriers for gene delivery. Certain properties are critical for a polymer to be used as a gene delivery vector. A new polymer was designed for the targeted delivery of genes into breast cancer cell lines, based on MPG peptide. It is composed of different functional domains, including HIV gp41, nuclear localization sequence of SV40 T-antigen, two C-terminus repeats of histone H1, and the scFv of anti-HER2 antibody. The results demonstrated that the vector can effectively condense plasmid DNA into nanoparticles with an average size of 250nm. Moreover, fusion of the scFv portion to the carrier brought about the specific recognition of HER2. Overall, the transfection efficiency of the vector demonstrated that it could deliver the desired gene into BT-474 HER2-positive breast cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. A Targeted and Tailored eHealth Weight Loss Program for Young Women: The Be Positive Be Healthe Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Melinda J. Hutchesson

    2018-05-01

    Full Text Available Young women are gaining weight rapidly. Evidence for effective weight loss interventions targeting young women is lacking. This randomized controlled trial assessed the efficacy and acceptability of a six-month targeted and tailored eHealth weight loss program for young women (Be Positive Be Healthe (BPBH. Women aged 18–35 years were randomized to BPBH (n = 29 or control (n = 28. BPBH supported participants to modify diet and physical activity behaviours using evidenced-based strategies (e.g., self-monitoring tailored for young women and delivered using e-health (website, social media, smartphone application, email, text messages. The primary outcome was a change in weight (kg at six months. Acceptability was assessed via a process evaluation survey and usage of intervention components. No significant between-group differences were observed for weight, with significant mean differences favouring the intervention group observed for body fat (kg (−3.10 (−5.69, 0.52, p = 0.019 and intakes of alcohol (g (−0.69 (−1.33, 0.04, p = 0.037, vegetables (% energy/day (4.71 (−2.20, 7.22, p < 0.001 and energy-dense, nutrient-poor foods (% energy/day (−9.23 (−16.94, 1.52, p = 0.018. Retention, intervention usage and satisfaction were moderate. BPBH facilitated positive improvements in body fat and dietary intake, but not weight. Intervention acceptability findings support the use of some intervention components (e.g., Facebook, Smartphone app with young women.

  10. miR-25-3p, Positively Regulated by Transcription Factor AP-2α, Regulates the Metabolism of C2C12 Cells by Targeting Akt1

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2018-03-01

    Full Text Available miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K gene expression and triglyceride (TG content, and enhancing the content of adenosine triphosphate (ATP and reactive oxygen species (ROS. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1 3′ untranslated region (3′UTR. The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2α (AP-2α significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP assay, and AP-2α binding also downregulated the expression of Akt1. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2α, enhances C2C12 cell metabolism by targeting the Akt1 gene.

  11. Target volume definition for {sup 18}F-FDG PET-positive lymph nodes in radiotherapy of patients with non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nestle, Ursula; Schaefer-Schuler, Andrea; Hellwig, Dirk; Kirsch, Carl-Martin [Saarland University Medical Centre, Department of Nuclear Medicine, Homburg/Saar (Germany); Kremp, Stephanie; Ruebe, Christian [Saarland University Medical Centre, Department of Radio-oncology, Homburg/Saar (Germany); Groeschel, Andreas [Saarland University Medical Centre, Department of Pneumology, Homburg/Saar (Germany)

    2007-04-15

    FDG PET is increasingly used in radiotherapy planning. Recently, we demonstrated substantial differences in target volumes when applying different methods of FDG-based contouring in primary lung tumours (Nestle et al., J Nucl Med 2005;46:1342-8). This paper focusses on FDG-positive mediastinal lymph nodes (LN{sub PET}). In our institution, 51 NSCLC patients who were candidates for radiotherapy prospectively underwent staging FDG PET followed by a thoracic PET scan in the treatment position and a planning CT. Eleven of them had 32 distinguishable non-confluent mediastinal or hilar nodal FDG accumulations (LN{sub PET}). For these, sets of gross tumour volumes (GTVs) were generated at both acquisition times by four different PET-based contouring methods (visual: GTV{sub vis}; 40% SUV{sub max}: GTV{sub 40}; SUV=2.5: GTV{sub 2.5}; target/background (T/B) algorithm: GTV{sub bg}). All differences concerning GTV sizes were within the range of the resolution of the PET system. The detectability and technical delineability of the GTVs were significantly better in the late scans (e.g. p = 0.02 for diagnostic application of SUV{sub max} = 2.5; p = 0.0001 for technical delineability by GTV{sub 2.5}; p = 0.003 by GTV{sub 40}), favouring the GTV{sub bg} method owing to satisfactory overall applicability and independence of GTVs from acquisition time. Compared with CT, the majority of PET-based GTVs were larger, probably owing to resolution effects, with a possible influence of lesion movements. For nodal GTVs, different methods of contouring did not lead to clinically relevant differences in volumes. However, there were significant differences in technical delineability, especially after early acquisition. Overall, our data favour a late acquisition of FDG PET scans for radiotherapy planning, and the use of a T/B algorithm for GTV contouring. (orig.)

  12. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer.

    Science.gov (United States)

    Thangavelu, Pulari U; Lin, Cheng-Yu; Vaidyanathan, Srividya; Nguyen, Thu H M; Dray, Eloise; Duijf, Pascal H G

    2017-09-22

    During cell division, chromosome segregation is facilitated by the mitotic checkpoint, or spindle assembly checkpoint (SAC), which ensures correct kinetochore-microtubule attachments and prevents premature sister-chromatid separation. It is well established that misexpression of SAC components on the outer kinetochores promotes chromosome instability (CIN) and tumorigenesis. Here, we study the expression of CENP-I, a key component of the HIKM complex at the inner kinetochores, in breast cancer, including ductal, lobular, medullary and male breast carcinomas. CENPI mRNA and protein levels are significantly elevated in estrogen receptor-positive (ER+) but not in estrogen receptor-negative (ER-) breast carcinoma. Well-established prognostic tests indicate that CENPI overexpression constitutes a powerful independent marker for poor patient prognosis and survival in ER+ breast cancer. We further demonstrate that CENPI is an E2F target gene. Consistently, it is overexpressed in RB1 -deficient breast cancers. However, CENP-I overexpression is not purely due to cell cycle-associated expression. In ER+ breast cancer cells, CENP-I overexpression promotes CIN, especially chromosome gains. In addition, in ER+ breast carcinomas the degree of CENPI overexpression is proportional to the level of aneuploidy and CENPI overexpression is one of the strongest markers for CIN identified to date. Our results indicate that overexpression of the inner kinetochore protein CENP-I promotes CIN and forecasts poor prognosis for ER+ breast cancer patients. These observations provide novel mechanistic insights and have important implications for breast cancer diagnostics and potentially therapeutic targeting.

  13. HES1, a target of Notch signaling, is elevated in canine osteosarcoma, but reduced in the most aggressive tumors.

    Science.gov (United States)

    Dailey, Deanna D; Anfinsen, Kristin P; Pfaff, Liza E; Ehrhart, E J; Charles, J Brad; Bønsdorff, Tina B; Thamm, Douglas H; Powers, Barbara E; Jonasdottir, Thora J; Duval, Dawn L

    2013-07-01

    Hairy and enhancer of split 1 (HES1), a basic helix-loop-helix transcriptional repressor, is a downstream target of Notch signaling. Notch signaling and HES1 expression have been linked to growth and survival in a variety of human cancer types and have been associated with increased metastasis and invasiveness in human osteosarcoma cell lines. Osteosarcoma (OSA) is an aggressive cancer demonstrating both high metastatic rate and chemotherapeutic resistance. The current study examined expression of Notch signaling mediators in primary canine OSA tumors and canine and human osteosarcoma cell lines to assess their role in OSA development and progression. Reverse transcriptase - quantitative PCR (RT-qPCR) was utilized to quantify HES1, HEY1, NOTCH1 and NOTCH2 gene expression in matched tumor and normal metaphyseal bone samples taken from dogs treated for appendicular OSA at the Colorado State University Veterinary Teaching Hospital. Gene expression was also assessed in tumors from dogs with a disease free interval (DFI) of  300 days following treatment with surgical amputation followed by standard chemotherapy. Immunohistochemistry was performed to confirm expression of HES1. Data from RT-qPCR and immunohistochemical (IHC) experiments were analyzed using REST2009 software and survival analysis based on IHC expression employed the Kaplan-Meier method and log rank analysis. Unbiased clustered images were generated from gene array analysis data for Notch/HES1 associated genes. Gene array analysis of Notch/HES1 associated genes suggested alterations in the Notch signaling pathway may contribute to the development of canine OSA. HES1 mRNA expression was elevated in tumor samples relative to normal bone, but decreased in tumor samples from dogs with a DFI 300 days. NOTCH2 and HEY1 mRNA expression was also elevated in tumors relative to normal bone, but was not differentially expressed between the DFI tumor groups. Survival analysis confirmed an association between

  14. Compatibility of reduced-risk insecticides with the non-target predatory mite Iphiseius degenerans (Acari: Phytoseiidae).

    Science.gov (United States)

    Döker, İsmail; Pappas, Maria L; Samaras, Konstantinos; Triantafyllou, Anneta; Kazak, Cengiz; Broufas, George D

    2015-09-01

    Iphiseius degenerans (Berlese) (Acari: Phytoseiidae) is a common predatory mite in citrus orchards in some areas of the Mediterranean basin and an important biological control agent of the thrips Frankliniella occidentalis (Pergande) in Integrated Pest Management (IPM) programmes in greenhouse crops. In this study, we evaluated the effects of the 'reduced-risk' insecticides acetamiprid, chlorantraniliprole, flubendiamide, metaflumizone, methoxyfenozide, spinetoram and thiamethoxam on I. degenerans, as a means of testing their compatibility in IPM programmes. Although all pesticides decreased immature survival, high mortality was only recorded for young larvae when exposed to acetamiprid, while metaflumizone, thiamethoxam and spinetoram resulted in intermediate lethal effects. The estimated LC50 values of acetamiprid, spinetoram and thiamethoxam for I. degenerans females were 0.52, 0.84 and 0.16-fold lower than the respective maximum recommended doses of the pesticides for field application. Although all pesticides tested significantly decreased fecundity, highest rates corresponded to the three pesticides already mentioned. Chlorantraniliprole, flubendiamide and methoxyfenozide may preliminarily be included in IPM programmes, whereas the effects of acetamiprid, metaflumizone, spinetoram and thiamethoxam on I. degenerans should be clarified in further field toxicological tests. This information could be useful for rationally planning and implementing pest management on a sustainable basis. © 2014 Society of Chemical Industry.

  15. Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

    Directory of Open Access Journals (Sweden)

    Kuo-Hsuan Chang

    2013-01-01

    Full Text Available Spinocerebellar ataxia (SCA types 1, 2, 3, 6, 7, and 17 as well as Huntington’s disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.

  16. One or many? Which and how many parenting variables should be targeted in interventions to reduce children's externalizing behavior?

    Science.gov (United States)

    Loop, Laurie; Mouton, Bénédicte; Stievenart, Marie; Roskam, Isabelle

    2017-05-01

    This research compared the efficacy of two parenting interventions that vary according to the number and the nature of variables in reducing preschoolers' externalizing behavior (EB). The goal was to identify which parenting intervention format (one-variable versus two-variable) caused higher behavioral adjustment in children. The first was a one-variable intervention manipulating parental self-efficacy beliefs. The second was a two-variable intervention manipulating both parents' self-efficacy beliefs and emotion coaching practices. The two interventions shared exactly the same design, consisting of eight parent group sessions. Effect on children's EB and observed behaviors were evaluated through a multi-method assessment at three points (pre-test, post-test and follow-up). The results highlighted that compared to the waitlist condition, the two intervention formats tended to cause a significant reduction in children's EB reported by their parent. However, the one-variable intervention was found to lead to a greater decrease in children's EB at follow-up. The opposite was reported for children's observed behavior, which was improved to a greater extent in the two-variable intervention at post-test and follow-up. The results illustrated that interventions' format cannot be considered as purely interchangeable since their impact on children's behavior modification is different. The results are discussed for their research and clinical implications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effect of DOTA position on melanoma targeting and pharmacokinetic properties of 111In-labeled lactam bridge-cyclized alpha-melanocyte stimulating hormone peptide.

    Science.gov (United States)

    Guo, Haixun; Yang, Jianquan; Gallazzi, Fabio; Prossnitz, Eric R; Sklar, Larry A; Miao, Yubin

    2009-11-01

    The purpose of this study was to examine the effect of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) position on melanoma targeting and pharmacokinetics of radiolabeled lactam bridge-cyclized alpha-melanocyte stimulating hormone (alpha-MSH) peptide. A novel lactam bridge-cyclized alpha-MSH peptide, Ac-GluGlu-CycMSH[DOTA] {Ac-Glu-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Lys(DOTA)]}, was synthesized using standard 9-fluorenylmethyloxycarbonyl (Fmoc) chemistry. DOTA was directly attached to the alpha-amino group of Lys in the cyclic ring, while the N-terminus of the peptide was acetylated to generate Ac-GluGlu-CycMSH[DOTA]. The MC1 receptor binding affinity of Ac-GluGlu-CycMSH[DOTA] was determined in B16/F1 melanoma cells. Melanoma targeting and pharmacokinetic properties of Ac-GluGlu-CycMSH[DOTA]-111In were determined in B16/F1 melanoma-bearing C57 mice and compared to that of 111In-DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp] (111In-DOTA-GlyGlu-CycMSH; DOTA was coupled to the N-terminus of the peptide). Ac-GluGlu-CycMSH[DOTA] displayed 0.6 nM MC1 receptor binding affinity in B16/F1 cells. Ac-GluGlu-CycMSH[DOTA]-111In was readily prepared with greater than 95% radiolabeling yield. Ac-GluGlu-CycMSH[DOTA]-111In exhibited high tumor uptake (11.42 +/- 2.20% ID/g 2 h postinjection) and prolonged tumor retention (9.42 +/- 2.41% ID/g 4 h postinjection) in B16/F1 melanoma-bearing C57 mice. The uptake values for nontarget organs were generally low (<1.3% ID/g) except for the kidneys 2, 4, and 24 h postinjection. DOTA position exhibited profound effect on melanoma targeting and pharmacokinetic properties of Ac-GluGlu-CycMSH[DOTA]-111In, providing a new insight into the design of lactam bridge-cyclized peptide for melanoma imaging and therapy.

  18. Reducing mortality in HIV-infected infants and achieving the 90–90–90 target through innovative diagnosis approaches

    Science.gov (United States)

    Essajee, Shaffiq; Vojnov, Lara; Penazzato, Martina; Jani, Ilesh; Siberry, George K; Fiscus, Susan A; Markby, Jessica

    2015-01-01

    -to-child transmission. Facility-based SMS printers speed up the return of laboratory results and may be of value for other testing services apart from HIV infant diagnosis. Conclusions New tools and strategies for HIV infant diagnosis could have a significant positive impact on the identification and retention of HIV-infected infants. In order to be most effective, national programmes should carefully consider which ideas to implement and how best to integrate novel strategies into existing systems. There is no single solution that will work everywhere. Rather, a number of approaches need to be considered and should be linked in order to achieve the greatest impact on the continuum of care from testing to treatment. PMID:26639120

  19. Reducing mortality in HIV-infected infants and achieving the 90-90-90 target through innovative diagnosis approaches.

    Science.gov (United States)

    Essajee, Shaffiq; Vojnov, Lara; Penazzato, Martina; Jani, Ilesh; Siberry, George K; Fiscus, Susan A; Markby, Jessica

    2015-01-01

    printers speed up the return of laboratory results and may be of value for other testing services apart from HIV infant diagnosis. New tools and strategies for HIV infant diagnosis could have a significant positive impact on the identification and retention of HIV-infected infants. In order to be most effective, national programmes should carefully consider which ideas to implement and how best to integrate novel strategies into existing systems. There is no single solution that will work everywhere. Rather, a number of approaches need to be considered and should be linked in order to achieve the greatest impact on the continuum of care from testing to treatment.

  20. Targeting early PKCθ-dependent T-cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy.

    Science.gov (United States)

    Lozanoska-Ochser, Biliana; Benedetti, Anna; Rizzo, Giuseppe; Marrocco, Valeria; Di Maggio, Rosanna; Fiore, Piera; Bouche, Marina

    2018-03-01

    Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions. We focused on protein kinase C θ (PKCθ, encoded by Prkcq), a critical regulator of effector T-cell activation, as a potential target to inhibit T-cell activity in dystrophic muscle. Lack of PKCθ not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in mdx/Prkcq -/- muscle. These changes were due to the inhibition of T cells, since PKCθ was necessary for T-cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKCθ inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T-cell infiltrate as a therapeutic target and highlight the potential of PKCθ inhibition as a therapeutic approach to muscular dystrophy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Multifactorial assessment and targeted intervention to reduce falls among the oldest-old: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ferrer A

    2014-02-01

    Full Text Available Assumpta Ferrer,1 Francesc Formiga,2,3 Héctor Sanz,4 Oscar J de Vries,5 Teresa Badia,6 Ramón Pujol2,3 On behalf of the OCTABAIX Study Group 1Primary Healthcare Centre "El Plà" CAP-I, Sant Feliu de Llobregat, 2Geriatric Unit, Internal Medicine Service, Hospital Universitari de Bellvitge, 3Bellvitge Biomedical Research Institute, IDIBELL, L'Hospitalet de Llobregat, 4Support Research Unit, Primary Health Department Costa Ponent, IDIAP Jordi Gol, Barcelona, Spain; 5Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands; 6Primary Healthcare Centre Martorell, Barcelona, Spain Background: The purpose of this study was to assess the effectiveness of a multifactorial intervention to reduce falls among the oldest-old people, including individuals with cognitive impairment or comorbidities. Methods: A randomized, single-blind, parallel-group clinical trial was conducted from January 2009 to December 2010 in seven primary health care centers in Baix Llobregat (Barcelona. Of 696 referred people who were born in 1924, 328 were randomized to an intervention group or a control group. The intervention model used an algorithm and was multifaceted for both patients and their primary care providers. Primary outcomes were risk of falling and time until falls. Data analyses were by intention-to-treat. Results: Sixty-five (39.6% subjects in the intervention group and 48 (29.3% in the control group fell during follow-up. The difference in the risk of falls was not significant (relative risk 1.28, 95% confidence interval [CI] 0.94–1.75. Cox regression models with time from randomization to the first fall were not significant. Cox models for recurrent falls showed that intervention had a negative effect (hazard ratio [HR] 1.46, 95% CI 1.03–2.09 and that functional impairment (HR 1.42, 95% CI 0.97–2.12, previous falls (HR 1.09, 95% CI 0.74–1.60, and cognitive impairment (HR 1.08, 95% CI 0.72–1.60 had no effect on the

  2. Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.

