WorldWideScience

Sample records for sphingolipids studies defining

  1. Current relevance of fungal and trypanosomatid glycolipids and sphingolipids: studies defining structures conspicuously absent in mammals

    Directory of Open Access Journals (Sweden)

    Helio K. Takahashi

    2009-09-01

    Full Text Available Recently, glycosphingolipids have been attracting attention due to their role on biological systems as second messengers or modulators of signal transduction, affecting several events, which range from apoptosis to regulation of the cell cycle. In pathogenic fungi, glycolipids are expressed in two classes: neutral monohexosylceramides (glucosyl-or galactosylceramide and acidic glycosylinositol phosphorylceramides (the latter class carries longer glycan chains. It is worth to mention that monohexosylceramides exhibit significant structural differences in their lipid moieties compared to their mammalian counterparts, whereas the glycosylinositol phosphorylceramides exhibit remarkable structural differences in their carbohydrate moieties in comparison to mammal glycosphingolipids counterpart. We observed that glycosylinositol phosphorylceramides are capable of promoting immune response in infected humans. In addition, inhibiting fungal glycosphingolipid biosynthetic pathways leads to an inhibition of colony formation, spore germination, cell cycle, dimorphism and hyphal growth. Other pathogens, such as trypanosomatids, also present unique glycolipids, which may have an important role for the parasite development and/or disease establishment. Regarding host-pathogen interaction, cell membrane rafts, which are enriched in sphingolipids and sterols, participate in parasite/fungal infection. In this review, it is discussed the different biological roles of (glyco (sphingolipids of pathogenic/opportunistic fungi and trypanosomatids.Recentemente, glicoesfingolipídeos têm atraído atenção devido ao seu papel na biologia celular como segundo-mensageiro ou moduladores da transdução de sinal, afetando vários eventos, desde apoptose até a regulação do ciclo celular. Em fungos patogênicos, existem duas classes de glicolipídeos: monohexosil ceramidas neutras (glucosil-ou galactosilceramida e glicosilinositol fosforilceramidas (os quais apresentam

  2. Sphingolipids in human synovial fluid--a lipidomic study.

    Directory of Open Access Journals (Sweden)

    Marta Krystyna Kosinska

    Full Text Available Articular synovial fluid (SF is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides and minor glycerophospholipid species, including (lysophosphatidic acid, (lysophosphatidylglycerol, and bis(monoacylglycerophosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA and late (lOA stages of osteoarthritis (OA, and rheumatoid arthritis (RA. SF without cells and cellular debris from 9 postmortem donors (control, 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry--directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.

  3. Sphingolipid trafficking - Sorted out?

    OpenAIRE

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into microdomains in membranes that concentrate sphingolipids into specific transport pathways. Gerrit van Meer and Koert Burger consider here the routes of sphingolipid biosynthesis and transport, and the rol...

  4. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  5. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

    2012-01-01

    , and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...

  6. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  7. Sphingolipid trafficking - Sorted out?

    NARCIS (Netherlands)

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into

  8. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    NARCIS (Netherlands)

    A. Demirkan (Ayşe); C.M. van Duijn (Cornelia); P. Ugocsai (Peter); A.J. Isaacs (Aaron); P.P. Pramstaller (Peter Paul); G. Liebisch (Gerhard); J.F. Wilson (James); A. Johansson (Åsa); I. Rudan (Igor); Y.S. Aulchenko (Yurii); A.V. Kirichenko (Anatoly); A.C.J.W. Janssens (Cécile); R.C. Jansen (Ritsert); C. Gnewuch (Carsten); I. Domingues (Inês); C. Pattaro (Cristian); S.H. Wild (Sarah); I. Jonasson (Inger); O. Polasek (Ozren); I.V. Zorkoltseva (Irina); A. Hofman (Albert); L.C. Karssen (Lennart); M.V. Struchalin (Maksim); J. Floyd (Jamie); W. Igl (Wilmar); Z. Biloglav (Zrinka); L. Broer (Linda); A. Pfeufer (Arne); I. Pichler (Irene); S. Campbell (Susan); G. Zaboli (Ghazal); I. Kolcic (Ivana); F. Rivadeneira Ramirez (Fernando); J.E. Huffman (Jennifer); N. Hastie (Nick); A.G. Uitterlinden (André); L. Franke (Lude); C.S. Franklin (Christopher); V. Vitart (Veronique); C.P. Nelson (Christopher P.); M. Preuss (Michael); J.C. Bis (Joshua); C.J. O'Donnell (Christopher); N. Franceschini (Nora); J.C.M. Witteman (Jacqueline); T.I. Axenovich (Tatiana); B.A. Oostra (Ben); T. Meitinger (Thomas); A.A. Hicks (Andrew); C. Hayward (Caroline); A.F. Wright (Alan); U. Gyllensten (Ulf); H. Campbell (Harry); G. Schmitz (Gerd)

    2012-01-01

    textabstractPhospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological,

  9. Sphingolipids in Congenital Diaphragmatic Hernia; Results from an International Multicenter Study.

    Directory of Open Access Journals (Sweden)

    Kitty G Snoek

    Full Text Available Congenital diaphragmatic hernia is a severe congenital anomaly with significant mortality and morbidity, for instance chronic lung disease. Sphingolipids have shown to be involved in lung injury, but their role in the pathophysiology of chronic lung disease has not been explored. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients. Furthermore, we hypothesized that sphingolipid profiles differ between ventilation modes; conventional mechanical ventilation versus high-frequency oscillation.Sphingolipid levels in tracheal aspirates were determined at days 1, 3, 7 and 14 in 72 neonates with congenital diaphragmatic hernia, born after > 34 weeks gestation at four high-volume congenital diaphragmatic hernia centers. Data were collected within a multicenter trial of initial ventilation strategy (NTR 1310.36 patients (50.0% died or developed chronic lung disease, 34 patients (47.2% by stratification were initially ventilated by conventional mechanical ventilation and 38 patients (52.8% by high-frequency oscillation. Multivariable logistic regression analysis with correction for side of the defect, liver position and observed-to-expected lung-to-head ratio, showed that none of the changes in sphingolipid levels were significantly associated with mortality /development of chronic lung disease. At day 14, long-chain ceramides 18:1 and 24:0 were significantly elevated in patients initially ventilated by conventional mechanical ventilation compared to high-frequency oscillation.We could not detect significant differences in temporal sphingolipid levels in congenital diaphragmatic hernia infants with mortality/development of chronic lung disease versus survivors without development of CLD. Elevated levels of ceramides 18:1 and 24:0 in the conventional mechanical ventilation group when compared to high

  10. Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

    Science.gov (United States)

    Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

    2017-09-01

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated

  11. The role of sphingolipids in neuronal plasticity of the brain.

    Science.gov (United States)

    Sonnino, Sandro; Prinetti, Alessandro

    2016-05-01

    This Editorial highlights a study by Müller et al. in which the authors suggest a new sphingolipid-dependent mechanism for behavioral extinction. Their study should be considered in the broad perspective of sphingolipid metabolic pathways and traffic (depicted in the graphic). Read the highlighted article 'A sphingolipid mechanism for behavioral extinction' on page 589. © 2016 International Society for Neurochemistry.

  12. Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

    Science.gov (United States)

    Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

    2016-08-01

    Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

  13. Sphingolipids in macroautophagy.

    Science.gov (United States)

    Lavieu, Grégory; Scarlatti, Francesca; Sala, Giusy; Carpentier, Stéphane; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2008-01-01

    Sphingolipids are constituents of biological membranes. Ceramide and sphingosine 1-phosphate (S1P) also act as second messengers and are part of a rheostat system, in which ceramide promotes cell death and growth arrest, and S1P induces proliferation and maintains cell survival. As macroautophagy is a lysosomal catabolic mechanism involved in determining the duration of the lifetime of cells, we raised the question of its regulation by sphingolipid messengers. Using chemical and genetic methods, we have shown by GFP-LC3 staining and analysis of the degradation of long-lived proteins that both ceramide and S1P stimulate autophagy.

  14. A comprehensive lipidomic screen of pancreatic β-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens

    Directory of Open Access Journals (Sweden)

    Gemma L. Pearson

    2016-06-01

    Full Text Available Objective: Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. Methods: Using mass spectrometry (MS we quantified changes in approximately 300 lipid metabolites in MIN6 β-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in 3H-sphinganine-labelled cells using TLC. Results: Glucose specifically activates the conversion of triacylglycerol (TAG to diacylglycerol (DAG. This leads indirectly to the formation of 18:1 monoacylglycerol (MAG, via degradation of saturated/monounsaturated DAG species, such as 16:0_18:1 DAG, which are the most abundant, immediate products of glucose-stimulated TAG hydrolysis. However, 16:0-containing, di-saturated DAG species are a better direct marker of TAG hydrolysis since, unlike the 18:1-containing DAGs, they are predominately formed via this route. Using multiple reaction monitoring, we confirmed that in islets under basal conditions, 18:1 MAG is the most abundant species. We further demonstrated a novel site of glucose to enhance the conversion of ceramide to sphingomyelin (SM and galactosylceramide (GalCer. Flux and product:precursor analyses suggest regulation of the enzyme SM synthase, which would constitute a separate mechanism for localized generation of DAG in response to glucose. Phosphatidylcholine (PC plasmalogen (P species, specifically those containing 20:4, 22:5 and 22:6 side chains, were also diminished in the presence of glucose, whereas the more abundant phosphatidylethanolamine plasmalogens were unchanged. Conclusion: Our results highlight 18:1 MAG, GalCer, PC(P and DAG/SM as potential contributors to metabolic stimulus-secretion coupling. Author Video: Author Video Watch what authors say about their articles Keywords: Pancreatic β-cell, Insulin

  15. Sphingolipid biosynthesis in man and microbes.

    Science.gov (United States)

    Harrison, Peter J; Dunn, Teresa M; Campopiano, Dominic J

    2018-06-04

    A new review covering up to 2018Sphingolipids are essential molecules that, despite their long history, are still stimulating interest today. The reasons for this are that, as well as playing structural roles within cell membranes, they have also been shown to perform a myriad of cell signalling functions vital to the correct function of eukaryotic and prokaryotic organisms. Indeed, sphingolipid disregulation that alters the tightly-controlled balance of these key lipids has been closely linked to a number of diseases such as diabetes, asthma and various neuropathologies. Sphingolipid biogenesis, metabolism and regulation is mediated by a large number of enzymes, proteins and second messengers. There appears to be a core pathway common to all sphingolipid-producing organisms but recent studies have begun to dissect out important, species-specific differences. Many of these have only recently been discovered and in most cases the molecular and biochemical details are only beginning to emerge. Where there is a direct link from classic biochemistry to clinical symptoms, a number a drug companies have undertaken a medicinal chemistry campaign to try to deliver a therapeutic intervention to alleviate a number of diseases. Where appropriate, we highlight targets where natural products have been exploited as useful tools. Taking all these aspects into account this review covers the structural, mechanistic and regulatory features of sphingolipid biosynthetic and metabolic enzymes.

  16. Abnormal islet sphingolipid metabolism in type 1 diabetes

    DEFF Research Database (Denmark)

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P

    2018-01-01

    AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis....... Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we...... diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1...

  17. Translational Aspects of Sphingolipid Metabolism in Renal Disorders

    Directory of Open Access Journals (Sweden)

    Alaa Abou Daher

    2017-11-01

    Full Text Available Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry’s and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules. In addition to being involved in dynamic cellular processes like apoptosis, senescence and differentiation, sphingolipids are implicated in critical physiological functions such as immune responses and pathophysiological conditions like inflammation and insulin resistance. Interestingly, the kidneys are among the most sensitive organ systems to sphingolipid alterations, rendering these molecules and the enzymes involved in their metabolism, promising therapeutic targets for numerous nephropathic complications that stand behind podocyte injury and renal failure.

  18. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  19. Sphingolipid metabolism diseases.

    Science.gov (United States)

    Kolter, Thomas; Sandhoff, Konrad

    2006-12-01

    Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

  20. Macrophage sphingolipids are essential for the entry of mycobacteria.

    Science.gov (United States)

    Viswanathan, Gopinath; Jafurulla, Md; Kumar, G Aditya; Raghunand, Tirumalai R; Chattopadhyay, Amitabha

    2018-07-01

    Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known. In this work, we explored the role of host membrane sphingolipids in the entry of Mycobacterium smegmatis into J774A.1 macrophages. Our results show that metabolic depletion of sphingolipids in host macrophages results in a significant reduction in the entry of M. smegmatis. Importantly, the entry of Escherichia coli into host macrophages under similar conditions remained invariant, implying the specificity of the requirement of sphingolipids in mycobacterial entry. To the best of our knowledge, our results constitute the first report demonstrating the role of host macrophage sphingolipids in the entry of mycobacteria. Our results could help in the development of novel therapeutic strategies targeting sphingolipid-mediated entry of mycobacteria into host cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Polarized sphingolipid transport from the subapical compartment : Evidence for distinct sphingolipid domains

    NARCIS (Netherlands)

    van Ijzendoorn, SCD; Hoekstra, D

    1999-01-01

    In polarized HepG2 cells, the sphingolipids glucosylceramide and sphingomyelin (SM), transported along the reverse transcytotic pathway, are sorted in subapical compartments (SACs), and subsequently targeted to either apical or basolateral plasma membrane domains, respectively. In the present study,

  2. The Role of Sphingolipids on Innate Immunity to Intestinal Salmonella Infection.

    Science.gov (United States)

    Huang, Fu-Chen

    2017-08-07

    Salmonella spp. remains a major public health problem for the whole world. To reduce the use of antimicrobial agents and drug-resistant Salmonella , a better strategy is to explore alternative therapy rather than to discover another antibiotic. Sphingolipid- and cholesterol-enriched lipid microdomains attract signaling proteins and orchestrate them toward cell signaling and membrane trafficking pathways. Recent studies have highlighted the crucial role of sphingolipids in the innate immunity against infecting pathogens. It is therefore mandatory to exploit the role of the membrane sphingolipids in the innate immunity of intestinal epithelia infected by this pathogen. In the present review, we focus on the role of sphingolipids in the innate immunity of intestinal epithelia against Salmonella infection, including adhesion, autophagy, bactericidal effect, barrier function, membrane trafficking, cytokine and antimicrobial peptide expression. The intervention of sphingolipid-enhanced foods to make our life healthy or pharmacological agents regulating sphingolipids is provided at the end.

