WorldWideScience

Sample records for randomly dividing cells

  1. DNA repair mechanisms in dividing and non-dividing cells.

    Science.gov (United States)

    Iyama, Teruaki; Wilson, David M

    2013-08-01

    DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease. Published by Elsevier B.V.

  2. High incidence of non-random template strand segregation and asymmetric fate determination in dividing stem cells and their progeny.

    Directory of Open Access Journals (Sweden)

    Michael J Conboy

    2007-05-01

    Full Text Available Decades ago, the "immortal strand hypothesis" was proposed as a means by which stem cells might limit acquiring mutations that could give rise to cancer, while continuing to proliferate for the life of an organism. Originally based on observations in embryonic cells, and later studied in terms of stem cell self-renewal, this hypothesis has remained largely unaccepted because of few additional reports, the rarity of the cells displaying template strand segregation, and alternative interpretations of experiments involving single labels or different types of labels to follow template strands. Using sequential pulses of halogenated thymidine analogs (bromodeoxyuridine [BrdU], chlorodeoxyuridine [CldU], and iododeoxyuridine [IdU], and analyzing stem cell progeny during induced regeneration in vivo, we observed extraordinarily high frequencies of segregation of older and younger template strands during a period of proliferative expansion of muscle stem cells. Furthermore, template strand co-segregation was strongly associated with asymmetric cell divisions yielding daughters with divergent fates. Daughter cells inheriting the older templates retained the more immature phenotype, whereas daughters inheriting the newer templates acquired a more differentiated phenotype. These data provide compelling evidence of template strand co-segregation based on template age and associated with cell fate determination, suggest that template strand age is monitored during stem cell lineage progression, and raise important caveats for the interpretation of label-retaining cells.

  3. Flagellation of Pseudomonas aeruginosa in newly divided cells

    Science.gov (United States)

    Zhao, Kun; Lee, Calvin; Anda, Jaime; Wong, Gerard

    2015-03-01

    For monotrichous bacteria, Pseudomonas aeruginosa, after cell division, one daughter cell inherits the old flagellum from its mother cell, and the other grows a new flagellum during or after cell division. It had been shown that the new flagellum grows at the distal pole of the dividing cell when the two daughter cells haven't completely separated. However, for those daughter cells who grow new flagella after division, it still remains unknown at which pole the new flagellum will grow. Here, by combining our newly developed bacteria family tree tracking techniques with genetic manipulation method, we showed that for the daughter cell who did not inherit the old flagellum, a new flagellum has about 90% chances to grow at the newly formed pole. We proposed a model for flagellation of P. aeruginosa.

  4. Actin in dividing cells: contractile ring filaments bind heavy meromyosin.

    Science.gov (United States)

    Schroeder, T E

    1973-06-01

    Many microfilaments and microtubules are well preserved after glycerol-extraction of HeLa cells at room temperature (22 degrees ). Incubation in heavy meromyosin from rabbit skeletal muscle results in conspicuous and characteristic "decoration" of microfilaments of the contractile ring. Decoration is completely prevented by 10 mM ATP or 2 mM pyrophosphate, and fails to occur if heavy meromyosin is either omitted or replaced by egg albumin, a nonspecific protein. Decorated microfilaments have a substructure consisting of polarized, repeating arrowheads 27-35 nm apart. The specificity of these results strongly suggests that microfilaments of the contractile ring in HeLa cells are closely related to muscle actin. Very thin undecorated strands among the microfilaments of the contractile ring possibly represent a myosin component. These findings are discussed in terms of: the actomyosin-like properties of the contractile ring as a mechanochemical organelle that causes cell cleavage; the probable universal occurrence of actin-like protein in all dividing animal cells; and the contractile ring's combined sensitivity to cytochalasin B and its affinity for heavy meromyosin, a combination unique among microfilamentous organelles.

  5. Robustness of synthetic oscillators in growing and dividing cells

    Science.gov (United States)

    Paijmans, Joris; Lubensky, David K.; Rein ten Wolde, Pieter

    2017-05-01

    Synthetic biology sets out to implement new functions in cells, and to develop a deeper understanding of biological design principles. Elowitz and Leibler [Nature (London) 403, 335 (2000), 10.1038/35002125] showed that by rational design of the reaction network, and using existing biological components, they could create a network that exhibits periodic gene expression, dubbed the repressilator. More recently, Stricker et al. [Nature (London) 456, 516 (2008), 10.1038/nature07389] presented another synthetic oscillator, called the dual-feedback oscillator, which is more stable. Detailed studies have been carried out to determine how the stability of these oscillators is affected by the intrinsic noise of the interactions between the components and the stochastic expression of their genes. However, as all biological oscillators reside in growing and dividing cells, an important question is how these oscillators are perturbed by the cell cycle. In previous work we showed that the periodic doubling of the gene copy numbers due to DNA replication can couple not only natural, circadian oscillators to the cell cycle [Paijmans et al., Proc. Natl. Acad. Sci. (USA) 113, 4063 (2016), 10.1073/pnas.1507291113], but also these synthetic oscillators. Here we expand this study. We find that the strength of the locking between oscillators depends not only on the positions of the genes on the chromosome, but also on the noise in the timing of gene replication: noise tends to weaken the coupling. Yet, even in the limit of high levels of noise in the replication times of the genes, both synthetic oscillators show clear signatures of locking to the cell cycle. This work enhances our understanding of the design of robust biological oscillators inside growing and diving cells.

  6. Isolating dividing neural and brain tumour cells for gene expression profiling.

    Science.gov (United States)

    Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

    2016-01-15

    The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Random Cell Identifiers Assignment

    Directory of Open Access Journals (Sweden)

    Robert Bestak

    2012-01-01

    Full Text Available Despite integration of advanced functions that enable Femto Access Points (FAPs to be deployed in a plug-and-play manner, the femtocell concept still cause several opened issues to be resolved. One of them represents an assignment of Physical Cell Identifiers (PCIs to FAPs. This paper analyses a random based assignment algorithm in LTE systems operating in diverse femtocell scenarios. The performance of the algorithm is evaluated by comparing the number of confusions for various femtocell densities, PCI ranges and knowledge of vicinity. Simulation results show that better knowledge of vicinity can significantly reduce the number of confusions events.

  8. Cortical microtubule labeling: Insight of AFH14 in non-dividing cells

    OpenAIRE

    Cai, Chao; Li, Yanhua; Shen, Yuan; Ren, Haiyun

    2010-01-01

    We recently reported that AFH14 participated in microtubule and actin filament interaction in cell division, and the AFH14 (FH1FH2) was important to the directly binding activity of microtubules and microfilaments. To preliminarily understand the function and localization of AFH14 in non-dividing cells, we overexpressed FH1FH2-RFP in onion epidermal cells, and found a fluorescence labeled filamentous network. The result of double labeling with different cytoskeleton reporter proteins indicate...

  9. Histone deacetylase inhibition activates transgene expression from integration-defective lentiviral vectors in dividing and non-dividing cells.

    Science.gov (United States)

    Pelascini, Laetitia P L; Janssen, Josephine M; Gonçalves, Manuel A F V

    2013-01-01

    Integration-defective lentiviral vectors (IDLVs) are being increasingly deployed in both basic and preclinical gene transfer settings. Often, however, the IDLV transgene expression profile is muted when compared to that of their integration-proficient counterparts. We hypothesized that the episomal nature of IDLVs turns them into preferential targets for epigenetic silencing involving chromatin-remodeling histone deacetylation. Therefore, vectors carrying an array of cis-acting elements and transcriptional unit components were assembled with the aid of packaging constructs encoding either the wild-type or the class I mutant D116N integrase moieties. The transduction levels and transgene-product yields provided by each vector class were assessed in the presence and absence of the histone deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A. To investigate the role of the target cell replication status, we performed experiments in growth-arrested human mesenchymal stem cells and in post-mitotic syncytial myotubes. We found that IDLVs are acutely affected by HDACs regardless of their genetic makeup or target cell replication rate. Interestingly, the magnitude of IDLV transgene expression rescue due to HDAC inhibition varied in a vector backbone- and cell type-dependent manner. Finally, investigation of histone modifications by chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) revealed a paucity of euchromatin marks distributed along IDLV genomes when compared to those measured on isogenic integration-competent vector templates. These findings support the view that IDLVs constitute preferential targets for epigenetic silencing involving histone deacetylation, which contributes to dampening their full transcriptional potential. Our data provide leads on how to most optimally titrate and deploy these promising episomal gene delivery vehicles.

  10. Assessing Impact and Bridging Methodological Divides: Randomized Trials in Countries Affected by Conflict

    Science.gov (United States)

    Burde, Dana

    2012-01-01

    Randomized trials have experienced a marked surge in endorsement and popularity in education research in the past decade. This surge reignited paradigm debates and spurred qualitative critics to accuse these experimental designs of eclipsing qualitative research. This article reviews a current iteration of this debate and examines two randomized…

  11. Integrating retroviral cassette extends gene delivery of HSV-1 expression vectors to dividing cells.

    Science.gov (United States)

    de Felipe, P; Izquierdo, M; Wandosell, F; Lim, F

    2001-08-01

    Retroviral vectors have long been used in a wide variety of gene transfer applications but have certain drawbacks, such as small cargo size, limited tropism, and low titers. HSV expression vectors overcome these disadvantages, but, because they persist in target cells as nonreplicative episomes, they are not retained in all the progeny of dividing cells. Chimeric HSV/AAV products that can mediate transgene integration in human mitotic cells have been constructed, but, to date, genetic modification of dividing cells in animal models using HSV products has not been possible. Here, we report the construction of hybrid HSV/retroviral vectors that exhibit up to 50-fold higher transgene integration efficiency compared to vectors containing only HSV-1 components. Efficient integration of a retroviral transgene cassette encoding pac in human cells required expression of the Moloney murine leukemia virus gag-pol genes, but in murine cells, could also be mediated by endogenous activities, albeit at a lower level. Gene delivery was equally efficient in BHK21, a cell line resistant to retroviral infection, and transgene retention and expression were observed to be stable for least one month in Hs683 human glioma cells. These vectors have wide applications for the genetic modification of many cell types.

  12. Particle-in-cell simulations of electron beam control using an inductive current divider

    Science.gov (United States)

    Swanekamp, S. B.; Angus, J. R.; Cooperstein, G.; Ottinger, P. F.; Richardson, A. S.; Schumer, J. W.; Weber, B. V.

    2015-11-01

    Kinetic, time-dependent, electromagnetic, particle-in-cell simulations of the inductive current divider are presented. The inductive current divider is a passive method for controlling the trajectory of an intense, hollow electron beam using a vacuum structure that inductively splits the beam's return current. The current divider concept was proposed and studied theoretically in a previous publication [Swanekamp et al., Phys. Plasmas 22, 023107 (2015)]. A central post carries a portion of the return current (I1), while the outer conductor carries the remainder (I2) with the injected beam current given by Ib = I1 + I2. The simulations are in agreement with the theory which predicts that the total force on the beam trajectory is proportional to (I2-I1) and the force on the beam envelope is proportional to Ib. Independent control over both the current density and the beam angle at the target is possible by choosing the appropriate current-divider geometry. The root-mean-square (RMS) beam emittance (ɛRMS) varies as the beam propagates through the current divider to the target. For applications where control of the beam trajectory is desired and the current density at the target is similar to the current density at the entrance foil, there is a modest 20% increase in ɛRMS at the target. For other applications where the beam is pinched to a current density ˜5 times larger at the target, ɛRMS is 2-3 times larger at the target.

  13. Actomyosin-generated tension on cadherin is similar between dividing and non-dividing epithelial cells in early Xenopus laevis embryos

    Science.gov (United States)

    Herbomel, Gaëtan; Hatte, Guillaume; Roul, Julien; Padilla-Parra, Sergi; Tassan, Jean-Pierre; Tramier, Marc

    2017-01-01

    Epithelia represent a unique situation where polarized cells must maintain sufficiently strong cell-cell contacts to guarantee the epithelial integrity indispensable for barrier functions. Nevertheless, epithelia must also keep sufficient plasticity which is crucial during development and morphogenesis. Adherens junctions and mechanical forces produced by the actomyosin cytoskeleton are major players for epithelial integrity maintenance and plasticity regulations. To understand how the epithelium is able to meet such a challenge, it is indispensable to determine how cellular junctions and mechanical forces acting at adherens junctions are regulated. Here, we investigate the tensile forces acting on adherens junctions via cadherin during cell division in the Xenopus embryos epithelium. Using the recently developed E-cadherin FRET tension sensor and a fastFLIM prototype microscope, we were able to measure mechanical forces applied on cadherin at cell-cell junctions. We have shown that the Xenopus epithelium is under tension, approximately 3 pN which remains stable, indicating that tensile forces acting on cadherin at the adherens junction are at equilibrium. Unexpectedly, mechanical tension across cadherin was similar between dividing and non-dividing epithelial cells. PMID:28327558

  14. The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells.

    Directory of Open Access Journals (Sweden)

    Conrad von Schubert

    2010-09-01

    Full Text Available The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

  15. Biosynthesis of copper nanoparticles and its effect on actively dividing cells of mitosis in Allium cepa.

    Science.gov (United States)

    Nagaonkar, Dipali; Shende, Sudhir; Rai, Mahendra

    2015-01-01

    Nanobiotechnological application of copper nanoparticles has paved the way for advancement in agriculture owing to its bactericidal and fungicidal activities. Recently, researchers have focussed on bioinspired synthesis of copper nanoparticles as a viable alternative to existing physicochemical techniques. For the commercialization of nanocopper, the toxicity evaluation is a major issue. In this context, Citrus medica (L.) fruit extract-mediated copper nanoparticles were synthesized and its different concentrations (10, 20, 40, 60, 80, and 100 µg mL(-1) ) were evaluated for its effect on actively dividing cells of Allium cepa. The study clearly revealed that copper nanoparticles increased mitotic index up to the concentration of 20 µg mL(-1) . In addition, a gradual decline in mitotic index and increase in abnormality index was observed as the concentration of copper nanoparticles and treatment duration were increased. Aberrations in chromosomal behavior such as sticky and disturbed chromosomes in metaphase and anaphase, c-metaphase, bridges, laggard, disturbed telophase, and vacuolated nucleus were also observed. © 2015 American Institute of Chemical Engineers.

  16. The association of peroxisomes with the developing cell plate in dividing onion root cells depends on actin microfilaments and myosin.

    Science.gov (United States)

    Collings, David A; Harper, John D I; Vaughn, Kevin C

    2003-12-01

    We have investigated changes in the distribution of peroxisomes through the cell cycle in onion ( Allium cepa L.) root meristem cells with immunofluorescence and electron microscopy, and in leek ( Allium porrum L.) epidermal cells with immunofluorescence and peroxisomal-targeted green fluorescent protein. During interphase and mitosis, peroxisomes distribute randomly throughout the cytoplasm, but beginning late in anaphase, they accumulate at the division plane. Initially, peroxisomes occur within the microtubule phragmoplast in two zones on either side of the developing cell plate. However, as the phragmoplast expands outwards to form an annulus, peroxisomes redistribute into a ring immediately inside the location of the microtubules. Peroxisome aggregation depends on actin microfilaments and myosin. Peroxisomes first accumulate in the division plane prior to the formation of the microtubule phragmoplast, and throughout cytokinesis, always co-localise with microfilaments. Microfilament-disrupting drugs (cytochalasin and latrunculin), and a putative inhibitor of myosin (2,3-butanedione monoxime), inhibit aggregation. We propose that aggregated peroxisomes function in the formation of the cell plate, either by regulating hydrogen peroxide production within the developing cell plate, or by their involvement in recycling of excess membranes from secretory vesicles via the beta-oxidation pathway. Differences in aggregation, a phenomenon which occurs in onion, some other monocots and to a lesser extent in tobacco BY-2 suspension cells, but which is not obvious in the roots of Arabidopsis thaliana (L.) Heynh., may reflect differences within the primary cell walls of these plants.

  17. The molecularly crowded cytoplasm of bacterialcCells : Dividing cells contrasted with viable but non-culturable (VBNC) bacterial cells

    NARCIS (Netherlands)

    Trevors, J. T.; van Elsas, J. D.; Bej, A. K.

    2013-01-01

    In this perspective, we discuss the cytoplasm in actively growing bacterial cells contrasted with viable but non-culturable (VBNC) cells. Actively growing bacterial cells contain a more molecularly crowded and organized cytoplasm, and are capable of completing their cell cycle resulting in cell

  18. Activated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide of melanoma cell clustering and cell migration?

    NARCIS (Netherlands)

    Swart, G.W.M.; Lunter, P.C.; Kilsdonk, J.W.J. van; Kempen, L.C. van

    2005-01-01

    Orchestrated modulation of cell adhesion is essential for development and homeostasis in multicellular organisms. It optimizes embedding of the cell in its dynamic environment and facilitates appropriate cell responses and intercellular communication. Chronic disturbance of this delicate equilibrium

  19. Metabolic Profiling of Dividing Cells in Live Rodent Brain by Proton Magnetic Resonance Spectroscopy (1HMRS) and LCModel Analysis

    DEFF Research Database (Denmark)

    Park, June-Hee; Lee, Hedok; Makaryus, Rany

    2014-01-01

    RATIONALE: Dividing cells can be detected in the live brain by positron emission tomography or optical imaging. Here we apply proton magnetic resonance spectroscopy (1HMRS) and a widely used spectral fitting algorithm to characterize the effect of increased neurogenesis after electroconvulsive sh...

  20. Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

    Directory of Open Access Journals (Sweden)

    Vijay Swahari

    2016-01-01

    Full Text Available Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells.

  1. Dividing Discipline

    DEFF Research Database (Denmark)

    Kristensen, Peter Marcus

    2012-01-01

    the periphery of the network—security studies and international political economy in particular—but communication is also divided along the lines of geography and policy/theory. The article concludes that divisions notwithstanding, IR communication remains centered around American, general, and theoretical IR...... than 20,000 articles published in 59 IR journals to construct a network among IR journals and finds a discipline with a center consisting of pedigreed IR journals, albeit closely related to political science. Divisions are identifiable as specialty areas that form clusters of specialized journals along...

  2. Electrochemical treatment of reverse osmosis concentrate on boron-doped electrodes in undivided and divided cell configurations

    Energy Technology Data Exchange (ETDEWEB)

    Bagastyo, Arseto Y. [Advanced Water Management Centre, The University of Queensland, St Lucia, QLD 4072 (Australia); Department of Environmental Engineering, Institut Teknologi Sepuluh Nopember, Surabaya 60111 (Indonesia); Batstone, Damien J. [Advanced Water Management Centre, The University of Queensland, St Lucia, QLD 4072 (Australia); Kristiana, Ina [Curtin Water Quality Research Centre, Resources and Chemistry Precinct, Department of Chemistry, Curtin University, Bentley, Perth, WA 6102 (Australia); Escher, Beate I. [National Research Centre for Environmental Toxicology (Entox), The University of Queensland, Brisbane, QLD 4108 (Australia); Joll, Cynthia [Curtin Water Quality Research Centre, Resources and Chemistry Precinct, Department of Chemistry, Curtin University, Bentley, Perth, WA 6102 (Australia); Radjenovic, Jelena, E-mail: j.radjenovic@uq.edu.au [Advanced Water Management Centre, The University of Queensland, St Lucia, QLD 4072 (Australia)

    2014-08-30

    Highlights: • 100% of COD and ∼70% of DOC was removed in both cell configurations. • ∼21.7 mg L{sup −1} of AOCl and ∼2.3 mg L{sup −1} of AOBr was formed regardless of the membrane use. • The TEQ was far lower than expected given the high AOCl concentrations. • The undivided cell consumed lower energy compared to the divided cell. - Abstract: An undivided electrolytic cell may offer lower electrochlorination through reduction of chlorine/hypochlorite at the cathode. This study investigated the performance of electrooxidation of reverse osmosis concentrate using boron-doped diamond electrodes in membrane-divided and undivided cells. In both cell configurations, similar extents of chemical oxygen demand and dissolved organic carbon removal were obtained. Continuous formation of chlorinated organic compounds was observed regardless of the membrane presence. However, halogenation of the organic matter did not result in a corresponding increase in toxicity (Vibrio fischeri bioassay performed on extracted samples), with toxicity decreasing slightly until 10 Ah L{sup −1}, and generally remaining near the initial baseline-toxicity equivalent concentration (TEQ) of the raw concentrate (i.e., ∼2 mg L{sup −1}). The exception was a high range toxicity measure in the undivided cell (i.e., TEQ = 11 mg L{sup −1} at 2.4 Ah L{sup −1}), which rapidly decreased to 4 mg L{sup −1}. The discrepancy between the halogenated organic matter and toxicity patterns may be a consequence of volatile and/or polar halogenated by-products formed in oxidation by OH· electrogenerated at the anode. The undivided cell exhibited lower energy compared to the divided cell, 0.25 kWh gCOD{sup −1} and 0.34 kWh gCOD{sup −1}, respectively, yet it did not demonstrate any improvement regarding by-products formation.

  3. Electrochemical treatment of reverse osmosis concentrate on boron-doped electrodes in undivided and divided cell configurations.

    Science.gov (United States)

    Bagastyo, Arseto Y; Batstone, Damien J; Kristiana, Ina; Escher, Beate I; Joll, Cynthia; Radjenovic, Jelena

    2014-08-30

    An undivided electrolytic cell may offer lower electrochlorination through reduction of chlorine/hypochlorite at the cathode. This study investigated the performance of electrooxidation of reverse osmosis concentrate using boron-doped diamond electrodes in membrane-divided and undivided cells. In both cell configurations, similar extents of chemical oxygen demand and dissolved organic carbon removal were obtained. Continuous formation of chlorinated organic compounds was observed regardless of the membrane presence. However, halogenation of the organic matter did not result in a corresponding increase in toxicity (Vibrio fischeri bioassay performed on extracted samples), with toxicity decreasing slightly until 10AhL(-1), and generally remaining near the initial baseline-toxicity equivalent concentration (TEQ) of the raw concentrate (i.e., ∼2mgL(-1)). The exception was a high range toxicity measure in the undivided cell (i.e., TEQ=11mgL(-1) at 2.4AhL(-1)), which rapidly decreased to 4mgL(-1). The discrepancy between the halogenated organic matter and toxicity patterns may be a consequence of volatile and/or polar halogenated by-products formed in oxidation by OH electrogenerated at the anode. The undivided cell exhibited lower energy compared to the divided cell, 0.25kWhgCOD(-1) and 0.34kWhgCOD(-1), respectively, yet it did not demonstrate any improvement regarding by-products formation. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. A microfluidic device for temporally controlled gene expression and long-term fluorescent imaging in unperturbed dividing yeast cells.

    Directory of Open Access Journals (Sweden)

    Gilles Charvin

    Full Text Available BACKGROUND: Imaging single cells with fluorescent markers over multiple cell cycles is a powerful tool for unraveling the mechanism and dynamics of the cell cycle. Over the past ten years, microfluidic techniques in cell biology have emerged that allow for good control of growth environment. Yet the control and quantification of transient gene expression in unperturbed dividing cells has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a microfluidic flow cell to grow Saccharomyces Cerevisiae for more than 8 generations (approximately 12 hrs starting with single cells, with controlled flow of the growth medium. This setup provides two important features: first, cells are tightly confined and grow in a remarkably planar array. The pedigree can thus be determined and single-cell fluorescence measured with 3 minutes resolution for all cells, as a founder cell grows to a micro-colony of more than 200 cells. Second, we can trigger and calibrate rapid and transient gene expression using reversible administration of inducers that control the GAL1 or MET3 promoters. We then show that periodic 10-20 minutes gene induction pulses can drive many cell division cycles with complete coherence across the cell cluster, with either a G1/S trigger (cln1 cln2 cln3 MET3-CLN2 or a mitotic trigger (cdc20 GALL-CDC20. CONCLUSIONS/SIGNIFICANCE: In addition to evident cell cycle applications, this device can be used to directly measure the amount and duration of any fluorescently scorable signal-transduction or gene-induction response over a long time period. The system allows direct correlation of cell history (e.g., hysteresis or epigenetics or cell cycle position with the measured response.

  5. The Zebrafish Anillin-eGFP Reporter Marks Late Dividing Retinal Precursors and Stem Cells Entering Neuronal Lineages

    Science.gov (United States)

    Guglielmi, Luca; Patzel, Eva; Sel, Saadettin; Auffarth, Gerd U.; Carl, Matthias; Poggi, Lucia

    2017-01-01

    Monitoring cycling behaviours of stem and somatic cells in the living animal is a powerful tool to better understand tissue development and homeostasis. The tg(anillin:anillin-eGFP) transgenic line carries the full-length zebrafish F-actin binding protein Anillin fused to eGFP from a bacterial artificial chromosome (BAC) containing Anillin cis-regulatory sequences. Here we report the suitability of the Anillin-eGFP reporter as a direct indicator of cycling cells in the late embryonic and post-embryonic retina. We show that combining the anillin:anillin-eGFP with other transgenes such as ptf1a:dsRed and atoh7:gap-RFP allows obtaining spatial and temporal resolution of the mitotic potentials of specific retinal cell populations. This is exemplified by the analysis of the origin of the previously reported apically and non-apically dividing late committed precursors of the photoreceptor and horizontal cell layers. PMID:28107513

  6. Disease-associated CAG·CTG triplet repeats expand rapidly in non-dividing mouse cells, but cell cycle arrest is insufficient to drive expansion.

    Science.gov (United States)

    Gomes-Pereira, Mário; Hilley, James D; Morales, Fernando; Adam, Berit; James, Helen E; Monckton, Darren G

    2014-06-01

    Genetically unstable expanded CAG·CTG trinucleotide repeats are causal in a number of human disorders, including Huntington disease and myotonic dystrophy type 1. It is still widely assumed that DNA polymerase slippage during replication plays an important role in the accumulation of expansions. Nevertheless, somatic mosaicism correlates poorly with the proliferative capacity of the tissue and rates of cell turnover, suggesting that expansions can occur in the absence of replication. We monitored CAG·CTG repeat instability in transgenic mouse cells arrested by chemical or genetic manipulation of the cell cycle and generated unequivocal evidence for the continuous accumulation of repeat expansions in non-dividing cells. Importantly, the rates of expansion in non-dividing cells were at least as high as those of proliferating cells. These data are consistent with a major role for cell division-independent expansion in generating somatic mosaicism in vivo. Although expansions can accrue in non-dividing cells, we also show that cell cycle arrest is not sufficient to drive instability, implicating other factors as the key regulators of tissue-specific instability. Our data reveal that de novo expansion events are not limited to S-phase and further support a cell division-independent mutational pathway. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Why Cells Grow and Divide? General Growth Mechanism and How it Defines Cells’ Growth, Reproduction and Metabolic Properties

    Science.gov (United States)

    Shestopaloff, Yuri K.

    2015-02-01

    We consider a general growth mechanism, which acts at cellular level and above (organs, systems and whole organisms). Using its mathematical representation, the growth equation, we study the growth and division mechanisms of amoeba and fission yeast Schizosaccharomyces pombe. We show how this mechanism, together with biomolecular machinery, governs growth and reproduction of cells, and these organisms in particular. This mechanism provides revealing answers to fundamental questions of biology, like why cells grow and divide, why and when cells’ growth stops. It also sheds light on questions like why and how life originated and developed. Solving the growth equation, we obtain analytical expression for the growth curve of fission yeast as a function of geometrical characteristics and nutrient influxes for RNA and protein synthesis, and compare the computed growth curves with 85 experiments. Statistical evaluation shows that these growth curves correspond to experimental data significantly better than all previous approximations. Also, using the general growth mechanism, we show how metabolic characteristics of cells, their size and evolutionary traits relate, considering fission yeast. In particular, we found that fission yeast S. pombe consumes about 16-18 times more nutrients for maintenance needs than for biomass synthesis.

  8. Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells

    Directory of Open Access Journals (Sweden)

    Smith Charlotte M

    2013-01-01

    Full Text Available Abstract Background During metaphase clathrin stabilises the mitotic spindle kinetochore(K-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2™ is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Results Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Conclusions Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.

  9. Removal of Polyvinyl Alcohol in Aqueous Solutions Using an Innovative Paired Photoelectrochemical Oxidative System in a Divided Electrochemical Cell

    Directory of Open Access Journals (Sweden)

    Kai-Yu Huang

    2015-01-01

    Full Text Available This study evaluates the performance of an innovative paired photoelectrochemical oxidative system fabricated in our laboratory to determine the removal efficiency of polyvinyl alcohol (PVA in aqueous solutions. An innovative paired photoelectrochemical oxidative system employed metal redox mediators with high redox potential for anodic oxidation (MEO process and UV assisted photoelectrochemical oxidation (PEO process for cathodic oxidation in a divided electrochemical cell. Several parameters were investigated to characterize the removal efficiency of PVA, such as the current density, initial Ce(III concentration, nitric acid concentration, oxygen flow rate, and UV irradiation intensity. The effects of these parameters on the specific energy consumption were also investigated. Additionally, the conversion yield of Ce(IV concentration and the electrogeneration of H2O2 were calculated in this study. The optimum current density, initial Ce(III concentration, nitric acid concentration, oxygen flow rate, and UV irradiation intensity were found to be 3 mA cm−2, 0.01 M, 0.3 M, 500 cm3 min−1, and 1.2 mW cm−2, respectively. The synergistic effect of combination process of MEO and PEO would be as a promising alternative for the removal efficiency of PVA.

  10. Strength-balance supplemented with computerized cognitive training to improve dual task gait and divided attention in older adults: a multicenter randomized-controlled trial.

    Science.gov (United States)

    van het Reve, Eva; de Bruin, Eling D

    2014-12-15

    Exercise interventions often do not combine physical and cognitive training. However, this combination is assumed to be more beneficial in improving walking and cognitive functioning compared to isolated cognitive or physical training. A multicenter parallel randomized controlled trial was conducted to compare a motor to a cognitive-motor exercise program. A total of 182 eligible residents of homes-for-the-aged (n = 159) or elderly living in the vicinity of the homes (n = 23) were randomly assigned to either strength-balance (SB) or strength-balance-cognitive (SBC) training. Both groups conducted similar strength-balance training during 12 weeks. SBC additionally absolved computerized cognitive training. Outcomes were dual task costs of walking, physical performance, simple reaction time, executive functions, divided attention, fear of falling and fall rate. Participants were analysed with an intention to treat approach. The 182 participants (mean age ± SD: 81.5 ± 7.3 years) were allocated to either SB (n = 98) or SBC (n = 84). The attrition rate was 14.3%. Interaction effects were observed for dual task costs of step length (preferred walking speed: F(1,174) = 4.94, p = 0.028, η2 = 0.027, fast walking speed: F(1,166) = 6.14, p = 0.009, η2 = 0.040) and dual task costs of the standard deviation of step length (F(1,166) = 6.14, p = 0.014, η2 = 0.036), in favor of SBC. Significant interactions in favor of SBC revealed for in gait initiation (F(1,166) = 9.16, p = 0.003, η2 = 0.052), 'reaction time' (F(1,180) = 5.243, p = 0.023, η² = 0.028) & 'missed answers' (F(1,180) = 11.839, p = 0.001, η² = 0.062) as part of the test for divided attention. Within-group comparison revealed significant improvements in dual task costs of walking (preferred speed; velocity (p = 0.002), step time (p = 0.018), step length (p = 0.028), fast speed; velocity (p

  11. Why do bacteria divide?

    Directory of Open Access Journals (Sweden)

    Vic eNorris

    2015-04-01

    Full Text Available The problem of not only how but also why cells divide can be tackled using recent ideas. One idea from the origins of life – Life as independent of its constituents – is that a living entity like a cell is a particular pattern of connectivity between its constituents. This means that if the growing cell were just to get bigger the average connectivity between its constituents per unit mass – its cellular connectivity – would decrease and the cell would lose its identity. The solution is division which restores connectivity. The corollary is that the cell senses decreasing cellular connectivity and uses this information to trigger division. A second idea from phenotypic diversity – Life on the Scales of Equilibria – is that a bacterium must find strategies that allow it to both survive and grow. This means that it has learnt to reconcile the opposing constraints that these strategies impose. The solution is that the cell cycle generates daughter cells with different phenotypes based on sufficiently complex equilibrium and non-equilibrium cellular compounds and structures appropriate for survival and growth, respectively, alias `hyperstructures'. The corollary is that the cell senses both the quantity of equilibrium material and the intensity of use of non-equilibrium material and then uses this information to trigger the cell cycle. A third idea from artificial intelligence – Competitive Coherence – is that a cell selects the active subset of elements that actively determine its phenotype from a much larger set of available elements. This means that the selection of an active subset of a specific size and composition must be done so as to generate both a coherent cell state, in which the cell’s contents work together harmoniously, and a coherent sequence of cell states, each coherent with respect to itself and to an unpredictable environment. The solution is the use of a range of mechanisms ranging from hyperstructure dynamics

  12. Probing cell activity in random access modality

    Science.gov (United States)

    Sacconi, L.; Crocini, C.; Lotti, J.; Coppini, R.; Ferrantini, C.; Tesi, C.; Yan, P.; Loew, L. M.; Cerbai, E.; Poggesi, C.; Pavone, F. S.

    2013-06-01

    We combined the advantage of an ultrafast random access microscope with novel labelling technologies to study the intra- and inter-cellular action potential propagation in neurons and cardiac myocytes with sub-millisecond time resolution. The random accesses microscopy was used in combination with a new fluorinated voltage sensitive dye with improved photostability to record membrane potential from multiple Purkinje cells with near simultaneous sampling. The RAMP system rapidly scanned between lines drawn in the membranes of neurons to perform multiplex measurements of the TPF signal. This recording was achieved by rapidly positioning the laser excitation with the AOD to sample a patch of membrane from each cell in <100 μs for recording from five cells, multiplexing permits a temporal resolution of 400 μs sufficient to capture every spike. The system is capable to record spontaneous activity over 800 ms from five neighbouring cells simultaneously, showing that spiking is not temporally correlated. The system was also used to investigate the electrical properties of tubular system (TATS) in isolated rat ventricular myocytes.

  13. Continental Divide Trail

    Data.gov (United States)

    Earth Data Analysis Center, University of New Mexico — This shapefile was created to show the proximity of the Continental Divide to the Continental Divide National Scenic Trail in New Mexico. This work was done as part...

  14. Molecular Interactions of the Min Protein System Reproduce Spatiotemporal Patterning in Growing and Dividing Escherichia coli Cells.

    Directory of Open Access Journals (Sweden)

    James C Walsh

    Full Text Available Oscillations of the Min protein system are involved in the correct midcell placement of the divisome during Escherichia coli cell division. Based on molecular interactions of the Min system, we formulated a mathematical model that reproduces Min patterning during cell growth and division. Specifically, the increase in the residence time of MinD attached to the membrane as its own concentration increases, is accounted for by dimerisation of membrane-bound MinD and its interaction with MinE. Simulation of this system generates unparalleled correlation between the waveshape of experimental and theoretical MinD distributions, suggesting that the dominant interactions of the physical system have been successfully incorporated into the model. For cells where MinD is fully-labelled with GFP, the model reproduces the stationary localization of MinD-GFP for short cells, followed by oscillations from pole to pole in larger cells, and the transition to the symmetric distribution during cell filamentation. Cells containing a secondary, GFP-labelled MinD display a contrasting pattern. The model is able to account for these differences, including temporary midcell localization just prior to division, by increasing the rate constant controlling MinD ATPase and heterotetramer dissociation. For both experimental conditions, the model can explain how cell division results in an equal distribution of MinD and MinE in the two daughter cells, and accounts for the temperature dependence of the period of Min oscillations. Thus, we show that while other interactions may be present, they are not needed to reproduce the main characteristics of the Min system in vivo.

  15. Expanding the potential of NAI-107 for treating serious ESKAPE pathogens: synergistic combinations against Gram-negatives and bactericidal activity against non-dividing cells.

    Science.gov (United States)

    Brunati, Cristina; Thomsen, Thomas T; Gaspari, Eleonora; Maffioli, Sonia; Sosio, Margherita; Jabes, Daniela; Løbner-Olesen, Anders; Donadio, Stefano

    2017-10-30

    To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce self-resistance in Gram-positive bacteria. We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms. Time-kill assays were used to evaluate killing of exponential and stationary-phase cells. The effects on biofilms (growth inhibition and biofilm eradication) were evaluated using biofilm-coated pegs. The frequency of spontaneous resistant mutants was evaluated by either direct plating or by continuous sub-culturing at 0.5 × MIC levels, followed by population analysis profiles. The results showed that NAI-107 and its brominated variant are highly active against Neisseria gonorrhoeae and some other fastidious Gram-negative pathogens. Furthermore, all compounds strongly synergized with polymyxin against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, and showed bactericidal activity. Surprisingly, NAI-107 alone was bactericidal against non-dividing A. baumannii cells. Against S. aureus, NAI-107 and related lantibiotics showed strong bactericidal activity against dividing and non-dividing cells. Activity was also observed against S. aureus biofilms. As expected for a lipid II binder, no significant resistance to NAI-107 was observed by direct plating or serial passages. Overall, the results of the current work, along with previously published results on the efficacy of NAI-107 in experimental models of infection, indicate that this lantibiotic represents a promising option in addressing the serious threat of antibiotic resistance.

  16. Omcg1 is critically required for mitosis in rapidly dividing mouse intestinal progenitors and embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Teddy Léguillier

    2012-05-01

    Recent studies have shown that factors involved in transcription-coupled mRNA processing are important for the maintenance of genome integrity. How these processes are linked and regulated in vivo remains largely unknown. In this study, we addressed in the mouse model the function of Omcg1, which has been shown to participate in co-transcriptional processes, including splicing and transcription-coupled repair. Using inducible mouse models, we found that Omcg1 is most critically required in intestinal progenitors. In absence of OMCG1, proliferating intestinal epithelial cells underwent abnormal mitosis followed by apoptotic cell death. As a consequence, the crypt proliferative compartment of the small intestine was quickly and totally abrogated leading to the rapid death of the mice. Lack of OMCG1 in embryonic stem cells led to a similar cellular phenotype, with multiple mitotic defects and rapid cell death. We showed that mutant intestinal progenitors and embryonic stem cells exhibited a reduced cell cycle arrest following irradiation, suggesting that mitotic defects may be consecutive to M phase entry with unrepaired DNA damages. These findings unravel a crucial role for pre-mRNA processing in the homeostasis of the small intestine and point to a major role of OMCG1 in the maintenance of genome integrity.

  17. Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum.

    Science.gov (United States)

    Winnicki, Konrad; Żabka, Aneta; Bernasińska, Joanna; Matczak, Karolina; Maszewski, Janusz

    2015-06-01

    In plants, phosphorylated MAPKs display constitutive nuclear localization; however, not all studied plant species show co-localization of activated MAPKs to mitotic microtubules. The mitogen-activated protein kinase (MAPK) signaling pathway is involved not only in the cellular response to biotic and abiotic stress but also in the regulation of cell cycle and plant development. The role of MAPKs in the formation of a mitotic spindle has been widely studied and the MAPK signaling pathway was found to be indispensable for the unperturbed course of cell division. Here we show cellular localization of activated MAPKs (dually phosphorylated at their TXY motifs) in both interphase and mitotic root meristem cells of Lupinus luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization of activated MAPKs has been found in all species. Co-localization of these kinases to mitotic microtubules was most evident in L. esculentum, while only about 50% of mitotic cells in the root meristems of P. sativum and V. faba displayed activated MAPKs localized to microtubules during mitosis. Unexpectedly, no evident immunofluorescence signals at spindle microtubules and phragmoplast were noted in L. luteus. Considering immunocytochemical analyses and studies on the impact of FR180204 (an inhibitor of animal ERK1/2) on mitotic cells, we hypothesize that MAPKs may not play prominent role in the regulation of microtubule dynamics in all plant species.

  18. SILICATE UPTAKE AND SILICA SHELL FORMATION BY SYNCHRONOUSLY DIVIDING CELLS OF THE DIATOM NAVICULA PELLICULOSA (BRÉB.) HILSE(1,2,3).

    Science.gov (United States)

    Busby, W F; Lewin, J

    1967-09-01

    Cells of the freshwater diatom Navicula pelliculosa were induced to divide synchronously by the addition of excess silicate (20 mg Si/liter) to a culture which had been silicate-starved for 14 hr. After a 3- to 4-hr lag period, characterized by rapid silicate uptake (6.5 mg Si/liter/4 hr) and silica shell formation, the cell number then doubled in the succeeding 2-3 hr. This system promises to have significance in the study of silicon metabolism, transport phenomena, and silica deposition.

  19. International Divider Walls

    NARCIS (Netherlands)

    Kruis, A.; Sneller, A.C.W.(L.)

    2013-01-01

    The subject of this teaching case is the Enterprise Resource Planning (ERP) system implementation at International Divider Walls, the world market leader in design, production, and sales of divider walls. The implementation in one of the divisions of this multinational company had been successful,

  20. The Open Access Divide

    Directory of Open Access Journals (Sweden)

    Jingfeng Xia

    2013-10-01

    Full Text Available This paper is an attempt to review various aspects of the open access divide regarding the difference between those academics who support free sharing of data and scholarly output and those academics who do not. It provides a structured description by adopting the Ws doctrines emphasizing such questions as who, what, when, where and why for information-gathering. Using measurable variables to define a common expression of the open access divide, this study collects aggregated data from existing open access as well as non-open access publications including journal articles and extensive reports. The definition of the open access divide is integrated into the discussion of scholarship on a larger scale.

  1. Effects of the concurrent use of a reduced dose of propofol with divided supplemental remifentanil and moderate hyperventilation on duration and morphology of electroconvulsive therapy-induced electroencephalographic seizure activity: A randomized controlled trial.

    Science.gov (United States)

    Nishikawa, Kohki; Yamakage, Michiaki

    2017-02-01

    The clinical adequacy of electroconvulsive therapy (ECT) depends on not only seizure duration but also seizure amplitude and postictal suppression. The objective of this study was to evaluate the effects of combination of a reduced dose of propofol and moderate hyperventilation on seizure duration and electrical stimulus requirement for adequate ictal amplitude and postictal suppression. Prospective, randomized, controlled trial. Operating room at a municipal hospital. Sixty ASA physical status I or II patients scheduled to receive a total of >300 ECT treatments. Patients were randomly assigned to have the three interventions: the use of a standard dose (1mg/kg) of propofol and normoventilation (ETCO2 of 40-45mmHg) (group P/N), the use of a reduced dose (0.5mg/kg) of propofol with divided remifentanil injections and normoventilation (group RP/N), and the use of a reduced dose of propofol with divided remifentanil injections and moderate hyperventilation (ETCO2 of 30-35mmHg) (group RP/H). Patients in groups RP/N and RP/H received remifentanil 1μg/kg followed by propofol 0.5mg/kg for unconsciousness and thereafter remifentanil 1μg/kg immediately before the electrical stimulus. Patients in group RP/H had significantly longer durations of electroencephalographic (EEG) seizures in the early phase of the ECT course (Ppropofol combined with divided supplemental remifentanil under moderate hyperventilation during ECT may contribute to reduced electrical dosage due to the ability of its augmentation of seizure amplitude and postictal suppression in the late phase of the ECT course. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Genome-wide screen identifies pathways that govern GAA/TTC repeat fragility and expansions in dividing and nondividing yeast cells.

    Science.gov (United States)

    Zhang, Yu; Shishkin, Alexander A; Nishida, Yuri; Marcinkowski-Desmond, Dana; Saini, Natalie; Volkov, Kirill V; Mirkin, Sergei M; Lobachev, Kirill S

    2012-10-26

    Triplex structure-forming GAA/TTC repeats pose a dual threat to the eukaryotic genome integrity. Their potential to expand can lead to gene inactivation, the cause of Friedreich's ataxia disease in humans. In model systems, long GAA/TTC tracts also act as chromosomal fragile sites that can trigger gross chromosomal rearrangements. The mechanisms that regulate the metabolism of GAA/TTC repeats are poorly understood. We have developed an experimental system in the yeast Saccharomyces cerevisiae that allows us to systematically identify genes crucial for maintaining the repeat stability. Two major groups of mutants defective in DNA replication or transcription initiation are found to be prone to fragility and large-scale expansions. We demonstrate that problems imposed by the repeats during DNA replication in actively dividing cells and during transcription initiation in nondividing cells can culminate in genome instability. We propose that similar mechanisms can mediate detrimental metabolism of GAA/TTC tracts in human cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. A dividing issue

    DEFF Research Database (Denmark)

    Gamborg, Christian; Jensen, Frank Søndergaard; Sandøe, Peter

    2016-01-01

    Why are organised shoots involving birds that are farm-reared and subsequently released a dividing issue in several countries? As a contribution to answering this question the paper reports a national survey of landowners (n = 1207), hunters (n = 1130) and the general public (n = 1001) in Denmark....... While there was broad agreement across all three groups that recreational hunting of naturally occurring “surplus” wildlife is acceptable, the release of farm-reared game birds for shooting was a dividing issue, both within the groups and between them. The majority of participants (51%) in the survey...... representing the general public were against the practice; a majority of hunters (61%) were in favour of it; and landowner approval rates lay between these two poles. Respondents with a “mutualist” or “distanced” wildlife value orientation according to the definitions by Teel et al. (2005) consistently...

  4. Facebook's gender divide

    OpenAIRE

    Garcia, David; Kassa, Yonas Mitike; Cuevas, Angel; Cebrian, Manuel; Moro, Esteban; Rahwan, Iyad; Cuevas, Ruben

    2017-01-01

    Online social media are information resources that can have a transformative power in society. While the Web was envisioned as an equalizing force that allows everyone to access information, the digital divide prevents large amounts of people from being present online. Online social media in particular are prone to gender inequality, an important issue given the link between social media use and employment. Understanding gender inequality in social media is a challenging task due to the neces...

  5. Cell motility as random motion: A review

    DEFF Research Database (Denmark)

    Selmeczi, Dávid; Li, Liwen; Pedersen, Leif

    2008-01-01

    The historical co-evolution of biological motility models with models of Brownian motion is outlined. Recent results for how to derive cell-type-specific motility models from experimental cell trajectories are reviewed. Experimental work in progress, which tests the generality of this phenomenolo...... of this phenomenological model building is reported. So is theoretical work in progress, which explains the characteristic time scales and correlations of phenomenological models in terms of the dynamics of cytoskeleton, lamellipodia, and pseudopodia.......The historical co-evolution of biological motility models with models of Brownian motion is outlined. Recent results for how to derive cell-type-specific motility models from experimental cell trajectories are reviewed. Experimental work in progress, which tests the generality...

  6. Melting the Divide

    Science.gov (United States)

    Gibson, S. M.

    2014-12-01

    Presenting Quaternary Environmental Change to students who fall into Widening Participation criteria at the University of Cambridge, gives a unique opportunity to present academic debate in an approachable and entertaining way. Literally by discussing the melting of our ice caps, melts the divide Cambridge has between its reputation and the reality for the brightest, underprivileged, students. There is a balance between presenting cutting edge research with the need to come across as accessible (and importantly valuable to "learning"). Climate change over the Quaternary lends itself well to this aim. By lecturing groups of potential students through the entire Quaternary in an hour, stopping to discuss how our ancestors interacted with past Interglacials and what are the mechanisms driving change (in generalized terms), you are able to introduce cutting edge research (such as the latest NEEM ice core) to the students. This shows the evolution and importance of higher education and academic research. The lecture leads well onto group discussions (termed "supervisions" in Cambridge), to explore their opinions on the concern for present Anthropogenic Climate Change in relation to Past Climate Change after being presented with images that our ancestors "made it". Here discussion thrives off students saying obvious things (or sarcastic comments!) which quickly can lead into a deep technical discussion on their terms. Such discussions give the students a zest for higher education, simply throwing Ruddiman's (2003) "The Anthroprocene Started Several Thousand Years Ago" at them, questions in a second their concept of Anthropogenic Climate Change. Supervisions lend themselves well to bright, articulate, students and by offering these experiences to students of Widening Participation criteria we quickly melt the divide between the reputation of Cambridge ( and higher education as a whole) and the day to day practice. Higher education is not for the privileged, but a free and

  7. Divide and Pacify

    DEFF Research Database (Denmark)

    Vanhuysse, Pieter

    unemployment benefits and many others onto early retirement and disability pensions. From a narrow economic viewpoint, these policies often appeared to be immensely costly or irresponsibly populist. Yet a more inclusive social-scientific perspective can shed new light on these seemingly irrational policies......, hundreds of thousands of people suddenly became disabled and retired or simply vanished from the labor market. … Pieter Vanhuysse, in his lucid and brilliantly argued slim book Divide and Pacify, shows how the second oddity goes a long way toward explaining the first one. By connecting two puzzles he...... about political economy as an art of analysis. Vanhuysse presents theory, methodology and empirical analysis with equal force, blends them into a powerful and very interesting narrative…. Highly recommended" – European Sociological Review "Pieter Vanhuysse has written a fascinating book on the phenomena...

  8. Clustering Single-Cell Expression Data Using Random Forest Graphs.

    Science.gov (United States)

    Pouyan, Maziyar Baran; Nourani, Mehrdad

    2017-07-01

    Complex tissues such as brain and bone marrow are made up of multiple cell types. As the study of biological tissue structure progresses, the role of cell-type-specific research becomes increasingly important. Novel sequencing technology such as single-cell cytometry provides researchers access to valuable biological data. Applying machine-learning techniques to these high-throughput datasets provides deep insights into the cellular landscape of the tissue where those cells are a part of. In this paper, we propose the use of random-forest-based single-cell profiling, a new machine-learning-based technique, to profile different cell types of intricate tissues using single-cell cytometry data. Our technique utilizes random forests to capture cell marker dependences and model the cellular populations using the cell network concept. This cellular network helps us discover what cell types are in the tissue. Our experimental results on public-domain datasets indicate promising performance and accuracy of our technique in extracting cell populations of complex tissues.

  9. Random matrix analysis for gene interaction networks in cancer cells

    CERN Document Server

    Kikkawa, Ayumi

    2016-01-01

    Motivation: The investigation of topological modifications of the gene interaction networks in cancer cells is essential for understanding the desease. We study gene interaction networks in various human cancer cells with the random matrix theory. This study is based on the Cancer Network Galaxy (TCNG) database which is the repository of huge gene interactions inferred by Bayesian network algorithms from 256 microarray experimental data downloaded from NCBI GEO. The original GEO data are provided by the high-throughput microarray expression experiments on various human cancer cells. We apply the random matrix theory to the computationally inferred gene interaction networks in TCNG in order to detect the universality in the topology of the gene interaction networks in cancer cells. Results: We found the universal behavior in almost one half of the 256 gene interaction networks in TCNG. The distribution of nearest neighbor level spacing of the gene interaction matrix becomes the Wigner distribution when the net...

  10. The digital divide: philosophical reflection

    Directory of Open Access Journals (Sweden)

    Dedyulina Marina Anatolevna

    2017-07-01

    Full Text Available The problem of digital divide itself is interesting for philosophical reflection as it lies at the crossroads of interests of social and political philosophy, philosophy of technology and epistemology, and these are just some of them. Due to the constant development of information technologies and the introduction of new technologies the digital divide is a dynamic problem. The main aim of this work is to analyse the conceptual and descriptive aspects of the problem of the digital divide, to get a more complete picture of the phenomenon. The digital divide is a complex problem that has social, political, cultural and ethical aspects.

  11. Rehabilitation programme after stem cell transplantation: randomized controlled trial.

    Science.gov (United States)

    Bird, Lydia; Arthur, Antony; Niblock, Tara; Stone, Rebecca; Watson, Lynn; Cox, Karen

    2010-03-01

    The aim of this study was to compare the effect of two methods of rehabilitation after stem cell transplantation on health and quality of life. Stem cell transplantation is routinely used in the treatment of haematological malignancy. However, it is an intensive treatment often associated with deterioration in wellbeing and the need for prolonged recovery. During a 14-month data collection period (August 2005 to October 2006), patients who had had a stem cell transplant (n = 58) were randomly allocated to either a healthcare professional-led rehabilitation programme or a self-managed rehabilitation programme. The primary outcome measure, physical functioning as measured by the 36-item Short Form Health Survey, was recorded at baseline and 6 months after randomization. Secondary health and quality of life measures included the seven other dimensions of the 36-item Short Form Health Survey, General Health Questionnaire, Graham and Longman Quality of Life Scale and a Shuttle Walk Test. There was no difference in change in Short Form 36 physical functioning scores between the two groups at follow-up (mean difference 0.19 points, 95% confidence interval 10.77-11.16). No evidence of a difference between the two modes of rehabilitation was observed for any of the trial outcomes. One approach for providing a flexible service may be for staff and individual patients to work together, selecting from a series of specified options a programme with the appropriate content and duration to meet that individual's needs.

  12. Spaceflight enhances cell aggregation and random budding in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Aurélie Crabbé

    Full Text Available This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation, which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p. infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the

  13. Transcriptional profiling of ParA and ParB mutants in actively dividing cells of an opportunistic human pathogen Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Aneta A Bartosik

    Full Text Available Accurate chromosome segregation to progeny cells is a fundamental process ensuring proper inheritance of genetic material. In bacteria with simple cell cycle, chromosome segregation follows replication initiation since duplicated oriC domains start segregating to opposite halves of the cell soon after they are made. ParA and ParB proteins together with specific DNA sequences are parts of the segregation machinery. ParA and ParB proteins in Pseudomonas aeruginosa are important for optimal growth, nucleoid segregation, cell division and motility. Comparative transcriptome analysis of parA null and parB null mutants versus parental P. aeruginosa PAO1161 strain demonstrated global changes in gene expression pattern in logarithmically growing planktonic cultures. The set of genes similarly affected in both mutant strains is designated Par regulon and comprises 536 genes. The Par regulon includes genes controlled by two sigma factors (RpoN and PvdS as well as known and putative transcriptional regulators. In the absence of Par proteins, a large number of genes from RpoS regulon is induced, reflecting the need for slowing down the cell growth rate and decelerating the metabolic processes. Changes in the expression profiles of genes involved in c-di-GMP turnover point out the role of this effector in such signal transmission. Microarray data for chosen genes were confirmed by RT-qPCR analysis. The promoter regions of selected genes were cloned upstream of the promoter-less lacZ gene and analyzed in the heterologous host E. coliΔlac. Regulation by ParA and ParB of P. aeruginosa was confirmed for some of the tested promoters. Our data demonstrate that ParA and ParB besides their role in accurate chromosome segregation may act as modulators of genes expression. Directly or indirectly, Par proteins are part of the wider regulatory network in P. aeruginosa linking the process of chromosome segregation with the cell growth, division and motility.

  14. miRNA expression profiling divides follicular dendritic cell sarcomas into two groups, related to fibroblasts and myopericytomas or Castleman's disease.

    Science.gov (United States)

    Hartmann, Sylvia; Döring, Claudia; Agostinelli, Claudio; Portscher-Kim, Soo-Jeong; Lonardi, Silvia; Lorenzi, Luisa; Fuligni, Fabio; Martinez, Daniel; Mehta, Jay; Borges, Anita; Hackstein, Holger; Kippenberger, Stefan; Piccaluga, Pier Paolo; Simonitsch-Klupp, Ingrid; Cabeçadas, José; Campo, Elias; Facchetti, Fabio; Pileri, Stefano A; Hansmann, Martin-Leo

    2016-09-01

    Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumours, which are fatal in 20% of the patients and usually occur in secondary lymphoid organs or extranodal localizations. Due to the rareness of these tumours, only few studies have been conducted on molecular level. In the present study, we performed microRNA (miRNA) profiling of 31 FDC sarcomas and identified two subgroups, one with high miRNA expression and the other group with low miRNA expression levels. The first group showed a strong similarity to fibroblasts and myopericytomas, whereas the second group was more closely related to FDCs from Castleman's disease. Both groups showed important differences compared with myeloid-derived dendritic cells, confirming mesenchymal origin of FDCs and their derived sarcomas. The two FDC sarcoma groups did not differ on morphological grounds, mitotic activity or BRAF mutation status. However, patients of group I presented a tendency to a shorter overall survival and more frequent podoplanin expression by immunohistochemistry. The importance of these newly recognized FDC sarcoma subgroups in terms of clinical behaviour and therapeutic implications should be assessed in a larger cohort in future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Dividing Fractions: A Pedagogical Technique

    Science.gov (United States)

    Lewis, Robert

    2016-01-01

    When dividing one fraction by a second fraction, invert, that is, flip the second fraction, then multiply it by the first fraction. To multiply fractions, simply multiply across the denominators, and multiply across the numerators to get the resultant fraction. So by inverting the division of fractions it is turned into an easy multiplication of…

  16. Dividing Attention Increases Operational Momentum

    Directory of Open Access Journals (Sweden)

    Koleen McCrink

    2017-12-01

    Full Text Available When adding or subtracting two quantities, adults often compute an estimated outcome that is larger or smaller, respectively, than the actual outcome, a bias referred to as “operational momentum”. The effects of attention on operational momentum were investigated. Participants viewed a display in which two arrays of objects were added, or one array was subtracted from another array, and judged whether a subsequent outcome (probe array contained the correct or incorrect number of objects. In a baseline condition, only the arrays to be added or subtracted were viewed. In divided attention conditions, participants simultaneously viewed a sequence of colors or shapes, and judged which color (a non-spatial judgment or shape (a spatial judgment was repeated. Operational momentum occurred in all conditions, but was higher in divided attention conditions than in the baseline condition, primarily for addition problems. This pattern suggests that dividing attention, rather than decreasing operational momentum by decreasing attentional shifts, actually increased operational momentum. These results are consistent with a heightened use of arithmetic heuristics under conditions of divided attention.