    Science.gov (United States)

    Byrareddy, Siddappa N; Kallam, Brianne; Arthos, James; Cicala, Claudia; Nawaz, Fatima; Hiatt, Joseph; Kersh, Ellen N; McNicholl, Janet M; Hanson, Debra; Reimann, Keith A; Brameier, Markus; Walter, Lutz; Rogers, Kenneth; Mayne, Ann E; Dunbar, Paul; Villinger, Tara; Little, Dawn; Parslow, Tristram G; Santangelo, Philip J; Villinger, Francois; Fauci, Anthony S; Ansari, Aftab A

    2014-12-01

    α4β7 integrin-expressing CD4(+) T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIVmac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4(+) T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.

  3. Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

    International Nuclear Information System (INIS)

    Hanley, J.; Debois, M.M.; Raben, A.; Mageras, G.S.; Lutz, W.R.; Mychalczak, B.; Schwartz, L.H.; Gloeggler, P.J.; Leibel, S.A.; Fuks, Z.; Kutcher, G.J.

    1996-01-01

    Purpose/Objective: Lung tumors are subject to movement due to respiratory motion. Conventionally, a margin is applied to the clinical target volume (CTV) to account for this and other treatment uncertainties. The purpose of this study is to evaluate the dosimetric benefits of a deep inspiration breath-hold (DIBH) technique which has two distinct features - deep inspiration which reduces lung density and breath-hold which immobilizes lung tumors. Both properties can potentially reduce the mass of normal lung tissue in the high dose region, thus improving the possibility of dose escalation. Methods and Materials: To study the efficacy of the DIBH technique, CT scans are acquired for each patient under 4 respiration conditions: free-breathing; DIBH; shallow inspiration breath-hold; shallow expiration breath-hold. The free-breathing and DIBH scans are used to generate treatment plans for comparison of standard and DIBH techniques, while the shallow inspiration and expiration scans provide information on the maximum extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry and slow vital capacity maneuvers. For the treatment plan comparison free-breathing and DIBH planning target volumes (PTVs) are constructed consisting of the CTV plus a margin for setup error and lung tumor motion. For both plans the margin for setup error is the same while the margin for lung tumor motion differs. The margin for organ motion in free-breathing is determined by the maximum tumor excursions in the shallow inspiration and expiration CT scans. For the DIBH, tumor motion is reduced to the extent to which DIBH can be maintained and the margin for any residual tumor motion is determined from repeat fluoroscopic movies, acquired with the patient monitored using spirometry. Three-dimensional treatment plans, generated using apertures based on the free-breathing and DIBH PTVs, are

  4. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    Energy Technology Data Exchange (ETDEWEB)

    McGurk, Ross J. [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Bowsher, James; Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Lee, John A [Molecular Imaging and Experimental Radiotherapy Unit, Universite Catholique de Louvain, 1200 Brussels (Belgium)

    2013-04-15

    Purpose: Many approaches have been proposed to segment high uptake objects in 18F-fluoro-deoxy-glucose positron emission tomography images but none provides consistent performance across the large variety of imaging situations. This study investigates the use of two methods of combining individual segmentation methods to reduce the impact of inconsistent performance of the individual methods: simple majority voting and probabilistic estimation. Methods: The National Electrical Manufacturers Association image quality phantom containing five glass spheres with diameters 13-37 mm and two irregularly shaped volumes (16 and 32 cc) formed by deforming high-density polyethylene bottles in a hot water bath were filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to-background contrasts for spherical objects and 4.5:1 and 9:1 for irregular objects. Five individual methods were used to segment each object: 40% thresholding, adaptive thresholding, k-means clustering, seeded region-growing, and a gradient based method. Volumes were combined using a majority vote (MJV) or Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of segmentations relative to CT ground truth volumes were assessed using the Dice similarity coefficient (DSC) and the symmetric mean absolute surface distances (SMASDs). Results: MJV had median DSC values of 0.886 and 0.875; and SMASD of 0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and 0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p= 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p= 0.0027). DSC was not significantly

  5. Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration*

    Science.gov (United States)

    Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B.; van der Hoorn, Frans A.

    2016-01-01

    The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. PMID:27226580

  6. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  7. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Directory of Open Access Journals (Sweden)

    Yongsoon Kim

    Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  8. ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

  9. Randomized controlled trial of a positive affect intervention to reduce stress in people newly diagnosed with HIV; protocol and design for the IRISS study

    Directory of Open Access Journals (Sweden)

    Moskowitz JT

    2014-09-01

    currently few established interventions for people who are newly diagnosed with HIV. We present the design and methods for a randomized trial in which we test the efficacy of one such skills-based intervention that targets positive affect as a novel mechanism of change. The proposed research builds on observational findings of the important unique functions of positive affect. We aim to determine whether a five-session theory- and evidence-based intervention designed to teach skills for increasing the frequency and intensity of daily positive affect does so, and whether this intervention has beneficial effects on subsequent psychological well-being, health behaviors, and physical health up to 15 months after diagnosis with HIV. This is a randomized controlled trial in a sample of adults recruited within 12 weeks of testing positive for HIV. The control group is attention-matched, and follow up assessments will be conducted immediately post intervention (approximately 5 months post diagnosis and at 10 and 15 months post diagnosis. This study is an important next step in research concerning the adaptive functions of positive affect for people coping with HIV or other health-related life stress. Keywords: positive affect, HIV diagnosis, stress, coping, RCT, intervention, physical health

  10. Encapsulation of temozolomide in a tumor-targeting nanocomplex enhances anti-cancer efficacy and reduces toxicity in a mouse model of glioblastoma.

    Science.gov (United States)

    Kim, Sang-Soo; Rait, Antonina; Kim, Eric; DeMarco, James; Pirollo, Kathleen F; Chang, Esther H

    2015-12-01

    Although temozolomide (TMZ) is the current first-line chemotherapy for glioblastoma multiforme (GBM), most patients either do not respond or ultimately fail TMZ treatment. Both intrinsic tumor resistance and limited access of TMZ to brain tumors as a result of the blood-brain barrier (BBB) contribute to poor response and ultimately to poor prognosis for GBM patients. We have developed a "dual-targeting" nanomedicine that both actively crosses the BBB and actively targets cancer cells once in the brain parenchyma. This nanomedicine (termed scL-TMZ) is sized ~40 nm and comprised of a cationic liposome (DOTAP:DOPE) encapsulating TMZ. The surface of liposome is decorated with anti-transferrin receptor single-chain antibody fragments to facilitate the crossing of the BBB by the scL-TMZ in addition to targeting GBM in the brain. This novel formulation was found to be markedly more effective than standard TMZ in both TMZ-resistant and TMZ-sensitive GBM. Encapsulation of TMZ also markedly enhanced its efficacy in killing a variety of non-GBM tumor cells. The scL-TMZ nanocomplex was shown to target cancer stem cells, which have been linked to both drug resistance and recurrence in GBM. Most significantly, systemically administered scL-TMZ significantly prolonged survival in mice bearing intracranial GBM tumors. The improved efficacy of scL-TMZ compared to standard TMZ was accompanied by reduced toxicity, so we conclude that the scL-TMZ nanomedicine holds great promise as a more effective therapy for GBM and other tumor types. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus.

    Directory of Open Access Journals (Sweden)

    Sabine Dittrich

    Full Text Available Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP. To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require 90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i time-to-result <10 min (but maximally <2 hrs; ii storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv minimal sample collection needs (50-100μL, capillary blood. This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.

  12. PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer

    International Nuclear Information System (INIS)

    Owadally, Waheeda; Hurt, Chris; Timmins, Hayley; Parsons, Emma; Townsend, Sarah; Patterson, Joanne; Hutcheson, Katherine; Powell, Ned; Beasley, Matthew; Palaniappan, Nachi; Robinson, Max; Jones, Terence M.; Evans, Mererid

    2015-01-01

    Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes. The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint. PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity

  13. Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine substitution at the 16α-position of fulvestrant (faslodex; ICI 182,780)

    International Nuclear Information System (INIS)

    Seimbille, Yann; Benard, Francois; Rousseau, Jacques; Pepin, Emilie; Aliaga, Antonio; Tessier, Guillaume; Lier, Johan E. van

    2004-01-01

    Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16α-[ 18 F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ERα and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18 F would have led to a product of low specific activity; instead we selected the 16α-position for 18 F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [ 18 F]fluoride at the 16- 18 F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16 18 F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators

  14. Tumor-Targeting Salmonella typhimurium A1-R in Combination with Trastuzumab Eradicates HER-2-Positive Cervical Cancer Cells in Patient-Derived Mouse Models.

    Directory of Open Access Journals (Sweden)

    Yukihiko Hiroshima

    Full Text Available We have previously developed mouse models of HER-2-positive cervical cancer. Tumors in nude mice had histological structures similar to the original tumor and were stained by anti-HER-2 antibody in the same pattern as the patient's cancer. We have also previously developed tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with trastuzumab on a patient-cancer nude-mouse model of HER-2 positive cervical cancer. Mice were randomized to 5 groups and treated as follows: (1 no treatment; (2 carboplatinum (30 mg/kg, ip, weekly, 5 weeks; (3 trastuzumab (20 mg/kg, ip, weekly, 5 weeks; (4 S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks; (5 S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks + trastuzumab (20 mg/kg, ip, weekly, 5 weeks. All regimens had significant efficacy compared to the untreated mice. The relative tumor volume of S. typhimurium A1-R + trastuzumab-treated mice was smaller compared to trastuzumab alone (p = 0.007 and S. typhimurium A1-R alone (p = 0.039. No significant body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021. Upon histological examination, viable tumor cells were not detected, and replaced by stromal cells in the tumors treated with S. typhimurium A1-R + trastuzumab. The results of the present study suggest that S. typhimurium A1-R and trastuzumab in combination are highly effective against HER-2-expressing cervical cancer.

  15. A Self-Paced, Web-Based, Positive Emotion Skills Intervention for Reducing Symptoms of Depression: Protocol for Development and Pilot Testing of MARIGOLD.

    Science.gov (United States)

    Cheung, Elaine O; Addington, Elizabeth L; Bassett, Sarah M; Schuette, Stephanie A; Shiu, Eva W; Cohn, Michael A; Leykin, Yan; Saslow, Laura R; Moskowitz, Judith T

    2018-06-05

    Living with elevated symptoms of depression can have debilitating consequences for an individual's psychosocial and physical functioning, quality of life, and health care utilization. A growing body of evidence demonstrates that skills for increasing positive emotion can be helpful to individuals with depression. Although Web-based interventions to reduce negative emotion in individuals with depression are available, these interventions frequently suffer from poor retention and adherence and do not capitalize on the potential benefits of increasing positive emotion. The aim of this study was to develop and test a Web-based positive emotion skills intervention tailored for individuals living with elevated depressive symptoms, as well as to develop and test enhancement strategies for increasing retention and adherence to that intervention. This study protocol describes the development and testing for Mobile Affect Regulation Intervention with the Goal of Lowering Depression (MARIGOLD), a Web-based positive emotion skills intervention, adapted for individuals with elevated depressive symptomatology. The intervention development is taking place in three phases. In phase 1, we are tailoring an existing positive emotion skills intervention for individuals with elevated symptoms of depression and are pilot testing the tailored version of the intervention in a randomized controlled trial with two control conditions (N=60). In phase 2, we are developing and testing three enhancements aimed at boosting retention and adherence to the Web-based intervention (N=75): facilitator contact, an online discussion board, and virtual badges. In phase 3, we are conducting a multifactorial, nine-arm pilot trial (N=600) to systematically test these enhancement strategies, individually and in combination. The primary outcome is depressive symptom severity. Secondary outcomes include positive and negative emotion, psychological well-being, and coping resources. The project was funded in

  16. Use of tuf as a target for sequence-based identification of Gram-positive cocci of the genus Enterococcus, Streptococcus, coagulase-negative Staphylococcus, and Lactococcus

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    Li Xuerui

    2012-11-01

    Full Text Available Abstract Background Accurate identification of isolates belonging to genus Enterococcus, Streptococcus, coagulase-negative Staphylococcus, and Lactococcus at the species level is necessary to provide a better understanding of their pathogenic potential, to aid in making clinical decisions, and to conduct epidemiologic investigations,especially when large blind samples must be analyzed. It is useful to simultaneously identify species in different genera using a single primer pair. Methods We developed a primer pair based on the tuf gene (encoding elongation factor sequence to identify 56 Gram-positive cocci isolates. Results The target sequences were amplified from all 56 samples. The sequencing results and the phylogenetic tree derived from the partial tuf gene sequences identified the isolates as three enterococcal species, two lactococcal species, two staphylococcal species, and six streptococcal species, as well as eight isolates that were novel species of the genus Streptococcus. Partial gene sequence analysis of the sodA, dnaK, and 16S RNA genes confirmed the results obtained by tuf gene sequencing. Conclusion Based on the uniform amplification of the tuf gene from all samples and the ability to identify all isolates at both the genus and species levels, we conclude that the primer pair developed in this research provides a powerful tool for identifying these organisms in clinical laboratories where large blind samples are used.

  17. Preparation and evaluation of a new neurotensin analog labeled with 99mTc for targeted imaging of neurotensin receptor positive tumors

    International Nuclear Information System (INIS)

    Nakisa Zarrabi Ahrabi; Kazem Parivar; Davood Beiki

    2014-01-01

    Neurotensin receptors are overexpressed in several human tumors and can be targets for tumors diagnosis and therapy. In this study, a new neurotensin analogue was labeled with 99m Tc via HYNIC and tricine/EDDA as coligands and investigated further. [HYNIC 0 , Gly 7 , Lys 9 , d-Tyr 11 ]-Neurotensin (7-13) was synthesized using a standard Fmoc strategy. Labeling with 99m Tc was performed at 100 deg C for 10 min and radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was checked in the presence of humane serum at 37 deg C up to 24 h. The receptor bound internalization and externalization rates were studied in neurotensin receptor expressing HT-29 cells. Biodistribution of radiopeptide was studied in nude mice bearing HT-29 tumor. Labeling yield of 98.6 ± 0.54 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed specific internalization into HT-29 cells (12.43 ± 0.52 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in neurotensin receptor positive organs so that after 1 h the uptakes in mouse intestine and tumor were 0.87 ± 0.16 and 0.63 ± 0.12 % ID/g respectively. (author)

  18. Comparative Proteomic Analysis of Desulfotomaculum reducens MI-1: Insights into the Metabolic Versatility of a Gram-positive Sulfate and Metal-reducing Bacterium

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    Anne Elyse Otwell

    2016-02-01

    Full Text Available The proteomes of the metabolically versatile and poorly characterized Gram-positive bacterium Desulfotomaculum reducens MI-1 were compared across four cultivation conditions including sulfate reduction, soluble Fe(III reduction, insoluble Fe(III reduction, and pyruvate fermentation. Collectively across conditions, we observed at high confidence ~38% of genome-encoded proteins. Here, we focus on proteins that display significant differential abundance on conditions tested. To the best of our knowledge, this is the first full-proteome study focused on a Gram-positive organism grown either on sulfate or metal-reducing conditions. Several proteins with uncharacterized function encoded within heterodisulfide reductase (hdr-containing loci were upregulated on either sulfate (Dred_0633-4, Dred_0689-90, and Dred_1325-30 or Fe(III-citrate-reducing conditions (Dred_0432-3 and Dred_1778-84. Two of these hdr-containing loci display homology to recently described flavin-based electron bifurcation (FBEB pathways (Dred_1325-30 and Dred_1778-84. Additionally, we propose that a cluster of proteins, which is homologous to a described FBEB lactate dehydrogenase (LDH complex, is performing lactate oxidation in D. reducens (Dred_0367-9. Analysis of the putative sulfate reduction machinery in D. reducens revealed that most of these proteins are constitutively expressed across cultivation conditions tested. In addition, peptides from the single multiheme c-type cytochrome (MHC in the genome were exclusively observed on the insoluble Fe(III condition, suggesting that this MHC may play a role in reduction of insoluble metals.

  19. Modified Reporting of Positive Urine Cultures to Reduce Inappropriate Treatment of Asymptomatic Bacteriuria Among Nonpregnant, Noncatheterized Inpatients: A Randomized Controlled Trial.

    Science.gov (United States)

    Daley, Peter; Garcia, David; Inayatullah, Raheel; Penney, Carla; Boyd, Sarah

    2018-05-28

    DESIGNWe conducted a randomized, parallel, unblinded, superiority trial of a laboratory reporting intervention designed to reduce antibiotic treatment of asymptomatic bacteriuria (ASB).METHODSResults of positive urine cultures from 110 consecutive inpatients at 2 urban acute-care hospitals were randomized to standard report (control) or modified report (intervention). The standard report included bacterial count, bacterial identification, and antibiotic susceptibility information including drug dosage and cost. The modified report stated: "This POSITIVE urine culture may represent asymptomatic bacteriuria or urinary tract infection. If urinary tract infection is suspected clinically, please call the microbiology laboratory … for identification and susceptibility results." We used the following exclusion criteria: age pregnancy, presence of an indwelling urinary catheter, samples from patients already on antibiotics, neutropenia, or admission to an intensive care unit. The primary efficacy outcome was the proportion of appropriate antibiotic therapy prescribed.RESULTSAccording to our intention-to-treat (ITT) analysis, the proportion of appropriate treatment (urinary tract infection treated plus ASB not treated) was higher in the modified arm than in the standard arm: 44 of 55 (80.0%) versus 29 of 55 (52.7%), respectively (absolute difference, -27.3%; RR, 0.42; P = .002; number needed to report for benefit, 3.7).CONCLUSIONSModified reporting resulted in a significant reduction in inappropriate antibiotic treatment without an increase in adverse events. Safety should be further assessed in a large effectiveness trial before implementationTRIAL REGISTRATION. clinicaltrials.gov#NCT02797613Infect Control Hosp Epidemiol 2018;1-6.

  20. Erratum to Visual priming through a boost of the target signal : Evidence from saccadic landing positions (Atten Percept Psychophys, 10.3758/s13414-013-0516-z)

    NARCIS (Netherlands)

    Meeter, M.; Van der Stigchel, S.