  3. Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

    Science.gov (United States)

    Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

    2015-01-01

    Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired

  4. Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Alfred N Fonteh

    Full Text Available Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but

  5. Abnormal islet sphingolipid metabolism in type 1 diabetes.

    Science.gov (United States)

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P; Kaur, Simranjeet; Claessens, Laura A; Russell, Mark A; Mathews, Clayton E; Hanssen, Kristian F; Morgan, Noel G; Koeleman, Bobby P C; Roep, Bart O; Gerling, Ivan C; Pociot, Flemming; Dahl-Jørgensen, Knut; Buschard, Karsten

    2018-04-18

    Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development. We found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals. These results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach. The RNA expression data is

  6. Tumor PDT-associated immune response: relevance of sphingolipids

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

    2010-02-01

    Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

  7. Genetic determinants of circulating sphingolipid concentrations in European populations.

    Directory of Open Access Journals (Sweden)

    Andrew A Hicks

    2009-10-01

    Full Text Available Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI, cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS between 318,237 single-nucleotide polymorphisms (SNPs and levels of circulating sphingomyelin (SM, dihydrosphingomyelin (Dih-SM, ceramide (Cer, and glucosylceramide (GluCer single lipid species (33 traits; and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32 in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3 associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4 or less. Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be

  8. A view on sphingolipids and disease.

    Science.gov (United States)

    Kolter, Thomas

    2011-09-01

    Sphingolipid and glycosphingolipid levels and expression of sphingolipid metabolizing enzymes are altered in a variety of diseases or in response to drug treatment. Inherited defects of enzymes and other proteins required for the lysosomal degradation of these lipids lead to human sphingolipidoses. Also genetic defects that affect sphingolipid biosynthesis are known. Although the molecular details are often far from clear, (glyco)sphingolipids have been implicated to play a role in atherosclerosis, insulin resistance, cancer, and infections by pathogens. More general aspects of selected diseases are discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.

    Science.gov (United States)

    Kraft, Mary L

    2016-01-01

    Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with

  10. Preanalytical Biases in the Measurement of Human Blood Sphingolipids

    Directory of Open Access Journals (Sweden)

    Robert Brunkhorst

    2018-05-01

    Full Text Available Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles, blood drawing (venous or arterial sampling, prolonged venous compression, and sample preparation (centrifugation, freezing on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P and sphinganine 1-phosphate (SA1P were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydroceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.

  11. Sphingolipids and plant defense/disease: the "death" connection and beyond

    Directory of Open Access Journals (Sweden)

    Robert eBerkey

    2012-04-01

    Full Text Available Sphingolipids comprise a major class of structural materials and lipid signaling molecules in all eukaryotic cells. Over the past two decades, there has been a phenomenal growth in the study of sphingolipids (i.e. sphingobiology at an average rate of >1000 research articles per year. Sphingolipid studies in plants, though accounting for only a small fraction (~6% of the total number of publications, have also enjoyed proportionally rapid growth in the past decade. Concomitant with the growth of sphingobiology, there has also been tremendous progress in our understanding of the molecular mechanisms of plant innate immunity. In this review, we (i cross examine and analyze the major findings that establish and strengthen the intimate connections between sphingolipid metabolism and plant programmed cell death (PCD associated with plant defense or disease; (ii highlight and compare key bioactive sphingolipids involved in the regulation of plant PCD and possibly defense; (iii discuss the potential role of sphingolipids in polarized membrane/protein trafficking and formation of lipid rafts as subdomains of cell membranes in relation to plant defense; and (iv where possible, attempt to identify potential parallels for immunity-related mechanisms involving sphingolipids across kingdoms.

  12. Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Simon A. Young

    2012-01-01

    Full Text Available Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions.

  13. Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

    Science.gov (United States)

    Young, Simon A.; Mina, John G.; Denny, Paul W.; Smith, Terry K.

    2012-01-01

    Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions. PMID:22400113

  14. Fiber Specific Changes in Sphingolipid Metabolism in Skeletal Muscles of Hyperthyroid Rats

    OpenAIRE

    Chabowski, A.; ?endzian-Piotrowska, M.; Mik?osz, A.; ?ukaszuk, B.; Kurek, K.; G?rski, J.

    2013-01-01

    Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, ...

  15. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  16. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation.

    Directory of Open Access Journals (Sweden)

    J Eduardo Rico

    Full Text Available Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition. Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in

  17. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation

    Science.gov (United States)

    Rico, J. Eduardo; Saed Samii, Sina; Mathews, Alice T.; Lovett, Jacqueline; Haughey, Norman J.; McFadden, Joseph W.

    2017-01-01

    Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids

  18. Membrane domains and polarized trafficking of sphingolipids

    NARCIS (Netherlands)

    Maier, O; Slimane, TA; Hoekstra, D

    The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid-cholesterol enriched membrane microdomains, so called rafts. In

  19. Altered Leukocyte Sphingolipid Pathway in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Larissa P. Maia

    2017-11-01

    Full Text Available Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

  20. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Yuichi Hirata

    Full Text Available Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2 encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

  1. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

    Science.gov (United States)

    Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

    2012-01-01

    Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

  2. Plant sphingolipids: decoding the enigma of the Sphinx.

    Science.gov (United States)

    Pata, Mickael O; Hannun, Yusuf A; Ng, Carl K-Y

    2010-02-01

    Sphingolipids are a ubiquitous class of lipids present in a variety of organisms including eukaryotes and bacteria. In the last two decades, research has focused on characterizing the individual species of this complex family of lipids, which has led to a new field of research called 'sphingolipidomics'. There are at least 500 (and perhaps thousands of) different molecular species of sphingolipids in cells, and in Arabidopsis alone it has been reported that there are at least 168 different sphingolipids. Plant sphingolipids can be divided into four classes: glycosyl inositol phosphoceramides (GIPCs), glycosylceramides, ceramides, and free long-chain bases (LCBs). Numerous enzymes involved in plant sphingolipid metabolism have now been cloned and characterized, and, in general, there is broad conservation in the way in which sphingolipids are metabolized in animals, yeast and plants. Here, we review the diversity of sphingolipids reported in the literature, some of the recent advances in our understanding of sphingolipid metabolism in plants, and the physiological roles that sphingolipids and sphingolipid metabolites play in plant physiology.

  3. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  4. Autophagy in the light of sphingolipid metabolism

    DEFF Research Database (Denmark)

    Harvald, Eva Bang; Olsen, Anne Sofie Braun; Færgeman, Nils J.

    2015-01-01

    Maintenance of cellular homeostasis requires tight and coordinated control of numerous metabolic pathways, which are governed by interconnected networks of signaling pathways and energy-sensing regulators. Autophagy, a lysosomal degradation pathway by which the cell self-digests its own components......, has over the past decade been recognized as an essential part of metabolism. Autophagy not only rids the cell of excessive or damaged organelles, misfolded proteins, and invading microorganisms, it also provides nutrients to maintain crucial cellular functions. Besides serving as essential structural...... moieties of biomembranes, lipids including sphingolipids are increasingly being recognized as central regulators of a number of important cellular processes, including autophagy. In the present review we describe how sphingolipids, with special emphasis on ceramides and sphingosine-1-phosphate, can act...

  5. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Directory of Open Access Journals (Sweden)

    Isabelle eGuillas

    2013-09-01

    Full Text Available Nitric oxide (NO emerged as one of the major signalling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of nitric oxide into complex signalling networks. Beside the close relationships between NO and calcium or phosphatidic acid signalling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids. This mini-review summarises our current knowledge of the influence NO and sphingolipids might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although sphingolipid-NO interplays are common features in signalling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  6. Sphingolipids and Lipoproteins in Health and Metabolic Disorders.

    Science.gov (United States)

    Iqbal, Jahangir; Walsh, Meghan T; Hammad, Samar M; Hussain, M Mahmood

    2017-07-01

    Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Understanding of the mechanisms involved in intracellular transport, secretion, and extracellular transport may provide novel information that might be amenable to therapeutic targeting for the treatment of various metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Transport and sorting of sphingolipids in polarized cells : the involvement of the sub-apical compartment

    NARCIS (Netherlands)

    IJzendoorn, Sven Christian David van

    1999-01-01

    The work described in this thesis has provided a novel insight into the process of sphingolipid transport and sorting in polarized cells. We have used HepG2 cells as a model system to study polarized traffic in hepatic cells. Under specific culture conditions, HepG2 cells acquire a polarized

  8. Sphingolipids as a new factor in the pathomechanism of preeclampsia - Mass spectrometry analysis.

    Directory of Open Access Journals (Sweden)

    Karol Charkiewicz

    Full Text Available The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells of women with mild preeclampsia.We recruited 21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group. To assess the concentration of 11 sphingolipids in the blood plasma and blood fractions, we used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS.We showed a significant increase in the concentration of eight sphingolipids in the plasma of women with preeclampsia in comparison to the control group: Sph (p = 0.0032, S1P (p = 0.0289, C20-Cer (p < 0.0001, C18-Cer (p < 0.0001, C16-Cer (p = 0.012, C18:1-Cer (p = 0.003, C22-Cer (p = 0.0071, and C24:1-Cer (p = 0.0085.We showed that selected sphingolipids, especially C20-Cer and C18-Cer, are totally new factors in the pathomechanism of PE and that these bioactive lipids may play an important role in apoptosis and autophagy.

  9. Defining contagion literacy: a Delphi study

    Science.gov (United States)

    Kilstadius, Margareta; Gericke, Niklas

    2017-11-01

    Against the background of climate change, which enables infectious diseases to move their frontiers and the increasing global mobility, which make people more exposed to contagion, we as citizens need to relate to this new scenario. A greater number of infectious diseases may also potentially lead to an increased need to use antibiotics and anti-parasitic substances. In view of this, the aim of this study was to identify the health literacy needed in the contemporary world and specify what should be taught in compulsory school. We present the findings of a Delphi study, performed in Sweden, regarding the opinions on contagion among experts in the field. We used Nutbeam's framework of health literacy and related it to Bloom's taxonomy of educational objectives in order to analyse and categorise the experts' responses, which were categorised into six main content themes: contagions, transmission routes, sexually transmitted diseases, hygiene, vaccinations and use of antibiotics and antibiotic resistance. These themes were then divided into the three levels of Nutbeam's framework: functional health literacy, which is about knowledge and understanding, interactive health literacy, which is about developing personal qualities and skills that promote health, and critical health literacy, which is about social and cognitive skills related to analysis and critical reflection. The implications for communication and education are then discussed and what should be taught in compulsory school is identified.

  10. The sphingolipid long-chain base-Pkh1/2-Ypk1/2 signaling pathway regulates eisosome assembly and turnover

    DEFF Research Database (Denmark)

    Luo, Guangzuo; Gruhler, Albrecht; Liu, Ying

    2008-01-01

    Eisosomes are recently described fungal structures that play roles in the organization of the plasma membrane and endocytosis. Their major protein components are Pil1 and Lsp1, and previous studies showed that these proteins are phosphorylated by the sphingolipid long-chain base-activated Pkh1...... that phosphorylation is critical for eisosome organization. We also found that eisosomes are dynamic structures and disassemble when the Ypk protein kinases, which are activated by the sphingolipid-Pkh signaling pathway, are inactivated or when the sphingolipid signal is pharmacologically blocked with myriocin. We...

  11. Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.

    Science.gov (United States)

    Sandhoff, Konrad

    2016-11-01

    Glycosphingolipids and sphingolipids of cellular plasma membranes (PMs) reach luminal intra-lysosomal vesicles (LVs) for degradation mainly by pathways of endocytosis. After a sorting and maturation process (e.g. degradation of sphingomyelin (SM) and secretion of cholesterol), sphingolipids of the LVs are digested by soluble enzymes with the help of activator (lipid binding and transfer) proteins. Inherited defects of lipid-cleaving enzymes and lipid binding and transfer proteins cause manifold and fatal, often neurodegenerative diseases. The review summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, an essential stimulation by anionic membrane lipids and an inhibition of crucial steps by cholesterol and SM. Reconstitution experiments in the presence of all proteins needed, hydrolase and activator proteins, reveal an up to 10-fold increase of ganglioside catabolism just by the incorporation of anionic lipids into the ganglioside carrying membranes, whereas an additional incorporation of cholesterol inhibits GM2 catabolism substantially. It is suggested that lipid and other low molecular modifiers affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  12. The GARP complex is required for cellular sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Fröhlich, Florian; Petit, Constance; Kory, Nora

    2015-01-01

    (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation...... analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many...