  17. Bridging the Health Data Divide.

    Science.gov (United States)

    Celi, Leo Anthony; Davidzon, Guido; Johnson, Alistair Ew; Komorowski, Matthieu; Marshall, Dominic C; Nair, Sunil S; Phillips, Colin T; Pollard, Tom J; Raffa, Jesse D; Salciccioli, Justin D; Salgueiro, Francisco Muge; Stone, David J

    2016-12-20

    Fundamental quality, safety, and cost problems have not been resolved by the increasing digitization of health care. This digitization has progressed alongside the presence of a persistent divide between clinicians, the domain experts, and the technical experts, such as data scientists. The disconnect between clinicians and data scientists translates into a waste of research and health care resources, slow uptake of innovations, and poorer outcomes than are desirable and achievable. The divide can be narrowed by creating a culture of collaboration between these two disciplines, exemplified by events such as datathons. However, in order to more fully and meaningfully bridge the divide, the infrastructure of medical education, publication, and funding processes must evolve to support and enhance a learning health care system. ©Leo Anthony Celi, Guido Davidzon, Alistair EW Johnson, Matthieu Komorowski, Dominic C Marshall, Sunil S Nair, Colin T Phillips, Tom J Pollard, Jesse D Raffa, Justin D Salciccioli, Francisco Muge Salgueiro, David J Stone. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.12.2016.

  18. Divided by the Market, Divided by the State

    DEFF Research Database (Denmark)

    Wulfgramm, Melike; Starke, Peter

    2017-01-01

    of the individual differences, the analysis also shows, for the first time, that both high inequality and strongly redistributive policies divide public opinion along the lines of socioeconomic position. Put differently, while market inequality may be associated with less cohesive attitudes, a highly redistributive...... welfare state does not seem to foster agreement among the public, either. These findings have important policy implications for advanced welfare states, including a renewed emphasis on ‘predistribution’ (i.e., policies that influence the primary distribution of income) in order to avoid the scenario...

  19. Soft tissue cell adhesion to titanium abutments after different cleaning procedures: preliminary results of a randomized clinical trial.

    Science.gov (United States)

    Canullo, L; Penarrocha-Oltra, D; Marchionni, S; Bagán, L; Peñarrocha-Diago, M-A; Micarelli, C

    2014-03-01

    A randomized controlled trial was performed to assess soft tissue cell adhesion to implant titanium abutments subjected to different cleaning procedures and test if plasma cleaning can enhance cell adhesion at an early healing time. Eighteen patients with osseointegrated and submerged implants were included. Before re-opening, 18 abutments were divided in 3 groups corresponding to different clinical conditions with different cleaning processes: no treatment (G1), laboratory customization and cleaning by steam (G2), cleaning by plasma of Argon (G3). Abutments were removed after 1 week and scanning electron microscopy was used to analyze cell adhesion to the abutment surface quantitatively (percentage of area occupied by cells) and qualitatively (aspect of adhered cells and presence of contaminants). Mean percentages of area occupied by cells were 17.6 ± 22.7%, 16.5 ± 12.9% and 46.3 ± 27.9% for G1, G2 and G3 respectively. Differences were statistically significant between G1 and G3 (p=0.030), close to significance between G2 and G3 (p=0.056), and non-significant between G1 and G2 (p=0.530). The proportion of samples presenting adhered cells was homogeneous among the 3 groups (p-valor = 1.000). In all cases cells presented a flattened aspect; in 2 cases cells were less efficiently adhered and in 1 case cells presented filipodia. Three cases showed contamination with cocobacteria. Within the limits of the present study, plasma of Argon may enhance cell adhesion to titanium abutments, even at the early stage of soft tissue healing. Further studies with greater samples are necessary to confirm these findings.

  20. Cell motility as persistent random motion: Theories from experiments

    DEFF Research Database (Denmark)

    Selmeczi, D.; Mosler, S.; Hagedorn, P.H.

    2005-01-01

    Experimental time series for trajectories of motile cells may contain so much information that a systematic analysis will yield cell-type- specific motility models. Here we demonstrate how, using human keratinocytes and fibroblasts as examples. The two resulting models reflect the cells' different...

  1. Crossroads - Bridging the Digital Divide

    Directory of Open Access Journals (Sweden)

    David Cobb

    2005-03-01

    Full Text Available It’s so good to be in Cambridge, it feels almost like home. Let me start by stating that in the past year ITMB, a successful map publisher in British Columbia, Canada published more paper map titles than at any time in their history. Similarly, the U.S. Geological Survey (USGS recently announced that they have ceased producing paper from their aerial photography archive and will only produce digital copies. I believe that both of these facts speak to the future of maps and digital data. It means there will be paper maps well into the future and there will be an increasing array of digital data - some of it reformatted, as in the USGS case, and most of it will be born digital. When asked to speak about GIS and its role in libraries I often find myself in a conundrum - am I here to slay the dragon, or to pet the dragon. The role of technology in libraries is not one that has been embraced by everyone, and often the technology itself seems to have been force-fed upon us. The library profession is not one that has historically been a proponent of change and the very nature of GIS is change. In one sense, we have been given the choice of becoming paper museums or, at the very least, making GIS technology available in our collections. Today, I would like to review the many ways that GIS is, or will, affect our collections. I will divide the presentation into a general overview of GIS in libraries, how it affects our acquisitions or collection development policies, its effect on cataloging, on reference services, staffing, and our web services. Then I will shift the focus a little and discuss the current situation at the Harvard Map Collection, the future role of legacy collections, and a look to the future.

  2. Causality, randomness, intelligibility, and the epistemology of the cell.

    Science.gov (United States)

    Dougherty, Edward R; Bittner, Michael L

    2010-06-01

    Because the basic unit of biology is the cell, biological knowledge is rooted in the epistemology of the cell, and because life is the salient characteristic of the cell, its epistemology must be centered on its livingness, not its constituent components. The organization and regulation of these components in the pursuit of life constitute the fundamental nature of the cell. Thus, regulation sits at the heart of biological knowledge of the cell and the extraordinary complexity of this regulation conditions the kind of knowledge that can be obtained, in particular, the representation and intelligibility of that knowledge. This paper is essentially split into two parts. The first part discusses the inadequacy of everyday intelligibility and intuition in science and the consequent need for scientific theories to be expressed mathematically without appeal to commonsense categories of understanding, such as causality. Having set the backdrop, the second part addresses biological knowledge. It briefly reviews modern scientific epistemology from a general perspective and then turns to the epistemology of the cell. In analogy with a multi-faceted factory, the cell utilizes a highly parallel distributed control system to maintain its organization and regulate its dynamical operation in the face of both internal and external changes. Hence, scientific knowledge is constituted by the mathematics of stochastic dynamical systems, which model the overall relational structure of the cell and how these structures evolve over time, stochasticity being a consequence of the need to ignore a large number of factors while modeling relatively few in an extremely complex environment.

  3. Live cell imaging based on surface plasmon-enhanced fluorescence microscopy using random nanostructures

    Science.gov (United States)

    Oh, Youngjin; Lee, Wonju; Son, Taehwang; Kim, Sook Young; Shin, Jeon-Soo; Kim, Donghyun

    2014-02-01

    Localized surface plasmon enhanced microscopy based on nanoislands of random spatial distribution was demonstrated for imaging live cells and molecular interactions. Nanoislands were produced without lithography by high temperature annealing under various processing conditions. The localization of near-field distribution that is associated with localized surface plasmon on metallic random nanoislands was analyzed theoretically and experimentally in comparison with periodic nanostructures. For experimental validation in live cell imaging, mouse macrophage-like cell line stained with Alexa Fluor 488 was prepared on nanoislands. The results suggest the possibility of attaining the imaging resolution on the order of 80 nm.

  4. Human mammary epithelial cells exhibit a bimodal correlated random walk pattern.

    Directory of Open Access Journals (Sweden)

    Alka A Potdar

    2010-03-01

    Full Text Available Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells that exist in multi-cellular organisms (humans follow a bimodal correlated random walk (BCRW.Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation.Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model.

  5. Early stage hot spot analysis through standard cell base random pattern generation

    Science.gov (United States)

    Jeon, Joong-Won; Song, Jaewan; Kim, Jeong-Lim; Park, Seongyul; Yang, Seung-Hune; Lee, Sooryong; Kang, Hokyu; Madkour, Kareem; ElManhawy, Wael; Lee, SeungJo; Kwan, Joe

    2017-04-01

    Due to limited availability of DRC clean patterns during the process and RET recipe development, OPC recipes are not tested with high pattern coverage. Various kinds of pattern can help OPC engineer to detect sensitive patterns to lithographic effects. Random pattern generation is needed to secure robust OPC recipe. However, simple random patterns without considering real product layout style can't cover patterning hotspot in production levels. It is not effective to use them for OPC optimization thus it is important to generate random patterns similar to real product patterns. This paper presents a strategy for generating random patterns based on design architecture information and preventing hotspot in early process development stage through a tool called Layout Schema Generator (LSG). Using LSG, we generate standard cell based on random patterns reflecting real design cell structure - fin pitch, gate pitch and cell height. The output standard cells from LSG are applied to an analysis methodology to assess their hotspot severity by assigning a score according to their optical image parameters - NILS, MEEF, %PV band and thus potential hotspots can be defined by determining their ranking. This flow is demonstrated on Samsung 7nm technology optimizing OPC recipe and early enough in the process avoiding using problematic patterns.

  6. Fast frequency divider circuit using combinational logic

    Science.gov (United States)

    Helinski, Ryan

    2017-05-30

    The various technologies presented herein relate to performing on-chip frequency division of an operating frequency of a ring oscillator (RO). Per the various embodiments herein, a conflict between RO size versus operational frequency can be addressed by dividing the output frequency of the RO to a frequency that can be measured on-chip. A frequency divider circuit (comprising NOR gates and latches, for example) can be utilized in conjunction with the RO on the chip. In an embodiment, the frequency divider circuit can include a pair of latches coupled to the RO to facilitate dividing the oscillating frequency of the RO by 2. In another embodiment, the frequency divider circuit can include four latches (operating in pairs) coupled to the RO to facilitate dividing the oscillating frequency of the RO by 4. A plurality of ROs can be MUXed to the plurality of ROs by a single oscillation-counting circuit.

  7. Random small interfering RNA library screen identifies siRNAs that induce human erythroleukemia cell differentiation.

    Science.gov (United States)

    Fan, Cuiqing; Xiong, Yuan; Zhu, Ning; Lu, Yabin; Zhang, Jiewen; Wang, Song; Liang, Zicai; Shen, Yan; Chen, Meihong

    2011-03-01

    Cancers are characterized by poor differentiation. Differentiation therapy is a strategy to alleviate malignant phenotypes by inducing cancer cell differentiation. Here we carried out a combinatorial high-throughput screen with a random siRNA library on human erythroleukemia K-562 cell differentiation. Two siRNAs screened from the library were validated to be able to induce erythroid differentiation to varying degrees, determined by CD235 and globin up-regulation, GATA-2 down-regulation, and cell growth inhibition. The screen we performed here is the first trial of screening cancer differentiation-inducing agents from a random siRNA library, demonstrating that a random siRNA library can be considered as a new resource in efforts to seek new therapeutic agents for cancers. As a random siRNA library has a broad coverage for the entire genome, including known/unknown genes and protein coding/non-coding sequences, screening using a random siRNA library can be expected to greatly augment the repertoire of therapeutic siRNAs for cancers.

  8. Random migration and signal integration promote rapid and robust T cell recruitment.

    Science.gov (United States)

    Textor, Johannes; Henrickson, Sarah E; Mandl, Judith N; von Andrian, Ulrich H; Westermann, Jürgen; de Boer, Rob J; Beltman, Joost B

    2014-08-01

    To fight infections, rare T cells must quickly home to appropriate lymph nodes (LNs), and reliably localize the antigen (Ag) within them. The first challenge calls for rapid trafficking between LNs, whereas the second may require extensive search within each LN. Here we combine simulations and experimental data to investigate which features of random T cell migration within and between LNs allow meeting these two conflicting demands. Our model indicates that integrating signals from multiple random encounters with Ag-presenting cells permits reliable detection of even low-dose Ag, and predicts a kinetic feature of cognate T cell arrest in LNs that we confirm using intravital two-photon data. Furthermore, we obtain the most reliable retention if T cells transit through LNs stochastically, which may explain the long and widely distributed LN dwell times observed in vivo. Finally, we demonstrate that random migration, both between and within LNs, allows recruiting the majority of cognate precursors within a few days for various realistic infection scenarios. Thus, the combination of two-scale stochastic migration and signal integration is an efficient and robust strategy for T cell immune surveillance.

  9. New Media and the Digital Divide

    NARCIS (Netherlands)

    van Deursen, Alexander Johannes Aloysius Maria; van Dijk, Johannes A.G.M.; Wright, James D.

    2015-01-01

    During the 1990s, researchers and policy makers began discussing the presence of a so-called ‘digital divide,’ a distinction of people who do and do not have access to information and communication technologies. The concept of the digital divide stems from a comparative perspective of social and

  10. Social Welfare Implications of the Digital Divide

    Science.gov (United States)

    Kim, Eunjin; Lee, Byungtae; Menon, Nirup M.

    2009-01-01

    The Internet plays a critical role in informing individuals about society, politics, business, and the environment. So much so that it has been said that the digital divide makes the segment of society on the ''right side'' of the divide (the digitally endowed group) better off and that on the ''wrong side'' (the digitally challenged group) worse…

  11. Relay-aided multi-cell broadcasting with random network coding

    DEFF Research Database (Denmark)

    Lu, Lu; Sun, Fan; Xiao, Ming

    2010-01-01

    We investigate a relay-aided multi-cell broadcasting system using random network codes, where the focus is on devising efficient scheduling algorithms between relay and base stations. Two scheduling algorithms are proposed based on different feedback strategies; namely, a one-step scheduling...

  12. Nanostructure-property relations for phase-change random access memory (PCRAM) line cells

    NARCIS (Netherlands)

    Kooi, B. J.; Oosthoek, J. L. M.; Verheijen, M. A.; Kaiser, M.; Jedema, F. J.; Gravesteijn, D. J.

    2012-01-01

    Phase-change random access memory (PCRAM) cells have been studied extensively using electrical characterization and rather limited by detailed structure characterization. The combination of these two characterization techniques has hardly been exploited and it is the focus of the present work.

  13. Cell-Mediated Cytotoxicity Toward Measles Virus-Infected Target Cells in Randomly Bred Syrian Hamsters

    OpenAIRE

    Cremer, Natalie E.; O'Keefe, Beatrice; Hagens, Shirley J.; Diggs, Janice

    1982-01-01

    Cell-mediated cytotoxicity (CMC) toward measles virus-infected cells was studied by a 51Cr release assay with spleen cells from hamsters inoculated with measles virus (strain Lec) or control antigen and with spleen cells from normal hamsters. Spleen cells from measles virus-inoculated hamsters showed greater CMC toward infected than toward noninfected target cells (designated specific CMC). Specific CMC was maximal 7 days after virus inoculation and was declining by 9 to 10 days. Effector cel...

  14. Guiding the orientation of smooth muscle cells on random and aligned polyurethane/collagen nanofibers.

    Science.gov (United States)

    Jia, Lin; Prabhakaran, Molamma P; Qin, Xiaohong; Ramakrishna, Seeram

    2014-09-01

    Fabricating scaffolds that can simulate the architecture and functionality of native extracellular matrix is a huge challenge in vascular tissue engineering. Various kinds of materials are engineered via nano-technological approaches to meet the current challenges in vascular tissue regeneration. During this study, nanofibers from pure polyurethane and hybrid polyurethane/collagen in two different morphologies (random and aligned) and in three different ratios of polyurethane:collagen (75:25; 50:50; 25:75) are fabricated by electrospinning. The fiber diameters of the nanofibrous scaffolds are in the range of 174-453 nm and 145-419 for random and aligned fibers, respectively, where they closely mimic the nanoscale dimensions of native extracellular matrix. The aligned polyurethane/collagen nanofibers expressed anisotropic wettability with mechanical properties which is suitable for regeneration of the artery. After 12 days of human aortic smooth muscle cells culture on different scaffolds, the proliferation of smooth muscle cells on hybrid polyurethane/collagen (3:1) nanofibers was 173% and 212% higher than on pure polyurethane scaffolds for random and aligned scaffolds, respectively. The results of cell morphology and protein staining showed that the aligned polyurethane/collagen (3:1) scaffold promote smooth muscle cells alignment through contact guidance, while the random polyurethane/collagen (3:1) also guided cell orientation most probably due to the inherent biochemical composition. Our studies demonstrate the potential of aligned and random polyurethane/collagen (3:1) as promising substrates for vascular tissue regeneration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. Stem cells propagate their DNA by random segregation in the flatworm Macrostomum lignano.

    Science.gov (United States)

    Verdoodt, Freija; Willems, Maxime; Mouton, Stijn; De Mulder, Katrien; Bert, Wim; Houthoofd, Wouter; Smith, Julian; Ladurner, Peter

    2012-01-01

    Adult stem cells are proposed to have acquired special features to prevent an accumulation of DNA-replication errors. Two such mechanisms, frequently suggested to serve this goal are cellular quiescence, and non-random segregation of DNA strands during stem cell division, a theory designated as the immortal strand hypothesis. To date, it has been difficult to test the in vivo relevance of both mechanisms in stem cell systems. It has been shown that in the flatworm Macrostomum lignano pluripotent stem cells (neoblasts) are present in adult animals. We sought to address by which means M. lignano neoblasts protect themselves against the accumulation of genomic errors, by studying the exact mode of DNA-segregation during their division. In this study, we demonstrated four lines of in vivo evidence in favor of cellular quiescence. Firstly, performing BrdU pulse-chase experiments, we localized 'Label-Retaining Cells' (LRCs). Secondly, EDU pulse-chase combined with Vasa labeling demonstrated the presence of neoblasts among the LRCs, while the majority of LRCs were differentiated cells. We showed that stem cells lose their label at a slow rate, indicating cellular quiescence. Thirdly, CldU/IdU- double labeling studies confirmed that label-retaining stem cells showed low proliferative activity. Finally, the use of the actin inhibitor, cytochalasin D, unequivocally demonstrated random segregation of DNA-strands in LRCs. Altogether, our data unambiguously demonstrated that the majority of neoblasts in M. lignano distribute their DNA randomly during cell division, and that label-retention is a direct result of cellular quiescence, rather than a sign of co-segregation of labeled strands.

  16. Stem cells propagate their DNA by random segregation in the flatworm Macrostomum lignano.

    Directory of Open Access Journals (Sweden)

    Freija Verdoodt

    Full Text Available Adult stem cells are proposed to have acquired special features to prevent an accumulation of DNA-replication errors. Two such mechanisms, frequently suggested to serve this goal are cellular quiescence, and non-random segregation of DNA strands during stem cell division, a theory designated as the immortal strand hypothesis. To date, it has been difficult to test the in vivo relevance of both mechanisms in stem cell systems. It has been shown that in the flatworm Macrostomum lignano pluripotent stem cells (neoblasts are present in adult animals. We sought to address by which means M. lignano neoblasts protect themselves against the accumulation of genomic errors, by studying the exact mode of DNA-segregation during their division. In this study, we demonstrated four lines of in vivo evidence in favor of cellular quiescence. Firstly, performing BrdU pulse-chase experiments, we localized 'Label-Retaining Cells' (LRCs. Secondly, EDU pulse-chase combined with Vasa labeling demonstrated the presence of neoblasts among the LRCs, while the majority of LRCs were differentiated cells. We showed that stem cells lose their label at a slow rate, indicating cellular quiescence. Thirdly, CldU/IdU- double labeling studies confirmed that label-retaining stem cells showed low proliferative activity. Finally, the use of the actin inhibitor, cytochalasin D, unequivocally demonstrated random segregation of DNA-strands in LRCs. Altogether, our data unambiguously demonstrated that the majority of neoblasts in M. lignano distribute their DNA randomly during cell division, and that label-retention is a direct result of cellular quiescence, rather than a sign of co-segregation of labeled strands.

  17. Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex.

    Directory of Open Access Journals (Sweden)

    Manuel Schottdorf

    2015-11-01

    Full Text Available The architecture of iso-orientation domains in the primary visual cortex (V1 of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1's intrinsic connectome and its functional architecture adhere to a single optimization principle with high precision and robustness. To validate this hypothesis, it is critical to closely examine the quantitative predictions of alternative candidate theories. Random feedforward wiring within the retino-cortical pathway represents a conceptually appealing alternative to dynamical circuit optimization because random dimension-expanding projections are believed to generically exhibit computationally favorable properties for stimulus representations. Here, we ask whether the quantitative invariants of V1 architecture can be explained as a generic emergent property of random wiring. We generalize and examine the stochastic wiring model proposed by Ringach and coworkers, in which iso-orientation domains in the visual cortex arise through random feedforward connections between semi-regular mosaics of retinal ganglion cells (RGCs and visual cortical neurons. We derive closed-form expressions for cortical receptive fields and domain layouts predicted by the model for perfectly hexagonal RGC mosaics. Including spatial disorder in the RGC positions considerably changes the domain layout properties as a function of disorder parameters such as position scatter and its correlations across the retina. However, independent of parameter choice, we find that the model predictions substantially deviate from the layout laws of iso-orientation domains observed experimentally. Considering random wiring with the currently most realistic model of RGC mosaic layouts, a pairwise interacting point

  18. Digital divide in Serbia from demographic perspective

    Directory of Open Access Journals (Sweden)

    Milovanović Slavoljub M.

    2013-01-01

    Full Text Available Digital divide is a term that defines differences and inequality between various groups of population considering opportunities and abilities for access and use of information and communication technologies (ICT, particularly the Internet. Digital divide can be viewed from regional and global aspect, so there are significant differences between regions in a country and between countries, considering the use of ICT. On the global level, there are the countries where a great part of the population has access to ICT and countries where that is not the case. Serbia as a country that is in transition period belongs to the second group of countries. In addition, digital divide exists on a country level, because in south-east region of Serbia relatively small number of people has access to ICT comparing to the other regions. The paper just treats problem of digital divide on the example of Republic of Serbia, with specific view to demographic aspect of the problem.

  19. Environmental Aesthetics. Crossing Divides and Breaking Ground

    NARCIS (Netherlands)

    Drenthen, M.; Keulartz, J.

    2014-01-01

    Environmental aesthetics crosses several commonly recognized divides: between analytic and continental philosophy, Eastern and Western traditions, universalizing and historicizing approaches, and theoretical and practical concerns. This volume sets out to show how these,perspectives can be brought

  20. Divide and Recombine for Large Complex Data

    Science.gov (United States)

    2017-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Divide and Recombine (D& R ) statistical approach was developed for analyzing ‘big data’ where the computational complexity...is very high. The analyst divides data into subsets by a D& R division technique, applying analytic methods to each subset independently, without...communication. Outputs of each analytic method are recombined by a D& R recombination procedure, which allows extensive parallel computation. DeltaRho

  1. Determining whether observed eukaryotic cell migration indicates chemotactic responsiveness or random chemokinetic motion.

    Science.gov (United States)

    Szatmary, A C; Nossal, R

    2017-07-21

    Chemotaxis, the motion of cells directed by a gradient of chemoattractant molecules, guides cells in immune response, development, wound healing, and cancer. Unfortunately, this process is difficult to distinguish from chemokinesis, i.e., stimulated random cell motion. Chemotaxis is frequently inferred by determining how many cells cross a boundary in a chemotaxis assay, for example how many cells crawl into a chemoattractant-infused filter, or how many cells enter a defined region in an under-agarose assay or agarose spot assay. To mitigate possible ambiguity in whether motion observed in these assays is directed by the chemoattractant gradient or by chemokinesis, we developed a mathematical model to determine when such methods indeed indicate directed motion of cells. In contrast to previous analyses of chemotaxis assays, we report not just the gradients that arise in the assays but also resulting cell motion. We applied the model to data obtained from rigorous measurements and show, as examples, that MDA-MB-231 breast-cancer cells are at least 20 times less sensitive to gradients of EGF or CXCL12 than neutrophils are to formyl peptides; we then used this information to determine the extent to which gradient sensing increases the rate of boundary crossing relative to a random-motility control. Results show, for example, that in the filter assay, 2-4 times as many neutrophils pass through the filter when exposed to a gradient as when the gradient is absent. However, in the other combinations of cells and assays we considered, only 10-20% more cells are counted as having migrated in a directed, rather than random, motility condition. We also discuss the design of appropriate controls for these assays, which is difficult for the under-agarose and agarose spot assays. Moreover, although straightforward to perform with the filter assay, reliable controls are often not done. Consequently, we infer that chemotaxis is frequently over-reported, especially for cells like

  2. Transfusion of red cells in hematopoietic stem cell transplantation (TRIST: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Tinmouth Alan

    2011-09-01

    Full Text Available Abstract Background Insight regarding transfusion practices in Hematopoietic Stem cell Transplantation (HSCT are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated. Red blood cell transfusion can be life-saving, however, liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit. A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality. The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospective randomized study of transfusion is required to gain insight and knowledge on best transfusion practices in this high risk population. Methods This report describes the design and methodological issues of a randomized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation. This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinicaltrials.gov NCT01237639. Results In 3 Canadian centres, 100 patients undergoing Hematopoietic Stem Cell Transplantation will be randomized to either a restrictive (target hemoglobin of 70-90 g/L or liberal (target hemoglobin of 90-110 g/L red cell transfusion strategy, based daily hemoglobin values up to 100 days post-transplant. The study will stratify participants by centre and type of transplant. The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1 Transfusion Requirements, 2 Transplant Related Mortality, 3 Maximum grade of acute Graft versus Host Disease, 4 Veno-occlusive Disease, 5 Serious Infections, 6 Bearman Toxicity Score, 7 Bleeding, 8 Quality of Life, 9 Number of Hospitalizations and 10 Number of Intensive Care Unit

  3. Perception of young adults with sickle cell disease or sickle cell trait about participation in the CHOICES randomized controlled trial.

    Science.gov (United States)

    Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Wilkie, Diana J

    2016-06-01

    To gain an in-depth understanding of the perceptions of young adults with sickle cell disease and sickle cell trait about parenthood and participating in the CHOICES randomized controlled trial that used computer-based, educational programmes. In the USA, there is insufficient education to assure that all young adults with sickle cell disease or sickle cell trait understand genetic inheritance risks and reproductive options to make informed reproductive decisions. To address this educational need, we developed a computer-based, multimedia program (CHOICES) and reformatted usual care into a computer-based (e-Book) program. We then conducted a two-year randomized controlled trial that included a qualitative component that would deepen understanding of young adults' perceptions of parenthood and use of computer-based, educational programmes. A qualitative descriptive approach completed after a randomized controlled trial. Sixty-eight men and women of childbearing age participated in semi-structured interviews at the completion of the randomized controlled trial from 2012-2013. Thematic content analysis guided the qualitative description. Three main themes were identified: (1) increasing knowledge and new ways of thinking and behaving; (2) rethinking parenting plans; and (3) appraising the program design and delivery. Most participants reported increased knowledge and rethinking of their parenting plans and were supportive of computer-based learning. Some participants expressed difficulty in determining individual transmission risks. Participants perceived the computer programs as beneficial to their learning. Future development of an Internet-based educational programme is warranted, with emphasis on providing tailored education or memory boosters about individual transmission risks. © 2015 John Wiley & Sons Ltd.

  4. Statistical analysis of the correlations between cell performance and its initial states in contact resistive random access memory cells

    Science.gov (United States)

    Kao, Yun Feng; Hsieh, Wei Ting; Che Chen, Chun; King, Ya-Chin; Lin, Chrong Jung

    2017-04-01

    Variability has been one of the critical challenges in the implementation of large resistive random access memory (RRAM) arrays. Wide variations in set/reset, read and cycling characteristics can significantly reduce the design margin and feasibility of a memory array. Predicting the characteristics of RRAM cells is constructive to provide insights and to adjust the memory operations accordingly. In this study, a strong correlation between the cell performance and its initial state is found in contact RRAM (CRRAM) cells by 28 nm CMOS logic technology. Furthermore, a verify-reset operation is proposed to identify the type of conductive filament (CF) in a cell. Distinctive CRRAM characteristics are found to be linked directly to initial CFs, enabling preliminary screening and adaptive resets to address the large variability problems in sizable CRRAM arrays.

  5. BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial.

    Science.gov (United States)

    Gasper, Melanie A; Hesseling, Anneke C; Mohar, Isaac; Myer, Landon; Azenkot, Tali; Passmore, Jo-Ann S; Hanekom, Willem; Cotton, Mark F; Crispe, I Nicholas; Sodora, Donald L; Jaspan, Heather B

    2017-04-06

    BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+ T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm). RESULTS. Of 149 infants randomized, 92% (n = 137) were retained at 6 weeks: 71 in the routine BCG arm and 66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in systemic activation of HIV target CD4+CCR5+ T cells (HLA-DR+CD38+) at 6 weeks (0.25% at birth versus 0.08% in delayed vaccination groups; P = 0.029), which persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination of the infants in the delayed arm at 8 weeks resulted in a similar increase in activated CD4+CCR5+ T cells. The increase in activated T cells was associated with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN-α1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells. CONCLUSION. BCG vaccination induces immune changes in HIV-exposed infants, including an increase in the proportion of activated CCR5+CD4+ HIV target cells. These findings provide insight into optimal BCG vaccine timing to minimize the risks of HIV transmissions to exposed infants while preserving potential benefits conferred by BCG vaccination. TRIAL REGISTRATION. ClinicalTrials.gov NCT02062580. FUNDING. This trial was sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the Thrasher Foundation (NR-0095); for details, see Acknowledgments.

  6. Proteome Analysis of Thyroid Cancer Cells After Long-Term Exposure to a Random Positioning Machine

    Science.gov (United States)

    Pietsch, Jessica; Bauer, Johann; Weber, Gerhard; Nissum, Mikkel; Westphal, Kriss; Egli, Marcel; Grosse, Jirka; Schönberger, Johann; Eilles, Christoph; Infanger, Manfred; Grimm, Daniela

    2011-11-01

    Annulling gravity during cell culturing triggers various types of cells to change their protein expression in a time dependent manner. We therefore decided to determine gravity sensitive proteins and their period of sensitivity to the effects of gravity. In this study, thyroid cancer cells of the ML-1 cell line were cultured under normal gravity (1 g) or in a random positioning machine (RPM), which simulated near weightlessness for 7 and 11 days. Cells were then sonicated and proteins released into the supernatant were separated from those that remained attached to the cell fragments. Subsequently, both types of proteins were fractionated by free-flow isoelectric focussing (FF-IEF). The fractions obtained were further separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) to which comparable FF-IEF fractions derived from cells cultured either under 1 g or on the RPM had been applied side by side. The separation resulted in pairs of lanes, on which a number of identical bands were observed. Selected gel pieces were excised and their proteins determined by mass spectrometry. Equal proteins from cells cultured under normal gravity and the RPM, respectively, were detected in comparable gel pieces. However, many of these proteins had received different Mascot scores. Quantifying heat shock cognate 71 kDa protein, glutathione S-transferase P, nucleoside diphosphate kinase A and annexin-2 by Western blotting using whole cell lysates indicated usefulness of Mascot scores for selecting the most efficient antibodies.

  7. Random skin biopsy and bone marrow biopsy for diagnosis of intravascular large B cell lymphoma.

    Science.gov (United States)

    Matsue, Kosei; Asada, Noboru; Odawara, Jun; Aoki, Takayoshi; Kimura, Shun-ichi; Iwama, Kan-ichi; Fujiwara, Hideaki; Yamakura, Masayuki; Takeuchi, Masami

    2011-04-01

    Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in the lumina of small vessels. The diagnosis of IVL requires histological confirmation. Although random skin biopsy from healthy-appearing skin in patients with suspected IVL appeared to be useful, the sensitivity of this method for the diagnosis of IVL remains unknown. We performed a random skin biopsy from 12 consecutive cases of IVL diagnosed at our institution over the past 4 years and evaluate its relevance of clinical and laboratory characteristics, presence or absence of skin lesions, and bone marrow involvement. All 12 patients were diagnosed antemortem by either random skin biopsy or bone marrow biopsy and treated with rituximab-containing chemotherapy. Random skin biopsy was performed in all 12 patients, and the results were positive in ten patients (83.3%). Erythematous skin lesions were seen in 3 of 12 patients, but biopsy was positive for lymphoma lesion in two patients. Bone marrow invasion was seen in 11 of the 12 patients (91.6%) by bone marrow smear and/or flow cytometric analysis, but was detected in only half of the patients by trephine biopsy. We concluded that random skin biopsy from normal-appearing skin is highly sensitive in the diagnosis of IVL comparable to bone marrow trephine biopsy. It should be performed irrespective of the presence or absence of skin lesions in patients who were suspicious of IVL.

  8. Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

    Directory of Open Access Journals (Sweden)

    Oliveira Sérgio A

    2007-01-01

    Full Text Available Abstract Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum. For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271

  9. Digital divide research, achievements and shortcomings

    NARCIS (Netherlands)

    van Dijk, Johannes A.G.M.

    2006-01-01

    From the end of the 1990s onwards the digital divide, commonly defined as the gap between those who have and do not have access to computers and the Internet, has been a central issue on the scholarly and political agenda of new media development. This article makes an inventory of 5 years of

  10. Democratisation and Conflict in Ethnically Divided Societies

    NARCIS (Netherlands)

    Vorrath, Judith; Krebs, Lutz

    2009-01-01

    This article reviews three important factors in the academic debate on ethnic civil wars: the role of ethnicity in causing and structuring violence, the spread of ethnic civil wars once they have started, and the influence of democratic transitions in divided societies. The review displays the range

  11. Divide and Multiply: Baptist Diversity in Appalachia.

    Science.gov (United States)

    Dorgan, Howard

    1996-01-01

    Baptists' propensity for splitting apart arises from the faith's avowed love of theological argument. Gives an overview of Baptist denominations, and identifies the main issues that divide them: atonement, predestination, the nature and origins of good and evil, worship practices, church governance, gender issues, and other social and cultural…

  12. Bridging the digital divide with mobile services

    CERN Document Server

    Yelton, Andromeda

    2013-01-01

    In this issue of Library Technology Reports, Andromeda Yelton shows how libraries can build on the breadth of this population to help bridge the digital divide and provide even greater access to information. Yelton breaks down the demographics of mobile internet users, provides examples of how different libraries are reaching out to these populations, and suggests what the future may hold for this trend.

  13. Project DIVIDE Instrument Development. Technical Report # 0810

    Science.gov (United States)

    Ketterlin-Geller, Leanne; Jung, Eunju; Geller, Josh; Yovanoff, Paul

    2008-01-01

    In this technical report, we describe the development of cognitive diagnostic test items that form the basis of the diagnostic system for Project DIVIDE (Dynamic Instruction Via Individually Designed Environments). The construct underlying the diagnostic test is division of fractions. We include a description of the process we used to identify the…

  14. TOWARDS BRIDGING ETHNIC AND RELIGIOUS DIVIDES IN ...

    African Journals Online (AJOL)

    NGOZI

    claim both common ancestry and a common cultural tradition”(p. 218). ... foundation. Among several other reasons that results to ethno- religious divide in Nigeria is the amalgamation event which is the hand work of the European imperial powers under the ... ethnicity is said to be rooted in the very set up of Nigeria,but it got.

  15. Comparison of cell behavior on pva/pva-gelatin electrospun nanofibers with random and aligned configuration

    Science.gov (United States)

    Huang, Chen-Yu; Hu, Keng-Hsiang; Wei, Zung-Hang

    2016-12-01

    Electrospinning technique is able to create nanofibers with specific orientation. Poly(vinyl alcohol) (PVA) have good mechanical stability but poor cell adhesion property due to the low affinity of protein. In this paper, extracellular matrix, gelatin is incorporated into PVA solution to form electrospun PVA-gelatin nanofibers membrane. Both randomly oriented and aligned nanofibers are used to investigate the topography-induced behavior of fibroblasts. Surface morphology of the fibers is studied by optical microscopy and scanning electron microscopy (SEM) coupled with image analysis. Functional group composition in PVA or PVA-gelatin is investigated by Fourier Transform Infrared (FTIR). The morphological changes, surface coverage, viability and proliferation of fibroblasts influenced by PVA and PVA-gelatin nanofibers with randomly orientated or aligned configuration are systematically compared. Fibroblasts growing on PVA-gelatin fibers show significantly larger projected areas as compared with those cultivated on PVA fibers which p-value is smaller than 0.005. Cells on PVA-gelatin aligned fibers stretch out extensively and their intracellular stress fiber pull nucleus to deform. Results suggest that instead of the anisotropic topology within the scaffold trigger the preferential orientation of cells, the adhesion of cell membrane to gelatin have substantial influence on cellular behavior.

  16. Discovering cell types in flow cytometry data with random matrix theory

    Science.gov (United States)

    Shen, Yang; Nussenblatt, Robert; Losert, Wolfgang

    Flow cytometry is a widely used experimental technique in immunology research. During the experiments, peripheral blood mononuclear cells (PBMC) from a single patient, labeled with multiple fluorescent stains that bind to different proteins, are illuminated by a laser. The intensity of each stain on a single cell is recorded and reflects the amount of protein expressed by that cell. The data analysis focuses on identifying specific cell types related to a disease. Different cell types can be identified by the type and amount of protein they express. To date, this has most often been done manually by labelling a protein as expressed or not while ignoring the amount of expression. Using a cross correlation matrix of stain intensities, which contains both information on the proteins expressed and their amount, has been largely ignored by researchers as it suffers from measurement noise. Here we present an algorithm to identify cell types in flow cytometry data which uses random matrix theory (RMT) to reduce noise in a cross correlation matrix. We demonstrate our method using a published flow cytometry data set. Compared with previous analysis techniques, we were able to rediscover relevant cell types in an automatic way. Department of Physics, University of Maryland, College Park, MD 20742.

  17. Elastic properties of model random three-dimensional open-cell solids

    Science.gov (United States)

    Roberts, A. P.; Garboczi, E. J.

    2002-01-01

    Most cellular solids are random materials, while practically all theoretical structure-property relations are for periodic models. To generate theoretical results for random models the finite element method (FEM) was used to study the elastic properties of open-cell solids. We have computed the density ( ρ) and microstructure dependence of the Young's modulus ( E) and Poisson's ratio ( ν) for four different isotropic random models. The models were based on Voronoi tessellations, level-cut Gaussian random fields, and nearest neighbour node-bond rules. These models were chosen to broadly represent the structure of foamed solids and other (non-foamed) cellular materials. At low densities, the Young's modulus can be described by the relation E∝ ρn. The exponent n and constant of proportionality depend on microstructure. We find 1.3common model of foams, became approximately incompressible ( ν≈0.5). This behaviour is not commonly observed experimentally. Our studies showed the result was robust to polydispersity and that a relatively large number (15%) of the bonds must be broken to significantly reduce the low-density Poission's ratio to ν≈0.33.

  18. Conquering the digital divide: Botswana and South Korea digital divide status and interventions

    Directory of Open Access Journals (Sweden)

    Nonofo C. Sedimo

    2011-11-01

    Objectives: Bridging the digital divide and narrowing the intra-national divide brings about global information and communication technology (ICT usage that translates into changing work patterns and eventually transformed economies. This article outlines the different interventions implemented in Botswana to bridge the divide. The South Korean experience in bridging the divide is discussed so as to serve as lessons on how to effectively bridge the divide to Botswana’s initiatives. Method: Using a mix of exploratory and empirical study, this article presents the findings on the status of ICT uptake in Botswana and investigates the level of the digital divide in the country. Results: The results of the study show that the digital divide is much more evident in Botswana than in South Korea. South Korea has put in place robust strategic initiatives towards reducing the digital divide and this has largely transcended into its transformation into a full-fledged knowledge society. Conclusion: This article is timely as it unearths the different pointers that may be utilised in policy formation and what interventions need to be taken at both the individual and national level to bridge the digital divide.

  19. Conquering the digital divide: Botswana and South Korea digital divide status and interventions

    Directory of Open Access Journals (Sweden)

    Nonofo C. Sedimo

    2011-03-01

    Full Text Available Background: Botswana is putting in place initiatives towards establishing itself as a knowledgebased economy. Transformation from a resource-based to a knowledge-based economy is partly hinged on innovation, research and development capability, knowledge channels, and the funding of research and development activities.Objectives: Bridging the digital divide and narrowing the intra-national divide brings about global information and communication technology (ICT usage that translates into changing work patterns and eventually transformed economies. This article outlines the different interventions implemented in Botswana to bridge the divide. The South Korean experience in bridging the divide is discussed so as to serve as lessons on how to effectively bridge the divide to Botswana’s initiatives.Method: Using a mix of exploratory and empirical study, this article presents the findings on the status of ICT uptake in Botswana and investigates the level of the digital divide in the country.Results: The results of the study show that the digital divide is much more evident in Botswana than in South Korea. South Korea has put in place robust strategic initiatives towards reducing the digital divide and this has largely transcended into its transformation into a full-fledged knowledge society.Conclusion: This article is timely as it unearths the different pointers that may be utilised in policy formation and what interventions need to be taken at both the individual and national level to bridge the digital divide.

  20. A Randomized Clinical Trial of Red Blood Cell Transfusion Triggers in Cardiac Surgery.

    Science.gov (United States)

    Koch, Colleen G; Sessler, Daniel I; Mascha, Edward J; Sabik, Joseph F; Li, Liang; Duncan, Andra I; Zimmerman, Nicole M; Blackstone, Eugene H

    2017-10-01

    Class I evidence supporting a threshold for transfusion in the cardiac surgical setting is scarce. We randomly allocated patients to a transfusion hematocrit trigger of 24% versus 28% to compare morbidity, mortality, and resource use. From March 2007 to August 2014, two centers randomly assigned 722 adults undergoing coronary artery bypass graft surgery or valve procedures to a 24% hematocrit trigger (n = 363, low group) or 28% trigger (n = 354, high group). One unit of red blood cells was transfused if the hematocrit fell below the designated threshold. The primary endpoint was a composite of postoperative morbidities and mortality. Treatment effect was primarily assessed using an average relative effect generalized estimating equation model. At the second planned interim analysis, the a priori futility boundary was crossed, and the study was stopped. There was no detected treatment effect on the composite outcome (average relative effect odds ratio, low versus high, 0.86, 95% confidence interval: 0.29 to 2.54, p = 0.71). However, the low group received fewer red blood cell transfusions than the high group (54% versus 75%, p < 0.001), mostly administered in the operating room (low group, 112 [31%]; high group, 208 [59%]), followed by intensive care unit (low, 105 [31%]; high, 115 [34%]) and floor (low, 41 [12%]; high, 42 [13%]). The low group was exposed to lower hematocrits: median before transfusion, 22% (Q1 = 21%, Q3 = 23%) versus 24% (Q1 = 22%, Q3 = 25%). Negative exposures differed between treatment groups, with lower hematocrit in the 24% trigger group and more red blood cells used in the 28% group, but adverse outcomes did not differ. Because red blood cell use was less with a 24% trigger without adverse effects, our randomized trial results support aggressive blood conservation efforts in cardiac surgery. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Interactions between mitochondrial and nuclear DNA in mammalian cells are non-random.

    Science.gov (United States)

    Doynova, M D; Berretta, A; Jones, M B; Jasoni, C L; Vickers, M H; O'Sullivan, J M

    2016-09-01

    Chromosome Conformation Capture techniques regularly detect physical interactions between mitochondrial and nuclear DNA (i.e. mito-nDNA interactions) in mammalian cells. We have evaluated mito-nDNA interactions captured by HiC and Circular Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions are statistically significant and shared between biological and technical replicates. The most frequent interactions occur with repetitive DNA sequences, including centromeres in human cell lines and the 18S rDNA in mouse cortical astrocytes. Our results demonstrate a degree of selective regulation in the identity of the interacting mitochondrial partners confirming that mito-nDNA interactions in mammalian cells are not random. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  2. Endothelial cell loss and visual outcome of deep anterior lamellar keratoplasty versus penetrating keratoplasty: a randomized multicenter clinical trial

    NARCIS (Netherlands)

    Cheng, Y.Y.; Visser, N.; Schouten, J.S.A.G.; Wijdh, R.J.; Pels, E.; Cleynenbreugel, H. van; Eggink, C.A.; Zaal, M.J.; Rijneveld, W.J.; Nuijts, R.M.

    2011-01-01

    OBJECTIVE: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). DESIGN: Randomized, multicenter clinical trial. PARTICIPANTS: Fifty-six eyes of 56 patients with a corneal stromal

  3. Endothelial Cell Loss and Visual Outcome of Deep Anterior Lamellar Keratoplasty versus Penetrating Keratoplasty : A Randomized Multicenter Clinical Trial

    NARCIS (Netherlands)

    Cheng, Yanny Y. Y.; Visser, Nienke; Schouten, Jan S.; Wijdh, Robert-Jan; Pels, Elisabeth; van Cleynenbreugel, Hugo; Eggink, Catharina A.; Zaal, Michel J. W.; Rijneveld, Wilhelmina J.; Nuijts, Rudy M. M. A.

    Objective: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). Design: Randomized, multicenter clinical trial. Participants: Fifty-six eyes of 56 patients with a corneal stromal

  4. High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

    National Research Council Canada - National Science Library

    Donald A. Berry; Naoto T. Ueno; Marcella M. Johnson; Xiudong Lei; Jean Caputo; Dori A. Smith; Linda J. Yancey; Michael Crump; Edward A. Stadtmauer; Pierre Biron; John P. Crown; Peter Schmid; Jean-Pierre Lotz; Giovanni Rosti; Marco Bregni; Taner Demirer

    2011-01-01

    ... to evaluate its effect in the treatment of metastatic breast cancer. We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support...

  5. Multi-Cell Random Beamforming: Achievable Rate and Degrees of Freedom Region

    CERN Document Server

    Nguyen, Hieu Duy; Hui, Hon Tat

    2012-01-01

    Random beamforming (RBF) is a practically favorable transmission scheme for multiuser multi-antenna downlink systems since it requires only partial channel state information (CSI) at the transmitter. Under the conventional single-cell setup, RBF is known to achieve the optimal sum-capacity scaling law as the number of users goes to infinity, thanks to the multiuser diversity effect that eliminates the inter-user interference. In this paper, we extend the study on RBF to a more practical multi-cell downlink system subject to the additional inter-cell interference (ICI). First, we consider the case of finite user's signal-to-noise ratio (SNR). We derive a closed-form expression of the achievable sum rate with the multi-cell RBF, based upon which we show the asymptotic sum-rate scaling law as the number of users goes to infinity. Next, we consider the high-SNR regime and for a tractable analysis assume that the number of users in each cell scales in a certain order with the per-cell SNR. Under this setup, we cha...

  6. Analyzing Broadband Divide in the Farming Sector

    DEFF Research Database (Denmark)

    Jensen, Michael; Gutierrez Lopez, Jose Manuel; Pedersen, Jens Myrup

    2013-01-01

    , upstream and downstream connection. The main constraint is that farms are naturally located in rural areas where the required access broadband data rates are not available. This paper studies the broadband divide in relation to the Danish agricultural sector. Results show how there is an important......Agriculture industry has been evolving for centuries. Currently, the technological development of Internet oriented farming tools allows to increase the productivity and efficiency of this sector. Many of the already available tools and applications require high bandwidth in both directions...... difference between the broadband availability for farms and the rest of the households/buildings the country. This divide may be slowing down the potential technological development of the farming industry, in order to keep their competitiveness in the market. Therefore, broadband development in rural areas...

  7. REGENERATIVE GAS TURBINES WITH DIVIDED EXPANSION

    DEFF Research Database (Denmark)

    Elmegaard, Brian; Qvale, Einar Bjørn

    2004-01-01

    their efficiency are always of interest. Recently, two independent studies have proposed recuperated gas turbines to be configured with the turbine expansion divided, in order to obtain higher efficiency. The idea is to operate the system with a gas generator and a power turbine, and use the gas from the gas......Recuperated gas turbines are currently drawing an increased attention due to the recent commercialization of micro gas turbines with recuperation. This system may reach a high efficiency even for the small units of less than 100 kW. In order to improve the economics of the plants, ways to improve...... divided expansion can be advantageous under certain circumstances. But, in order for todays micro gas turbines to be competitive, the thermodynamic efficiencies will have to be rather high. This requires that all component efficiencies including the recuperator effectiveness will have to be high...

  8. Cellular forces : adhering, shaping, sensing and dividing

    NARCIS (Netherlands)

    Hoorn, Hedde van

    2014-01-01

    Life’s building block is a cell. Different cell types are differentiated by specific functional properties. A white blood cell, for instance, can get rid of bacteria and many muscle cells contract together for proper muscle function. Deformation and force exertion play important roles in these

  9. Mast cell stabilizers as a potential treatment for Irritable bowel syndrome: A randomized placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    N Ebrahimi Daryani

    2009-08-01

    Full Text Available Objectives: Mast cells are believed to play a role in irritable bowel syndrome pathogenesis and symptom genesis due to their close neighborhood to gastrointestinal innervations. This study was designed to evaluate the efficacy of orally administered cromolyn for reduction of symptoms in patients with irritable bowel syndrome (IBS. Material and Methods s: A randomized placebo-controlled double-blinded 6×6 weeks cross-over study was performed in a private gastrointestinal clinic. 10 patients were allocated to group A and 6 patients to group B. Patients in group A received 150 mg cromolyn divided in three equal doses for the first 6 weeks and placebo for the next 6 weeks but patients in group B received placebo for the first 6 weeks and cromolyn in the next 6 weeks. Weekly evaluation was performed and visual analogue scale was used to determine severity of symptoms. Results: Sixteen patients completed the study. Mean age of the patients was 40.3 ± 10.9 years old [range: 24-57]. Eight patients had D-IBS (Diarrhea dominant and other 8 had C-IBS (Constipation dominant. Both cromolyn sodium and the placebo decreased the severity of bloating (Freidman test, p 0.001 and 0.006 respectively. The severity of the main symptom (diarrhea or constipation did not decrease in patients of group A and B who were treated with different sequences of the drug or placebo. The severity of pain decreased drastically after 6th week of treatment with cromolyn. Freidman test showed a significant difference between the pain levels of the former defined treatment spots (p 0.01, and 0.02 for patients in group A and B, respectively. No adverse drug reactions were observed during the study. Conclusion: In conclusion, long term administration of cromolyn seems to be partially effective for treatment of abdominal pain in patients with IBS while main symptoms (diarrhea or constipation might not decrease during this treatment.

  10. A Phase Ib open label, randomized, safety study of SANGUINATE™ in patients with sickle cell anemia.

    Science.gov (United States)

    Misra, Hemant; Bainbridge, James; Berryman, John; Abuchowski, Abraham; Galvez, Kenneth Mauricio; Uribe, Luis Fernando; Hernandez, Angel Luis; Sosa, Nestor Rodolfo

    Treatment of sickle cell anemia is a challenging task and despite the well understood genetic and biochemical pathway of sickle hemoglobin, current therapy continues to be limited to the symptomatic treatment of pain, supplemental oxygen, antibiotics, red blood cell transfusions and hydroxyurea. SANGUINATE is a carbon monoxide releasing molecule and oxygen transfer agent under clinical development for the treatment of sickle cell anemia and comorbidities. An open-label randomized Phase Ib study was performed in adult sickle cell anemia patients. Two dose levels of SANGUINATE were compared to hydroxyurea in 24 homozygotes for Hb SS. Twelve subjects received either a low dose (160mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. Another 12 subjects received either a high dose (320mg/kg) of SANGUINATE or 15mg/kg hydroxyurea. The primary endpoint was the safety of SANGUINATE versus hydroxyurea in sickle cell anemia patients. Secondary endpoints included determination of the plasma pharmacokinetics and assessment of hematologic measurements. Musculoskeletal related adverse events were the most common. Transient troponin I levels increased in three patients, one of whom had an increase in tricuspid regurgitant velocity; however, no clinical signs were noted. Following an assessment of vital signs, tricuspid regurgitant velocity, electrocardiogram, serum biochemistry, hematology, urinalysis, and analysis of reported adverse events, SANGUINATE was found to be safe in stable sickle cell anemia patients. The clinical trial met its primary objective of demonstrating an acceptable safety profile for SANGUINATE in patients with sickle cell anemia. This trial established the safety of SANGUINATE at both dose levels and permitted its advance to Phase II trials. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  11. EXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Chamorro-Viña Carolina

    2012-09-01

    Full Text Available Abstract Background Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of exercise in the hematological and immunological recovery of children undergoing hematopoietic stem cell transplant. The primary objective of this randomized-controlled trial (RCT is to study the effect of an exercise program (in- and outpatient on immune cell recovery in patients undergoing an autologous stem cell transplantation. The secondary objective is to determine if an exercise intervention diminishes the usual deterioration in quality of life, physical fitness, and the acquisition of a sedentary lifestyle. Methods This RCT has received approval from The Conjoint Health Research Ethics Board (CHREB of the University of Calgary (Ethics ID # E-24476. Twenty-four participants treated for a malignancy with autologous stem cell transplant (5 to 18 years in the Alberta Children’s Hospital will be randomly assigned to an exercise or control group. The exercise group will participate in a two-phase exercise intervention (in- and outpatient from hospitalization until 10 weeks after discharge. The exercise program includes strength, flexibility and aerobic exercise. During the inpatient phase this program will be performed 5 times/week and will be supervised. The outpatient phase will combine a supervised session with two home-based exercise sessions with the use of the Wii device. The control group will follow the standard protocol without any specific exercise program. A range of outcomes, including quantitative and functional recovery of immune system

  12. A specific library of randomly integrated reporter genes for the isolation of inducible functions by cell sorting

    Energy Technology Data Exchange (ETDEWEB)

    Lapeyre, J.N.; Marini, F.; Gratzner, H.G. (M. D. Anderson Cancer Center, Houston, TX (United States) AMC ImmunoDiagnostics, Houston, TX (United States))

    1993-01-01

    A library of cells containing randomly integrated reporter genes has been constructed. The purpose of this library is to enable the isolation of genes of interest which are inducible by radiation, biological response modifiers, cytokines, or other agents. These genes are located near reporter genes which can be induced by the upstream promoter of the gene of interest. The reporter gene, Lac Z, was randomly inserted into the genome by retroviral transduction and subsequent selection of the neo[sup r] gene with gentamycin. Studies of radiation inducible genes were undertaken, whereby cells with the radiation sensitive function were isolated by sorting the cells fluorescent after staining with the beta gal substrate, fluorescein digalactoside (FDG). This gene-tagging approach is an improvement over the cDNA library subtraction protocol in that a single library of cells with random marker gene integration can be repeatedly and sequentially probed by sorting under different, selective conditions, dependent upon the genes to be characterized.

  13. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

    Science.gov (United States)

    Motzer, Robert J.; Rini, Brian I.; McDermott, David F.; Redman, Bruce G.; Kuzel, Timothy M.; Harrison, Michael R.; Vaishampayan, Ulka N.; Drabkin, Harry A.; George, Saby; Logan, Theodore F.; Margolin, Kim A.; Plimack, Elizabeth R.; Lambert, Alexandre M.; Waxman, Ian M.; Hammers, Hans J.

    2015-01-01

    Purpose Nivolumab is a fully human immunoglobulin G4 programmed death–1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety. Results A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs. Conclusion Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting. PMID:25452452

  14. Bridging the transatlantic divide in privacy

    Directory of Open Access Journals (Sweden)

    Paula Kift

    2013-08-01

    Full Text Available In the context of the US National Security Agency surveillance scandal, the transatlantic privacy divide has come back to the fore. In the United States, the right to privacy is primarily understood as a right to physical privacy, thus the protection from unwarranted government searches and seizures. In Germany on the other hand, it is also understood as a right to spiritual privacy, thus the right of citizens to develop into autonomous moral agents. The following article will discuss the different constitutional assumptions that underlie American and German attitudes towards privacy, namely privacy as an aspect of liberty or as an aspect of dignity. As data flows defy jurisdictional boundaries, however, policymakers across the Atlantic are faced with a conundrum: how can German and American privacy cultures be reconciled?

  15. RANdom SAmple Consensus (RANSAC) algorithm for material-informatics: application to photovoltaic solar cells.

    Science.gov (United States)

    Kaspi, Omer; Yosipof, Abraham; Senderowitz, Hanoch

    2017-06-06

    An important aspect of chemoinformatics and material-informatics is the usage of machine learning algorithms to build Quantitative Structure Activity Relationship (QSAR) models. The RANdom SAmple Consensus (RANSAC) algorithm is a predictive modeling tool widely used in the image processing field for cleaning datasets from noise. RANSAC could be used as a "one stop shop" algorithm for developing and validating QSAR models, performing outlier removal, descriptors selection, model development and predictions for test set samples using applicability domain. For "future" predictions (i.e., for samples not included in the original test set) RANSAC provides a statistical estimate for the probability of obtaining reliable predictions, i.e., predictions within a pre-defined number of standard deviations from the true values. In this work we describe the first application of RNASAC in material informatics, focusing on the analysis of solar cells. We demonstrate that for three datasets representing different metal oxide (MO) based solar cell libraries RANSAC-derived models select descriptors previously shown to correlate with key photovoltaic properties and lead to good predictive statistics for these properties. These models were subsequently used to predict the properties of virtual solar cells libraries highlighting interesting dependencies of PV properties on MO compositions.

  16. A video-based educational pilot for basal cell carcinoma (BCC) treatment: A randomized controlled trial.

    Science.gov (United States)

    Love, Elyse M; Manalo, Iviensan F; Chen, Suephy C; Chen, Kuang-Ho; Stoff, Benjamin K

    2016-03-01

    Several treatment options exist for uncomplicated basal cell carcinoma. Standardized and effective informed consent is difficult in busy dermatology clinics. We investigated whether an educational video depicting 3 treatment options for uncomplicated basal cell carcinoma-excision, electrodessication and curettage, and topical therapy-before standard in-office informed consent affected patient knowledge and consent time compared with standard in-office consent alone. Patients were randomized to receive video education plus verbal discussion (video) or standard verbal discussion alone (control). Both groups completed baseline and final knowledge assessments. The primary outcome measure was change in knowledge scores between groups. Secondary outcomes were patient satisfaction, physician satisfaction, and informed consent time. In all, 32 eligible patients (16 control, 16 video) from an academic institution and affiliate Department of Veterans Affairs Medical Center dermatology clinics participated. The video group had significantly greater gains in knowledge compared with the control group (mean ± SD: 9 ± 3.6 vs 2.9 ± 2.2) (P = .0048). There was no significant difference in total consent time between groups. Patients and physicians were highly satisfied with the video. Small sample size and slight methodological difference between recruitment sites are limitations. Video-based education for basal cell carcinoma improved patient knowledge with no additional physician time when compared with standard communication. Published by Elsevier Inc.