    2014-01-01

    Searching for a target is slower when target features change from trial to trial than when they are repeated. Although heavily studied, it is still not wholly clear what process is influenced by such visual priming. Here, we introduce a new measure to study priming. When a target and distractor are

  1. A new three-dimensional conformal radiotherapy (3DCRT) technique for large breast and/or high body mass index patients: evaluation of a novel fields assessment aimed to reduce extra–target-tissue irradiation

    Science.gov (United States)

    Stimato, Gerardina; Ippolito, Edy; Silipigni, Sonia; Venanzio, Cristina Di; Gaudino, Diego; Fiore, Michele; Trodella, Lucio; D'Angelillo, Rolando Maria; Ramella, Sara

    2016-01-01

    Objective: To develop an alternative three-dimensional treatment plan with standardized fields class solution for whole-breast radiotherapy in patients with large/pendulous breast and/or high body mass index (BMI). Methods: Two treatment plans [tangential fields and standardized five-fields technique (S5F)] for a total dose of 50 Gy/25 fractions were generated for patients with large breasts [planning target volume (PTV) >1000 cm3 and/or BMI >25 kg m−2], supine positioned. S5F plans consist of two wedged tangential beams, anteroposterior: 20° for the right breast and 340° for the left breast, and posteroanterior: 181° for the right breast and 179° for the left breast. A field in field in medial–lateral beam and additional fields were added to reduce hot spot areas and extra–target-tissue irradiation and to improve dose distribution. The percentage of PTV receiving 95% of the prescribed dose (PTV V95%), percentage of PTV receiving 105% of the prescribed dose (PTV V105%), maximal dose to PTV (PTV Dmax), homogeneity index (HI) and conformity index were recorded. V10%, V20%, V105% and V107% of a “proper” normal tissue structure (body-PTV healthy tissue) were recorded. Statistical analyses were performed using SYSTAT v.12.0 (SPSS, Chicago, IL). Results: In 38 patients included, S5F improved HI (8.4 vs 10.1; p ≤ 0.001) and significantly reduced PTV Dmax and PTV V105%. The extra–target-tissue irradiation was significantly reduced using S5F for V105% (cm3) and V107% (cm3) with a very high difference in tissue irradiation (46.6 vs 3.0 cm3, p ≤ 0.001 for V105% and 12.2 vs 0.0 cm3, p ≤ 0.001 for V107% for tangential field and S5F plans, respectively). Only a slight increase in low-dose extra–target-tissue irradiation (V10%) was observed (2.2719 vs 1.8261 cm3, p = 0.002). Conclusion: The S5F technique in patients with large breast or high BMI increases HI and decreases hot spots in extra-target-tissues and can therefore be

  2. Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive ‘Chronic Lyme Disease’ Patients: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2012-03-01

    Full Text Available Background: An open label 8-week preliminary study was conducted in a small number of patients to determine if a combination oral supplement containing a mixture of phosphoglycolipids, coenzyme Q10 and microencapsulated NADH and other nutrients could affect fatigue levels in long-term, Western blot-positive, multi-symptom ‘chronic Lyme disease’ patients (also called ‘post-treatment Lyme disease’ or ‘post Lyme syndrome’ with intractable fatigue. Methods: The subjects in this study were 6 males (mean age = 45.1 ± 12.4 years and 10 females (mean age = 54.6 ± 7.4 years with ‘chronic Lyme disease’ (determined by multiple symptoms and positive Western blot analysis that had been symptomatic with chronic fatigue for an average of 12.7 ± 6.6 years. They had been seen by multiple physicians (13.3 ± 7.6 and had used many other remedies, supplements and drugs (14.4 ± 7.4 without fatigue relief. Fatigue was monitored at 0, 7, 30 and 60 days using a validated instrument, the Piper Fatigue Scale.Results: Patients in this preliminary study responded to the combination test supplement, showing a 26% reduction in overall fatigue by the end of the 8-week trial (p< 0.0003. Analysis of subcategories of fatigue indicated that there were significant improvements in the ability to complete tasks and activities as well as significant improvements in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were consistent and occurred with a high degree of confidence (R2= 0.998. Functional Foods in Health and Disease 2012, 2(3:35-47 Conclusions: The combination supplement was a safe and effective method to significantly reduce intractable fatigue in long-term patients with Western blot-positive ‘chronic Lyme disease.’

  3. Medical Students' Exposure to the Humanities Correlates with Positive Personal Qualities and Reduced Burnout: A Multi-Institutional U.S. Survey.

    Science.gov (United States)

    Mangione, Salvatore; Chakraborti, Chayan; Staltari, Giuseppe; Harrison, Rebecca; Tunkel, Allan R; Liou, Kevin T; Cerceo, Elizabeth; Voeller, Megan; Bedwell, Wendy L; Fletcher, Keaton; Kahn, Marc J

    2018-05-01

    Literature, music, theater, and visual arts play an uncertain and limited role in medical education. One of the arguments often advanced in favor of teaching the humanities refers to their capacity to foster traits that not only improve practice, but might also reduce physician burnout-an increasing scourge in today's medicine. Yet, research remains limited. To test the hypothesis that medical students with higher exposure to the humanities would report higher levels of positive physician qualities (e.g., wisdom, empathy, self-efficacy, emotional appraisal, spatial skills), while reporting lower levels of negative qualities that are detrimental to physician well-being (e.g., intolerance of ambiguity, physical fatigue, emotional exhaustion, and cognitive weariness). An online survey. All students enrolled at five U.S. medical schools during the 2014-2015 academic year were invited by email to take part in our online survey. Students reported their exposure to the humanities (e.g., music, literature, theater, visual arts) and completed rating scales measuring selected personal qualities. In all, 739/3107 medical students completed the survey (23.8%). Regression analyses revealed that exposure to the humanities was significantly correlated with positive personal qualities, including empathy (p humanities and both a higher level of students' positive qualities and a lower level of adverse traits. These findings may carry implications for medical school recruitment and curriculum design. "[Science and humanities are] twin berries on one stem, grievous damage has been done to both in regarding [them]... in any other light than complemental." (William Osler, Br Med J. 1919;2:1-7).

  4. Reducing prejudice and promoting positive intergroup attitudes among elementary-school children in the context of the Israeli-Palestinian conflict.

    Science.gov (United States)

    Berger, Rony; Benatov, Joy; Abu-Raiya, Hisham; Tadmor, Carmit T

    2016-08-01

    The current investigation tested the efficacy of the Extended Class Exchange Program (ECEP) in reducing prejudicial attitudes. Three hundred and twenty-two 3rd and 4th grade students from both Israeli-Jewish and Israeli-Palestinian schools in the ethnically mixed city of Jaffa were randomly assigned to either intervention or control classes. Members of the intervention classes engaged in ECEP's activities, whereas members of the control classes engaged in a social-emotional learning program. The program's outcomes were measured a week before, immediately after, and 15months following termination. Results showed that the ECEP decreased stereotyping and discriminatory tendencies toward the other group and increased positive feelings and readiness for social contact with the other group upon program termination. Additionally, the effects of the ECEP were generalized to an ethnic group (i.e., Ethiopians) with whom the ECEP's participants did not have any contact. Finally, the ECEP retained its significant effect 15months after the program's termination, despite the serious clashes between Israel and the Palestinians that occurred during that time. This empirical support for the ECEP'S utility in reducing prejudice makes it potentially applicable to other areas in the world, especially those that are characterized by ethnic tension and violent conflicts. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  5. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    Science.gov (United States)

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. MicroRNA-200b Suppresses Arsenic-transformed Cell Migration by Targeting Protein Kinase Cα and Wnt5b-Protein Kinase Cα Positive Feedback Loop and Inhibiting Rac1 Activation*

    Science.gov (United States)

    Wang, Zhishan; Humphries, Brock; Xiao, Hua; Jiang, Yiguo; Yang, Chengfeng

    2014-01-01

    MicroRNA-200b (miR-200b) is a member of miR-200 family that has been found to inhibit cell migration and cancer metastasis; however, the underlying mechanism is not well understood. We previously reported that miR-200 expression is depleted in arsenic-transformed human bronchial epithelial cells with highly migratory and invasive characteristics, whereas stably re-expressing miR-200b strongly suppresses arsenic-transformed cell migration. This study was performed to investigate how miR-200b inhibits arsenic-transformed cell migration. We found that protein kinase Cα (PKCα) is significantly up-regulated in arsenic-transformed cells. Combining bioinformatics analysis with PKCα 3′-untranslated region vector luciferase reporter assays, we showed that PKCα is a direct target of miR-200b. Inhibiting PKCα activity or knocking down PKCα expression drastically reduced cell migration, phenocoping the inhibitory effect of overexpressing miR-200b. In contrast, forced expression of PKCα in miR-200b overexpressing cells impaired the inhibitory effect of miR-200b on cell migration. In addition, we also found a positive feedback loop between Wnt5b and PKCα in arsenic-transformed cells. Knocking down Wnt5b expression reduced phospho-PKC levels and cell migration; and knocking down PKCα expression decreased Wnt5b level and cell migration. Moreover, forced expression of PKCα increased Wnt5b and phospho-PKC levels and cell migration. Further mechanistic studies revealed that Rac1 is highly activated in arsenic-transformed cells and stably expressing miR-200b abolishes Rac1 activation changing actin cytoskeleton organization. Manipulating PKCα or Wnt5b expression levels significantly altered the level of active Rac1. Together, these findings indicate that miR-200b suppresses arsenic-transformed cell migration by targeting PKCα and Wnt5b-PKCα positive feedback loop and subsequently inhibiting Rac1 activation. PMID:24841200

  7. MicroRNA-200b suppresses arsenic-transformed cell migration by targeting protein kinase Cα and Wnt5b-protein kinase Cα positive feedback loop and inhibiting Rac1 activation.

    Science.gov (United States)

    Wang, Zhishan; Humphries, Brock; Xiao, Hua; Jiang, Yiguo; Yang, Chengfeng

    2014-06-27

    MicroRNA-200b (miR-200b) is a member of miR-200 family that has been found to inhibit cell migration and cancer metastasis; however, the underlying mechanism is not well understood. We previously reported that miR-200 expression is depleted in arsenic-transformed human bronchial epithelial cells with highly migratory and invasive characteristics, whereas stably re-expressing miR-200b strongly suppresses arsenic-transformed cell migration. This study was performed to investigate how miR-200b inhibits arsenic-transformed cell migration. We found that protein kinase Cα (PKCα) is significantly up-regulated in arsenic-transformed cells. Combining bioinformatics analysis with PKCα 3'-untranslated region vector luciferase reporter assays, we showed that PKCα is a direct target of miR-200b. Inhibiting PKCα activity or knocking down PKCα expression drastically reduced cell migration, phenocoping the inhibitory effect of overexpressing miR-200b. In contrast, forced expression of PKCα in miR-200b overexpressing cells impaired the inhibitory effect of miR-200b on cell migration. In addition, we also found a positive feedback loop between Wnt5b and PKCα in arsenic-transformed cells. Knocking down Wnt5b expression reduced phospho-PKC levels and cell migration; and knocking down PKCα expression decreased Wnt5b level and cell migration. Moreover, forced expression of PKCα increased Wnt5b and phospho-PKC levels and cell migration. Further mechanistic studies revealed that Rac1 is highly activated in arsenic-transformed cells and stably expressing miR-200b abolishes Rac1 activation changing actin cytoskeleton organization. Manipulating PKCα or Wnt5b expression levels significantly altered the level of active Rac1. Together, these findings indicate that miR-200b suppresses arsenic-transformed cell migration by targeting PKCα and Wnt5b-PKCα positive feedback loop and subsequently inhibiting Rac1 activation. © 2014 by The American Society for Biochemistry and Molecular

  8. Comparison of two cross-bridged macrocyclic chelators for the evaluation of 64Cu-labeled-LLP2A, a peptidomimetic ligand targeting VLA-4-positive tumors

    International Nuclear Information System (INIS)

    Jiang, Majiong; Ferdani, Riccardo; Shokeen, Monica; Anderson, Carolyn J.

    2013-01-01

    Integrin α 4 β 1 (also called very late antigen-4 or VLA-4) plays an important role in tumor growth, angiogenesis and metastasis, and there has been increasing interest in targeting this receptor for cancer imaging and therapy. In this study, we conjugated a peptidomimetic ligand known to have good binding affinity for α 4 β 1 integrin to a cross-bridged macrocyclic chelator with a methane phosphonic acid pendant arm, CB-TE1A1P. CB-TE1A1P-LLP2A was labeled with 64 Cu under mild conditions in high specific activity, in contrast to conjugates based on the “gold standard” di-acid cross-bridged chelator, CB-TE2A, which require high temperatures for efficient radiolabeling. Saturation binding assays demonstrated that 64 Cu-CB-TE1A1P-LLP2A had comparable binding affinity (1.2 nM vs 1.6 nM) but more binding sites (B max = 471 fmol/mg) in B16F10 melanoma tumor cells than 64 Cu-CB-TE2A-LLP2A (B max = 304 fmol/mg, p 64 Cu-CB-TE1A1P-LLP2A had less renal retention but higher uptake in tumor (11.4 ± 2.3 %ID/g versus 3.1 ± 0.6 %ID/g, p 64 Cu-CB-TE2A-LLP2A. At 2 h post-injection, 64 Cu-CB-TE1A1P-LLP2A also had significantly higher tumor:blood and tumor:muscle ratios than 64 Cu-CB-TE2A-LLP2A (CB-TE1A1P = 19.5 ± 3.0 and 13.0 ± 1.4, respectively, CB-TE2A = 4.2 ± 1.4 and 5.5 ± 0.9, respectively, p 64 Cu-CB-TE1A1P-LLP2A is an excellent PET radiopharmaceutical for the imaging of α 4 β 1 positive tumors and also has potential for imaging other α 4 β 1 positive cells such as those of the pre-metastatic niche

  9. Preclinical evaluation of isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu for folate receptor-positive tumor targeting.

    Science.gov (United States)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Myoung Hyoun; Kim, Dae-Weung; Park, Cho Rong; Park, Ji Yong; Lee, Yun-Sang; Youn, Hyewon; Kang, Keon Wook; Jeong, Jae Min; Chung, June-Key

    2016-06-01

    The purpose of the present study was to prepare isostructural Tc-99m- and Re-188-folate-Gly-Gly-Cys-Glu (folate-GGCE), and to evaluate the feasibility of their use for folate receptor (FR)-targeted molecular imaging and as theranostic agents in a mouse tumor model. Folate-GGCE was synthesized using solid-phase peptide synthesis and radiolabeled with Tc-99m or Re-188. Radiochemical characterization was performed by radio-high-performance liquid chromatography. The biodistribution of Tc-99m-folate-GGCE was studied, with or without co-injection of excess free folate, in mice bearing both FR-positive (KB cell) and FR-negative (HT1080 cell) tumors. Biodistribution of Re-188-folate-GGCE was studied in mice bearing KB tumors. Serial planar scintigraphy was performed in the dual tumor mouse model after intravenous injection of Tc-99m-folate-GGCE. Serial micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies were performed, with or without co-injection of excess free folate, in the mouse tumor model after injection of Tc-99m-folate-GGCE or Re-188-folate-GGCE. The radiolabeling efficiency and radiochemical stability of Tc-99m- and Re-188-folate-GGCE were more than 95 % for up to 4 h after radiolabeling. Uptake of Tc-99m-folate-GGCE at 1, 2, and 4 h after injection in KB tumor was 16.4, 23.2, and 17.6 % injected dose per gram (%ID/g), respectively. This uptake was suppressed by 97.4 % when excess free folate was co-administered. Tumor:normal organ ratios at 4 h for blood, liver, lung, muscle, and kidney were 54.3, 25.2, 38.3, 97.8, and 0.3, respectively. Tumor uptake of Re-188-folate-GGCE at 2, 4, 8, and 16 h after injection was 17.4, 21.7, 24.1, and 15.6 %ID/g, respectively. Tumor:normal organ ratios at 8 h for blood, liver, lung, muscle, and kidney were 126.8, 21.9, 54.8, 80.3, and 0.4, respectively. KB tumors were clearly visualized at a high intensity using serial scintigraphy and micro-SPECT/CT in mice injected with Tc-99m- or Re

  10. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example

    International Nuclear Information System (INIS)

    Rosewall, Tara; Alasti, Hamideh; Bayley, Andrew; Yan, Jing

    2017-01-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2 = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were −0.4 to 1.8 mm (LR), −1.2 to 5.2 mm (SI) and −1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer.

  11. 'Compromise position' image alignment to accommodate independent motion of multiple clinical target volumes during radiotherapy: A high risk prostate cancer example.

    Science.gov (United States)

    Rosewall, Tara; Yan, Jing; Alasti, Hamideh; Cerase, Carla; Bayley, Andrew

    2017-04-01

    Inclusion of multiple independently moving clinical target volumes (CTVs) in the irradiated volume causes an image guidance conundrum. The purpose of this research was to use high risk prostate cancer as a clinical example to evaluate a 'compromise' image alignment strategy. The daily pre-treatment orthogonal EPI for 14 consecutive patients were included in this analysis. Image matching was performed by aligning to the prostate only, the bony pelvis only and using the 'compromise' strategy. Residual CTV surrogate displacements were quantified for each of the alignment strategies. Analysis of the 388 daily fractions indicated surrogate displacements were well-correlated in all directions (r 2  = 0.95 (LR), 0.67 (AP) and 0.59 (SI). Differences between the surrogates displacements (95% range) were -0.4 to 1.8 mm (LR), -1.2 to 5.2 mm (SI) and -1.2 to 5.2 mm (AP). The distribution of the residual displacements was significantly smaller using the 'compromise' strategy, compared to the other strategies (p 0.005). The 'compromise' strategy ensured the CTV was encompassed by the PTV in all fractions, compared to 47 PTV violations when aligned to prostate only. This study demonstrated the feasibility of a compromise position image guidance strategy to accommodate simultaneous displacements of two independently moving CTVs. Application of this strategy was facilitated by correlation between the CTV displacements and resulted in no geometric excursions of the CTVs beyond standard sized PTVs. This simple image guidance strategy may also be applicable to other disease sites that concurrently irradiate multiple CTVs, such as head and neck, lung and cervix cancer. © 2016 The Royal Australian and New Zealand College of Radiologists.