  13. Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

    Science.gov (United States)

    Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

  14. Making Sense of the Yeast Sphingolipid Pathway.

    Science.gov (United States)

    Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

    2016-12-04

    Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    2016-09-19

    Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

  16. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Fikadu G Tafesse

    2015-10-01

    Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

  17. Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?

    DEFF Research Database (Denmark)

    Rog, T.; Vattulainen, I.

    2014-01-01

    Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units with pote......Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units...... with potential specific functions. Although the understanding of the structure of rafts in living cells is quite limited, the possible functions of rafts are widely discussed in the literature, highlighting their importance in cellular functions. In this review, we discuss the understanding of rafts that has...... emerged based on recent atomistic and coarse-grained molecular dynamics simulation studies on the key lipid raft components, which include cholesterol, sphingolipids, glycolipids, and the proteins interacting with these classes of lipids. The simulation results are compared to experiments when possible...

  18. Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

    Science.gov (United States)

    Chabowski, A; Zendzian-Piotrowska, M; Mikłosz, A; Łukaszuk, B; Kurek, K; Górski, J

    2013-07-01

    Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

  19. Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.

    Science.gov (United States)

    Mina, John G M; Denny, P W

    2018-02-01

    Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.

  20. Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

    Science.gov (United States)

    Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

    2017-10-01

    The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Occurrence of bioactive sphingolipids in meat and fish products

    DEFF Research Database (Denmark)

    Hellgren, Lars

    2001-01-01

    /neutral glycolipids varied from 1 to 2.9, while in poultry this ratio varied between 5.2 to 19.2 and in red meat it varied from 1.6 to 8.3. The fatty acid composition of sphingomyelin in fish was dominated by C24:1 (Delta (9)) or C22:1 (Delta (9)), while C16:0 and C18:0 were the dominating sphingomyelin species....... Therefore we investigated the contents of sphingomyelin and neutral glycosphingolipids in commonly consumed meat and fish products. Sphingomyelin and glycosphingolipids were found in all foodstuffs studied. The total amount varied between 118 +/- 17 nmol/g (cod) to 589 +/- 39 nmol/g (chicken leg). Generally......, lower amounts of sphingolipids were determined in fish meat than in red meat and poultry, while poultry was the richest source of this class of lipids. However, fish meat contained a relatively high content of neutral glycolipids compared with other types of meat. Thus, in fish the ratio sphingomyelin...

  2. Women's Leadership Development: A Study of Defining Moments

    Science.gov (United States)

    Dahlvig, Jolyn E.; Longman, Karen A.

    2010-01-01

    This article reports the findings of a grounded theory study of "defining moments" that were described as pivotal in the personal and professional journeys of women who had been identified as emerging leaders within Christian higher education. Analysis of transcripts from interviews with 16 participants in a Women's Leadership Development…

  3. Two New Sphingolipids from the Leaves of Piper betle L.

    OpenAIRE

    Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

    2013-01-01

    Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  4. Two new sphingolipids from the leaves of Piper betle L.

    Science.gov (United States)

    Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

    2013-09-12

    Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  5. Two New Sphingolipids from the Leaves of Piper betle L.

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Jiang

    2013-09-01

    Full Text Available Two new sphingolipids, pipercerebrosides A (1 and B (2, were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  6. Sphingolipid trafficking and protein sorting in epithelial cells

    NARCIS (Netherlands)

    Slimane, TA; Hoekstra, D

    2002-01-01

    Sphingolipids represent a minor, but highly dynamic subclass of lipids in all eukaryotic cells. They are involved in functions that range from structural protection to signal transduction and protein sorting, and participate in lipid raft assembly. In polarized epithelial cells, which display an

  7. Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

    Czech Academy of Sciences Publication Activity Database

    Žebrakovská, Iva; Máša, Martin; Srp, Jaroslav; Horn, Martin; Vávrová, K.; Mareš, Michael

    2011-01-01

    Roč. 1811, č. 12 (2011), s. 1097-1104 ISSN 1388-1981 R&D Projects: GA AV ČR IAA400550705 Institutional research plan: CEZ:AV0Z40550506 Keywords : sphingolipid * phospholipid * inhibition * activation * cathepsin D * enzyme regulation Subject RIV: CE - Biochemistry Impact factor: 5.269, year: 2011

  8. Sphingolipid base modifying enzymes in sunflower (Helianthus annuus): cloning and characterization of a C4-hydroxylase gene and a new paralogous Δ8-desaturase gene.

    Science.gov (United States)

    Moreno-Pérez, Antonio J; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

    2011-05-15

    Sphingolipids are components of plant cell membranes that participate in the regulation of important physiological processes. Unlike their animal counterparts, plant sphingolipids are characterized by high levels of base C4-hydroxylation. Moreover, desaturation at the Δ8 position predominates over the Δ4 desaturation typically found in animal sphingolipids. These modifications are due to the action of C4-hydroxylases and Δ8-long chain base desaturases, and they are important for complex sphingolipids finally becoming functional. The long chain bases of sunflower sphingolipids have high levels of hydroxylated and unsaturated moieties. Here, a C4-long chain base hydroxylase was functionally characterized in sunflower plant, an enzyme that could complement the sur2Δ mutation when heterologously expressed in this yeast mutant deficient in hydroxylation. This hydroxylase was ubiquitously expressed in sunflower, with the highest levels found in the developing cotyledons. In addition, we identified a new Δ8-long base chain desaturase gene that displays strong homology to a previously reported desaturase gene. This desaturase was also expressed in yeast and was able to change the long chain base composition of the transformed host. We studied the expression of this desaturase and compared it with that of the other isoform described in sunflower. The desaturase form studied in this paper displayed higher expression levels in developing seeds. Copyright © 2010 Elsevier GmbH. All rights reserved.

  9. How Do We Define Congenital Heart Defects for Scientific Studies?

    DEFF Research Database (Denmark)

    Garne, Ester; Olsen, Morten Smaerup; Johnsen, Søren Paaske

    2012-01-01

    of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data...... practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD....

  10. SPHINGOLIPID-DEPENDENT FUSION OF SEMLIKI FOREST VIRUS WITH CHOLESTEROL-CONTAINING LIPOSOMES REQUIRES BOTH THE 3-HYDROXYL GROUP AND THE DOUBLE-BOND OF THE SPHINGOLIPID BACKBONE

    NARCIS (Netherlands)

    CORVER, J; MOESBY, L; ERUKULLA, RK; REDDY, KC; BITTMAN, R; WILSCHUT, J

    Low-pH-induced membrane fusion of Semliki Forest virus (SFV) in a model system is mediated by sphingolipids in the target membrane; ceramide is the sphingolipid minimally required (J. L. Nieva, R. Bron, J. Corver, and J. Wilschut, EMBO J. 13:2797-2804, 1994). Here, using various ceramide analogs, we

  11. The way we view cellular (glyco)sphingolipids.

    Science.gov (United States)

    Hoetzl, Sandra; Sprong, Hein; van Meer, Gerrit

    2007-11-01

    Mammalian cells synthesize ceramide in the endoplasmic reticulum (ER) and convert this to sphingomyelin and complex glycosphingolipids on the inner, non-cytosolic surface of Golgi cisternae. From there, these lipids travel towards the outer, non-cytosolic surface of the plasma membrane and all membranes of the endocytic system, where they are eventually degraded. At the basis of the selective, anterograde traffic out of the Golgi lies the propensity of the sphingolipids to self-aggregate with cholesterol into microdomains termed 'lipid rafts'. At the plasma membrane surface these rafts are thought to function as the scaffold for various types of (glyco) signaling domains of different protein and lipid composition that can co-exist on one and the same cell. In the past decade, various unexpected findings on the sites where sphingolipid-mediated events occur have thrown a new light on the localization and transport mechanisms of sphingolipids. These findings are largely based on biochemical experiments. Further progress in the field is hampered by a lack of morphological techniques to localize lipids with nanometer resolution. In the present paper, we critically evaluate the published data and discuss techniques and potential improvements.

  12. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    Science.gov (United States)

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

  13. Membrane organization determines barrier properties of endothelial cells and short-chain sphingolipid-facilitated doxorubicin influx.

    Science.gov (United States)

    van Hell, A J; Klymchenko, A; Gueth, D M; van Blitterswijk, W J; Koning, G A; Verheij, M

    2014-09-01

    The endothelial lining and its outer lipid membrane are the first major barriers drug molecules encounter upon intravenous administration. Our previous work identified lipid analogs that counteract plasma membrane barrier function for a series of amphiphilic drugs. For example, short-chain sphingolipids (SCS), like N-octanoyl-glucosylceramide, effectively elevated doxorubicin accumulation in tumor cells, both in vitro and in vivo, and in endothelial cells, whereas other (normal) cells remained unaffected. We hypothesize here that local membrane lipid composition and the degree of lipid ordering define SCS efficacy in individual cells. To this end, we study the differential effect of SCS on bovine aortic endothelial cells (BAEC) in its confluent versus proliferative state, as a model system. While their (plasma membrane) lipidome stays remarkably unaltered when BAECs reach confluency, their lipids segregate to form apical and basolateral domains. Using probe NR12S, we reveal that lipids in the apical membrane are more condensed/liquid-ordered. SCS preferentially attenuate the barrier posed by these condensed membranes and facilitate doxorubicin influx in these particular membrane regions. We confirm these findings in MDCK cells and artificial membranes. In conclusion, SCS-facilitated drug traversal acts on condensed membrane domains, elicited by confluency in resting endothelium. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Study to define NDE research for inspection of stainless steels

    International Nuclear Information System (INIS)

    Reinhart, E.R.

    1978-08-01

    After the boiling water reactor (BWR) stress corrosion cracking incidents on 4- and 10-inch stainless steel piping, the Electric Power Research Institute (EPRI) organized a round-robin ultrasonic examination of piping removed from service (TPS-75-609). Five inspection teams participated in this program, using both a standard procedure and the individual team procedure. The original intent was to section the piping after the program to evaluate the effectiveness of state-of-the-art ultrasonics in finding stress corrosion cracking. The sectioning was delayed, however, to allow research and development (R and D) groups time to perform basic measurements aimed at determining optimum search unit and instrument characteristics for the ultrasonic examination of stainless steel piping and to study the applicability of various advanced inspection methods. This additional effort was funded as part of an EPRI technical planning study (TPS-75-620), A Study to Define NDE Research for Inspection of Stainless Steels. Inspection methods evaluated in this study included (1) processing of manual scan data using a miniature programmable calculator (Aerojet Nuclear); (2) investigation into the performance characteristics of three experimental ultrasonic transducers (Battelle-Columbus Laboratories); (3) analysis of fundamental ultrasonic response data from intergranular stress corrosion cracks in stainless steels (Southwest Research Institute); and (4) a feasibility study of advanced signal processing and pattern recognition for analyzing flaws in stainless steel piping (Ultrasonics International). The results of the studies compiled in the report have indicated the direction for future research and development and have formed the basis for the recently initiated EPRI Research Project 892, Ultrasonic System Optimization

  15. Fumonisin B₁ (FB₁) Induces Lamellar Separation and Alters Sphingolipid Metabolism of In Vitro Cultured Hoof Explants.

    Science.gov (United States)

    Reisinger, Nicole; Dohnal, Ilse; Nagl, Veronika; Schaumberger, Simone; Schatzmayr, Gerd; Mayer, Elisabeth

    2016-03-24

    One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to the onset of laminitis. In this respect, fumonsins are of special interest since horses are regarded as species most susceptible to this group of mycotoxins. The aim of our study was to investigate the influence of fumonisin B₁ (FB₁) on primary isolated epidermal and dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid metabolism of hoof explants in vitro. There was no effect of FB₁ at any concentration on dermal or epidermal cells. However, FB₁ significantly reduced the separation force of explants after 24 h of incubation. The Sa/So ratio was significantly increased in supernatants of explants incubated with FB₁ (2.5-10 µg/mL) after 24 h. Observed effects on Sa/So ratio were linked to significantly increased sphinganine concentrations. Our study showed that FB₁ impairs the sphingolipid metabolism of explants and reduces lamellar integrity at non-cytotoxic concentrations. FB₁ might, therefore, affect hoof health. Further in vitro and in vivo studies are necessary to elucidate the effects of FB₁ on the equine hoof in more detail.

  16. Synthesis and processing of sphingolipid activator protein-2 (SAP-2) in cultured human fibroblasts

    International Nuclear Information System (INIS)

    Fujibayashi, S.; Wenger, D.A.

    1986-01-01

    Sphingolipid activator proteins (SAP) are relatively small molecular weight proteins that stimulate the enzymatic hydrolysis of sphingolipids in the presence of specific lysosomal hydrolases. SAP-2 has previously been demonstrated to activate the hydrolysis of glucosylceramide, galactosylceramide, and, possibly, sphingomyelin. Using monospecific rabbit antibodies against human spleen SAP-2, the synthesis and processing of SAP-2 were studied in cultured human fibroblasts. When [ 35 S]methionine was presented in the medium to control human cells for 4 h, five major areas of radiolabeling were found. These had apparent molecular weights of 73,000, 68,000, 50,000, 12,000, and 9000. Further studies indicated that the major extracellular product in normal cells given NH4Cl along with the [ 35 S]methionine and in medium from cultures from patients with I cell disease had an apparent molecular weight of 73,000. The Mr = 68,000 and 73,000 species can be converted to a species with an apparent molecular weight of 50,000 by the action of endoglycosidase F. After labeling cells for 1 h followed by a 1-h chase, the Mr = 12,000 and 9000 species appear. Treatment of the immunoprecipitated mixture with endoglycosidase F resulted in conversion of these species to one band with an apparent molecular weight of 7600. These studies indicate that this relatively low molecular weight protein is rapidly synthesized from a relatively large molecular weight highly glycosylated precursor

  17. DEFINING SPATIAL VIOLENCE. BUCHAREST AS A STUDY CASE

    Directory of Open Access Journals (Sweden)

    Celia GHYKA

    2015-05-01

    Full Text Available The paper looks at the spatial manifestations of violence, aiming to define the category of spatial violence by focusing on the recent urban history of Bucharest; it establishes links with the longer history of natural and inflicted disasters that defined the city, and it explores the spatial, urban, social and symbolical conflicts that occured during the last 25 years, pointing at their consequences on the social and urban substance of the city.