  17. Music therapy improves the mood of patients undergoing hematopoietic stem cells transplantation (controlled randomized study).

    Science.gov (United States)

    Dóro, Carlos Antonio; Neto, José Zanis; Cunha, Rosemyriam; Dóro, Maribel Pelaez

    2017-03-01

    The allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic medical treatment for various neoplastic hematologic, congenital, genetic, or acquired disorders. In this procedure which combines high-dose chemotherapy and/or radiotherapy and has a high degree of cytotoxicity, the patient experiences solitary confinement, which causes psychological distress, pain, anxiety, mood disorders and can lead him/her to depression. Music therapy was applied with the purpose of decreasing this social confinement. This is a randomized controlled trial. Patients (n = 100) were selected randomly. Patients (n = 50) were selected for the Experimental Music Therapy Group (EMG) and n = 50 for the control group (CG) who received the standard treatment. The intervention of live music was applied using music therapy techniques. Assessment and quantification were made using the visual analog scale (VAS). The dependent variables were pain, anxiety, and mood of patients. The Mann-Whitney test (p Music therapy proved to be a strong ally in the treatment of patients undergoing allo-HSCT, providing bio-psychosocial welfare.

  18. Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma.

    Science.gov (United States)

    Guidolin, Diego; Marinaccio, Christian; Tortorella, Cinzia; Annese, Tiziana; Ruggieri, Simona; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico

    2017-02-01

    Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites.

  19. Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

    Science.gov (United States)

    Cassileth, Barrie R; Vickers, Andrew J; Magill, Lucanne A

    2003-12-15

    High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT. Copyright 2003 American Cancer Society.

  20. Metformin: a case of divide and conquer

    Science.gov (United States)

    2013-01-01

    Metformin is a widely prescribed anti-diabetic drug and its use is associated with lower cancer incidence. The mechanisms by which metformin attenuates tumorigenesis are not clearly understood. In a paper published in Proceedings of the National Academy of Sciences of the United States of America, Hirsch and colleagues show that metformin interferes with a signaling pathway, mediated by the transcription factor NF-κB, which drives cell transformation and is required for the maintenance of cancer stem cells. PMID:23510106

  1. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial.

    Science.gov (United States)

    Vega, Aurelio; Martín-Ferrero, Miguel Angel; Del Canto, Francisco; Alberca, Mercedes; García, Veronica; Munar, Anna; Orozco, Lluis; Soler, Robert; Fuertes, Juan Jose; Huguet, Marina; Sánchez, Ana; García-Sancho, Javier

    2015-08-01

    Osteoarthritis is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. Conventional treatments demonstrate only modest clinical benefits without lesion reversal. Autologous mesenchymal stromal cell (MSC) treatments have shown feasibility, safety, and strong indications for clinical efficacy. We performed a randomized, active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs, and we obtain information regarding the efficacy of this treatment. We randomized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients. The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 10(6) cells. The control group received intra-articular hyaluronic acid (60 mg, single dose). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping. Feasibility and safety were confirmed and indications of clinical efficacy were identified. The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid. Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas, with cartilage quality improvements in MSC-treated patients. Allogeneic MSC therapy may be a valid alternative for the treatment of chronic knee osteoarthritis that is more logistically convenient than autologous MSC treatment. The intervention is simple, does not require surgery, provides pain relief, and significantly improves cartilage quality.

  2. Geometrical versus Random β-TCP Scaffolds: Exploring the Effects on Schwann Cell Growth and Behavior.

    Directory of Open Access Journals (Sweden)

    Lauren Sweet

    Full Text Available Numerous studies have demonstrated that Schwann cells (SCs play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on β-tricalcium phosphate (β-TCP scaffolds arranged in 3D printed-lattice (P-β-TCP and randomly-porous, template-casted (N-β-TCP structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-β subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-β-TCP scaffolds, seen to a lesser degree in the N-β-TCP scaffold. The gene expressions of nerve growth factor (β-ngf, neutrophin-3 (nt-3, platelet-derived growth factor (pdgf-bb, and vascular endothelial growth factor (vegf-a were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the β-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.

  3. Geometrical versus Random β-TCP Scaffolds: Exploring the Effects on Schwann Cell Growth and Behavior.

    Science.gov (United States)

    Sweet, Lauren; Kang, Yunqing; Czisch, Christopher; Witek, Lukasz; Shi, Yang; Smay, Jim; Plant, Giles W; Yang, Yunzhi

    2015-01-01

    Numerous studies have demonstrated that Schwann cells (SCs) play a role in nerve regeneration; however, their role in innervating a bioceramic scaffold for potential application in bone regeneration is still unknown. Here we report the cell growth and functional behavior of SCs on β-tricalcium phosphate (β-TCP) scaffolds arranged in 3D printed-lattice (P-β-TCP) and randomly-porous, template-casted (N-β-TCP) structures. Our results indicate that SCs proliferated well and expressed the phenotypic markers p75LNGFR and the S100-β subunit of SCs as well as displayed growth morphology on both scaffolds, but SCs showed spindle-shaped morphology with a significant degree of SCs alignment on the P-β-TCP scaffolds, seen to a lesser degree in the N-β-TCP scaffold. The gene expressions of nerve growth factor (β-ngf), neutrophin-3 (nt-3), platelet-derived growth factor (pdgf-bb), and vascular endothelial growth factor (vegf-a) were higher at day 7 than at day 14. While no significant differences in protein secretion were measured between these last two time points, the scaffolds promoted the protein secretion at day 3 compared to that on the cell culture plates. These results together imply that the β-TCP scaffolds can support SC cell growth and that the 3D-printed scaffold appeared to significantly promote the alignment of SCs along the struts. Further studies are needed to investigate the early and late stage relationship between gene expression and protein secretion of SCs on the scaffolds with refined characteristics, thus better exploring the potential of SCs to support vascularization and innervation in synthetic bone grafts.

  4. The Gender Digital Divide in Developing Countries

    Directory of Open Access Journals (Sweden)

    Amy Antonio

    2014-10-01

    Full Text Available Empirical studies clearly show that women in the developing world have significantly lower technology participation rates than men; a result of entrenched socio-cultural attitudes about the role of women in society. However, as studies are beginning to show, when those women are able to engage with Internet technology, a wide range of personal, family and community benefits become possible. The key to these benefits is on-line education, the access to which sets up a positive feedback loop. This review gives an overview of the digital divide, before focusing specifically on the challenges women in developing countries face in accessing the Internet. Current gender disparities in Internet use will be outlined and the barriers that potentially hinder women’s access and participation in the online world will be considered. We will then look at the potential opportunities for women’s participation in a global digital society along with a consideration of current initiatives that have been developed to mitigate gender inequity in developing countries. We will also consider a promising avenue for future research.

  5. Quantitative Measurement of the Digital Divide

    Science.gov (United States)

    Cottrell, Roger

    2007-04-01

    Bandwidth and the Internet infrastructure are the life-blood of the world's knowledge economy, but they are often scarcest where most needed. Measuring the numbers of users of the Internet infrastructure is not easy in developing countries because many people share accounts, use corporate and academic networks, or visit the rapidly growing number of cyber cafes, telecentres and business services. Also measuring the number of users does not take into account the level of use. One valuable indicator for measuring the Internet infrastructure is the international Internet performance of a country or region. One of the major aims of the PingER project is to provide an historical archive of extensive, publicly accessible, up-to-date, measurements, analyses and reports of multiple Internet performance indicators (such as delay, loss, throughput, reachability, and jitter) between sites, countries and regions of the world. This talk will briefly describe the PingER project and then compare and contrast the Internet performance and its trends within and between countries and regions of the world. By means of extensive case studies it will also identify which regions need the greatest attention, together with their major issues and possible approaches to reducing the divide.

  6. The Digital Divide and urban older adults.

    Science.gov (United States)

    Cresci, M Kay; Yarandi, Hossein N; Morrell, Roger W

    2010-01-01

    Computers and the Internet offer older adults opportunities and resources for independent living. However, many urban older adults do not use computers. This study examined the demographic, health, and social activities of urban older adults to determine variables that might predict the use and nonuse of computers in this population. A secondary data analysis was performed using the 2001 Detroit City-Wide Needs Assessment of Older Adults (n = 1410) data set. Logistic regression was used to explore potential differences in predictor variables between computer users and nonusers. Overall, computer users were younger (27%), had a higher level of education, were more likely to be employed, had an annual income greater than $20,000, and were healthier and more active than nonusers. They also were more likely to have memberships in community organizations and do volunteer work. Preferred computer activities included conducting Internet searches, playing games, writing, and communicating with family members and friends. The results suggest significant differences in demographic and health-related characteristics between computer users and nonusers among urban older adults. Although about a quarter of participants in this study used computers, the Digital Divide continues to exist in urban settings for scores of others.

  7. Bridging the divide between science and journalism.

    Science.gov (United States)

    Van Eperen, Laura; Marincola, Francesco M; Strohm, Jennifer

    2010-03-10

    There are countless reasons nearly every scientist should learn how to communicate effectively with the media, including increased understanding of critical research findings to attract or sustain funding and build new professional partnerships that will further propel forward research. But where do scientists begin? Bridging the Divide between Science and Journalism offers practical tips for any scientist looking to work with the media.Given the traditional and internet-based sources for medical research and healthcare-related news now available, it is imperative that scientists know how to communicate their latest findings through the appropriate channels. The credible media channels are managed by working journalists, so learning how to package vast, technical research in a form that is appetizing and "bite-sized" in order to get their attention, is an art. Reducing years of research into a headline can be extremely difficult and certainly doesn't come naturally to every scientist, so this article provides suggestions on how to work with the media to communicate your findings.

  8. Bridging the Divide between Science and Journalism

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2010-03-01

    Full Text Available Abstract There are countless reasons nearly every scientist should learn how to communicate effectively with the media, including increased understanding of critical research findings to attract or sustain funding and build new professional partnerships that will further propel forward research. But where do scientists begin? Bridging the Divide between Science and Journalism offers practical tips for any scientist looking to work with the media. Given the traditional and internet-based sources for medical research and healthcare-related news now available, it is imperative that scientists know how to communicate their latest findings through the appropriate channels. The credible media channels are managed by working journalists, so learning how to package vast, technical research in a form that is appetizing and "bite-sized" in order to get their attention, is an art. Reducing years of research into a headline can be extremely difficult and certainly doesn't come naturally to every scientist, so this article provides suggestions on how to work with the media to communicate your findings.

  9. The private-public law divide

    DEFF Research Database (Denmark)

    Svendsen, Idamarie Leth; Kronborg, Annette; Gyldenløve Jeppesen-De Boer, Christina

    2013-01-01

    In a Scandinavian perspective, the family and the individual have changed places during the 20th Century. Today, the law takes its starting point in the individual - not in the family. A consequence of this development is that it is no longer legally possible to relate the good family to a partic......In a Scandinavian perspective, the family and the individual have changed places during the 20th Century. Today, the law takes its starting point in the individual - not in the family. A consequence of this development is that it is no longer legally possible to relate the good family...... to a particular societal institution. Marriage as an institution has been individualized and the goodness of the family has to relate to the well-being of the individuals instead. This article shows that within this historical development the private-public law divide has not been seriously challenged...... that the historical development neccessitates a re-thinking of the distinction between child welfare law and family law. It shows how the distinction is nationally and institutionally embedded. Further, that the distinction has only been superficially adressed by the CRC Committee....

  10. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa.

    Science.gov (United States)

    Birch, David G; Weleber, Richard G; Duncan, Jacque L; Jaffe, Glenn J; Tao, Weng

    2013-08-01

    To evaluate the safety and effect on visual function of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Ciliary neurotrophic factor for late-stage retinitis pigmentosa study 3 (CNTF3; n = 65) and ciliary neurotrophic factor for early-stage retinitis pigmentosa study 4 (CNTF4; n = 68) were multicenter, sham-controlled dose-ranging studies. Patients were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoints were change in best-corrected visual acuity (BCVA) at 12 months for CNTF3 and change in visual field sensitivity at 12 months for CNTF4. Patients had the choice of retaining or removing the implant at 12 months for CNTF3 and 24 months for CNTF4. There were no serious adverse events related to either the encapsulated cell implant or the surgical procedure. In CNTF3, there was no change in acuity in either ciliary neurotrophic factor- or sham-treated eyes at 1 year. In CNTF4, eyes treated with the high-dose implant showed a significant decrease in sensitivity while no change was seen in sham- and low dose-treated eyes at 12 months. The decrease in sensitivity was reversible upon implant removal. In both studies, ciliary neurotrophic factor treatment resulted in a dose-dependent increase in retinal thickness. Long-term intraocular delivery of ciliary neurotrophic factor is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit in the primary outcome variable. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. In vitro phospholipid biosynthesis for growing and dividing minimal cells

    NARCIS (Netherlands)

    Scott, A.D.D.

    2016-01-01

    Natural life is extraordinarily complex, which by definition means that it has many interconnected and functioning parts. The goal of synthetic biology is to engineer living systems, though due to their very complexity they remain recalcitrant to engineering. What if it were possible to reduce the

  12. Mechanisms of Mutation in Non-Dividing Cells

    Science.gov (United States)

    2003-05-01

    strains and plasmids formation in the TGV system (14). SMR5201, a transformant Strain or Reference carrying ampRC+ replacing attX (confirmed by PCR as de...6 0.895 1.4 structed using the TGV (transgenic vector) system for integrat- 7 1.69 1.4 ing linear DNA cassettes into the E. coli chromosome (14). E. I...negative bacteria: global trends and clinical impact. Clin. Infect. Dis. 15:824- berg. 2001. The TGV transgenic vectors for single-copy gene expression

  13. Electrohydrodynamic spinning of random-textured silver webs for electrodes embedded in flexible organic solar cells

    Science.gov (United States)

    Yoon, Dai Geon; Chin, Byung Doo; Bail, Robert

    2017-03-01

    A convenient process for fabricating a transparent conducting electrode on a flexible substrate is essential for numerous low-cost optoelectronic devices, including organic solar cells (OSCs), touch sensors, and free-form lighting applications. Solution-processed metal-nanowire arrays are attractive due to their low sheet resistance and optical clarity. However, the limited conductance at wire junctions and the rough surface topology still need improvement. Here, we present a facile process of electrohydrodynamic spinning using a silver (Ag) - polymer composite paste with high viscosity. Unlike the metal-nanofiber web formed by conventional electrospinning, a relatively thick, but still invisible-to-naked eye, Ag-web random pattern was formed on a glass substrate. The process parameters such as the nozzle diameter, voltage, flow rate, standoff height, and nozzle-scanning speed, were systematically engineered. The formed random texture Ag webs were embedded in a flexible substrate by in-situ photo-polymerization, release from the glass substrate, and post-annealing. OSCs with a donor-acceptor polymeric heterojunction photoactive layer were prepared on the Ag-web-embedded flexible films with various Ag-web densities. The short-circuit current and the power conversion efficiency of an OSC with a Ag-web-embedded electrode were not as high as those of the control sample with an indium-tin-oxide electrode. However, the Ag-web textures embedded in the OSC served well as electrodes when bent (6-mm radius), showing a power conversion efficiency of 2.06% (2.72% for the flat OSC), and the electrical stability of the Ag-web-textured patterns was maintained for up to 1,000 cycles of bending.

  14. Randomized controlled trial of expressive writing for patients with renal cell carcinoma.

    Science.gov (United States)

    Milbury, Kathrin; Spelman, Amy; Wood, Christopher; Matin, Surena F; Tannir, Nizar; Jonasch, Eric; Pisters, Louis; Wei, Qi; Cohen, Lorenzo

    2014-03-01

    This randomized controlled trial examined the quality-of-life benefits of an expressive writing (EW) intervention for patients with renal cell carcinoma (RCC) and identified a potential underlying mechanism of intervention efficacy. Patients (N = 277) with stage I to IV RCC were randomly assigned to write about their deepest thoughts and feelings regarding their cancer (EW) or about neutral topics (neutral writing [NW]) on four separate occasions. Patients completed the Center for Epidemiologic Studies Depression Scale (CES-D), MD Anderson Symptom Inventory (MDASI), Brief Fatigue Inventory (BFI), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Short Form-36 (SF-36), and Impact of Event Scale (IES) at baseline and 1, 4, and 10 months after the intervention. The mean age of participants (28% stage IV; 41% female) was 58 years. Multilevel modeling analyses, using a Bonferroni-corrected α = .021 for six outcomes adjusted for the correlation among outcomes, revealed that, relative to the NW group, patients in the EW group reported significantly lower MDASI scores (P = .003) and higher physical component summary scores on the SF-36 (P = .019) at 10 months after the intervention. Mediation analyses revealed that significant group differences for MDASI scores at 10 months were mediated by lower IES scores at 1 month after the intervention in the EW group (P = .042). No significant group differences were observed in the BFI, CES-D, PSQI, and mental component summary of the SF-36. EW may reduce cancer-related symptoms and improve physical functioning in patients with RCC. Evidence suggests that this effect may occur through short-term improvements in cognitive processing.

  15. Exercise training for people following curative intent treatment for non-small cell lung cancer: a randomized controlled trial ?

    OpenAIRE

    Cavalheri, Vinicius; Jenkins, Sue; Cecins, Nola; Gain, Kevin; Phillips, Martin J; Sanders, Lucas H.; Hill, Kylie

    2017-01-01

    Objective In people following curative intent treatment for non-small cell lung cancer, to investigate the effects of supervised exercise training on exercise capacity, physical activity and sedentary behavior, peripheral muscle force, health-related quality of life, fatigue, feelings of anxiety and depression, and lung function. Method This pilot randomized controlled trial included participants 6?10 weeks after lobectomy for non-small cell lung cancer or, for those who required adjuvant che...

  16. "Enlivening and - Dividing": An Aporia of Illumination

    Directory of Open Access Journals (Sweden)

    Hans Christian Hönes

    2015-08-01

    Full Text Available Normal 0 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Verdana;} In 1798, Karl August Böttiger paid a nocturnal visit to the Gallery of Antiques in Dresden, illuminating the statues with a torch. At first glance, this seems to be yet another example of a popular practice for visiting galleries c.1800. Illuminating the sculptures by torchlight was a popular means of enlivening the objects, set in motion by the light flickering on their surfaces. The collections were thus meant to become a place where cold, white stone comes to life, and where the beholder becomes part of a revived antiquity.This was precisely what Böttiger intended, too. But to him, the effect of the torchlight appeared to be, as he wrote, “enlivening and – dividing!” The torchlight highlighted not only the beauty of the sculptures but also their modern restorations. Böttiger apparently failed to experience the living presence of the antique celebrated by many of his contemporaries (e.g. Goethe, Moritz.This essay focuses on the consequence of such a perception of sculptures as historically multi-layered objects. Böttiger’s experience resulted in a problematic situation. In trying to view the sculptures as contemporaries, he hoped to become ancient himself. But this operation failed in the moment when the sculptures themselves appeared to be anachronistic, impure palimpsests. In consequence, galleries may not only be the place were art history as chronological Stilgeschichte was born. They may also be the site where this perception changed into the experience of a more chaotic shape of time.

  17. Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial

    NARCIS (Netherlands)

    Rhodes, Lesley E.; de Rie, Menno; Enström, Ylva; Groves, Richard; Morken, Tore; Goulden, Victoria; Wong, Gavin A. E.; Grob, Jean-Jacques; Varma, Sandeep; Wolf, Peter

    2004-01-01

    Photodynamic therapy (PDT) is increasingly used as a noninvasive treatment for nodular basal cell carcinoma (BCC), without a sound evidence base. To compare topical PDT, with the use of the sensitizer methyl aminolevulinate, and standard excision surgery in nodular BCC. Prospective, randomized

  18. Physical exercise for patients undergoing hematopoietic stem cell transplantation: systematic review and meta-analyses of randomized controlled trials

    NARCIS (Netherlands)

    Haren, I.E.P.M.; Timmerman, H.; Potting, C.M.J.; Blijlevens, N.M.A.; Staal, J.B.; Nijhuis-Van der Sanden, M.W.G.

    2013-01-01

    BACKGROUND: The treatment-related burden for patients undergoing hematopoietic stem cell transplantation (HSCT) may be relieved by physical exercises. PURPOSE: The purpose of this study was to summarize and analyze the evidence provided by randomized controlled trials (RCTs) on physical exercise

  19. Digital Divide and Social Media: Connectivity Doesn’t End the Digital Divide, Skills Do

    OpenAIRE

    Radovanovic, Danica

    2011-01-01

    Whether we like it or not, we live in a very unequal and stratified world. We live in societies in which inequality is ignored in education, science, and in the social media. As Internet technologies are rapidly evolving and new digital divides on the Internet emerge, we must move beyond, at some point, a singular concern over Internet access and technological infrastructure issues. We must tackle socio-cultural differences, we must focus on Internet skills, literacies and social media usage.

  20. Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

    Science.gov (United States)

    Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

    2015-12-15

    Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95

  1. Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Eduardo Lasalvia-Prisco

    2008-09-01

    Full Text Available Eduardo Lasalvia-Prisco1,4, Emilio Garcia-Giralt2, Jesús Vázquez2,4, Marta Aghazarian4, Eduardo Lasalvia-Galante3,4, Joshemaria Larrañaga3,4, Gonzalo Spera31Interdoctors Medical Procedures, North Miami Beach, FL, USA; 2Centre De Cancérologie Hartmann, Neuilly Sur Seine, France; 3Interdoctors Medical Procedures, Montevideo, Uruguay; 4National Institute of Oncology, Montevideo, Uruguay (initial dataAbstract: The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate, duration, median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a phytohemaglutinin-induced lymphocyte proliferation, b prevalence of T-Regulatory (CD4+CD25+ cells and for specific immunity: a lymphocyte proliferation induced by tumor-associated antigens (TAA contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy in response rate induced by the two treatments (39.0% and 35.0% was not statistically significant. However, the response duration (22 and 31 weeks, the median survival time (32

  2. The Escherichia coli divisome: born to divide.

    Science.gov (United States)

    Natale, Paolo; Pazos, Manuel; Vicente, Miguel

    2013-12-01

    Septation in Escherichia coli involves complex molecular mechanisms that contribute to the accuracy of bacterial division. The proto-ring, a complex made up by the FtsZ, FtsA and ZipA proteins, forms at the beginning of the process and directs the assembly of the full divisome. Central to this complex is the FtsZ protein, a GTPase able to assemble into a ring-like structure that responds to several modulatory inputs including mechanisms to position the septum at midcell. The connection with the cell wall synthesising machinery stabilizes the constriction of the cytoplasmic membrane. Although a substantial amount of evidence supports this description, many details on how individual divisome elements are structured or how they function are subjected to controversial interpretations. We discuss these discrepancies arising from incomplete data and from technical difficulties imposed by the small size of bacteria. Future work, including more powerful imaging and reconstruction technologies, will help to clarify the missing details on the architecture and function of the bacterial division machinery. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Design Optimization of Back-Gated Thin-Body Silicon-on-Insulator Capacitorless Dynamic Random Access Memory Cell

    Science.gov (United States)

    Cho, Min Hee; Shin, Changhwan; King Liu, Tsu-Jae

    2012-02-01

    Highly scaled (22 nm-node) capacitorless single-transistor dynamic random access memory (DRAM) cell design is investigated via technology computer-aided design (TCAD) simulations. It is found that the gate-sidewall spacer width and operating voltages can be adjusted to reduce band-to-band tunneling (BTBT) and thereby increase data retention time for bipolar junction transistor (BJT)-based operation. Read current variations due to random dopant fluctuations (RDF) are investigated via three-dimensional Kinetic Monte Carlo (KMC) simulations. It is found that BJT-based operation is more robust to RDF effects than metal-oxide-semiconductor field-effect transistor (MOSFET)-based operation.

  4. Gene repositioning within the cell nucleus is not random and is determined by its genomic neighborhood.

    Science.gov (United States)

    Jost, K Laurence; Bertulat, Bianca; Rapp, Alexander; Brero, Alessandro; Hardt, Tanja; Domaing, Petra; Gösele, Claudia; Schulz, Herbert; Hübner, Norbert; Cardoso, M Cristina

    2015-01-01

    Heterochromatin has been reported to be a major silencing compartment during development and differentiation. Prominent heterochromatin compartments are located at the nuclear periphery and inside the nucleus (e.g., pericentric heterochromatin). Whether the position of a gene in relation to some or all heterochromatin compartments matters remains a matter of debate, which we have addressed in this study. Answering this question demanded solving the technical challenges of 3D measurements and the large-scale morphological changes accompanying cellular differentiation. Here, we investigated the proximity effects of the nuclear periphery and pericentric heterochromatin on gene expression and additionally considered the effect of neighboring genomic features on a gene's nuclear position. Using a well-established myogenic in vitro differentiation system and a differentiation-independent heterochromatin remodeling system dependent on ectopic MeCP2 expression, we first identified genes with statistically significant expression changes by transcriptional profiling. We identified nuclear gene positions by 3D fluorescence in situ hybridization followed by 3D distance measurements toward constitutive and facultative heterochromatin domains. Single-cell-based normalization enabled us to acquire morphologically unbiased data and we finally correlated changes in gene positioning to changes in transcriptional profiles. We found no significant correlation of gene silencing and proximity to constitutive heterochromatin and a rather unexpected inverse correlation of gene activity and position relative to facultative heterochromatin at the nuclear periphery. In summary, our data question the hypothesis of heterochromatin as a general silencing compartment. Nonetheless, compared to a simulated random distribution, we found that genes are not randomly located within the nucleus. An analysis of neighboring genomic context revealed that gene location within the nucleus is rather

  5. Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors: results of a randomized crossover trial.

    Science.gov (United States)

    Pantin, Jeremy; Purev, Enkhtsetseg; Tian, Xin; Cook, Lisa; Donohue-Jerussi, Theresa; Cho, Elena; Reger, Robert; Hsieh, Matthew; Khuu, Hanh; Calandra, Gary; Geller, Nancy L; Childs, Richard W

    2017-03-01

    Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 μg/kg) plerixafor in CD34+ cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34+ count in the blood, with secondary endpoints of CD34+ cell area under the curve (AUC), CD34+ count at 24 hours, and time to peak CD34+ following the administration of plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of plerixafor. Peak CD34+ count in the blood was significantly increased (mean 32.2 versus 27.8 cells/μL, P=0.0009) and CD34+ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/μL, Phealthy donors and mobilizes greater numbers of CD34+ cells than conventional-dose plerixafor, which may improve CD34+ graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation. (ClinicalTrials.gov, identifier: NCT00322127). Copyright© Ferrata Storti Foundation.

  6. A Wide-Band CMOS Injection Locked Frequency Divider

    NARCIS (Netherlands)

    Acar, M.; Leenaerts, Domine; Nauta, Bram

    In this paper we propose a novel inductorless injection-locked frequency divider (ILFD) that can make divisions with ratios 2,4,6 and 8 with wide locking ranges. Fabricated in a digital 0.18 μm CMOS process the divider can operate up to 15 GHz. The measured locking ranges of the divider for division

  7. Bridging the digital divide: with special reference to Nigeria ...

    African Journals Online (AJOL)

    This paper describes the digital divide in Africa with special reference to Nigeria. It presents the causes of digital divided such as; the general poor economic conditions in Africa; local content; telecommunications constraints; lack of investment in ICT infrastructure, etc. Benefits derivable from bridging the digital divide such ...

  8. The digital divide as a complex and dynamic phenomenon

    NARCIS (Netherlands)

    van Dijk, Johannes A.G.M.; Hacker, Kenneth

    2003-01-01

    The purpose of this article is to propose a fruitful analytical framework for data supposedly related to the concept of the socalled “digital divide.” The extent and the nature of this divide depend on the kind of access defined. Considering the possession of hardware, growing divides among

  9. Divided attention and mental effort after severe traumatic brain injury.

    Science.gov (United States)

    Azouvi, Philippe; Couillet, Josette; Leclercq, Michel; Martin, Yves; Asloun, Sybille; Rousseaux, Marc

    2004-01-01

    The aim of this study was to assess dual-task performance in TBI patients, under different experimental conditions, with or without explicit emphasis on one of two tasks. Results were compared with measurement of the subjective mental effort required to perform each task. Forty-three severe TBI patients at the subacute or chronic phase performed two tasks under single- and dual-task conditions: (a) random generation; (b) visual go-no go reaction time task. Three dual-task conditions were given, requiring either to consider both tasks as equally important or to focus preferentially on one of them. Patients were compared to matched controls. Subjective mental effort was rated on a visual analogic scale. TBI patients showed a disproportionate increase in reaction time in the go-no go task under the dual-task condition. However, they were just as able as controls to adapt performance to the specific instructions about the task to be emphasised. Patients reported significantly higher subjective mental effort, but the variation of mental effort according to task condition was similar to that of controls. These results suggest that the divided attention deficit of TBI patients is related to a reduction in available processing resources rather than an impairment of strategic processes responsible for attentional allocation and switching. The higher level of subjective mental effort may explain why TBI patients frequently complain of mental fatigue, although this subjective complaint seems to be relatively independent of cognitive impairment.

  10. Music Therapy for Symptom Management After Autologous Stem Cell Transplantation: Results From a Randomized Study.

    Science.gov (United States)

    Bates, Debbie; Bolwell, Brian; Majhail, Navneet S; Rybicki, Lisa; Yurch, Melissa; Abounader, Donna; Kohuth, Joseph; Jarancik, Shannon; Koniarczyk, Heather; McLellan, Linda; Dabney, Jane; Lawrence, Christine; Gallagher, Lisa; Kalaycio, Matt; Sobecks, Ronald; Dean, Robert; Hill, Brian; Pohlman, Brad; Hamilton, Betty K; Gerds, Aaron T; Jagadeesh, Deepa; Liu, Hien D

    2017-09-01

    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day -1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  11. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    T. Eisen

    2014-08-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

  12. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    T. Eisen

    2009-01-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

  13. Research of the method of pseudo-random number generation based on asynchronous cellular automata with several active cells

    Directory of Open Access Journals (Sweden)

    Bilan Stepan

    2017-01-01

    Full Text Available To date, there are many tasks that are aimed at studying the dynamic changes in physical processes. These tasks do not give advance known result. The solution of such problems is based on the construction of a dynamic model of the object. Successful structural and functional implementation of the object model can give a positive result in time. This approach uses the task of constructing artificial biological objects. To solve such problems, pseudo-random number generators are used, which also find wide application for information protection tasks. Such generators should have good statistical properties and give a long repetition period of the generated pseudo-random bit sequence. This work is aimed at improving these characteristics. The paper considers the method of forming pseudo-random sequences of numbers on the basis of aperiodic cellular automata with two active cells. A pseudo-random number generator is proposed that generates three bit sequences. The first two bit sequences are formed by the corresponding two active cells in the cellular automaton. The third bit sequence is the result of executing the XOR function over the bits of the first two sequences and it has better characteristics compared to them. The use of cellular automata with two active cells allowed to improve the statistical properties of the formed bit sequence, as well as its repetition period. This is proved by using graphical tests for generators built based on cellular automata using the neighborhoods of von Neumann and Moore. The tests showed high efficiency of the generator based on an asynchronous cellular automaton with the neighborhood of Moore. The proposed pseudo-random number generators have good statistical properties, which makes it possible to use them in information security systems, as well as for simulation tasks of various dynamic processes.

  14. Introducing the RadBioStat Educational Software: Computer-Assisted Teaching of the Random Nature of Cell Killing

    Directory of Open Access Journals (Sweden)

    Safari A

    2014-06-01

    Full Text Available The interaction of radiation with cells and tissues has a random nature. Therefore, understanding the random nature of cell killing that is determined by Poisson distribution statistics is an essential point in education of radiation biology. RadBioStat is a newly developed educational MATLAB-based software designed for computer-assisted learning of the target theory in radiation biology. Although its potential applications is developing rapidly, currently RadBioStat software can be a useful tool in computerassisted education of radiobiological models such as single target single hit, multiple target single hit and multiple target multiple hit. Scholars’ feedback is valuable to the producers of this software and help them continuously improve this product, add new features and increase its desirability and functionality.

  15. Disclosing the Parameters Leading to High Productivity of Retroviral Producer Cells Lines: Evaluating Random Versus Targeted Integration.

    Science.gov (United States)

    Bandeira, Vanessa S; Tomás, Hélio A; Alici, Evren; Carrondo, Manuel J T; Coroadinha, Ana S

    2017-04-01

    Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination). The retroviral vector contains a thymidine kinase suicide gene fused with a ouabain-resistant Na + ,K + -ATPase gene, a potential safer and faster marker. The establishment of retroviral vector producer cells is traditionally performed by randomly integrating the retroviral vector expression cassette codifying the transgene. More recently, recombinase-mediated cassette exchange methodologies have been introduced to achieve targeted integration. Herein we compared random and targeted integration of the retroviral vector transgene construct. Two retroviral producer cell lines, 293 OuaS and 293 FlexOuaS, were generated by random and targeted integration, respectively, producing high titers (on the order of 10 7 infectious particles·ml -1 ). Results showed that the retroviral vector transgene cassette is the key retroviral vector component determining the viral titers notwithstanding, single-copy integration is sufficient to provide high titers. The expression levels of the three retroviral constructs (gag-pol, GaLV env, and retroviral vector transgene) were analyzed. Although gag-pol and GaLV env gene expression levels should surpass a minimal threshold, we found that relatively modest expression levels of these two expression cassettes are required. Their levels of

  16. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma: a Nordic Myeloma Study Group randomized phase 3 trial

    Science.gov (United States)

    Gimsing, Peter; Hjertner, Oyvind; Lenhoff, Stig; Laane, Edward; Remes, Kari; Steingrimsdottir, Hlif; Abildgaard, Niels; Ahlberg, Lucia; Blimark, Cecilie; Dahl, Inger Marie; Forsberg, Karin; Gedde-Dahl, Tobias; Gregersen, Henrik; Gruber, Astrid; Guldbrandsen, Nina; Haukås, Einar; Carlson, Kristina; Kvam, Ann Kristin; Nahi, Hareth; Lindås, Roald; Andersen, Niels Frost; Turesson, Ingemar; Waage, Anders; Westin, Jan; Gregersen, Henrik; Frost Andersen, Niels; Gimsing, Peter; Toffner-Clausen, Nilsaage; Abildgaard, Niels; Laane, Edward; Silvennoinen, Raija; Remes, Kari; Steingrimsdottir, Hlif; Lindås, Roald; Gedde-Dahl, Tobias; Guldbrandsen, Nina; Kristin Kvam, Ann; Haukås, Einar; Marie Dahl, Inger; Hjertner, Oyvind; Waage, Anders; Blimark, Cecilie; Mellqvist, Ulf-Henrik; Westin, Jan; Ahlberg, Lucia; Lenhoff, Stig; Turesson, Ingemar; Linder, Olle; Gruber, Astrid; Nahi, Hareth; Forsberg, Karin; Carlson, Kristina

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370 patients were centrally randomly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation. The hypothesis was that consolidation therapy would prolong progression-free survival (PFS). The PFS after randomization was 27 months for the bortezomib group compared with 20 months for the control group (P = .05). Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after randomization (P = .007). No difference in overall survival was seen. Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality-of-life (QOL) questionnaires, whereas no other major differences in QOL were recorded between the groups. Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response (VGPR) but not for patients in the ≥ VGPR category at randomization. Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL. This trial was registered at www.clinicaltrials.gov as #NCT00417911. PMID:23616624

  17. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  18. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy: a randomized controlled trial

    OpenAIRE

    Christensen, J F; Jones, L W; Tolver, A.; J?rgensen, L W; Andersen, J. L.; Adamsen, L; H?jman, P; Nielsen, R.H.; R?rth, M; Daugaard, G.

    2014-01-01

    Background: Bleomycin?etoposid?cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety and efficacy of resistance training to modulate these changes. Methods: Thirty GCC patients were randomly assigned to resistance training (resistance training group (INT), n=15) or usual care (CON, n=15) during 9 weeks...

  19. Low-level laser therapy prevents severe oral mucositis in patients submitted to hematopoietic stem cell transplantation: a randomized clinical trial.

    Science.gov (United States)

    Ferreira, Betânia; da Motta Silveira, Fabiana Moura; de Orange, Flávia Augusta

    2016-03-01

    The purpose of this study is to evaluate the effectiveness of low-level laser therapy for the prevention of oral mucositis in patients undergoing hematopoietic stem cell transplantation. This is a randomized, parallel, superiority trial including 35 patients divided into the following: laser (n = 17) and sham (n = 18). The variables assessed were oral mucositis (grade 2 of the World Health Organization oral toxicity scale), severe oral mucositis (grade 3 or 4), and pain (according to a visual analogue scale). In the laser group, a InGaAlP laser, wavelength of 650 nm, power 100 mW, energy per point of 2 J, time 20 s by point, extremity fiber optic 0.028 cm(2), and energy density 70 J/cm(2), was used, applied the first day of conditioning until D + 5, while the sham group received simulated laser over the same period. No statistically significant difference was found in the incidence of oral mucositis (p = 0.146). Severe mucositis was found in 40% of the patients (14/35), 3 in the intervention group (17.65%) and 11 in the sham group (61.11%) (p = 0.015). The cumulative probability of survival with respect to the development of severe oral mucositis was >0.6 for the intervention group and 0 for the control group (p = 0.0397). On the day on which pain was considered the worst, patients in the sham group were more likely to classify their pain as severe compared to those in the laser group (p = 0.041). Low-level laser therapy proved effective for the prevention of severe oral mucositis and intense oral pain in patients submitted to hematopoietic stem cell transplantation.

  20. Early diagnosis of recurrent diffuse large B-cell lymphoma showing intravascular lymphoma by random skin biopsy.

    Science.gov (United States)

    Kasuya, Akira; Hashizume, Hideo; Takigawa, Masahiro

    2011-06-01

    A 66-year-old man was admitted to our hospital presenting 2 weeks' history of fever of unknown origin with elevated levels of lactate dehydrogenase and C-reactive protein. Six years before this episode, he had developed diffuse large B-cell lymphoma, which had been successfully treated with chemoradiation. While recurrence of diffuse large B-cell lymphoma was suspected, there was neither lymphadenopathy nor tumor formation by the imaging study. Random biopsy from normal-appearing abdominal skin showed extensive infiltration of CD20(+), CD79a(+), CD3(-) atypical lymphoid cells in the lumen of vessels in subcutaneous tissues. These findings led us to the diagnosis of intravascular B-cell lymphoma. Following rituximab plus cyclophosphamide, adriamycin, vincristine and prednisolone therapy, high fever subsided, and lactate dehydrogenase and C-reactive protein levels returned to the normal range. In conclusion, random skin biopsy is useful for the early diagnosis of intravascular B-cell lymphoma. © 2010 Japanese Dermatological Association.

  1. Randomized phase 2 trial of regadenoson for treatment of acute vaso-occlusive crises in sickle cell disease.

    Science.gov (United States)

    Field, Joshua J; Majerus, Elaine; Gordeuk, Victor R; Gowhari, Michel; Hoppe, Carolyn; Heeney, Matthew M; Achebe, Maureen; George, Alex; Chu, Hillary; Sheehan, Brian; Puligandla, Maneka; Neuberg, Donna; Lin, Gene; Linden, Joel; Nathan, David G

    2017-09-12

    Adenosine A 2A receptor (A 2A R) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A 2A R agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A 2A R agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A 2A R agonist regadenoson (1.44 μg/kg per hour) to patients with SCD during VO crises to produce a plasma concentration of ∼5 nM, a concentration known from prior studies to suppress iNKT cell activation in SCD. The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to receive a 48-hour infusion of regadenoson or placebo, in addition to standard-of-care treatment, during hospital admission for a VO crisis and had analyzable iNKT cell samples. The proportion of subjects who demonstrated a reduction of >30% in activated iNKT cells was not significantly different between the regadenoson and placebo arms (43% vs 23%; P = .07). There were also no differences between regadenoson and placebo groups in length of hospital stay, mean total opioid use, or pain scores. These data demonstrate that a low-dose infusion of regadenoson intended to reduce the activity of iNKT cells is not sufficient to produce a statistically significant reduction in such activation or in measures of clinical efficacy. This trial was registered at www.clinicaltrials.gov as #NCT01788631.

  2. Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes

    NARCIS (Netherlands)

    Schepers, A.G.; Vries, R.G.J.; van den Born, M.M.W.; van de Wetering, M.L.; Clevers, H.

    2011-01-01

    Somatic cells have been proposed to be limited in the number of cell divisions they can undergo. This is thought to be a mechanism by which stem cells retain their integrity preventing disease. However, we have recently discovered intestinal crypt stem cells that persist for the lifetime of a mouse,

  3. A randomized double blind control trial comparing filgrastim and pegfilgrastim in cyclophosphamide peripheral blood hematopoietic stem cell mobilization.

    Science.gov (United States)

    Kuan, Jew-Win; Su, Anselm-Ting; Wong, Shu-Ping; Sim, Xavier Yoon-Han; Toh, See-Guan; Ong, Tee-Chuan; Rajasuriarr, Jay-Suria; Lim, Su-Hong; Guan, Yong-Khee; Liew, Hong-Keng; Liew, Pek-Kuen; Tan, Jerome Tsen-Chuen; Kori, Ahlam-Naila; Cheng, Yuin-Yin; Tan, Sen-Mui; Chang, Kian-Meng

    2015-10-01

    There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥ 2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Novel random peptide libraries displayed on AAV serotype 9 for selection of endothelial cell-directed gene transfer vectors.

    Science.gov (United States)

    Varadi, K; Michelfelder, S; Korff, T; Hecker, M; Trepel, M; Katus, H A; Kleinschmidt, J A; Müller, O J

    2012-08-01

    We have demonstrated the potential of random peptide libraries displayed on adeno-associated virus (AAV)2 to select for AAV2 vectors with improved efficiency for cell type-directed gene transfer. AAV9, however, may have advantages over AAV2 because of a lower prevalence of neutralizing antibodies in humans and more efficient gene transfer in vivo. Here we provide evidence that random peptide libraries can be displayed on AAV9 and can be utilized to select for AAV9 capsids redirected to the cell type of interest. We generated an AAV9 peptide display library, which ensures that the displayed peptides correspond to the packaged genomes and performed four consecutive selection rounds on human coronary artery endothelial cells in vitro. This screening yielded AAV9 library capsids with distinct peptide motifs enabling up to 40-fold improved transduction efficiencies compared with wild-type (wt) AAV9 vectors. Incorporating sequences selected from AAV9 libraries into AAV2 capsids could not increase transduction as efficiently as in the AAV9 context. To analyze the potential on endothelial cells in the intact natural vascular context, human umbilical veins were incubated with the selected AAV in situ and endothelial cells were isolated. Fluorescence-activated cell sorting analysis revealed a 200-fold improved transduction efficiency compared with wt AAV9 vectors. Furthermore, AAV9 vectors with targeting sequences selected from AAV9 libraries revealed an increased transduction efficiency in the presence of human intravenous immunoglobulins, suggesting a reduced immunogenicity. We conclude that our novel AAV9 peptide library is functional and can be used to select for vectors for future preclinical and clinical gene transfer applications.

  5. 37 CFR 2.87 - Dividing an application.

    Science.gov (United States)

    2010-07-01

    .... (1) When the International Bureau of the World Intellectual Property Organization notifies the Office... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Classification § 2.87 Dividing an application. (a... accordance with paragraph (d) of this section. (b) Fee. In the case of a request to divide out one or more...

  6. The Digital Divide and University Education Systems in Sub ...

    African Journals Online (AJOL)

    This paper examined the concept of the digital divide, how the divide can relegate Africa to the background and how a transformed tertiary educational system can help to minimise the bridge between the information-rich countries of the North and the information-poor African countries. It is argued that if the barriers to ...

  7. Digital Natives and Digital Divide: Analysing Perspective for Emerging Pedagogy

    Science.gov (United States)

    Onye, Uriel U.; Du, Yunfei

    2016-01-01

    This paper addresses the concepts of digital natives and digital divide from the perspective of the digital outsiders (part of digital natives). It takes a critical look at the implications of available ICT in both developed and underdeveloped countries in the fight against digital divide. The major contribution to literature is by drawing…

  8. 7 CFR 800.163 - Divided-lot certificates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Divided-lot certificates. 800.163 Section 800.163... Certificates § 800.163 Divided-lot certificates. (a) General. When shiplot grain is offered for inspection or Class X weighing as a single lot and is certificated as a single lot, the applicant may exchange the...

  9. 7 CFR 868.74 - Divided-lot certificates.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Divided-lot certificates. 868.74 Section 868.74... FOR CERTAIN AGRICULTURAL COMMODITIES Regulations Official Certificates § 868.74 Divided-lot certificates. (a) General. When commodities are offered for inspection and are certificated as a single lot...

  10. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma

    NARCIS (Netherlands)

    Rhodes, Lesley E.; de Rie, Menno A.; Leifsdottir, Ragna; Yu, Raymond C.; Bachmann, Ingeborg; Goulden, Victoria; Wong, Gavin A. E.; Richard, Marie-Aleth; Anstey, Alex; Wolf, Peter

    2007-01-01

    To compare 5-year lesion recurrence rates in primary nodular basal cell carcinoma treated with topical methyl aminolevulinate photodynamic therapy (PDT) or simple excision surgery. Prospective, randomized, multicenter study. University hospital dermatology departments. A total of 97 patients, 50

  11. The Relativity of Sociodemographic Determinism on the Digital Divide in High School Students in Ecuador

    OpenAIRE

    Tirado Morueta, Ramón; Mendoza Zambrano, Damian Marilú; Marín Gutiérrez, Isidro; Mendoza Zambrano, Mariuxi

    2017-01-01

    Although the digital divide on physical access to the Internet in developing countries is closing with respect to developed countries, a new gap on the social usage of the Internet is opening. This study focuses on Ecuador for the purpose of (a) determining the level of access to Internet use of the younger sector of the population (high school students) and (b) understanding to what extent sociodemographic factors determine Internet access and its use. This study uses a random sample (3,754 ...

  12. [Design of broadband power divider in microwave hyperthermia system].

    Science.gov (United States)

    Sun, Bing; Jiang, Guotai; Lu, Xiaofeng; Cao, Yi

    2010-10-01

    In clinical application of microwave hyperthermia, multi-applicators are often simultaneously required to irradiate the tumor because of its large volume or its deep location. Power divider separates the input microwave energy into equal, or unequal, energy to each applicator. In this paper, the design procedure for the three-section transmission-line transformer based one-to-two equal-split Wilkinson power divider is introduced. By impedance analysis on equivalent scheme, the design parameter of power divider is provided, and by simulation and optimization on Ansoft HFSS, a microstrip structure Wilkinson power divider operating frequency 2. 45 GHz is given. Measurement test results from network analyzer show that it has 25% bandwidth and good isolation in output with this structure. Besides, it is characterized by small size and easy processing. This power divider suits microwave hyperthermia.

  13. Data on the recurrence of breast tumors fit a model in which dormant cells are subject to slow attrition but can randomly awaken to become malignant

    DEFF Research Database (Denmark)

    Stein, Wilfred D; Litman, Thomas

    2006-01-01

    by the body's immune system, or by random apoptosis or senescence. (iv) Recurrence suppressor mechanisms exist. (v) When such genes are disabled by random mutations, the dormant metastatic cell is activated, and will develop to a cancer recurrence. The model was also fitted to data on the survival......We successfully modeled the recurrence of tumors in breast cancer patients, assuming that: (i) A breast cancer patient is likely to have some circulating metastatic cells, even after initial surgery. (ii) These metastatic cells are dormant. (iii) The dormant cells are subject to attrition...

  14. Efficacy and safety of autologous cell therapies for knee cartilage defects (autologous stem cells, chondrocytes or the two): randomized controlled trial design.

    Science.gov (United States)

    Richardson, James B; Wright, Karina T; Wales, Johanna; Kuiper, Jan Herman; McCarthy, Helen S; Gallacher, Peter; Harrison, Paul E; Roberts, Sally

    2017-07-01

    The main aim of this trial is to test the safety and efficacy of autologous stromal/stem cells, chondrocytes or the two combined in the treatment of knee cartilage defects. Patients with symptomatic chondral/osteochondral defects will be randomized to cell therapy treatment with one of three cell populations (1:1:1). The primary efficacy outcome is a functional knee score (Lysholm) at 15 months post-treatment and the primary safety outcome is the incidence of adverse events. Secondary objectives are to analyze repair tissues, quality of life and cost-utility assessments. Exploratory objectives are to identify predictors for success/potency and dose-response relationships. This trial has been carefully designed so that valuable scientific and clinical information can be gathered throughout and in the final analysis.

  15. Exercise training for people following curative intent treatment for non-small cell lung cancer: a randomized controlled trial.

    Science.gov (United States)

    Cavalheri, Vinicius; Jenkins, Sue; Cecins, Nola; Gain, Kevin; Phillips, Martin J; Sanders, Lucas H; Hill, Kylie

    In people following curative intent treatment for non-small cell lung cancer, to investigate the effects of supervised exercise training on exercise capacity, physical activity and sedentary behavior, peripheral muscle force, health-related quality of life, fatigue, feelings of anxiety and depression, and lung function. This pilot randomized controlled trial included participants 6-10 weeks after lobectomy for non-small cell lung cancer or, for those who required adjuvant chemotherapy, 4-8 weeks after their last cycle. Participants were randomized to either 8 weeks of supervised exercise training (exercise group) or 8 weeks of usual care (control group). Prior to and following the intervention period, both groups completed measurements of exercise capacity, physical activity and sedentary behavior, quadriceps and handgrip force, HRQoL, fatigue, feelings of anxiety and depression, and lung function. Intention-to-treat analysis was undertaken. Seventeen participants (mean age 67, SD=9 years; 12 females) were included. Nine and eight participants were randomized to the exercise and control groups, respectively. Four participants (44%) adhered to exercise training. Compared with any change seen in the control group, those in the exercise group demonstrated greater gains in the peak rate of oxygen consumption (mean difference, 95% confidence interval for between-group difference: 0.19 [0.04-0.33]Lmin(-1)) and 6-minute walk distance (52 [12-93]m). No other between-group differences were demonstrated. In people following curative intent treatment for non-small cell lung cancer, 8 weeks of supervised exercise training improved exercise capacity, measured by both laboratory- and field-based exercise tests. These results suggest that this clinical population may benefit from attending exercise training programs. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. Simulation of microgravity by magnetic levitation and random positioning: Effect on human A431 cell morphology

    NARCIS (Netherlands)

    Moes, M.J.A.; Gielen, J.C.; Bleichrodt, R.J.; van Loon, J.J.W.A.; Christianen, P.C.M.; Boonstra, J.

    2011-01-01

    Simulation of weightlessness is a desired replenishment for research in microgravity since access to space flights is limited. In real microgravity conditions, the human epidermoid cell line A431 exhibits specific changes in the actin cytoskeleton resulting ultimately in the rounding-up of cells.

  17. The digital divide as a complex and dynamic phenomenon

    OpenAIRE

    van Dijk, Johannes A.G.M.; Hacker, Kenneth

    2003-01-01

    The purpose of this article is to propose a fruitful analytical framework for data supposedly related to the concept of the socalled “digital divide.” The extent and the nature of this divide depend on the kind of access defined. Considering the possession of hardware, growing divides among different categories of income, employment, education, age, and ethnicity can be proved to have existed in the 1980s and 1990s according to official American and Dutch statistics. If only by effects of sat...

  18. Impact of usability on efforts to bridge the digital divide

    CSIR Research Space (South Africa)

    Adebesin, F

    2010-11-01

    Full Text Available to Bridge the Digital Divide Funmi Adebesin Meraka Institute of the CSIR and School of Computing, UNISA P.O. Box 395 Pretoria, 0001, South Africa fadebesin@csir.co.za Paula Kotzé Meraka Institute of the CSIR and School of Computing, UNISA P.O. Box.... To address the problem, international and national initiatives are ongoing to provide access to technologies with the aim of bridging the digital divide. Many of the efforts to narrow the divide have been concerned with the provision of physical...

  19. A novel multiplexer-based structure for random access memory cell in quantum-dot cellular automata

    Science.gov (United States)

    Naji Asfestani, Mazaher; Rasouli Heikalabad, Saeed

    2017-09-01

    Quantum-dot cellular automata (QCA) is a new technology in scale of nano and perfect replacement for CMOS circuits in the future. Memory is one of the basic components in any digital system, so designing the random access memory (RAM) with high speed and optimal in QCA is important. In this paper, by employing the structure of multiplexer, a novel RAM cell architecture is proposed. The proposed architecture is implemented without the coplanar crossover approach. The proposed architecture is simulated using the QCADesigner version 2.0.3 and QCAPro. The simulation results demonstrate that the proposed QCA RAM architecture has the best performance in terms of delay, circuit complexity, area, cell count and energy consumption in comparison with other QCA RAM architectures.

  20. Efficient light trapping in inverted polymer solar cells by a randomly nanostructured electrode using monodispersed polymer nanoparticles.

    Science.gov (United States)

    Kang, Dong Jin; Kang, Hyunbum; Cho, Changsoon; Kim, Ki-Hyun; Jeong, Seonju; Lee, Jung-Yong; Kim, Bumjoon J

    2013-03-07

    The randomly nanotextured back electrode provides a simple and efficient route for enhancing photocurrent in polymer solar cells (PSCs) by light trapping, which can increase light absorption within a finite thickness of the active layer. In this study, we incorporated mono-disperse 60 nm polystyrene nanoparticles (PS NPs) into a 50 nm thick poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) anode buffer layer (ABL) to create a randomly nanotextured back electrode with 10 nm height variations in inverted-type PSCs. The roughened interface between the PS NP-PEDOT:PSS ABL and the Ag electrode scatters light in the visible range, leading to efficient light trapping within the device and enhanced light absorption in the active layer. Inverted PSCs with randomly nanotextured electrodes (φ(NP) = 0.31) showed short-circuit current density (J(SC)) and power conversion efficiency (PCE) values that were 15% higher than those of control devices with flat electrodes. External quantum efficiency, reflectance, and optical light scattering as a function of ϕ(NP) were examined to determine the origin of the enhancement in J(SC) and PCE.

  1. Mesenchymal stem cells versus mesenchymal stem cells combined with cord blood for engraftment failure after autologous hematopoietic stem cell transplantation: a pilot prospective, open-label, randomized trial.

    Science.gov (United States)

    Xiong, Yi-Ying; Fan, Qian; Huang, Fen; Zhang, Yu; Wang, Yu; Chen, Xiao-Yong; Fan, Zhi-Ping; Zhou, Hong-Sheng; Xiao, Yang; Xu, Xiao-Jun; Dai, Min; Xu, Na; Sun, Jing; Xiang, Peng; Huang, Xiao-Jun; Liu, Qi-Fa

    2014-02-01

    Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Lifestyle intervention using an internet-based curriculum with cell phone reminders for obese Chinese teens: a randomized controlled study.

    Directory of Open Access Journals (Sweden)

    Anisha A Abraham

    Full Text Available Obesity is an increasing public health problem affecting young people. The causes of obesity are multi-factorial among Chinese youth including lack of physical activity and poor eating habits. The use of an internet curriculum and cell phone reminders and texting may be an innovative means of increasing follow up and compliance with obese teens. The objectives of this study were to determine the feasibility of using an adapted internet curriculum and existing nutritional program along with cell phone follow up for obese Chinese teens.This was a randomized controlled study involving obese teens receiving care at a paediatric obesity clinic of a tertiary care hospital in Hong Kong. Forty-eight subjects aged 12 to 18 years were randomized into three groups. The control group received usual care visits with a physician in the obesity clinic every three months. The first intervention (IT group received usual care visits every three months plus a 12-week internet-based curriculum with cell phone calls/texts reminders. The second intervention group received usual care visits every three months plus four nutritional counselling sessions.The use of the internet-based curriculum was shown to be feasible as evidenced by the high recruitment rate, internet log-in rate, compliance with completing the curriculum and responses to phone reminders. No significant differences in weight were found between IT, sLMP and control groups.An internet-based curriculum with cell phone reminders as a supplement to usual care of obesity is feasible. Further study is required to determine whether an internet plus text intervention can be both an effective and a cost-effective adjunct to changing weight in obese youth.Chinese Clinical Trial Registry ChiCTR-TRC-12002624.

  3. Alternating Treatment With Pazopanib and Everolimus vs Continuous Pazopanib to Delay Disease Progression in Patients With Metastatic Clear Cell Renal Cell Cancer: The ROPETAR Randomized Clinical Trial.

    Science.gov (United States)

    Cirkel, Geert A; Hamberg, Paul; Sleijfer, Stefan; Loosveld, Olaf J L; Dercksen, M Wouter; Los, Maartje; Polee, Marco B; van den Berkmortel, Franchette; Aarts, Maureen J; Beerepoot, Laurens V; Groenewegen, Gerard; Lolkema, Martijn P; Tascilar, Metin; Portielje, Johanna E A; Peters, Frank P J; Klümpen, Heinz-Josef; van der Noort, Vincent; Haanen, John B A G; Voest, Emile E

    2017-04-01

    To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. This was an open-label, randomized (1:1) study (ROPETAR trial). In total, 101 patients with treatment-naive progressive metastatic clear cell renal cell carcinoma were enrolled between September 2012 and April 2014 from 17 large peripheral or academic hospitals in The Netherlands and followed for at least one year. First-line treatment consisted of either an 8-week alternating treatment schedule of pazopanib 800 mg/d and everolimus 10 mg/d (rotating arm) or continuous pazopanib 800 mg/d (control arm) until progression. After progression, patients made a final rotation to either pazopanib or everolimus monotherapy (rotating arm) or initiated everolimus (control arm). The primary end point was survival until first progression or death. Secondary end points included time to second progression or death, toxic effects, and quality of life. A total of 52 patients were randomized to the rotating arm (median [range] age, 65 [44-87] years) and 49 patients to the control arm (median [range] age, 67 [38-82] years). Memorial Sloan Kettering Cancer Center risk category was favorable in 26% of patients, intermediate in 58%, and poor in 15%. Baseline characteristics and risk categories were well balanced between arms. One-year PFS1 for rotating treatment was 45% (95% CI, 33-60) and 32% (95% CI, 21-49) for pazopanib (control). Median time until first progression or death for rotating treatment was 7.4 months (95% CI, 5.6-18.4) and 9.4 months (95% CI, 6.6-11.9) for pazopanib (control) (P = .37). Mucositis, anorexia, and dizziness were more prevalent in

  4. Annan warns of 'content divide' between rich and poor

    CERN Multimedia

    Dickson, D

    2003-01-01

    "The Secretary-General of the United Nations, Kofi Annan, warned today (10 December) that a "content divide" is threatening to deprive developing countries of the full benefits offered by information and communications technologies (ICTs)" (1 page)

  5. Methane Isotopes from the WAIS Divide Ice Core, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes methane (CH4) isotope data from the West Antarctic Ice Sheet (WAIS) Divide ice core, WDC05A, in Antarctica. The data include depth, gas age,...