  12. EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: Role of c-Jun N-terminal kinase

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuya; Digumarthi, Hari; Aranbayeva, Zina; Wataha, John; Lewis, Jill; Messer, Regina; Qin, Haiyan; Dickinson, Douglas; Osaki, Tokio; Schuster, George S.; Hsu, Stephen

    2007-01-01

    The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57 often is associated with advanced tumors, and tumor cells with inactivated p57 undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is not well understood. Here, we show that in NHEK, EGCG-induces p57 via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase (JNK). We also found that restoration of p57 expression in tumor cells significantly reduced tumorigenicity in athymic mice. These results suggest that p57 expression may be an useful indicator for the clinical course of cancers, and could be potentially useful as a target for cancer therapies

  13. Effectiveness of a pragmatic school-based universal intervention targeting student resilience protective factors in reducing mental health problems in adolescents.

    Science.gov (United States)

    Dray, Julia; Bowman, Jenny; Campbell, Elizabeth; Freund, Megan; Hodder, Rebecca; Wolfenden, Luke; Richards, Jody; Leane, Catherine; Green, Sue; Lecathelinais, Christophe; Oldmeadow, Christopher; Attia, John; Gillham, Karen; Wiggers, John

    2017-06-01

    Worldwide, 10-20% of adolescents experience mental health problems. Strategies aimed at strengthening resilience protective factors provide a potential approach for reducing mental health problems in adolescents. This study evaluated the effectiveness of a universal, school-based intervention targeting resilience protective factors in reducing mental health problems in adolescents. A cluster randomised controlled trial was conducted in 20 intervention and 12 control secondary schools located in socio-economically disadvantaged areas of NSW, Australia. Data were collected from 3115 students at baseline (Grade 7, 2011), of whom 2149 provided data at follow up (Grade 10, 2014; enrolments in Grades 7 to 10 typically aged 12-16 years; 50% male; 69.0% retention). There were no significant differences between groups at follow-up for three mental health outcomes: total SDQ, internalising problems, and prosocial behaviour. A small statistically significant difference in favour of the control group was found for externalising problems. Findings highlight the continued difficulties in developing effective, school-based prevention programs for mental health problems in adolescents. ANZCTR (Ref no: ACTRN12611000606987). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Extralevatory abdominoperineal excision (ELAPE) does not result in reduced rate of tumor perforation or rate of positive circumferential resection margin: a nationwide database study.

    Science.gov (United States)

    Klein, Mads; Fischer, Anders; Rosenberg, Jacob; Gögenur, Ismail

    2015-05-01

    To evaluate the oncological results and possible benefits associated with extralevatory abdominoperineal excision (ELAPE) when compared with conventional abdominoperineal excision (APE). ELAPE was introduced in 2007 with the purpose of reducing the rate of positive resection margins after resection of low rectal cancers. Preliminary studies have shown promising results. No large-scale or nationwide data have been presented. Database study based on data from the Danish Colorectal Cancer Group's prospective database. Data on all ELAPEs and APEs performed in Denmark in the period January 1, 2009, through August 2012 were retrieved and evaluated for differences in demography, tumor characteristics, and oncological results. Uni- and multivariate logistic regression analyses were performed to identify risk factors for resection with a positive circumferential resection margin (CRM+). A total of 554 patients were included, 301(54%) were operated by ELAPE; 253(46%) by APE. Sixty-three percent were men, median (interquartile range) age was 69 (61-76 years) years, and tumors removed had predominantly T-stages T2 and T3 (32% and 45%, respectively). Overall, CRM+ was found in 13% of patients. When divided according to type of procedure, we found no significant differences in demography and tumor T- and N-stages. Resections with a CRM+ were more common after ELAPE (16% vs 7%; P = 0.006). After uni- and multivariate logistic regression analyses, surgery by ELAPE remained a risk factor for a CRM+ [odds ratio, 2.59 (95% confidence interval, 1.31-5.12); P = 0.006). In this nationwide study, resection of low rectal cancers by ELAPE did not improve short-term oncological results, when compared with conventional APE.

  15. Downregulation of IL6 Targeted MiR-376b May Contribute to a Positive IL6 Feedback Loop During Early Liver Regeneration in Mice

    Directory of Open Access Journals (Sweden)

    Shan Lu

    2015-08-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a group of endogenous, small, noncoding RNAs implicated in a variety of biological processes, including cell proliferation, apoptosis, differentiation and metabolism. The present study aims to explore the potential role and molecular mechanism of miR-376b during the early phase of liver regeneration. Methods: MiRNA profiling microarrays were used to assess the changes in miRNA expression. For functional analysis, cell proliferation, apoptosis assays, real time quantitative PCR and westernblot analysis were performed. Results: The comprehensive miRNA expression profiling assays on regenerating liver tissues 4 h after partial hepatectomy (PH showed that three miRNAs (miR-127, miR-376b and miR-494 located in the Dlk1-Gtl2 miRNA cluster were significantly downregulated. In vitro functional studies demonstrated that high-level interleukin 6 (IL6 inhibited the expression of miR-376b, and miR-376b mimics treatment decreased cell proliferation and increased apoptosis. Further target analysis showed that miR-376b reduced the mRNA and protein expression levels of NF-kappa-B inhibitor zeta (NFKBIZ and signal transducers and transcription activators 3 (STAT3. Additionally, IL6-induced miR-376b downregulation would, in turn, increase the expression of IL-6 possibly via a feedback loop involving NFKBIZ or/and STAT3. Conclusion: During the early phase of liver regeneration, miR-376b expression was significantly decreased. Our findings reveal that a regulatory circuitry between miR-376b and IL-6 may exist, which trigger the initiation of liver regeneration.

  16. Reducing and preventing internalizing and externalizing behavior problems in children with type 1 diabetes: a randomized controlled trial of the Triple P-Positive Parenting Program.

    Science.gov (United States)

    Westrupp, E M; Northam, E; Lee, K J; Scratch, S E; Cameron, F

    2015-11-01

    Children with type 1 diabetes are at increased risk of mental health problems, which in turn are associated with poor glycemic control, diabetes-related complications, and long-term psychiatric morbidity. We tested the efficacy of the Triple P-Positive Parenting Program in reducing or preventing mental health problems and improving glycemic control in children with type 1 diabetes in a randomized controlled trial. Participants were recruited from the Diabetes Clinic, Royal Children's Hospital, Melbourne, Australia, and randomized to Triple P or standard diabetes care. The primary outcome was child internalizing and externalizing behavior problems 3 and 12 months postrandomization. Secondary outcomes were glycemic control, parent mental health, parenting skills, and family functioning at 3 and 12 months, and glycemic control at 24 months. A total of 76 participants were randomized (38 to intervention and 38 to control), 60 completed 3-month, and 57 completed 12-month assessments. Benefits of Triple P were evident at 3 months for parent mental health, parenting skills, and family functioning (p externalizing behavior problems indicated greater improvements in child mental health, parent mental health, parenting skills, and diabetes family conflict (p parenting self-efficacy at 3 months. Improvements in parent mental health and parenting competency associated with Triple P were sustained to 12 months for children with pre-existing mental health problems. This study provides some support for the efficacy of Triple P in improving parent and family outcomes, and reducing child internalizing and externalizing behavior problems primarily in children who have pre-existing mental health problems. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

    Science.gov (United States)

    Olichney, John M; Riggins, Brock R; Hillert, Dieter G; Nowacki, Ralph; Tecoma, Evelyn; Kutas, Marta; Iragui, Vicente J

    2002-07-01

    We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

  18. Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system.

    Directory of Open Access Journals (Sweden)

    Jennifer E Richard

    Full Text Available The gut/brain peptide, glucagon like peptide 1 (GLP-1, suppresses food intake by acting on receptors located in key energy balance regulating CNS areas, the hypothalamus or the hindbrain. Moreover, GLP-1 can reduce reward derived from food and motivation to obtain food by acting on its mesolimbic receptors. Together these data suggest a neuroanatomical segregation between homeostatic and reward effects of GLP-1. Here we aim to challenge this view and hypothesize that GLP-1 can regulate food reward behavior by acting directly on the hindbrain, the nucleus of the solitary tract (NTS, GLP-1 receptors (GLP-1R. Using two models of food reward, sucrose progressive ratio operant conditioning and conditioned place preference for food in rats, we show that intra-NTS microinjections of GLP-1 or Exendin-4, a stable analogue of GLP-1, inhibit food reward behavior. When the rats were given a choice between palatable food and chow, intra-NTS Exendin-4 treatment preferentially reduced intake of palatable food but not chow. However, chow intake and body weight were reduced by the NTS GLP-1R activation if chow was offered alone. The NTS GLP-1 activation did not alter general locomotor activity and did not induce nausea, measured by PICA. We further show that GLP-1 fibers are in close apposition to the NTS noradrenergic neurons, which were previously shown to provide a monosynaptic connection between the NTS and the mesolimbic system. Central GLP-1R activation also increased NTS expression of dopamine-β-hydroxylase, a key enzyme in noradrenaline synthesis, indicating a biological link between these two systems. Moreover, NTS GLP-1R activation altered the expression of dopamine-related genes in the ventral tegmental area. These data reveal a food reward-suppressing role of the NTS GLP-1R and indicate that the neurobiological targets underlying food reward control are not limited to the mesolimbic system, instead they are distributed throughout the CNS.

  19. Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system.

    Science.gov (United States)

    Richard, Jennifer E; Anderberg, Rozita H; Göteson, Andreas; Gribble, Fiona M; Reimann, Frank; Skibicka, Karolina P

    2015-01-01

    The gut/brain peptide, glucagon like peptide 1 (GLP-1), suppresses food intake by acting on receptors located in key energy balance regulating CNS areas, the hypothalamus or the hindbrain. Moreover, GLP-1 can reduce reward derived from food and motivation to obtain food by acting on its mesolimbic receptors. Together these data suggest a neuroanatomical segregation between homeostatic and reward effects of GLP-1. Here we aim to challenge this view and hypothesize that GLP-1 can regulate food reward behavior by acting directly on the hindbrain, the nucleus of the solitary tract (NTS), GLP-1 receptors (GLP-1R). Using two models of food reward, sucrose progressive ratio operant conditioning and conditioned place preference for food in rats, we show that intra-NTS microinjections of GLP-1 or Exendin-4, a stable analogue of GLP-1, inhibit food reward behavior. When the rats were given a choice between palatable food and chow, intra-NTS Exendin-4 treatment preferentially reduced intake of palatable food but not chow. However, chow intake and body weight were reduced by the NTS GLP-1R activation if chow was offered alone. The NTS GLP-1 activation did not alter general locomotor activity and did not induce nausea, measured by PICA. We further show that GLP-1 fibers are in close apposition to the NTS noradrenergic neurons, which were previously shown to provide a monosynaptic connection between the NTS and the mesolimbic system. Central GLP-1R activation also increased NTS expression of dopamine-β-hydroxylase, a key enzyme in noradrenaline synthesis, indicating a biological link between these two systems. Moreover, NTS GLP-1R activation altered the expression of dopamine-related genes in the ventral tegmental area. These data reveal a food reward-suppressing role of the NTS GLP-1R and indicate that the neurobiological targets underlying food reward control are not limited to the mesolimbic system, instead they are distributed throughout the CNS.

  20. Use of a molecular diagnostic test in AFB smear positive tuberculosis suspects greatly reduces time to detection of multidrug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nestani Tukvadze

    Full Text Available The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB. There are limited data on the performance and impact of these tests in field settings.The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program.Among 500 AFB smear-positive sputum specimens, 458 (91.6% had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH resistance directly from the sputum specimen in 159 (89.8% of 177 specimens and MDR-TB in 109 (95.6% of 114 specimens compared to conventional methods. There was high agreement between the MTBDRplus assay and conventional DST results in detecting MDR-TB (kappa = 0.95, p<0.01. The most prevalent INH resistance mutation was S315T (78% in the katG codon and the most common rifampicin resistance mutation was S531L (68% in the rpoB codon. Among 13 specimens from TB suspects with negative sputum cultures, 7 had a positive MTBDRplus assay (3 with MDR-TB. The time to detection of MDR-TB was significantly less using the MTBDRplus assay (4.2 days compared to the use of standard phenotypic tests (67.3 days with solid media and 21.6 days with broth-based media.Compared to conventional methods, the MTBDRplus assay had high accuracy and significantly reduced time to detection of MDR-TB in an area with high MDR-TB prevalence. The use of rapid molecular diagnostic tests for TB and drug resistance should increase the proportion of patients promptly placed on appropriate therapy.

  1. Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT trademark (B-mode acquisition and targeting system) for prostate cancer

    International Nuclear Information System (INIS)

    Bohrer, Markus; Schroeder, Peter; Welzel, Grit; Wertz, Hansjoerg; Lohr, Frank; Wenz, Frederik; Mai, Sabine Kathrin

    2008-01-01

    To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. Patients and Methods 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. Results In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity > grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. Conclusion Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT). (orig.)

  2. A Community-Based Positive Deviance/Hearth Infant and Young Child Nutrition Intervention in Ecuador Improved Diet and Reduced Underweight.

    Science.gov (United States)

    Roche, Marion L; Marquis, Grace S; Gyorkos, Theresa W; Blouin, Brittany; Sarsoza, Julieta; Kuhnlein, Harriet V

    2017-03-01

    Underweight and stunting are serious problems in Ecuador that require interventions in the first 2 years of life. The researchers assessed the effectiveness of a Positive Deviance (PD)/Hearth community-based intervention using local foods to improve infant and young children's nutrition. A quasi-experimental nonrandomized study was conducted between March and October, 2009. The intervention and study were implemented in the Ecuadorian highlands provinces of Chimborazo and Tungurahua. Eighty mother-child pairs in 6 intervention communities and 184 mother-child pairs in 9 comparison communities. Mothers met in participatory peer-led PD/Hearth cooking and nutrition education sessions for 12 days. Dietary intake and nutritional status were collected at baseline and 6-month follow-up. Multiple linear and logistic regression were used for growth outcomes, and ANCOVA for mean dietary intakes. Mothers in the intervention were 1.3-5.7 times more likely to feed their children the promoted foods (P Hearth interventions support mothers to improve infant and young children's nutrition practices and reduce underweight. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

  3. Positive effect of reduced aeration rate on growth and stereospecificity of DL-malic acid consumption by Azospirillum brasilense: improving the shelf life of a liquid inoculant formulation.

    Science.gov (United States)

    Carrasco-Espinosa, Karen; García-Cabrera, Ramsés I; Bedoya-López, Andrea; Trujillo-Roldán, Mauricio A; Valdez-Cruz, Norma A

    2015-02-10

    Azospirillum brasilense has significance as a growth promoter in plants of commercial interest. Two industrial native strains (Start and Calf), used as a part of an inoculant formulation in Mexico during the last 15 years, were incubated in laboratory-scale pneumatic bioreactors at different aeration rates. In both strains, the positive effect of decreased aeration was observed. At the lowest (0.1 vvm, air volume/liquid volume×minute), the highest biomass were obtained for Calf (7.8 × 10(10)CFU/ml), and Start (2.9 × 10(9)CFU/ml). These were higher in one magnitude order compared to cultures carried out at 0.5 vvm, and two compared to those at 1.0 vvm. At lower aeration, both stereoisomeric forms of malic acid were consumed, but at higher aeration, just L-malate was consumed. A reduction in aeration allows an increase of the shelf life and the microorganism saved higher concentrations of polyhydroxybutyrate. The selected fermentation conditions are closely related to those prevalent in large-scale bioreactors and offer the possibility of achieving high biomass titles with high shelf life at a reduced costs, due to the complete use of a carbon source at low aeration of a low cost raw material as DL-malic acid mixture in comparison with the L-malic acid stereoisomer. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yue He

    2015-01-01

    Full Text Available Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  5. miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.

    Science.gov (United States)

    Götte, M; Mohr, C; Koo, C-Y; Stock, C; Vaske, A-K; Viola, M; Ibrahim, S A; Peddibhotla, S; Teng, Y H-F; Low, J-Y; Ebnet, K; Kiesel, L; Yip, G W

    2010-12-16

    Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.

  6. Investigating maternal risk factors as potential targets of intervention to reduce socioeconomic inequality in small for gestational age: a population-based study.

    Science.gov (United States)

    Hayward, Irene; Malcoe, Lorraine Halinka; Cleathero, Lesley A; Janssen, Patricia A; Lanphear, Bruce P; Hayes, Michael V; Mattman, Andre; Pampalon, Robert; Venners, Scott A

    2012-06-13

    The major aim of this study was to investigate whether maternal risk factors associated with socioeconomic status and small for gestational age (SGA) might be viable targets of interventions to reduce differential risk of SGA by socioeconomic status (socioeconomic SGA inequality) in the metropolitan area of Vancouver, Canada. This study included 59,039 live, singleton births in the Vancouver Census Metropolitan Area (Vancouver) from January 1, 2006 to September 17, 2009. To identify an indicator of socioeconomic SGA inequality, we used hierarchical logistic regression to model SGA by area-level variables from the Canadian census. We then modelled SGA by area-level average income plus established maternal risk factors for SGA and calculated population attributable SGA risk percentages (PAR%) for each variable. Associations of maternal risk factors for SGA with average income were investigated to identify those that might contribute to SGA inequality. Finally, we estimated crude reductions in the percentage and absolute differences in SGA risks between highest and lowest average income quintiles that would result if interventions on maternal risk factors successfully equalized them across income levels or eliminated them altogether. Average income produced the most linear and statistically significant indicator of socioeconomic SGA inequality with 8.9% prevalence of SGA in the lowest income quintile compared to 5.6% in the highest. The adjusted PAR% of SGA for variables were: bottom four quintiles of height (51%), first birth (32%), bottom four quintiles of average income (14%), oligohydramnios (7%), underweight or hypertension, (6% each), smoking (3%) and placental disorder (1%). Shorter height, underweight and smoking during pregnancy had higher prevalence in lower income groups. Crude models assuming equalization of risk factors across income levels or elimination altogether indicated little potential change in relative socioeconomic SGA inequality and reduction

  7. A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAA Receptors in the Lung.

    Science.gov (United States)

    Forkuo, Gloria S; Nieman, Amanda N; Kodali, Revathi; Zahn, Nicolas M; Li, Guanguan; Rashid Roni, M S; Stephen, Michael Rajesh; Harris, Ted W; Jahan, Rajwana; Guthrie, Margaret L; Yu, Olivia B; Fisher, Janet L; Yocum, Gene T; Emala, Charles W; Steeber, Douglas A; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

    2018-05-07

    We describe lead compound MIDD0301 for the oral treatment of asthma based on previously developed positive allosteric α 5 β 3 γ 2 selective GABA A receptor (GABA A R) ligands. MIDD0301 relaxed airway smooth muscle at single micromolar concentrations as demonstrated with ex vivo guinea pig tracheal rings. MIDD0301 also attenuated airway hyperresponsiveness (AHR) in an ovalbumin murine model of asthma by oral administration. Reduced numbers of eosinophils and macrophages were observed in mouse bronchoalveolar lavage fluid without changing mucous metaplasia. Importantly, lung cytokine expression of IL-17A, IL-4, and TNF-α were reduced for MIDD0301-treated mice without changing antiinflammatory cytokine IL-10 levels. Automated patch clamp confirmed amplification of GABA induced current mediated by α 1-3,5 β 3 γ 2 GABA A Rs in the presence of MIDD0301. Pharmacodynamically, transmembrane currents of ex vivo CD4 + T cells from asthmatic mice were potentiated by MIDD0301 in the presence of GABA. The number of CD4 + T cells observed in the lung of MIDD0301-treated mice were reduced by an oral treatment of 20 mg/kg b.i.d. for 5 days. A half-life of almost 14 h was demonstrated by pharmacokinetic studies (PK) with no adverse CNS effects when treated mice were subjected to sensorimotor studies using the rotarod. PK studies also confirmed very low brain distribution. In conclusion, MIDD0301 represents a safe and improved oral asthma drug candidate that relaxes airway smooth muscle and attenuates inflammation in the lung leading to a reduction of AHR at a dosage lower than earlier reported GABA A R ligands.