  18. Synthesis of a Panel of Carbon-13-Labelled (Glyco)Sphingolipids

    NARCIS (Netherlands)

    Wisse, Patrick; Gold, Henrik; Mirzaian, Mina; Ferraz, Maria J.; Lutteke, Ginger; van den Berg, Richard J. B. H. N.; van den Elst, Hans; Lugtenburg, Johan; van der Marel, Gijsbert A.; Aerts, Johannes M. F. G.; Codee, Jeroen D. C.; Overkleeft, Herman S.

    2015-01-01

    The synthesis of a focussed library of sphingolipids differing in the number and position of C-13 labels is described. The synthesised sphingolipids differ in substitution at both the sphingosine amine (either palmitoylated or unmodified) and the sphingosine primary hydroxyl (unmodified or

  19. Defining palliative care in cystic fibrosis: A Delphi study.

    Science.gov (United States)

    Dellon, E P; Goggin, J; Chen, E; Sabadosa, K; Hempstead, S E; Faro, A; Homa, K

    2018-05-01

    The goal of palliative care is to improve quality of life for people with serious illness. We aimed to create a cystic fibrosis (CF)-specific definition of palliative care. A working group of 36 CF care providers, researchers, palliative care providers, quality improvement experts, individuals with CF, and CF caregivers completed a series of questionnaires to rate the value of each of 22 attributes of palliative care, rank top attributes to construct definitions of palliative care, and then rate proposed definitions. An average of 28 participants completed each of four questionnaires, with consistent distribution of stakeholder roles across questionnaires. Many identified overlaps in routine CF care and palliative care and highlighted the importance of a definition that feels relevant across the lifespan. Modified Delphi methodology was used to define palliative care in CF. The definition will be used as the foundation for development of CF-specific palliative care guidelines. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Defining childhood severe falciparum malaria for intervention studies.

    Directory of Open Access Journals (Sweden)

    Philip Bejon

    2007-08-01

    Full Text Available Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no "gold standard" individual test for severe malaria, malaria-attributable fractions (MAFs can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints.A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor, lower respiratory tract infection (clinician's final diagnosis, meningitis (on cerebrospinal fluid [CSF] examination, and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%-86.1% without excluding these conditions, 89% (95% CI 88.4%-90.2% after exclusions, and 95% (95% CI 94.0%-95.5% when a threshold of 2,500 parasites/mul was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%-83%.The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis, bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition.

  1. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Science.gov (United States)

    Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel

    2013-09-12

    Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL-NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  2. Defining a data management strategy for USGS Chesapeake Bay studies

    Science.gov (United States)

    Ladino, Cassandra

    2013-01-01

    The mission of U.S. Geological Survey’s (USGS) Chesapeake Bay studies is to provide integrated science for improved understanding and management of the Chesapeake Bay ecosystem. Collective USGS efforts in the Chesapeake Bay watershed began in the 1980s, and by the mid-1990s the USGS adopted the watershed as one of its national place-based study areas. Great focus and effort by the USGS have been directed toward Chesapeake Bay studies for almost three decades. The USGS plays a key role in using “ecosystem-based adaptive management, which will provide science to improve the efficiency and accountability of Chesapeake Bay Program activities” (Phillips, 2011). Each year USGS Chesapeake Bay studies produce published research, monitoring data, and models addressing aspects of bay restoration such as, but not limited to, fish health, water quality, land-cover change, and habitat loss. The USGS is responsible for collaborating and sharing this information with other Federal agencies and partners as described under the President’s Executive Order 13508—Strategy for Protecting and Restoring the Chesapeake Bay Watershed signed by President Obama in 2009. Historically, the USGS Chesapeake Bay studies have relied on national USGS databases to store only major nationally available sources of data such as streamflow and water-quality data collected through local monitoring programs and projects, leaving a multitude of other important project data out of the data management process. This practice has led to inefficient methods of finding Chesapeake Bay studies data and underutilization of data resources. Data management by definition is “the business functions that develop and execute plans, policies, practices and projects that acquire, control, protect, deliver and enhance the value of data and information.” (Mosley, 2008a). In other words, data management is a way to preserve, integrate, and share data to address the needs of the Chesapeake Bay studies to better

  3. Defining an anaesthetic curriculum for medical undergraduates. A Delphi study.

    LENUS (Irish Health Repository)

    Rohan, Denise

    2009-01-01

    Anaesthesia is commonly taught to medical students. The duration and content of such teaching varies however and no consensus exists as to what constitutes an optimal curriculum. Anaesthetists possess the necessary knowledge and skills and operate in clinical settings suitable to provide training for medical undergraduates, especially in areas where deficiencies have been identified. This Delphi study was directed towards developing a consensus on an optimal anaesthesia, intensive care and pain medicine curriculum for medical undergraduates.

  4. Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

    Science.gov (United States)

    McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

    2015-09-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

  5. 4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

    Directory of Open Access Journals (Sweden)

    Caroline Camaré

    2017-01-01

    Full Text Available The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs contribute to the formation of tubes via the generation of sphingosine 1-phosphate (S1P, a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE, an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM elicited the formation of tubes by human microvascular endothelial cells (HMEC-1, whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1 pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

  6. Regulation of stem-cell mediated host immunity by the sphingolipid ...

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

    Regulation of stem-cell mediated host immunity by the sphingolipid pathway ... in the generation of mature immune cells and the functioning of the surrounding ... methods with human cells and genetically engineered mice to examine how the ...

  7. Sphingolipid topology and the dynamic organization and function of membrane proteins.

    Science.gov (United States)

    van Meer, Gerrit; Hoetzl, Sandra

    2010-05-03

    When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi then allowed them to create membranes of different lipid composition, notably a thin, flexible ER membrane, consisting of glycerolipids, and a sturdy plasma membrane containing at least 50% sphingolipids and sterols. Besides sorting membrane proteins, in the course of evolution the simple sphingolipids obtained key positions in cellular physiology by developing specific interactions with (membrane) proteins involved in the execution and control of signaling. The few signaling sphingolipids in mammals must provide basic transmission principles that evolution has built upon for organizing the specific regulatory pathways tuned to the needs of the different cell types in the body. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    OpenAIRE

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

  9. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

  10. Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids.

    Science.gov (United States)

    Li, Guangtao; Kim, JiHyun; Huang, Zhen; St Clair, Johnna R; Brown, Deborah A; London, Erwin

    2016-12-06

    Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell. The data also provided a rough estimate for the total cellular lipids residing in the plasma membrane (about half). In addition to such lipidomics applications, the exchange method should have wide potential for investigations of lipid function and modification of cellular behavior by modification of lipids.

  11. Sphingoid bases and the serine catabolic enzyme CHA1 define a novel feedforward/feedback mechanism in the response to serine availability.

    Science.gov (United States)

    Montefusco, David J; Newcomb, Benjamin; Gandy, Jason L; Brice, Sarah E; Matmati, Nabil; Cowart, L Ashley; Hannun, Yusuf A

    2012-03-16

    Targets of bioactive sphingolipids in Saccharomyces cerevisiae were previously identified using microarray experiments focused on sphingolipid-dependent responses to heat stress. One of these heat-induced genes is the serine deamidase/dehydratase Cha1 known to be regulated by increased serine availability. This study investigated the hypothesis that sphingolipids may mediate the induction of Cha1 in response to serine availability. The results showed that inhibition of de novo synthesis of sphingolipids, pharmacologically or genetically, prevented the induction of Cha1 in response to increased serine availability. Additional studies implicated the sphingoid bases phytosphingosine and dihydrosphingosine as the likely mediators of Cha1 up-regulation. The yeast protein kinases Pkh1 and Pkh2, known sphingoid base effectors, were found to mediate CHA1 up-regulation via the transcription factor Cha4. Because the results disclosed a role for sphingolipids in negative feedback regulation of serine metabolism, we investigated the effects of disrupting this mechanism on sphingolipid levels and on cell growth. Intriguingly, exposure of the cha1Δ strain to high serine resulted in hyperaccumulation of endogenous serine and in turn a significant accumulation of sphingoid bases and ceramides. Under these conditions, the cha1Δ strain displayed a significant growth defect that was sphingolipid-dependent. Together, this work reveals a feedforward/feedback loop whereby the sphingoid bases serve as sensors of serine availability and mediate up-regulation of Cha1 in response to serine availability, which in turn regulates sphingolipid levels by limiting serine accumulation.

  12. A combined fluorescence spectroscopy, confocal and 2-photon microscopy approach to re-evaluate the properties of sphingolipid domains.

    Science.gov (United States)

    Pinto, Sandra N; Fernandes, Fábio; Fedorov, Alexander; Futerman, Anthony H; Silva, Liana C; Prieto, Manuel

    2013-09-01

    The aim of this study is to provide further insight about the interplay between important signaling lipids and to characterize the properties of the lipid domains formed by those lipids in membranes containing distinct composition. To this end, we have used a combination of fluorescence spectroscopy, confocal and two-photon microscopy and a stepwise approach to re-evaluate the biophysical properties of sphingolipid domains, particularly lipid rafts and ceramide (Cer)-platforms. By using this strategy we were able to show that, in binary mixtures, sphingolipids (Cer and sphingomyelin, SM) form more tightly packed gel domains than those formed by phospholipids with similar acyl chain length. In more complex lipid mixtures, the interaction between the different lipids is intricate and is strongly dictated by the Cer-to-Chol ratio. The results show that in quaternary phospholipid/SM/Chol/Cer mixtures, Cer forms gel domains that become less packed as Chol is increased. Moreover, the extent of gel phase formation is strongly reduced in these mixtures, even though Cer molar fraction is increased. These results suggest that in biological membranes, lipid domains such as rafts and ceramide platforms, might display distinctive biophysical properties depending on the local lipid composition at the site of the membrane where they are formed, further highlighting the potential role of membrane biophysical properties as an underlying mechanism for mediating specific biological processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Establishment of HeLa cell mutants deficient in sphingolipid-related genes using TALENs.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yamaji

    Full Text Available Sphingolipids are essential components in eukaryotes and have various cellular functions. Recent developments in genome-editing technologies have facilitated gene disruption in various organisms and cell lines. We here show the disruption of various sphingolipid metabolic genes in human cervical carcinoma HeLa cells by using transcription activator-like effector nucleases (TALENs. A TALEN pair targeting the human CERT gene (alternative name COL4A3BP encoding a ceramide transport protein induced a loss-of-function phenotype in more than 60% of HeLa cells even though the cell line has a pseudo-triploid karyotype. We have isolated several loss-of-function mutant clones for CERT, UGCG (encoding glucosylceramide synthase, and B4GalT5 (encoding the major lactosylceramide synthase, and also a CERT/UGCG double-deficient clone. Characterization of these clones supported previous proposals that CERT primarily contributes to the synthesis of SM but not GlcCer, and that B4GalT5 is the major LacCer synthase. These newly established sphingolipid-deficient HeLa cell mutants together with our previously established stable transfectants provide a 'sphingolipid-modified HeLa cell panel,' which will be useful to elucidate the functions of various sphingolipid species against essentially the same genomic background.

  14. Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

    Science.gov (United States)

    In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

  15. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

    Science.gov (United States)

    Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2007-01-01

    Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

  16. Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows, Passer domesticus L., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry.

    Science.gov (United States)

    Muñoz-Garcia, Agustí; Ro, Jennifer; Brown, Johnie C; Williams, Joseph B

    2008-02-01

    Because cutaneous water loss (CWL) represents half of total water loss in birds, selection to reduce CWL may be strong in desert birds. We previously found that CWL of house sparrows from a desert population was about 25% lower than that of individuals from a mesic environment. The stratum corneum (SC), the outer layer of the epidermis, serves as the primary barrier to water vapor diffusion through the skin. The avian SC is formed by layers of corneocytes embedded in a lipid matrix consisting of cholesterol, free fatty acids and two classes of sphingolipids, ceramides and cerebrosides. The SC of birds also serves a thermoregulatory function; high rates of CWL keep body temperatures under lethal limits in episodes of heat stress. In this study, we used high-performance liquid chromatography coupled with atmospheric pressure photoionization-mass spectrometry (HPLC/APPI-MS) to identify and quantify over 200 sphingolipids in the SC of house sparrows from desert and mesic populations. Principal components analysis (PCA) led to the hypotheses that sphingolipids in the SC of desert sparrows have longer carbon chains in the fatty acid moiety and are more polar than those found in mesic sparrows. We also tested the association between principal components and CWL in both populations. Our study suggested that a reduction in CWL found in desert sparrows was, in part, the result of modifications in chain length and polarity of the sphingolipids, changes that apparently determine the interactions of the lipid molecules within the SC.

  17. Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

    Science.gov (United States)

    Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  18. Sphingolipid topology and the dynamic organization and function of membrane proteins

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368; Hoetzl, S.