  6. The information divide: publishing and access issues | Baker ...

    African Journals Online (AJOL)

    information as commodity\\". Some global and local developments in information access and the Open Access movement are highlighted, and the National Library of South Africa\\'s interim strategies to bridge the information and digital divide are identified ...

  7. Continental Divide of the United States - Direct Download

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This map layer portrays the Continental Divide of the United States. The map layer was created by extracting Hydrologic Unit Boundary line features from an existing...

  8. Divided attention: an undesirable difficulty in memory retention.

    Science.gov (United States)

    Gaspelin, Nicholas; Ruthruff, Eric; Pashler, Harold

    2013-10-01

    How can we improve memory retention? A large body of research has suggested that difficulty encountered during learning, such as when practice sessions are distributed rather than massed, can enhance later memory performance (see R. A. Bjork & E. L. Bjork, 1992). Here, we investigated whether divided attention during retrieval practice can also constitute a desirable difficulty. Following two initial study phases and one test phase with Swahili-English word pairs (e.g., vuvi-snake), we manipulated whether items were tested again under full or divided attention. Two days later, participants were brought back for a final cued-recall test (e.g., vuvi-?). Across three experiments (combined N = 122), we found no evidence that dividing attention while practicing retrieval enhances memory retention. This finding raises the question of why many types of difficulty during practice do improve long-term retention, but dividing attention does not.

  9. Divide-and-conquer approach for the exemplar breakpoint distance

    National Research Council Canada - National Science Library

    Nguyen, C Thach; Tay, Y C; Zhang, Louxin

    2005-01-01

    .... Unfortunately, the problem is NP-hard even for the breakpoint distance. This paper proposes a divide-and-conquer approach for calculating the exemplar breakpoint distance between two genomes with multiple gene families...

  10. Justifying the Classical-Quantum Divide of the Copenhagen Interpretation

    OpenAIRE

    Bolotin, Arkady

    2014-01-01

    Perhaps the most significant drawback, which the Copenhagen interpretation (still the most popular interpretation of quantum theory) suffers from, is the classical-quantum divide between the large classical systems that carry out measurements and the small quantum systems that they measure. So, an "ideal" alternative interpretation of quantum theory would either eliminate this divide or justify it in some reasonable way. The present paper demonstrates that it is possible to justify the classi...

  11. The road to sustainability must bridge three great divides.

    Science.gov (United States)

    Aronson, James; Blignaut, James N; de Groot, Rudolf S; Clewell, Andre; Lowry, Porter P; Woodworth, Paddy; Cowling, Richard M; Renison, Daniel; Farley, Joshua; Fontaine, Christelle; Tongway, David; Levy, Samuel; Milton, Suzanne J; Rangel, Orlando; Debrincat, Bev; Birkinshaw, Chris

    2010-01-01

    The world's large and rapidly growing human population is exhausting Earth's natural capital at ever-faster rates, and yet appears mostly oblivious to the fact that these resources are limited. This is dangerous for our well-being and perhaps for our survival, as documented by numerous studies over many years. Why are we not moving instead toward sustainable levels of use? We argue here that this disconnection between our knowledge and our actions is largely caused by three "great divides": an ideological divide between economists and ecologists; an economic development divide between the rich and the poor; and an information divide, which obstructs communications between scientists, public opinion, and policy makers. These divides prevent our economies from responding effectively to urgent signals of environmental and ecological stress. The restoration of natural capital (RNC) can be an important strategy in bridging all of these divides. RNC projects and programs make explicit the multiple and mutually reinforcing linkages between environmental and economic well-being, while opening up a promising policy road in the search for a sustainable and desirable future for global society. The bridge-building capacity of RNC derives from its double focus: on the ecological restoration of degraded, overexploited natural ecosystems, and on the full socio-economic and ecological interface between people and their environments.

  12. Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Stephen R. [Environmental Toxicology Graduate Program, Department of Cell Biology and Neuroscience, University of California, Riverside, CA (United States); Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire (United Kingdom); Papworth, David [Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire (United Kingdom); Grosovsky, Andrew J. [Environmental Toxicology Graduate Program, Department of Cell Biology and Neuroscience, University of California, Riverside, CA (United States)]. E-mail: Grosovsky@ucr.edu

    2006-08-30

    Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p < 0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p < 0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p = 0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms.

  13. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial

    NARCIS (Netherlands)

    Hunt, P.W.; Shulman, N.S.; Hayes, T.L.; Dahl, V.; Somsouk, M.; Funderburg, N.T.; McLaughlin, B.; Landay, A.L.; Adeyemi, O.; Gilman, L.E.; Clagett, B.; Rodriguez, B.; Martin, J.N.; Schacker, T.W.; Shacklett, B.L.; Palmer, S.; Lederman, M.M.; Deeks, S.G.

    2013-01-01

    The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm(3) and plasma HIV

  14. Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

    Directory of Open Access Journals (Sweden)

    Aribi Mourad

    2010-01-01

    Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

  15. Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial.

    Science.gov (United States)

    Badaki-Makun, Oluwakemi; Scott, J Paul; Panepinto, Julie A; Casper, T Charles; Hillery, Cheryl A; Dean, J Michael; Brousseau, David C

    2014-06-01

    Multiple recent Sickle Cell Disease studies have been terminated due to poor enrollment. We developed methods to overcome past barriers and utilized these to study the efficacy and safety of intravenous magnesium for vaso-occlusive crisis (VOC). We describe the methods of the Intravenous Magnesium in Sickle Vaso-occlusive Crisis (MAGiC) trial and discuss methods used to overcome past barriers. MAGiC was a multi-center randomized double-blind placebo-controlled trial of intravenous magnesium versus normal saline for treatment of VOC. The study was a collaboration between Pediatric Hematologists and Emergency Physicians in the Pediatric Emergency Care Applied Research Network (PECARN). Eligible patients were randomized within 12 hours of receiving intravenous opioids in the Emergency Department (ED) and administered study medication every 8 hours. The primary outcome was hospital length of stay. Associated plasma studies elucidated magnesium's mechanism of action and the pathophysiology of VOC. Health-related quality of life was measured. Site-, protocol-, and patient-related barriers from prior studies were identified and addressed. Limited study staff availability, lack of collaboration with the ED, and difficulty obtaining consent were previously identified barriers. Leveraging PECARN resources, forging close collaborations between Sickle Cell Centers and EDs of participating sites, and approaching eligible patients for prior consent helped overcome these barriers. Participation in the PECARN network and establishment of collaborative arrangements between Sickle Cell Centers and their affiliated EDs are major innovative features of the MAGiC study that allowed improved subject capture. These methods could serve as a model for future studies of VOCs. © 2014 Wiley Periodicals, Inc.

  16. The VOLMAX Transient Electromagnetic Modeling System, Including Sub-Cell Slots and Wires on Random Non-Orthogonal Cells

    Energy Technology Data Exchange (ETDEWEB)

    Riley, D.J.; Turner, C.D.

    1997-12-31

    VOLMAX is a three-dimensional transient volumetric Maxwell equation solver that operates on standard rectilinear finite-difference time-domain (FDTD) grids, non-orthogonal unstructured grids, or a combination of both types (hybrid grids). The algorithm is fully explicit. Open geometries are typically solved by embedding multiple unstructured regions into a simple rectilinear FDTD mesh. The grid types are fully connected at the mesh interfaces without the need for complex spatial interpolation. The approach permits detailed modeling of complex geometry while mitigating the large cell count typical of non-orthogonal cells such as tetrahedral elements. To further improve efficiency, the unstructured region carries a separate time step that sub-cycles relative to the time-step used in the FDTD mesh.

  17. The effect of divided attention on novices and experts in laparoscopic task performance.

    Science.gov (United States)

    Ghazanfar, Mudassar Ali; Cook, Malcolm; Tang, Benjie; Tait, Iain; Alijani, Afshin

    2015-03-01

    Attention is important for the skilful execution of surgery. The surgeon's attention during surgery is divided between surgery and outside distractions. The effect of this divided attention has not been well studied previously. We aimed to compare the effect of dividing attention of novices and experts on a laparoscopic task performance. Following ethical approval, 25 novices and 9 expert surgeons performed a standardised peg transfer task in a laboratory setup under three randomly assigned conditions: silent as control condition and two standardised auditory distracting tasks requiring response (easy and difficult) as study conditions. Human reliability assessment was used for surgical task analysis. Primary outcome measures were correct auditory responses, task time, number of surgical errors and instrument movements. Secondary outcome measures included error rate, error probability and hand specific differences. Non-parametric statistics were used for data analysis. 21109 movements and 9036 total errors were analysed. Novices had increased mean task completion time (seconds) (171 ± 44SD vs. 149 ± 34, p 0.05). Divided attention conditions in theatre environment require careful consideration during surgical training as the junior surgeons are less able to focus their attention during these conditions.

  18. Is there a second level divide in students Internet skills?

    DEFF Research Database (Denmark)

    Dau, Susanne; Purushothaman, Aparna

    2015-01-01

    The concept of digital divide have moved beyond physical disparities in usage and also encompasses issues impending access like human (skills) social, cultural, and psychological barriers that affect the usage of existing available technologies apart from ownership. This paper focuses on the insu......The concept of digital divide have moved beyond physical disparities in usage and also encompasses issues impending access like human (skills) social, cultural, and psychological barriers that affect the usage of existing available technologies apart from ownership. This paper focuses...... on the insufficient level of skills which students have in making the best use of available Internet technology. Varying online skills of the students in higher education from two countrywide scenarios - Denmark and India are discussed. The paper emphasizes on the reflective and conceptual issues which the students...... face to take information from the Internet that brings a second level of divide. Through a cross-national comparison the paper hopes to contribute to the literature to learn from each other´s experiences and giving insights to researchers on digital divide. The digital divide in Internet skills...

  19. Effects of total sleep deprivation on divided attention performance.

    Directory of Open Access Journals (Sweden)

    Eric Chern-Pin Chua

    Full Text Available Dividing attention across two tasks performed simultaneously usually results in impaired performance on one or both tasks. Most studies have found no difference in the dual-task cost of dividing attention in rested and sleep-deprived states. We hypothesized that, for a divided attention task that is highly cognitively-demanding, performance would show greater impairment during exposure to sleep deprivation. A group of 30 healthy males aged 21-30 years was exposed to 40 h of continuous wakefulness in a laboratory setting. Every 2 h, subjects completed a divided attention task comprising 3 blocks in which an auditory Go/No-Go task was 1 performed alone (single task; 2 performed simultaneously with a visual Go/No-Go task (dual task; and 3 performed simultaneously with both a visual Go/No-Go task and a visually-guided motor tracking task (triple task. Performance on all tasks showed substantial deterioration during exposure to sleep deprivation. A significant interaction was observed between task load and time since wake on auditory Go/No-Go task performance, with greater impairment in response times and accuracy during extended wakefulness. Our results suggest that the ability to divide attention between multiple tasks is impaired during exposure to sleep deprivation. These findings have potential implications for occupations that require multi-tasking combined with long work hours and exposure to sleep loss.

  20. Investigation on Locking and Pulling Modes in Analog Frequency Dividers

    Directory of Open Access Journals (Sweden)

    Antonio Buonomo

    2013-01-01

    Full Text Available We compare the main analytical results available to estimate the locking range, which is the key figure-of-merit of LC frequency dividers based on the injection locking phenomenon. Starting from the classical result by Adler concerning injection-locked oscillators, we elucidate the merits and the shortcomings of the different approaches to study injection-locked frequency dividers, with particular emphasis on divider-by-2. In particular, we show the potential of a perturbation approach which enables a more complete analysis of frequency dividers, making it possible to calculate not only the amplitude and the phase of the locked oscillation, but also the region where it exists and is stable, which defines the locking region. Finally, we analyze the dynamical behaviour of the dividers in the vicinity of the boundary of the locking region, showing that there exists a border region where the occurrence of the locking or the pulling operation mode is possible, depending on the initial conditions of the system.

  1. Romania's Digital Divide and the Failures of E-Government

    Directory of Open Access Journals (Sweden)

    Sorin Dan ŞANDOR

    2006-02-01

    Full Text Available This paper tries to measure the level of the digital divide existing in Romania and also to verify its relationship with e-government. At the country level, Romania is one of the least digitally developed countries in Europe, but it has shown a sharp increase in recent years. At the social level, based on data from public opinion surveys, digital divide is analyzed at two levels: lack of access and lack of knowledge. The results are similar to those in other countries: digital divide appears along the same dimensions: rural/urban, age, education, wealth and, to a lesser extent, gender. E-government services, while presumed to be at an adequate level, are used only by a very small number of citizens, thus having no impact upon the digital divide. Confronted with a serious divide, and with great possibility of its increasing, Romania needs to promote policies designed to increase access and knowledge. Also, e-government is not possible, unless administrative culture and procedures change.

  2. Randomized clinical trial of autologous skin cell suspension for accelerating re-epithelialization of split-thickness donor sites.

    Science.gov (United States)

    Hu, Z; Guo, D; Liu, P; Cao, X; Li, S; Zhu, J; Tang, B

    2017-06-01

    Split-thickness skin graft (STSG) is used frequently, but may result in complications at the donor site. Rapid healing of donor-site wounds is critical to relieving morbidity. This study investigated whether autologous skin cell suspension could improve healing of STSG donor-site wounds. Between September 2014 and February 2016, patients requiring STSGs were randomized to receive autologous skin cell suspension plus hydrocolloid dressings (experimental group) or hydrocolloid dressings alone (control group) for the donor site. The primary outcome was time to complete re-epithelialization. Secondary outcomes included pain and itching scores measured on a visual analogue scale, and adverse events. Patients were followed for 12 weeks to evaluate quality of healing. Analysis was by intention to treat. Some 106 patients were included, 53 in each group. Median time to complete re-epithelialization was 9·0 (95 per cent c.i. 8·3 to 9·7) days in the experimental group, compared with 13·0 (12·4 to 13·6) days in the control group (P suspension had been used. The use of autologous skin cell suspension with hydrocolloid dressings accelerated epithelialization and improved healing quality of the donor site compared with hydrocolloid dressings alone. Registration number: UMIN000015000 ( http://www.umin.ac.jp/ctr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  3. BRIDGING THE INFORMATION AND DIGITAL DIVIDE AT HIGHER EDUCATIONAL INSTITUTIONS

    Directory of Open Access Journals (Sweden)

    Alla M. Kolomiiets

    2014-05-01

    Full Text Available The article deals with the notion of information and digital divide on the grounds of the world processes of the information society establishment. This paper presents a research of the level of informatization of the main spheres of life activity of citizens of foreign countries, and the analysis of the experience of the leading countries in organization and implementation of a complex of measures, aimed at crossing the digital divide. Also, there have been outlined the peculiarities and problems of the development of higher education in Ukraine in the context of information and digital inequality. On the basis of the analysis of scientific literature and personal professional experience, the ways of the solution of the problem of teacher’s selection of the adequate and the most effective pedagogical technologies, forms and methods of study in the process of overcoming the information and digital divide at higher educational institutions have been determined in this article.

  4. Echocardiographic diagnosis of divided right atrium-cor triatriatum dextrum.

    Science.gov (United States)

    Bejiqi, Ramush; Retkoceri, Ragip; Bejiqi, Hana; Zeka, Naim; Kelmendi, Myrvete

    2010-01-01

    First reported in 1868, cor triatriatum, that is, a heart with 3 atria (triatrial heart), is a congenital anomaly in which the left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is divided into two parts by a fold of tissue, a membrane, or a fibromuscular band. As far as division of the morphologically left atrium (cor triatriatum) is a recognized clinical and surgical entity. Division of the right atrium (prominence of the eustachian and thebesian valves) is recognized pathologically, but is rare. A partition division the right atrium was attached to the orifice of the inferior caval vei. The dividing partition is placed between the systemic venous sinus and the distal part of the right atrium, made up of the vestibule and appendage. This report describes a case of a divided right atrium, associated with a large atrial septal defect and valvular pulmonary stenosis.

  5. Selectively Distracted: Divided Attention and Memory for Important Information.

    Science.gov (United States)

    Middlebrooks, Catherine D; Kerr, Tyson; Castel, Alan D

    2017-08-01

    Distractions and multitasking are generally detrimental to learning and memory. Nevertheless, people often study while listening to music, sitting in noisy coffee shops, or intermittently checking their e-mail. The current experiments examined how distractions and divided attention influence one's ability to selectively remember valuable information. Participants studied lists of words that ranged in value from 1 to 10 points while completing a digit-detection task, while listening to music, or without distractions. Though participants recalled fewer words following digit detection than in the other conditions, there were no significant differences between conditions in terms of selectively remembering the most valuable words. Similar results were obtained across a variety of divided-attention tasks that stressed attention and working memory to different degrees, which suggests that people may compensate for divided-attention costs by selectively attending to the most valuable items and that factors that worsen memory do not necessarily impair the ability to selectively remember important information.

  6. Dividing traffic cluster into parts by signal control

    Science.gov (United States)

    Nagatani, Takashi

    2018-02-01

    When a cluster of vehicles with various speeds moves through the series of signals, the cluster breaks down by stopping at signals and results in smaller groups of vehicles. We present the nonlinear-map model of the motion of vehicles controlled by the signals. We study the breakup of a cluster of vehicles through the series of signals. The cluster of vehicles is divided into various groups by controlling the cycle time of signals. The vehicles within each group move with the same mean velocity. The breakup of the traffic cluster depends highly on the signal control. The dependence of dividing on both cycle time and vehicular speed is clarified. Also, we investigate the effect of the irregular interval between signals on dividing.

  7. Ouroboros: A Tool for Building Generic, Hybrid, Divide& Conquer Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J R; Foster, I

    2003-05-01

    A hybrid divide and conquer algorithm is one that switches from a divide and conquer to an iterative strategy at a specified problem size. Such algorithms can provide significant performance improvements relative to alternatives that use a single strategy. However, the identification of the optimal problem size at which to switch for a particular algorithm and platform can be challenging. We describe an automated approach to this problem that first conducts experiments to explore the performance space on a particular platform and then uses the resulting performance data to construct an optimal hybrid algorithm on that platform. We implement this technique in a tool, ''Ouroboros'', that automatically constructs a high-performance hybrid algorithm from a set of registered algorithms. We present results obtained with this tool for several classical divide and conquer algorithms, including matrix multiply and sorting, and report speedups of up to six times achieved over non-hybrid algorithms.

  8. Hybrid Lentivirus-transposon Vectors With a Random Integration Profile in Human Cells

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas H; Moldt, Brian; Mátés, Lajos

    2009-01-01

    Gene delivery by human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) is efficient, but genomic integration of the viral DNA is strongly biased toward transcriptionally active loci resulting in an increased risk of insertional mutagenesis in gene therapy protocols. Nonviral...... Sleeping Beauty (SB) transposon vectors have a significantly safer insertion profile, but efficient delivery into relevant cell/tissue types is a limitation. In an attempt to combine the favorable features of the two vector systems we established a novel hybrid vector technology based on SB transposase......-mediated insertion of lentiviral DNA circles generated during transduction of target cells with integrase (IN)-defective LVs (IDLVs). By construction of a lentivirus-transposon hybrid vector allowing transposition exclusively from circular viral DNA substrates, we demonstrate that SB transposase added in trans...

  9. Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex.

    OpenAIRE

    Manuel Schottdorf; Wolfgang Keil; David Coppola; White, Leonard E.; Fred Wolf

    2015-01-01

    The architecture of iso-orientation domains in the primary visual cortex (V1) of placental carnivores and primates apparently follows species invariant quantitative laws. Dynamical optimization models assuming that neurons coordinate their stimulus preferences throughout cortical circuits linking millions of cells specifically predict these invariants. This might indicate that V1's intrinsic connectome and its functional architecture adhere to a single optimization principle with high precisi...

  10. Interrogating cell division errors using random and chromosome-specific missegregation approaches.

    Science.gov (United States)

    Ly, Peter; Cleveland, Don W

    2017-07-03

    Accurate segregation of the duplicated genome in mitosis is essential for maintaining genetic stability. Errors in this process can cause numerical and/or structural chromosome abnormalities - hallmark genomic features commonly associated with both tumorigenesis and developmental disorders. A cell-based approach was recently developed permitting inducible missegregation of the human Y chromosome by selectively disrupting kinetochore assembly onto the Y centromere. Although this strategy initially requires several steps of genetic manipulation, it is easy to use, highly efficient and specific for the Y without affecting the autosomes or the X, and does not require cell cycle synchronization or mitotic perturbation. Here we describe currently available tools for studying chromosome segregation errors, aneuploidy, and micronuclei, as well as discuss how the Y-specific missegregation system has been used to elucidate how chromosomal micronucleation can trigger a class of extensive rearrangements termed chromothripsis. The combinatorial use of these different tools will allow unresolved aspects of cell division defects and chromosomal instability to be experimentally explored.

  11. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

    Science.gov (United States)

    Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

    2017-06-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright

  12. Transformer-based design techniques for oscillators and frequency dividers

    CERN Document Server

    Luong, Howard Cam

    2016-01-01

    This book provides in-depth coverage of transformer-based design techniques that enable CMOS oscillators and frequency dividers to achieve state-of-the-art performance.  Design, optimization, and measured performance of oscillators and frequency dividers for different applications are discussed in detail, focusing on not only ultra-low supply voltage but also ultra-wide frequency tuning range and locking range.  This book will be an invaluable reference for anyone working or interested in CMOS radio-frequency or mm-Wave integrated circuits and systems.

  13. Enhanced Model of Nonlinear Spiral High Voltage Divider

    Directory of Open Access Journals (Sweden)

    V. Panko

    2015-04-01

    Full Text Available This paper deals with the enhanced accurate DC and RF model of nonlinear spiral polysilicon voltage divider. The high resistance polysilicon divider is a sensing part of the high voltage start-up MOSFET transistor that can operate up to 700 V. This paper presents the structure of a proposed model, implemented voltage, frequency and temperature dependency, and scalability. A special attention is paid to the ability of the created model to cover the mismatch and influence of a variation of process parameters on the device characteristics. Finally, the comparison of measured data vs. simulation is presented in order to confirm the model validity and a typical application is demonstrated.

  14. Google and the digital divide the bias of online knowledge

    CERN Document Server

    Segev, Elad

    2010-01-01

    Beneficial to scholars and students in the fields of media and communication, politics and technology, this book outlines the significant role of search engines in general and Google in particular in widening the digital divide between individuals, organisations and states. It uses innovative methods and research approaches to assess and illustrate the digital divide by comparing the popular search queries in Google and Yahoo in different countries as well as analysing the various biases in Google News and Google Earth. The different studies developed and presented in this book provide various

  15. Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

    Science.gov (United States)

    Wallen, Gwenyth R; Middleton, Kimberly R; Ames, Nancy; Brooks, Alyssa T; Handel, Daniel

    2014-01-01

    Sickle cell disease (SCD) is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality), anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION ClinicalTrials.gov: NCT00393250 PMID:25520557

  16. A randomized control trial of a psychosocial intervention for caregivers of allogeneic hematopoietic stem cell transplant patients: effects on distress.

    Science.gov (United States)

    Laudenslager, M L; Simoneau, T L; Kilbourn, K; Natvig, C; Philips, S; Spradley, J; Benitez, P; McSweeney, P; Mikulich-Gilbertson, S K

    2015-08-01

    Caregivers of patients receiving allogeneic hematopoietic stem cell transplants (allo-HSCT) serve a pivotal role in patient care but experience high stress, anxiety and depression as a result. We theorized that stress management adapted for allo-HSCT caregivers would reduce distress compared with treatment as usual (TAU). Of 267 consecutive caregivers of allo-HSCT patients approached, 148 (mean=53.5 years, 75.7% female) were randomized to either psychosocial intervention (i=74) or TAU (n=74). Eight one-on-one stress management sessions delivered across the 100-day post-transplant period focused on understanding stress, changing role(s) as caregiver, cognitive behavioral stress management, pacing respiration and identifying social support. Primary outcomes included perceived stress (psychological) and salivary cortisol awakening response (CAR) (physiological). Randomized groups were not statistically different at baseline. Mixed models analysis of covariance (intent-to-treat) showed that intervention was associated with significantly lower caregiver stress 3 months post transplant (mean=20.0, 95% confidence interval (95% CI)=17.9-22.0) compared with TAU (mean=23.0, 95% CI=21.0-25.0) with an effect size (ES) of 0.39 (P=0.039). Secondary psychological outcomes, including depression and anxiety, were significantly reduced with ESs of 0.46 and 0.66, respectively. Caregiver CAR did not differ from non-caregiving controls at baseline and was unchanged by intervention. Despite significant caregiving burden, this psychosocial intervention significantly mitigated distress in allo-HSCT caregivers.

  17. Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Gwenyth R. Wallen

    2014-01-01

    Full Text Available Sickle cell disease (SCD is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality, anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00393250

  18. A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

    Directory of Open Access Journals (Sweden)

    Wun Ted

    2013-02-01

    Full Text Available Abstract Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41 or placebo (n = 21 for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

  19. Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial

    DEFF Research Database (Denmark)

    Ravaud, Alain; Hawkins, Robert; Gardner, Jason P

    2008-01-01

    of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks......PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib...... was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number...

  20. Single-chain lipopeptide vaccines for the induction of virus-specific cytotoxic T cell responses in randomly selected populations.

    Science.gov (United States)

    Gras-Masse, H

    2001-12-01

    Effective vaccine development is now taking advantage of the rapidly accumulating information concerning the molecular basis of a protective immune response. Analysts and medicinal chemists have joined forces with immunologists and taken up the clear challenge of identifying immunologically active structural elements and synthesizing them in pure, reproducible forms. Current literature reveals the growing interest for extremely reductionist approaches aiming at producing totally synthetic vaccines that would be fully defined at the molecular level and particularly safe. The sequential information contained in these formulations tends to be minimized to those epitopes which elicit neutralizing antibodies, or cell-mediated responses. In the following review, we describe some of our results in developing fully synthetic, clinically acceptable lipopeptide vaccines for inducing cytotoxic T lymphocytes (CTL) responses in randomly selected populations.

  1. Genetic correlations between the cumulative pseudo-survival rate, milk yield, and somatic cell score during lactation in Holstein cattle in Japan using a random regression model.

    Science.gov (United States)

    Sasaki, O; Aihara, M; Nishiura, A; Takeda, H

    2017-09-01

    Trends in genetic correlations between longevity, milk yield, and somatic cell score (SCS) during lactation in cows are difficult to trace. In this study, changes in the genetic correlations between milk yield, SCS, and cumulative pseudo-survival rate (PSR) during lactation were examined, and the effect of milk yield and SCS information on the reliability of estimated breeding value (EBV) of PSR were determined. Test day milk yield, SCS, and PSR records were obtained for Holstein cows in Japan from 2004 to 2013. A random subset of the data was used for the analysis (825 herds, 205,383 cows). This data set was randomly divided into 5 subsets (162-168 herds, 83,389-95,854 cows), and genetic parameters were estimated in each subset independently. Data were analyzed using multiple-trait random regression animal models including either the residual effect for the whole lactation period (H0), the residual effects for 5 lactation stages (H5), or both of these residual effects (HD). Milk yield heritability increased until 310 to 351 d in milk (DIM) and SCS heritability increased until 330 to 344 DIM. Heritability estimates for PSR increased with DIM from 0.00 to 0.05. The genetic correlation between milk yield and SCS increased negatively to under -0.60 at 455 DIM. The genetic correlation between milk yield and PSR increased until 342 to 355 DIM (0.53-0.57). The genetic correlation between the SCS and PSR was -0.82 to -0.83 at around 180 DIM, and decreased to -0.65 to -0.71 at 455 DIM. The reliability of EBV of PSR for sires with 30 or more recorded daughters was 0.17 to 0.45 when the effects of correlated traits were ignored. The maximum reliability of EBV was observed at 257 (H0) or 322 (HD) DIM. When the correlations of PSR with milk yield and SCS were considered, the reliabilities of PSR estimates increased to 0.31-0.76. The genetic parameter estimates of H5 were the same as those for HD. The rank correlation coefficients of the EBV of PSR between H0 and H5 or HD were

  2. A randomized blind trial on dry cow antibiotic infusion in a low somatic cell count herd.

    Science.gov (United States)

    Schukken, Y H; Vanvliet, J; Vandegeer, D; Grommers, F J

    1993-10-01

    The objective of the study was to evaluate the effect of administration of antibiotics to cows at dry-off in a low SCC herd. Cows were infused at dry-off with an intramammary antibiotic on the left or the right side of the udder. Selection of the infused quarters was random, and all people evaluating the occurrence of mastitis were unaware of which half of the udder was infused. The quarters that were infused with an antibiotic showed a significantly lower incidence of clinical mastitis in the dry period. Quarters that were uninfused had 10 cases of clinical mastitis versus 1 case in quarters that were infused with antibiotics. The quarters that were infused showed a reduction of minor pathogens at calving. The uninfused quarters showed little evidence of spontaneous cure during the dry period. Milk leaking was frequent during the drying off period. Milk leaking was also associated with the occurrence of clinical mastitis later in the dry period. Cows that leaked milk had a four times greater risk of clinical mastitis in the dry period.

  3. Response Styles and the Rural-Urban Divide

    Science.gov (United States)

    Thomas, Troy D.; Abts, Koen; Vander Weyden, Patrick

    2014-01-01

    This article investigates the effect of the rural-urban divide on mean response styles (RSs) and their relationships with the sociodemographic characteristics of the respondents. It uses the Representative Indicator Response Style Means and Covariance Structure (RIRSMACS) method and data from Guyana--a developing country in the Caribbean. The…

  4. The impact of digital divide on skills development amongst ...

    African Journals Online (AJOL)

    Today library function/services are carried out with the help of ICT facilities. This has forced academic librarians to shift from manual library services to the use of ICT facilities in carrying out library functions. The paper is on the impact of digital divide on skills development amongst academic librarians in Imo State.

  5. The Credit/Non-Credit Divide: Breaking Down the Wall

    Science.gov (United States)

    Fouts, Susan; Mallory, Judy

    2010-01-01

    Programs awarding academic credit and programs awarding continuing education credit coexist on university campuses but often do not communicate or collaborate. This article explores the components of a successful program that reaches across the credit-noncredit divide to engage and serve the community. While most theoretical models are based on a…

  6. Leadership Analysis in K-12 Case Study: "Divided Loyalties"

    Science.gov (United States)

    Alsubaie, Merfat Ayesh

    2016-01-01

    This report mainly aims to provide a critical and in-depth analysis of the K-12 Case, "Divided Loyalty" by Holy and Tartar (2004). The case recounts how the manifestation of inadequate leadership skills in a school setting could affect negatively the performance of students.

  7. Divided dreamworlds? The cultural cold war in East and West

    NARCIS (Netherlands)

    Romijn, P.; Scott-Smith, G.; Segal, J.

    2012-01-01

    While the divide between capitalism and communism, embodied in the image of the Iron Curtain, seemed to be as wide and definitive as any cultural rift, Giles Scott-Smith, Joes Segal, and Peter Romijn have compiled a selection of essays on how culture contributed to the blurring of ideological

  8. Social partners divided over government plan to raise retirement age

    NARCIS (Netherlands)

    Grünell, M.

    2009-01-01

    The social partners have given a divided response to the Dutch cabinet’s plans to raise the retirement age - first to 66 years in 2020 and then to 67 years in 2025. This also applies to the age at which company pension schemes will be paid out. The trade unions argue that poorly paid workers who

  9. Communication in a Divided World: Opportunities and Constraints.

    Science.gov (United States)

    Lasswell, Harold

    Communication systems in a divided world can perpetuate tension and violence or can be instrumental in developing unity. In response to this power, communicators must focus on generating worldwide recognition of interdependence in the shaping and sharing of values. Likewise, a responsible communication policy must stimulate the invention and…

  10. Monitoring Progress Toward the Information Society : Digital Divide ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Orbicom's Digital Divide Index is a rigorous statistical tool for benchmarking access to and use of information and communication technologies (ICT), and monitoring progress toward the information society over time. ... Businesses can understand trade trends and future challenges in the ASEAN Economic community.

  11. Measuring and Bridging the Gender Digital Divide in Rural Pakistan ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Measuring and Bridging the Gender Digital Divide in Rural Pakistan. Despite that approximately 70% of Pakistan's 160 million inhabitants living in rural villages, nearly 90% of the ICT-related infrastructure is installed in urban areas. ... Sustainable Development Policy Institute. Institution Country. Pakistan. Institution Website.

  12. Geothermal resources of the Washakie and Great Divide basins, Wyoming

    Science.gov (United States)

    Heasler, H. P.; Buelow, K. L.

    1985-05-01

    The geothermal resources of the Great Divide and Washakie Basins of southern Wyoming are described. Oil well bottomhole temperatures, thermal logs of wells, and heat flow data were interpreted within a framework of geologic and hydrologic constraints. It was concluded large areas in Wyoming are underlain by water hotter than 120 F. Isolated areas with high temperature gradients exist within each basin.

  13. Dividing Attention Lowers Children's but Increases Adults' False Memories

    Science.gov (United States)

    Otgaar, Henry; Peters, Maarten; Howe, Mark L.

    2012-01-01

    The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a…

  14. A Technique to Avoid the Marginal Artery During Divided Colostomy ...

    African Journals Online (AJOL)

    Colostomy is a frequently performed procedure in neonates presenting with anorectal malformation and Hirschsprungs disease. A divided colostomy is more commonly performed but has a definite risk of injury to the marginal artery during the procedure, leading to stoma necrosis. This is a description of a technique which ...

  15. Loop versus divided colostomy for the management of anorectal malformations.

    Science.gov (United States)

    Oda, Omar; Davies, Dafydd; Colapinto, Kimberly; Gerstle, J Ted

    2014-01-01

    The purpose of this study was to compare the clinical outcomes of loop and divided colostomies in patients with anorectal malformations (ARM). We performed a retrospective cohort study reviewing the medical records of all patients with ARM managed with diverting colostomies between 2000 and 2010 at our institution. Independent variables and outcomes of stoma complications were analyzed by parametric measures and logistic regression. One hundred forty-four patients managed with a colostomy for ARM were evaluated (37.5% females, 50.7% loop, 49.3% divided). The incidence of patients with loop and divided colostomies who developed stoma-related complications was 31.5 and 15.5%, respectively (p=0.031). The incidence of prolapse was 17.8 and 2.8%, respectively (p=0.005). Multivariable-logistic regression controlling for other significant independent variables found loop colostomies to be positively associated with the development of a stoma complication (OR 3.13, 95%CI (1.09, 8.96), p=0.033). When individual complications were evaluated, it was only stoma prolapse that was more likely in patients with loop colostomies (OR 8.75, 95%CI (1.74, 44.16), p=0.009). Because of the higher incidence of prolapse, loop colostomies were found to be associated with a higher total incidence of complications than divided stomas. The development of other complications, including urinary tract infections (UTIs) and megarectum, were independent of the type of colostomy performed. © 2014.

  16. Competing discourses on Europe: the divided case of Estonia

    NARCIS (Netherlands)

    Moes, Jeroen

    2010-01-01

    Historical and cultural context and individual experience are likely to influence the ‘imagination of Europe’. Such discourses exist according to specific social patterns that may critically divide societies into different and competing social constructions of Europe. Is there a transnational

  17. Theories of Learning in Educational Development: Relocating the Paradigmatic Divide.

    Science.gov (United States)

    Inglis, Alistair

    1996-01-01

    Offers a critique of a previous discussion on instructional industrialism in distance education based on instructional design. Topics include the psychological foundations of instructional design, competing paradigms in educational development, behaviorism and cognitivism, theories of learning and the paradigmatic divide, and implications for…

  18. Crossing the digital divide: the contribution of information technology ...

    African Journals Online (AJOL)

    Crossing the digital divide: the contribution of information technology to the professional performance of ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL · RESOURCES. African Health Sciences ... MIMCom makes possible enhanced access to the Internet and to medical literature.

  19. Crossing the digital divide: the contribution of information technology ...

    African Journals Online (AJOL)

    Crossing the digital divide: the contribution of information technology to the professional performance of malaria researchers in Africa. ... retrieve information, obtain documents, write proposals, and prepare papers for publication; and to determine the contribution of this intervention to their professional performance.

  20. Interacting divided channel method for compound channel flow

    NARCIS (Netherlands)

    Huthoff, Freek; Roos, Pieter C.; Augustijn, Dionysius C.M.; Hulscher, Suzanne J.M.H.

    2008-01-01

    A new method to calculate flow in compound channels is proposed: the interacting divided channel method (IDCM), based on a new parametrization of the interface stress between adjacent flow compartments, typically between the main channel and floodplain of a two-stage channel. This expression is

  1. Divide and conquer? Size adjustment with allometry and intermediate outcomes.

    Science.gov (United States)

    Nakagawa, Shinichi; Kar, Fonti; O'Dea, Rose E; Pick, Joel L; Lagisz, Malgorzata

    2017-11-09

    Many trait measurements are size-dependent, and while we often divide these traits by size before fitting statistical models to control for the effect of size, this approach does not account for allometry and the intermediate outcome problem. We describe these problems and outline potential solutions.

  2. Tamil Nadu and the Diagonal Divide in Sex Ratios

    NARCIS (Netherlands)

    A.S. Bedi (Arjun Singh); S. Srinivasan (Sharada)

    2009-01-01

    textabstractBetween 1961 and 2001, India’s 0-6 sex ratio has steadily declined. Despite evidence to the contrary, this ratio is often characterised in terms of a diagonal divide with low 0-6 sex ratios in northern and western India and normal 0-6 sex ratios in eastern and southern India. While

  3. Reconciling Ethnic and National Identities in a Divided Society: The ...

    African Journals Online (AJOL)

    ... as a valuable lesson for nation-state building in post-colonial multiethnic countries. In addition to the institutional design approach, the paper points to the importance of civic education, collective history, and democracy in promoting national integration in a divided society. Democracy & Development Vol.4(2) 2004: 31-48 ...

  4. Dynamical system modeling to simulate donor T cell response to whole exome sequencing-derived recipient peptides: Understanding randomness in alloreactivity incidence following stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Vishal Koparde

    Full Text Available Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA and graft versus host disease (GVHD pathophysiology in stem cell transplant (SCT donor-recipient pairs (DRP is not established. In order to elucidate this relationship, whole exome sequencing (WES was performed on 27 HLA matched related (MRD, & 50 unrelated donors (URD, to identify nonsynonymous single nucleotide polymorphisms (SNPs. An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01; resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0 and the tissue expression of proteins these were derived from determined (GTex. MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA with an IC50 of <500 nM, and URD, had 5,386 (p<0.01. To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.

  5. Problems Related to the Abolition of Divided Real Estate Ownership

    Directory of Open Access Journals (Sweden)

    Dinsberga Jolanta

    2016-12-01

    Full Text Available Legal relationship between apartment owners in residential buildings and the land owners, that is, divided real estate ownership, was created in the Republic of Latvia in 1990, within the framework of the Land Reform, restoring property rights of the former owners or their heirs or privatising apartments in multi-apartment residential buildings. The existence of such legal relationship created different lease problems and restrictions on the property rights to the owners of both the building and the land. To abolish the legal relationship related to divided real estate ownership, the Ministry of Justice of the Republic of Latvia has developed a draft law Regarding the Abolition of Mandatory Divided Real Estate Ownership in Multi-Apartment Buildings (hereinafter referred to as Draft Law. Unfortunately, in the opinion of authors of this article, there are serious shortcomings to the Draft Law which must be corrected. The aim of the research is to identify the problematic issues by selecting and analysing the legislation on the abolition of the divided real estate ownership, which is related to the calculation of redemption price, payment method and consequences of non-payment, which are not regulated by the new Draft Law. The article reflects research on the determination and calculation of redemption price reglamented by the Draft Law and also analyses the Law of December 8, 1938, On the Abolition of Divided Real Estate Ownership and its practical implementation, which may significantly influence the redemption price and the method of its calculation; however, the mentioned law has been disregarded in developing the Draft Law. Thus the research has both theoretical and practical significance. For the research purposes general research methods, such as historical, analytical, inductive, deductive, logical-constructive and descriptive methods, are used. For the interpretation of legislation norms, grammatical, systemic, teleological and historical

  6. Finding Oxygen Reservoir by Using Extremely Small Test Cell Structure for Resistive Random Access Memory with Replaceable Bottom Electrode.

    Science.gov (United States)

    Kinoshita, Kentaro; Koh, Sang-Gyu; Moriyama, Takumi; Kishida, Satoru

    2015-12-22

    Although the presence of an oxygen reservoir (OR) is assumed in many models that explain resistive switching of resistive random access memory (ReRAM) with electrode/metal oxide (MO)/electrode structures, the location of OR is not clear. We have previously reported a method, which involved the use of an AFM cantilever, for preparing an extremely small ReRAM cell that has a removable bottom electrode (BE). In this study, we used this cell structure to specify the location of OR. Because an anode is often assumed to work as OR, we investigated the effect of changing anodes without changing the MO layer and the cathode on the occurrence of reset. It was found that the reset occurred independently of the catalytic ability and Gibbs free energy (ΔG) of the anode. Our proposed structure enabled to determine that the reset was caused by repairing oxygen vacancies of which a filament consists due to the migration of oxygen ions from the surrounding area when high ΔG anode metal is used, whereas by oxidizing the anode due to the migration of oxygen ions from the MO layer when low ΔG anode metal is used, suggesting the location of OR depends on ΔG of the anode.

  7. Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait: Randomized Controlled Trial Outcomes over Two Years.

    Science.gov (United States)

    Gallo, Agatha M; Wilkie, Diana J; Yao, Yingwei; Molokie, Robert E; Stahl, Christiane; Hershberger, Patricia E; Zhao, Zhongsheng; Suarez, Marie L; Johnson, Bonnye; Angulo, Rigoberto; Carrasco, Jesus; Angulo, Veronica; Thompson, Alexis A

    2016-04-01

    Interventions to assist reproductive health decision-making in populations affected by sickle cell disease (SCD) or trait (SCT) lack proven efficacy over time. Our aim was to compare effects of CHOICES, a Web-based multimedia education program on implementing informed reproductive plans, and usual care education (e-Book) on reproductive knowledge, intention, and behavior over 24 months. We randomized 234 participants with SCD (n = 138) or SCT (n = 96) (age 18-35 years, 35 % male, 94 % African American) to CHOICES and e-Book groups. Participants completed a sickle cell-specific reproductive measure before and four times after the intervention (6, 12, 18 and 24 months). Compared to the e-Book group the CHOICES group had significantly more improvement in knowledge over time (p = .004) but not intention (p = .18) or behavior (p = .69). At baseline, 114 (48.7 %) participants reported having partners who would not put the couple at risk for their children inheriting SCD. Of the 116 (49.6 %) at-risk participants, a higher poroportion of those who were in the CHOICES group chose partners that reduced their risk by the last visit than the e-Book group (p = .04). Study findings provide important insights for designing a national trial of the CHOICES intervention focusing on subjects whose partner status puts them at risk for having a child with SCD.

  8. Unusual features of non-dividing somatic macronuclei in the ciliate class Karyorelictea.

    Science.gov (United States)

    Yan, Ying; Rogers, Anna J; Gao, Feng; Katz, Laura A

    2017-10-01

    Genome structure and nuclear organization have been intensely studied in model ciliates such as Tetrahymena and Paramecium, yet few studies have focused on nuclear features of other ciliate clades including the class Karyorelictea. In most ciliates, both the somatic macronuclei and germline micronuclei divide during cell division and macronuclear development only occurs after conjugation. However, the macronuclei of Karyorelictea are non-dividing (i.e. division minus (Div-)) and develop anew from micronuclei during each asexual division. As macronuclei age within Karyorelictea, they undergo changes in morphology and DNA content until they are eventually degraded and replaced by newly developed macronuclei. No less than two macronuclei and one micronucleus are present in karyorelictid species, which suggests that a mature macronucleus 1) might be needed to sustain the cell while a new macronucleus is developing and 2) likely plays a role in guiding the development of the new macronucleus. Here we use a phylogenetic framework to compile information on the morphology and development of nuclei in Karyorelictea, largely relying on the work of Dr. Igor Raikov (1932-1998). We synthesize data to speculate on the functional implications of key features of Karyorelictea including the presence of at least two macronuclei in each cell and the inability for macronuclei to divide. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  9. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap.

    Directory of Open Access Journals (Sweden)

    Luisa Laureti

    2015-12-01

    Full Text Available DNA Damage Tolerance (DDT mechanisms help dealing with unrepaired DNA lesions that block replication and challenge genome integrity. Previous in vitro studies showed that the bacterial replicase is able to re-prime downstream of a DNA lesion, leaving behind a single-stranded DNA gap. The question remains of what happens to this gap in vivo. Following the insertion of a single lesion in the chromosome of a living cell, we showed that this gap is mostly filled in by Homology Directed Gap Repair in a RecA dependent manner. When cells fail to repair this gap, or when homologous recombination is impaired, cells are still able to divide, leading to the loss of the damaged chromatid, suggesting that bacteria lack a stringent cell division checkpoint mechanism. Hence, at the expense of losing one chromatid, cell survival and proliferation are ensured.

  10. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap.

    Science.gov (United States)

    Laureti, Luisa; Demol, Julien; Fuchs, Robert P; Pagès, Vincent

    2015-12-01

    DNA Damage Tolerance (DDT) mechanisms help dealing with unrepaired DNA lesions that block replication and challenge genome integrity. Previous in vitro studies showed that the bacterial replicase is able to re-prime downstream of a DNA lesion, leaving behind a single-stranded DNA gap. The question remains of what happens to this gap in vivo. Following the insertion of a single lesion in the chromosome of a living cell, we showed that this gap is mostly filled in by Homology Directed Gap Repair in a RecA dependent manner. When cells fail to repair this gap, or when homologous recombination is impaired, cells are still able to divide, leading to the loss of the damaged chromatid, suggesting that bacteria lack a stringent cell division checkpoint mechanism. Hence, at the expense of losing one chromatid, cell survival and proliferation are ensured.

  11. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

  12. Prediction of conformational B-cell epitopes from 3D structures by random forests with a distance-based feature.

    Science.gov (United States)

    Zhang, Wen; Xiong, Yi; Zhao, Meng; Zou, Hua; Ye, Xinghuo; Liu, Juan

    2011-08-17

    Antigen-antibody interactions are key events in immune system, which provide important clues to the immune processes and responses. In Antigen-antibody interactions, the specific sites on the antigens that are directly bound by the B-cell produced antibodies are well known as B-cell epitopes. The identification of epitopes is a hot topic in bioinformatics because of their potential use in the epitope-based drug design. Although most B-cell epitopes are discontinuous (or conformational), insufficient effort has been put into the conformational epitope prediction, and the performance of existing methods is far from satisfaction. In order to develop the high-accuracy model, we focus on some possible aspects concerning the prediction performance, including the impact of interior residues, different contributions of adjacent residues, and the imbalanced data which contain much more non-epitope residues than epitope residues. In order to address above issues, we take following strategies. Firstly, a concept of 'thick surface patch' instead of 'surface patch' is introduced to describe the local spatial context of each surface residue, which considers the impact of interior residue. The comparison between the thick surface patch and the surface patch shows that interior residues contribute to the recognition of epitopes. Secondly, statistical significance of the distance distribution difference between non-epitope patches and epitope patches is observed, thus an adjacent residue distance feature is presented, which reflects the unequal contributions of adjacent residues to the location of binding sites. Thirdly, a bootstrapping and voting procedure is adopted to deal with the imbalanced dataset. Based on the above ideas, we propose a new method to identify the B-cell conformational epitopes from 3D structures by combining conventional features and the proposed feature, and the random forest (RF) algorithm is used as the classification engine. The experiments show that our

  13. Prediction of conformational B-cell epitopes from 3D structures by random forests with a distance-based feature

    Directory of Open Access Journals (Sweden)

    Zou Hua

    2011-08-01

    Full Text Available Abstract Background Antigen-antibody interactions are key events in immune system, which provide important clues to the immune processes and responses. In Antigen-antibody interactions, the specific sites on the antigens that are directly bound by the B-cell produced antibodies are well known as B-cell epitopes. The identification of epitopes is a hot topic in bioinformatics because of their potential use in the epitope-based drug design. Although most B-cell epitopes are discontinuous (or conformational, insufficient effort has been put into the conformational epitope prediction, and the performance of existing methods is far from satisfaction. Results In order to develop the high-accuracy model, we focus on some possible aspects concerning the prediction performance, including the impact of interior residues, different contributions of adjacent residues, and the imbalanced data which contain much more non-epitope residues than epitope residues. In order to address above issues, we take following strategies. Firstly, a concept of 'thick surface patch' instead of 'surface patch' is introduced to describe the local spatial context of each surface residue, which considers the impact of interior residue. The comparison between the thick surface patch and the surface patch shows that interior residues contribute to the recognition of epitopes. Secondly, statistical significance of the distance distribution difference between non-epitope patches and epitope patches is observed, thus an adjacent residue distance feature is presented, which reflects the unequal contributions of adjacent residues to the location of binding sites. Thirdly, a bootstrapping and voting procedure is adopted to deal with the imbalanced dataset. Based on the above ideas, we propose a new method to identify the B-cell conformational epitopes from 3D structures by combining conventional features and the proposed feature, and the random forest (RF algorithm is used as the

  14. SIW based multilayer transition and power divider in LTCC technology

    KAUST Repository

    Abuzaid, Hattan

    2013-06-01

    A multilayer transition and balanced power divider are presented for millimeter-wave system-on-package (SoP). These two components operate at Ka-band and exploit the substrate integrate waveguide (SIW) technology with its shielding characteristics and the Low-temperature co-fired ceramics (LTCC) technology for its high density integration. A coupling slot has been used to perform vertical integration, which can be easily optimized through its length. The measured input return loss within the bandwidth of interest (32 GHz-38 GHz) is less than -15 dB and -18 dB for the multilayer transition and the power divider, respectively. The lateral dimensions of a multilayer system, such as a feed network of an array, can be greatly reduced by employing these 3D slot-coupled components. © 2013 IEEE.

  15. The New Digital Divide For Digital BioMarkers.

    Science.gov (United States)

    Torous, John; Rodriguez, Jorge; Powell, Adam

    2017-09-01

    As smartphone and sensors continue to become more ubiquitous across the world, digital biomarkers have emerged as a scalable and practical tool to explore disease states and advance health. But as the digital divide of access and ownership begins to fade, a new digital divide is emerging. Who are the types of people that own smartphones or smart watches, who are the types of people that download health apps or partake in digital biomarker studies, and who are the types of people that are actually active with digital biomarkers apps and sensors - the people providing the high quality and longitudinal data that this field is being founded upon? Understanding the people behind digital biomarkers, the very people this emerging field aims to help, may actually be the real challenge as well as opportunity for digital biomarkers.

  16. Randomized trial comparing weekly versus 3-week chemotherapy in small-cell lung cancer: a Cancer Research Campaign trial.

    Science.gov (United States)

    Souhami, R L; Rudd, R; Ruiz de Elvira, M C; James, L; Gower, N; Harper, P G; Tobias, J S; Partridge, M R; Davison, A G; Trask, C

    1994-09-01

    A randomized trial of chemotherapy, given on either a 1-week or a 3-week schedule, was performed in small-cell lung cancer (SCLC) patients. The aim was to determine if weekly scheduling produced survival superior to conventional treatment. Four hundred thirty-eight patients with SCLC with either limited disease (LD; 276 patients) or good-prognosis extensive disease (ED; 162 patients) were randomized. Weekly chemotherapy was 12 alternating cycles of ifosfamide/doxorubicin and cis-platin/etoposide (PE), while 3-week treatment was six alternating cycles of cyclophosphamide/doxorubicin/vincristine (CAV) and PE. Thoracic irradiation was administered 3 weeks after completion of chemotherapy to LD patients who attained a complete response (CR) or partial response (PR). Patients were well matched for clinical characteristics and prognostic factors. Overall response was the same in both arms: 82.3% (39.4% CR) with weekly and 81.1% (36.9% CR) with 3-week treatment. The median survival (MS) durations were 10.8 and 10.6 months for weekly and 3-week chemotherapy, respectively. The 2-year survival rates were 11.8% and 11.7% in the weekly and 3-week arms, respectively. Received dose-intensity (DI) was 73.9% of projected for weekly treatment and 92.7% for 3-week treatment. Hematologic toxicity was the major dose-limiting toxicity for the weekly treatment. This trial excludes at 90% power a benefit of greater than 10% for 2-year survival for weekly treatment. The received DI was reduced to a greater extent with weekly treatment, mainly due to hematologic toxicity.

  17. The UN Security Council Divided: Syria in Crisis

    OpenAIRE

    Gifkins, J

    2012-01-01

    The UN Security Council has been deeply divided over how to respond to the Arab Spring crisis in Syria. Since the uprising began in Syria in March 2011 the Syrian Government has responded with extreme violence against civilians and civilian areas to suppress protests. In the face of escalating violence, the Security Council has experienced protracted deadlock. Divisions on how to interpret the situation in Syria left the Security Council unable to find consensus on issuing a non-binding Presi...

  18. Digital divide and body size disparities among Chinese adults

    OpenAIRE

    Chih-Chien Huang; Scott T. Yabiku

    2018-01-01

    Background: The rapid development of information and communication technology (ICT) in China has increased people's sedentary behavior and raised a number of related issues. ICT screen-viewing activities are increasingly considered to contribute to obesity, and sociodemographic characteristics such as gender, income, age, education, and geographical location seem to magnify the digital divide. Objective: This study first examines dissimilar stages of ICT transition, and then establishes ho...

  19. Bridging the Digital Divide: Enhancing Empowerment and Social Capital

    OpenAIRE

    Diane Marie Charleson

    2012-01-01

    In the contemporary world, the digital divide constitutes a significant inequality and thus poses a very real problem of social justice – this being particularly the case for those already burdened with disadvantage and marginalisation. In this paper, As part of its commitment to Social Justice the Australian Catholic University runs a Catalyst Clemente program. Catalyst-Clemente provides people experiencing multiple disadvantage with university level education by means of a program that aims...

  20. Dividing Streamline Formation Channel Confluences by Physical Modeling

    Directory of Open Access Journals (Sweden)

    Minarni Nur Trilita

    2010-02-01

    Full Text Available Confluence channels are often found in open channel network system and is the most important element. The incoming flow from the branch channel to the main cause various forms and cause vortex flow. Phenomenon can cause erosion of the side wall of the channel, the bed channel scour and sedimentation in the downstream confluence channel. To control these problems needed research into the current width of the branch channel. The incoming flow from the branch channel to the main channel flow bounded by a line distributors (dividing streamline. In this paper, the wide dividing streamline observed in the laboratory using a physical model of two open channels, a square that formed an angle of 30º. Observations were made with a variety of flow coming from each channel. The results obtained in the laboratory observation that the width of dividing streamline flow is influenced by the discharge ratio between the channel branch with the main channel. While the results of a comparison with previous studies showing that the observation in the laboratory is smaller than the results of previous research.

  1. CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Escudier, Bernard; Sharma, Padmanee; McDermott, David F

    2017-01-01

    BACKGROUND: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). OBJECTIV...

  2. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.

    NARCIS (Netherlands)

    Morton, C.; Horn, M.; Leman, J.; Tack, B.; Bedane, C.; Tjioe, M.; Ibbotson, S.; Khemis, A.; Wolf, P.

    2006-01-01

    OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ. DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and

  3. Why Cortical Neurons Cannot Divide, and Why Do They Usually Die in the Attempt?

    Science.gov (United States)

    Aranda-Anzaldo, Armando; Dent, Myrna A R

    2017-04-01

    Cortical neurons are prime examples of terminally differentiated, postmitotic cells. However, under experimental or pathological conditions, they can re-enter the cell cycle and replicate DNA but are unable to divide, dying by apoptosis or becoming either polyploid or aneuploid. Any cellular state that depends on the action of genes and their products can be reverted or bypassed by spontaneous or induced mutations, yet there are currently no reports of dividing cortical neurons. Thus, it seems unlikely that the remarkably stable postmitotic condition of cortical neurons depends on specific gene functions. This Review summarizes evidence that the postmitotic state of cortical neurons depends on the high stability of its underlying nuclear structure that results from an entropy-driven process aimed at dissipating the intrinsic structural stress present in chromosomal DNA in such a way that the structural stability of the neuronal nucleus becomes an insurmountable energy barrier for karyokinesis and mitosis. From this perspective, the integral properties of the nuclear higher order structure in neurons provide an explanation not only for why cortical neurons cannot divide but also for why they usually die if they happen to replicate their DNA. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Safety and immunogenicity of an inactivated whole virus Vero cell-derived Ross River virus vaccine: a randomized trial.