  8. Transmission of Turnip yellows virus by Myzus persicae Is Reduced by Feeding Aphids on Double-Stranded RNA Targeting the Ephrin Receptor Protein

    Directory of Open Access Journals (Sweden)

    Michaël Mulot

    2018-03-01

    Full Text Available Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family by Myzus persicae. The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta- or in vitro-synthesized dsRNA targeting Eph-mRNA (dsRNAEph did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNAEph-treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNAEph acquisition was also observed for two other poleroviruses transmitted by M. persicae, suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNAEph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages.

  9. Transmission of Turnip yellows virus by Myzus persicae Is Reduced by Feeding Aphids on Double-Stranded RNA Targeting the Ephrin Receptor Protein.

    Science.gov (United States)

    Mulot, Michaël; Monsion, Baptiste; Boissinot, Sylvaine; Rastegar, Maryam; Meyer, Sophie; Bochet, Nicole; Brault, Véronique

    2018-01-01

    Aphid-transmitted plant viruses are a threat for major crops causing massive economic loss worldwide. Members in the Luteoviridae family are transmitted by aphids in a circulative and non-replicative mode. Virions are acquired by aphids when ingesting sap from infected plants and are transported through the gut and the accessory salivary gland (ASG) cells by a transcytosis mechanism relying on virus-specific receptors largely unknown. Once released into the salivary canal, virions are inoculated to plants, together with saliva, during a subsequent feeding. In this paper, we bring in vivo evidence that the membrane-bound Ephrin receptor (Eph) is a novel aphid protein involved in the transmission of the Turnip yellows virus (TuYV, Polerovirus genus, Luteoviridae family) by Myzus persicae . The minor capsid protein of TuYV, essential for aphid transmission, was able to bind the external domain of Eph in yeast. Feeding M. persicae on in planta - or in vitro -synthesized dsRNA targeting Eph -mRNA (dsRNA Eph ) did not affect aphid feeding behavior but reduced accumulation of TuYV genomes in the aphid's body. Consequently, TuYV transmission efficiency by the dsRNA Eph -treated aphids was reproducibly inhibited and we brought evidence that Eph is likely involved in intestinal uptake of the virion. The inhibition of virus uptake after dsRNA Eph acquisition was also observed for two other poleroviruses transmitted by M. persicae , suggesting a broader role of Eph in polerovirus transmission. Finally, dsRNA Eph acquisition by aphids did not affect nymph production. These results pave the way toward an ecologically safe alternative of insecticide treatments that are used to lower aphid populations and reduce polerovirus damages.

  10. Use of 16S rRNA-targeted oligonucleotide probes to investigate the distribution of sulphate-reducing bacteria in estuarine sediments.

    Science.gov (United States)

    Purdy, K J.; Nedwell, D B.; Embley, T M.; Takii, S

    2001-07-01

    The distribution of sulphate-reducing bacteria (SRBs) in three anaerobic sediments, one predominantly freshwater and low sulphate and two predominantly marine and high sulphate, on the River Tama, Tokyo, Japan, was investigated using 16S rRNA-targeted oligonucleotide probes. Hybridisation results and sulphate reduction measurements indicated that SRBs are a minor part of the bacterial population in the freshwater sediments. Only Desulfobulbus and Desulfobacterium were detected, representing 1.6% of the general bacterial probe signal. In contrast, the SRB community detected at the two marine-dominated sites was larger and more diverse, representing 10-11.4% of the bacterial signal and with Desulfobacter, Desulfovibrio, Desulfobulbus and Desulfobacterium detected. In contrast to previous reports our results suggest that Desulfovibrio may not always be the most abundant SRB in anaerobic sediments. Acetate-utilising Desulfobacter were the dominant SRB in the marine-dominated sediments, and Desulfobulbus and Desulfobacterium were active in low-sulphate sediments, where they may utilise electron acceptors other than sulphate.

  11. Low pulmonary artery flush perfusion pressure combined with high positive end-expiratory pressure reduces oedema formation in isolated porcine lungs

    International Nuclear Information System (INIS)

    Schumann, Stefan; Schließmann, Stephan J; Wagner, Giskard; Goebel, Ulrich; Priebe, Hans-Joachim; Guttmann, Josef; Kirschbaum, Andreas

    2010-01-01

    Flush perfusion of the pulmonary artery with organ protection solution is a standard procedure before lung explantation. However, rapid flush perfusion may cause pulmonary oedema which is deleterious in the lung transplantation setting. In this study we tested the hypotheses that high pulmonary perfusion pressure contributes to the development of pulmonary oedema and positive end-expiratory pressure (PEEP) counteracts oedema formation. We expected oedema formation to increase weight and decrease compliance of the lungs on the basis of a decrease in alveolar volume as fluid replaces alveolar air spaces. The pulmonary artery of 28 isolated porcine lungs was perfused with a low-potassium dextrane solution at low (mean 27 mmHg) or high (mean 40 mmHg) pulmonary artery pressure (PAP) during mechanical ventilation at low (4 cmH 2 O) or high (8 cmH 2 O) PEEP, respectively. Following perfusion and storage, relative increases in lung weight were smaller (p < 0.05) during perfusion at low PAP (62 ± 32% and 42 ± 26%, respectively) compared to perfusion at high PAP (133 ± 54% and 87 ± 30%, respectively). Compared to all other PAP–PEEP combinations, increases in lung weight were smallest (44 ± 9% and 27 ± 12%, respectively), nonlinear intratidal lung compliance was largest (46% and 17% respectively, both p < 0.05) and lung histology showed least infiltration of mononuclear cells in the alveolar septa, and least alveolar destruction during the combination of low perfusion pressure and high PEEP. The findings suggest that oedema formation during pulmonary artery flush perfusion in isolated and ventilated lungs can be reduced by choosing low perfusion pressure and high PEEP. PAP–PEEP titration to minimize pulmonary oedema should be based on lung mechanics and PAP monitoring

  12. A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Santoro, J. P.; McNamara, J.; Yorke, E.; Pham, H.; Rimner, A.; Rosenzweig, K. E.; Mageras, G. S. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York 10065 (United States); Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York 10065 (United States); Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York 10065 (United States)

    2012-10-15

    Purpose: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. Methods: Eleven stage II-IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. Results: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction

  13. A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer

    International Nuclear Information System (INIS)

    Santoro, J. P.; McNamara, J.; Yorke, E.; Pham, H.; Rimner, A.; Rosenzweig, K. E.; Mageras, G. S.

    2012-01-01

    Purpose: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone. A second study goal compares respiration-correlated vs respiration-averaged images for determining tumor deviations. Methods: Eleven stage II–IV nonsmall cell lung cancer patients are enrolled in an IRB-approved prospective off-line protocol using RC-CBCT guidance to correct for systematic errors in GTV position. Patients receive a respiration-correlated planning CT (RCCT) at simulation, daily kilovoltage RC-CBCT scans during the first week of treatment and weekly scans thereafter. Four types of correction methods are compared: (1) systematic error in gross tumor volume (GTV) position, (2) systematic error in skeletal anatomy, (3) daily skeletal corrections, and (4) weekly skeletal corrections. The comparison is in terms of weighted average of the residual GTV deviations measured from the RC-CBCT scans and representing the estimated residual deviation over the treatment course. In the second study goal, GTV deviations computed from matching RCCT and RC-CBCT are compared to deviations computed from matching respiration-averaged images consisting of a CBCT reconstructed using all projections and an average-intensity-projection CT computed from the RCCT. Results: Of the eleven patients in the GTV-based systematic correction protocol, two required no correction

  14. Reducing stress and supporting positive relations in families of young children with type 1 diabetes: A randomized controlled study for evaluating the effects of the DELFIN parenting program

    Directory of Open Access Journals (Sweden)

    Saßmann Heike

    2012-09-01

    Full Text Available Abstract Background To assess initial efficacy and feasibility of a structured behavioural group training (DELFIN for parents of children with diabetes type 1, in order to reduce parenting stress and to improve parenting skills. Methods A randomized controlled study was conducted between July 2008 and September 2010, at a children’s hospital in Hannover with parents of children with type 1 diabetes (2–10 yrs (intervention group n = 37; control group n = 28. Parenting skills, parents’ psychological burden, children’s behavioural difficulties and quality of metabolic control were assessed before, 3 months after and 12 months after participating in the training program. Results In the intervention group parenting behaviour in conflict situations improved significantly after 3 months (Z = −3.28; p ≤ 0.001. It remained stable over 12 months (Z = −2.94; p ≤ 0.01. Depression and anxiety scores of parents decreased (Z = −1.93; p ≤ .05; Z = −2.02; p ≤ .05. Even though the outcome in the intervention group was more positive, the differences between both study arms failed to reach statistical significance. Unexpectedly parenting behaviour in the control group improved also (Z = −2.45; p ≤ .05. Anxiety as well as stress scores decreased in this group (Z = −2.02; p ≤ .05 and Z = −2.11; p ≤ .05. In both groups the initial metabolic control was good and without significant differences (A1c 7.2±0.8% vs. 7.1±0.4%; p > 0.5. It remained stable in the DELFIN group (A1c 7.1±0.8%; p > 0.5, but it increased slightly in controls (A1c 7.3±0.5%; Z = −2.79; p = .005. Conclusions This study has brought first evidence for the efficacy and feasibility of the program. A multicentre study with a larger sample is necessary to confirm these first results.

  15. Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial.

    Science.gov (United States)

    Sack, M; Spieler, D; Wizelman, L; Epple, G; Stich, J; Zaba, M; Schmidt, U

    2017-02-17

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans. To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST). Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects. This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the

  16. Increasing Knowledge and Self-Efficacy through a Pre-Service Course on Promoting Positive School Climate: The Crucial Role of Reducing Moral Disengagement

    Science.gov (United States)

    Crooks, Claire V.; Jaffe, Peter G.; Rodriguez, Arely

    2017-01-01

    Teachers play an important role in promoting a positive school climate, which in turns supports academic achievement and positive mental health among students. This study evaluated the impact of a pre-service teacher education course addressing a range of contributors to school climate. Participants included a cohort of 212 pre-service teachers…

  17. TARGET-DIRECTED RUNNING IN GYMNASTICS: THE ROLE OF THE SPRINGBOARD POSITION AS AN INFORMATIONAL SOURCE TO REGULATE HANDSPRINGS ON VAULT

    Directory of Open Access Journals (Sweden)

    T. Heinen

    2011-11-01

    Full Text Available Empirical evidence highlights the role of visual information to control gymnastics vaulting and thus neglects a stereotyped approach run. However, there is no evidence on which informational source this regulation is based on. The aim of this study was to examine the position of the springboard as an informational source in the regulation of the handspring on vault. The hypothesis tested was that the action of running towards the springboard brings about changes in the approach run kinematics and handspring kinematics that relate directly to the position of the springboard. Therefore, kinematics of N = 14 female expert gymnasts’ handsprings on vault and their approach runs were examined while manipulating the position of the springboard. The results revealed that expert gymnasts placed their feet on average in the same position on the springboard and adapted to the springboard position during the last three steps of the approach run. A smaller springboard distance to the front edge of the vaulting table resulted in a different hand placement on the vaulting table, a shorter first flight phase, a take-off angle closer to 90° and a longer second flight phase. Findings suggest that the position of the springboard is a relevant informational source in gymnastics vaulting. We state that knowledge about relationships between informational sources in the environment and the resulting regulatory processes in athletes may help coaches to develop specific training programmes in order to optimize performance in complex skills.

  18. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

    International Nuclear Information System (INIS)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

    2009-01-01

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  19. Long-circulating and passively tumor-targeted polymer-drug conjugates improve the efficacy and reduce the toxicity of radiochemotherapy

    Czech Academy of Sciences Publication Activity Database

    Lammers, T.; Šubr, Vladimír; Ulbrich, Karel; Peschke, P.; Huber, P. E.; Hennink, W. E.; Storm, G.; Kiessling, F.

    2010-01-01

    Roč. 12, č. 9 (2010), B413-B421 ISSN 1438-1656 R&D Projects: GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505 Keywords : HPMA copolymers * targeting * tumor targeting Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.746, year: 2010

  20. Cognitive processing load during listening is reduced more by decreasing voice similarity than by increasing spatial separation between target and masker speech

    NARCIS (Netherlands)

    Zekveld, A.A.; Rudner, M.; Kramer, S.E.; Lyzenga, J.; Ronnberg, J.

    2014-01-01

    We investigated changes in speech recognition and cognitive processing load due to the masking release attributable to decreasing similarity between target and masker speech. This was achieved by using masker voices with either the same (female) gender as the target speech or different gender (male)

  1. Study on the adaptation of the VICKSI-accelerator to the beam guidance system. Model of a target position with a vertical beam. Pt. 1, 2

    International Nuclear Information System (INIS)

    Hinterberger, F.

    1974-09-01

    The problem of matching an extracted beam onto the entrance slit of a monochromator system is studied under the special assumption of very restricted free space. The investigation refers to the matching of the VICKSI beam. Systems of 2, 3 and 4 quadrupole lenses are discussed. The constraints which have to be imposed upon the phase space distribution of the extracted beam are established in a general form. In order to realize a target area with vertical incoming beam two designs are proposed which can be combined with the planned beam handling system. Each one of the two designs provides the additional installation of only one 90 0 -bending magnet. It is shown that the ionoptical problem to focus the beam onto the target can be solved in a satisfactory manner. (orig.) [de

  2. 4D-CT scans reveal reduced magnitude of respiratory liver motion achieved by different abdominal compression plate positions in patients with intrahepatic tumors undergoing helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yong, E-mail: hu.yong@zs-hospital.sh.cn; Zhou, Yong-Kang, E-mail: zhouyk2009@163.com; Chen, Yi-Xing, E-mail: chen.yixing@zs-hospital.sh.cn; Shi, Shi-Ming, E-mail: shiming32@126.com; Zeng, Zhao-Chong, E-mail: zeng.zhaochong@zs-hospital.sh.cn [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032 (China)

    2016-07-15

    Purpose: While abdominal compression (AC) can be used to reduce respiratory liver motion in patients receiving helical tomotherapy for hepatocellular carcinoma, the nature and extent of this effect is not well described. The purpose of this study was to evaluate the changes in magnitude of three-dimensional liver motion with abdominal compression using four-dimensional (4D) computed tomography (CT) images of several plate positions. Methods: From January 2012 to October 2015, 72 patients with intrahepatic carcinoma and divided into four groups underwent 4D-CT scans to assess respiratory liver motion. Of the 72 patients, 19 underwent abdominal compression of the cephalic area between the subxiphoid and umbilicus (group A), 16 underwent abdominal compression of the caudal region between the subxiphoid area and the umbilicus (group B), 11 patients underwent abdominal compression of the caudal umbilicus (group C), and 26 patients remained free breathing (group D). 4D-CT images were sorted into ten-image series, according to the respiratory phase from the end inspiration to the end expiration, and then transferred to treatment planning software. All liver contours were drawn by a single physician and confirmed by a second physician. Liver relative coordinates were automatically generated to calculate the liver respiratory motion in different axial directions to compile the 10 ten contours into a single composite image. Differences in respiratory liver motion were assessed with a one-way analysis of variance test of significance. Results: The average respiratory liver motion in the Y axial direction was 4.53 ± 1.16, 7.56 ± 1.30, 9.95 ± 2.32, and 9.53 ± 2.62 mm in groups A, B, C, and D, respectively, with a significant change among the four groups (p < 0.001). Abdominal compression was most effective in group A (compression plate on the subxiphoid area), with liver displacement being 2.53 ± 0.93, 4.53 ± 1.16, and 2.14 ± 0.92 mm on the X-, Y-, and Z

  3. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  4. α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Miller, Brian W.; Back, Tom; Santos, E. B.; Hamlin, Donald K.; Knoblaugh, E.; Frayo, Shani; Kenoyer, Aimee L.; Storb, Rainer; Press, O. W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, B. M.