    2010-01-01

    When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi

  19. Low serum sphingolipids in children with attention deficit-hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Marcela Patricia Henríquez-Henríquez

    2015-08-01

    Full Text Available Background: Attention deficit-hyperactivity disorder (ADHD is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects. Methods: We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non-affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls and 21 unrelated controls. ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR. Diagnostic criteria were assessed by 2 independent observers. Groups were compared by parametrical statistics. Results: Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0 and deoxy-ceramide C24:1 were significantly decreased in ADHD patients at 20-30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity. Conclusions: Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD.

  20. A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise.

    Science.gov (United States)

    Saleem, Mahwesh; Herrmann, Nathan; Dinoff, Adam; Mielke, Michelle M; Oh, Paul I; Shammi, Prathiba; Cao, Xingshan; Venkata, Swarajya Lakshmi Vattem; Haughey, Norman J; Lanctôt, Krista L

    2017-01-01

    Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program. Patients with CAD (n = 120, mean age = 64±6 y, 84% male, years of education = 16±3) underwent CR with neuropsychological assessments and blood collected at baseline, 3-, and 6-months. Z-scores based on age, gender, and education were combined for verbal memory, visuospatial memory, processing speed, executive function, and global cognition tasks to calculate cognitive domain Z-scores. Plasma sphingolipid concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Mixed models were used to identify sphingolipids significantly associated with performance in verbal memory and other cognitive domains, adjusting for potential confounders. A decrease in ceramide C18:0 concentration was significantly associated with improvement in verbal memory performance (b[SE] = -0.51 [0.25], p = 0.04), visuospatial memory (b[SE] = -0.44 [0.22], p = 0.05), processing speed (b[SE] = -0.89 [0.32], p = 0.007), and global cognition (b[SE] = -1.47 [0.59], p = 0.01) over 6 months of CR. Plasma ceramide C18:0 concentrations may be a sensitive marker of cognitive response to exercise in patients with CAD.

  1. Defining the Constructs of Expert Coaching: A Q-Methodological Study of Olympic Sport Coaches

    Science.gov (United States)

    DeWeese, Brad Heath

    2012-01-01

    The purpose of this study was to enhance the development of coaches for participation at International level competition through the improvement of coaching education programming. Although many studies have alluded to the benefit of various coaching education tactics, no study to date had set out to determine the constructs that define an expert…

  2. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

    Science.gov (United States)

    Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

    2016-10-01

    Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

  3. Three principles to define the success of a diagnostic study could be identified

    DEFF Research Database (Denmark)

    Vach, Werner; Gerke, Oke; Høilund-Carlsen, Poul Flemming

    2012-01-01

    of a diagnostic study on a single binary test and investigation of common statistical approaches in relation to these criteria. RESULTS: Three criteria for defining the overall success of a diagnostic study could be identified: a strong criterion, a liberal criterion, and a weak criterion. The strong criterion...... can be implemented by comparing the lower bounds of the confidence intervals for sensitivity and specificity with prespecified target values, as is typically done in many diagnostic studies. The liberal criterion allows a clinically meaningful compensation between sensitivity and specificity and can...... be implemented in different ways. If the liberal criterion is applied instead of the strong criterion, this can lead to a substantial reduction in the sample size required for a diagnostic study. The weak criterion is not very adequate for defining the success of a diagnostic study. CONCLUSION: When planning...

  4. Defining elite athletes: Issues in the study of expert performance in sport psychology

    OpenAIRE

    Swann, C; Moran, A; Piggott, D

    2015-01-01

    © 2014 Elsevier Ltd. Objectives: There has been considerable inconsistency and confusion in the definition of elite/expert athletes in sport psychology research, which has implications for studies conducted in this area and for the field as a whole. This study aimed to: (i) critically evaluate the ways in which recent research in sport psychology has defined elite/expert athletes; (ii) explore the rationale for using such athletes; and (iii) evaluate the conclusions that research in this fiel...

  5. The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

    Czech Academy of Sciences Publication Activity Database

    Paulenda, Tomáš; Dráber, Petr

    2016-01-01

    Roč. 71, č. 7 (2016), s. 918-930 ISSN 0105-4538 R&D Projects: GA ČR(CZ) GA14-00703S; GA ČR(CZ) GA14-09807S; GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : asthma * cellular membranes * endoplasmic * reticulum * ORMDL3 * sphingolipids Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.361, year: 2016

  6. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

    International Nuclear Information System (INIS)

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

    2004-01-01

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  7. A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast.

    Science.gov (United States)

    Clarke, Jesse; Dephoure, Noah; Horecka, Ira; Gygi, Steven; Kellogg, Douglas

    2017-10-01

    In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth--dependent signals control cell growth and the cell cycle. © 2017 Clarke et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  8. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

    Directory of Open Access Journals (Sweden)

    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  9. Development of a chemically defined medium for studying foodborne bacterial-fungal interactions

    DEFF Research Database (Denmark)

    Aunsbjerg, Stina Dissing; Honoré, Anders Hans; Vogensen, Finn Kvist

    2015-01-01

    judged by ultra-performance liquid chromatography/mass spectrometry) a chemically defined interaction medium (CDIM) was developed. The medium supported growth of antifungal cultures such as Lactobacillus paracasei and Propionibacterium freudenreichii, as well as spoilage moulds and yeasts isolated from...... fermented milk products. Both strong and weak antifungal interactions observed in milk could be reproduced in CDIM. The medium seems suitable for studying antifungal activity of bacterial cultures....

  10. Studies of isotopic defined hydrogen beams scattering from Pd single-crystal surfaces

    International Nuclear Information System (INIS)

    Varlam, Mihai; Steflea, Dumitru

    2001-01-01

    An experimental investigation of hydrogen isotopes interaction with Pd single-crystal surface has been carried out using molecular beam technique. The energy dependence of the sticking probability and its relation with the trapping probability into the precursor state is studied by integrating the scattered angular distribution of hydrogen Isotopic defined beams from Pd (111) surface in the 40-400 K surface temperature range. The dependence has been evaluated by defining hydrogen molecular beams with different isotopic concentration - from the natural one to the 5% D/(D+H) ratio - and for different incident energies. The beam was directed onto a single-crystal Pd (111) surface. In the paper, we report the experimental results and some considerations related to it. (authors)

  11. Studies of isotopic defined hydrogen beams scattering from Pd single-crystal surfaces

    International Nuclear Information System (INIS)

    Varlam, Mihai; Steflea, Dumitru

    1999-01-01

    An experimental investigation of hydrogen isotopes interaction with Pd single-crystal surfaces has been carried out using molecular beam technique. The energy dependence of the sticking probability and its relation with the trapping probability into the precursor state is studied by integrating the scattered angular distribution of hydrogen isotopic defined beams from Pd (111) surfaces in the 40 - 400 K surface temperature range. The dependence has been evaluated by defining hydrogen molecular beams with different isotopic concentration - from the natural one until 5% D/(D + H) and different incident energies and directed onto a single - crystal Pd (111) surface. In the paper, we report the experimental results and some considerations related to them. (authors)

  12. Factors defining the mentoring competencies of clinical midwives: An exploratory quantitative research study in Japan.

    Science.gov (United States)

    Hishinuma, Yuri; Horiuchi, Shigeko; Yanai, Haruo

    2016-01-01

    Clinical education is an extremely important process in cultivating healthcare professionals, and the quality of educators has a major impact on the quality of future practitioners. Although practicing clinical midwives contribute to the education of pre-registered midwives and those qualified within the past year (new midwives), the factors defining the educational competencies of clinical midwives have not been clarified. The purpose of this study was to explore the factors that define the mentoring competencies of clinical midwives involved in educating new midwives. An exploratory quantitative research study. Questionnaires were distributed to 694 midwives who had previously conducted educational activities with new midwives at the 63 facilities whose administrator or nurse manager in charge of all staff, including midwives, consented to participate. Of the 694 midwives, 464 (66.9%) returned the questionnaire and 451 (65.1%) valid responses were analyzed. Exploratory factor analyses were performed on the following three concepts: [competency as a professional], [competency as an educator], and [personal characteristics]. [Competency as a professional] consisted of two factors: and ; [competency as an educator] consisted of four factors: , , and ; and [personal characteristics consisted of three factors: exercising leadership> , and . These three concepts were defined by a total of nine sub-concepts (factors), and 41 items were extracted with a reliability coefficient (Cronbach's α) of 0.944 CONCLUSIONS: "Mentoring competencies of clinical midwives (MCCM)" are defined by three concepts and nine sub-concepts, which can be evaluated by 41 items regarding the behavior, thoughts, and characteristics that clinical midwives exhibit when they educate new midwives in clinical settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Defining episodes of diarrhoea: results from a three-country study in Sub Saharan Africa

    CSIR Research Space (South Africa)

    Wright, Jarrad A

    2006-03-01

    Full Text Available in the study Monday Tuesday Wednesday Thursday Friday Saturday Sunday ? ? ? ? ? ? ? Normal stool Diarrhoea With blood and/or mucus ���� ���� ���� ���� ���� ���� ���� the shape of a container... prospective study. J Trop Pediatr 1991;37:293-9. 5. Morris SS, Cousens SN, Lanata CF, Kirkwood BR. Diarrhea__defining the episode. Int J Epidemiol 1994;23:617-23. 6. Wyrsch M, Coakley K, Alexander N, Saleu G, Taime J, Kakazo M. Diarrhoea morbidity in children...

  14. [The importance of defining methodology for post-marketing observational studies on cardiovascular therapies].

    Science.gov (United States)

    Pelliccia, Francesco; Barillà, Francesco; Tanzilli, Gaetano; Viceconte, Nicola; Paravati, Vincenzo; Mangieri, Enrico; Gaudio, Carlo

    2017-01-01

    In recent years, a growing number of observational studies in cardiology have been carried out following the criticism that rigid design of randomized clinical trials produces information that is not applicable to the general patient. This approach is very common in several branches of medicine, first of all oncology, but has often been considered marginal in cardiology. The recent introduction of new oral anticoagulants (NOACs) on the market, however, has seen a proliferation of "real-life" studies, drawing the attention of cardiologists to the advantages and limitations of post-marketing studies. NOACs have been approved for use on the basis of large randomized clinical trials that have clearly documented their efficacy and safety. Since they have become available, the analysis of phase IV data has been considered crucial and therefore a great amount of information on the use of NOACs in daily practice has become available. It should be considered, however, that the possibility exists that results obtained from "real-world" studies, which do not apply rigid scientific criteria, may lead to incorrect conclusions. Accordingly, it is mandatory to fully define the operational standards of observational studies. All the protagonists of post-marketing analysis (physicians, epidemiologists, pharmacologists, statisticians) should handle the data strictly in order to ensure their reliability and comparability with other studies. To this end, it is crucial that researchers follow rigorous operational protocols for phase IV studies. Briefly, any "real-life" study should be prospective and adhere to what is prespecified by the research protocol - which must illustrate the background and rationale of the study, define its primary endpoint, and detail the methods, i.e. study design, population and variables.

  15. Using MFM methodology to generate and define major accident scenarios for quantitative risk assessment studies

    DEFF Research Database (Denmark)

    Hua, Xinsheng; Wu, Zongzhi; Lind, Morten

    2017-01-01

    to calculate likelihood of each MAS. Combining the likelihood of each scenario with a qualitative risk matrix, each major accident scenario is thereby ranked for consideration for detailed consequence analysis. The methodology is successfully highlighted using part of BMA-process for production of hydrogen......Generating and defining Major Accident Scenarios (MAS) are commonly agreed as the key step for quantitative risk assessment (QRA). The aim of the study is to explore the feasibility of using Multilevel Flow Modeling (MFM) methodology to formulating MAS. Traditionally this is usually done based...

  16. Vitamin E γ-Tocotrienol Inhibits Cytokine-Stimulated NF-κB Activation by Induction of Anti-Inflammatory A20 via Stress Adaptive Response Due to Modulation of Sphingolipids.

    Science.gov (United States)

    Wang, Yun; Park, Na-Young; Jang, Yumi; Ma, Averil; Jiang, Qing

    2015-07-01

    NF-κB plays a central role in pathogenesis of inflammation and cancer. Many phytochemicals, including γ-tocotrienol (γTE), a natural form of vitamin E, have been shown to inhibit NF-κB activation, but the underlying mechanism has not been identified. In this study, we show that γTE inhibited cytokine-triggered activation of NF-κB and its upstream regulator TGF-β-activated kinase-1 in murine RAW 264.7 macrophages and primary bone marrow-derived macrophages. In these cells, γTE induced upregulation of A20, an inhibitor of NF-κB. Knockout of A20 partially diminished γTE's anti-NF-κB effect, but γTE increased another NF-κB inhibitor, Cezanne, in A20(-/-) cells. In search of the reason for A20 upregulation, we found that γTE treatment increased phosphorylation of translation initiation factor 2, IκBα, and JNK, indicating induction of endoplasmic reticulum stress. Liquid chromatography-tandem mass spectrometry analyses revealed that γTE modulated sphingolipids, including enhancement of intracellular dihydroceramides, sphingoid bases in de novo synthesis of the sphingolipid pathway. Chemical inhibition of de novo sphingolipid synthesis partially reversed γTE's induction of A20 and the anti-NF-κB effect. The importance of dihydroceramide increase is further supported by the observation that C8-dihydroceramide mimicked γTE in upregulating A20, enhancing endoplasmic reticulum stress, and attenuating TNF-triggered NF-κB activation. Our study identifies a novel anti-NF-κB mechanism where A20 is induced by stress-induced adaptive response as a result of modulation of sphingolipids, and it demonstrates an immunomodulatory role of dihydrocermides. Copyright © 2015 by The American Association of Immunologists, Inc.