    Science.gov (United States)

    Aichinger, Gerald; Ehrlich, Hartmut J; Aaskov, John G; Fritsch, Sandor; Thomasser, Christiane; Draxler, Wolfgang; Wolzt, Michael; Müller, Markus; Pinl, Fritz; Van Damme, Pierre; Hens, Annick; Levy, Jack; Portsmouth, Daniel; Holzer, Georg; Kistner, Otfried; Kreil, Thomas R; Barrett, P Noel

    2011-11-21

    Ross River virus (RRV) is endemic in Australia and several South Pacific Islands. Approximately 5000 cases of RRV disease, which is characterized by debilitating polyarthritis, are recorded each year in Australia. This study describes the first clinical trial of a candidate RRV vaccine. An inactivated whole-virus Vero cell-derived RRV vaccine was tested in 382 healthy, RRV-naïve adults in a phase 1/2 dose-escalation study at ten sites in Austria, Belgium and The Netherlands. Subjects were equally randomized to receive 1.25 μg, 2.5 μg, 5 μg, or 10 μg aluminum hydroxide-adjuvanted or non-adjuvanted RRV vaccine, with a second dose after three weeks and a booster at six months. Vaccine immunogenicity was determined by measurements of serum IgG and neutralizing antibody titers. Vaccine tolerability and safety were monitored over the entire study period. The optimal vaccine formulation was the adjuvanted 2.5 μg dose, as calculated using a repeated mixed model analysis of covariance comparing log-transformed RRV-specific IgG titers between different dose groups. Geometric means of RRV-specific serum antibodies measured 21 days after the third vaccination with the 2.5 μg adjuvanted formulation were 520.9 (90% CI 377.2-719.4) as determined by IgG ELISA and 119.9 (82.6-173.9) as determined by virus neutralization assay, resulting in seropositivity rates of 92.9% (82.6-98.0) and 92.7% (82.2-98.0), respectively. All vaccine formulations and doses were well tolerated after the first, second and third vaccination. The adjuvanted, inactivated whole-virus Vero cell-derived Ross River virus vaccine is highly immunogenic in RRV-naïve adults and well tolerated at all dose levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper.

    Science.gov (United States)

    Saccardi, R; Freedman, M S; Sormani, M P; Atkins, H; Farge, D; Griffith, L M; Kraft, G; Mancardi, G L; Nash, R; Pasquini, M; Martin, R; Muraro, P A

    2012-06-01

    Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of them having been recruited in small, single-centre, phase 1-2 uncontrolled trials. Clinical and magnetic resonance imaging outcomes from case series reports or Registry-based analyses suggest that a major response is achieved in most patients; quality and duration of response are better in patients transplanted during the relapsing-remitting phase than in those in the secondary progressive stage. An interdisciplinary group of neurologists and haematologists has been formed, following two international meetings supported by the European and American Blood and Marrow Transplantation Societies, for the purpose of discussing a controlled clinical trial, to be designed within the new scenarios of evolving MS treatments. Objectives of the trial, patient selection, transplant technology and outcome assessment were extensively discussed. The outcome of this process is summarized in the present paper, with the goal of establishing the background and advancing the development of a prospective, randomized, controlled multicentre trial to assess the clinical efficacy of HSCT for the treatment of highly active MS.

  6. Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors

    Directory of Open Access Journals (Sweden)

    Belen Cuervo

    2014-07-01

    Full Text Available Purpose: The aim of this study was to compare the efficacy and safety of a single intra-articular injection of adipose mesenchymal stem cells (aMSCs versus plasma rich in growth factors (PRGF as a treatment for reducing symptoms in dogs with hip osteoarthritis (OA. Methods: This was a randomized, multicenter, blinded, parallel group. Thirty-nine dogs with symptomatic hip OA were assigned to one of the two groups, to receive aMSCs or PRGF. The primary outcome measures were pain and function subscales, including radiologic assessment, functional limitation and joint mobility. The secondary outcome measures were owners’ satisfaction questionnaire, rescue analgesic requirement and overall safety. Data was collected at baseline, then, 1, 3 and 6 months post-treatment. Results: OA degree did not vary within groups. Functional limitation, range of motion (ROM, owner’s and veterinary investigator visual analogue scale (VAS, and patient’s quality of life improved from the first month up to six months. The aMSCs group obtained better results at 6 months. There were no adverse effects during the study. Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog’s pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months.

  7. Random vibrations theory and practice

    CERN Document Server

    Wirsching, Paul H; Ortiz, Keith

    1995-01-01

    Random Vibrations: Theory and Practice covers the theory and analysis of mechanical and structural systems undergoing random oscillations due to any number of phenomena— from engine noise, turbulent flow, and acoustic noise to wind, ocean waves, earthquakes, and rough pavement. For systems operating in such environments, a random vibration analysis is essential to the safety and reliability of the system. By far the most comprehensive text available on random vibrations, Random Vibrations: Theory and Practice is designed for readers who are new to the subject as well as those who are familiar with the fundamentals and wish to study a particular topic or use the text as an authoritative reference. It is divided into three major sections: fundamental background, random vibration development and applications to design, and random signal analysis. Introductory chapters cover topics in probability, statistics, and random processes that prepare the reader for the development of the theory of random vibrations a...

  8. Surface Tension and Adsorption without a Dividing Surface.

    Science.gov (United States)

    Marmur, Abraham

    2015-11-24

    The ingenious concept of a dividing surface of zero thickness that was introduced by Gibbs is the basis of the theory of surface tension and adsorption. However, some fundamental questions, mainly those related to the location of the dividing surface and the proper definition of relative adsorption, have remained open over the years. To avoid these questions, the present paper proposes to analyze an interfacial phase by defining a thermodynamic system of constant, but nonzero thickness. The interfacial phase is analyzed as it really is, namely a nonuniform three-dimensional entity. The current analysis redevelops the equation for calculating surface tension, though with different assumptions. However, the main point in the proposed model is that the thermodynamic interfacial system, due to its fixed thickness, conforms to the requirement of first-order homogeneity of the internal energy. This property is the key that allows using the Gibbs adsorption isotherm. It is also characteristic of the Gibbs dividing surface model, but has not always been discussed with regard to subsequent models. The resulting equation leads to a simple, "natural" expression for the relative adsorption. This expression may be compared with simulations and sophisticated surface concentration measurements, and from which the dependence of interfacial tension on the solution composition can be derived. Finally, it is important to point out that in order to calculate the interfacial tension as well as the relative adsorption from data on the properties of the interfacial phase, there is no need to know its exact thickness, as long as it is bigger than the actual thickness but sufficiently small.

  9. APPLICATION OF HIGH VOLTAGE DIVIDERS FOR POWER QUALITY INDICES MEASUREMENT

    Directory of Open Access Journals (Sweden)

    Y. L. Anokhin

    2017-12-01

    Full Text Available Introduction. Determination of power quality indices in high-voltage power grids allows to find the reasons for the deterioration of the power quality. The relevant national and International Standards for power quality contain relevant norms of quality indices and requirements for their accuracy measurement. Problem. The most complicated part in the process of measuring the power quality indices at high voltage is the selection of the corresponding high-voltage scale voltage converters. Therefore, comparing the requirements of IEC 61000-4-30 to high voltage scale voltage converters is an important task. Goal. Analysis of the International Standard IEC 61000-4-30 requirements feasibility for measuring the indices of power quality in high-voltage electrical networks using different types of high-voltage scale voltage converters. Methodology. Comparison of the requirements of IEC 61000-4-30 Standard to high-voltage scale voltage converters, when measuring power quality indices, with the characteristics of high voltage electromagnetic transformers used in Ukraine, and with promising developments of high-voltage converters of other types. Results. It is shown in the study that in order to fulfill some of the requirements for class A of IEC 61000-4-30, the characteristics of electromagnetic voltage transformers should be determined in the substation conditions using mobile calibration high-voltage laboratories. To meet all the requirements for Class A IEC 61000-4-30, it is recommended to use broadband high-voltage dividers of resistive-capacitive type. Originality. In study it is shown firstly that all the requirements of the IEC 61000-4-30 Standard for high-voltage scale voltage converters can be performed on the basis of the use of broadband resistive-capacitive damped voltage dividers. Practical value. Expositions of specific types of resistive-capacitive high-voltage dividers are presented, their parameters are confirmed by the results of state

  10. A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

    2017-01-01

    with low grade inflammation and increased risk of metabolic syndrome. However, so far, no studies have evaluated whether testosterone substitution improves metabolic dysfunction in TC survivors with mild Leydig cell insufficiency. Methods/design: This is a single-center, randomized, double-blind, placebo......Background: Elevated serum levels of luteinizing hormone and slightly decreased serum levels of testosterone (mild Leydig cell insufficiency) is a common hormonal disturbance in testicular cancer (TC) survivors. A number of studies have shown that low serum levels of testosterone is associated......-controlled study, designed to evaluate the effect of testosterone replacement therapy in TC survivors with mild Leydig cell insufficiency. Seventy subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed...

  11. A NEW DIVIDE: A ROMANTIC VERSUS A CLASSICAL ORTHODOXY

    Directory of Open Access Journals (Sweden)

    J. MILBANK

    2011-08-01

    Full Text Available In his contribution, the author wishes to trace a few of the contemporary trends of western European theology. He notes that alongside the growing infl uence of Roman Catholic theological thought in the West, there also arose a new theological divide between, what he terms, the romantic and the classical modes of theological orthodoxy. Both positions use diff erent methodological approaches in their common attempt at off ering resistance to secular modernity: the former appealing to the senses, the imagination and the fantasy, and the latter to unadulterated human reason.

  12. Digital Television, Convergence, and the Public: Another Digital Divide?

    Directory of Open Access Journals (Sweden)

    Jason Smith

    2009-06-01

    Full Text Available While 85 percent of Americans pay to receive television signals through satellite or cable companies, 15 percent still receive their television using over-the-air signals. With the elminination of analog television signals, the 15 percent of households have had to make significant changes in their viewing technology. These households tend to be elderly, poor, minority and rural. Signal coverage areas will be cut back, since government assumed a viewer would have an antenna on a 30 foot pole. Few do, and governmental programs delibertely hid this engineering fact. It is argued that digitalism has neglected the public use of the airways and created yet one more digital divide.

  13. Affinity and Hostility in Divided Communities: a Mathematical Model

    CERN Document Server

    Thron, Christopher

    2015-01-01

    We propose, develop, and analyze a mathematical model of intergroup attitudes in a community that is divided between two distinct social groups (which may be distinguished by religion, ethnicity, or some other socially distinguishing factor). The model is based on very simple premises that are both intuitive and justified by sociological research. We investigate the behavior of the model in various special cases, for various model configurations. We discuss the stability of the model, and the continuous or discontinuous dependence of model behavior on various parameters. Finally, we discuss possible implications for strategies to improve intergroup affinity, and to defuse tension and prevent deterioration of intergroup relationships.

  14. Green and sustainable median on a divided multilane highway

    Science.gov (United States)

    Ambak, K.; Bajuri, F. A. A.; Yusoff, N. A.; Madun, A.; Prasetijo, J.

    2017-11-01

    The road system in Malaysia showed good growth with increasing number of vehicles on the road. However, statistic of road accident is still at an alarming rate. There are many factor can contribute to the occurrence of an accident. If the accident was caused by road facilities such as street furniture, it is shown that the street furniture was failed to improve the safety of the road users. In this study, a new concept of materials for the construction of road dividers was purpose. The sustainable materials such as laterite soil, Cow Grass, tires and PVC pipes was used to replace the cement and iron guardrails in road divider construction. The main objectives of this study is to design characteristics of a road divider using natural material such as laterite soil, sand, grass and recycle material like used a tyre. A series of experiments such as test liquid limit, plastic limit test, standard proctor test and observations of root growth in 30 days were conducted. The result shows that the plastic index value of 35% was obtained. From the proctor compaction test, the optimum water content was 23% and maximum dry density at 15.3 kN/m3. This value was used to build a prototype of green and sustainable raised road median. The suitability of sand used as the medium in irrigation system was approved. Permeability of sand is 10-2 mm/s to 10 mm/s which is having a high rate of flow. The growth of Cow Grass roots was increased by 4.9 cm in 30 days. This shows that, the grass is suitable to grow in laterite soil and can be used as vegetation material. Through the impact test conducted on a model with a scale of 1:7.5, indicate the initial damage occurred when a force reaches 10N. However, the condition of the model is still stable. From the impact test conducted, the prototype of green and sustainable raised road median has a good potential to be used as existing road divider as it can absorb the impact of an accident.

  15. Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial.

    Science.gov (United States)

    Kamwesiga, Julius; Mutabazi, Vincent; Kayumba, Josephine; Tayari, Jean-Claude K; Uwimbabazi, Jean Claude; Batanage, Gad; Uwera, Grace; Baziruwiha, Marcel; Ntizimira, Christian; Murebwayire, Antoinette; Haguma, Jean Pierre; Nyiransabimana, Julienne; Nzabandora, Jean Bosco; Nzamwita, Pascal; Mukazayire, Ernestine

    2015-06-01

    To examine the effect of selenium supplementation on CD4 T-cell counts, viral suppression, and time to antiretroviral therapy (ART) initiation in ART-naive HIV-infected patients in Rwanda. A multicenter, double-blinded, placebo-controlled, randomized clinical trial was conducted. Eligible patients were HIV-infected adults (≥21 years) who had a CD4 cell count between 400 and 650 cells/μl (ART eligibility was ≤350 cells/μl throughout the trial), and were willing to practice barrier methods of birth control. Patients were randomized to receive once-daily 200 μg selenium tablets or identical placebo. They were followed for 24 months with assessments every 6 months. Declines in CD4 cell counts were modeled using linear regressions with generalized estimating equations and effect modification, and the composite outcome (ART eligible or ART initiation) using Cox proportional-hazards regression, both conducted with intention to treat. Of the 300 participants, 149 received selenium, 202 (67%) were women, and median age was 33.5 years. The rate of CD4 depletion was reduced by 43.8% [95% confidence interval (CI) 7.8-79.8% decrease] in the treatment arm - from mean 3.97 cells/μl per month to mean 2.23 cells/μl per month. We observed 96 composite outcome events - 45 (47%) in the treatment arm. We found no treatment effect for the composite outcome (hazard ratio 1.00, 95% CI 0.66-1.54) or viral suppression (odds ratio 1.18, 95% CI 0.71-1.94). The trial was underpowered for the composite outcome due to a lower-than-anticipated event rate. Adverse events were comparable throughout. This randomized clinical trial demonstrated that 24-month selenium supplementation significantly reduces the rate of CD4 cell count decline among ART-naive patients.

  16. Stratified Flow Past a Hill: Dividing Streamline Concept Revisited

    Science.gov (United States)

    Leo, Laura S.; Thompson, Michael Y.; Di Sabatino, Silvana; Fernando, Harindra J. S.

    2016-06-01

    The Sheppard formula (Q J R Meteorol Soc 82:528-529, 1956) for the dividing streamline height H_s assumes a uniform velocity U_∞ and a constant buoyancy frequency N for the approach flow towards a mountain of height h, and takes the form H_s/h=( {1-F} ) , where F=U_{∞}/Nh. We extend this solution to a logarithmic approach-velocity profile with constant N. An analytical solution is obtained for H_s/h in terms of Lambert-W functions, which also suggests alternative scaling for H_s/h. A `modified' logarithmic velocity profile is proposed for stably stratified atmospheric boundary-layer flows. A field experiment designed to observe H_s is described, which utilized instrumentation from the spring field campaign of the Mountain Terrain Atmospheric Modeling and Observations (MATERHORN) Program. Multiple releases of smoke at F≈ 0.3-0.4 support the new formulation, notwithstanding the limited success of experiments due to logistical constraints. No dividing streamline is discerned for F≈ 10, since, if present, it is too close to the foothill. Flow separation and vortex shedding is observed in this case. The proposed modified logarithmic profile is in reasonable agreement with experimental observations.

  17. On a nonlinear Kalman filter with simplified divided difference approximation

    KAUST Repository

    Luo, Xiaodong

    2012-03-01

    We present a new ensemble-based approach that handles nonlinearity based on a simplified divided difference approximation through Stirling\\'s interpolation formula, which is hence called the simplified divided difference filter (sDDF). The sDDF uses Stirling\\'s interpolation formula to evaluate the statistics of the background ensemble during the prediction step, while at the filtering step the sDDF employs the formulae in an ensemble square root filter (EnSRF) to update the background to the analysis. In this sense, the sDDF is a hybrid of Stirling\\'s interpolation formula and the EnSRF method, while the computational cost of the sDDF is less than that of the EnSRF. Numerical comparison between the sDDF and the EnSRF, with the ensemble transform Kalman filter (ETKF) as the representative, is conducted. The experiment results suggest that the sDDF outperforms the ETKF with a relatively large ensemble size, and thus is a good candidate for data assimilation in systems with moderate dimensions. © 2011 Elsevier B.V. All rights reserved.

  18. Embodied ideas and divided selves: revisiting Laing via Bakhtin.

    Science.gov (United States)

    Burkitt, Ian; Sullivan, Paul

    2009-09-01

    In this article, we apply Mikhail Bakhtin's model of a 'divided self' to R.D. Laing's eponymous work on the lived experience of divided selves in 'psychosis'. Both of these authors offer intriguing insights into the fracturing of self through its social relationships (including the 'micro-dialogues' staged for oneself) but from uniquely different perspectives. Bakhtin (1984) uses Dostoevsky's novels as his material for a theory of self, centrally concerned with moments of split identity, crisis, and personal transformation, while Laing relies on his patient's accounts of 'psychosis'. We will outline how two key Bakhtinian divisions of the self (spirit/soul and authoritative/internally persuasive discourse) help to make sense of Laing's descriptions of his patient's experiences and micro-dialogues. Conversely, when refracted through Laing's phenomenology Bakhtin's account of the self becomes richer and somewhat darkened in terms of a double-edged ontology, which describes a maximally open self but one that is consumed by ideas, unable to manage their contradictions. The implications of this for managing the dilemmas of self-identity will be drawn out.

  19. Divided attention impairs human motor adaptation but not feedback control.

    Science.gov (United States)

    Taylor, Jordan A; Thoroughman, Kurt A

    2007-07-01

    When humans experience externally induced errors in a movement, the motor system's feedback control compensates for those errors within the movement. The motor system's predictive control then uses information about those errors to inform future movements. The role of attention in these two distinct motor processes is unclear. Previous experiments have revealed a role for attention in motor learning over the course of many movements; however, these experimental paradigms do not determine how attention influences within-movement feedback control versus across-movement adaptation. Here we develop a dual-task paradigm, consisting of movement and audio tasks, which can differentiate and expose attention's role in these two processes of motor control. Over the course of several days, subjects performed horizontal reaching movements, with and without the audio task; movements were occasionally subjected to transient force perturbations. On movements with a force perturbation, subjects compensated for the force-induced movement errors, and on movements immediately after the force perturbation subjects exhibited adaptation. On every movement trial, subjects performed a two-tone frequency-discrimination task. The temporal specificity of the frequency-discrimination task allowed us to divide attention within and across movements. We find that divided attention did not impair the within-movement feedback control of the arm, but did reduce subsequent movement adaptation. We suggest that the secondary task interfered with the encoding and transformation of errors into changes in predictive control.

  20. Crossing the Sacred/Secular Divide; Unraveling Turkish Identities

    Directory of Open Access Journals (Sweden)

    Morrow Lisa

    2016-06-01

    Full Text Available This paper unpacks the ideas in the poem “Pull Down My Statues” by Süleyman Apaydın, to examine some common descriptors in use about modern Turkey. Taking his inspiration from Mustafa Kemal Atatürk, the founder of the modern Turkish republic, Apaydın ponders the success of Atatürk’s vision, based on the idea of a secular/sacred divide. Combining this with the way travel in Turkey is heavily promoted using the same themes, I explore how this divide, with its underlying connotations of West versus East and modernity versus tradition (as found in Turkey’s Ottoman past, is applied to Turkish identity. Turks are commonly portrayed as a homogenous people only differentiated by their degree of religiosity, but I argue that this analysis is too simplistic. Turkish identity has never been based on a single clear cut model, and this is becoming obvious as more traditional Islamic ways of life are being reworked by new forms of Islam based on capitalism. Consequently, although it is important to acknowledge Turkey’s past, looking to history for a way to steer through the complexities of the present is no longer useful or even relevant.

  1. Phase 3 Randomized Low-Dose Paclitaxel Chemoradiotherapy Study for Locally Advanced Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Lin, Hongmei; Chen, Yuhchyau; Shi, Anhui; Pandya, Kishan J; Yu, Rong; Yuan, Yannan; Li, Jiancheng; Li, Hang; Wang, Yingjie; Xia, Tingyi; Feng, Linchun; Ma, Huimin; Geng, Jianhao; Zhu, Guangying

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with poor chest tumor control. Here, we report results of a randomized phase 3 study comparing two CCRT regimens in improving chest tumor control by low-dose paclitaxel chemoradiation for LA-NSCLC. Due to the logistics of local referral pattern, the study was designed to enroll patients with stage III LA-NSCLC who had completed 2-4 cycles of full-dose chemotherapy. One hundred thirty four were randomized to either Arm 1 [paclitaxel at 15 mg/m2, three times per week (Monday, Wednesday, and Friday) for 6 weeks, n = 74] or Arm 2 (weekly paclitaxel at 45 mg/m2 for 6 weeks, n = 60). Chest radiotherapy was 60-70 Gy in standard fractionation. Response rate was the primary endpoint, with recurrence-free survival (RFS) as the secondary endpoint. From March 2006 to February 2013, 71 patients completed Arm 1 treatment and 59 completed Arm 2 treatment. The response rate for Arm 1 was significantly higher (83.1%) than Arm 2 (54.2%) (p=0.001). RFS was superior in Arm 1: median 14.6 vs. 9.4 months, p = 0.005, Hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.20, 2.90]. Overall survival was not significantly different: median 32.6 months in Arm 1 vs. 31.3 months in Arm 2, p = 0.91, HR 0.97 (95% CI 0.55, 1.70). Toxicity was significantly lower in Arm 1 for Grade 3 and 4 leukopenia/neutropenia (p < 0.001). Pulsed low-dose paclitaxel CCRT resulted in significantly better RFS and tumor response rate, and less hematologic toxicities than weekly CCRT for LA-NSCLC.

  2. Comparison of Ivor-Lewis vs Sweet esophagectomy for esophageal squamous cell carcinoma: a randomized clinical trial.

    Science.gov (United States)

    Li, Bin; Xiang, Jiaqing; Zhang, Yawei; Li, Hecheng; Zhang, Jie; Sun, Yihua; Hu, Hong; Miao, Longsheng; Ma, Longfei; Luo, Xiaoyang; Chen, Sufeng; Ye, Ting; Zhang, Yiliang; Zhang, Yang; Chen, Haiquan

    2015-04-01

    Sweet esophagectomy is performed widely in China, while the Ivor-Lewis procedure, with potential benefit of an extended lymphadenectomy, is limitedly conducted owing to concern for a higher risk for morbidity. Thus, the role of the Ivor-Lewis procedure for thoracic esophageal cancer needs further investigation. To determine whether Ivor-Lewis esophagectomy is associated with increased postoperative complications compared with the Sweet procedure. A randomized clinical trial was conducted from May 2010 to July 2012 at Fudan University Shanghai Cancer Center, Shanghai, China, of 300 patients with resectable squamous cell carcinoma in the middle and lower third of the thoracic esophagus. Intent-to-treat analysis was performed. Patients were randomly assigned to receive either the Ivor-Lewis (n = 150) or Sweet (n = 150) esophagectomy. The primary outcome of this clinical trial was operative morbidity (any surgical or nonsurgical complications). Secondary outcomes included oncologic efficacy (number of lymph nodes resected and positive lymph nodes), postoperative mortality (30-day and in-hospital mortality), and patient discharge. Resection without macroscopical residual (R0/R1) was achieved in 149 of 150 patients in each group. Although there was no significant difference between the 2 groups regarding the incidence of each single complication, a significantly higher morbidity rate was found in the Sweet group (62 of 150 [41.3%]) than in the Ivor-Lewis group (45 of 150 [30%]) (P = .04). More patients in the Sweet group (8 of 150 [5.3%]) received reoperations than in the Ivor-Lewis group (1 of 150 [0.7%]) (P = .04). The median hospital stay was 18 days in the Sweet group vs 16 days in the Ivor-Lewis group (P = .002). Postoperative mortality rates in the Ivor-Lewis (1 of 150) and Sweet (3 of 150) groups were 0.7% and 2.0%, respectively (P = .25). More lymph nodes were removed during Ivor-Lewis esophagectomy than during the Sweet procedure (22 vs

  3. A Prospective Randomized Study of the Radiotherapy Volume for Limited-stage Small Cell Lung Cancer: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Xiao HU

    2010-07-01

    Full Text Available Background and objective Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC. The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS between patients received different target volumes irradiation after induction chemotherapy. Methods LSCLC patients received 2 cycles of etoposide and cisplatin (EP induction chemotherapy and were randomly assigned to receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T as study arm and control arm, CTV-N included the positive nodal drainage area for both arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was administered concurrently with the third cycle of EP regimen. After that, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation (PCI was administered to patients with a complete response. Results Thirty-seven and 40 patients were randomly assigned to study arm and control arm. The local recurrence rates were 32.4% and 28.2% respectively (P=0.80; the isolated nodal failure (INF rate were 3.0% and 2.6% respectively (P=0.91; all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3 disease was the risk factor for INF (P=0.02, OR=14.13, 95%CI: 1.47-136.13. During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and 56.4%, 7.7% patients respectively (P=0.04. Grade 0-I and II-III late pulmonary injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P=0.07. Median survival time was 22.1 months and 26.9 months respectively. The 1 to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P=0.79. Conclusion The preliminary results of this study indicate that irradiant the post-chemotherapy tumor extent (GTV-T and positive nodal drainage area did not decrease local control and overall

  4. Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic Heart Disease (MyStromalCell Trial: A Randomized Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Abbas Ali Qayyum

    2017-01-01

    Full Text Available We aimed to evaluate the effect of intramyocardial injections of autologous VEGF-A165-stimulated adipose-derived stromal cells (ASCs in patients with refractory angina. MyStromalCell trial is a randomized double-blind placebo-controlled study including sixty patients with CCS/NYHA class II-III, left ventricular ejection fraction > 40%, and at least one significant coronary artery stenosis. Patients were treated with ASC or placebo in a 2 : 1 ratio. ASCs from the abdomen were culture expanded and stimulated with VEGF-A165. At 6 months follow-up, bicycle exercise tolerance increased significantly in time duration 22 s (95%CI −164 to 208 s (P=0.034, in watt 4 (95%CI −33 to 41, 0.048, and in METs 0.2 (95%CI −1.4 to 1.8 (P=0.048 in the ASC group while there was a nonsignificant increase in the placebo group in time duration 9 s (95%CI −203 to 221 s (P=0.053, in watt 7 (95%CI −40 to 54 (P=0.41, and in METs 0.1 (95%CI −1.7 to 1.9 (P=0.757. The difference between the groups was not significant (P=0.680, P=0.608, and P=0.720 for time duration, watt, and METs, resp.. Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not improve exercise capacity compared to placebo. However, exercise capacity increased in the ASC but not in the placebo group. This trial is registered with ClinicalTrials.gov NCT01449032.

  5. Matrix analysis of the digital divide in eHealth services using awareness, want, and adoption gap.

    Science.gov (United States)

    Liang, Te-Hsin

    2012-02-13

    The digital divide usually refers to access or usage, but some studies have identified two other divides: awareness and demand (want). Given that the hierarchical stages of the innovation adoption process of a customer are interrelated, it is necessary and meaningful to analyze the digital divide in eHealth services through three main stages, namely, awareness, want, and adoption. By following the three main integrated stages of the innovation diffusion theory, from the customer segment viewpoint, this study aimed to propose a new matrix analysis of the digital divide using the awareness, want, and adoption gap ratio (AWAG). I compared the digital divide among different groups. Furthermore, I conducted an empirical study on eHealth services to present the practicability of the proposed methodology. Through a review and discussion of the literature, I proposed hypotheses and a new matrix analysis. To test the proposed method, 3074 Taiwanese respondents, aged 15 years and older, were surveyed by telephone. I used the stratified simple random sampling method, with sample size allocation proportioned by the population distribution of 23 cities and counties (strata). This study proposed the AWAG segment matrix to analyze the digital divide in eHealth services. First, awareness and want rates were divided into two levels at the middle point of 50%, and then the 2-dimensional cross of the awareness and want segment matrix was divided into four categories: opened group, desire-deficiency group, perception-deficiency group, and closed group. Second, according to the degrees of awareness and want, each category was further divided into four subcategories. I also defined four possible strategies, namely, hold, improve, evaluate, and leave, for different regions in the proposed matrix. An empirical test on two recently promoted eHealth services, the digital medical service (DMS) and the digital home care service (DHCS), was conducted. Results showed that for both e

  6. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial.

    Science.gov (United States)

    Bergeron, Anne; Chevret, Sylvie; Granata, Angela; Chevallier, Patrice; Vincent, Laure; Huynh, Anne; Tabrizi, Reza; Labussiere-Wallet, Hélène; Bernard, Marc; Chantepie, Sylvain; Bay, Jacques-Olivier; Thiebaut-Bertrand, Anne; Thepot, Sylvain; Contentin, Nathalie; Fornecker, Luc-Matthieu; Maillard, Natacha; Risso, Karine; Berceanu, Ana; Blaise, Didier; Peffault de La Tour, Regis; Chien, Jason W; Coiteux, Valérie; Socié, Gérard

    2017-08-08

    Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome. To evaluate if the early administration of azithromycin can improve airflow decline-free survival after allogeneic HSCT. The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who were at least 16 years old, had undergone allogeneic HSCT for a hematological malignancy, and had available pretransplant pulmonary function test results. Enrollment was from February 2014 to August 2015 with follow-up through April 26, 2017. Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. The primary efficacy end point was airflow decline-free survival at 2 years after randomization. Main secondary end points were overall survival and bronchiolitis obliterans syndrome at 2 years. Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped December 26, 2016. Among 480 randomized participants, 465 (97%) were included in the modified intention-to-treat analysis (mean age, 52 [SD, 14] years; 75 women [35%]). At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). Two-year airflow decline-free survival was 32.8% (95% CI, 25.9%-41.7%) with azithromycin and 41.3% (95% CI, 34.1%-50.1%) with placebo (unadjusted hazard ratio [HR], 1.3; 95% CI, 1.02-1.70; P = .03). Of the 22 patients (5%) who experienced bronchiolitis obliterans syndrome, 15 (6%) were in

  7. Asymmetricity Between Sister Cells of Pluripotent Stem Cells at the Onset of Differentiation.

    Science.gov (United States)

    Nakamura, Shogo; Maruyama, Atsushi; Kondo, Yuki; Kano, Ayumu; De Sousa, Olga M; Iwahashi, Masahiro; Hexig, Bayar; Akaike, Toshihiro; Li, Jingyue; Hayashi, Yohei; Ohnuma, Kiyoshi

    2018-02-21

    Various somatic stem cells divide asymmetrically; however, it is not known whether embryonic stem cells (ESCs) divide symmetrically or asymmetrically, not only while maintaining an undifferentiated state but also at the onset of differentiation. In this study, we observed single ESCs using time-lapse imaging and compared sister cell pairs derived from the same mother cell in either the maintenance or differentiation medium. Mouse ESCs were cultured on E-cadherin-coated glass-based dishes, which allowed us to trace single cells. The undifferentiated cell state was detected by green fluorescent protein (GFP) expression driven by the Nanog promoter, which is active only in undifferentiated cells. Cell population analysis using flow cytometry showed that the peak width indicating distribution of GFP expression broadened when cells were transferred to the differentiation medium compared to when they were in the maintenance medium. This finding suggested that the population of ESCs became more heterogeneous at the onset of differentiation. Using single-cell analysis by time-lapse imaging, we found that although the total survival ratio decreased by changing to differentiation medium, the one-live-one-dead ratio of sister cell pairs was smaller compared with randomly chosen non-sister cell pairs, defined as an unsynchronized cell pair control, in both media. This result suggested that sister cell pairs were more positively synchronized with each other compared to non-sister cell pairs. The differences in interdivision time (the time interval between mother cell division and the subsequent cell division) between sister cells was smaller than that between non-sister cell pairs in both media, suggesting that sister cells divided synchronously. Although the difference in Nanog-GFP intensity between sister cells was smaller than that between non-sister cells in the maintenance medium, it was the same in differentiation medium, suggesting asymmetrical Nanog-GFP intensity. These

  8. Attitude estimation by divided difference filter in quaternion space

    Science.gov (United States)

    Ahmadi, Mohammad; Khayatian, Alireza; Karimaghaee, Paknoush

    2012-06-01

    This article considers the application of Divided Difference Filter (DDF) to the orientation estimation, based on a quaternion-error continuous-discrete time model. DDF is a nonlinear estimator that in contrast to Taylor's expansion of extended Kalman Filter (EKF), exploit the polynomial approximations as a multivariable extension of Stirling's interpolation formula and require no derivatives. The DDF can be based on 1st and 2nd order Stirling's interpolation, which is named the divided difference filter-1st order (DDF1) and the divided difference filter-2nd order (DDF2). The orientation kinematics is defined in a quaternion vector space that unlike the Euler angle representation does not have any singularity problem. The presented nonlinear orientation model is an exact error model and is independent of the rigid body dynamics. The nonlinear process model includes six error-states in which only non-scalar elements of quaternion error vector are included in the error-state equations. The fourth element of quaternion error vector, which obeys unit norm constraint, is removed from system states to alleviate the estimated error covariance matrix divergence. The measurement system is a MARG sensor, which consists of a tri-axial rate gyro, a tri-axial accelerometer and a tri-axial magnetometer. The nonlinear measurement model is obtained based on the principals of magnetometer and accelerometer and the properties of the quaternion vector space. For the presented nonlinear orientation model, the performance of three filters namely DDF, EKF and Unscented Kalman Filter (UKF) is compared for different sampling frequencies in terms of the rms error, the captured area under the error norm curve, the estimated state variance and the computational cost. It is shown that under the same initial angle-error conditions, DDFs and UKF are more robust than EKF. The DDFs perform better than unscented Kalman filter (UKF) although the computational load for UKF is less. Among DDF1 and

  9. Revolutions in Global Networking and Collaborations, and the Digital Divide

    Science.gov (United States)

    Newman, Harvey

    2007-04-01

    The major physics experiments of the next twenty five years, such as those at the Large Hadron Collider and the International Linear Collider, will break new ground in our understanding of the fundamental interactions, structures and symmetries that govern the nature of matter and spacetime. In order to realize the scientific wealth of these experimental programs, physicists have formed global-scale collaborations and built grid systems where the data is processed, distributed and collaboratively analyzed using networked computing facilities at more than 100 sites around the world. Effective use of these emerging ensembles of facilities and networks presents new challenges in Petabyte-scale data access, processing and distribution, and collaboration across national and international networks on a scale unprecedented in the history of science. The key to meeting these challenges is the effective use of data networks. The bandwidth use by high energy physicists, paralleled by scientists in other fields of data intensive science, continues to grow at several hundred times per decade, and there are indications that this growth is accelerating. This is helping to drive the growth of the major networks serving research and education, as well as mission-oriented networks in the US, Europe, Asia-Pacific, Latin America and across the Atlantic and Pacific oceans. Physicists and computer scientists have together made striking technological advances in recent years, and have developed tools that allow full use of long range 10 gigabit/sec links on a routine basis for the first time. As the science community continues to advance in its development of networks and grid systems, a key concern is the rising Digital Divide between the favored and less-favored regions of the world. Closing the Divide is vital for the health of our global collaborations and our field. In this talk I will review these trends, and focus on the means to reduce the Digital Divide, from the perspective of

  10. The effects of music therapy in patients with high-dose chemotherapy and stem cell support: a randomized pilot study.

    Science.gov (United States)

    Tuinmann, Gert; Preissler, Pia; Böhmer, Hauke; Suling, Anna; Bokemeyer, Carsten

    2017-03-01

    Patients with high dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) are highly distressed. Psycho-oncological support might be beneficial but is not routinely provided. Our aim was to investigate whether music therapy (MT) in addition to standard supportive treatment had any effect on quality of life, depression, anxiety, side effects of therapy, medication, and immunological changes during and within three months after HDC plus ASCT. Patients (n = 66) with HDC plus ASCT were randomly assigned to either MT (Intervention Group = IG) or standard supportive treatment (Control Group = CG). Quality of life was measured by EORTC QLQ-C30. Depression and anxiety were measured by the HADS-D before transplantation, during and after the inpatient stay. In addition, adverse events (AE), medication, and immunological parameters were observed. There was no improvement of global quality of life for patients receiving additional MT, but their perception of pain significantly changed (p = 0.027). Patients were neither depressed nor anxious on admission, therefore no improvements were found. IG patients had less 3-4° toxicities (e.g., mucositis). Aprepitant for antiemetic therapy was administered significantly more often in the CG (p = 0.040). The IgA decline and T4 count was less in IG, T8, and NK count decreased most in IG. These findings failed significance. MT may improve pain perception in patients receiving HDC plus ASCT. Additionally positive effects on toxicities, use of antiemetic medication, and immunological changes were observed. As some of these findings failed significance, studies with larger sample sizes are needed. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. [Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer].

    Science.gov (United States)

    Gao, Jian-Fei; Li, Chang-Sheng; Zhang, Bi-Cheng; Du, Guang-Zu; Zhang, Xin-Hua; Wang, Jun; Zhu, Yu-Ze; Ou, Wu-Ling; Yang, Bo

    2004-04-01

    Non-small cell lung cancer (NSCLC) is hyposensitive to the normal first and second-line chemotherapy regimens. Camptothecin derivative is becoming a hot point in the treatment of advanced NSCLC. The objective of this article was to evaluate the response, toxicity, and survival time of HMVP, MVP, and HVP regimens (detail in below) in the treatment of advanced NSCLC. A total of 134 cases with advanced NSCLC was randomized into three groups: HMVP group [46 patients, hydroxycamptothecin (HCPT) 12 mg/m(2) from d1 to d5, mitomycin C (MMC) 6 mg/m(2) d1, vindesine (VDS) 2.5-3 mg/m(2) d1 and d8, cisplatin (DDP) 50 mg/m(2) d2 and d3], MVP group (44 patients, MMC, VDS and DDP were the same as HMVP group) and HVP group (44 patients, HCPT, VDS, DDP were the same as HMVP group). The response rates were 39.54% (17/43), 35.57% (15/42), and 26.19% (11/42) in HMVP, MVP, and HVP groups, respectively; no significant difference was detected among the three groups (P >0.05). No significant difference was detected in the median time of remission, median survival time, and 1-, 2-year survival rates among the three groups. Moreover, no significant difference was detected in grade III-IV leukopenia, grade III-IV thrombocytopenia, grade III-IV nausea and vomiting and grade III-IV constipation among the three groups. The response rate of MVP regimen is slightly lower than that of HMVP regimen, but HMVP regimen do not show obvious superiority. It may increase toxicities such as leukopenia, nausea/vomiting, and constipation. The response rate of HVP regimen is slightly lower than that of MVP regimen.

  12. Amniotic membrane graft to reconstruct divided nevi of eyelids.

    Science.gov (United States)

    Bhattacharjee, Kasturi; Singh, Manpreet; Bhattacharjee, Harsha

    2015-05-24

    Two patients with congenital divided nevi of the eyelids presented with chief symptoms of cosmetic blemish (n=2) and epiphora (n=1). All the lesions were surgically excised with histological free margins and amniotic membrane graft (AMG) was used to cover the mucosal and eyelid marginal defects. Caruncular and punctal involvement was managed with complete excision and monocanalicular stent insertion to prevent punctal stenosis. AMG provided an adequate scaffold for conjunctival regenesis and anatomic continuity was found within 6 weeks in both patients. None of them had any residual pigmentation or disease recurrence after a follow-up of more than 2.5 years. Local absence of eyelashes was the only drawback which patients masked with modern artificial eyelashes or make-up. This novel utility of AMG illustrates effective conjunctival regenesis and maintenance of mucocutaneous junction functionality. 2015 BMJ Publishing Group Ltd.

  13. Envy Up, Scorn Down: How Comparison Divides Us

    Science.gov (United States)

    Fiske, Susan T.

    2013-01-01

    Comparison compels people, even as it stresses, depresses, and divides us. Comparison is only natural, but the collateral damage reveals envy upward and scorn downward, and these emotions, arguably, poison people and their relationships. Summaries of several experiments—using questionnaire, psychometric, response-time, electromyographic, and neuroimaging data—illustrate the dynamics of envy up and scorn down, as well as proposing how to mitigate their effects. Initial studies suggest the importance of status. Other data show how scorn down minimizes thought about another’s mind; power deactivates mental concepts. Regarding envy up, other studies demonstrate that Schadenfreude (malicious joy) targets envied outgroups. However, counterstereotypic information, empathy, and outcome dependency can mitigate both scorn and envy. PMID:21058760

  14. Bridging the Digital Divide through Educational Initiatives: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Tom Butler

    2002-01-01

    Full Text Available Being on the wrong side of the digital divide limits the life chances of the socially excluded, who have had neither the wherewithal nor the opportunity to obtain highly paid, skilled positions in IT. Irish policy makers see education as the solution to this problem. However, provid-ing institutional support for the socially disadvantaged who wish to avail of third level education in IT poses significant challenges. This paper describes these problems and explains how they were overcome in implementing an undergraduate university programme called the Diploma in Applied Business Computing. This targeted initiative was an unqualified success in that it achieved its primary objectives--academic and social. However, what made it so was the commitment of concerned stakeholders, from members of the executive steering committee who developed and implemented the course, to the lecturers who delivered it, the companies who supported it, and the students who participated in it.

  15. Universal Service in a Broader Perspective: The European Digital Divide

    Directory of Open Access Journals (Sweden)

    Maria Concepcion GARCIA-JIMENEZ

    2009-01-01

    Full Text Available Ensuring universal service is a top objective in many countries in order that all the citizens can have access basic communications services. Although the ICT equipment in households and its usage by individuals are essential prerequisites for benefiting from ICTs, the situation in the European Union is far from uniform. This article provides a description of the European information society development scenario using the values reached by the member states in a set of indicators selected for measuring said progress in households. Two tools are used for providing a broader perspective of the digital divide: a composite index and the cluster analysis. Below, a study is provided on what variables are relevant for interpreting the situation that is presented.

  16. Bridging the Mass Divide: Super & Massive AGB Star Yields

    Science.gov (United States)

    Doherty, C. L.; Gil-Pons, P.; Lau, H. H. B.; Lattanzio, J. C.

    2012-08-01

    Super Asymptotic Giant Branch Stars (Super AGBs) lie in the mass range 6-11 M⊙, which bridges the divide between low/intermediate mass AGB and massive stars. During the thermally pulsing phase of evolution competition between hot bottom burning (HBB) and third dredge up (3DU) events determine the stellar yields. Obtaining these yields is far more computationally demanding than those of most AGB stars because Super AGBs undergo up to a few thousand thermal pulses. We describe results from evolutionary and nucleosynthetic calculations for these stellar models. We examine element production in these Super AGB stars over time, with results from five metallicities spanning the range Z = 0.02-10-4 ([Fe/H] 0 to -2.3). Super AGB star nucleosynthetic yields have hitherto been neglected in galactic chemical evolution modelling.

  17. Nationality Divides and Shared Leadership in Multinational Teams

    DEFF Research Database (Denmark)

    Paunova, Minna

    2015-01-01

    dynamics, shared leadership within the team, and team performance. We conduct two empirical studies, and find that the number and balance of identity subgroups have important implications for multinational team functioning, in line with social identity approaches. Interestingly, the number and balance......How shared leadership is enacted in teams that are nationally diverse is currently under- researched, despite the increasing presence of multinational teams in the workplace. To better understand the phenomenon of shared leadership in multinational team contexts, we propose two ways in which...... nationality-based characteristics of members may divide teams and affect leadership. We argue that the national belonging of members may result in both identity subgroups and status ranks. However, the configurational properties of identity subgroups and status ranks will have distinct effects on team...

  18. Envy up, scorn down: how comparison divides us.

    Science.gov (United States)

    Fiske, Susan T

    2010-11-01

    Comparison compels people, even as it stresses, depresses, and divides us. Comparison is only natural, but the collateral damage reveals envy upward and scorn downward, and these emotions, arguably, poison people and their relationships. Summaries of several experiments--using questionnaire, psychometric, response-time, electromyographic, and neuroimaging data--illustrate the dynamics of envy up and scorn down, as well as proposing how to mitigate their effects. Initial studies suggest the importance of status. Other data show how scorn down minimizes thought about another's mind; power deactivates mental concepts. Regarding envy up, other studies demonstrate that Schadenfreude (malicious joy) targets envied outgroups. However, counterstereotypic information, empathy, and outcome dependency can mitigate both scorn and envy. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  19. The cultural divide: exploring communication barriers between scientists and clinicians

    Directory of Open Access Journals (Sweden)

    Linda L. Restifo

    2011-07-01

    Despite remarkable advances in basic biomedical science that have led to improved patient care, there is a wide and persistent gap in the abilities of researchers and clinicians to understand and appreciate each other. In this Editorial, the authors, a scientist and a clinician, discuss the rift between practitioners of laboratory research and clinical medicine. Using their first-hand experience and numerous interviews throughout the United States, they explore the causes of this ‘cultural divide’. Members of both professions use advanced problem-solving skills and typically embark on their career paths with a deeply felt sense of purpose. Nonetheless, differences in classroom education, professional training environments, reward mechanisms and sources of drive contribute to obstacles that inhibit communication, mutual respect and productive collaboration. More than a sociological curiosity, the cultural divide is a significant barrier to the bench-to-bedside goals of translational medicine. Understanding its roots is the first step towards bridging the gap.

  20. Effect of dividing daylight in symmetric prismatic daylight collector

    Science.gov (United States)

    Yeh, Shih-Chuan; Lu, Ju-Lin; Cheng, Yu-Chin

    2017-04-01

    This paper presented a symmetric prismatic daylight collector to collect daylight for the natural light illumination system. We analyzed the characteristics of the emerging light when the parallel light beam illuminate on the horizontally placed symmetric prismatic daylight collector. The ratio of the relative intensities of collected daylight that emerging from each surface of the daylight collector shown that the ratio is varied with the incident angle during a day. The simulation of the emerging light of the daylight collector shown that the ratio of emerging light is varied with the tilted angle when sunshine illuminated on a symmetric prismatic daylight collector which was not placed horizontally. The integration of normalized intensity is also varied with the tilted angle. The symmetric prismatic daylight collector with the benefits of reducing glare and dividing intensity of incident daylight, it is applicable to using in the natural light illumination system and hybrid system for improving the efficiency of utilizing of solar energy.

  1. Further reflections on the humanistic psychology-positive psychology divide.

    Science.gov (United States)

    Waterman, Alan S

    2014-01-01

    Replies to comments by Morley (see record 2014-01475-010), Serlin (see record 2014-01475-011), Friedman (see record 2014-01475-012), Churchill and Mruk (see record 2014-01475-013), and Schneider (see record 2014-01475-014) on the current author's original article "The humanistic psychology-positive psychology divide: Contrasts in philosophical foundations" (see record 2013-12501-001). The article contrasting humanistic psychology and positive psychology with respect to their ontological, epistemological, and practical philosophical foundations has generated commentaries from leading proponents of varying perspectives within humanistic psychology. There is a great deal of material within those commentaries with which the current author is in full accord. It is worth noting at the outset that no one appears to be challenging the observations (a) that published exchanges between proponents of humanistic and positive psychology have been marked by tension and ambivalence, albeit with occasional efforts at reconciliation and rapprochement; (b) that proponents of the two perspectives differ with respect to the philosophers they most frequently cite in their writings; or (c) that such citations reflect the philosophical assumptions serving as foundations for the theoretical, research, and counseling/therapeutic endeavors of psychologists in both groups. The principal points of concurrence in the critiques published here are that the current underestimates the extent to which mutually supportive, collaborative work can be accomplished across the philosophical divide and that the recommendations the current author has made has advanced serious potential negative consequences for the field. The current author will address these points here in the reply, although space does not permit him to address other substantive points raised by individual commentators. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  2. Spike sorting for polytrodes: a divide and conquer approach

    Directory of Open Access Journals (Sweden)

    Nicholas V. Swindale

    2014-02-01

    Full Text Available In order to determine patterns of neural activity, spike signals recorded by extracellular electrodes have to be clustered (sorted with the aim of ensuring that each cluster represents all the spikes generated by an individual neuron. Many methods for spike sorting have been proposed but few are easily applicable to recordings from polytrodes which may have 16 or more recording sites. As with tetrodes, these are spaced sufficiently closely that signals from single neurons will usually be recorded on several adjacent sites. Although this offers a better chance of distinguishing neurons with similarly shaped spikes, sorting is difficult in such cases because of the high dimensionality of the space in which the signals must be classified. This report details a method for spike sorting based on a divide and conquer approach. Clusters are initially formed by assigning each event to the channel on which it is largest. Each channel-based cluster is then sub-divided into as many distinct clusters as possible. These are then recombined on the basis of pairwise tests into a final set of clusters. Pairwise tests are also performed to establish how distinct each cluster is from the others. A modified gradient ascent clustering (GAC algorithm is used to do the clustering. The method can sort spikes with minimal user input in times comparable to real time for recordings lasting up to 45 minutes. Our results illustrate some of the difficulties inherent in spike sorting, including changes in spike shape over time. We show that some physiologically distinct units may have very similar spike shapes. We show that RMS measures of spike shape similarity are not sensitive enough to discriminate clusters that can otherwise be separated by principal components analysis. Hence spike sorting based on least-squares matching to templates may be unreliable. Our methods should be applicable to tetrodes and scaleable to larger multi-electrode arrays (MEAs.

  3. Brain activity associated with selective attention, divided attention and distraction.

    Science.gov (United States)

    Salo, Emma; Salmela, Viljami; Salmi, Juha; Numminen, Jussi; Alho, Kimmo

    2017-06-01

    Top-down controlled selective or divided attention to sounds and visual objects, as well as bottom-up triggered attention to auditory and visual distractors, has been widely investigated. However, no study has systematically compared brain activations related to all these types of attention. To this end, we used functional magnetic resonance imaging (fMRI) to measure brain activity in participants performing a tone pitch or a foveal grating orientation discrimination task, or both, distracted by novel sounds not sharing frequencies with the tones or by extrafoveal visual textures. To force focusing of attention to tones or gratings, or both, task difficulty was kept constantly high with an adaptive staircase method. A whole brain analysis of variance (ANOVA) revealed fronto-parietal attention networks for both selective auditory and visual attention. A subsequent conjunction analysis indicated partial overlaps of these networks. However, like some previous studies, the present results also suggest segregation of prefrontal areas involved in the control of auditory and visual attention. The ANOVA also suggested, and another conjunction analysis confirmed, an additional activity enhancement in the left middle frontal gyrus related to divided attention supporting the role of this area in top-down integration of dual task performance. Distractors expectedly disrupted task performance. However, contrary to our expectations, activations specifically related to the distractors were found only in the auditory and visual cortices. This suggests gating of the distractors from further processing perhaps due to strictly focused attention in the current demanding discrimination tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Older people and digital disengagement: a fourth digital divide?

    Science.gov (United States)

    Olphert, Wendy; Damodaran, Leela

    2013-01-01

    Digital technologies are becoming more pervasive in all areas of society. Enabling everyone to have access and capability to use the Internet and associated digital technologies, summed up in the term 'digital inclusion', is seen to have wide-ranging benefits to the individual, to the economy and to society. For older people, being digitally included can help them to maintain their independence, social connectedness and sense of worth in the face of declining health or limited capabilities, as well as also offering new opportunities to improve their quality of life. At present however, access to the technology and to the benefits is not equally distributed either between or within nations, and older people tend to be on the 'wrong' side of what is termed the 'digital divide'. Governments globally are developing strategies to promote digital inclusion and indeed Internet uptake is increasing steadily, including amongst older people. However, such strategies have focussed on getting people online, and there appears to be an assumption that once someone is online they will remain 'digitally engaged'. In fact statistics show that some users give up using the Internet, and there is emerging evidence that older people are more vulnerable to the factors which can lead to this outcome. The authors see this phenomenon as a potential but largely unrecognised 'fourth digital divide' which has serious implications for social inclusion. The objectives of this article are (a) to raise awareness of the phenomenon of digital disengagement by considering some of the emerging evidence, (b) to explore some of the potential implications of not recognising and therefore not addressing the needs of the digitally disengaged older population, and (c) to reveal the prevailing gap in knowledge which future research should address. Copyright © 2013 S. Karger AG, Basel.

  5. Divided Attention and Processes Underlying Sense of Agency

    Directory of Open Access Journals (Sweden)

    Wen eWen

    2016-01-01

    Full Text Available Sense of agency refers to the subjective feeling of controlling events through one’s behavior or will. Sense of agency results from matching predictions of one’s own actions with actual feedback regarding the action. Furthermore, when an action involves a cued goal, performance-based inference contributes to sense of agency. That is, if people achieve their goal, they would believe themselves to be in control. Previous studies have shown that both action-effect comparison and performance-based inference contribute to sense of agency; however, the dominance of one process over the other may shift based on task conditions such as the presence or absence of specific goals. In this study, we examined the influence of divided attention on these two processes underlying sense of agency in two conditions. In the experimental task, participants continuously controlled a moving dot for 10 s while maintaining a string of three or seven digits in working memory. We found that when there was no cued goal (no-cued-goal condition, sense of agency was impaired by high cognitive load. Contrastingly, when participants controlled the dot based on a cued goal (cued-goal-directed condition, their sense of agency was lower than in the no-cued-goal condition and was not affected by cognitive load. The results suggest that the action-effect comparison process underlying sense of agency requires attention. On the other hand, the weaker influence of divided attention in the cued-goal-directed condition could be attributed to the dominance of performance-based inference, which is probably automatic.

  6. Performance of inverted polymer solar cells with randomly oriented ZnO nanorods coupled with atomic layer deposited ZnO

    Energy Technology Data Exchange (ETDEWEB)

    Zafar, Muhammad [School of Chemical Engineering, Chonnam National University, 300 Youngbong-dong, Gwangju 500-757 (Korea, Republic of); Yun, Ju-Young [Center for Vacuum, Korea Research Institute of Standards and Science, 267 Gajeong-ro, Daejeon 305-600 (Korea, Republic of); Kim, Do-Heyoung, E-mail: kdhh@chonnam.ac.kr [School of Chemical Engineering, Chonnam National University, 300 Youngbong-dong, Gwangju 500-757 (Korea, Republic of)

    2017-03-15

    Highlights: • Hydrothermally grown, randomly oriented, and low areal density ZnO nanorods have been successfully adopted as the electron transport layer in inverted organic solar cells. • The addition of atomic layer deposited ZnO on the ZnO nanorods effectively enhance the photovoltaic performances of inverted organic solar cells. • The inverted organic solar cells with 5 nm thick-ALD ZnO showed the highest power conversion efficiency of 3.08%, which is an enhancement of approximately 80% compared to the cells without the ALD ZnO layer (PCE = 1.67%). - Abstract: Nanostructuring of the electron transport layer (ETL) in organic photovoltaic cells (OPV) is of great interest because it increases the surface area of the cell and electron transport. In this work, hydrothermally grown, randomly oriented, and low areal density ZnO nanorods (NRs) have been adopted as the ETL, and the effect of adding atomic layer deposited (ALD) ZnO on the ZnO NRs on the inverted organic solar cell performance has been investigated. The fabricated inverted organic solar cell with 5-nm-thick ALD-ZnO grown on the ZnO NRs showed the highest power conversion efficiency (PCE) of 3.08%, which is an enhancement of 85% from that of the cell without ALD-ZnO (PCE = 1.67%). The ultrathin ALD-ZnO was found to act as a curing layer of the surface defects on the hydrothermally grown ZnO NRs, resulting in an improvement in photovoltaic performance.

  7. Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

    Directory of Open Access Journals (Sweden)

    Loretta Müller

    Full Text Available Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13 or placebo (alfalfa sprout homogenate, ASH; N = 16 on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1 and post (day2, day21 LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21 and T cell (day2 populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2. BSH supplementation further increased LAIV-induced granzyme B production (day2 in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses.ClinicalTrials.gov NCT01269723.

  8. Improving exercise prescriptions for hematological cancer patients during and after allogeneic stem cell transplantation. Conclusions from two large randomized controlled trials

    OpenAIRE

    Kühl, Rea Maria

    2016-01-01

    The evidence of exercise as adjuvant therapy option in cancer patients is increasing. Exercise constitutes a promising intervention to reduce treatment-related side-effects and to improve the rehabilitation process. Thus, there is growing interest in determining optimally targeted exercise prescriptions to maximize effects. However, few randomized controlled trials (RCTs) were conducted in haematological cancer patients during and after allogeneic stem cell transplantation (allo-HCT). Consequ...

  9. Nanoscale CuO solid-electrolyte-based conductive-bridging, random-access memory cell with a TiN liner

    Science.gov (United States)

    Lee, Jong-Sun; Kim, Dong-Won; Kim, Hea-Jee; Jin, Soo-Min; Song, Myung-Jin; Kwon, Ki-Hyun; Park, Jea-Gun; Jalalah, Mohammed; Al-Hajry, Ali

    2018-01-01

    The Conductive-bridge random-access memory (CBRAM) cell is a promising candidate for a terabit-level non-volatile memory due to its remarkable advantages. We present for the first time TiN as a diffusion barrier in CBRAM cells for enhancing their reliability. CuO solid-electrolyte-based CBRAM cells implemented with a 0.1-nm TiN liner demonstrated better non-volatile memory characteristics such as 106 AC write/erase endurance cycles with 100-μs AC pulse width and a long retention time of 7.4-years at 85 °C. In addition, the analysis of Ag diffusion in the CBRAM cell suggests that the morphology of the Ag filaments in the electrolyte can be effectively controlled by tuning the thickness of the TiN liner. These promising results pave the way for faster commercialization of terabit-level non-volatile memories.

  10. Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial.