    2015-09-03

    Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

  5. Open table-top device positioning technique to reduce small bowel obstruction. Positioning accuracy and impact on conformal radiation therapy techniques; Lochbrettechnik zur Duenndarmschonung. Untersuchungen zur Lagerungsgenauigkeit unter Beruecksichtigung konformierender Bestrahlungstechniken

    Energy Technology Data Exchange (ETDEWEB)

    Rudat, V. [Abteilung Strahlentherapie, Klinische Radiologie, Universitaetsklinikum Heidelberg (Germany); Flentje, M. [Abteilung Strahlentherapie, Klinische Radiologie, Universitaetsklinikum Heidelberg (Germany); Engenhart, R. [Abteilung Strahlentherapie, Klinische Radiologie, Universitaetsklinikum Heidelberg (Germany); Metzger, M. [Abteilung Strahlentherapie, Klinische Radiologie, Universitaetsklinikum Heidelberg (Germany); Wannenmacher, M. [Abteilung Strahlentherapie, Klinische Radiologie, Universitaetsklinikum Heidelberg (Germany)

    1995-08-01

    The immobilization error of patients positioned on the opern table-top device in prone prosition as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformal radiotherapy. The positioning error was determined by superposing 106 portal films with the corresponding simultor films from 21 patients with carcinoma of the rectum who received 3D-planned conformal radiotherapy (o-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. The positioning error along the medio-lateral, dorso-ventral und cranio-caudal axis was 1.4/-0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a media of 5.1 . Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the tratment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top decive. (orig.) [Deutsch] Die Anwendung der Lochbrettechnik sowie konformierender Bestrahlungstechnik laesst eine Verminderung der Duenndarmbelastung bei der Bestrahlung pelviner Tumoren erwarten. Die Lagerungsgenauigkeit der Patienten als wichtiger Gesichtspunkt bei der dreidimensionalen Bestrahlungsplanung wurde bestimmt und die Duenndarmverlagerung aus dem Bestrahlungsfeld bei der Patientenlagerung im Lochbrett untersucht. Saemtliche zu untersuchende Patienten erhielten eine dreidimensional geplante

  6. Target-Searching on Percolation

    International Nuclear Information System (INIS)

    Yang Shijie

    2005-01-01

    We study target-searching processes on a percolation, on which a hunter tracks a target by smelling odors it emits. The odor intensity is supposed to be inversely proportional to the distance it propagates. The Monte Carlo simulation is performed on a 2-dimensional bond-percolation above the threshold. Having no idea of the location of the target, the hunter determines its moves only by random attempts in each direction. For lager percolation connectivity p ∼> 0.90, it reveals a scaling law for the searching time versus the distance to the position of the target. The scaling exponent is dependent on the sensitivity of the hunter. For smaller p, the scaling law is broken and the probability of finding out the target significantly reduces. The hunter seems trapped in the cluster of the percolation and can hardly reach the goal.

  7. Translational and rotational intra- and inter-fractional errors in patient and target position during a short course of frameless stereotactic body radiotherapy

    DEFF Research Database (Denmark)

    Josipovic, Mirjana; Persson, Gitte Fredberg; Logadottir, Ashildur

    2012-01-01

    Implementation of cone beam computed tomography (CBCT) in frameless stereotactic body radiotherapy (SBRT) of lung tumours enables setup correction based on tumour position. The aim of this study was to compare setup accuracy with daily soft tissue matching to bony anatomy matching and evaluate...

  8. The Positive Outcome of MRI-Guided Vacuum Assisted Core Needle Breast Biopsies Is Not Influenced by a Prior Negative Targeted Second-Look Ultrasound.

    Science.gov (United States)

    Ferré, Romuald; AlSharif, Shaza; Aldis, Ann; Mesurolle, Benoît

    2017-11-01

    The study sought to investigate the outcome of breast magnetic resonance-guided biopsies as a function of the indication for magnetic resonance imaging (MRI), the MRI features of the lesions, and the performance or not of a targeted second-look ultrasound (SLUS) prior breast MRI-guided biopsy. We identified 158 women with MRI-detected breast lesions scheduled for MRI-guided biopsy (2007-2013). Patient demographics, performance of targeted SLUS, imaging characteristics, and subsequent pathology results were reviewed. Three biopsies were deferred, and 155 lesions were biopsied under MRI guidance (155 women; median age 55.14 years; range 27-80 years). Ninety-eight women underwent a SLUS prior to the MRI-guided biopsy (63%). Of the 155 biopsied lesions, 23 (15%) were malignant, 106 (68%) were benign, and 26 (17%) were high risk. Four of 15 surgically excised high-risk lesions were upgraded to malignancy (27%). Most of the biopsied lesions corresponded to non-mass-like enhancement (81%, 126 of 155) and most of the biopsies (52%, 81 of 155) were performed in a screening context. No demographic or MRI features were associated with malignancy. No differences were noted between the 2 subgroups (prior SLUS vs no prior SLUS) except for the presence of a synchronous carcinoma associated with a likelihood of targeted SLUS before MRI-guided biopsy (P = .001). A negative SLUS does not influence the pathology outcome of a suspicious lesion biopsied under MR guidance. Copyright © 2017 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  9. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications.

    Science.gov (United States)

    Imaduwage, Kasun P; Go, Eden P; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have K i values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods. Graphical Abstract ᅟ.

  10. Effect of laser beam focus position on ion emission from plasmas produced by picosecond and sub-nanosecond laser pulses from solid targets

    Czech Academy of Sciences Publication Activity Database

    Woryna, E.; Badziak, J.; Makowski, J.; Parys, P.; Wolowski, J.; Krása, Josef; Láska, Leoš; Rohlena, Karel; Vankov, A. B.

    2001-01-01

    Roč. 31, č. 4 (2001), s. 791-798 ISSN 0078-5466 R&D Projects: GA AV ČR IAA1010105 Grant - others:KBN(PL) 2 P03B 082 19 Institutional research plan: CEZ:AV0Z1010921 Keywords : laser-produced plasma * laser beam focus position influence Subject RIV: BH - Optics, Masers, Lasers Impact factor: 0.298, year: 2001

  11. Population and patient-specific target margins for 4D adaptive radiotherapy to account for intra- and inter-fraction variation in lung tumour position

    International Nuclear Information System (INIS)

    Hugo, Geoffrey D; Di Yan; Jian Liang

    2007-01-01

    In this work, five 4D image-guidance strategies (two population, an offline adaptive and two online strategies) were evaluated that compensated for both inter- and intra-fraction variability such as changes to the baseline tumour position and respiratory pattern. None of the strategies required active motion compensation such as gating or tracking; all strategies simulated a free-breathing-based treatment technique. Online kilovoltage fluoroscopy was acquired for eight patients with lung tumours, and used to construct inter- and intra-fraction tumour position variability models. Planning was performed on a mid-ventilation image acquired from a respiration-correlated CT scan. The blurring effect of tumour position variability was included in the dose calculation by convolution. CTV to PTV margins were calculated for variability in the cranio-caudal direction. A population margin of 9.0 ± 0.7 mm was required to account for setup error and respiration in the study population without the use of image-guidance. The greatest mean margin reduction was introduced by the offline adaptive strategy. A daily online correction strategy produced a small reduction (1.6 mm) in the mean margin from the offline strategy. Adaptively correcting for an inter-fraction change in the respiratory pattern had little effect on margin size due to most patients having only small daily changes in the respiratory pattern. A daily online correction strategy would be useful for patients who exhibit large variations in the daily mean tumour position, while an offline adaptive strategy is more applicable to patients with less variation

  12. [Identification, during development, of a methodology targeted at determining the positioning of new drugs for therapeutic strategies: examples of rheumatoid arthritis and cardiac insufficiency].

    Science.gov (United States)

    Le Jeunne, C; Plétan, Y; Boissel, J P

    2002-01-01

    The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned.

  13. Placing symptoms in context: the role of contextual criteria in reducing false positives in Diagnostic and Statistical Manual of Mental Disorders diagnoses.

    Science.gov (United States)

    Wakefield, Jerome C; First, Michael B

    2012-02-01

    The Diagnostic and Statistical Manual of Mental Disorders (DSM) definition of mental disorder requires that symptoms be caused by a dysfunction in the individual; when dysfunction is absent, symptoms represent normal-range distress or eccentricity and, if diagnosed as a mental disorder, are false positives. We hypothesized that because of psychiatry's lack of direct laboratory tests to distinguish dysfunction from normal-range distress, the context in which symptoms occur (eg, lack of imminent danger in a panic attack) is often essential to determining whether symptoms are caused by a dysfunction. If this is right, then the DSM diagnostic criteria should include many contextual criteria added to symptom syndromes to prevent dysfunction false positives. Despite their potential importance, such contextual criteria have not been previously reviewed. We, thus, systematically reviewed DSM categories to establish the extent of such uses of contextual criteria and created a typology of such uses. Of 111 sampled categories, 68 (61%) used context to prevent dysfunction false positives. Contextual criteria fell into 7 types: (1) exclusion of specific false-positive scenarios; (2) requiring that patients experience preconditions for normal responses (eg, requiring that individuals experience adequate sexual stimulation before being diagnosed with sexual dysfunctions); (3) requiring that symptoms be disproportionate relative to circumstances; (4) for childhood disorders, requiring that symptoms be developmentally inappropriate; (5) requiring that symptoms occur in multiple contexts; (6) requiring a substantial discrepancy between beliefs and reality; and (7) a residual category. Most DSM categories include contextual criteria to eliminate false-positive diagnoses and increase validity of descriptive criteria. Future revisions should systematically evaluate each category's need for contextual criteria. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Back to Sleep: Reduce the Risk of Sudden Infant Death Syndrome (SIDS) [and] Questions and Answers for Professionals on Infant Sleeping Position and SIDS.

    Science.gov (United States)

    Health Resources and Services Administration (DHHS/PHS), Washington, DC. Maternal and Child Health Bureau.

    The "Back to Sleep" public health campaign, which recommends that infants be placed on their backs for sleeping help reduce the risk of Sudden Infant Death Syndrome (SIDS), was initiated in 1994. The campaign was led by the National Institute of Child Health and Human Development, and co-sponsored by the U.S. Public Health Service, the…

  15. Cancer: Towards a general theory of the target: All successful cancer therapies, actual or potential, are reducible to either (or both) of two fundamental strategies.

    Science.gov (United States)

    Vincent, Mark D

    2017-09-01

    General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and 'acausal' recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable. © 2017 The Authors. BioEssays Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  16. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    International Nuclear Information System (INIS)

    Zhang, Hanwen; Maecke, Helmut R.; Schuhmacher, Jochen; Eisenhut, Michael; Waser, Beatrice; Reubi, Jean Claude; Wild, Damian

    2007-01-01

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG 4 -BN(7-14) (DOTA-PESIN), with the goal of labelling it with 67/68 Ga and 177 Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG 4 ). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga III /Lu III ]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [ 67 Ga/ 177 Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [ 67 Ga/ 177 Lu]-DOTA-PESIN. [ 67 Ga/ 177 Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [ 68 Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the 177 Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with 68/67 Ga and targeted radionuclide therapy with 177 Lu. (orig.)

  17. Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

    Science.gov (United States)

    Turner, Bruce; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

    2016-01-01

    Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

  18. Negative and positive externalities in intergroup conflict: exposure to the opportunity to help the outgroup reduces the inclination to harm it.

    Science.gov (United States)

    Weisel, Ori

    2015-01-01

    Outgroup hate, in the context of intergroup conflict, can be expressed by harming the outgroup, but also by denying it help. Previous work established that this distinction-whether the externality on the outgroup is negative or positive-has an important effect on the likelihood of outgroup hate emerging as a motivation for individual participation in intergroup conflict. The current work uses a within-subject design to examine the behavior of the same individuals in intergroup conflict with negative and positive externalities on the outgroup. Each participant made two choices, one for each type of externality, and the order was counter balanced. The main results are that (1) behavior is fairly consistent across negative and positive externalities, i.e., the tendency to display outgroup hate by harming the outgroup is correlated with the tendency to display outgroup hate by avoiding to help the outgroup; (2) People are reluctant to harm the outgroup after being exposed to the opportunity to help it; (3) Groupness-the degree to which people care about their group and its well-being-is related to outgroup hate only when participants encounter the opportunity to harm the outgroup first (before they encounter the opportunity to help it). In this setting the relationship between groupness and outgroup hate spilled over to the subsequent interaction, where it was possible to help the outgroup. When the opportunity to help the outgroup was encountered first, groupness was not related to outgroup hate.

  19. Negative and positive externalities in intergroup conflict: Exposure to the opportunity to help the outgroup reduces the inclination to harm it

    Directory of Open Access Journals (Sweden)

    Ori eWeisel

    2015-10-01

    Full Text Available Outgroup hate, in the context of intergroup conflict, can be expressed by harming the outgroup, but also by denying it help.Previous work established that this distinction---whether the externality on the outgroup is negative or positive---has an important effect on the likelihood of outgroup hate emerging as a motivation for individual participation in intergroup conflict.The current work uses a within-subject design to examine the behaviour of the same individuals in intergroup conflict with negative and positive externalities on the outgroup.Each participant made two choices, one for each type of externality, and the order was counter balanced.The main results are that(1 behaviour is fairly consistent across negative and positive externalities, i.e., the tendency to display outgroup hate by harming the outgroup is correlated with the tendency to display outgroup hate by avoiding to help the outgroup; (2 People are reluctant to harm the outgroup after being exposed to the opportunity to help it; (3 emph{Groupness}---the degree to which people care about their group and its well-being---is related to outgroup hate only when participants encounter the opportunity to harm the outgroup first (before they encounter the opportunity to help it. In this setting the relationship between groupness and outgroup hate spilled over to the subsequent interaction, where it was possible to help the outgroup. When the opportunity to help the outgroup was encountered first, groupness was not related to outgroup hate.

  20. The Benefit of Targeting Trending Niche Marketing Segments and Re-positioning of a Company : Choosing the winning marketing strategies for Reebok

    OpenAIRE

    Erus, Oscar

    2016-01-01

    This thesis will discuss different phases of Reebok’s development and study the underlying causes. The thesis will seek to understand which factors of strategic marketing made the company a market leader in the late 1980s and which factors caused the company to be unsuccessful in keeping the position. The company got lost in the process and failed to bounce back even though Reebok had the knowhow and financial capability to take seri-ous actions. This seemed to eventually lead to a bankrupt u...

  1. The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes Association Position Statement regarding individualized A1C targets

    OpenAIRE

    Bieszk, Nella; Grabner, Michael; Wei, Wenhui; Bonine, Nicole G; Stephenson, Judith J

    2016-01-01

    Nella Bieszk,1 Michael Grabner,2 Wenhui Wei,1 Nicole G Bonine,2 Judith J Stephenson,2 1Sanofi US, Inc., Bridgewater, NJ, 2HealthCore, Inc., Wilmington, DE, USA Objective: To evaluate awareness of the 2012 American Diabetes Association (ADA) Position Statement among physicians and assess its effects on patient-centered glycated hemoglobin (A1C) goals in the management of type 2 diabetes (T2D). Research design and methods: The Summarizing Real-World Individualized TrEatmEnT GoalS and Potential ...

  2. Toward an individualized target motion management for IMRT of cervical cancer based on model-predicted cervix-uterus shape and position

    International Nuclear Information System (INIS)

    Bondar, Luiza; Hoogeman, Mischa; Mens, Jan Willem; Dhawtal, Glenn; Pree, Ilse de; Ahmad, Rozilawati; Quint, Sandra; Heijmen, Ben

    2011-01-01

    Background and Purpose: To design and evaluate a 3D patient-specific model to predict the cervix-uterus shape and position. Methods and Materials: For 13 patients lying in prone position, 10 variable bladder filling CT-scans were acquired, 5 at planning and 5 after 40 Gy. The delineated cervix-uterus volumes in 2-5 pre-treatment CT-scans were used to generate patient-specific models that predict the cervix-uterus geometry by bladder volume. Model predictions were compared to delineations, excluding those used for model construction. The prediction error was quantified by the margin required around the predicted volumes to accommodate 95% of the delineated volume and by the predicted-to-delineated surface distance. Results: The prediction margin was significantly smaller (average 50%) than the margin encompassing the cervix-uterus motion. The prediction margin could be decreased (from 7 to 5 mm at planning and from 10 to 8 mm after 40 Gy) by increasing (from 2 to 5) the number of CT-scans used for the model construction. Conclusion: For most patients, even with a model based on only two CT-scans, the prediction error was well below the margin encompassing the cervix-uterus motion. The described approach could be used to create prior to treatment, an individualized treatment strategy.

  3. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hanwen; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Department of Radiology, Basel (Switzerland); Schuhmacher, Jochen; Eisenhut, Michael [German Cancer Research Centre, Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Berne (Switzerland); Wild, Damian [University Hospital, Clinic and Institute of Nuclear Medicine, Department of Radiology, Basel (Switzerland)

    2007-08-15

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG{sub 4}-BN(7-14) (DOTA-PESIN), with the goal of labelling it with {sup 67/68}Ga and {sup 177}Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG{sub 4}). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga{sup III}/Lu{sup III}]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [{sup 68}Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the {sup 177}Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with {sup 68/67}Ga and targeted radionuclide therapy with {sup 177}Lu. (orig.)

  4. Reasons for living, meaning in life, and suicide ideation: investigating the roles of key positive psychological factors in reducing suicide risk in community-residing older adults.

    Science.gov (United States)

    Heisel, Marnin J; Neufeld, Eva; Flett, Gordon L

    2016-01-01

    To investigate the roles of reasons for living (RFL) and meaning in life (MIL) in potentially promoting mental health and well-being and protecting against suicide ideation among community-residing older adults and to investigate the psychometric properties of the Reasons for Living Scale-Older Adult version (RFL-OA). Of 173 older adults initially recruited into a longitudinal study on late-life suicide ideation, 109 completed the RFL-OA and measures of cognitive and physical functioning and positive and negative psychological factors at a two-year follow-up assessment. We tested a model in which RFL and MIL protect against suicide ideation, controlling for demographic and clinical factors. We also assessed the psychometric properties of the RFL-OA in community-residing older adults, investigating its internal consistency and its convergent (MIL, perceived social support, and life satisfaction), divergent (loneliness, depressive symptom severity, and suicide ideation), and discriminant validity (cognitive and physical functioning). RFL-OA scores explained significant variance in suicide ideation, controlling for age, sex, depressive symptom severity, and loneliness. MIL explained significant unique variance in suicide ideation, controlling for these factors and RFL, and MIL significantly mediated the association between RFL and suicide ideation. Psychometric analyses indicated strong internal consistency (α = .94), convergent, divergent, and discriminant validity for the RFL-OA relative to positive and negative psychological factors and cognitive and physical functioning. These findings add to a growing body of literature suggesting merit in investigating positive psychological factors together with negative factors when assessing suicide risk and planning psychological services for older adults.

  5. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

    Directory of Open Access Journals (Sweden)

    Chia PL

    2014-11-01

    Full Text Available Puey Ling Chia,1 Paul Mitchell,1 Alexander Dobrovic,2–4 Thomas John1,2,4 1Department of Medical Oncology, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia; 2Ludwig Institute for Cancer Research, Austin Health, Victoria, Australia; 3Department of Pathology, University of Melbourne, Victoria, Australia; 4School of Cancer Medicine, La Trobe University, Victoria, Australia Abstract: Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC with anaplastic lymphoma kinase (ALK gene rearrangements constitute about 4%–5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients. Keywords: anaplastic lymphoma kinase (ALK, gene rearrangements, lung cancer, kinase inhibitors, lung adenocarcinoma

  6. Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target.