  17. Clinical prediction in defined populations: a simulation study investigating when and how to aggregate existing models

    Directory of Open Access Journals (Sweden)

    Glen P. Martin

    2017-01-01

    Full Text Available Abstract Background Clinical prediction models (CPMs are increasingly deployed to support healthcare decisions but they are derived inconsistently, in part due to limited data. An emerging alternative is to aggregate existing CPMs developed for similar settings and outcomes. This simulation study aimed to investigate the impact of between-population-heterogeneity and sample size on aggregating existing CPMs in a defined population, compared with developing a model de novo. Methods Simulations were designed to mimic a scenario in which multiple CPMs for a binary outcome had been derived in distinct, heterogeneous populations, with potentially different predictors available in each. We then generated a new ‘local’ population and compared the performance of CPMs developed for this population by aggregation, using stacked regression, principal component analysis or partial least squares, with redevelopment from scratch using backwards selection and penalised regression. Results While redevelopment approaches resulted in models that were miscalibrated for local datasets of less than 500 observations, model aggregation methods were well calibrated across all simulation scenarios. When the size of local data was less than 1000 observations and between-population-heterogeneity was small, aggregating existing CPMs gave better discrimination and had the lowest mean square error in the predicted risks compared with deriving a new model. Conversely, given greater than 1000 observations and significant between-population-heterogeneity, then redevelopment outperformed the aggregation approaches. In all other scenarios, both aggregation and de novo derivation resulted in similar predictive performance. Conclusion This study demonstrates a pragmatic approach to contextualising CPMs to defined populations. When aiming to develop models in defined populations, modellers should consider existing CPMs, with aggregation approaches being a suitable modelling

  18. Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.

    Science.gov (United States)

    Mina, John G; Thye, Julie K; Alqaisi, Amjed Q I; Bird, Louise E; Dods, Robert H; Grøftehauge, Morten K; Mosely, Jackie A; Pratt, Steven; Shams-Eldin, Hosam; Schwarz, Ralph T; Pohl, Ehmke; Denny, Paul W

    2017-07-21

    Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells--new opportunities in regenerative medicine.

    Science.gov (United States)

    Marycz, Krzysztof; Śmieszek, Agnieszka; Jeleń, Marta; Chrząstek, Klaudia; Grzesiak, Jakub; Meissner, Justyna

    2015-09-01

    Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

  20. Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

    Directory of Open Access Journals (Sweden)

    Sandra M Eldridge

    Full Text Available We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

  1. Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

    Science.gov (United States)

    Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M

    2016-01-01

    We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

  2. Development of a defined-sequence DNA system for use in DNA misrepair studies

    International Nuclear Information System (INIS)

    Sutton, S.; Tobias, C.A.

    1984-01-01

    The authors have developed a system that allows them to study cellular DNA repair processes at the molecular level. In particular, the authors are using this system to examine the consequences of a misrepair of radiation-induced DNA damage, as a function of dose. The cells being used are specially engineered haploid yeast cells. Maintained in the cells, at one copy per cell, is a cen plasmid, a plasmid that behaves like a functional chromosome. This plasmid carries a small defined sequence of DNA from the E. coli lac z gene. It is this lac z region (called the alpha region) that serves as the target for radiation damage. Two copies of the complimentary portion of the lac z gene are integrated into the yeast genome. Irradiated cells are screened for possible mutation in the alpha region by testing the cells' ability to hydrolyze xgal, a lactose substrate. The DNA of interest is then extracted from the cells, sequenced, and the sequence is compared to that of the control. Unlike the usual defined-sequence DNA systems, theirs is an in vivo system. A disadvantage is the relatively high background mutation rate. Results achieved with this system, as well as future applications, are discussed

  3. Small angle neutron scattering study of polyelectrolyte brushes grafted to well-defined gold nanoparticle interfaces.

    Science.gov (United States)

    Jia, Haidong; Grillo, Isabelle; Titmuss, Simon

    2010-05-18

    Small angle neutron scattering (SANS) has been used to study the conformations, and response to added salt, of a polyelectrolyte layer grafted to the interfaces of well-defined gold nanoparticles. The polyelectrolyte layer is prepared at a constant coverage by grafting thiol-functionalized polystyrene (M(w) = 53k) to gold nanoparticles of well-defined interfacial curvature (R(c) = 26.5 nm) followed by a soft-sulfonation of 38% of the segments to sodium polystyrene sulfonate (NaPSS). The SANS profiles can be fit by Fermi-Dirac distributions that are consistent with a Gaussian distribution but are better described by a parabolic distribution plus an exponential tail, particularly in the high salt regime. These distributions are consistent with the predictions and measurements for osmotic and salted brushes at interfaces of low curvature. When the concentration of added salt exceeds the concentration of counterions inside the brush, there is a salt-induced deswelling, but even at the highest salt concentration the brush remains significantly swollen due to a short-ranged excluded volume interaction. This is responsible for the observed resistance to aggregation of these comparatively high concentration polyelectrolyte stabilized gold nanoparticle dispersions even in the presence of a high concentration of added salt.

  4. Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance

    Directory of Open Access Journals (Sweden)

    Paola Giussani

    2014-03-01

    Full Text Available Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (αNeu5Ac(2-8αNeu5Ac(2-3βGal(1-4βGlc(1-1Cer or N-glycolyl GM3 (αNeu5Ac (2-3βGal(1-4βGlc(1-1Cer and de-N-acetyl GM3 (NeuNH(2βGal(1-4βGlc(1-1Cer endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy.

  5. Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium ophioglossum.

    Science.gov (United States)

    Firdous, Sadiqa; Ansari, Nida Hassan; Fatima, Itrat; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Lateef, Mehreen

    2012-07-01

    Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n-hexane subfraction of the MeOH extract of the whole plant of Heliotropium ophioglossum along with glycerol monopalmitate (3) and β-sitosterol 3-O-β-D: -glucoside (4) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme urease.

  6. Actin filaments and microtubules are involved in different membrane traffic pathways that transport sphingolipids to the apical surface of polarized HepG2 cells

    NARCIS (Netherlands)

    Zegers, MMP; Zaal, KJM; van Ijzendoorn, SCD; Klappe, K; Hoekstra, D

    In polarized HepG2 hepatoma cells, sphingolipids are transported to the apical, bile canalicular membrane by two different transport routes, as revealed with fluorescently tagged sphingolipid analogs. One route involves direct, transcytosis-independent transport of Golgi-derived glucosylceramide and

  7. Stability studies needed to define the handling and transport conditions of sensitive pharmaceutical or biotechnological products.

    Science.gov (United States)

    Ammann, Claude

    2011-12-01

    Many pharmaceutical or biotechnological products require transport using temperature-controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.

  8. A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

    Science.gov (United States)

    Clay, Lori; Caudron, Fabrice; Denoth-Lippuner, Annina; Boettcher, Barbara; Buvelot Frei, Stéphanie; Snapp, Erik Lee; Barral, Yves

    2014-01-01

    In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging. DOI: http://dx.doi.org/10.7554/eLife.01883.001 PMID:24843009

  9. Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys.

    Science.gov (United States)

    Benlasher, Emad; Geng, Xiuyu; Nguyen, Ngoc Thanh Xuan; Tardieu, Didier; Bailly, Jean-Denis; Auvergne, Alain; Guerre, Philippe

    2012-03-01

    Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.

  10. Defining post-sternotomy mediastinitis for clinical evidence-based studies.

    Science.gov (United States)

    van Wingerden, Jan J; de Mol, Bas A J M; van der Horst, Chantal M A M

    2016-05-01

    Considerable advances have already been made in the treatment of deep thoracic wound infections following a median sternotomy for cardiac surgery. Further improvement in diagnosis, treatment, and outcome will require a targeted approach by multidisciplinary teams. Clear communication and synergy between the various clinical and supportive disciplines would assist in removing the last barriers to standardized evidence-based studies and the development of improved evidence-based guidelines. An extensive literature search without language restrictions was carried out on PubMed (Medline), EMBASE, and Web of Science, covering the period 1988 to week 16, 2014, and a manual search of the reference lists was performed regarding all possible definitions and classifications of post-sternotomy mediastinitis. Two hundred and eighteen papers describing post-sternotomy infections in a multitude of terms were identified, and the strengths and weaknesses of the most popular definitions and terms relating specifically to post-sternotomy infections were examined. This study revealed that clinicians use a multitude of terms to describe post-sternotomy infections without defining the condition under treatment. Occasionally, older epidemiological (surveillance) definitions were used. It also shows that supportive disciplines have their own definitions, or interpretations of existing definitions, to describe these infections. The outcome of this study is that clinicians have adopted no single definition, which is essential for further improvement for evidence-based studies. We suggest that it is possible to adopt a single term for thoracic infection after a sternotomy (and only sternotomy), and propose a clinical definition for this purpose. © The Author(s) 2016.

  11. The equationally-defined commutator a study in equational logic and algebra

    CERN Document Server

    Czelakowski, Janusz

    2015-01-01

    This monograph introduces and explores the notions of a commutator equation and the equationally-defined commutator from the perspective of abstract algebraic logic.  An account of the commutator operation associated with equational deductive systems is presented, with an emphasis placed on logical aspects of the commutator for equational systems determined by quasivarieties of algebras.  The author discusses the general properties of the equationally-defined commutator, various centralization relations for relative congruences, the additivity and correspondence properties of the equationally-defined commutator, and its behavior in finitely generated quasivarieties. Presenting new and original research not yet considered in the mathematical literature, The Equationally-Defined Commutator will be of interest to professional algebraists and logicians, as well as graduate students and other researchers interested in problems of modern algebraic logic.

  12. How Do Women Entrepreneurs Define Success? A Qualitative Study of Differences Among Women Entrepreneurs in Ethiopia

    OpenAIRE

    Atsede Tesfaye Hailemariam; Brigitte Kroon

    2014-01-01

    This paper describes how women entrepreneurs in Ethiopia define success in their own terms. Semi structured in-depth interviews were conducted with 24 women entrepreneurs from various sectors in Addis Ababa. The interview formats allowed the women to tell their life history and define success in their own terms. A common stereotype is that women entrepreneurs in Ethiopia operate businesses out of necessity and therefore women measure success in terms of financial rewards than personal rewards...

  13. Evaluation of a practical expert defined approach to patient population segmentation: a case study in Singapore

    Directory of Open Access Journals (Sweden)

    Lian Leng Low

    2017-11-01

    Full Text Available Abstract Background Segmenting the population into groups that are relatively homogeneous in healthcare characteristics or needs is crucial to facilitate integrated care and resource planning. We aimed to evaluate the feasibility of segmenting the population into discrete, non-overlapping groups using a practical expert and literature driven approach. We hypothesized that this approach is feasible utilizing the electronic health record (EHR in SingHealth. Methods In addition to well-defined segments of “Mostly healthy”, “Serious acute illness but curable” and “End of life” segments that are also present in the Ministry of Health Singapore framework, patients with chronic diseases were segmented into “Stable chronic disease”, “Complex chronic diseases without frequent hospital admissions”, and “Complex chronic diseases with frequent hospital admissions”. Using the electronic health record (EHR, we applied this framework to all adult patients who had a healthcare encounter in the Singapore Health Services Regional Health System in 2012. ICD-9, 10 and polyclinic codes were used to define chronic diseases with a comprehensive look-back period of 5 years. Outcomes (hospital admissions, emergency attendances, specialist outpatient clinic attendances and mortality were analyzed for years 2012 to 2015. Results Eight hundred twenty five thousand eight hundred seventy four patients were included in this study with the majority being healthy without chronic diseases. The most common chronic disease was hypertension. Patients with “complex chronic disease” with frequent hospital admissions segment represented 0.6% of the eligible population, but accounted for the highest hospital admissions (4.33 ± 2.12 admissions; p < 0.001 and emergency attendances (ED (3.21 ± 3.16 ED visits; p < 0.001 per patient, and a high mortality rate (16%. Patients with metastatic disease accounted for the highest specialist outpatient

  14. Defining fitness to practise in Australian radiation therapy: A focus group study

    International Nuclear Information System (INIS)

    Wright, Caroline A.; Jolly, Brian; Schneider-Kolsky, Michal E.; Baird, Marilyn A.

    2011-01-01

    Purpose: This paper presents the results of a study undertaken to investigate how Australian radiation therapists define fitness to practise. Method: A qualitative approach was taken to data collection with focus groups being employed to gather the data. Analysis was informed by grounded theory. Following ethics approval, three homogeneous focus groups were conducted comprising a total of 21 participants, with 5-8 participants per group. The discussions were transcribed, verified by the researcher and participants, then unitised, coded and a sample checked by a second coder. Findings: There was no consensus on the definition of fitness to practise. The terms professionalism and competence were used interchangeably in some definitions. Four themes emerged from the data, these were; fitness as a continuum (individual differences and longevity in the profession), fitness as behaviour and conduct (professionalism and competence), fitness as a state of mind (attitudes and intangible elements) and fitness as being qualified (course completion means fitness to practise). Three concepts which were not raised were illegal behaviour, impaired practice and dose errors. Conclusion: There is no consensus among radiation therapists about fitness to practise. There was confusion with how Fitness to practise relates to professionalism and competence with little mention of how impairment is interwoven into the notion of fitness to practise. Without an unambiguous definition and robust criteria, making the 'judgement call' as to whether a practitioners' fitness to practise is impaired will continue to be a challenge for educators, departmental managers and registration boards.