    Science.gov (United States)

    Williams, Hywel C; Bath-Hextall, Fiona; Ozolins, Mara; Armstrong, Sarah J; Colver, Graham B; Perkins, William; Miller, Paul S J

    2017-03-01

    We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review. Five-year success was defined as 3-year success plus absence of recurrences identified through hospital, histopathology, and general practitioner records. Of 501 participants randomized, 401 contributed to the modified intention-to-treat analyses at year 3 (primary outcome), 383 (96%) of whom had data at year 5. Five-year success rates for imiquimod were 82.5% (170/206) compared with 97.7% (173/177) for surgery (relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001). These were comparable to year 3 success rates of 83.6% (178/213) and 98.4% (185/188) for imiquimod and surgery, respectively. Most imiquimod treatment failures occurred in year 1. Although surgery is clearly superior to imiquimod, this study shows sustained benefit for lesions that respond early to topical imiquimod. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Randomization tests

    CERN Document Server

    Edgington, Eugene

    2007-01-01

    Statistical Tests That Do Not Require Random Sampling Randomization Tests Numerical Examples Randomization Tests and Nonrandom Samples The Prevalence of Nonrandom Samples in Experiments The Irrelevance of Random Samples for the Typical Experiment Generalizing from Nonrandom Samples Intelligibility Respect for the Validity of Randomization Tests Versatility Practicality Precursors of Randomization Tests Other Applications of Permutation Tests Questions and Exercises Notes References Randomized Experiments Unique Benefits of Experiments Experimentation without Mani

  12. SMALL-DOSE CYTOKINES IN COMBINATION WITH 5-FLUOROURACIL IN OLISSEMINATED RENAL CELL CARCINOMA: FINAL RESULTS OF A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    L. V. Demidov

    2009-01-01

    Full Text Available Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity and efficacy is not sufficient. We suggest that a combination of very low-dose cytokines is effective and safe in metastatic renal cell carcinoma (MRCC patients (pts. A prospective randomized study was started in 2003. The primary end-point was a response rate. Methods: The eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0-2, no autoimmune diseases, no brain metastases, and normal organ function. All pts were randomized in three arms: IL-2 alone, 1.5 MIU, iv, t.i.w., weeks 1—3 or IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w, weeks 1—3 or biochemotherapy group 5-FU, 500 mg/m2, iv, once a week, weeks 1—3 plus IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w., weeks 1—3. Courses were repeated every three weeks. A response was assessed according to the RECIST every 2 courses.Results: 64 pts were enrolled, of whom 63 were analyzed. Their median age was 55.4 years (range 16—74. 42.9% of the patients had pre- viously received chemo- or immunotherapy. 55.6 percent of the pts had poor prognosis (according to Motzer et al., 2002. Bone metastases were present in 52.4% of the pts. Sixteen patients treated with IL-2 alone showed no CR, PR, 2 SD, or 14 PD. Of 23 patients in the IL-2+IFN group, there were 5 PR, 8 SD, and 10 PD, with a response rate of 21.7%. Amongst 24 patients in the 5-FU+IL-2+IFN group, there were 1 CR, 3 PR, 10 SD, and 10 PD, with a response rate of 16.7%. One-year survival was 20.0%, 81.3% and 81.0%, respectively. The influenza-like syndrome was the most common side effect in the pts who received IFN (89.1%, grade 1, CTC. Hypotension associated with IL-2 (all groups was seen in 56.3% (50%, grade 1 and 6.3%, grade 2. The other adverse reactions were 12.7% grade 1 neutropenia and vomiting in 4.7% pts (Group 3.Conclusion: All regimens are well tolerated. Small-dose IL-2

  13. Energetics and genetics across the prokaryote-eukaryote divide

    Science.gov (United States)

    2011-01-01

    Background All complex life on Earth is eukaryotic. All eukaryotic cells share a common ancestor that arose just once in four billion years of evolution. Prokaryotes show no tendency to evolve greater morphological complexity, despite their metabolic virtuosity. Here I argue that the eukaryotic cell originated in a unique prokaryotic endosymbiosis, a singular event that transformed the selection pressures acting on both host and endosymbiont. Results The reductive evolution and specialisation of endosymbionts to mitochondria resulted in an extreme genomic asymmetry, in which the residual mitochondrial genomes enabled the expansion of bioenergetic membranes over several orders of magnitude, overcoming the energetic constraints on prokaryotic genome size, and permitting the host cell genome to expand (in principle) over 200,000-fold. This energetic transformation was permissive, not prescriptive; I suggest that the actual increase in early eukaryotic genome size was driven by a heavy early bombardment of genes and introns from the endosymbiont to the host cell, producing a high mutation rate. Unlike prokaryotes, with lower mutation rates and heavy selection pressure to lose genes, early eukaryotes without genome-size limitations could mask mutations by cell fusion and genome duplication, as in allopolyploidy, giving rise to a proto-sexual cell cycle. The side effect was that a large number of shared eukaryotic basal traits accumulated in the same population, a sexual eukaryotic common ancestor, radically different to any known prokaryote. Conclusions The combination of massive bioenergetic expansion, release from genome-size constraints, and high mutation rate favoured a protosexual cell cycle and the accumulation of eukaryotic traits. These factors explain the unique origin of eukaryotes, the absence of true evolutionary intermediates, and the evolution of sex in eukaryotes but not prokaryotes. Reviewers This article was reviewed by: Eugene Koonin, William Martin

  14. The Digital Divide in Romania – A Statistical Analysis

    Directory of Open Access Journals (Sweden)

    Daniela BORISOV

    2012-06-01

    Full Text Available The digital divide is a subject of major importance in the current economic circumstances in which Information and Communication Technologies (ICT are seen as a significant determinant of increasing the domestic competitiveness and contribute to better life quality. Latest international reports regarding various aspects of ICT usage in modern society reveal a decrease of overall digital disparity towards the average trends of the worldwide ITC’s sector – this relates to latest advances of mobile and computer penetration rates, both for personal use and for households/ business. In Romania, the low starting point in the development of economy and society in the ICT direction was, in some extent, compensated by the rapid annual growth of the last decade. Even with these dynamic developments, the statistical data still indicate poor positions in European Union hierarchy; in this respect, the prospects of a rapid recovery of the low performance of the Romanian ICT endowment and usage and the issue continue to be regarded as a challenge for progress in economic and societal terms. The paper presents several methods for assessing the current state of ICT related aspects in terms of Internet usage based on the latest data provided by international databases. The current position of Romanian economy is judged according to several economy using statistical methods based on variability measurements: the descriptive statistics indicators, static measures of disparities and distance metrics.

  15. Digital divide, biometeorological data infrastructures and human vulnerability definition

    Science.gov (United States)

    Fdez-Arroyabe, Pablo; Lecha Estela, Luis; Schimt, Falko

    2017-06-01

    The design and implementation of any climate-related health service, nowadays, imply avoiding the digital divide as it means having access and being able to use complex technological devices, massive meteorological data, user's geographic location and biophysical information. This article presents the co-creation, in detail, of a biometeorological data infrastructure, which is a complex platform formed by multiple components: a mainframe, a biometeorological model called Pronbiomet, a relational database management system, data procedures, communication protocols, different software packages, users, datasets and a mobile application. The system produces four daily world maps of the partial density of the atmospheric oxygen and collects user feedback on their health condition. The infrastructure is shown to be a useful tool to delineate individual vulnerability to meteorological changes as one key factor in the definition of any biometeorological risk. This technological approach to study weather-related health impacts is the initial seed for the definition of biometeorological profiles of persons, and for the future development of customized climate services for users in the near future.

  16. Cultural safety and nursing education in divided societies.

    Science.gov (United States)

    Arieli, Daniella; Mashiach, Michal; Hirschfeld, Miriam J; Friedman, Victor

    2012-01-01

    This research explores the experiences of cultural safety among nursing students from majority and minority groups in a divided society with implications for academic satisfaction and success. The study takes place in an academic nursing program in Israel, where Arab and Jewish students study together. A researcher-developed questionnaire was used with 17 statements concerning social relations between students, faculty support, and the effects of social relations on academic satisfaction and outcomes. Significant differences were found in the ways Arab and Jewish students perceived the cultural safety of the environment. Arab students perceived social relations and faculty attitude as less positive than Jewish students and perceived cultural safety as having greater influence on academic satisfaction and success. The findings indicate that students from different groups will perceive the same shared reality in significantly different ways. Nurse faculty and administrators need to make efforts to bring perceptions into closer alignment and to minimize the negative impact of external conflicts on feelings of cultural safety.

  17. Combas & Co. or the Figure and the Great Divide

    Directory of Open Access Journals (Sweden)

    Monique Yaari

    1996-06-01

    Full Text Available The young painter, Robert Combas, leader of the 1980s "figuration libre" 'free figuration' movement, is seen here both as representative of stylistic and thematic trends in contemporary French art, and as illustrative, through the unfolding of his career, of the object "painting" and its sociology in contemporary France. Examined are: first, the "Postmodern convergence" of figurative, indeed narrative art, with the collapse of the "great divide" between elite and popular art forms; and second, traits such as hypertrophic verbal paratext, high erotic content, and political stand. Similar threads are followed in the work of a number of other artists, old and young, established or not, female and male—hence the "& Co." of the title. The essay raises, without claiming to solve, a set of sociologically and politically informed questions: What forces have shaped Combas' sensibility and style? What forces have made him a minor celebrity domestically, one that France's awesome cultural apparatus considers worthy of export? What, in the formation of contemporary mentalities and tastes, may account for the parallels found among artists as diverse as Combas, Quardon, Pierre and Gilles, Ben, and Klossowski?

  18. Movement Synchrony Forges Social Bonds Across Group Divides

    Directory of Open Access Journals (Sweden)

    Bahar eTuncgenc

    2016-05-01

    Full Text Available Group dynamics play an important role in the social interactions of both children and adults. A large amount of research has shown that merely being allocated to arbitrarily defined groups can evoke disproportionately positive attitudes toward one’s in-group and negative attitudes toward out-groups, and that these biases emerge in early childhood. This prompts important empirical questions with far-reaching theoretical and applied significance. How robust are these inter-group biases? Can biases be mitigated by behaviors known to bond individuals and groups together? How can bonds be forged across existing group divides? To explore these questions, we examined the bonding effects of interpersonal synchrony on minimally constructed groups in a controlled experiment. In-group and out-group bonding were assessed using questionnaires administered before and after a task in which groups performed movements either synchronously or non-synchronously in a between-participants design. We also developed an implicit behavioral measure, the Island Game, in which physical proximity was used as an indirect measure of interpersonal closeness. Self-report and behavioral measures showed increased bonding between groups after synchronous movement. Bonding with the out-group was significantly higher in the condition in which movements were performed synchronously than when movements were performed non-synchronously between groups. The findings are discussed in terms of their importance for the developmental social psychology of group dynamics as well as their implications for applied intervention programs.

  19. The influence of spatial separation on divided listening.

    Science.gov (United States)

    Best, Virginia; Gallun, Frederick J; Ihlefeld, Antje; Shinn-Cunningham, Barbara G

    2006-09-01

    If spatial attention acts like a "spotlight," focusing on one location and excluding others, it may be advantageous to have all targets of interest within the same spatial region. This hypothesis was explored using a task where listeners reported keywords from two simultaneous talkers. In Experiment 1, the two talkers were placed symmetrically about the frontal midline with various angular separations. While there was a small performance improvement for moderate separations, the improvement decreased for larger separations. However, the dependency of the relative talker intensities on spatial configuration accounted for these effects. Experiment 2 tested whether spatial separation improved the intelligibility of each source, an effect that could counteract any degradation in performance as sources fell outside the spatial spotlight of attention. In this experiment, intelligibility of individual sources was equalized across configurations by adding masking noise. Under these conditions, the cost of divided listening (the drop in performance when reporting both messages compared to reporting just one) was smaller when the spatial separation was small. These results suggest that spatial separation enhances the intelligibility of individual sources in a competing pair but increases the cost associated with having to process both sources simultaneously, consistent with the attentional spotlight hypothesis.

  20. Viatical settlement tax reform: Republicans support relief, Democrats divided.

    Science.gov (United States)

    James, J S; Roehr, B

    1995-03-03

    Congress is considering the tax exempt status on money received from a life insurance policy before death of a person with a short life expectancy due to illness. Tax exempt status is being considered for both accelerated benefits and viatical settlement. Accelerated benefits allows for pre-payment in advance of death. A viatical settlement is the purchase of an insurance policy by third parties with the condition of their becoming the irrevocable beneficiary of the policy being purchased. While House Republicans on the House Ways and Means Committee are generally supportive of not taxing viatical settlements, Democrats are divided. Letters to Congress are needed, especially to House Ways and Means Democrats from voters in their districts and states to encourage their support of the reform bill (HR 8, the Senior Citizens' Equity Act) which includes tax relief for both accelerated benefits and viatical settlements. More information can be obtained by calling Gary Rose, National Association of People with AIDS, (202) 898-0414, or Tom McCormack, Affording Care, (202) 479-2543.

  1. Divided Universities: The Postcolonial Experience of Contemporary Ukrainian Higher Education

    Directory of Open Access Journals (Sweden)

    Denys Svyrydenko

    2017-07-01

    Full Text Available The paper considers the problem of Ukrainian divided universities, which appear at the result of Revolution of Dignity, annexation of Crimea by Russia as well as formation of quasi-republics of the East of Ukraine. Most of educational institutions form these territories were evacuated (students and teaching stuff, but “twin universities” appeared using campus and facilities of migrated ones. Author demonstrates the heuristic potential of using the interdisciplinary approaches for understanding the essence of this situation applying metaphors like “university cloning”, “university mitosis” and so on. This approach is strengthened by the ethical judgment through the basic axiological values of modern “idea of university” (freedom of thinking, academic freedom, institutional autonomy, will of knowledge and truth etc. collected at Magna Charta Universitatum. From these positions, migrated universities comprehend as an active bearer and translator of “idea of university”. The “twin universities” have a lot of formal arguments to be comprehended as authentic ones, but author stresses on the fact that these institutions don’t fit the universities axiological criteria: these universities rejected ones’ own tradition; teachers are ready to work in censored conditions and manipulate the knowledge; teachers and students risk to became subjects of violence; the autonomy and academic freedom are absent. Author also appeals the historical facts on the example of Cambridge University origination that let make the optimistic conclusion concerning the perspectives of migrated universities

  2. Universal logic gates via liquid-electronic hybrid divider.

    Science.gov (United States)

    Zhou, Bingpu; Wang, Limu; Li, Shunbo; Wang, Xiang; Hui, Yu Sanna; Wen, Weijia

    2012-12-21

    We demonstrated two-input microdroplet-based universal logic gates using a liquid-electronic hybrid divider. All 16 Boolean logic functions have been realized by manipulating the applied voltages. The novel platform consists of a microfluidic chip with integrated microdroplet detectors and external electronic components. The microdroplet detectors act as the communication media for fluidic and electronic information exchange. The presence or absence of microdroplets at the detector translates into the binary signal 1 or 0. The embedded micro-mechanical pneumatically actuated valve (PAV), fabricated using the well-developed multilayer soft lithography technique, offers biocompatibility, flexibility and accuracy for the on-chip realization of different logic functions. The microfluidic chip can be scaled up to construct large-scale microfluidic logic computation. On the other hand, the microfluidic chip with a specific logic function can be applied to droplet-based chemical reactions for on-demand bio or chemical analysis. Our experimental results have presented an autonomously driven, precision-controlled microfluidic chip for chemical reactions based on the IF logic function.

  3. Does fish ecology predict dispersal across a river drainage divide?

    Science.gov (United States)

    Burridge, Christopher P; Craw, Dave; Jack, Daniel C; King, Tania M; Waters, Jonathan M

    2008-06-01

    Obligate freshwater taxa are frequently distributed among catchments isolated by marine and terrestrial barriers. Such distributions can arise through vicariant changes in drainage geometry, or dispersal via intermittent freshwater connections. We employed two adjacent rivers in southern New Zealand to test for interdrainage dispersal while controlling for historical drainage geometry, and analyzed four ecologically distinct freshwater-limited fish taxa to assess any relationship with habitat preference. Individuals from the Mararoa and Oreti catchments (n >100 per species) were sequenced for a minimum of 1297 bp of mitochondrial DNA (cytochrome b and control region). Phylogeographic relationships were consistent with ecological expectations of interdrainage dispersal capability, with the two obligate riverine taxa each exhibiting reciprocal monophyly between catchments, whereas the two facultative swamp dwellers revealed paraphyletic relationships, one of which shared a haplotype between catchments. Statistical phylogeography, accommodating taxon-specific mutation rates and the known age of the last major riverine connection between these catchments, rejected complete isolation of populations for one of the swamp dwellers. Therefore, dispersal across a young (145-240 kyr) drainage divide is inferred for one species, and can be predicted to some extent by species ecology. Moreover, our study highlights the importance of historical drainage geometry when assessing the causes of contemporary genetic structuring in freshwater taxa.

  4. Informaticiens Sans Frontieres: Helping to bridge the Digital Divide

    CERN Document Server

    CERN. Geneva

    2009-01-01

    ISF was formed as a CERN club during the World Summit for the Information Society, in Geneva, in 2003. Today we are involved in a number of international projects aimed to helping Africa bridge the Digital Divide, as well as using computing power (BOINCs) in the research against Malaria, or creating GRIDs that could allow African universities to join us in scientific research projects such as the LHC. Our latest project, named MANGO Net, is aimed at capacity building, by creating a network of computer assembly schools across the continent, which would form hardware and software technicians, create assembly centres, and lay the foundation for a future IT industry. ISF est né comme un club du CERN, en 2003, pendant le Sommet Mondiale de la Société de l'information à Genève. Aujourd'hui nous participons à plusieurs projets avec le but d'aider l'Afrique à reduire la Fracture Numérique, ou de fournir de la puissance de calcul (BOINC) à la recherche contre le Paludisme, ou en créant des GRIDs qui pourra...

  5. Universal logic gates via liquid-electronic hybrid divider

    KAUST Repository

    Zhou, Bingpu

    2012-01-01

    We demonstrated two-input microdroplet-based universal logic gates using a liquid-electronic hybrid divider. All 16 Boolean logic functions have been realized by manipulating the applied voltages. The novel platform consists of a microfluidic chip with integrated microdroplet detectors and external electronic components. The microdroplet detectors act as the communication media for fluidic and electronic information exchange. The presence or absence of microdroplets at the detector translates into the binary signal 1 or 0. The embedded micro-mechanical pneumatically actuated valve (PAV), fabricated using the well-developed multilayer soft lithography technique, offers biocompatibility, flexibility and accuracy for the on-chip realization of different logic functions. The microfluidic chip can be scaled up to construct large-scale microfluidic logic computation. On the other hand, the microfluidic chip with a specific logic function can be applied to droplet-based chemical reactions for on-demand bio or chemical analysis. Our experimental results have presented an autonomously driven, precision-controlled microfluidic chip for chemical reactions based on the IF logic function. © 2012 The Royal Society of Chemistry.

  6. Radiolabeled red blood cells: status, problems, and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1983-01-01

    Radionuclidic labels for red cells can be divided into two main categories - cohort or pulse labels, and random labels. The random labels are incorporated into circulating cells of all ages and the labeling process is usually carried out in vitro. The red cell labels in predominant use involve random labeling and employ technetium-99m, chromium-51, indium-111, and gallium-68, roughly in that order. The extent of usefulness depends on the properties of the label such as the half-life, decay mode, and in-vivo stability, etc. Labeled cells can be used for red cell survival measurements when the half-life of the radionuclide is sufficiently long. The major portion of this article deals with random labels.

  7. Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats.

    Science.gov (United States)

    Quimby, Jessica M; Webb, Tracy L; Randall, Elissa; Marolf, Angela; Valdes-Martinez, Alex; Dow, Steve W

    2016-02-01

    Feline chronic kidney disease (CKD) is characterized by chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. Mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and antifibrotic effects in rodent CKD models. However, few randomized trials evaluating the effectiveness of MSC therapy for diseases in companion animals have been reported. The purpose of this study was to evaluate the effectiveness of allogeneic MSCs for the treatment of feline CKD using a randomized, placebo-controlled trial. MSCs were isolated from the cryopreserved adipose tissues of specific pathogen-free research cats and culture expanded. CKD cats were enrolled in a randomized, placebo-controlled, blinded one-way crossover clinical study. Four CKD cats were randomized to receive 2 × 10(6) MSCs/kg intravenously at 2, 4 and 6 weeks. Four CKD cats were randomized to receive placebo, with two cats crossing over to the MSC treatment group and one cat failing to complete the trial. Complete blood counts, chemistry and urinalysis were performed at weeks 0, 2, 4, 6 and 8. Glomerular filtration rate (GFR) via nuclear scintigraphy and urine protein:creatinine ratio (UPC) were determined at weeks 0 and 8. Six cats received three doses of allogeneic MSC culture expanded from cryopreserved adipose without adverse effects. No significant change in serum creatinine, blood urea nitrogen, potassium, phosphorus, GFR by nuclear scintigraphy, UPC or packed cell volume was seen in cats treated with MSCs. Individual changes in GFR were 12%, 8%, 8%, 2%, -13% and -67% in treated cats compared with 16%, 36% and 0% in placebo-treated cats. While administration of MSC culture expanded from cryopreserved adipose was not associated with adverse effects, significant improvement in renal function was not observed immediately after administration. Long-term follow-up is necessary to determine whether MSC administration affects disease progression in cats with CKD

  8. Crossing cultural divides: moral conflict and the Cairo population conference.

    Science.gov (United States)

    Davis, J E

    1995-01-01

    This essay considers the public conflict that arose during the drafting of the Programme of Action of the 1994 International Conference on Population and Development (ICPD) as reflecting a moral argument between interest groups holding different world views. These differences are seen as running through and across civilizations rather than being civilization-specific. The essay opens with background information on the development of the concepts of population control and population stabilization as well as the adoption of national population policies and the goals of population programs. The public conflict over the ICPD is then reiterated and is seen to be something other than the usual "West versus the rest" tension or a "religious" versus "secular" battle. Instead the divide can be broadly categorized as "orthodox" versus "progressive." The contested issues included a conflict over language relating to abortion, marriage and the family, promiscuity and adultery, and development and international migration. The conflict over human rights involved health rights versus nonmedicalized moral norms, individual rights versus family rights, and sustainable development versus integral development. The underriding conflict is seen to be a conflict between those holding orthodox versus progressive world views over who will shape the future. The tactics of this high-stakes conflict included portraying the other side as fanatics, treating the moral debate as a distraction from more important issues, charging the other side with having a hidden agenda, and isolating certain ideas from the possibility of discussion. With 92% of the Draft Programme of Action uncontested, both sides made compromises that resulted in the gist of the text remaining intact. Because the result of implementation of the Programme of Action will be cultural change, the conflict did not end with the ICPD. As the globalization of Western culture proceeds, cross-cultural moral conflicts may arise.

  9. BRIDGING THE KNOWLEDGE DIVIDE Educational Technology for Development

    Directory of Open Access Journals (Sweden)

    Reviewed by Ozlem OZAN,

    2009-10-01

    Full Text Available BRIDGING THE KNOWLEDGE DIVIDEEducational Technology for DevelopmentMarshall,S., Kinuthia, W. & Wallace Taylor., Ed.D.; Information Age Publishing, Charlotte, NC, SBN: 978-1-60752-109-9, p.433, 2009Reviewed by Ozlem OZANFaculty of EducationEskişehir Osmangazi UniversityEskisehir, TURKEYThe concept of a knowledge divide is used to describe the gap in living conditions between those who can find, manage and process information or knowledge, and those who are impaired in this, for one reason or another. In the 21st century, the emergence of the knowledge society becomes pervasive hence the information and ICT systems that support knowledge are very important.This book discusses how educational technology can be used to transform education and assist developing communities to close the knowledge divide. Its broader audience is anyone who is interested in educational technology for development. In the book you can find best practices and case studies especially from countries in Africa.The book is edited by Stewart Marshall, Wanjira Kinuthia, Wallace Taylor. Professor Stewart Marshall, PhD, is the director of the Academic Division of the University of the West Indies Open Campus (UWIOC and holds the UNESCO Chair in Educational Technologies.Dr. Wanjira Kinuthia is assistant professor of Learning Technologies at Georgia State University. She works as an instructional designer in higher education and business and industry for several years. Professor Wallace Taylor, PhD, is a founding director of The Information Society Institute (TISI, a non-profit academic, research, and policy development organization based in South Africa.The book is consisted of 433 pages (+xxxv covering 24 articles divided into four sections and provides information about flexible learning for empowerment, managing and communicating knowledge, flexible delivery in higher education and preparing teacher using flexible approaches.Topics covered in the book are as follows

  10. Weight loss intervention for young adults using mobile technology: design and rationale of a randomized controlled trial – Cell phone Intervention for You (CITY)

    Science.gov (United States)

    Batch, Bryan C.; Tyson, Crystal; Bagwell, Jacqueline; Corsino, Leonor; Intille, Stephen; Lin, Pao-Hwa; Lazenka, Tony; Bennett, Gary; Bosworth, Hayden B.; Voils, Corrine; Grambow, Steven; Sutton, Aziza; Bordogna, Rachel; Pangborn, Matthew; Schwager, Jenifer; Pilewski, Kate; Caccia, Carla; Burroughs, Jasmine; Svetkey, Laura P.

    2014-01-01

    Background The obesity epidemic has spread to young adults, leading to significant public health implications later in adulthood. Intervention in early adulthood may be an effective public health strategy for reducing the long-term health impact of the epidemic. Few weight loss trials have been conducted in young adults. It is unclear what weight loss strategies are beneficial in this population. Purpose To describe the design and rationale of the NHLBI-sponsored Cell Phone Intervention for You (CITY) study, which is a single center, randomized three-arm trial that compares the impact on weight loss of 1) a behavioral intervention that is delivered almost entirely via cell phone technology (Cell Phone group); and 2) a behavioral intervention delivered mainly through monthly personal coaching calls enhanced by self-monitoring via cell phone (Personal Coaching group), each compared to; 3) a usual care, advice-only control condition. Methods A total of 365 community-dwelling overweight/obese adults aged 18–35 years were randomized to receive one of these three interventions for 24 months in parallel group design. Study personnel assessing outcomes were blinded to group assignment. The primary outcome is weight change at 12 months. We hypothesize that each active intervention will cause more weight loss than the usual care condition. Study completion is anticipated in 2014. Conclusions If effective, implementation of the CITY interventions could mitigate the alarming rates of obesity in young adults through promotion of weight loss. PMID:24462568

  11. Quantifying the roles of random motility and directed motility using advection-diffusion theory for a 3T3 fibroblast cell migration assay stimulated with an electric field.

    Science.gov (United States)

    Simpson, Matthew J; Lo, Kai-Yin; Sun, Yung-Shin

    2017-03-17

    Directed cell migration can be driven by a range of external stimuli, such as spatial gradients of: chemical signals (chemotaxis); adhesion sites (haptotaxis); or temperature (thermotaxis). Continuum models of cell migration typically include a diffusion term to capture the undirected component of cell motility and an advection term to capture the directed component of cell motility. However, there is no consensus in the literature about the form that the advection term takes. Some theoretical studies suggest that the advection term ought to include receptor saturation effects. However, others adopt a much simpler constant coefficient. One of the limitations of including receptor saturation effects is that it introduces several additional unknown parameters into the model. Therefore, a relevant research question is to investigate whether directed cell migration is best described by a simple constant tactic coefficient or a more complicated model incorporating saturation effects. We study directed cell migration using an experimental device in which the directed component of the cell motility is driven by a spatial gradient of electric potential, which is known as electrotaxis. The electric field (EF) is proportional to the spatial gradient of the electric potential. The spatial variation of electric potential across the experimental device varies in such a way that there are several subregions on the device in which the EF takes on different values that are approximately constant within those subregions. We use cell trajectory data to quantify the motion of 3T3 fibroblast cells at different locations on the device to examine how different values of the EF influences cell motility. The undirected (random) motility of the cells is quantified in terms of the cell diffusivity, D, and the directed motility is quantified in terms of a cell drift velocity, v. Estimates D and v are obtained under a range of four different EF conditions, which correspond to normal

  12. Can the Lung Cancer Pie Be Divided into Angiogenic Slices?

    Science.gov (United States)

    Cascone, Tina; Heymach, John V

    2015-12-01

    There are no validated markers for predicting benefit from angiogenesis inhibitors or classifying tumors with distinct angiogenic phenotypes. In patients with non-small cell lung cancer treated with bevacizumab and erlotinib, Franzini and colleagues find that angiogenesis- and hypoxia-associated gene expression signatures predict tumor response and/or clinical outcome, and may define distinct angiogenic patterns. ©2015 American Association for Cancer Research.

  13. Bridging the divide between genomic science and indigenous peoples.

    Science.gov (United States)

    Jacobs, Bette; Roffenbender, Jason; Collmann, Jeff; Cherry, Kate; Bitsói, LeManuel Lee; Bassett, Kim; Evans, Charles H

    2010-01-01

    definition of "rigorous scientific research," one that includes both community development and scientific progress as legitimate objectives of genomic research. Innovative translational research is needed to develop practical, mutually acceptable methods for crossing the divide between genomic researchers and indigenous communities. This may mean the difference between success and failure in genomic science, and in improving health for all peoples. © 2010 American Society of Law, Medicine & Ethics, Inc.

  14. Health literacy and the digital divide among older Americans.

    Science.gov (United States)

    Levy, Helen; Janke, Alexander T; Langa, Kenneth M

    2015-03-01

    digital divide.

  15. Randomized controlled trial on the effects of a supervised high intensity exercise program in patients with a hematologic malignancy treated with autologous stem cell transplantation : Results from the EXIST study

    NARCIS (Netherlands)

    Persoon, S.; ChinAPaw, M.J.M.; Buffart, L.M.; Liu, R.D.K.; Wijermans, P.; Koene, H.R.; Minnema, M.C.; Lugtenburg, P.J.; Marijt, E.W.A.; Brug, J.; Nollet, F.; Kersten, M.J.

    2017-01-01

    Background This single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation. Methods

  16. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of Natural Killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial)

    Science.gov (United States)

    2012-01-01

    Background In vitro and animal studies have demonstrated that Chlorella is a potent biological response modifier on immunity. However, there were no direct evidences for the effect of Chlorella supplementation on immune/inflammation response in healthy humans. Methods This study was designed for an 8-week randomized, double-blinded, placebo-controlled trial: 5g of Chlorella (n=23) or Placebo (n=28) as form of tablets. Mainly, cytotoxic activities of Natural killer (NK) cells and serum concentrations of interferon-γ, interleukin-1β and interleukin-12 were measured. Results After the 8-week, serum concentrations of interferon-γ (pChlorella group. The increments of these cytokines after the intervention were significantly bigger in the Chlorella group than those in the placebo group. In addition, NK cell activities (%) were significantly increased in Chlorella group, but not in Placebo group. The increments of NK cell activities (%) were also significantly bigger in the Chlorella group than the placebo group. Additionally, changed levels of NK cell activity were positively correlated with those of serum interleukin-1β (r=0.280, p=0.047) and interferon-γ (r=0.271, pChlorella supplementation which enhances the NK cell activity and produces interferon-γ and interleukin-12 as well as interleukin-1β, the Th-1 cell-induced cytokines in healthy people. PMID:22849818

  17. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial.

    Science.gov (United States)

    Tan, Jianming; Wu, Weizhen; Xu, Xiumin; Liao, Lianming; Zheng, Feng; Messinger, Shari; Sun, Xinhui; Chen, Jin; Yang, Shunliang; Cai, Jinquan; Gao, Xia; Pileggi, Antonello; Ricordi, Camillo

    2012-03-21

    Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease. To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor. One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed. Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs. The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events. Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04

  18. Medium area, flexible single and tandem junction solar cells based on roll coated semi-random copolymers

    DEFF Research Database (Denmark)

    Andersen, Thomas Rieks; Dam, Henrik Friis; Burkhart, Beate

    2014-01-01

    We report on medium area (1 cm2) slot-die coated organic photovoltaic devices (OPVs) of a recently developed semi-random copolymer of poly-3-hexylthiophene and diketopyrrolopyrrole (P3HTT–DPP- 10%) mixed with phenyl-C61-butyric acid methyl ester ([60]PCBM). The devices were prepared using a compa...

  19. An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

    2013-01-01

    This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer.......This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

  20. Randomized Controlled Trial Examining the Effects of Fish Oil and Multivitamin Supplementation on the Incorporation of n-3 and n-6 Fatty Acids into Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Andrew Pipingas

    2014-05-01

    Full Text Available The present randomized, placebo-controlled, double-blind, parallel-groups clinical trial examined the effects of fish oil and multivitamin supplementation on the incorporation of n-3 and n-6 fatty acids into red blood cells. Healthy adult humans (n = 160 were randomized to receive 6 g of fish oil, 6 g of fish oil plus a multivitamin, 3 g of fish oil plus a multivitamin or a placebo daily for 16 weeks. Treatment with 6 g of fish oil, with or without a daily multivitamin, led to higher eicosapentaenoic acid (EPA composition at endpoint. Docosahexaenoic acid (DHA composition was unchanged following treatment. The long chain LC n-3 PUFA index was only higher, compared to placebo, in the group receiving the combination of 6 g of fish oil and the multivitamin. Analysis by gender revealed that all treatments increased EPA incorporation in females while, in males, EPA was only significantly increased by the 6 g fish oil multivitamin combination. There was considerable individual variability in the red blood cell incorporation of EPA and DHA at endpoint. Gender contributed to a large proportion of this variability with females generally showing higher LC n-3 PUFA composition at endpoint. In conclusion, the incorporation of LC n-3 PUFA into red blood cells was influenced by dosage, the concurrent intake of vitamin/minerals and gender.

  1. Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Ramroth, Johanna; Cutter, David J.; Darby, Sarah C. [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Higgins, Geoff S. [Department of Oncology, University of Oxford, Oxford, Oxfordshire (United Kingdom); McGale, Paul [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Partridge, Mike [CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, Oxfordshire (United Kingdom); Taylor, Carolyn W., E-mail: carolyn.taylor@ndph.ox.ac.uk [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom)

    2016-11-15

    Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no

  2. A Randomized study on the Effects of Paclitaxel Liposme and Cisplatin Induction Chemotherapy Followed Concurrent Chemoradiotherapy and Sequential Radiotherapy on Locally Advanced Non-small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Youyi DAI

    2011-02-01

    Full Text Available Background and objective Sequential and concurrent chemoradiotherapy were widely studied in locally advanced non-small cell lung cancer (NSCLC, but the reports of induction chemotherapy followed concurrent chemoradiotherapy are rare so far. The little side effects of paclitaxel liposme may be convenient to carry out induction chemotherapy followed concurrent chemoradiotherapy. The aim of this study is to compare the effects and side effects of TP regimen (Paclitaxel liposme and cisplatin induction chemotherapy followed concurrent chemoradiotherapy with sequential radiotherapy on locally advanced NSCLC. Methods Sixty locally advanced NSCLC patients were randomly divided into group A, induction chemotherapy followed concurrent chemoradiotherapy and group B, sequential radiotherapy group. The patients in group A received 2-3 cycles of induced chemotherapy included of Paclitaxel liposme 135 mg/m2-175 mg/m2, d1 and cisplatin 70 mg/m2-80 mg/m2, d2, 3 weeks repeat and after 2-3 cycles followed by concurrent chemoradiotherapy. The patients in group B received chemotherapy, (as described above in group A 4-6 cycles of chemotherapy followed one cycle of radiotherapy. The three-dimensional conformal radiotherapy at the total dose of 56 Gy-70 Gy was applied in all patients. Results The response rate in group A and group B were 80.3% and 60%, respectively (P=0.042. 1-year survival rates were 71.4% and 53.2%, respectively (P=0.18. And there were no significant difference of myelosuppression, radiation esophagitis and pulmonary fibrosis between the two groups (P=0.09, P=0.147, P=0.276, respectively. Conclusion The recent effects of induction chemotherapy followed by concurrent chemoradiotherapy group were better than sequential radiotherapy group on locally advanced NSCLC and there was no significant difference in side effects between the two groups.

  3. Rationale and design of mDOT-HuA study: a randomized trial to assess the effect of mobile-directly observed therapy on adherence to hydroxyurea in adults with sickle cell anemia in Tanzania

    Directory of Open Access Journals (Sweden)

    Abel Makubi

    2016-10-01

    Full Text Available Abstract Background Hydroxyurea (HU has been demonstrated to be efficacious in reducing complications in individuals with sickle cell anemia (SCA but poor adherence is a barrier. Directly Observed Therapy (DOT has been shown to improve adherence in various chronic diseases but there is limited data in adults with SCA. Methods and design To examine the effect of mobile-directly observed therapy (mDOT on adherence to HU (mDOT-HuA in adults with SCA at Muhimbili National Hospital in Tanzania. The mDOT-HuA study is a single centre, prospective, randomized, open label clinical trial. One-hundred individuals with SCA with haemoglobin SS genotype, aged ≥18 years, living in Dar es Salaam, able and willing to record and submit videos electronically will be included. Participants will be divided into two treatment arms; 50 in the standard monitoring (SM arm will receive mobile phones and fixed dose HU therapy with standard monitoring; 50 in the mDOT arm will receive mobile phones, fixed dose HU therapy with standard monitoring and a mobile directly observed web based medication adherence monitoring system. The primary outcome is the proportion of participants achieving ≥80 % HU adherence compared between the two arms as assessed through medication possession ratio at the end of 3 months of treatment. REDCap, an open source software application will be used to collect data using clinical research forms. The proportions of adherence in the two arms will be compared by Fisher’s exact test. Analysis of outcomes will have performed by both the intention-to treat and per-protocol methods. Discussion Should this study become sucessful, it will have the potential for the development of novel strategies for improving HU adherence in SCA. Trial registration ClinicalTrials.gov Identifier: NCT02844673 , registered on 25tht July 2016 (retrospectively registered.

  4. A GAP that Divides [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Angika Basant

    2017-10-01

    Full Text Available Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the early Caenorhabditis elegans embryo, RhoA activation and furrow ingression require the centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation in C. elegans. Centralspindlin contains CYK-4 which contains a predicted Rho family GTPase-activating protein (GAP domain. The function of this domain has been the subject of considerable debate. Some publications suggest that the GAP domain promotes RhoA activation (for example, Zhang and Glotzer, 2015; Loria, Longhini and Glotzer, 2012, whereas others suggest that it functions to inactivate the GTPase Rac1 (for example, Zhuravlev et al., 2017. Here, we review the mechanisms underlying RhoA activation during cytokinesis, primarily focusing on data in C. elegans. We highlight the importance of considering the parallel pathway for RhoA activation and detailed analyses of cyk-4 mutant phenotypes when evaluating the role of the GAP domain of CYK-4.

  5. Bridging the divide between neuroprosthetic design, tissue engineering and neurobiology

    Directory of Open Access Journals (Sweden)

    Jennie Leach

    2010-02-01

    Full Text Available Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system (CNS implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell (NPC biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration towards novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

  6. Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology.

    Science.gov (United States)

    Leach, Jennie B; Achyuta, Anil Kumar H; Murthy, Shashi K

    2010-01-01

    Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years) due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration toward novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

  7. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

    Energy Technology Data Exchange (ETDEWEB)

    Mehrasa, Mohammad [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of); Asadollahi, Mohammad Ali, E-mail: ma.asadollahi@ast.ui.ac.ir [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Nasri-Nasrabadi, Bijan [Department of Chemical Engineering, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Ghaedi, Kamran [Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Salehi, Hossein [Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Dolatshahi-Pirouz, Alireza [DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark (DTU), DK-2800 Kgs. Lyngby (Denmark); Arpanaei, Ayyoob, E-mail: arpanaei@yahoo.com [Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of)

    2016-09-01

    Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974 ± 68 nm for the pure PLGA scaffolds vs 832 ± 70, 764 ± 80, and 486 ± 64 for the PLGA/gelatin, PLGA/10 wt% MSNPs, and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. - Highlights: • PLGA-based random nanofibers embedded with mesoporous silica nanoparticles were fabricated using electrospinning method • Incorporation of gelatin and MSNPs into PLGA-based scaffolds increased the hydrophilicity of scaffold • Addition of nanoparticles also improved the tensile mechanical properties of scaffolds • Introduction of MSNPs led to improved cell attachment and proliferation.

  8. A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count Africa.

    Science.gov (United States)

    Ratsela, Andrew; Polis, Michael; Dhlomo, Sibongiseni; Emery, Sean; Grandits, Greg; Khabo, Paul; Khanyile, Thandeka; Komati, Stephanus; Neaton, James D; Naidoo, Lionel Chris David; Magongoa, Daphne; Qolohle, Duma

    2010-11-15

    Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings. In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events. In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84-1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93-1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%). EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy. ClinicalTrials.gov identifier: NCT00342355.

  9. Cell Division and Evolution of Biological Tissues

    Science.gov (United States)

    Rivier, Nicolas; Arcenegui-Siemens, Xavier; Schliecker, Gudrun

    A tissue is a geometrical, space-filling, random cellular network; it remains in this steady state while individual cells divide. Cell division (fragmentation) is a local, elementary topological transformation which establishes statistical equilibrium of the structure. Statistical equilibrium is characterized by observable relations (Lewis, Aboav) between cell shapes, sizes and those of their neighbours, obtained through maximum entropy and topological correlation extending to nearest neighbours only, i.e. maximal randomness. For a two-dimensional tissue (epithelium), the distribution of cell shapes and that of mother and daughter cells can be obtained from elementary geometrical and physical arguments, except for an exponential factor favouring division of larger cells, and exponential and combinatorial factors encouraging a most symmetric division. The resulting distributions are very narrow, and stationarity severely restricts the range of an adjustable structural parameter

  10. The supply voltage scaled dependency of the recovery of single event upset in advanced complementary metal—oxide—semiconductor static random-access memory cells

    Science.gov (United States)

    Li, Da-Wei; Qin, Jun-Rui; Chen, Shu-Ming

    2013-02-01

    Using computer-aided design three-dimensional simulation technology, the supply voltage scaled dependency of the recovery of single event upset and charge collection in static random-access memory cells are investigated. It reveals that the recovery linear energy transfer threshold decreases with the supply voltage reducing, which is quite attractive for dynamic voltage scaling and subthreshold circuit radiation-hardened design. Additionally, the effect of supply voltage on charge collection is also investigated. It is concluded that the supply voltage mainly affects the bipolar gain of the parasitical bipolar junction transistor (BJT) and the existence of the source plays an important role in supply voltage variation.

  11. Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

    Science.gov (United States)

    Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

    2013-01-01

    This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

  12. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans Erik; Knudsen, Lene Meldgaard; Mylin, Anne Kærsgaard

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p lower than 0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles......The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  13. Up-front fludarabine impairs stem cell harvest in multiple myeloma: report of the NMSG 13/03 randomized placebo controlled phase II trial

    DEFF Research Database (Denmark)

    Johnsen, Hans E.; Meldgaard Knudsen, Lene; Mylin, Anne K.

    2009-01-01

    toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p...The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conlusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim...

  14. Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD)--a study protocol for a pilot randomized controlled trial.

    Science.gov (United States)

    Lascar, Nadia; Kennedy, Amy; Jackson, Nikki; Daley, Amanda; Dowswell, George; Thompson, Dylan; Stokes, Keith; Greenfield, Sheila; Holder, Roger; Andrews, Rob; Narendran, Parth

    2013-06-18

    Exercise has a beta cell preserving effect in patients with type 2 diabetes. This benefit of exercise has not been examined in type 1 diabetes. Significant beta cell function is present at the time of diagnosis of type 1 diabetes and therefore studies of beta cell preservation are ideally conducted immediately after diagnosis.Many of the variables required to design and power such a study are currently unknown. The aim of EXTOD is to obtain the information required to design a formal study of exercise and beta cell preservation in newly diagnosed patients with type 1 diabetes. Barriers to exercise will initially be assessed in a qualitative study of newly diagnosed patients. Then, sixty newly diagnosed adult type 1 diabetes patients will be randomized to either conventional treatment or exercise, stratified on beta cell function and fitness. The exercise group will be encouraged to increase their level of activity to a minimum of 150 minutes of moderate to vigorous intensity exercise per week, aiming for 240 minutes per week of exercise for 12 months. Beta cell function will be measured by meal-stimulated C peptide. Primary outcomes are recruitment, adherence to exercise, loss to follow-up, and exercise levels in the non-intervention arm (contamination). The secondary outcome of the study is rate of loss of beta cell function. The outcomes of the EXTOD study will help define the barriers, uptake and benefits of exercise in adults newly diagnosed with type 1 diabetes. This information will enable design of a formal study to assess the effect of exercise on beta cell preservation in newly diagnosed patients with type 1 diabetes. Current controlled trials ISRCTN91388505.

  15. Performance of inverted polymer solar cells with randomly oriented ZnO nanorods coupled with atomic layer deposited ZnO

    Science.gov (United States)

    Zafar, Muhammad; Yun, Ju-Young; Kim, Do-Heyoung

    2017-03-01

    Nanostructuring of the electron transport layer (ETL) in organic photovoltaic cells (OPV) is of great interest because it increases the surface area of the cell and electron transport. In this work, hydrothermally grown, randomly oriented, and low areal density ZnO nanorods (NRs) have been adopted as the ETL, and the effect of adding atomic layer deposited (ALD) ZnO on the ZnO NRs on the inverted organic solar cell performance has been investigated. The fabricated inverted organic solar cell with 5-nm-thick ALD-ZnO grown on the ZnO NRs showed the highest power conversion efficiency (PCE) of 3.08%, which is an enhancement of 85% from that of the cell without ALD-ZnO (PCE = 1.67%). The ultrathin ALD-ZnO was found to act as a curing layer of the surface defects on the hydrothermally grown ZnO NRs, resulting in an improvement in photovoltaic performance.

  16. A Randomized Phase I/II Trial to Compare Weekly Usage with Triple Weekly Usage of Paclitaxel in Concurrent Radiochemotherapy for Patients with Locally Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Anhui SHI

    2011-03-01

    Full Text Available Background and objective Although the guidelines of the National Comprehensive Cancer Network of USA recommend that the standard therapy for locally advanced non-small cell lung cancer (LANSCLC is concurrent chemoradiotherapy. There is ongoing controversy about the treatment regimen which combines chemotherapy concurrently with radiotherapy. The aim of this study is to compare weekly usage with triple weekly usage of paclitaxel in concurrent radiochemotherapy for patients with LANSCLC, and to obtain the best paclitaxel regimen in the concurrent radiochemotherapy. Methods From April 2006 to April 2009, some LANSCLC patients in multicenter were randomly divided into weekly usage (45 mg/m2, 1 times/week, a total of 270 mg/m2 in six weeks and triple weekly usage (15 mg/m2, 3 times/week, a total of 270 mg/m2 in six weeks group of paclitaxel by a random number table. All patients were treated with 3D radiotherapy, and 95% planning target volume (PTV received a prescription dose of (60-70 Gy/(30-35times/(6-7weeks, (1.8-2.0 Gy/fraction. Then the side effects, response and overall survival rate were compared between two groups of patients. Results Thirty-eight LANSCLC patients were enrolled. Weekly usage and triple weekly usage group were 20 and 18 patients, respectively. In the triple weekly usage group, the side effects were 12 patients had radiation esophagitis of I-II degree, 1 patient had radiation esophagitis of III degree, 2 patients had radiation pneumonitis of I degree, 1 patient had radiation pneumonitis of II degree, 1 patient had radiation pneumonitis of III degree and died of respiratory failure, 2 patients developed weight loss of I degree. In the weekly usage group, the side effects were 11 patients had radiation esophagitis of I-III degree, 6 patients had radiation pneumonitis of II-III degree, 2 patients developed weight loss of I degree, 6 patients developed leucopenia of III-IV degree. The response rate of two groups was 88.8% and 50

  17. The random co-polymer glatiramer acetate rapidly kills primary human leukocytes through sialic-acid-dependent cell membrane damage

    DEFF Research Database (Denmark)

    Christiansen, Stig Hill; Zhang, Xianwei; Juul-Madsen, Kristian

    2017-01-01

    in innate immunity. It shares the positive charge and amphipathic character of GA, and, as shown here, also the ability to kill human leukocyte. The cytotoxicity of both compounds depends on sialic acid in the cell membrane. The killing was associated with the generation of CD45 + debris, derived from cell...... membrane deformation. Nanoparticle tracking analysis confirmed the formation of such debris, even at low GA concentrations. Electric cell-substrate impedance sensing measurements also recorded stable alterations in T lymphocytes following such treatment. LL-37 forms oligomers through weak hydrophobic...

  18. Outcome of burns treated with autologous cultured proliferating epidermal cells: a prospective randomized multicenter intrapatient comparative trial

    NARCIS (Netherlands)

    Gardien, K.L.M.; Marck, R.E.; Bloemen, M.C.T.; Waaijman, T.; Gibbs, S.; Uhlrich, M.M.W.; Middelkoop, E.

    2016-01-01

    Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative,

  19. Phase II Multicenter, Randomized, Double-Blind Controlled Study of Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cells in the Prophylaxis of Chronic Graft-Versus-Host Disease After HLA-Haploidentical Stem-Cell Transplantation.

    Science.gov (United States)

    Gao, Lei; Zhang, Yanqi; Hu, Baoyang; Liu, Jia; Kong, Peiyan; Lou, Shifeng; Su, Yi; Yang, Tonghua; Li, Huimin; Liu, Yao; Zhang, Cheng; Gao, Li; Zhu, Lidan; Wen, Qin; Wang, Ping; Chen, Xinghua; Zhong, Jiangfan; Zhang, Xi

    2016-08-20

    Although mesenchymal stromal cells (MSCs) possess immunomodulatory properties and exhibit promising efficacy against chronic graft-versus-host disease (cGVHD), little is known about the efficacy of MSCs in the prophylaxis of cGVHD after HLA-haploidentical hematopoietic stem-cell transplantation (HLA-haplo HSCT). In this multicenter, double-blind, randomized controlled trial, we investigated the incidence and severity of cGVHD among patients, and the changes in T, B, and natural killer (NK) cells after the repeated infusion of MSCs. The 2-year cumulative incidence of cGVHD in the MSCs group was 27.4% (95% CI, 16.2% to 38.6%), compared with 49.0% (95% CI, 36.5% to 61.5%) in the non-MSCs control group (P = .021). Seven patients in the non-MSCs control group had severe lung cGVHD, but no patients in the MSCs group developed typical lung cGVHD (P = .047). After the MSC infusions, increasing memory B lymphocytes and regulatory T cells, as well as the ratio of type 1 T helper to type 2 T helper cells, were observed, whereas the number of NK cells decreased. Our findings suggest that the repeated infusion of MSCs might inhibit cGVHD symptoms in patients after HLA-haplo HSCT, accompanied by changes in the numbers and subtypes of T, B, and NK cells, leading to the acquisition of immune tolerance. © 2016 by American Society of Clinical Oncology.

  20. The random co-polymer glatiramer acetate rapidly kills primary human leukocytes through sialic-acid-dependent cell membrane damage

    DEFF Research Database (Denmark)

    Christiansen, Stig Hill; Zhang, Xianwei; Juul-Madsen, Kristian

    2017-01-01

    in innate immunity. It shares the positive charge and amphipathic character of GA, and, as shown here, also the ability to kill human leukocyte. The cytotoxicity of both compounds depends on sialic acid in the cell membrane. The killing was associated with the generation of CD45 + debris, derived from cell...... of certain oligomeric and chemical properties to support cytotoxic effects of cationic polymers targeting human leukocytes....

  1. Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial.

    Directory of Open Access Journals (Sweden)

    Dinesh Bansal

    Full Text Available Measures to prevent chronic calcineurin inhibitor (CNI toxicity have included limiting exposure by switching to sirolimus (SIR. SIR may favorably influence T regulator cell (T(reg population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR and T(reg frequency.In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR at 180 days. T(reg population was estimated by flowcytometry.Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94 ± 11.78 vs 80.59 ± 16.51 mL/min, p = 0.038. Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in T(reg population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event.A deferred pre-emptive switch over from CNI to SIR safely improves renal function and T(reg population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034.

  2. Reducing the Digital Divide among Children Who Received Desktop or Hybrid Computers for the Home

    Science.gov (United States)

    Zilka, Gila Cohen

    2016-01-01

    Researchers and policy makers have been exploring ways to reduce the digital divide. Parameters commonly used to examine the digital divide worldwide, as well as in this study, are: (a) the digital divide in the accessibility and mobility of the ICT infrastructure and of the content infrastructure (e.g., sites used in school); and (b) the digital…

  3. Divided attention capacity in adults with autism spectrum disorders and without intellectual disability

    NARCIS (Netherlands)

    Bogte, H; Flamma, B; Van der Meere, J.J.; van Engeland, H.

    Earlier research showed that divided attention, an aspect of executive function, is limited in both children and adults with autism spectrum disorders (ASDs). The current study explored divided attention capacity in adults with ASD and without intellectual disability (n = 36). Divided attention was

  4. Government Information Focus. The Digital Divide: Understanding and Addressing the Challenge.

    Science.gov (United States)

    Latimer, Christopher P.

    This report discusses the challenges of the Digital Divide. Part I examines the issues concerning access as it relates to schools, communities, free Internet service providers, and broadband. Part II defines technological literacy and how it pertains to the Digital Divide debate. Part III examines those who are affected by the divide and…

  5. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial.

    Science.gov (United States)

    Black, Linda L; Gaynor, James; Gahring, Dean; Adams, Cheryl; Aron, Dennis; Harman, Susan; Gingerich, Daniel A; Harman, Robert

    2007-01-01

    Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue, such as fat, from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous adipose-derived stem cell therapy has been commercially available since 2003, and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip. Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs. This is the first randomized, blinded, placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs.

  6. First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial

    DEFF Research Database (Denmark)

    Grønhøj, Christian; Jensen, David H; Glovinski, Peter V

    2017-01-01

    and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months...... has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. Methods This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial...

  7. Excellent scalability including self-heating phenomena of vertical-channel field-effect-diode type capacitor-less one transistor dynamic random access memory cell

    Science.gov (United States)

    Imamoto, Takuya; Endoh, Tetsuo

    2014-01-01

    The scalability study and the impact of the self-heating effect (SHE) on memory operation of the bulk vertical-channel field effect diode (FED) type capacitorless one transistor (1T) dynamic random access memory (DRAM) cell are investigated via device simulator for the first time. The vertical-channel FED type 1T-DRAM cell shows the excellent hold characteristics (100 ms at 358 K of ambient temperature) with large enough read current margin (1 µA/cell) even when silicon pillar diameter (D) is scaled down from 20 to 12 nm. It is also shown that by employing the vertical-channel FED type, maximum lattice temperature in the memory cell due to SHE (T_{\\text{L}}^{\\text{Max}}) can be suppressed to a negligible small value and only reach 300.6 from 300 K ambient temperature due to the low lateral electric field, while the vertical-channel bipolar junction transistor (BJT) type 1T-DRAM shows significant SHE (T_{\\text{L}}^{\\text{Max}} = 330.6 K). Moreover, this excellent thermal characteristic can be maintained even when D is scaled down from 20 to 12 nm.

  8. Randomized trial of stopping or continuing ART among postpartum women with pre-ART CD4 ≥ 400 cells/mm3.

    Science.gov (United States)

    Currier, Judith S; Britto, Paula; Hoffman, Risa M; Brummel, Sean; Masheto, Gaerolwe; Joao, Esau; Santos, Breno; Aurpibul, Linda; Losso, Marcelo; Pierre, Marie F; Weinberg, Adriana; Gnanashanmugam, Devasena; Chakhtoura, Nahida; Klingman, Karin; Browning, Renee; Coletti, Anne; Mofenson, Lynne; Shapiro, David; Pilotto, Jose

    2017-01-01

    Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen. The sample size was selected to provide 88% power to detect a 50% reduction from an annualized primary event rate of 2.07%. A post-hoc analysis evaluated HIV/AIDS-related and World Health Organization (WHO) Stage 2 and 3 events. All analyses were intent to treat. 1652 women from 52 sites in Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand and the US were enrolled (1/2010-11/2014). Median age was 28 years and major racial categories were Black African (28%), Asian (25%) White (15%). Median entry CD4 count was 696 cells/mm3 (IQR 575-869), median ART exposure prior to delivery was 19 weeks (IQR 13-24) and 94% had entry HIV-1 RNA ART (2.08/100 py vs. 4.36/100 py in the discontinue arm; HR 0.48, 95%CI: 0.33, 0.70). Toxicity rates did not differ significantly between arms. Among women randomized to continue ART, 189/827 (23%) had virologic failure; of the 155 with resistance testing, 103 (66%) failed without resistance to their current regimen, suggesting non-adherence. Overall, serious clinical events were rare among young HIV-positive post-partum women with high CD4 cell counts. Continued ART was safe and was associated with a halving of the rate of WHO 2/3 conditions. Virologic failure rates were high, underscoring the urgent need to improve adherence in this population. ClinicalTrials.gov NCT00955968.

  9. Randomized clinical trial of mast cell inhibition in patients with a medium-sized abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Sillesen, H; Eldrup, N; Hultgren, R

    2015-01-01

    BACKGROUND: Abdominal aortic aneurysm (AAA) is thought to develop as a result of inflammatory processes in the aortic wall. In particular, mast cells are believed to play a central role. The AORTA trial was undertaken to investigate whether the mast cell inhibitor, pemirolast, could retard...... surgery, diabetes mellitus, and severe concomitant disease with a life expectancy of less than 2 years. Included patients were treated with 10, 25 or 40 mg pemirolast, or matching placebo for 52 weeks. The primary endpoint was change in aortic diameter as measured from leading edge adventitia...

  10. Concurrent versus Sequential Chemoradiotherapy with Cisplatin and Vinorelbine in Locally Advanced Non-Small Cell Lung Cancer: A Randomized Study

    Czech Academy of Sciences Publication Activity Database

    Zatloukal, P.; Petruželka, L.; Zemanová, M.; Havel, L.; Janků, F.; Judas, L.; Kubík, A.; Křepela, E.; Fiala, P.; Pecen, Ladislav

    2004-01-01

    Roč. 46, - (2004), s. 87-98 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z1030915 Keywords : concurrent chemoradiotherapy * sequential chemoradiotherapy * locally advanced non-small cell lung cancer * cisplatin * vinorelbine Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.914, year: 2004

  11. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

    NARCIS (Netherlands)

    Laar, J.M. van; Farge, D.; Sont, J.K.; Naraghi, K.; Marjanovic, Z.; Larghero, J.; Schuerwegh, A.J.; Marijt, E.W.; Vonk, M.C.; Schattenberg, A.V.M.B.; Matucci-Cerinic, M.; Voskuyl, A.E.; Loosdrecht, A.A. van de; Daikeler, T.; Kotter, I.; Schmalzing, M.; Martin, T.; Lioure, B.; Weiner, S.M.; Kreuter, A.; Deligny, C.; Durand, J.M.; Emery, P.; Machold, K.P.; Sarrot-Reynauld, F.; Warnatz, K.; Adoue, D.F.; Constans, J.; Tony, H.P.; Papa, N. Del; Fassas, A.; Himsel, A.; Launay, D. de; Monaco, A. Lo; Philippe, P.; Quere, I.; Rich, E.; Westhovens, R.; Griffiths, B.; Saccardi, R.; Hoogen, F.H.J. van den; Fibbe, W.E.; Socie, G.; Gratwohl, A.; Tyndall, A.