    Science.gov (United States)

    Budiarto, E; Keijzer, M; Storchi, P R M; Heemink, A W; Breedveld, S; Heijmen, B J M

    2014-01-20

    Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.

  7. Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit

    2016-06-01

    This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  8. Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target

    International Nuclear Information System (INIS)

    Budiarto, E; Keijzer, M; Heemink, A W; Storchi, P R M; Breedveld, S; Heijmen, B J M

    2014-01-01

    Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements. (paper)

  9. [111In-DOTA]LTT-SS28, a first pansomatostatin radioligand for in vivo targeting of somatostatin receptor-positive tumors.

    Science.gov (United States)

    Maina, Theodosia; Cescato, Renzo; Waser, Beatrice; Tatsi, Aikaterini; Kaloudi, Aikaterini; Krenning, Eric P; de Jong, Marion; Nock, Berthold A; Reubi, Jean Claude

    2014-08-14

    Radiolabeled pansomatostatin-like analogues are expected to enhance the diagnostic sensitivity and to expand the clinical indications of currently applied sst2-specific radioligands. In this study, we present the somatostatin mimic [DOTA]LTT-SS28 {[(DOTA)Ser1,Leu8,D-Trp22,Tyr25]SS28} and its 111In radioligand. [DOTA]LTT-SS28 exhibited a pansomatostatin-like profile binding with high affinity to all five hsst1-hsst5 subtypes (IC50 values in the lower nanomolar range). Furthermore, [DOTA]LTT-SS28 behaved as an agonist at hsst2, hsst3, and hsst5, efficiently stimulating internalization of the three receptor subtypes. Radioligand [111In-DOTA]LTT-SS28 showed good stability in the mouse bloodstream. It displayed strong and specific uptake in AR42J tumors 4 h postinjection (9.3±1.6% ID/g vs 0.3±0.0% ID/g during sst2 blockade) in mice. Significant and specific uptake was also observed in HEK293-hsst2-, HEK293-hsst3-, and HEK293-hsst5-expressing tumors (4.43±1.5, 4.88±1.1, and DOTA]LTT-SS28 specifically localizes in sst2-, sst3-, and sst5-expressing xenografts in mice showing promise for multi-sst1-sst5 targeted tumor imaging.

  10. CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate

    DEFF Research Database (Denmark)

    Herrik, Kjartan F; Redrobe, John P; Holst, Dorte

    2012-01-01

    Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological......]-amine (CyPPA), a subtype-selective positive modulator of SK channels (SK3¿>¿SK2¿>¿>¿>¿SK1, IK), decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both...

  11. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer.

    Science.gov (United States)

    Taylor, Graham S; Jia, Hui; Harrington, Kevin; Lee, Lip Wai; Turner, James; Ladell, Kristin; Price, David A; Tanday, Manjit; Matthews, Jen; Roberts, Claudia; Edwards, Ceri; McGuigan, Lesley; Hartley, Andrew; Wilson, Steve; Hui, Edwin P; Chan, Anthony T C; Rickinson, Alan B; Steven, Neil M

    2014-10-01

    Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations. Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 10(8) pfu) is recommended for investigation in current phase IB and II trials. ©2014 American Association for Cancer Research.

  12. Avian metapneumovirus RT-nested-PCR: a novel false positive reducing inactivated control virus with potential applications to other RNA viruses and real time methods.

    Science.gov (United States)

    Falchieri, Marco; Brown, Paul A; Catelli, Elena; Naylor, Clive J

    2012-12-01

    Using reverse genetics, an avian metapneumovirus (AMPV) was modified for use as a positive control for validating all stages of a popular established RT-nested PCR, used in the detection of the two major AMPV subtypes (A and B). Resultant amplicons were of increased size and clearly distinguishable from those arising from unmodified virus, thus allowing false positive bands, due to control virus contamination of test samples, to be identified readily. Absorption of the control virus onto filter paper and subsequent microwave irradiation removed all infectivity while its function as an efficient RT-nested-PCR template was unaffected. Identical amplicons were produced after storage for one year. The modified virus is likely to have application as an internal standard as well as in real time methods. Additions to AMPV of RNA from other RNA viruses, including hazardous examples such HIV and influenza, are likely to yield similar safe RT-PCR controls. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Tc-labeling of Peptidomimetic Antagonist to Selectively Target alpha(v)beta(3) Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands.

    Science.gov (United States)

    Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C P; Wood, Bradford; Carrasquillo, Jorge A; Danthi, S Narasimhan; Paik, Chang H

    2010-01-01

    OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonist with (99m)Tc for rapid targeting of integrin alpha(v)beta(3) receptors in tumor to produce a high tumor to background ratio. METHODS: The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-beta-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with (99m)Tc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. The products, (99m)Tc EDDA(2)/HYNIC-IAC (P1) and (99m)Tc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. RESULTS: P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 degrees C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 +/- 13.48 vs 51.05 +/- 14.05%) when incubated with alpha(v)beta(3) at a molar excess (0.8 muM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17+/-0.52 and 2.13+/-0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 +/- 3.67% ID at 4 h whereas 54.04 +/- 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by

  14. Model selection and averaging in the assessment of the drivers of household food waste to reduce the probability of false positives

    Science.gov (United States)

    Aramyan, Lusine; Piras, Simone; Quested, Thomas Edward; Righi, Simone; Setti, Marco; Vittuari, Matteo; Stewart, Gavin Bruce

    2018-01-01

    Food waste from households contributes the greatest proportion to total food waste in developed countries. Therefore, food waste reduction requires an understanding of the socio-economic (contextual and behavioural) factors that lead to its generation within the household. Addressing such a complex subject calls for sound methodological approaches that until now have been conditioned by the large number of factors involved in waste generation, by the lack of a recognised definition, and by limited available data. This work contributes to food waste generation literature by using one of the largest available datasets that includes data on the objective amount of avoidable household food waste, along with information on a series of socio-economic factors. In order to address one aspect of the complexity of the problem, machine learning algorithms (random forests and boruta) for variable selection integrated with linear modelling, model selection and averaging are implemented. Model selection addresses model structural uncertainty, which is not routinely considered in assessments of food waste in literature. The main drivers of food waste in the home selected in the most parsimonious models include household size, the presence of fussy eaters, employment status, home ownership status, and the local authority. Results, regardless of which variable set the models are run on, point toward large households as being a key target element for food waste reduction interventions. PMID:29389949

  15. Model selection and averaging in the assessment of the drivers of household food waste to reduce the probability of false positives.

    Science.gov (United States)

    Grainger, Matthew James; Aramyan, Lusine; Piras, Simone; Quested, Thomas Edward; Righi, Simone; Setti, Marco; Vittuari, Matteo; Stewart, Gavin Bruce

    2018-01-01

    Food waste from households contributes the greatest proportion to total food waste in developed countries. Therefore, food waste reduction requires an understanding of the socio-economic (contextual and behavioural) factors that lead to its generation within the household. Addressing such a complex subject calls for sound methodological approaches that until now have been conditioned by the large number of factors involved in waste generation, by the lack of a recognised definition, and by limited available data. This work contributes to food waste generation literature by using one of the largest available datasets that includes data on the objective amount of avoidable household food waste, along with information on a series of socio-economic factors. In order to address one aspect of the complexity of the problem, machine learning algorithms (random forests and boruta) for variable selection integrated with linear modelling, model selection and averaging are implemented. Model selection addresses model structural uncertainty, which is not routinely considered in assessments of food waste in literature. The main drivers of food waste in the home selected in the most parsimonious models include household size, the presence of fussy eaters, employment status, home ownership status, and the local authority. Results, regardless of which variable set the models are run on, point toward large households as being a key target element for food waste reduction interventions.

  16. Controlling for Prior Attainment Reduces the Positive Influence that Single-Gender Classroom Initiatives Exert on High School Students' Scholastic Achievements.

    Science.gov (United States)

    Pennington, Charlotte R; Kaye, Linda K; Qureshi, Adam W; Heim, Derek

    2018-01-01

    Research points to the positive impact that gender-segregated schooling and classroom initiatives exert on academic attainment. An evaluation of these studies which reveal positive effects highlights, however, that students are typically selectively assigned to single- or mixed-gender instructional settings, presenting a methodological confound. The current study controls for students' prior attainment to appraise the efficacy of a single-gender classroom initiative implemented in a co-educational high school in the United Kingdom. Secondary data analysis (using archived data) was performed on 266 middle-ability, 11-12 year-old students' standardized test scores in Languages (English, foreign language), STEM-related (Mathematics, Science, Information and Communication Technology), and Non-STEM subjects (art, music, drama). Ninety-eight students (54, 55% female) were taught in single-gender and 168 (69, 41% female) in mixed-gender classrooms. Students undertook identical tests irrespective of classroom type, which were graded in accordance with U.K national curriculum guidelines. Controlling for students' prior attainment, findings indicate that students do not appear to benefit from being taught in single-gender relative to mixed-gender classrooms in Language and STEM-related subjects. Young women benefitted from being taught in mixed-gender relative to single-gender classes for Non-STEM subjects. However, when prior ability is not controlled for, the intervention appears to be effective for all school subjects, highlighting the confounding influence of selective admissions. These findings suggest that gender-segregated classroom initiatives may not bolster students' grades. It is argued that studies that do not control for selection effects may tell us little about the effectiveness of such interventions on scholastic achievement.

  17. X-ray flux and X-ray burn through experiments on reduced-scale targets at the Nif and OMEGA lasers

    International Nuclear Information System (INIS)

    Schneider, M.B.; Hinkel, D.E.; Young, B.K.; Holder, J.P.; Langdon, A.B.; Bower, D.E.; Bruns, H.C.; Campbell, K.M.; Celeste, J.R.; Compton, S.; Costa, R.L.; Dewald, E.L.; Dixit, S.N.; Eckart, M.J.; Eder, D.C.; Edwards, M.J.; Ellis, A.D.; Emig, J.A.; Froula, D.H.; Glebov, V.; Glenzer, S.H.; Hargrove, D.; Haynam, C.A.; Heeter, R.F.; Henesian, M.A.; Holtmeier, G.; James, D.L.; Jancaitis, K.S.; Kalantar, D.H.; Kamperschroer, J.H.; Kauffman, R.L.; Kimbrough, J.; Kirkwood, R.; Koniges, A.E.; Landen, O.L.; Landon, M.; Lee, F.D.; MacGowan, B.J.; Mackinnon, A.J.; Manes, K.R.; Marshall, C.; May, M.J.; McDonald, J.W.; Menapace, J.; Moon, S.J.; Moses, E.I.; Munro, D.H.; Murray, J.R.; Niemann, C.; Piston, K.; Power, G.D.; Rekow, V.; Ruppe, J.A.; Schein, J.; Shepherd, R.; Singh, M.S.; Sorce, C.; Springer, P.T.; Still, C.H.; Suter, L.J.; Tietbohl, G.L.; Turner, R.E.; Van Wonterghem, B.M.; Wallace, R.J.; Warrick, A.; Weber, F.; Wegner, P.J.; Williams, E.A.; Young, P.E.; Baldis, H.A.; Constantin, C.G.; Bahr, R.; Roberts, S.; Seka, W.; Stoeckl, C.; Pellinen, D.; Watts, P.

    2006-01-01

    An experimental campaign to maximize radiation drive in small-scale hohlraums has been carried out at the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory (Livermore, USA) and at the OMEGA laser at the Laboratory for Laser Energetics (Rochester, USA). The small-scale hohlraums, laser energy, laser pulse, and diagnostics were similar at both facilities but the geometries were very different. The NIF experiments used on-axis laser beams whereas the OMEGA experiments used 19 beams in three beam cones. In the cases when the lasers coupled well and produced similar radiation drive, images of X-ray burn-through and laser deposition indicate the pattern of plasma filling is very different. The OMEGA targets fill faster than the NIF targets, which helps explain the time behavior of the X-ray fluences. (authors)

  18. X-ray flux and X-ray burn through experiments on reduced-scale targets at the Nif and OMEGA lasers

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.B.; Hinkel, D.E.; Young, B.K.; Holder, J.P.; Langdon, A.B.; Bower, D.E.; Bruns, H.C.; Campbell, K.M.; Celeste, J.R.; Compton, S.; Costa, R.L.; Dewald, E.L.; Dixit, S.N.; Eckart, M.J.; Eder, D.C.; Edwards, M.J.; Ellis, A.D.; Emig, J.A.; Froula, D.H.; Glebov, V.; Glenzer, S.H.; Hargrove, D.; Haynam, C.A.; Heeter, R.F.; Henesian, M.A.; Holtmeier, G.; James, D.L.; Jancaitis, K.S.; Kalantar, D.H.; Kamperschroer, J.H.; Kauffman, R.L.; Kimbrough, J.; Kirkwood, R.; Koniges, A.E.; Landen, O.L.; Landon, M.; Lee, F.D.; MacGowan, B.J.; Mackinnon, A.J.; Manes, K.R.; Marshall, C.; May, M.J.; McDonald, J.W.; Menapace, J.; Moon, S.J.; Moses, E.I.; Munro, D.H.; Murray, J.R.; Niemann, C.; Piston, K.; Power, G.D.; Rekow, V.; Ruppe, J.A.; Schein, J.; Shepherd, R.; Singh, M.S.; Sorce, C.; Springer, P.T.; Still, C.H.; Suter, L.J.; Tietbohl, G.L.; Turner, R.E.; Van Wonterghem, B.M.; Wallace, R.J.; Warrick, A.; Weber, F.; Wegner, P.J.; Williams, E.A.; Young, P.E. [Lawrence Livermore National Lab., Livermore, CA (United States); Baldis, H.A.; Constantin, C.G. [California at Davis Univ., CA (United States); Bahr, R.; Roberts, S.; Seka, W.; Stoeckl, C. [Laboratory for Laser Energetics, Rochester, NY (United States); Pellinen, D.; Watts, P. [Bechtel Nevada Corporation, Livermore, CA (United States)

    2006-06-15

    An experimental campaign to maximize radiation drive in small-scale hohlraums has been carried out at the National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory (Livermore, USA) and at the OMEGA laser at the Laboratory for Laser Energetics (Rochester, USA). The small-scale hohlraums, laser energy, laser pulse, and diagnostics were similar at both facilities but the geometries were very different. The NIF experiments used on-axis laser beams whereas the OMEGA experiments used 19 beams in three beam cones. In the cases when the lasers coupled well and produced similar radiation drive, images of X-ray burn-through and laser deposition indicate the pattern of plasma filling is very different. The OMEGA targets fill faster than the NIF targets, which helps explain the time behavior of the X-ray fluences. (authors)

  19. HPMA copolymer conjugates with reduced anti-CD20 antibody for cell-specific drug targeting. I. Synthesis and in vitro evaluation of binding efficacy and cytostatic activity

    Czech Academy of Sciences Publication Activity Database

    Etrych, Tomáš; Strohalm, Jiří; Kovář, Lubomír; Kabešová, Martina; Říhová, Blanka; Ulbrich, Karel

    2009-01-01

    Roč. 140, č. 1 (2009), s. 18-26 ISSN 0168-3659 R&D Projects: GA MŠk 1M0505; GA AV ČR IAAX00500803 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : HPMA copolymers * drug delivery systems * doxorubicin * monoclonal anti-CD20 antibody * drug targeting Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.949, year: 2009

  20. Topical grape seed proanthocyandin extract reduces sunburn cells and mutant p53 positive epidermal cell formation, and prevents depletion of Langerhans cells in an acute sunburn model.

    Science.gov (United States)

    Yuan, Xiao-Ying; Liu, Wei; Hao, Jian-Chun; Gu, Wei-Jie; Zhao, Yan-Shuang

    2012-01-01

    The purpose of this study was to investigate whether grape seed proanthocyanidin extract (GSPE) can provide photoprotection against ultraviolet (UV) irradiation. Study has shown that GSPE is a natural oxidant, and is used in many fields such as ischemia-reperfusion injury, chronic pancreatitis, and even cancer. However, the effect of GSPE on UV irradiation is as yet unknown. Cutaneous areas on the backs of normal volunteers were untreated or treated with GSPE solutions or vehicles 30 min before exposure to two minimal erythema doses (MED) of solar simulated radiation. Cutaneous areas at different sites were examined histologically for the number of sunburn cells, or immunohistochemically for Langerhans cells and mutant p53 epidermal cells. On histological and immunohistochemical examination, skin treated with GSPE before UV radiation showed fewer sunburn cells and mutant p53-positive epidermal cells and more Langerhans cells compared with skin treated with 2-MED UV radiation only (p<0.001, p<0.001, and p<0.01, respectively). GSPE may be a possible preventive agent for photoprotection.

  1. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival.

    Science.gov (United States)

    Cosgrove, Casey M; Cohn, David E; Hampel, Heather; Frankel, Wendy L; Jones, Dan; McElroy, Joseph P; Suarez, Adrian A; Zhao, Weiqiang; Chen, Wei; Salani, Ritu; Copeland, Larry J; O'Malley, David M; Fowler, Jeffrey M; Yilmaz, Ahmet; Chassen, Alexis S; Pearlman, Rachel; Goodfellow, Paul J; Backes, Floor J

    2017-09-01

    To determine the relationship between mismatch repair (MMR) classification and clinicopathologic features including tumor volume, and explore outcomes by MMR class in a contemporary cohort. Single institution cohort evaluating MMR classification for endometrial cancers (EC). MMR immunohistochemistry (IHC)±microsatellite instability (MSI) testing and reflex MLH1 methylation testing was performed. Tumors with MMR abnormalities by IHC or MSI and MLH1 methylation were classified as epigenetic MMR deficiency while those without MLH1 methylation were classified as probable MMR mutations. Clinicopathologic characteristics were analyzed. 466 endometrial cancers were classified; 75% as MMR proficient, 20% epigenetic MMR defects, and 5% as probable MMR mutations. Epigenetic MMR defects were associated with advanced stage, higher grade, presence of lymphovascular space invasion, and older age. MMR class was significantly associated with tumor volume, an association not previously reported. The epigenetic MMR defect tumors median volume was 10,220mm 3 compared to 3321mm 3 and 2,846mm 3 , for MMR proficient and probable MMR mutations respectively (PMLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Sleep apnea-related risk of motor vehicle accidents is reduced by continuous positive airway pressure: Swedish Traffic Accident Registry data.