  15. Defining fitness to practise in Australian radiation therapy: A focus group study

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Caroline A., E-mail: caroline.wright@med.monash.edu.a [Monash University, Medical Imaging and Radiation Sciences, Clayton Campus, Wellington Road Clayton, Melbourne, Victoria 3800 (Australia); Jolly, Brian [Monash University, Centre for Medical and Health Sciences Education (Australia); Schneider-Kolsky, Michal E.; Baird, Marilyn A. [Monash University, Medical Imaging and Radiation Sciences, Clayton Campus, Wellington Road Clayton, Melbourne, Victoria 3800 (Australia)

    2011-02-15

    Purpose: This paper presents the results of a study undertaken to investigate how Australian radiation therapists define fitness to practise. Method: A qualitative approach was taken to data collection with focus groups being employed to gather the data. Analysis was informed by grounded theory. Following ethics approval, three homogeneous focus groups were conducted comprising a total of 21 participants, with 5-8 participants per group. The discussions were transcribed, verified by the researcher and participants, then unitised, coded and a sample checked by a second coder. Findings: There was no consensus on the definition of fitness to practise. The terms professionalism and competence were used interchangeably in some definitions. Four themes emerged from the data, these were; fitness as a continuum (individual differences and longevity in the profession), fitness as behaviour and conduct (professionalism and competence), fitness as a state of mind (attitudes and intangible elements) and fitness as being qualified (course completion means fitness to practise). Three concepts which were not raised were illegal behaviour, impaired practice and dose errors. Conclusion: There is no consensus among radiation therapists about fitness to practise. There was confusion with how Fitness to practise relates to professionalism and competence with little mention of how impairment is interwoven into the notion of fitness to practise. Without an unambiguous definition and robust criteria, making the 'judgement call' as to whether a practitioners' fitness to practise is impaired will continue to be a challenge for educators, departmental managers and registration boards.

  16. Physiological Study of Lactobacillus delbrueckii subsp. bulgaricus Strains in a Novel Chemically Defined Medium

    Science.gov (United States)

    Chervaux, Christian; Ehrlich, S. Dusko; Maguin, Emmanuelle

    2000-01-01

    We developed a chemically defined medium called milieu proche du lait (MPL), in which 22 Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) strains exhibited growth rates ranging from 0.55 to 1 h−1. MPL can also be used for cultivation of other lactobacilli and Streptococcus thermophilus. The growth characteristics of L. bulgaricus in MPL containing different carbon sources were determined, including an initial characterization of the phosphotransferase system transporters involved. For the 22 tested strains, growth on lactose was faster than on glucose, mannose, and fructose. Lactose concentrations below 0.4% were limiting for growth. We isolated 2-deoxyglucose-resistant mutants from strains CNRZ397 and ATCC 11842. CNRZ397-derived mutants were all deficient for glucose, fructose, and mannose utilization, indicating that these three sugars are probably transported via a unique mannose-specific-enzyme-II-like transporter. In contrast, mutants of ATCC 11842 exhibited diverse phenotypes, suggesting that multiple transporters may exist in that strain. We also developed a protein labeling method and verified that exopolysaccharide production and phage infection can occur in MPL. The MPL medium should thus be useful in conducting physiological studies of L. bulgaricus and other lactic acid bacteria under well controlled nutritional conditions. PMID:11097906

  17. A COMPREHENSIVE STUDY OF HYDROGEN ADSORBING TO AMORPHOUS WATER ICE: DEFINING ADSORPTION IN CLASSICAL MOLECULAR DYNAMICS

    Energy Technology Data Exchange (ETDEWEB)

    Dupuy, John L.; Lewis, Steven P.; Stancil, P. C. [Department of Physics and Astronomy and the Center for Simulational Physics, University of Georgia, Athens, GA 30602 (United States)

    2016-11-01

    Gas–grain and gas–phase reactions dominate the formation of molecules in the interstellar medium (ISM). Gas–grain reactions require a substrate (e.g., a dust or ice grain) on which the reaction is able to occur. The formation of molecular hydrogen (H{sub 2}) in the ISM is the prototypical example of a gas–grain reaction. In these reactions, an atom of hydrogen will strike a surface, stick to it, and diffuse across it. When it encounters another adsorbed hydrogen atom, the two can react to form molecular hydrogen and then be ejected from the surface by the energy released in the reaction. We perform in-depth classical molecular dynamics simulations of hydrogen atoms interacting with an amorphous water-ice surface. This study focuses on the first step in the formation process; the sticking of the hydrogen atom to the substrate. We find that careful attention must be paid in dealing with the ambiguities in defining a sticking event. The technical definition of a sticking event will affect the computed sticking probabilities and coefficients. Here, using our new definition of a sticking event, we report sticking probabilities and sticking coefficients for nine different incident kinetic energies of hydrogen atoms [5–400 K] across seven different temperatures of dust grains [10–70 K]. We find that probabilities and coefficients vary both as a function of grain temperature and incident kinetic energy over the range of 0.99–0.22.

  18. Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Paul J Leo

    2017-08-01

    Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

  19. Ten Year Study of the Stringently Defined Otitis Prone Child in Rochester, NY

    Science.gov (United States)

    Pichichero, Michael E.

    2016-01-01

    This review summarizes a prospective, longitudinal 10-year study in Rochester NY with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently-defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often RSV infection led to AOM in sOP than non-otitis prone (NOP) children that correlated with diminished total RSV-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following NP colonization and AOM than NOP children and they had defects in antigen presenting cells. PMID:27273691

  20. Defining a Bobath clinical framework - A modified e-Delphi study.

    Science.gov (United States)

    Vaughan-Graham, Julie; Cott, Cheryl

    2016-11-01

    To gain consensus within the expert International Bobath Instructors Training Association (IBITA) on a Bobath clinical framework on which future efficacy studies can be based. A three-round modified e-Delphi approach was used with 204 full members of the IBITA. Twenty-one initial statements were generated from the literature. Consensus was defined a priori as at least 80% of the respondents with a level of agreement on a Likert scale of 4 or 5. The Delphi questionnaire for each round was available online for two weeks. Summary reports and subsequent questionnaires were posted within four weeks. Ninety-four IBITA members responded, forming the Delphi panel, of which 68 and 66 responded to Rounds Two and Three, respectively. The 21 initial statements were revised to 17 statements and five new statements in Round Two in which eight statements were accepted and two statements were eliminated. Round Three presented 12 revised statements, all reaching consensus. The Delphi was successful in gaining consensus on a Bobath clinical framework in a geographically diverse expert association, identifying the unique components of Bobath clinical practice. Discussion throughout all three Rounds revolved primarily around the terminology of atypical and compensatory motor behavior and balance.

  1. Defining a Leader Role curriculum for radiation oncology: A global Delphi consensus study.

    Science.gov (United States)

    Turner, Sandra; Seel, Matthew; Trotter, Theresa; Giuliani, Meredith; Benstead, Kim; Eriksen, Jesper G; Poortmans, Philip; Verfaillie, Christine; Westerveld, Henrike; Cross, Shamira; Chan, Ming-Ka; Shaw, Timothy

    2017-05-01

    The need for radiation oncologists and other radiation oncology (RO) professionals to lead quality improvement activities and contribute to shaping the future of our specialty is self-evident. Leadership knowledge, skills and behaviours, like other competencies, can be learned (Blumenthal et al., 2012). The objective of this study was to define a globally applicable competency set specific to radiation oncology for the CanMEDS Leader Role (Frank et al., 2015). A modified Delphi consensus process delivering two rounds of on-line surveys was used. Participants included trainees, radiation/clinical oncologists and other RO team members (radiation therapists, physicists, and nurses), professional educators and patients. 72 of 95 (76%) invitees from nine countries completed the Round 1 (R1) survey. Of the 72 respondents to RI, 70 completed Round 2 (R2) (97%). In R1, 35 items were deemed for 'inclusion' and 21 for 'exclusion', leaving 41 'undetermined'. After review of items, informed by participant comments, 14 competencies from the 'inclusion' group went into the final curriculum; 12 from the 'undetermined' group went to R2. In R2, 6 items reached consensus for inclusion. This process resulted in 20 RO Leader Role competencies with apparent global applicability. This is the first step towards developing learning, teaching and assessment tools for this important area of training. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. (Glyco)sphingolipids are sorted in sub-apical compartments in HepG2 cells : A role for non-Golgi-related intracellular sites in the polarized distribution of (glyco)sphingolipids

    NARCIS (Netherlands)

    van IJzendoorn, SCD; Hoekstra, D

    1998-01-01

    In polarized HepG2 cells, the fluorescent sphingolipid analogues of glucosylceramide (C-6-NBD-GlcCer) and sphingomyelin (C-6-NBD-SM) display a preferential localization at the apical and basolateral domain, respectively, which is expressed during apical to basolateral transcytosis of the lipids (van

  3. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  4. Defining the Simulation Technician Role: Results of a Survey-Based Study.

    Science.gov (United States)

    Bailey, Rachel; Taylor, Regina G; FitzGerald, Michael R; Kerrey, Benjamin T; LeMaster, Thomas; Geis, Gary L

    2015-10-01

    In health care simulation, simulation technicians perform multiple tasks to support various educational offerings. Technician responsibilities and the tasks that accompany them seem to vary between centers. The objectives were to identify the range and frequency of tasks that technicians perform and to determine if there is a correspondence between what technicians do and what they feel their responsibilities should be. We hypothesized that there is a core set of responsibilities and tasks for the technician position regardless of background, experience, and type of simulation center. We conducted a prospective, survey-based study of individuals currently functioning in a simulation technician role in a simulation center. This survey was designed internally and piloted within 3 academic simulation centers. Potential respondents were identified through a national mailing list, and the survey was distributed electronically during a 3-week period. A survey request was sent to 280 potential participants, 136 (49%) responded, and 73 met inclusion criteria. Five core tasks were identified as follows: equipment setup and breakdown, programming scenarios into software, operation of software during simulation, audiovisual support for courses, and on-site simulator maintenance. Independent of background before they were hired, technicians felt unprepared for their role once taking the position. Formal training was identified as a need; however, the majority of technicians felt experience over time was the main contributor toward developing knowledge and skills within their role. This study represents a first step in defining the technician role within simulation-based education and supports the need for the development of a formal job description to allow recruitment, development, and certification.

  5. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions

    Science.gov (United States)

    Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G.; Módos, Károly; Kardos, József; Liliom, Károly

    2010-01-01

    Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin–sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well.—Kovacs, E., Harmat, V., Tóth, J., Vértessy, B. G., Módos, K., Kardos, J., Liliom, K. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions. PMID:20522785

  6. Violent crime exposure classification and adverse birth outcomes: a geographically-defined cohort study

    Directory of Open Access Journals (Sweden)

    Herring Amy

    2006-05-01

    Full Text Available Abstract Background Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the reproductive and public health literature. When crime has been used in research, it has been variably defined, resulting in non-comparable associations across studies. Methods Using geocoded linked birth record, crime and census data in multilevel models, this paper explored the relevance of four spatial violent crime exposures: two proximal violent crime categorizations (count of violent crime within a one-half mile radius of maternal residence and distance from maternal residence to nearest violent crime and two area-level crime categorizations (count of violent crimes within a block group and block group rate of violent crimes for adverse birth events among women in living in the city of Raleigh NC crime report area in 1999–2001. Models were adjusted for maternal age and education and area-level deprivation. Results In black and white non-Hispanic race-stratified models, crime characterized as a proximal exposure was not able to distinguish between women experiencing adverse and women experiencing normal birth outcomes. Violent crime characterized as a neighborhood attribute was positively associated with preterm birth and low birth weight among non-Hispanic white and black women. No statistically significant interaction between area-deprivation and violent crime category was observed. Conclusion Crime is variably categorized in the literature, with little rationale provided for crime type or categorization employed. This research represents the first time multiple crime categorizations have been directly compared in association with health outcomes. Finding an effect of area-level violent crime suggests crime may best be characterized as a neighborhood attribute with important implication for adverse birth outcomes.