    2014-01-01

    IMPORTANCE: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of

  12. Distress and quality of life after autologous stem cell transplantation: a randomized clinical trial to evaluate the outcome of a web-based stepped care intervention

    Directory of Open Access Journals (Sweden)

    Huijgens Peter C

    2010-07-01

    Full Text Available Abstract Background Psychological distress (i.e. depression and anxiety is a strong predictor of functional status and other aspects of quality of life in autologous stem cell transplantation following high-dose chemotherapy. Treatment of psychological distress is hypothesized to result in improvement of functional status and other aspects of quality of life. The aim is to evaluate the outcome of stepped care for psychological distress on functional status and other aspects of quality of life in patients with hematological malignancy treated with autologous stem cell transplantation. Methods/Design The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention program versus care as usual. Patients are randomized immediately pre transplant. Stepped care and care as usual are initiated after a 6 weeks buffer period. Outcome is evaluated at 13, 30, and 42 weeks post transplant. In the experimental group, the first step includes an Internet-based self-help program. If psychological distress persists after the self-help intervention, the second step of the program is executed, i.e. a diagnostic evaluation and a standardized interview, yielding a problem analysis. Based on this information, a contract is made with the patient and treatment is provided consisting of individual face-to-face counseling, medication, or referral to other services. Care as usual comprises an interview with the patient, on ad hoc basis; emotional support and advice, on ad hoc basis; if urgent problems emerge, the patient is referred to other services. Primary outcome variables are psychological distress and functional status. Data are analyzed according to the intention to treat-principle. Discussion This study has several innovative characteristics. First, the outcome of the intervention for psychological distress in patients with hematological malignancy treated with autologous stem cell transplantation is evaluated in a randomized

  13. Distress and quality of life after autologous stem cell transplantation: a randomized clinical trial to evaluate the outcome of a web-based stepped care intervention.

    Science.gov (United States)

    Braamse, Annemarie M J; van Meijel, Berno; Visser, Otto; van Oppen, Patricia; Boenink, Annette D; Eeltink, Corien; Cuijpers, Pim; Huijgens, Peter C; Beekman, Aartjan T F; Dekker, Joost

    2010-07-07

    Psychological distress (i.e. depression and anxiety) is a strong predictor of functional status and other aspects of quality of life in autologous stem cell transplantation following high-dose chemotherapy. Treatment of psychological distress is hypothesized to result in improvement of functional status and other aspects of quality of life. The aim is to evaluate the outcome of stepped care for psychological distress on functional status and other aspects of quality of life in patients with hematological malignancy treated with autologous stem cell transplantation. The study is designed as a randomized clinical trial with 2 treatment arms: a stepped care intervention program versus care as usual. Patients are randomized immediately pre transplant. Stepped care and care as usual are initiated after a 6 weeks buffer period. Outcome is evaluated at 13, 30, and 42 weeks post transplant.In the experimental group, the first step includes an Internet-based self-help program. If psychological distress persists after the self-help intervention, the second step of the program is executed, i.e. a diagnostic evaluation and a standardized interview, yielding a problem analysis. Based on this information, a contract is made with the patient and treatment is provided consisting of individual face-to-face counseling, medication, or referral to other services. Care as usual comprises an interview with the patient, on ad hoc basis; emotional support and advice, on ad hoc basis; if urgent problems emerge, the patient is referred to other services.Primary outcome variables are psychological distress and functional status. Data are analyzed according to the intention to treat-principle. This study has several innovative characteristics. First, the outcome of the intervention for psychological distress in patients with hematological malignancy treated with autologous stem cell transplantation is evaluated in a randomized controlled study. Second, the impact of the intervention on

  14. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  15. A Prospective, Randomized, Masked and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs

    Directory of Open Access Journals (Sweden)

    Robert J Harman

    2016-09-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease with a high prevalence in dogs. Mesenchymal stem cells have been used to treat humans, dogs, and horses with OA. This report describes a prospective, randomized, blinded, and placebo-controlled clinical efficacy study of intraarticular allogeneic adipose stem cells for the treatment of dogs with osteoarthritis. Health assessments and measurements of pain and activity impairment were performed at baseline and at selected time points through day 60. The primary outcome variable was the owner Client-Specific Outcome Measurement (CSOM and secondary measures included veterinary pain on manipulation, veterinary global score, and owner global score. The dogs were treated with either a saline placebo or a single dose of allogeneic adipose-derived mesenchymal stem cells in either one or two joints. Seventy-four dogs were statistically analyzed for efficacy outcomes. Success in the primary outcome variable, CSOM, was statistically improved in the treated dogs compared to the placebo dogs (79.2% versus 55.4%, p=0.029. The veterinary pain on manipulation score (92.8% versus 50.2%, p=0.017 and the veterinary global score (86.9% versus 30.8%, p= 0.009 were both statistically improved in treated dogs compared to placebo. There was no detected significant difference between treated and placebo dogs in the incidence of adverse events or negative health findings. Allogeneic adipose-derived stem cell treatment was shown to be efficacious compared to placebo. This large study of dogs also provides valuable animal clinical safety and efficacy outcome data to our colleagues developing human stem cell therapy.

  16. Cell-Based Systems Biology Analysis of Human AS03-Adjuvanted H5N1 Avian Influenza Vaccine Responses: A Phase I Randomized Controlled Trial.

    Science.gov (United States)

    Howard, Leigh M; Hoek, Kristen L; Goll, Johannes B; Samir, Parimal; Galassie, Allison; Allos, Tara M; Niu, Xinnan; Gordy, Laura E; Creech, C Buddy; Prasad, Nripesh; Jensen, Travis L; Hill, Heather; Levy, Shawn E; Joyce, Sebastian; Link, Andrew J; Edwards, Kathryn M

    2017-01-01

    Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines. In a double-blinded clinical trial, we randomized twenty adults aged 18-49 to receive two doses of either AS03-adjuvanted (n = 10) or unadjuvanted (n = 10) H5N1 vaccine 28 days apart. We used a systems biology approach to characterize and correlate changes in serum cytokines, antibody titers, and gene expression levels in six immune cell types at 1, 3, 7, and 28 days after the first vaccination. Both vaccines were well-tolerated. Nine of 10 subjects in the adjuvanted group and 0/10 in the unadjuvanted group exhibited seroprotection (hemagglutination inhibition antibody titer > 1:40) at day 56. Within 24 hours of AS03-adjuvanted vaccination, increased serum levels of IL-6 and IP-10 were noted. Interferon signaling and antigen processing and presentation-related gene responses were induced in dendritic cells, monocytes, and neutrophils. Upregulation of MHC class II antigen presentation-related genes was seen in neutrophils. Three days after AS03-adjuvanted vaccine, upregulation of genes involved in cell cycle and division was detected in NK cells and correlated with serum levels of IP-10. Early upregulation of interferon signaling-related genes was also found to predict seroprotection 56 days after first vaccination. Using this cell-based systems approach, novel mechanisms of action for AS03-adjuvanted pandemic influenza vaccination were observed. ClinicalTrials.gov NCT01573312.

  17. A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial.

    Science.gov (United States)

    Sarveazad, Arash; Newstead, Graham L; Mirzaei, Rezvan; Joghataei, Mohammad Taghi; Bakhtiari, Mehrdad; Babahajian, Asrin; Mahjoubi, Bahar

    2017-02-21

    Anal sphincter defects are a major cause of fecal incontinence causing negative effects on daily life, social interactions, and mental health. Because human adipose-derived stromal/stem cells (hADSCs) are easier and safer to access, secrete high levels of growth factor, and have the potential to differentiate into muscle cells, we investigated the ability of hADSCs to improve anal sphincter incontinence. The present randomized double-blind clinical trial was performed on patients with sphincter defects. They were categorized into a cell group (n = 9) and a control group (n = 9). Either 6 × 106 hADSCs per 3 ml suspended in phosphate buffer saline (treatment) or 3 ml phosphate buffer saline (placebo) was injected. Two months after surgery, the Wexner score, endorectal sonography, and electromyography (EMG) results were recorded. Comparing Wexner scores in the cell group and the control group showed no significant difference. In our EMG and endorectal sonography analysis using ImageJ/Fiji 1.46 software, the ratio of the area occupied by the muscle to total area of the lesion showed a 7.91% increase in the cell group compared with the control group. The results of the current study show that injection of hADSCs during repair surgery for fecal incontinence may cause replacement of fibrous tissue, which acts as a mechanical support to muscle tissue with contractile function. This is a key point in treatment of fecal incontinence especially in the long term and may be a major step forward. Iranian Registry of Clinical Trials IRCT2016022826316N2 . Retrospectively registered 7 May 2016.

  18. Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial.

    Science.gov (United States)

    Jansen of Lorkeers, Sanne J; Gho, Johannes M I H; Koudstaal, Stefan; van Hout, Gerardus P J; Zwetsloot, Peter Paul M; van Oorschot, Joep W M; van Eeuwijk, Esther C M; Leiner, Tim; Hoefer, Imo E; Goumans, Marie-José; Doevendans, Pieter A; Sluijter, Joost P G; Chamuleau, Steven A J

    2015-01-01

    Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls. Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes. We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals. Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction.

  19. Role of sudarshan kriya and pranayam on lipid profile and blood cell parameters during exam stress: A randomized controlled trial.

    Science.gov (United States)

    Subramanian, Swapna; Elango, Tamilselvi; Malligarjunan, Hemamalini; Kochupillai, Vinod; Dayalan, Haripriya

    2012-01-01

    Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis. Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters. Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals. ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels. Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters.

  20. Randomized Phase III Trial of Low Molecular Weight Heparin Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Ek, L; Gezelius, E; Bergman, B

    2017-01-01

    Background: Coagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low molecular weight heparin (LMWH) may improve survival specifically in small cell lung cancer (SCLC...... in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted. ClinicalTrials.gov: NCT00717938....

  1. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

    Energy Technology Data Exchange (ETDEWEB)

    Di Pendina, G., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; Zianbetov, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr [Univ. Grenoble Alpes, INAC-SPINTEC, F-38000 Grenoble (France); CNRS, SPINTEC, F-38000 Grenoble (France); CEA, INAC-SPINTEC, F-38000 Grenoble (France); Beigne, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr [Univ. Grenoble Alpes, CEA, LETI, F-38000 Grenoble (France)

    2015-05-07

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

  2. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

    Science.gov (United States)

    Di Pendina, G.; Zianbetov, E.; Beigne, E.

    2015-05-01

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

  3. Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

    Science.gov (United States)

    Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

    2015-07-01

    In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

  4. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network

    DEFF Research Database (Denmark)

    Hoster, Eva; Klapper, Wolfram; Hermine, Olivier

    2014-01-01

    PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned.......9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI...

  5. Mobility Divides

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    Contemporary mobilities are cultural and social manifestations, and the mobile practices in the everyday life of billions of humans are re-configuring senses of place, self, other and relationships to the built environment. The way ‘mobile situations’ are staged in designed and built environments......’ in the everyday life and cast light on how design and ‘materialities of mobilites’ are creating differential mobilities across societies, social networks, and communities of practices....... are increasingly becoming ‘second nature’ but also expressions of power, exclusion, and difference. In this talk I will be applying a perspective of ‘mobile situationism’ illustrating how mobile everyday life practices are staged ‘from above’ in planning and policy frameworks, design codes and architectural...

  6. Divided Uncertainty

    DEFF Research Database (Denmark)

    Frederiksen, Morten

    institutions. This conceptual stretching takes place at the expense of accuracy and clarity clouding our understanding of the multiple levels involved in trusting. This chapter seeks to clarify this issue conceptually by comparing and developing Niklas Luhmann’s system theoretical investigation of trust...... and confidence with Knud E. Løgstrup’s phenomenology of trust. The main argument presented here is that while Luhmann’s analysis of trust and confidence remains one of the most powerful and persuasive it is only when combining it with Løgstrup’s phenomenology of trusting as situated process that the linkages...

  7. Randomized Trial of Hyperfractionation Versus Conventional Fractionation in T2 Squamous Cell Carcinoma of the Vocal Cord (RTOG 9512)

    Energy Technology Data Exchange (ETDEWEB)

    Trotti, Andy, E-mail: andy.trotti@moffitt.org [Department of Radiation Oncology, University of South Florida H. Lee Moffittt Cancer Center, Tampa, Florida (United States); Zhang, Qiang [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Bentzen, Søren M. [Department of Human Oncology, University of Wisconsin School of Medicine, Madison, Wisconsin (United States); Emami, Bahman [Department of Radiation Therapy, Loyola University Medical Center, Maywood, Illinois (United States); Hammond, M. Elizabeth [Department of Pathology, LDS Hospital, Salt Lake City, Utah (United States); Jones, Christopher U. [Radiological Associates of Sacramento, Sacramento, California (United States); Morrison, William H. [University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sagar, Stephen M. [McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Ridge, John A. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Fu, Karen K. [Department of Radiation Oncology, University of California (emeritus), San Francisco, California (United States); Ang, K. Kian [Department of Radiotherapy, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-08-01

    Purpose: To compare hyperfractionation versus standard fractionation for T2N0 vocal cord carcinoma in a randomized controlled trial. Methods and Materials: Patients with T2 vocal cord cancer were stratified by substage (T2a vs T2b) and randomly assigned to receive either hyperfractionation (HFX) to 79.2 Gy in 66 fractions of 1.2 Gy given twice a day, or standard fractionation (SFX) to 70 Gy in 35 fractions given once a day. The trial was designed to detect a 55% reduction in the local failure hazard rate with 80% statistical power. Results: Between April 1996 and July 2003, a total of 250 patients were enrolled. Of 239 patients analyzable for outcomes, 94% were male, 83% had a Karnofsky performance status of 90-100, and 62% had T2a tumor. Median follow-up for all surviving patients was 7.9 years (range, 0.6-13.1 years). The 5-year local control (LC) rate was 8 points higher but not statistically significant (P=.14 for HFX [78%] vs SFX [70%]), corresponding to a 30% hazard rate reduction. The 5-year disease-free survival (DFS) was 49% versus 40% (P=.13) and overall survival (OS) was 72% versus 63% (P=.29). HFX was associated with higher rates of acute skin, mucosal, and laryngeal toxicity. Grade 3-4 late effects were similar with a 5-year cumulative incidence of 8.5% (3.4%-13.6%) after SFX and 8.5% (3.4%-13.5%) after HFX. Conclusions: The 5-year local control was modestly higher with HFX compared to SFX for T2 glottic carcinoma, but the difference was not statistically significant. These results are consistent with prior studies of hyperfractionation showing a benefit in local control. Substaging by T2a versus T2b carries prognostic value for DFS and OS. For cost and convenience reasons other altered fractionation schedules have been adopted in routine practice.

  8. A non-randomized comparative study using different doses of acyclovir to prevent herpes simplex reactivation in patients submitted to autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Angelo Atalla

    Full Text Available The reactivation of Herpes Simplex virus (HSV occurs in 70% to 80% of patients submitted to autologous stem cell transplantation (ASCT; it increases the severity of chemotherapy-induced mucositis. Therefore, the use of acyclovir in ASCT patients is considered standard practice. However, the minimum dose needed to prevent reactivation is a matter of debate. We compared two doses of acyclovir in a non-randomized fashion in 59 patients submitted to ASCT: 32 patients received a dose of 125 mg/m² IV every six hours and the subsequent 27 patients received a dose of 60 mg/m² IV every six hours. Viral excretion was evaluated through weekly viral culture of oral swabs. Grade 4 mucositis was more frequent in Group 1 (p= 0.03. The reactivation rates in Groups 1 and 2 were 9% and 4%, respectively (p= 0.62, 95% confidence interval -7 - 18. Prophylaxis with reduced doses of intravenous acyclovir seems to be as effective as a higher dose in inhibiting HSV reactivation, with a significant reduction in cost. Prospective randomized studies are needed to confirm our conclusions.

  9. Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.

    Science.gov (United States)

    Ruutu, Tapani; Juvonen, Eeva; Remberger, Mats; Remes, Kari; Volin, Liisa; Mattsson, Jonas; Nihtinen, Anne; Hägglund, Hans; Ringdén, Olle

    2014-01-01

    We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemo therapy-radiotherapy in unresectable non small cell carcinoma of the lung

    Directory of Open Access Journals (Sweden)

    Dasgupta Anirban

    2006-01-01

    Full Text Available Purpose: Treatment of advanced Non small cell lung cancer (NSCLC often produces dismal results. Combination of available treatment modalities has reportedly improved the outcome. A prospectively randomized trial was conducted, comparing combined treatment modalities versus radiotherapy alone, in treatment of unresectable NSCLC. Materials and Methods: A total of 103 patients were randomized to three groups. In group ′A′, 32 patients received radiotherapy alone (6500 cGy/30 fraction. In group ′B′, 35 patients received neoadjuvant chemotherapy (Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1-3 intravenously q3 weeks for 3 cycles, followed by radiotherapy (6000 cGy/30 fractions and 3 more cycles of Chemotherapy, with the same regimen. In group ′C′, 36 patients received radiotherapy (5000 cGy/25 fractions with concurrent chemotherapy (ciplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1-5 and day 22-26, followed by 2 more cycles of chemotherapy,q3 weeks with the same regimen. Results: Initial treatment responses were significantly higher in group ′B′ ( P P Conclusion: Addition of chemotherapy with radiation in unresectable NSCLC improves response rates, time to tumour progression and disease free survival, though the same effect is not translated in overall survival.

  11. A multi-center, randomized, controlled trial of parenteral nutrition titrated to resting energy expenditure in children undergoing hematopoietic stem cell transplantation (“PNTREE”): Rationale and design

    Science.gov (United States)

    Bechard, Lori J.; Feldman, Henry A.; Gordon, Catherine; Gura, Kathleen; Sonis, Andrew; Leung, Kathryn; Venick, Robert; Guinan, Eva C.; Duggan, Christopher

    2013-01-01

    Background Children undergoing hematopoietic stem cell transplantation (HSCT) frequently require prolonged courses of parenteral nutrition (PN) as a consequence of gastrointestinal dysfunction related to preparative chemotherapy and radiation. PN has been associated with shorter engraftment time and decreased mortality during HSCT, however, it is also linked with complications, including infections, liver disease, and metabolic disturbances. Some of these complications may be a result of providing PN in excess of nutrient requirements. We previously described significant reductions in resting energy expenditure (REE), as measured by indirect calorimetry, over the course of HSCT. We also documented a decline in mid-arm muscle area, suggesting depletion of muscle mass, while triceps skinfold, a marker of fat stores, was unchanged. These results suggested the need for further study of energy expenditure, body composition and nutritional intake in this group of high risk patients. Design and hypothesis We hypothesize that changes in body composition affect REE during HSCT, and that standard nutritional support may lead to overfeeding. We are performing a randomized controlled trial of parenteral nutrition among children undergoing allogeneic HSCT. Subjects are randomized to receive PN designed to provide 100% of measured REE, or standard PN, i.e., 140% of estimated energy expenditure. The primary outcome variable is change in percent body fat. Secondary outcomes include glycemic control and frequency of infections, changes in REE and body composition. Conclusion This study will provide unique and comprehensive nutritional data and its results will guide nutritional therapy for children undergoing HSCT and possibly other catabolic patients. PMID:20004739

  12. Pulsed CO2 Laser Ablation of Superficial Basal Cell of Limbs and Trunk: A Comparative Randomized Clinical Trial With Cryotherapy and Surgical Ablation.

    Science.gov (United States)

    Zane, Cristina; Facchinetti, Elena; Arisi, Mariachiara; Ortel, Bernhard; Calzavara-Pinton, Piergiacomo

    2017-07-01

    Pulsed CO2 laser is a treatment of superficial basal cell carcinoma (sBCC) although robust clinical evidence has not been reported so far. The authors investigated efficacy, safety, time to wound healing, cosmetic outcome, patient satisfaction, and cost-effectiveness ratio of pulsed CO2 laser in comparison to cryotherapy and surgery. BCCs of the trunk and extremities were randomized to one of the treatments. After 90 days, efficacy and cosmetic outcome were assessed. Patients recorded the time to complete healing of the wound and scored their overall satisfaction. Two hundred forty patients were randomized. After 3 months, complete remission (CR) rate with pulsed CO2 laser was 78.8%. This was significantly lower than surgery, whereas the CR rate with cryotherapy was not significantly different. Cosmetic result was better with surgery. High satisfaction was reported by 65.0% of patients treated with CO2 ablation. Time of wound healing was significantly shorter with CO2 laser. In comparison to cryotherapy, pulsed CO2 laser showed no statistically significant difference in efficacy, cosmetic outcome, and patient satisfaction. Time to healing was shorter; the cost and cost-effectiveness ratio were similar. Surgery had the greatest efficacy rate. The main limitation of this study was the short duration of follow-up (3 months).

  13. Changes in Coping, Pain and Activity following Cognitive-Behavioral Training: A Randomized Clinical Trial for Pediatric Sickle Cell Disease using Smartphones

    Science.gov (United States)

    Schatz, Jeffrey; Schlenz, Alyssa; McClellan, Catherine B.; Puffer, Eve S.; Hardy, Steven; Pfeiffer, Matthew; Roberts, Carla W.

    2014-01-01

    Objectives We examined the outcomes of a cognitive-behavioral therapy (CBT) intervention for pain in pediatric sickle cell disease (SCD) using smartphones as a novel delivery method. Methods Forty-six children with SCD received CBT coping skills training using a randomized, waitlist control design. The intervention involved a single-session of CBT training and home-based practice using smartphones for eight weeks. Pre-post questionnaires between the randomized groups were used to evaluate changes in active psychological coping and negative thinking using the Coping Strategies Questionnaire. Daily diaries completed by the full sample during the treatment period were used to assess if CBT skill use was related to reductions in next day pain intensity and increases in same day functional activity. Results The pre-post group comparison suggested that youth increased active psychological coping attempts with the intervention. Daily diary data indicated that when children used CBT skills on days with higher pain, there were reductions in next day pain intensity. There was no such association between skill use and functional activity. Discussion CBT coping skills training supported via smartphones can increase coping and reduce pain intensity for children with SCD; however, additions to the study protocols are recommended in future studies. Advantages and caveats of using smartphones are also discussed. PMID:25503599

  14. Harnessing benefits of helping others: a randomized controlled trial testing expressive helping to address survivorship problems after hematopoietic stem cell transplant.

    Science.gov (United States)

    Rini, Christine; Austin, Jane; Wu, Lisa M; Winkel, Gary; Valdimarsdottir, Heiddis; Stanton, Annette L; Isola, Luis; Rowley, Scott; Redd, William H

    2014-12-01

    Prior research supports the hypothesis that cancer survivors who help others face treatment experience a range of psychosocial and health-related benefits as a result of peer helping. This study investigates an expressive helping (EH) intervention designed to harness those benefits by targeting survivorship problems among cancer survivors treated with hematopoietic stem cell transplant. EH includes two components: (a) emotionally expressive writing (EW; writing one's deepest thoughts and feelings about the transplant experience in a series of brief, structured writing sessions) followed by (b) peer helping (PH; helping other people prepare for transplant by sharing one's own transplant experiences along with advice and encouragement through a written narrative). EH was compared with neutral writing (NW), EW (without PH), and PH (without EW) in a 4-arm randomized controlled trial in which survivors completed baseline measures, 4 structured writing exercises (with instructions depending on randomization), and postintervention measures including validated measures of general psychological distress, physical symptoms, and health-related quality of life (HRQOL). Among survivors with moderate-severe survivorship problems, EH reduced distress (compared with NW and PH; ps writing benefits transplant survivors with moderate-severe survivorship problems, but only if they have first completed expressive writing.

  15. The effect of intracameral anesthesia on macular thickness and ganglion cell-inner plexiform layer thickness after uneventful phacoemulsification surgery: prospective and randomized controlled trial.

    Science.gov (United States)

    Sari, Esin Sogutlu; Ermis, Sitki Samet; Yazici, Alper; Koytak, Arif; Sahin, Gözde; Kilic, Adil

    2014-03-01

    To evaluate the effect of intracameral lidocaine anesthesia on macular thickness and macular ganglion cell-inner plexiform layer (GC-IPL) thickness following uneventful phacoemusification in healthy subjects. This is a prospective, randomized and double- masked study. One hundred eyes of 74 consecutive patients were randomized to receive intracameral preservative-free lidocaine 1 % (intracameral lidocaine group) or intracameral injection of balanced salt solution (sham injection group) at the time of the phacoemulsification surgery. Preoperative and postoperative macular thickness analyses with spectral domain optical coherence tomography (SD-ODT) were performed and the results between the two groups were compared. Postoperatively, both the central foveal thickness (CFT) and the thickness of perifoveal macula were significantly improved in both groups (p thicknesses of the two groups at any follow-up time. In both groups, GC-IPL thickness was significantly increased at the first week and first month visits (p thickness measurements of the two groups at any follow-up time. The current study demonstrated that supplementary intracameral lidocaine 1 % did not cause more macular thickening than the intracameral sham injection during a follow-up period of 3 months. The present study also showed a tendency for a transient increase in high definition SD-OCT-based GC-IPL thickness measurements within a few months following cataract surgery under both intracameral lidocaine anesthesia and intracameral sham injection.

  16. When are cellular automata random?

    Science.gov (United States)

    Coe, J. B.; Ahnert, S. E.; Fink, T. M. A.

    2008-12-01

    A random cellular automaton is one in which a cell's behaviour is independent of its previous states. We derive analytical conditions which must be satisfied by random cellular automata and find deterministic and probabilistic cellular automata that satisfy these conditions. Many random cellular automata are seen to have a flow as they are updated through time. We define a correlation current that describes this flow and develop an analytical expression for its size. We compare results from this analytical expression with those from simulation. The randomness in a cell comes from randomness in adjacent cells or from the stochastic nature of update rules. We give an expression for how much randomness comes from each of these two sources.

  17. Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Lai XX

    2016-04-01

    Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

  18. Cholecalciferol supplementation does not influence β-cell function and insulin action in obese adolescents: a prospective double-blind randomized trial.

    Science.gov (United States)

    Javed, Asma; Vella, Adrian; Balagopal, P Babu; Fischer, Philip R; Weaver, Amy L; Piccinini, Francesca; Dalla Man, Chiara; Cobelli, Claudio; Giesler, Paula D; Laugen, Jeanette M; Kumar, Seema

    2015-02-01

    There is increasing interest in the extraskeletal effects of vitamin D, particularly in the obese state with regard to the development of insulin resistance and diabetes. The objective of the study was to determine the effect of 2 doses of cholecalciferol (vitamin D3) supplementation on insulin action (Si) and pancreatic β-cell function in obese adolescents. We performed a 12-wk double-blind, randomized comparison of the effect of vitamin D3 supplementation on Si and β-cell function in obese Caucasian adolescents (body mass index > 95(th) percentile). The subjects were randomly assigned to receive either 400 IU/d (n = 25) or 2000 IU/d (n = 26) of vitamin D3. Each subject underwent a 7-sample 75 g oral glucose tolerance test, with glucose, insulin, and C-peptide measurements, to calculate Si and β-cell function as assessed by the disposition index (DI), with use of the oral minimal model before and after supplementation. A total of 51 subjects aged 15.0 ± 1.9 y were enrolled. Included for analysis at follow-up were a total of 46 subjects (20 male and 26 female adolescents), 23 in each group. Initial serum 25-hydroxyvitamin D [25(OH)D] was 24.0 ± 8.1 μg/L. There was no correlation between 25(OH)D concentrations and Si or DI. There was a modest but significant increase in 25(OH)D concentration in the 2000 IU/d group (3.1 ± 6.5 μg/L, P = 0.04) but not in the 400 IU/d group (P = 0.39). There was no change in Si or DI following vitamin D3 supplementation in either of the treatment groups (all P > 0.10). The current study shows no effect from vitamin D3 supplementation, irrespective of its dose, on β-cell function or insulin action in obese nondiabetic adolescents with relatively good vitamin D status. Whether obese adolescents with vitamin D deficiency and impaired glucose metabolism would respond differently to vitamin D3 supplementation remains unclear and warrants further studies. This trial was registered at clinicaltrials.gov as NCT00858247. © 2015

  19. Alginate Inhibits Iron Absorption from Ferrous Gluconate in a Randomized Controlled Trial and Reduces Iron Uptake into Caco-2 Cells

    Science.gov (United States)

    Wawer, Anna A.; Harvey, Linda J.; Dainty, Jack R.; Perez-Moral, Natalia; Sharp, Paul; Fairweather-Tait, Susan J.

    2014-01-01

    Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n = 15) were given a test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p = 0.003). Sub-group B (n = 9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p = 0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p = 0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009) and 35% (p = 0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (palginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification. Trial Registration ClinicalTrials.gov NCT01528644 PMID:25391138

  20. Alginate inhibits iron absorption from ferrous gluconate in a randomized controlled trial and reduces iron uptake into Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Anna A Wawer

    Full Text Available Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n = 15 were given a test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p = 0.003. Sub-group B (n = 9 consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p = 0.014, and from alginate beads by 37%, from 8.3% to 5.2% (p = 0.009. In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009 and 35% (p = 0.003 respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p < 0.001 of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification.ClinicalTrials.gov NCT01528644.

  1. SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2010-01-01

    Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

  2. Transition State Theory for solvated reactions beyond recrossing-free dividing surfaces

    OpenAIRE

    Revuelta, F.; Bartsch, Thomas; Garcia-Muller, P. L.; Hernandez, Rigoberto; Benito, R. M.; Borondo, F.

    2016-01-01

    The accuracy of rate constants calculated using transition state theory depends crucially on the correct identification of a recrossing--free dividing surface. We show here that it is possible to define such optimal dividing surface in systems with non--Markovian friction. However, a more direct approach to rate calculation is based on invariant manifolds and avoids the use of a dividing surface altogether, Using that method we obtain an explicit expression for the rate of crossing an anharmo...

  3. Zones of silence: A framework beyond the digital divide (originally published in May 2006)

    OpenAIRE

    Potter, Amelia Bryne

    2007-01-01

    There is no doubt that much digital divide work — including connectivity initiatives, technology transfer programs, and other projects — is done with good intention. Yet, as has been widely recognized, the conceptual framework of the digital divide is limiting. The language of the digital divide not only places people into simplistic “have”/“have not” categories, making assumptions about the solution to “information poverty” with little attention to local contexts, its logic also continues a ...

  4. Radiolaria divided into Polycystina and Spasmaria in combined 18S and 28S rDNA phylogeny.

    Directory of Open Access Journals (Sweden)

    Anders K Krabberød

    Full Text Available Radiolarians are marine planktonic protists that belong to the eukaryote supergroup Rhizaria together with Foraminifera and Cercozoa. Radiolaria has traditionally been divided into four main groups based on morphological characters; i.e. Polycystina, Acantharia, Nassellaria and Phaeodaria. But recent 18S rDNA phylogenies have shown that Phaeodaria belongs within Cerocozoa, and that the previously heliozoan group Taxopodida should be included in Radiolaria. 18S rDNA phylogenies have not yet resolved the sister relationship between the main Radiolaria groups, but nevertheless suggests that Spumellaria, and thereby also Polycystina, are polyphyletic. Very few sequences other than 18S rDNA have so far been generated from radiolarian cells, mostly due to the fact that Radiolaria has been impossible to cultivate and single cell PCR has been hampered by low success rate. Here we have therefore investigated the mutual evolutionary relationship of the main radiolarian groups by using the novel approach of combining single cell whole genome amplification with targeted PCR amplification of the 18S and 28S rDNA genes. Combined 18S and 28S phylogeny of sequences obtained from single cells shows that Radiolaria is divided into two main lineages: Polycystina (Spumellaria+Nassellaria and Spasmaria (Acantharia+Taxopodida. Further we show with high support that Foraminifera groups within Radiolaria supporting the Retaria hypothesis.

  5. Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up.

    Science.gov (United States)

    Liu, W W; Wang, H X; Yu, W; Bi, X Y; Chen, J Y; Chen, L Z; Ding, L; Han, D M; Guo, Z K; Lei, Y X

    2015-09-09

    Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

  6. AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 study.

    Science.gov (United States)

    Rini, Brian; Szczylik, Cezary; Tannir, Nizar M; Koralewski, Piotr; Tomczak, Piotr; Deptala, Andrzej; Dirix, Luc Y; Fishman, Mayer; Ramlau, Rodryg; Ravaud, Alain; Rogowski, Wojciech; Kracht, Karolyn; Sun, Yu-Nien; Bass, Michael B; Puhlmann, Markus; Escudier, Bernard

    2012-12-15

    This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study. Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS). A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386. In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib. Copyright © 2012 American Cancer Society.

  7. P(MMA-EMA Random Copolymer Electrolytes Incorporating Sodium Iodide for Potential Application in a Dye-Sensitized Solar Cell

    Directory of Open Access Journals (Sweden)

    Nurul Akmaliah Dzulkurnain

    2015-02-01

    Full Text Available Polymer electrolytes based on 90 wt% of methyl methacrylate and 10 wt% of ethyl methacrylate (90MMA-co-10EMA incorporating different weight ratios of sodium iodide were prepared using the solution casting method. The complexation between salt and copolymer host has been investigated using Fourier transform infrared spectroscopy. The ionic conductivity and thermal stability of the electrolytes were measured using impedance spectroscopy and differential scanning calorimetry, respectively. Scanning electron microscopy was used to study the morphology of the polymer electrolytes. The ionic conductivity and glass transition temperature increased up to 20 wt% of sodium iodide (5.19 × 10−6 S·cm−1 and decreased with the further addition of salt concentration, because of the crosslinked effect. The morphology behavior of the highest conducting sample also showed smaller pores compared to the other concentration. The total ionic transference number proved that this system was mainly due to ions, and the electrochemical stability window was up to 2.5 V, which is suitable for a dye-sensitized solar cell application. This sample was then tested in a dye-sensitized solar cell and exhibited an efficiency of 0.62%.

  8. Role of sudarshan kriya and pranayam on lipid profile and blood cell parameters during exam stress: A randomized controlled trial

    Science.gov (United States)

    Subramanian, Swapna; Elango, Tamilselvi; Malligarjunan, Hemamalini; Kochupillai, Vinod; Dayalan, Haripriya

    2012-01-01

    Background: Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis. Aim: Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters. Materials and Methods: Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals. Results: ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels. Conclusion: Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters. PMID:22346062

  9. A low-power digital frequency divider for system-on-a-chip applications

    KAUST Repository

    Omran, Hesham

    2011-08-01

    In this paper, an idea for a new frequency divider architecture is proposed. The divider is based on a coarse-fine architecture. The coarse block operates at a low frequency to save power consumption and it selectively enables the fine block which operates at the high input frequency. The proposed divider has the advantages of synchronous divider, but with lower power consumption and higher operation speed. The design can achieve a wide division range with a minor effect on power consumption and speed. The architecture was implemented on a complex programmable logic device (CPLD) to verify its operation. Experimental measurements validate system operation with power reduction greater than 40%. © 2011 IEEE.

  10. Microparticle, Conductivity, and Density Measurements from the WAIS Divide Deep Ice Core, Antarctica, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes microparticle concentration, electrical conductivity, and density measurements from the West Antarctic Ice Sheet (WAIS) Divide deep ice core,...

  11. A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria

    DEFF Research Database (Denmark)

    Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C

    2014-01-01

    BACKGROUND: Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria....../57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group...

  12. Cluster randomization and political philosophy.

    Science.gov (United States)

    Chwang, Eric

    2012-11-01

    In this paper, I will argue that, while the ethical issues raised by cluster randomization can be challenging, they are not new. My thesis divides neatly into two parts. In the first, easier part I argue that many of the ethical challenges posed by cluster randomized human subjects research are clearly present in other types of human subjects research, and so are not novel. In the second, more difficult part I discuss the thorniest ethical challenge for cluster randomized research--cases where consent is genuinely impractical to obtain. I argue that once again these cases require no new analytic insight; instead, we should look to political philosophy for guidance. In other words, the most serious ethical problem that arises in cluster randomized research also arises in political philosophy. © 2011 Blackwell Publishing Ltd.

  13. Random nanowires of nickel doped TiO2 with high surface area and electron mobility for high efficiency dye-sensitized solar cells.

    Science.gov (United States)

    Archana, P S; Naveen Kumar, E; Vijila, C; Ramakrishna, S; Yusoff, M M; Jose, R

    2013-01-28

    Mesoporous TiO(2) with a large specific surface area (~150 m(2) g(-1)) is the most successful material in dye-sensitized solar cells so far; however, its inferior charge mobility is a major efficiency limiter. This paper demonstrates that random nanowires of Ni-doped TiO(2) (Ni:TiO(2)) have a dramatic influence on the particulate and charge transport properties. Nanowires (dia ~60 nm) of Ni:TiO(2) with a specific surface area of ~80 m(2) g(-1) were developed by an electrospinning technique. The band gap of the Ni:TiO(2) shifted to the visible region upon doping of 5 at% Ni atoms. The Mott-Schottky analysis shows that the flat band potential of Ni:TiO(2) shifts to a more negative value than the undoped samples. The electrochemical impedance spectroscopic measurements showed that the Ni:TiO(2) offer lower charge transport resistance, higher charge recombination resistance, and enhanced electron lifetime compared to the undoped samples. The dye-sensitized solar cells fabricated using the Ni:TiO(2) nanowires showed an enhanced photoconversion efficiency and short-circuit current density compared to the undoped analogue. The transient photocurrent measurements showed that the Ni:TiO(2) has improved charge mobility compared with TiO(2) and is several orders of magnitude higher compared to the P25 particles.

  14. Does the Couse of Astragalus-Containing Chinese Herbal Prescriptions and Radiotherapy Benefit to Non-Small-Cell Lung Cancer Treatment: A Meta-Analysis of Randomized Trials

    Directory of Open Access Journals (Sweden)

    Hailang He

    2013-01-01

    Full Text Available Background. Radiotherapy has been widely used for non-small-cell lung cancer (NSCLC, while its low efficacy and high toxicity raise big concerns. Astragalus (as a monarch drug-containing Chinese herbal prescriptions and radiotherapy were frequently coused for NSCLC in China; however, the effects were not systematically analyzed. Objective. To evaluate the benefits of Astragalus-containing Chinese herbal prescriptions combined with radiotherapy for NSCLC. Methods. The randomized controlled trials involving NSCLC treatment with Astragalus-containing Chinese herbal prescriptions combined with radiotherapy were searched. The Review Manager 5.1 software was employed for data analysis. Funnel plot and Egger’s test were applied to evaluate publication bias. Results. 29 eligible studies met our criteria. Of the studies, 8, 6, and 4 reported reduced risk of death at one year, two years, and three years, respectively. 26 studies revealed amended tumor response. Six studies showed improved Karnofsky performance status. Among the studies, 14 and 18 displayed a lowered white blood cells (WBC toxicity and an ameliorated radiation pneumonia, respectively. Conclusion. Couse of Astragalus-containing Chinese herbal prescriptions and radiotherapy may benefit the patients with NSCLC via increasing the therapeutic effectiveness and reducing the toxicity of radiotherapy. To confirm the exact merits, further rigorously designed trials are warranted.

  15. Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Haas, Naomi B; Donskov, Frede

    2017-01-01

    Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1......, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib...... 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety...

  16. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.

    Science.gov (United States)

    Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D'Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

    2016-11-16

    (1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p tea consumption counteracted FMD impairment (p tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

  17. A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal.

    Science.gov (United States)

    Simondon, F; Preziosi, M P; Yam, A; Kane, C T; Chabirand, L; Iteman, I; Sanden, G; Mboup, S; Hoffenbach, A; Knudsen, K; Guiso, N; Wassilak, S; Cadoz, M

    1997-10-01

    A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly during two visits after vaccination. Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days, in children under 15 years of age, was made by weekly home visits. Examining physicians, blind to vaccination status, took samples for culture and serologic testing. Pertussis was defined as 21 or more days of cough confirmed by culture, serology, or contact with a culture-confirmed person. Beginning 28 days after the third vaccine dose, the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group (RRac/wc) was 1.54 (95% CI, 1.23-1.93). In children younger than 18 months of age, RRac/wc was 1.16 (95% CI, 0.77-1.73) and 1.76 (95% CI, 1.33-2.33) in children older than 18 months, which suggests a shorter duration of protection with the acellular vaccine (P = 0.090). Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine: 31% (95% CI, 7-49) versus 55% against the protocol case definition, and 85% (95% CI, 66-93) versus 96% for the more severe WHO case definition. Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP, this difference was less prominent before 18 months of age, the customary age for a fourth dose. The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose.

  18. Observation of the limit cycle in the asymmetric plasma divided by the magnetic filter

    Energy Technology Data Exchange (ETDEWEB)

    Ohi, K.; Naitou, H.; Tauchi, Y.; Fukumasa, O. [Department of Electrical and Electronic Engineering, Yamaguchi Univ., Ube, Yamaguchi (Japan)

    2000-08-01

    Asymmetric plasma divided by the magnetic filter (MF) is numerically simulated by the one-dimensional particle-in-cell code VSIM1D. Depending on the asymmetry, the system behaves static or dynamic. In the static state, the potentials of the main plasma and the sub-plasma are given by the sheath potentials, {phi}{sub M} - 3T{sub Me}/e and {phi}{sub S} - 3T{sub Se}/e, respectively, with e being an electron charge and T{sub Me} and T{sub Se} being electron temperatures (T{sub Me} > T{sub Se}). In the dynamics state, while {phi}{sub M} - 3T{sub Me}/e, {phi}{sub S} oscillates periodically between {phi}{sub S,min} - 3T{sub Se}/e and {phi}{sub S,max} - 3T{sub Me}/e. The ions accelerated by the time varying potential gap get into the sub-plasma and excite the laminar shock waves. This periodic phenomenon can be understood as a limit cycle due to transitions between two bifurcated states of {phi}{sub S,min} and {phi}{sub S,max}. (author)

  19. Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine booster in adults primed with BCG: A randomized, controlled trial of DAR-901.

    Directory of Open Access Journals (Sweden)

    C Fordham von Reyn

    Full Text Available Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic.We performed a single site, randomized, double-blind, controlled, Phase 1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the United States. Healthy adult subjects age 18-65 with prior BCG immunization and a negative interferon-gamma release assay (IGRA were enrolled in cohorts of 16 subjects and randomized to three injections of DAR-901 (n = 10 per cohort, or saline placebo (n = 3 per cohort, or two injections of saline followed by an injection of BCG (n = 3 per cohort; 1-8 x 106 CFU. Three successive cohorts were enrolled representing DAR-901 at 0.1, 0.3, and 1 mg per dose. Randomization was performed centrally and treatments were masked from staff and volunteers. Subsequent open label cohorts of HIV-negative/IGRA-positive subjects (n = 5 and HIV-positive subjects (n = 6 received three doses of 1 mg DAR-901. All subjects received three immunizations at 0, 2 and 4 months administered as 0.1 mL injections over the deltoid muscle alternating between right and left arms. The primary outcomes were safety and immunogenicity. Subjects were followed for 6 months after dose 3 for safety and had phlebotomy performed for safety studies and immune assays before and after each injection. Immune assays using peripheral blood mononuclear cells included cell-mediated IFN-γ responses to DAR-901 lysate and to Mycobacterium tuberculosis (MTB lysate; serum antibody to M. tuberculosis lipoarabinomannan was assayed by ELISA.DAR-901 had an acceptable safety profile and was well-tolerated at all

  20. Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine booster in adults primed with BCG: A randomized, controlled trial of DAR-901.

    Science.gov (United States)

    von Reyn, C Fordham; Lahey, Timothy; Arbeit, Robert D; Landry, Bernard; Kailani, Leway; Adams, Lisa V; Haynes, Brenda C; Mackenzie, Todd; Wieland-Alter, Wendy; Connor, Ruth I; Tvaroha, Sue; Hokey, David A; Ginsberg, Ann M; Waddell, Richard

    2017-01-01

    Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic. We performed a single site, randomized, double-blind, controlled, Phase 1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the United States. Healthy adult subjects age 18-65 with prior BCG immunization and a negative interferon-gamma release assay (IGRA) were enrolled in cohorts of 16 subjects and randomized to three injections of DAR-901 (n = 10 per cohort), or saline placebo (n = 3 per cohort), or two injections of saline followed by an injection of BCG (n = 3 per cohort; 1-8 x 106 CFU). Three successive cohorts were enrolled representing DAR-901 at 0.1, 0.3, and 1 mg per dose. Randomization was performed centrally and treatments were masked from staff and volunteers. Subsequent open label cohorts of HIV-negative/IGRA-positive subjects (n = 5) and HIV-positive subjects (n = 6) received three doses of 1 mg DAR-901. All subjects received three immunizations at 0, 2 and 4 months administered as 0.1 mL injections over the deltoid muscle alternating between right and left arms. The primary outcomes were safety and immunogenicity. Subjects were followed for 6 months after dose 3 for safety and had phlebotomy performed for safety studies and immune assays before and after each injection. Immune assays using peripheral blood mononuclear cells included cell-mediated IFN-γ responses to DAR-901 lysate and to Mycobacterium tuberculosis (MTB) lysate; serum antibody to M. tuberculosis lipoarabinomannan was assayed by ELISA. DAR-901 had an acceptable safety profile and was well-tolerated at all dose levels

  1. Economia da cibercultura: A exclusão digital (Digital Divide)

    OpenAIRE

    Andrade, Pedro José de Oliveira

    2015-01-01

    Exclusão Digital (Digital Divide): Estatísticas da desigualdade; The Global Digital Divide; The Exploding Internet 2008; Uso da Internet em 2013. Nuvem semântica dos Media Sociais. Natureza qualitativa da exclusão. Exclusão de poder. Economia política da cibercultura. Classes e ciberpoder. Conetados e não-conetados.

  2. From Digital Divides to Digital Inequality -- The Emerging Digital Inequality in the Norwegian Unitarian School

    Science.gov (United States)

    Krumsvik, Rune J.

    2008-01-01

    This position paper highlights existing and emerging, prospective digital divides in Norwegian schools and asks whether we are now moving from traditional digital divides to digital inequality in our digitized society and schools. Despite very good technology density in Norwegian society and schools in general, there is the reason to pay attention…

  3. Dynamic crossmodal links revealed by steady-state responses in auditory-visual divided attention

    NARCIS (Netherlands)

    de Jong, Ritske; Toffanin, Paolo; Harbers, Marten; Martens, Sander

    Frequency tagging has been often used to study intramodal attention but not intermodal attention. We used EEG and simultaneous frequency tagging of auditory and visual sources to study intermodal focused and divided attention in detection and discrimination performance. Divided-attention costs were

  4. Is the Serpent Eating Its Tail? The Digital Divide and African Americans

    Science.gov (United States)

    Horton, Jacqueline

    2004-01-01

    The Digital Divide is alive and well in America. What this means is the technology haves and the have-nots are continually growing further apart. Due to the pace of change in the field of computer technology, this divide widens faster in less time. Playing catch-up becomes an increasingly more difficult game to endure, with the government, public,…

  5. Analysing the role of ICT in bridging the digital divide amongst ...

    African Journals Online (AJOL)

    We also investigate the nature of this digital divide while focusing on the local perspective. A short pilot study was done at four schools and one adult education centre in South Africa regarding their access to ICT. The results are used to indicate how and why ICT can be used in South Africa to overcome the digital divide that ...

  6. Combination N-Way Power Divider/Combiner and Noninvasive Reflected Power Detection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An N-way RF/microwave power divider/combiner utilizes one input and N outputs, or conversely N inputs and one output to divide (or combine) RF/microwave power while...

  7. Digital Divide in Sub Saharan Africa: Implications for E-governance ...

    African Journals Online (AJOL)

    The phrase 'digital divide' has now come of age, having been conceptualized in the 1990s with various interpretations tied to it. Now, governments the world over are striving to bridge the digital divide in order to reap digital dividends in the social, economic and political spheres and lately to achieve Millennium ...

  8. An Empirical Study of Education Divide Diminishment through Online Learning Courses

    Science.gov (United States)

    Hsieh, Ming-Yuan

    2017-01-01

    According to the swift development of education system, Taiwanese government is always devoting diminishing the educational divide between rural and urban regions. This research focuses on this educational divide by cross-employing the Grey Relational Analysis (GRA) of quantitative analysis and the Fuzzy Set Qualitative Comparative Analysis…

  9. Determinants of the digital divide: A study on IT development in Cambodia

    NARCIS (Netherlands)

    Wijers, G.D.M.

    2010-01-01

    The global digital divide is generally described as the inequality in use and ownership of computers and the internet across and within nations. While it is mostly approached from an economic point of view, this article argues for a more inclusive approach. The characteristics of the digital divide,

  10. Statistical and numerical methods to improve the transient divided bar method

    DEFF Research Database (Denmark)

    Bording, Thue Sylvester; Nielsen, S.B.; Balling, N.

    The divided bar method is a commonly used method to measure thermal conductivity of rock samples in laboratory. We present improvements to this method that allows for simultaneous measurements of both thermal conductivity and thermal diffusivity. The divided bar setup is run in a transient mode...

  11. Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.

    Science.gov (United States)

    Suncion, Viky Y; Ghersin, Eduard; Fishman, Joel E; Zambrano, Juan Pablo; Karantalis, Vasileios; Mandel, Nicole; Nelson, Katarina H; Gerstenblith, Gary; DiFede Velazquez, Darcy L; Breton, Elayne; Sitammagari, Kranthi; Schulman, Ivonne H; Taldone, Sabrina N; Williams, Adam R; Sanina, Cristina; Johnston, Peter V; Brinker, Jeffrey; Altman, Peter; Mushtaq, Muzammil; Trachtenberg, Barry; Mendizabal, Adam M; Tracy, Melissa; Da Silva, Jose; McNiece, Ian K; Lardo, Alberto C; George, Richard T; Hare, Joshua M; Heldman, Alan W

    2014-04-11

    Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7 ± 4.4%; n=95; PTESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

  12. Wave propagation and scattering in random media

    CERN Document Server

    Ishimaru, Akira

    1978-01-01

    Wave Propagation and Scattering in Random Media, Volume 2, presents the fundamental formulations of wave propagation and scattering in random media in a unified and systematic manner. The topics covered in this book may be grouped into three categories: waves in random scatterers, waves in random continua, and rough surface scattering. Random scatterers are random distributions of many particles. Examples are rain, fog, smog, hail, ocean particles, red blood cells, polymers, and other particles in a state of Brownian motion. Random continua are the media whose characteristics vary randomly an

  13. Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes.

    Science.gov (United States)

    Dei Cas, Alessandra; Spigoni, Valentina; Cito, Monia; Aldigeri, Raffaella; Ridolfi, Valentina; Marchesi, Elisabetta; Marina, Michela; Derlindati, Eleonora; Aloe, Rosalia; Bonadonna, Riccardo C; Zavaroni, Ivana

    2017-02-23

    Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown. Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed. Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers. V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.

  14. Pilot randomized controlled trial to evaluate the effect of aquatic and land physical therapy on musculoskeletal dysfunction of sickle cell disease patients

    Directory of Open Access Journals (Sweden)

    Camila Tatiana Zanoni

    2015-04-01

    Full Text Available Objective: To compare the effect of aquatic and land-based physiotherapy in reducing musculoskeletal hip and lower back pain and increasing overall physical capabilities of sickle cell disease patients. Methods: Informed written consent was obtained from all volunteers who were submitted to evaluations using different functional scales: Lequesne's Algofunctional Questionnaire and Oswestry Disability Index, trunk and hip range of motion, goniometry, trunk and hip muscle strength assessment using load cell, and surface electromyography of the iliocostalis, long dorsal (longissimus, gluteus maximus, gluteus medius and tensor fasciae latae muscles. Ten patients were randomized into two groups: aquatic physiotherapy with a mean age of 42 years (range: 25-67 and conventional physiotherapy with a mean age of 49 years (range: 43-59. Both groups were submitted to a twelve-week program of two sessions weekly. Results: After the intervention, significant improvements were observed regarding the Lequesne index (p-value = 0.0217, Oswestry Disability Index (p-value = 0.0112, range of motion of trunk extension (p-value = 0.0320, trunk flexion muscle strength (p-value = 0.0459, hip extension and abduction muscle strength (p-value = 0.0062 and p-value = 0.0257, respec- tively. Range of motion of trunk and hip flexion, extension, adduction and abduction, trunk extensor muscle strength and all surface electromyography variables showed no significant statistical difference. Conclusion: Physical therapy is efficient to treat musculoskeletal dysfunctions in sickle cell disease patients, irrespective of the technique; however, aquatic therapy showed a trend toward improvement in muscle strength. Further studies with a larger patient sample and longer periods of therapy are necessary to confirm these results.

  15. A Plant-Based Dietary Intervention Improves Beta-Cell Function and Insulin Resistance in Overweight Adults: A 16-Week Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Hana Kahleova

    2018-02-01

    Full Text Available The aim of this study was to test the effect of a plant-based dietary intervention on beta-cell function in overweight adults with no history of diabetes. Participants (n = 75 were randomized to follow a low-fat plant-based diet (n = 38 or to make no diet changes (n = 37 for 16 weeks. At baseline and 16 weeks, beta-cell function was quantified with a mathematical model. Using a standard meal test, insulin secretory rate was calculated by C-peptide deconvolution. The Homeostasis Model Assessment (HOMA-IR index was used to assess insulin resistance while fasting. A marked increase in meal-stimulated insulin secretion was observed in the intervention group compared with controls (interaction between group and time, Gxt, p < 0.001. HOMA-IR index fell significantly (p < 0.001 in the intervention group (treatment effect −1.0 (95% CI, −1.2 to −0.8; Gxt, p = 0.004. Changes in HOMA-IR correlated positively with changes in body mass index (BMI and visceral fat volume (r = 0.34; p = 0.009 and r = 0.42; p = 0.001, respectively. The latter remained significant after adjustment for changes in BMI (r = 0.41; p = 0.002. Changes in glucose-induced insulin secretion correlated negatively with BMI changes (r = −0.25; p = 0.04, but not with changes in visceral fat. Beta-cell function and insulin sensitivity were significantly improved through a low-fat plant-based diet in overweight adults.

  16. Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Sanne J Jansen of Lorkeers

    Full Text Available Recently cardiomyocyte progenitor cells (CMPCs were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls.Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes.We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA. Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals.Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction.

  17. Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: a phase II randomized trial.

    Science.gov (United States)

    Zwitter, Matjaz; Kovac, Viljem; Rajer, Mirjana; Vrankar, Martina; Smrdel, Uros

    2010-07-01

    We present experience from a phase II randomized clinical trial, comparing standard gemcitabine as monotherapy with low-dose gemcitabine in long infusion in a doublet with cisplatin at reduced dose for patients with non-small cell lung cancer (NSCLC) and who are unfit for standard platin-based chemotherapy. Eligible patients had microscopically confirmed NSCLC in stage IIIB (wet) or IV, were chemo-naive, and were in poor performance status or presented with significant comorbidity. Standard treatment with gemcitabine, 1250 mg/m in 20-30 min on days 1 and 8 as monotherapy (arm A) was compared with low-dose gemcitabine in long infusion (200 mg/m in 6 h on day 1) and cisplatin at 60 mg/m on day 2 (arm B). Both treatment schedules were repeated every 3 weeks until disease progression, unacceptable toxicity, or to a maximum of six cycles. A total of 112 patients (83 male, 29 female, median age 66 years) were randomized between arm A (57 patients) and B (55 patients). The two groups were balanced for prognostic factors. Fifty-three patients in arm A and 52 in arm B received at least one application of chemotherapy and were evaluable for toxicity and response. The median number of cycles was four and five for arms A and B, respectively. Except for grade 3 anemia (one patient in arm A and two in arm B), no other major toxicity was seen. Regarding response to treatment, arm B was superior: 1 complete response and 13 partial remissions (response rate 26.9%) as compared with five partial remissions (response rate 9.4%) in arm A (Psuperior to monotherapy with gemcitabine in standard doses, and is suitable for patients with NSCLC who cannot tolerate a standard platin-based doublet.

  18. Neuromuscular electrical stimulation of the quadriceps in patients with non-small cell lung cancer receiving palliative chemotherapy: a randomized phase II study.

    Directory of Open Access Journals (Sweden)

    Matthew Maddocks

    Full Text Available A reduced exercise capacity is associated with increased morbidity and mortality in patients with advanced non-small cell lung cancer (NSCLC. Therapeutic exercise can be beneficial and neuromuscular electrical stimulation (NMES of the quadriceps muscles may represent a practical approach. The primary aim of this study was to determine the acceptability of NMES of the quadriceps to patients with NSCLC used alongside palliative chemotherapy. Secondary aims explored aspects of safety and efficacy of NMES in this setting.Patients with advanced NSCLC due to receive first-line palliative chemotherapy were randomized to usual care with or without NMES. They were asked to undertake 30 minute sessions of NMES, ideally daily, but as a minimum, three times weekly. For NMES to be considered acceptable, it was predetermined that ≥80% of patients should achieve this minimum level of adherence. Qualitative interviews were held with a subset of patients to explore factors influencing adherence. Safety was assessed according to the Common Terminology Criteria for Adverse Events. Quadriceps muscle strength, thigh lean mass, and physical activity level were assessed at baseline and after three cycles of chemotherapy.49 patients (28 male, median (IQR age 69 (64-75 years participated. Of 30 randomized to NMES, 18 were eligible for the primary endpoint, of whom 9 (50% [90% CI, 29 to 71] met the minimum level of adherence. Adherence was enhanced by incorporating sessions into a daily routine and hindered by undesirable effects of chemotherapy. There were no serious adverse events related to NMES, nor significant differences in quadriceps muscle strength, thigh lean mass or physical activity level between groups.NMES is not acceptable in this setting, nor was there a suggestion of benefit. The need remains to explore NMES in patients with cancer in other settings.Current Controlled Trials ISRCTN 42944026 www.controlled-trials.com/ISRCTN42944026.

  19. Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group.