    Science.gov (United States)

    Karimi, Mahssa; Hedner, Jan; Häbel, Henrike; Nerman, Olle; Grote, Ludger

    2015-03-01

    Obstructive sleep apnea (OSA) is associated with an increased risk of motor vehicle accidents (MVAs). The rate of MVAs in patients suspected of having OSA was determined and the effect of continuous positive airway pressure (CPAP) was investigated. MVA rate in patients referred for OSA was compared to the rate in the general population using data from the Swedish Traffic Accident Registry (STRADA), stratified for age and calendar year. The risk factors for MVAs, using demographic and polygraphy data, and MVA rate before and after CPAP were evaluated in the patient group. Clinical sleep laboratory and population based control (n = 635,786). There were 1,478 patients, male sex 70.4%, mean age 53.6 (12.8) y. CPAP. The number of accidents (n = 74) among patients was compared with the expected number (n = 30) from a control population (STRADA). An increased MVA risk ratio of 2.45 was found among patients compared with controls (P accident risk was most prominent in the elderly patients (65-80 y, seven versus two MVAs). In patients, driving distance (km/y), EDS (Epworth Sleepiness score ≥ 16), short habitual sleep time (≤5 h/night), and use of hypnotics were associated with increased MVA risk (odds ratios 1.2, 2.1, 2.7 and 2.1, all P ≤ 0.03). CPAP use ≥ 4 h/night was associated with a reduction of MVA incidence (7.6 to 2.5 accidents/1,000 drivers/y). The MVA risk in this large cohort of unselected patients with OSA suggests a need for accurate tools to identify individuals at risk. Sleep apnea severity (e.g., apnea-hypopnea index) failed to identify patients at risk. © 2015 Associated Professional Sleep Societies, LLC.

  3. Continuous positive airway pressure reduces blood pressure in patients with obstructive sleep apnea; a systematic review and meta-analysis with 1000 patients.

    Science.gov (United States)

    Schein, Andressa S O; Kerkhoff, Alessandra C; Coronel, Christian C; Plentz, Rodrigo D M; Sbruzzi, Graciele

    2014-09-01

    Obstructive sleep apnea (OSA) may lead to the development of hypertension and therapy with continuous positive airway pressure (CPAP) can promote reduction in blood pressure. The objective of this study is to review systematically the effects of CPAP on blood pressure in patients with OSA. The search was conducted in the following databases, from their beginning until February 2013: MEDLINE, Embase, Cochrane CENTRAL, Lilacs and PEDro. In addition, a manual search was performed on references of published studies. Randomized clinical trials (RCTs) that used CPAP compared with placebo CPAP or subtherapeutic CPAP for treatment of patients with OSA and that evaluated office SBP and DBP and 24-h ambulatory blood pressure were selected. Sixteen RCTs were included among 3409 publications, totaling 1166 patients. The use of CPAP resulted in reductions in office SBP [-3.20  mmHg; 95% confidence interval (CI) -4.67 to -1.72] and DBP (-2.87  mmHg; 95% CI -5.18 to -0.55); in night-time SBP (-4.92  mmHg; 95% CI -8.70 to -1.14); in mean 24-h blood pressure (-3.56  mmHg; 95% CI -6.79 to -0.33), mean night-time blood pressure (-2.56  mmHg; 95% CI -4.43 to -0.68) and 24-h DBP (-3.46  mmHg; 95% CI -6.75 to -0.17). However, no significant change was observed in daytime SBP (-0.74  mmHg; 95% CI -3.90 to 2.41) and daytime DBP (-1.86  mmHg; 95% CI -4.55 to 0.83). Treatment with CPAP promoted significantly but small reductions in blood pressure in individuals with OSA. Further studies should be performed to evaluate the effects of long-term CPAP and the impact on cardiovascular risk.

  4. The challenge of reducing scientific complexity for different target groups (without losing the essence) - experiences from interdisciplinary audio-visual media production

    Science.gov (United States)

    Hezel, Bernd; Broschkowski, Ephraim; Kropp, Jürgen

    2013-04-01

    The Climate Media Factory originates from an interdisciplinary media lab run by the Film and Television University "Konrad Wolf" Potsdam-Babelsberg (HFF) and the Potsdam Institute for Climate Impact Research (PIK). Climate scientists, authors, producers and media scholars work together to develop media products on climate change and sustainability. We strive towards communicating scientific content via different media platforms reconciling the communication needs of scientists and the audience's need to understand the complexity of topics that are relevant in their everyday life. By presenting four audio-visual examples, that have been designed for very different target groups, we show (i) the interdisciplinary challenges during the production process and the lessons learnt and (ii) possibilities to reach the required degree of simplification without the need for dumbing down the content. "We know enough about climate change" is a short animated film that was produced for the German Agency for International Cooperation (GIZ) for training programs and conferences on adaptation in the target countries including Indonesia, Tunisia and Mexico. "Earthbook" is a short animation produced for "The Year of Science" to raise awareness for the topics of sustainability among digital natives. "What is Climate Engineering?". Produced for the Institute for Advanced Sustainability Studies (IASS) the film is meant for an informed and interested public. "Wimmelwelt Energie!" is a prototype of an iPad application for children from 4-6 years of age to help them learn about different forms of energy and related greenhouse gas emissions.

  5. Chronic Alcohol Consumption Alters Mammalian Target of Rapamycin (mTOR), Reduces Ribosomal p70S6 Kinase and p4E-BP1 Levels in Mouse Cerebral Cortex

    OpenAIRE

    Li, Qun; Ren, Jun

    2007-01-01

    Reduced insulin sensitivity following chronic alcohol consumption may contribute to alcohol-induced brain damage although the underlying mechanism(s) has not been elucidated. This study was designed to examine the effect of chronic alcohol intake on insulin signaling in mouse cerebral cortex. FVB mice were fed with a 4% alcohol diet for 16 weeks. Insulin receptor substrates (IRS-1, IRS-2) and post-receptor signaling molecules Akt, mammalian target of rapamycin (mTOR), ribosomal p70s6 kinase (...

  6. Instruments to reduce pollutant emissions of the existing inland vessel fleet. Position paper for international workshop 'Emissions from the Legacy Fleet'

    Energy Technology Data Exchange (ETDEWEB)

    Den Boer, E.

    2011-11-15

    Inland waterway transport (IWT) has a key performance on the GHG emissions per tonne kilometre shipped. Due to its potential to limit climate change, the recent EU Transport White Paper has set high goals for the non-road modes. The Ports of Rotterdam (NL), Antwerp (BE) and others strive to increase the use of IWT in their hinterland transport. The Port of Rotterdam authority has imposed a modal split on the newly built container terminals, thus increasing the use of rail and IWT. The growth is estimated to result in a quadrupling of inland barge container traffic on the Rhine corridor in the timeframe 2010-2035. Local air quality is another environmental issue, however, that plays a key role. Due to reasons of long ship engine lifetimes and progress made in road transport emissions, IWT needs to improve its air pollution profile. To turn the potential of IWT into real growth, it is important to: improve the air pollutant profile of inland shipping; take responsibility to maintain the air quality levels along inland waterway corridors over Europe, especially in urban areas where road transport, industry and IWT contribute to levels that will need to be in accordance with the EU air quality directive 2008/51. A new set of standards for new engines will shortly be proposed by the European Commission to be introduced in 2016. However, these will probably not be as tight as the Euro-VI standards for road transport. In addition, the long lifetime of inland barge engines (30,000 to over 200,000 hours, depending on the engine type) will result in a slow uptake of the phase-IV engines in the fleet. The German and Dutch authorities have the opinion that not only the air pollutant emissions of new engines need to be curbed, but deliberate over the development of instruments that will reduce the pollutant emissions of the existing fleet (legacy fleet), in addition to the limitedly effective subsidy schemes applied in recent years. This paper demonstrates the need for measures

  7. Sex in the shadow of HIV: A systematic review of prevalence, risk factors, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa

    Science.gov (United States)

    Haghighat, Roxanna; Cluver, Lucie

    2017-01-01

    Background Evidence on sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa is urgently needed. This systematic review synthesizes the extant research on prevalence, factors associated with, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa. Methods Studies were located through electronic databases, grey literature, reference harvesting, and contact with researchers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quantitative studies that reported on HIV-positive participants (10–24 year olds), included data on at least one of eight outcomes (early sexual debut, inconsistent condom use, older partner, transactional sex, multiple sexual partners, sex while intoxicated, sexually transmitted infections, and pregnancy), and were conducted in sub-Saharan Africa were included. Two authors piloted all processes, screened studies, extracted data independently, and resolved any discrepancies. Due to variance in reported rates and factors associated with sexual risk-taking, meta-analyses were not conducted. Results 610 potentially relevant titles/abstracts resulted in the full text review of 251 records. Forty-two records (n = 35 studies) reported one or multiple sexual practices for 13,536 HIV-positive adolescents/youth from 13 sub-Saharan African countries. Seventeen cross-sectional studies reported on individual, relationship, family, structural, and HIV-related factors associated with sexual risk-taking. However, the majority of the findings were inconsistent across studies, and most studies scored HIV-positive status and accessing HIV support groups were associated with reduced sexual risk-taking. Of the four intervention studies (three RCTs), three evaluated group-based interventions, and one evaluated an individual-focused combination intervention. Three of the interventions were effective at reducing sexual risk-taking, with one

  8. Expression of trypsin modulating oostatic factor (TMOF in an entomopathogenic fungus increases its virulence towards Anopheles gambiae and reduces fecundity in the target mosquito

    Directory of Open Access Journals (Sweden)

    Kamareddine Layla

    2013-01-01

    Full Text Available Abstract Background Adult and larval mosquitoes regulate food digestion in their gut with trypsin modulating oostatic factor (TMOF, a decapeptide hormone synthesized by the ovaries and the neuroendocrine system. TMOF is currently being developed as a mosquitocide, however, delivery of the peptide to the mosquito remains a significant challenge. Entomopathogenic fungi offer a means for targeting mosquitoes with TMOF. Findings The efficacy of wild type and transgenic Beauveria bassiana strains expressing Aedes aegypti TMOF (Bb-Aa1 were evaluated against larvae and sugar- and blood-fed adult Anopheles gambiae mosquitoes using insect bioassays. Bb-Aa1 displayed increased virulence against larvae, and sugar and blood fed adult A. gambiae when compared to the wild type parent strain. Median lethal dose (LD50 values decreased by ~20% for larvae, and ~40% for both sugar and blood-fed mosquitoes using Bb-Aa1 relative to the wild type parent. Median lethal time (LT50 values were lower for blood-fed compared to sugar-fed mosquitoes in infections with both wild type and Bb-Aa1. However, infection using Bb-Aa1 resulted in 15% to 25% reduction in LT50 values for sugar- and blood fed mosquitoes, and ~27% for larvae, respectively, relative to the wild type parent. In addition, infection with Bb-Aa1 resulted in a dramatic reduction in fecundity of the target mosquitoes. Conclusions B. bassiana expressing Ae. aegypti TMOF exhibited increased virulence against A. gambiae compared to the wild type strain. These data expand the range and utility of entomopathogenic fungi expressing mosquito-specific molecules to improve their biological control activities against mosquito vectors of disease.

  9. Voluntary Deep Inspiration Breath-hold Reduces the Heart Dose Without Compromising the Target Volume Coverage During Radiotherapy for Left-sided Breast Cancer.

    Science.gov (United States)

    Al-Hammadi, Noora; Caparrotti, Palmira; Naim, Carole; Hayes, Jillian; Rebecca Benson, Katherine; Vasic, Ana; Al-Abdulla, Hissa; Hammoud, Rabih; Divakar, Saju; Petric, Primoz

    2018-03-01

    During radiotherapy of left-sided breast cancer, parts of the heart are irradiated, which may lead to late toxicity. We report on the experience of single institution with cardiac-sparing radiotherapy using voluntary deep inspiration breath hold (V-DIBH) and compare its dosimetric outcome with free breathing (FB) technique. Left-sided breast cancer patients, treated at our department with postoperative radiotherapy of breast/chest wall +/- regional lymph nodes between May 2015 and January 2017, were considered for inclusion. FB-computed tomography (CT) was obtained and dose-planning performed. Cases with cardiac V25Gy ≥ 5% or risk factors for heart disease were coached for V-DIBH. Compliant patients were included. They underwent additional CT in V-DIBH for planning, followed by V-DIBH radiotherapy. Dose volume histogram parameters for heart, lung and optimized planning target volume (OPTV) were compared between FB and BH. Treatment setup shifts and systematic and random errors for V-DIBH technique were compared with FB historic control. Sixty-three patients were considered for V-DIBH. Nine (14.3%) were non-compliant at coaching, leaving 54 cases for analysis. When compared with FB, V-DIBH resulted in a significant reduction of mean cardiac dose from 6.1 +/- 2.5 to 3.2 +/- 1.4 Gy (p FB and V-DIBH, respectively (p FB- and V-DIBH-derived mean lung dose (11.3 +/- 3.2 vs. 10.6 +/- 2.6 Gy), lung V20Gy (20.5 +/- 7 vs. 19.5 +/- 5.1 Gy) and V95% for the OPTV (95.6 +/- 4.1 vs. 95.2 +/- 6.3%) were non-significant. V-DIBH-derived mean shifts for initial patient setup were ≤ 2.7 mm. Random and systematic errors were ≤ 2.1 mm. These results did not differ significantly from historic FB controls. When compared with FB, V-DIBH demonstrated high setup accuracy and enabled significant reduction of cardiac doses without compromising the target volume coverage. Differences in lung doses were non-significant.

  10. Reduced Activity of SRY and its Target Enhancer Sox9-TESCO in a Mouse Species with X*Y Sex Reversal.

    Science.gov (United States)

    Zhao, Liang; Quinn, Alexander; Ng, Ee Ting; Veyrunes, Frederic; Koopman, Peter

    2017-02-03

    In most eutherian mammals, sex determination is governed by the Y-linked gene Sry, but in African pygmy mice Mus minutoides, Sry action is overridden by a variant X chromosome (X*), yielding X*Y females. We hypothesized that X*Y sex reversal may be underpinned not only by neomorphic X chromosome functionality, but also by a compromised Sry pathway. Here, we show that neither M. minutoides SRY nor its target, the Sox9-TESCO enhancer, had appreciable transcriptional activity in in vitro assays, correlating with sequence degradation compared to Mus musculus counterparts. However, M. minutoides SRY activated its cognate TESCO to a moderate degree, and can clearly engage the male pathway in M. minutoides in the wild, indicating that SRY and TESCO may have co-evolved in M. minutoides to retain function above a threshold level. We suggest that weakening of the SRY/TESCO nexus may have facilitated the rise and spread of a variant X* chromosome carrying female-inducing modifier gene(s).

  11. Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

    Science.gov (United States)

    Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.

  12. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve.

    Science.gov (United States)

    de la Barca, J M Chao; Boueilh, T; Simard, G; Boucret, L; Ferré-L'Hotellier, V; Tessier, L; Gadras, C; Bouet, P E; Descamps, P; Procaccio, V; Reynier, P; May-Panloup, P

    2017-11-01

    Does the metabolomic profile of the follicular fluid (FF) of patients with a diminished ovarian reserve (DOR) differ from that of patients with a normal ovarian reserve (NOR)? The metabolomic signature of the FF reveals a significant decrease in polyunsaturated choline plasmalogens and methyl arginine transferase activity in DOR patients compared to NOR patients. The composition of the FF reflects the exchanges between the oocyte and its microenvironment during its acquisition of gametic competence. Studies of the FF have allowed identification of biomarkers and metabolic pathways involved in various pathologies affecting oocyte quality, but no large metabolomic analysis in the context of ovarian ageing and DOR has been undertaken so far. This was an observational study of the FF retrieved from 57 women undergoing in vitro fertilization at the University Hospital of Angers, France, from November 2015 to September 2016. The women were classified in two groups: one including 28 DOR patients, and the other including 29 NOR patients, serving as controls. Patients were enrolled in the morning of oocyte retrieval after ovarian stimulation. Once the oocytes were isolated for fertilization and culture, the FF was pooled and centrifuged for analysis. A targeted quantitative metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels of 188 metabolites and several sums and ratios of metabolic significance were assessed by multivariate and univariate analyses. A total of 136 metabolites were accurately quantified and used for calculating 23 sums and ratios. Samples were randomly divided into training and validation sets. The training set, allowed the construction of multivariate statistical models with a projection-supervised method, i.e. orthogonal partial least squares discriminant analysis (OPLS-DA), applied to the full set of metabolites, or the penalized

  13. Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

    Science.gov (United States)

    Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

    2016-10-01

    In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  14. Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson’s rats

    Directory of Open Access Journals (Sweden)

    Song L

    2016-02-01

    Full Text Available Lu Song,1,* Zhanzhao Zhang,2,* Rongguo Hu,1 Jie Cheng,1 Lin Li,1 Qinyi Fan,1 Na Wu,1 Jing Gan,1 Mingzhu Zhou,1 Zhenguo Liu11Department of Neurology, Xinhua Hospital, 2Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: L-3,4-dihydroxyphenylalanine (L-dopa remains the most effective therapy for Parkinson’s disease (PD, but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID. Enhanced function of dopamine D1 receptor (D1R and N-methyl-d-aspartate receptor (NMDAR is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1 interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2. In this study, we demonstrated in 6-hydroxydopamine (6-OHDA-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson’s patients.Keywords: 6-hydroxydopamine, Parkinson’s disease, dyskinesia, L-dopa, D1 receptor, NMDA, protein–protein interaction

  15. Image thresholding in the high resolution target movement monitor

    Science.gov (United States)

    Moss, Randy H.; Watkins, Steve E.; Jones, Tristan H.; Apel, Derek B.; Bairineni, Deepti

    2009-03-01

    Image thresholding in the High Resolution Target Movement Monitor (HRTMM) is examined. The HRTMM was developed at the Missouri University of Science and Technology to detect and measure wall movements in underground mines to help reduce fatality and injury rates. The system detects the movement of a target with sub-millimeter accuracy based on the images of one or more laser dots projected on the target and viewed by a high-resolution camera. The relative position of the centroid of the laser dot (determined by software using thresholding concepts) in the images is the key factor in detecting the target movement. Prior versions of the HRTMM set the image threshold based on a manual, visual examination of the images. This work systematically examines the effect of varying threshold on the calculated centroid position and describes an algorithm for determining a threshold setting. First, the thresholding effects on the centroid position are determined for a stationary target. Plots of