    Science.gov (United States)

    Robb, Sheri L; Burns, Debra S; Stegenga, Kristin A; Haut, Paul R; Monahan, Patrick O; Meza, Jane; Stump, Timothy E; Cherven, Brooke O; Docherty, Sharron L; Hendricks-Ferguson, Verna L; Kintner, Eileen K; Haight, Ann E; Wall, Donna A; Haase, Joan E

    2014-03-15

    To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers. © 2013 American Cancer Society.

  20. Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study.

    Science.gov (United States)

    Johnson, Casey; Hohenboken, Matthew; Poling, Terry; Jaehnig, Peter; Kanesa-Thasan, Niranjan

    2015-07-01

    A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥ 3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Randomized, open-label trial evaluating the preventive effect of tetracycline on afatinib induced-skin toxicities in non-small cell lung cancer patients.

    Science.gov (United States)

    Arrieta, Oscar; Vega-González, María Teresa; López-Macías, Diego; Martínez-Hernández, Jorge Negueb; Bacon-Fonseca, Ludwing; Macedo-Pérez, Eleazar Omar; Ramírez-Tirado, Laura Alejandra; Flores-Estrada, Diana; de la Garza-Salazar, Jaime

    2015-06-01

    Afatinib has shown long progression free survival and improvement in quality of life in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Although afatinib causes acneiform rash, it can be manageable. Tetracyclines are usually used to treat it; nonetheless, there is no trial that evaluates their prophylactic efficacy on afatinib induced-skin toxicities (AIST). This open-label, randomized, controlled trial assessed the preventive effect of tetracycline for reducing afatinib-skin toxicities in NSCLC patients receiving afatinib 40 mg/day. Patients were randomly assigned to receive pre-emptive treatment with tetracycline 250 mg every 12h for 4 weeks or not. Reactive treatment in both groups included general dermatological recommendations such as use of skin moisturizers, sunscreen and topical steroids, according to toxicity severity. All patients were blindly monitored for skin toxicities by an expert dermatologist at the start of treatment with afatinib (day 0), weeks 2 and 4 of treatment. The protocol is registered on clinicaltrials.gov (NCT01880515). We included 90 patients, no differences were found in clinical and dermatological baseline characteristics. Rash incidence of any grade, and grade ≥2 was less frequent in the pre-emptive arm vs. the control arm (44.5 vs. 75.6%, RR 0.4 [95% CI 0.17-0.99], p=0.046 and 15.6 vs. 35.6%, RR 0.35 [95% CI, 0.12-0.91], p=0.030, respectively). No difference was found in paronychia, xerosis, mucositis, folliculitis, and skin fissure. No adverse event was associated with tetracycline. Neither rash nor pre-emptive tetracycline impacted on response rate, progression-free or overall survivals. Pre-emptive tetracycline was well tolerated and reduced the rash incidence and severity associated with afatinib in more than 60%. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. A multi-center prospective study randomizing the use of fat emulsion in intensive glucose control after allogeneic hematopoietic stem cell transplantation using a myeloablative conditioning regimen.

    Science.gov (United States)

    Fuji, Shigeo; Kim, Sung-Won; Kamiya, Shigemi; Nakane, Takahiko; Matsumoto, Kenji; Onishi, Yasushi; Yakushijin, Kimikazu; Yamazaki, Etsuko; Hino, Masayuki; Kurosawa, Saiko; Yoshimura, Ken-Ichi; Fukuda, Takahiro

    2017-11-16

    Although parenteral nutrition (PN) is often used after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there is controversy regarding PN management, for instance in the use of fat emulsion and glucose control (GC). To clarify these issues, we conducted a multi-center prospective study with intensive GC, randomizing the use of fat emulsion after allo-HSCT using a myeloablative conditioning regimen. The primary endpoint was the cumulative incidence of documented infectious disease, namely bacterial and fungal infection, at day 100 after allo-HSCT. Between August 2007 and March 2012, we enrolled 81 patients at 5 centers. Excluding 5 ineligible patients, 76 patients received the protocol treatment. The target fasting glucose level was 80-110 mg/dL. The median follow-up of surviving patients was 1796 days. The cumulative incidences of documented infectious disease at day 100 were 16% (95% confidence interval [CI] 6-29%) in the no-fat group and 19% (95% CI 8-32%) in the fat group, indicating no significant difference. The mean glucose level at 28 days after allo-HSCT was 107 mg/dL in the no-fat group and 111 mg/dL in the fat group. Grade 3 hyperglycemia (>250 mg/dL) and grade 3 hypoglycemia (fat group and 69% and 8% in the fat group, respectively. Irrespective of the use of fat emulsion, the long-term clinical outcomes of the enrolled patients were favorable under intensive GC. To further clarify the benefits of GC after allo-HSCT, a prospective study randomizing the level of GC is warranted. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  3. Non-random geographic distribution of patients with cutaneous T-cell lymphoma in the Greater Pittsburgh Area.

    Science.gov (United States)

    Moreau, Jacqueline F; Buchanich, Jeanine M; Geskin, Jacob Z; Akilov, Oleg E; Geskin, Larisa J

    2014-07-15

    Environmental hazards may play a role in the etiology of cutaneous T-cell lymphoma (CTCL). Some studies have found an increased incidence of CTCL among workers in chemical science, transportation, and manufacturing industries, but other studies have not. This discrepancy may be attributable to population migration, complicating accurate assessment of lifetime exposures. The Pittsburgh population has very low migration rates and most CTCL patients seen at the University of Pittsburgh Medical Center (UPMC) Cutaneous Lymphoma Center are life-long local residents. The Greater Pittsburgh Area used to be an industrial hub. There are residential communities positioned within close proximity to inactive industrial sites that continue to contain pollutants. To determine whether CTCL patients' residences cluster within specific Pittsburgh regions, in particular, those with high levels of environmental pollutants. Our study included patients diagnosed with CTCL at the UPMC Cutaneous Lymphoma Center between 2000 and 2012. We mapped the longitudinal and latitudinal coordinates of patients' residences at diagnosis, superfund sites, toxic release inventory sites, particular matter levels, and dermatologists' offices using ArcMap 10.1. We then performed a SaTScan analysis using zip codes to assess for geographic clustering of patients' residences in the Pittsburgh metropolitan statistical area. We assessed for a correlation between case distribution and both environmental hazards sites and dermatologist density in the area. We identified 274 patients with CTCL in the Greater Pittsburgh area. We identified a statistically significant geographic cluster (pPittsburgh and the site of the region's only CTCL clinic. We observed no relationship between the locations of superfund sites, toxic release inventory sites, or particular matter levels and CTCL case distribution. Our findings do not support an association between exposure to environmental toxins and CTCL. CTCL cases clustered in

  4. A randomized, double-blind, phase II study of erlotinib with or without sunitinib for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC)

    NARCIS (Netherlands)

    Groen, H. J. M.; Socinski, M. A.; Grossi, F.; Juhasz, E.; Gridelli, C.; Baas, P.; Butts, C. A.; Chmielowska, E.; Usari, T.; Selaru, P.; Harmon, C.; Williams, J. A.; Gao, F.; Tye, L.; Chao, R. C.; Blumenschein, G. R.

    Combined inhibition of vascular, platelet-derived, and epidermal growth factor receptor (EGFR) pathways may overcome refractoriness to single agents in platinum-pretreated non-small-cell lung cancer (NSCLC). This randomized, double-blind, multicenter, phase II trial evaluated sunitinib 37.5 mg/day

  5. Randomized controlled trial on the effects of a supervised high intensity exercise program in patients with a hematologic malignancy treated with autologous stem cell transplantation: Results from the EXIST study

    NARCIS (Netherlands)

    Persoon, Saskia; Chinapaw, Mai J. M.; Buffart, Laurien M.; Liu, Roberto D. K.; Wijermans, Pierre; Koene, Harry R.; Minnema, Monique C.; Lugtenburg, Pieternella J.; Marijt, Erik W. A.; Brug, Johannes; Nollet, Frans; Kersten, Marie José

    2017-01-01

    This single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation. 109 patients were

  6. Random thoughts

    Science.gov (United States)

    ajansen; kwhitefoot; panteltje1; edprochak; sudhakar, the

    2014-07-01

    In reply to the physicsworld.com news story “How to make a quantum random-number generator from a mobile phone” (16 May, http://ow.ly/xFiYc, see also p5), which describes a way of delivering random numbers by counting the number of photons that impinge on each of the individual pixels in the camera of a Nokia N9 smartphone.

  7. Complex Systems Analysis of Cell Cycling Models in Carcinogenesis:II. Cell Genome and Interactome, Neoplastic Non-random Transformation Models in Topoi with Lukasiewicz-Logic and MV Algebras

    CERN Document Server

    Baianu, I C

    2004-01-01

    Quantitative Biology, abstract q-bio.OT/0406045 From: I.C. Baianu Dr. [view email] Date (v1): Thu, 24 Jun 2004 02:45:13 GMT (164kb) Date (revised v2): Fri, 2 Jul 2004 00:58:06 GMT (160kb) Complex Systems Analysis of Cell Cycling Models in Carcinogenesis: II. Authors: I.C. Baianu Comments: 23 pages, 1 Figure Report-no: CC04 Subj-class: Other Carcinogenesis is a complex process that involves dynamically inter-connected modular sub-networks that evolve under the influence of micro-environmentally induced perturbations, in non-random, pseudo-Markov chain processes. An appropriate n-stage model of carcinogenesis involves therefore n-valued Logic treatments of nonlinear dynamic transformations of complex functional genomes and cell interactomes. Lukasiewicz Algebraic Logic models of genetic networks and signaling pathways in cells are formulated in terms of nonlinear dynamic systems with n-state components that allow for the generalization of previous, Boolean or "fuzzy", logic models of genetic activities in vivo....

  8. Microtubule networks for plant cell division

    NARCIS (Netherlands)

    Keijzer, de Jeroen; Mulder, B.M.; Janson, M.E.

    2014-01-01

    During cytokinesis the cytoplasm of a cell is divided to form two daughter cells. In animal cells, the existing plasma membrane is first constricted and then abscised to generate two individual plasma membranes. Plant cells on the other hand divide by forming an interior dividing wall, the so-called

  9. The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.

    Science.gov (United States)

    Dummer, Reinhard; Guminski, Alexander; Gutzmer, Ralf; Dirix, Luc; Lewis, Karl D; Combemale, Patrick; Herd, Robert M; Kaatz, Martin; Loquai, Carmen; Stratigos, Alexander J; Schulze, Hans-Joachim; Plummer, Ruth; Gogov, Sven; Pallaud, Celine; Yi, Tingting; Mone, Manisha; Chang, Anne Lynn S; Cornélis, Frank; Kudchadkar, Ragini; Trefzer, Uwe; Lear, John T; Sellami, Dalila; Migden, Michael R

    2016-07-01

    The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study. This report provides long-term follow-up data collected up to 12 months after the last patient was randomized. In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review. Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively). No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved. With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Identification of two linear B-cell epitopes from West Nile virus NS1 by screening a phage-displayed random peptide library

    Directory of Open Access Journals (Sweden)

    Qin Yong-Li

    2011-07-01

    Full Text Available Abstract Background The West Nile virus (WNV nonstructural protein 1 (NS1 is an important antigenic protein that elicits protective antibody responses in animals and can be used for the serological diagnosis of WNV infection. Although previous work has demonstrated the vital role of WNV NS1-specific antibody responses, the specific epitopes in the NS1 have not been identified. Results The present study describes the identification of two linear B-cell epitopes in WNV NS1 through screening a phage-displayed random 12-mer peptide library with two monoclonal antibodies (mAbs 3C7 and 4D1 that directed against the NS1. The mAbs 3C7 and 4D1 recognized phages displaying peptides with the consensus motifs LTATTEK and VVDGPETKEC, respectively. Exact sequences of both motifs were found in the NS1 (895LTATTEK901 and 925VVDGPETKEC934. Further identification of the displayed B cell epitopes were conducted using a set of truncated peptides expressed as MBP fusion proteins. The data indicated that 896TATTEK901 and925VVDGPETKEC934 are minimal determinants of the linear B cell epitopes recognized by the mAbs 3C7 and 4D1, respectively. Antibodies present in the serum of WNV-positive horses recognized the minimal linear epitopes in Western blot analysis, indicating that the two peptides are antigenic in horses during infection. Furthermore, we found that the epitope recognized by 3C7 is conserved only among WNV strains, whereas the epitope recognized by 4D1 is a common motif shared among WNV and other members of Japanese encephalitis virus (JEV serocomplex. Conclusions We identified TATTEK and VVDGPETKEC as NS1-specific linear B-cell epitopes recognized by the mAbs 3C7 and 4D1, respectively. The knowledge and reagents generated in this study may have potential applications in differential diagnosis and the development of epitope-based marker vaccines against WNV and other viruses of JEV serocomplex.

  11. Digital divide: a national security argumentative analysis within a South African context

    CSIR Research Space (South Africa)

    Phahlamohlaka, J

    2010-10-01

    Full Text Available . This is followed by an analysis of the digital divide framed within the determinants of national power as embedded in the National Security definition. It is within this analysis that the five mostly argued dimensions of the digital divide are contrasted against... and the Determinants of National Power In this section we perform an analysis of the digital divide framed within the determinants of national power as embedded in the National Security definition. It is within this analysis that the five mostly argued dimensions...

  12. A case against a divide and conquer approach to the nonsymmetric eigenvalue problem

    Energy Technology Data Exchange (ETDEWEB)

    Jessup, E.R.

    1991-12-01

    Divide and conquer techniques based on rank-one updating have proven fast, accurate, and efficient in parallel for the real symmetric tridiagonal and unitary eigenvalue problems and for the bidiagonal singular value problem. Although the divide and conquer mechanism can also be adapted to the real nonsymmetric eigenproblem in a straightforward way, most of the desirable characteristics of the other algorithms are lost. In this paper, we examine the problems of accuracy and efficiency that can stand in the way of a nonsymmetric divide and conquer eigensolver based on low-rank updating. 31 refs., 2 figs.

  13. Illusory recollection in older adults and younger adults under divided attention.

    Science.gov (United States)

    Skinner, Erin I; Fernandes, Myra A

    2009-03-01

    The authors investigated the effect of divided attention, study-list repetition, and age on recollection and familiarity. Older and younger adults under full attention and younger adults under divided attention at study viewed word lists highly associated with a single unstudied word (critical lure) once or three times, and subsequently performed a remember-know recognition test. Younger adults made fewer false remember responses to critical lures from repeated study lists, whereas younger adults under divided attention and older adults both showed an increase with repetition. Findings suggest older adults' susceptibility to illusory memories is related to a deficit in available attention during encoding.

  14. Transition state theory for solvated reactions beyond recrossing-free dividing surfaces.

    Science.gov (United States)

    Revuelta, F; Bartsch, Thomas; Garcia-Muller, P L; Hernandez, Rigoberto; Benito, R M; Borondo, F

    2016-06-01

    The accuracy of rate constants calculated using transition state theory depends crucially on the correct identification of a recrossing-free dividing surface. We show here that it is possible to define such optimal dividing surface in systems with non-Markovian friction. However, a more direct approach to rate calculation is based on invariant manifolds and avoids the use of a dividing surface altogether, Using that method we obtain an explicit expression for the rate of crossing an anharmonic potential barrier. The excellent performance of our method is illustrated with an application to a realistic model for LiNC⇌LiCN isomerization.

  15. A Single-Center, Randomized Double-Blind Placebo-Controlled Study Evaluating the Effects of Poly-Gamma-Glutamate on Human NK Cell Activity after an 8-Week Oral Administration in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Kyung-Soo Kim

    2013-01-01

    Full Text Available A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly-γ-glutamate (γ-PGA on human natural killer (NK cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL containing 0 mg (placebo, 250 mg (low dosage, or 500 mg (high dosage of γ-PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ-PGA group were significantly higher (P<0.05 for all comparisons compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production. These results suggest that the oral administration of γ-PGA induces a cell-mediated immunity by increasing the NK cell activity in humans.

  16. Stem Cell Information: Glossary

    Science.gov (United States)

    ... it is called a fetus . Embryoid bodies - Rounded collections of cells that arise when embryonic stem cells ... dividing without differentiating for a prolonged period in culture, and are known to develop into cells and ...

  17. Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma.

    Science.gov (United States)

    Motzer, Robert J; Haas, Naomi B; Donskov, Frede; Gross-Goupil, Marine; Varlamov, Sergei; Kopyltsov, Evgeny; Lee, Jae Lyun; Melichar, Bohuslav; Rini, Brian I; Choueiri, Toni K; Zemanova, Milada; Wood, Lori A; Reaume, M Neil; Stenzl, Arnulf; Chowdhury, Simon; Lim, Ho Yeong; McDermott, Ray; Michael, Agnieszka; Bao, Weichao; Carrasco-Alfonso, Marlene J; Aimone, Paola; Voi, Maurizio; Doehn, Christian; Russo, Paul; Sternberg, Cora N

    2017-12-10

    Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT 600mg ), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT 800mg ) and safety. Results The primary analysis results of DFS ITT 600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT 800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT 600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.

  18. IL-2 in combination with IFN-αand 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial

    Science.gov (United States)

    Atzpodien, J; Kirchner, H; Illiger, H J; Metzner, B; Ukena, D; Schott, H; Funke, P J; Gramatzki, M; Jürgenson, S von; Wandert, T; Patzelt, T; Reitz, M

    2001-01-01

    We conducted a prospectively randomized clinical trial to compare the efficacy and safety of subcutaneous interferon-α2a, subcutaneous interleukin-2 and intravenous 5-fluorouracil as home therapy against oral tamoxifen in 78 patients with progressive metastatic renal cell carcinoma. Treatment courses consisted of interferon-α2a 5 × 106 IU m−2day 1 weeks 1 + 4; days 1, 3, 5 weeks 2 + 3; 10 × 106 IU m−2days 1, 3, 5 weeks 5–8; interleukin-2 10 × 106 IU m−2twice daily days 3–5 weeks 1 + 4; 5 × 106 IU m−2days 1, 3, 5 weeks 2 + 3; and 5-fluorouracil 1000 mg m−2day 1 weeks 5–8. The tamoxifen group received tamoxifen 80 mg twice daily over 8 weeks. Among 41 patients treated with interleukin-2, interferon-α2a and 5-fluorouracil there were 7 complete (17.1%) and 9 partial responders (21.9%), with an overall objective response rate of 39.1% (95% CI, 24.2–55.5). An additional 15 patients (36.6%) were stable throughout therapy. The overall survival was 24 months (range 5–76+). In 37 patients receiving tamoxifen no objective remissions occurred. 13 patients (35.1%) had stable disease and 24 patients (64.9%) showed continued disease progression. The overall survival was 13 months (range 3–73+). In summary, this home-based therapy regimen of interferon-α2a, interleukin-2 and 5-fluorouracil demonstrated significant therapeutic efficacy in patients with progressive renal cell carcinoma when compared to hormonal therapy. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11710825

  19. Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized, double-blind, multi-center, phase 3 clinical trial.

    Science.gov (United States)

    Song, Joon Young; Cheong, Hee Jin; Lee, Jacob; Woo, Heung Jeong; Wie, Seong-Heon; Lee, Jin-Soo; Kim, Shin Woo; Noh, Ji Yun; Choi, Won Suk; Kim, Hun; Kim, Kyung-Ho; Kim, Woo Joo

    2015-10-05

    Cell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity. A randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (AgrippalS1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number-NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination. A total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups. NBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Effects of pioglitazone versus metformin on circulating endothelial microparticles and progenitor cells in patients with newly diagnosed type 2 diabetes--a randomized controlled trial.

    Science.gov (United States)

    Esposito, K; Maiorino, M I; Di Palo, C; Gicchino, M; Petrizzo, M; Bellastella, G; Saccomanno, F; Giugliano, D

    2011-05-01

    Endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are markers of endothelial injury and repair. We compared the effects of pioglitazone versus metformin on the circulating numbers of EMPs and EPCs in patients with newly diagnosed type 2 diabetes. This was a randomized, double-blind, comparator-controlled, 24-week single-centre trial conducted in a Teaching Hospital in Naples, Italy. One hundred and ten people with newly diagnosed type 2 diabetes who were never treated with antihyperglycaemic drugs and had haemoglobin A1c (HbA1c) levels between 7 and 10% were given pioglitazone hydrochloride (15-45 mg/day) (n = 55) or metformin (1000-2000 mg/day) (n = 55) as an active comparator. Absolute change from baseline to final visit in circulating EMPs and EPCs and their ratio were the main outcomes. Baseline characteristics did not differ between the study groups. The decrease in circulating EMPs CD31+ [intergroup difference, -32 counts/µl (95% CI -51 to -9)] and the increase in EPCs CD34+/KDR+ [intergroup difference, 33 cells/10(6) events (95% CI 13 to 55)] were greater with pioglitazone versus metformin. EMPs/EPCs ratio was reduced with pioglitazone and unchanged with metformin [difference, -1.5 (95% CI -2.6 to -0.5), p pioglitazone gained more weight and experienced greater improvements in some coronary risk measures [high-density lipoprotein (HDL)-cholesterol, triglycerides, adiponectin and C-reactive protein (CRP)] than did those assigned to metformin. Compared with metformin, pioglitazone treatment improved the imbalance between endothelial damage and repair capacity and led to more favourable changes in coronary risk factors in patients with newly diagnosed type 2 diabetes. © 2011 Blackwell Publishing Ltd.

  1. Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study.

    Science.gov (United States)

    Tostes, Glauce Cordeiro Ulhôa; Cunha, Maria Rosário; Fukui, Rosa Tsumeshiro; Correia, Márcia Regina Silva; Rocha, Dalva Marreiro; Dos Santos, Rosa Ferreira; da Silva, Maria Elizabeth Rossi

    2016-01-01

    To compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2). A prospective study was performed in 20 patients with DM2, mean age 51.82 ± 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4-8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-α, leptin, sICAM and TGFβ levels. Both therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa β, PAI-1 activity, CRP, fibrinogen, TGFβ, FFA and triglyceride levels. Nateglinide and rosiglitazone were effective in improving glucose and lipid profile and β cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.

  2. Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes.

    Science.gov (United States)

    McCloskey, Morgan L; Tarazona-Meza, Carla E; Jones-Smith, Jessica C; Miele, Catherine H; Gilman, Robert H; Bernabe-Ortiz, Antonio; Miranda, J Jaime; Checkley, William

    2017-07-11

    Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in

  3. eHealth literacy: extending the digital divide to the realm of health information.

    Science.gov (United States)

    Neter, Efrat; Brainin, Esther

    2012-01-27

    eHealth literacy is defined as the ability of people to use emerging information and communications technologies to improve or enable health and health care. The goal of this study was to explore whether literacy disparities are diminished or enhanced in the search for health information on the Internet. The study focused on (1) traditional digital divide variables, such as sociodemographic characteristics, digital access, and digital literacy, (2) information search processes, and (3) the outcomes of Internet use for health information purposes. We used a countrywide representative random-digital-dial telephone household survey of the Israeli adult population (18 years and older, N = 4286). We measured eHealth literacy; Internet access; digital literacy; sociodemographic factors; perceived health; presence of chronic diseases; as well as health information sources, content, search strategies, and evaluation criteria used by consumers. Respondents who were highly eHealth literate tended to be younger and more educated than their less eHealth-literate counterparts. They were also more active consumers of all types of information on the Internet, used more search strategies, and scrutinized information more carefully than did the less eHealth-literate respondents. Finally, respondents who were highly eHealth literate gained more positive outcomes from the information search in terms of cognitive, instrumental (self-management of health care needs, health behaviors, and better use of health insurance), and interpersonal (interacting with their physician) gains. The present study documented differences between respondents high and low in eHealth literacy in terms of background attributes, information consumption, and outcomes of the information search. The association of eHealth literacy with background attributes indicates that the Internet reinforces existing social differences. The more comprehensive and sophisticated use of the Internet and the subsequent increased

  4. A Randomized Trial of Liposomal Paclitaxel plus Cisplatin as First-line Therapy for Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xi LI

    2012-04-01

    Full Text Available Background and objective Paclitaxel plus cisplatin (TP is used as the standard regimen for patients with advanced non-small cell lung cancer (NSCLC. In this study, we compared the response rate (RR, overall survival (OS, and toxicity of the combined chemotherapy regimen of liposomal paclitaxel plus cisplatin (LP with those of TP as first-line treatments for advanced NSCLC. Methods A total of 100 patients were randomly selected to be treated with liposomal paclitaxel or paclitaxel at a dose of 150 mg/m2 on day 1 plus cisplatin at a dose of 75 mg/m2 on days 1 and 2 per cycle every 21 days. Results All 100 patients were eligible. The median progression free survival was 5.1 months vs 4.2 months, the median OS was 9.0 months vs 9.3 months, and RR was 26% vs 24% in the LP and TP arms, respectively. No significant difference was observed (P=0.110, 0.342 and 0.890, respectively. There was no significant difference between grades 3 and 4 toxicity of the arms (P>0.05. Peripheral neuritis observed in the LP arm was significantly lower than that in the TP arm (8% vs 28%, and the difference was statistically significant (P=0.030. Conclusion The effects of LP and TP as first-line therapies for NSCLC are similar. However, peripheral neuritis in the LP arm is significantly lower than in the TP arm.

  5. Prevention of central nervous system sequelae in sickle cell disease without evidence from randomized controlled trials: the case for a team-based learning collaborative.

    Science.gov (United States)

    DeBaun, Michael R; King, Allison A

    2016-12-02

    Since 1998, the National Institutes of Health has funded 5 randomized controlled trials (RCTs) for primary and secondary prevention of strokes in children with sickle cell anemia (SCA). In a systematic fashion, these trials have significantly advanced the care of children with SCA. In the absence of an RCT, clinicians are often compelled to make decisions at the bedside, based on experience, observational studies, and principles of hematology. We will provide an initial example that describes how a team-based, learning collaborative developed a multisite standard care protocol with a low budget (children and adults with SCD will be discussed: (1) secondary stroke prevention in high-income countries; (2) primary stroke prevention in low- and middle-income countries (LMICs); (3) poor academic performance in students; and (4) cognitive disability in adults. With a commitment to a team-based learning collaborative, incremental advances are possible for the neurologic care of children and adults with SCD. © 2016 by The American Society of Hematology. All rights reserved.

  6. Lessons Learned From a Randomized Controlled Trial of a Family-Based Intervention to Promote School Functioning for School-Age Children With Sickle Cell Disease.

    Science.gov (United States)

    Daniel, Lauren C; Li, Yimei; Smith, Kelsey; Tarazi, Reem; Robinson, M Renee; Patterson, Chavis A; Smith-Whitley, Kim; Stuart, Marie; Barakat, Lamia P

    2015-01-01

    Tested a family-based group problem-solving intervention, "Families Taking Control," (FTC) to improve school functioning and health-related quality of life (HRQL) for children with sickle cell disease. Children and caregivers completed questionnaires assessing HRQL and school functioning and children completed performance-based measures of IQ and achievement at baseline and 6 months later. Families were randomized to the intervention (FTC, n = 42) or delayed intervention control (DIC, n = 41) group. FTC involved a full-day workshop followed by 3 booster calls. There were no differences between FTC completers (n = 24) and noncompleters (n = 18). FTC group (n = 24) and DIC group (n = 38) did not differ significantly on primary outcomes at follow-up: number of formal academic and disease-related accommodations, individualized education plan/504 service plan, school absences, school HRQL, or academic skills. Although families found FTC to be acceptable, there were no intervention effects. Challenges of the trial and implications for future research are discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Random insertion of split-cans of the fluorescent protein venus into Shaker channels yields voltage sensitive probes with improved membrane localization in mammalian cells.

    Science.gov (United States)

    Jin, Lei; Baker, Bradley; Mealer, Robbie; Cohen, Lawrence; Pieribone, Vincent; Pralle, Arnd; Hughes, Thomas

    2011-07-15

    FlaSh-YFP, a fluorescent protein (FP) voltage sensor that is a fusion of the Shaker potassium channel with yellow fluorescent protein (YFP), is primarily expressed in the endoplasmic reticulum (ER) of mammalian cells, possibly due to misfolded monomers. In an effort to improve plasma membrane expression, the FP was split into two non-fluorescent halves. Each half was randomly inserted into Shaker monomers via a transposon reaction. Shaker subunits containing the 5' half were co-expressed with Shaker subunits containing the 3' half. Tetramerization of Shaker subunits is required for re-conjugation of the FP. The misfolded monomers trapped in ER are unlikely to tetramerize and reconstitute the beta-can structure, and thus intracellular fluorescence might be reduced. This split-can transposon approach yielded 56 fluorescent probes, 30 (54%) of which were expressed at the plasma membrane and were capable of optically reporting changes in membrane potential. The largest signal from these novel FP-sensors was a -1.4% in ΔF/F for a 100 mV depolarization, with on time constants of about 15 ms and off time constants of about 200 ms. This split-can transposon approach has the potential to improve other multimeric probes. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Reduction of allogeneic red blood cell usage during cardiac surgery by an integrated intra- and postoperative blood salvage strategy: results of a randomized comparison.

    Science.gov (United States)

    Weltert, Luca; Nardella, Saverio; Rondinelli, Maria Beatrice; Pierelli, Luca; De Paulis, Ruggero

    2013-04-01

    The amount of allogeneic blood transfusion may relate to worse outcome in cardiac surgery. The reinfusion of red blood cells (RBCs) lost by patients, including those of chest drains, is a promising strategy to minimize allogeneic transfusions. To verify this hypotheis, 1047 cardiac surgery patients were randomly assigned to either traditional intraoperative blood salvage followed by chest drain insertion or intra- and postoperative strategy with the Haemonetics cardioPAT system. Allogeneic RBC transfusion rate (primary endpoint) and postoperative complications (secondary endpoint) were recorded at the time of discharge from the hospital and at first month follow-up visit, respectively. The cardioPAT arm received 1.20 units of allogeneic RBCs per patient, whereas the control group required 2.11 units per patient, and this difference proved to be highly significant (p=0.02). We observed a comparable 45-day mortality rate but a lower rate of deep vein thrombosis (p=0.04) and atrial fibrillation (p=0.04) in the cardioPAT arm. A significant reduction in patient exposure to allogeneic RBCs was observed in the cardioPAT system arm. Complications were slightly less frequent in the cardioPAT group. The use of the cardioPAT is a safe and effective strategy to reduce allogeneic RBC transfusions in cardiac surgery. © 2012 American Association of Blood Banks.

  9. Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Brocks, Bouvien A W; Neyens, Isabelle J S; Teske, Erik; Kirpensteijn, Jolle

    2008-07-01

    To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT). Double-blinded, placebo-controlled, prospective, randomized study. Dogs (n=30) with spontaneous, cutaneous, solitary MCT. The wound bed of MCT, resected with margins hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner. Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods. No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT. Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.

  10. Intra-operative intravenous fluid restriction reduces perioperative red blood cell transfusion in elective cardiac surgery, especially in transfusion-prone patients: a prospective, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Georgopoulou Stavroula

    2010-02-01

    Full Text Available Abstract Background Cardiac surgery is a major consumer of blood products, and hemodilution increases transfusion requirements during cardiac surgery under CPB. As intraoperative parenteral fluids contribute to hemodilution, we evaluated the hypothesis that intraoperative fluid restriction reduces packed red-cell (PRC use, especially in transfusion-prone adults undergoing elective cardiac surgery. Methods 192 patients were randomly assigned to restrictive (group A, 100 pts, or liberal (group B, 92 pts intraoperative intravenous fluid administration. All operations were conducted by the same team (same surgeon and perfusionist. After anesthesia induction, intravenous fluids were turned off in Group A (fluid restriction patients, who only received fluids if directed by protocol. In contrast, intravenous fluid administration was unrestricted in group B. Transfusion decisions were made by the attending anesthesiologist, based on identical transfusion guidelines for both groups. Results 137 of 192 patients received 289 PRC units in total. Age, sex, weight, height, BMI, BSA, LVEF, CPB duration and surgery duration did not differ between groups. Fluid balance was less positive in Group A. Fewer group A patients (62/100 required transfusion compared to group B (75/92, p Conclusions Our data suggest that fluid restriction reduces intraoperative PRC transfusions without significantly increasing postoperative transfusions in cardiac surgery; this effect is more pronounced in transfusion-prone patients. Trial registration NCT00600704, at the United States National Institutes of Health.

  11. Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

    Science.gov (United States)

    Jeong, Han Saem; Kim, Sohyeon; Hong, Soon Jun; Choi, Seung Cheol; Choi, Ji-Hyun; Kim, Jong-Ho; Park, Chi-Yeon; Cho, Jae Young; Lee, Tae-Bum; Kwon, Ji-Wung; Joo, Hyung Joon; Park, Jae Hyoung; Yu, Cheol Woong; Lim, Do-Sun

    2016-04-01

    Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% ± 10% vs. 3% ± 14%, P raspberry group compared to the placebo group (19 ± 109/μL vs. -28 ± 57/μL, P raspberry group compared to the placebo group (-0.5 ± 1.4 pg/mL vs. -0.1 ± 1.1 pg/mL, P raspberry group. The use of black raspberry significantly lowered the augmentation index and increased circulating EPCs, thereby improving CV risks in patients with metabolic syndrome during the 12-week follow-up.

  12. Optimization of Wind Farm Layout: A Refinement Method by Random Search

    DEFF Research Database (Denmark)

    Feng, Ju; Shen, Wen Zhong

    2013-01-01

    Wind farm layout optimization is to find the optimal positions of wind turbines inside a wind farm, so as to maximize and/or minimize a single objective or multiple objectives, while satisfying certain constraints. Most of the works in the literature divide the wind farm into cells in which...... turbines can be placed, hence, simplifying the problem from with continuous variables to with discrete variables. In this paper, a refinement method, based on continuous formulation, by using random search is proposed to improve the optimization results based on discrete formulations. Two sets...

  13. The random projection method

    CERN Document Server

    Vempala, Santosh S

    2005-01-01

    Random projection is a simple geometric technique for reducing the dimensionality of a set of points in Euclidean space while preserving pairwise distances approximately. The technique plays a key role in several breakthrough developments in the field of algorithms. In other cases, it provides elegant alternative proofs. The book begins with an elementary description of the technique and its basic properties. Then it develops the method in the context of applications, which are divided into three groups. The first group consists of combinatorial optimization problems such as maxcut, graph coloring, minimum multicut, graph bandwidth and VLSI layout. Presented in this context is the theory of Euclidean embeddings of graphs. The next group is machine learning problems, specifically, learning intersections of halfspaces and learning large margin hypotheses. The projection method is further refined for the latter application. The last set consists of problems inspired by information retrieval, namely, nearest neig...

  14. "Is There a Second Level Divide in Student’s Internet Skills?

    DEFF Research Database (Denmark)

    Purushothaman, Aparna; Dau, Susanne

    2015-01-01

    The concept of a digital divide has moved beyond only physical disparities in technology usage and now also encompasses issues impeding access such as human social, cultural, and psychological barriers that affect the usage of existing available technologies. This paper focuses on students......’ insufficient skill levels in making the best use of available Internet technology, discussing students in higher education in scenarios in Denmark and India. The paper emphasizes the reflective and conceptual issues which the students face in retrieving information from the Internet, which result in a second......-level divide. Through a cross-national comparison, the paper hopes to contribute to the literature through experiences of students in the two countries, providing researchers with insights into the digital divide. This divide in Internet skills is illuminated from different perspectives in the context of two...

  15. Review: Funston, John (ed. (2009, Divided Over Thaksin: Thailand’s Coup and Problematic Transition

    Directory of Open Access Journals (Sweden)

    Paul Chambers

    2010-04-01

    Full Text Available Review of the edited volume: Funston, John (ed. (2009, Divided Over Thaksin: Thailand’s Coup and Problematic Transition, Chiangmai: Silkworm Books, Singapore: ISEAS. ISBN 978-981-230-961-7, 203 pages.

  16. Near-Earth Asteroid Lightcurve at CS3-Palmer Divide Station: 2017 April thru June

    Science.gov (United States)

    Warner, Brian D.

    2017-10-01

    Lightcurves for 31 near-Earth asteroids (NEAs) obtained at the Center for Solar System Studies-Palmer Divide Station (CS3-PDS) from 2017 April thru June were analyzed for rotation period and signs of satellites or tumbling.

  17. Ultra-trace Measurements in the WAIS Divide 06A Ice Core, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — These data contain the results of gas chromatography mass spectrometry (GC-MS) analysis of 207 samples from the WAIS Divide 06A ice core. The trace gases found in...

  18. WAIS Divide Microparticle Concentration and Size Distribution, 0-2400 ka, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set includes raw dust microparticle data for the WAIS Divide deep core, WDC06A, from the surface to 577 m. Data were collected in 2010 using a Klotz Abakus...

  19. Obtaining time-dependent multi-dimensional dividing surfaces using Lagrangian descriptors

    Science.gov (United States)

    Feldmaier, Matthias; Junginger, Andrej; Main, Jörg; Wunner, Günter; Hernandez, Rigoberto

    2017-11-01

    Dynamics between reactants and products are often mediated by a rate-determining barrier and an associated dividing surface leading to the transition state theory rate. This framework is challenged when the barrier is time-dependent because its motion can give rise to recrossings across the fixed dividing surface. A non-recrossing time-dependent dividing surface can nevertheless be attached to the TS trajectory resulting in recrossing-free dynamics. We extend the formalism-constructed using Lagrangian Descriptors-to systems with additional bath degrees of freedom. The propagation of reactant ensembles provides a numerical demonstration that our dividing surface is recrossing-free and leads to exact TST rates.

  20. Definig the Paradigm of ICTs and its dialogue with Global Digital Divide

    National Research Council Canada - National Science Library

    Rafael Pinto da Silva

    2014-01-01

    ...) and the advent of the informational economy have unleashed changes in economic relations that were not uniform across the globe and lead these phenomena to a direct dialogue with the effects of Global Digital Divide...

  1. Poor need knowledge not only technology to bridge digital divide: experts

    CERN Multimedia

    2003-01-01

    "Developing countries need to gain knowledge rather than technology to latch onto the booming information society, experts said Monday ahead of a major conference on bridging the digital divide between rich and poor" (1/2 page).

  2. A Fast Divide-and-Conquer Algorithm for Indexing Human Genome Sequences

    National Research Council Canada - National Science Library

    LOH, Woong-Kee; MOON, Yang-Sae; LEE, Wookey

    2011-01-01

    .... Moreover, they do not fully utilize the recent CPUs with multiple cores. In this paper, we propose a fast algorithm based on 'divide-and-conquer' strategy for indexing the human genome sequences...

  3. Variable-geometry turbocharger with asymmetric divided volute for engine exhaust gas pulse optimization

    Science.gov (United States)

    Serres, Nicolas

    2010-11-09

    A turbine assembly for a variable-geometry turbocharger includes a turbine housing defining a divided volute having first and second scrolls, wherein the first scroll has a substantially smaller volume than the second scroll. The first scroll feeds exhaust gas to a first portion of a turbine wheel upstream of the throat of the wheel, while the second scroll feeds gas to a second portion of the wheel at least part of which is downstream of the throat. Flow from the second scroll is regulated by a sliding piston. The first scroll can be optimized for low-flow conditions such that the turbocharger can operate effectively like a small fixed-geometry turbocharger when the piston is closed. The turbine housing defines an inlet that is divided by a dividing wall into two portions respectively feeding gas to the two scrolls, a leading edge of the dividing wall being downstream of the inlet mouth.

  4. Quasi-resonant converter with divided resonant capacitor on primary and secondary side

    OpenAIRE

    Shiroyama, Hironobu; Matsuo, Hirofumi; Ishizuka, Yoichi

    2009-01-01

    This paper presents a quasi-resonant converter with divided resonant capacitor on primary and secondary side of the isolation transformer. A conventional quasi-resonant converter using flyback topology can realize soft switching with simple circuit. However, relatively large surge voltage is generated in the switching device. To suppress such surge voltage, resonant capacitor is divided on primary side and secondary side in the proposed converter. In case of prototype 95W converter, the volta...

  5. Outcome of loop versus divided colostomy in the management of anorectal malformations.

    Science.gov (United States)

    Almosallam, Osama Ibrahim; Aseeri, Ali; Shanafey, Saud Al

    2016-01-01

    Colostomy is a common part of the management of high anorectal malformation (ARM) in the pediatric population. To evaluate whether the type of colostomy (loop vs divided) has an impact on outcome in patients with ARM. A retrospective study. King Faisal Specialist Hospital and Research Center, a tertiary care center. All patients who were managed with colostomy for ARM and had definitive repair during the period of January 2000 to December 2014. Outcomes relative to the type of the colostomy were compared. Morbidities associated with each type of colostomy. There were 104 patients managed for ARM with colostomy as staged procedures, 63 males and 41 females. Patients had a colostomy at a median age of 6 days and were closed at a median of 11 months. Definitive repair was at a median age of 17 months. Type of fistula was 8 perineal, 21 rectovestibular, 35 rectourethral, 11 rectovesical and there were 16 without fistula and 13 cloaca anomalies. There were 55 loop and 49 divided colostomies. There were 91 descending/sigmoid and 13 transverse colostomies. Operative time for loop colostomy closure was shorter than with divided colo6stomy (76 minutes vs 94 minutes, P=.002). Three patients among the divided group had reversed orientation of the colostomy that had affected bowel preparations negatively prior to its repair. There was no differences in complications of creation and closure of loop and divided colostomies except in occurrence of skin excoriation. There was more skin excoriation with divided colostomy compared to loop colostomy (17 vs 10, P=.04). Loop colostomy has a shorter closure operative time and relatively fewer complications compared to the divided colostomy. Our data suggests that loop colostomy may be more favorable than divided colostomy for ARM patients. Retrospective nature of the study and some colostomies performed at other hospitals.

  6. The robotics divide a new frontier in the 21st century?

    CERN Document Server

    López Peláez, Antonio

    2013-01-01

    Analyzes how robotics will shape our societies in the twenty-first century; a time when industrial and service robotics, particularly for military and aerospace purposes, will become an essential technology Examines an emerging divide: the "robotics divide"; a phenomenon linked to the model to integrate advanced robotics in economic, social and military spheres Focuses on the main technological trends in the field of robotics, and the impact that robotics will have on different facets of social life

  7. 110-KV optical fiber voltage transformer using a porcelain capacitor divider

    Science.gov (United States)

    Ye, Miaoyuan; Ou, Chaolong; Cui, Ying; Zhou, Jianying; Li, Kaicheng; Chen, Zhiping; Xu, Yan; Luo, Sunan

    1998-08-01

    In this paper, a new type of optical fiber voltage transformer is introduced, which utilizes new porcelain capacitor divider. The optical; fiber voltage sensor is based on the BGO crystal Pockels effect modulated horizontally, sealed in a glass box with low expansion rate. Both the divider and the sensor are sealed in the compound silicon rubber insulator filled with SF6 gas. It has many advantages such as small volume, light weight, low price and high precision.

  8. Analysis and Design of Ultra-Wideband 3-Way Bagley Power Divider Using Tapered Lines Transformers

    Directory of Open Access Journals (Sweden)

    Khair Al Shamaileh

    2012-01-01

    Full Text Available An ultra-wideband (UWB modified 3-way Bagley polygon power divider (BPD that operates over a frequency range of 2–16 GHz is presented. To achieve the UWB operation, the conventional quarter-wave transformers in the BPD are substituted by two tapered line transformers. For verification purposes, the proposed divider is simulated, fabricated, and measured. The agreement between the full-wave simulation results and the measurement ones validates the design procedure.

  9. Universal randomness

    Energy Technology Data Exchange (ETDEWEB)

    Dotsenko, Viktor S [Landau Institute for Theoretical Physics, Russian Academy of Sciences, Moscow (Russian Federation)

    2011-03-31

    In the last two decades, it has been established that a single universal probability distribution function, known as the Tracy-Widom (TW) distribution, in many cases provides a macroscopic-level description of the statistical properties of microscopically different systems, including both purely mathematical ones, such as increasing subsequences in random permutations, and quite physical ones, such as directed polymers in random media or polynuclear crystal growth. In the first part of this review, we use a number of models to examine this phenomenon at a simple qualitative level and then consider the exact solution for one-dimensional directed polymers in a random environment, showing that free energy fluctuations in such a system are described by the universal TW distribution. The second part provides detailed appendix material containing the necessary mathematical background for the first part. (reviews of topical problems)

  10. Definig the Paradigm of ICTs and its dialogue with Global Digital Divide

    Directory of Open Access Journals (Sweden)

    Rafael Pinto da Silva

    2014-03-01

    Full Text Available The paper aims to present how the development of Information and Communication Technologies (ICTs and the advent of the informational economy have unleashed changes in economic relations that were not uniform across the globe and lead these phenomena to a direct dialogue with the effects of Global Digital Divide. In this regard, the essay has been divided into three parts. On the firs part, after a comparative analysis with other concepts, is presented the concept of Paradigm of ICTs. The second part explores the dialogue between the Paradigm of ICTs and Global Digital Divide and how it allowed a dynamic that activate economically certain places on the planet while leaving others on standby. The third part presents the numbers of the Global Digital Divide based on studies of international institutions to strengthen the argument empirically. The essay concludes that quantitative and qualitative inequality in accessibility, trade and development of ICTs field between the two extremes of the Global Digital Divide indicates the need to change the current standard that divides the world into regions with easy access and developers of advanced ICTs (turn on areas and regions with limited access, intensive manpower at low cost and absent in terms of research for the sector (standby areas.

  11. The Design and Characterization of a Prototype Wideband Voltage Sensor Based on a Resistive Divider.

    Science.gov (United States)

    Garnacho, Fernando; Khamlichi, Abderrahim; Rovira, Jorge

    2017-11-17

    The most important advantage of voltage dividers over traditional voltage transformers is that voltage dividers do not have an iron core with non-linear hysteresis characteristics. The voltage dividers have a linear behavior with respect to over-voltages and a flat frequency response larger frequency range. The weak point of a voltage divider is the influence of external high-voltage (HV) and earth parts in its vicinity. Electrical fields arising from high voltages in neighboring phases and from ground conductors and structures are one of their main sources for systematic measurement errors. This paper describes a shielding voltage divider for a 24 kV medium voltage network insulated in SF6 composed of two resistive-capacitive dividers, one integrated within the other, achieving a flat frequency response up to 10 kHz for ratio error and up to 5 kHz for phase displacement error. The metal shielding improves its immunity against electric and magnetic fields. The characterization performed on the built-in voltage sensor shows an accuracy class of 0.2 for a frequency range from 20 Hz to 5 kHz and a class of 0.5 for 1 Hz up to 20 Hz. A low temperature effect is also achieved for operation conditions of MV power grids.

  12. The Design and Characterization of a Prototype Wideband Voltage Sensor Based on a Resistive Divider

    Directory of Open Access Journals (Sweden)

    Fernando Garnacho

    2017-11-01

    Full Text Available The most important advantage of voltage dividers over traditional voltage transformers is that voltage dividers do not have an iron core with non-linear hysteresis characteristics. The voltage dividers have a linear behavior with respect to over-voltages and a flat frequency response larger frequency range. The weak point of a voltage divider is the influence of external high-voltage (HV and earth parts in its vicinity. Electrical fields arising from high voltages in neighboring phases and from ground conductors and structures are one of their main sources for systematic measurement errors. This paper describes a shielding voltage divider for a 24 kV medium voltage network insulated in SF6 composed of two resistive-capacitive dividers, one integrated within the other, achieving a flat frequency response up to 10 kHz for ratio error and up to 5 kHz for phase displacement error. The metal shielding improves its immunity against electric and magnetic fields. The characterization performed on the built-in voltage sensor shows an accuracy class of 0.2 for a frequency range from 20 Hz to 5 kHz and a class of 0.5 for 1 Hz up to 20 Hz. A low temperature effect is also achieved for operation conditions of MV power grids.

  13. Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

    Directory of Open Access Journals (Sweden)

    Babu KG

    2014-06-01

    Full Text Available K Govind Babu,1 Kumar Prabhash,2 Ashok K Vaid,3 Bhawna Sirohi,3 Ravi B Diwakar,4 Raghunadha Rao,5 Madhuchanda Kar,6 Hemant Malhotra,7 Shona Nag,8 Chanchal Goswami,9 Vinod Raina,10 Ravi Mohan111Kidwai Memorial Institute of Oncology, Bangalore, 2Tata Memorial Hospital, Mumbai, 3Artemis Health Institute, Delhi, 4Bangalore Institute of Oncology, Bangalore, 5Nizam Institute of Medical Sciences, Hyderabad, 6B R Singh Hospital, Kolkata, 7Birla Cancer Centre, Jaipur, 8Jehangir Hospital, Pune, 9B P Poddar Hospital and Medical Research Ltd, Kolkata, 10Institute Rotary Cancer Hospital, New Delhi, 11King George Hospital, Visakhapatnam, IndiaBackground: The purpose of this study was to evaluate the safety and efficacy of nimotuzumab in combination with chemotherapy (docetaxel and carboplatin versus chemotherapy alone in patients with stage IIIB/IV non-small-cell lung cancer.Methods: This multicenter, open-label, Phase II study randomized 110 patients to receive nimotuzumab plus chemotherapy (nimotuzumab group or chemotherapy alone (control group, and comprised concomitant, maintenance, and follow-up phases. Nimotuzumab 200 mg was administered once weekly for 13 weeks during the first two phases with four cycles of chemotherapy and docetaxel 75 mg/m2 and carboplatin (area under the curve 5 mg/mL*min every 3 weeks for a maximum of four cycles during the concomitant phase. The primary endpoint was objective response rate (sum of complete response and partial response. Secondary endpoints, ie, overall survival and progression-free survival, were estimated using the Kaplan–Meier method. Efficacy was evaluated on the intent-to-treat and efficacy-evaluable sets. Safety was assessed from adverse event and serious adverse event data.Results: The objective response rate was significantly higher in the nimotuzumab group than in the control group in the intent-to-treat population (54% versus 34.5%; P=0.04. A complete response and partial response were achieved in 3

  14. Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

    Science.gov (United States)

    Bartolucci, Jorge; Verdugo, Fernando J; González, Paz L; Larrea, Ricardo E; Abarzua, Ema; Goset, Carlos; Rojo, Pamela; Palma, Ivan; Lamich, Ruben; Pedreros, Pablo A; Valdivia, Gloria; Lopez, Valentina M; Nazzal, Carolina; Alcayaga-Miranda, Francisca; Cuenca, Jimena; Brobeck, Matthew J; Patel, Amit N; Figueroa, Fernando E; Khoury, Maroun

    2017-10-27

    Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10 6 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography ( P =0.0167 versus baseline) and cardiac MRI ( P =0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P =0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class ( P =0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire ( P <0.05 versus baseline). At study completion

  15. Determinants of Internet skills, use and outcomes : A systematic review of the second- and third-level digital divide

    NARCIS (Netherlands)

    Scheerder, Anique; van Deursen, Alexander; van Dijk, Jan

    2017-01-01

    Recently, several digital divide scholars suggested that a shift is needed from a focus on binary Internet access (first-level digital divide) and Internet skills and use (second-level digital divide) to a third-level digital divide in which the tangible outcomes of Internet use are highlighted. A

  16. Random triangles

    OpenAIRE

    Matula, Dominik

    2013-01-01

    The author summarizes some previous results concerning random triangles. He describes the Gaussian triangle and random triangles whose vertices lie in a unit n-dimensional ball, in a rectangle or in a general bounded convex set. In the second part, the author deals with an inscribed triangle in a triangle - let ABC be an equilateral triangle and let M, N, O be three points, each laying on one side of the ABC. We call MNO inscribed triangle (in an equi- laterral triangle). The median triangle ...

  17. Random matrices

    CERN Document Server

    Mehta, Madan Lal

    1990-01-01

    Since the publication of Random Matrices (Academic Press, 1967) so many new results have emerged both in theory and in applications, that this edition is almost completely revised to reflect the developments. For example, the theory of matrices with quaternion elements was developed to compute certain multiple integrals, and the inverse scattering theory was used to derive asymptotic results. The discovery of Selberg's 1944 paper on a multiple integral also gave rise to hundreds of recent publications. This book presents a coherent and detailed analytical treatment of random matrices, leading

  18. First line chemotherapy with gemcitabine in advanced non-small cell lung cancer elderly patients: a randomized phase II study of 3-week versus 4-week schedule.

    Science.gov (United States)

    Quoix, Elisabeth; Breton, Jean-Luc; Ducoloné, Alain; Mennecier, Bertrand; Depierre, Alain; Lemarié, Etienne; Moro-Sibilot, Denis; Germa, Caroline; Neidhardt, Anne-Catherine

    2005-03-01

    This randomized phase II multicenter trial aimed at evaluating the efficacy and safety of the 4-week versus 3-week schedules of gemcitabine monotherapy in previously untreated elderly patients with advanced non-small cell lung cancer (NSCLC). Chemonaive patients with stage IIIB or IV NSCLC, and age between 70 and 90 years, were randomized to receive gemcitabine dose of either 1000 mg/m2 on days 1, 8, 15, every 28 days (arm Q4W), or 1125 mg/m2 on days 1 and 8, every 21 days (arm Q3W). From June 1999 to January 2001, 81 patients (42 on arm Q4W; 39 on arm Q3W) were included. The median age was 75 on both arms; most patients (82.7%) were male, and had a Karnofsky performance status of 80 or 90 (76.5%). For arms Q4W and Q3W, respectively, the median time to treatment failure was 83 days (95% CI, 69-98 days) versus 92 days (95% CI, 63-113), and the median survival was 154 days (95% CI, 108-227) versus 205 days (95% CI, 125-344). The objective response rate was higher on arm Q3W (28.2%) than on arm Q4W (14.3%). Total number of cycles administered was 132 on arm Q4W (median 3, range 1-10 cycles) and 169 on arm Q3W (median 4, range 1-9 cycles). Patients on arm Q4W and Q3W, respectively, received 100.1 and 99.8% of the planned weekly mean dose. The most common grade, three to four toxicities, was neutropenia (17.1% on arm Q4W versus 18.9% on arm Q3W) and thrombocytopenia (12.2% on arm Q4W versus 2.6% on arm Q3W). Although both 3- and 4-week gemcitabine regimens were safely and effectively administered in chemonaive elderly patients with advanced NSCLC, the 3-week schedule appears to be the more convenient for this population. Moreover, even if this is only a phase II study this 3-week schedule appears to be at least as efficient as the 4-week regimen.

  19. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer.

    Science.gov (United States)

    Chiappori, A A; Kolevska, T; Spigel, D R; Hager, S; Rarick, M; Gadgeel, S; Blais, N; Von Pawel, J; Hart, L; Reck, M; Bassett, E; Burington, B; Schiller, J H

    2015-02-01

    Continuation or 'switch' maintenance therapy is commonly used in patients with advancd non-small-cell lung cancer (NSCLC). Here, we evaluated the efficacy of the telomerase inhibitor, imetelstat, as switch maintenance therapy in patients with advanced NSCLC. The primary end point of this open-label, randomized phase II study was progression-free survival (PFS). Patients with non-progressive, advanced NSCLC after platinum-based doublet (first-line) chemotherapy (with or without bevacizumab), any histology, with Eastern Cooperative Oncology Group performance status 0-1 were eligible. Randomization was 2 : 1 in favor of imetelstat, administered at 9.4 mg/kg on days 1 and 8 of a 21-day cycle, or observation. Telomere length (TL) biomarker exploratory analysis was carried out in tumor tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization. Of 116 patients enrolled, 114 were evaluable. Grade 3/4 neutropenia and thrombocytopenia were more frequent with imetelstat. Median PFS was 2.8 and 2.6 months for imetelstat-treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54-1.31; P = 0.446]. Median survival time favored imetelstat (14.3 versus 11.5 months), although not significantly (HR = 0.68; 95% CI 0.41-1.12; P = 0.129). Exploratory analysis demonstrated a trend toward longer median PFS (HR = 0.43; 95% CI 0.14-1.3; P = 0.124) and overall survival (OS; HR = 0.41; 95% CI 0.11-1.46; P = 0.155) in imetelstat-treated patients with short TL, but no improvement in median PFS and OS in patients with long TL (HR = 0.86; 95% CI 0.39-1.88; and HR = 0.51; 95% CI 0.2-1.28; P = 0.145). Maintenance imetelstat failed to improve PFS in advanced NSCLC patients responding to first-line therapy. There was a trend toward a improvement in median PFS and OS in patients with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of imetelstat. © The Author 2014. Published by Oxford University Press on behalf

  20. Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study.

    Science.gov (United States)

    Wu, Yi-Long; Kim, Joo-Hang; Park, Keunchil; Zaatar, Adel; Klingelschmitt, Gaëlle; Ng, Christina

    2012-08-01

    Maintenance therapy, commenced immediately after the completion of first-line chemotherapy, is a promising strategy for improving treatment outcomes in patients with non-small-cell lung cancer (NSCLC). The global phase III SequentiAl Tarceva in UnResectable NSCLC (SATURN) study evaluated the efficacy and safety of the epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib as maintenance treatment in NSCLC patients without progression after first-line chemotherapy. We report a retrospective subanalysis of Asian patients enrolled in SATURN. Patients with advanced NSCLC with no evidence of progression after four cycles of chemotherapy were randomized to receive erlotinib 150 mg/day or placebo, until progressive disease or limiting toxicity. The co-primary endpoints of SATURN were progression-free survival (PFS) in all patients and in those with positive EGFR immunohistochemistry (IHC) status. Secondary endpoints included overall survival (OS), disease control rate, safety, quality of life (QoL) and biomarker analyses. In total, 126 patients from East and South-East Asian centers were randomized (14% of the intent-to-treat population): 88 from Korea, 28 from China and 10 from Malaysia; one patient was excluded from this analysis due to Indian ethnicity. PFS was significantly prolonged in the erlotinib treatment arm, both overall (hazard ratio [HR]: 0.57; p=0.0067) and in patients with EGFR IHC-positive disease (HR=0.50; p=0.0057). There was a trend towards an increase in OS, which reached statistical significance in the EGFR IHC-positive subgroup (p=0.0233). The overall response rate was significantly higher with erlotinib compared with placebo (24% versus 5%; p=0.0025). Erlotinib was generally well tolerated and had no negative impact on QoL in this subpopulation. The most common treatment-related adverse events were rash, diarrhea and pruritus. Erlotinib was effective and well tolerated in Asian patients, producing benefits consistent with those