  7. Defining degree of aortic occlusion for partial-REBOA: A computed tomography study on large animals.

    Science.gov (United States)

    Reva, Viktor A; Matsumura, Yosuke; Samokhvalov, Igor M; Pochtarnik, Alexander A; Zheleznyak, Igor S; Mikhailovskaya, Ekaterina M; Morrison, Jonathan J

    2018-04-20

    Partial resuscitative endovascular balloon occlusion of the aorta (P-REBOA) is a modified REBOA technique designed to help ameliorate ischemia-reperfusion injury. The balloon is partially deflated, allowing a proportion of aortic flow distal to the balloon. The aim of this study is to use an ovine model of haemorrhagic shock to correlate the degree of occlusion to several hemodynamic indices. Six sheep weighing 35-46 kg underwent a controlled venous haemorrhage inside a CT scanner until the systolic arterial pressure (AP) dropped to fashion (proximal: r 2  = 0.85, p trend (r 2  = 0.90, p < 0.001). The relationship between percentage occlusion and IBP was sigmoid. MAP values became significantly different at 40-49% occlusion and more (p < 0.01). Furthermore, a drop in the distal pulse pressure from 7.0 (5.5-16.5) to 2.0 (1.5-5.0) mmHg was observed at 80% occlusion. All animals had femoral pulse pressure <5 mmHg at 80% of occlusion and more, which also coincided with the observed loss of pulsatility of the femoral wave-form. Serial CT angiography at an ovine model of haemorrhagic shock demonstrates a correlation between the femoral MAP, F/C pressure gradient and degree of zone I P-REBOA during the staged partial aortic occlusion. These parameters should be considered potential parameters to define the degree of P-REBOA during animal research and clinical practice. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Defining disease phenotypes using national linked electronic health records: a case study of atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Katherine I Morley

    Full Text Available National electronic health records (EHR are increasingly used for research but identifying disease cases is challenging due to differences in information captured between sources (e.g. primary and secondary care. Our objective was to provide a transparent, reproducible model for integrating these data using atrial fibrillation (AF, a chronic condition diagnosed and managed in multiple ways in different healthcare settings, as a case study.Potentially relevant codes for AF screening, diagnosis, and management were identified in four coding systems: Read (primary care diagnoses and procedures, British National Formulary (BNF; primary care prescriptions, ICD-10 (secondary care diagnoses and OPCS-4 (secondary care procedures. From these we developed a phenotype algorithm via expert review and analysis of linked EHR data from 1998 to 2010 for a cohort of 2.14 million UK patients aged ≥ 30 years. The cohort was also used to evaluate the phenotype by examining associations between incident AF and known risk factors.The phenotype algorithm incorporated 286 codes: 201 Read, 63 BNF, 18 ICD-10, and four OPCS-4. Incident AF diagnoses were recorded for 72,793 patients, but only 39.6% (N = 28,795 were recorded in primary care and secondary care. An additional 7,468 potential cases were inferred from data on treatment and pre-existing conditions. The proportion of cases identified from each source differed by diagnosis age; inferred diagnoses contributed a greater proportion of younger cases (≤ 60 years, while older patients (≥ 80 years were mainly diagnosed in SC. Associations of risk factors (hypertension, myocardial infarction, heart failure with incident AF defined using different EHR sources were comparable in magnitude to those from traditional consented cohorts.A single EHR source is not sufficient to identify all patients, nor will it provide a representative sample. Combining multiple data sources and integrating information on treatment and

  9. Define Project

    DEFF Research Database (Denmark)

    Munk-Madsen, Andreas

    2005-01-01

    "Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

  10. "Dermatitis" defined.

    Science.gov (United States)

    Smith, Suzanne M; Nedorost, Susan T

    2010-01-01

    The term "dermatitis" can be defined narrowly or broadly, clinically or histologically. A common and costly condition, dermatitis is underresourced compared to other chronic skin conditions. The lack of a collectively understood definition of dermatitis and its subcategories could be the primary barrier. To investigate how dermatologists define the term "dermatitis" and determine if a consensus on the definition of this term and other related terms exists. A seven-question survey of dermatologists nationwide was conducted. Of respondents (n  =  122), half consider dermatitis to be any inflammation of the skin. Nearly half (47.5%) use the term interchangeably with "eczema." Virtually all (> 96%) endorse the subcategory "atopic" under the terms "dermatitis" and "eczema," but the subcategories "contact," "drug hypersensitivity," and "occupational" are more highly endorsed under the term "dermatitis" than under the term "eczema." Over half (55.7%) personally consider "dermatitis" to have a broad meaning, and even more (62.3%) believe that dermatologists as a whole define the term broadly. There is a lack of consensus among experts in defining dermatitis, eczema, and their related subcategories.

  11. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

    Science.gov (United States)

    Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

    2014-01-01

    As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

  12. The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marcus O. W. Grimm

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is a devastating neurodegenerative disorder currently affecting over 35 million people worldwide. Pathological hallmarks of AD are massive amyloidosis, extracellular senile plaques, and intracellular neurofibrillary tangles accompanied by an excessive loss of synapses. Major constituents of senile plaques are 40–42 amino acid long peptides termed β-amyloid (Aβ. Aβ is produced by sequential proteolytic processing of the amyloid precursor protein (APP. APP processing and Aβ production have been one of the central scopes in AD research in the past. In the last years, lipids and lipid-related issues are more frequently discussed to contribute to the AD pathogenesis. This review summarizes lipid alterations found in AD postmortem brains, AD transgenic mouse models, and the current understanding of how lipids influence the molecular mechanisms leading to AD and Aβ generation, focusing especially on cholesterol, docosahexaenoic acid (DHA, and sphingolipids/glycosphingolipids.

  13. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

    DEFF Research Database (Denmark)

    Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

    2009-01-01

    The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...... trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN...... than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery....

  14. Defining health-related quality of life for young wheelchair users: A qualitative health economics study.

    Directory of Open Access Journals (Sweden)

    Nathan Bray

    Full Text Available Wheelchairs for children with impaired mobility provide health, developmental and psychosocial benefits, however there is limited understanding of how mobility aids affect the health-related quality of life of children with impaired mobility. Preference-based health-related quality of life outcome measures are used to calculate quality-adjusted life years; an important concept in health economics. The aim of this research was to understand how young wheelchair users and their parents define health-related quality of life in relation to mobility impairment and wheelchair use.The sampling frame was children with impaired mobility (≤18 years who use a wheelchair and their parents. Data were collected through semi-structured face-to-face interviews conducted in participants' homes. Qualitative framework analysis was used to analyse the interview transcripts. An a priori thematic coding framework was developed. Emerging codes were grouped into categories, and refined into analytical themes. The data were used to build an understanding of how children with impaired mobility define health-related quality of life in relation to mobility impairment, and to assess the applicability of two standard measures of health-related quality of life.Eleven children with impaired mobility and 24 parents were interviewed across 27 interviews. Participants defined mobility-related quality of life through three distinct but interrelated concepts: 1 participation and positive experiences; 2 self-worth and feeling fulfilled; 3 health and functioning. A good degree of consensus was found between child and parent responses, although there was some evidence to suggest a shift in perception of mobility-related quality of life with child age.Young wheelchair users define health-related quality of life in a distinct way as a result of their mobility impairment and adaptation use. Generic, preference-based measures of health-related quality of life lack sensitivity in this

  15. Toward defining and measuring social accountability in graduate medical education: a stakeholder study.

    Science.gov (United States)

    Reddy, Anjani T; Lazreg, Sonia A; Phillips, Robert L; Bazemore, Andrew W; Lucan, Sean C

    2013-09-01

    Since 1965, Medicare has publically financed graduate medical education (GME) in the United States. Given public financing, various advisory groups have argued that GME should be more socially accountable. Several efforts are underway to develop accountability measures for GME that could be tied to Medicare payments, but it is not clear how to measure or even define social accountability. We explored how GME stakeholders perceive, define, and measure social accountability. Through purposive and snowball sampling, we completed semistructured interviews with 18 GME stakeholders from GME training sites, government agencies, and health care organizations. We analyzed interview field notes and audiorecordings using a flexible, iterative, qualitative group process to identify themes. THREE THEMES EMERGED IN REGARDS TO DEFINING SOCIAL ACCOUNTABILITY: (1) creating a diverse physician workforce to address regional needs and primary care and specialty shortages; (2) ensuring quality in training and care to best serve patients; and (3) providing service to surrounding communities and the general public. All but 1 stakeholder believed GME institutions have a responsibility to be socially accountable. Reported barriers to achieving social accountability included training time constraints, financial limitations, and institutional resistance. Suggestions for measuring social accountability included reviewing graduates' specialties and practice locations, evaluating curricular content, and reviewing program services to surrounding communities. Most stakeholders endorsed the concept of social accountability in GME, suggesting definitions and possible measures that could inform policy makers calls for increased accountability despite recognized barriers.

  16. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    International Nuclear Information System (INIS)

    Kamendi, Harriet; Zhou, Ying; Crosby, Meredith; Keirstead, Natalie; Snow, Debra; Bentley, Patricia; Patel, Nilaben; Barthlow, Herbert; Luo, Wenli; Dragan, Yvonne; Bialecki, Russell

    2015-01-01

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  17. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Zhou, Ying, E-mail: yingzhou526@gmail.com [Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA 02451 (United States); Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Keirstead, Natalie, E-mail: Nkeirstead@alnylam.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Snow, Debra, E-mail: Debra.snow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bentley, Patricia, E-mail: patricia.bentley@abbvie.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Patel, Nilaben, E-mail: patelnilaben@yahoo.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Barthlow, Herbert, E-mail: Herbert.barthlow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Luo, Wenli, E-mail: Wenli.luo@astrazeneca.com [Discovery Sciences, Innovative Medicines, AstraZeneca, Waltham, MA 02451 (United States); Dragan, Yvonne, E-mail: Yvonne.P.Dragan@takeda.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States)

    2015-12-15

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  18. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

    OpenAIRE

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho

    2015-01-01

    Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 contr...

  19. Definably compact groups definable in real closed fields. I

    OpenAIRE

    Barriga, Eliana

    2017-01-01

    We study definably compact definably connected groups definable in a sufficiently saturated real closed field $R$. We introduce the notion of group-generic point for $\\bigvee$-definable groups and show the existence of group-generic points for definably compact groups definable in a sufficiently saturated o-minimal expansion of a real closed field. We use this notion along with some properties of generic sets to prove that for every definably compact definably connected group $G$ definable in...

  20. Defining chaos.

    Science.gov (United States)

    Hunt, Brian R; Ott, Edward

    2015-09-01

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call "expansion entropy," and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  1. Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population

    Directory of Open Access Journals (Sweden)

    Wilmar Igl

    2013-08-01

    Full Text Available Background . The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. Objective . To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. Study design . We compared a group with traditional lifestyle (TLS based on reindeer herding (TLS group with those from the same area with a non-traditional lifestyle (NTLS typical of more industrialized regions of Sweden (NTLS group. The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs and the serum blood level of a number of lipids [total cholesterol (TC, low-density lipoprotein cholesterol (LDL, high-density lipoprotein cholesterol (HDL, triglycerides (TG, glycerophospholipids and sphingolipids]. Results . The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥240 mg/dl, as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. Conclusions . The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

  2. Defining Cyberbullying.

    Science.gov (United States)

    Englander, Elizabeth; Donnerstein, Edward; Kowalski, Robin; Lin, Carolyn A; Parti, Katalin

    2017-11-01

    Is cyberbullying essentially the same as bullying, or is it a qualitatively different activity? The lack of a consensual, nuanced definition has limited the field's ability to examine these issues. Evidence suggests that being a perpetrator of one is related to being a perpetrator of the other; furthermore, strong relationships can also be noted between being a victim of either type of attack. It also seems that both types of social cruelty have a psychological impact, although the effects of being cyberbullied may be worse than those of being bullied in a traditional sense (evidence here is by no means definitive). A complicating factor is that the 3 characteristics that define bullying (intent, repetition, and power imbalance) do not always translate well into digital behaviors. Qualities specific to digital environments often render cyberbullying and bullying different in circumstances, motivations, and outcomes. To make significant progress in addressing cyberbullying, certain key research questions need to be addressed. These are as follows: How can we define, distinguish between, and understand the nature of cyberbullying and other forms of digital conflict and cruelty, including online harassment and sexual harassment? Once we have a functional taxonomy of the different types of digital cruelty, what are the short- and long-term effects of exposure to or participation in these social behaviors? What are the idiosyncratic characteristics of digital communication that users can be taught? Finally, how can we apply this information to develop and evaluate effective prevention programs? Copyright © 2017 by the American Academy of Pediatrics.

  3. Defining the impact of hemophilia: the Academic Achievement in Children with Hemophilia Study.

    Science.gov (United States)

    Shapiro, A D; Donfield, S M; Lynn, H S; Cool, V A; Stehbens, J A; Hunsberger, S L; Tonetta, S; Gomperts, E D

    2001-12-01

    We characterized a population-based cohort of school-aged children with severe hemophilia with respect to type of treatment, on-demand versus prophylaxis, and frequency of bleeding episodes in the year before enrollment. We also investigated the association between hemophilia-related morbidity, measured by number of bleeding episodes in the year before enrollment, and academic performance after adjustment for other factors known to have an effect on achievement. Finally, we explored the mechanisms for the association between bleeding episodes and academic achievement. This study was a multicenter investigation of boys 6 to 12 years old with severe factor VIII deficiency (clotting factor level 2 months with a goal of preventing bleeding episodes. Academic achievement was measured by the Wechsler Individual Achievement Test. Quality of life was measured by the Child Health Questionnaire. Of particular interest was the Physical Summary (PhS) measure of the Child Health Questionnaire. The type of information captured by the PhS includes limitations in physical activity, limitations in the kind or amount of schoolwork or social activities the child engaged in, and presence of pain or discomfort. One hundred thirty-one children were enrolled, a median center recruitment rate of 77%. The mean age of the participants was 9.6 years, and approximately half of the participants had completed less than the fourth grade at the time of enrollment. Sixty-two percent of the children were on prophylaxis at enrollment, and 9% had previously been on prophylaxis but were currently on on-demand therapy. Two groups were defined: ever treated with prophylaxis and never treated with prophylaxis. For those ever treated, treatment duration ranged from 2.7 months to 7.7 years, with one half of the children treated with prophylaxis for >40% of their lifetimes; 29% had always been on on-demand therapy. Children in both treatment groups were similar with respect to age, clotting factor level

  4. Identification of Two Suppressors of CSG2 Calcium Sensitivity, SCS7 and SUR2, as Genes Encoding Hydroxylases of the Sphingolipid Biosynthetic Pathway of Saccharomyces cerevisiae

    National Research Council Canada - National Science Library

    Haak, Dale A

    1997-01-01

    .... The biochemical significance of much of this structural variability is not well understood. The sphingolipids of the yeast Saccharomyces cerevisiae undergo the a-hydroxylation of the very long chain fatty acid (VLCFA...

  5. Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

    Directory of Open Access Journals (Sweden)

    Jian-Jun Liu

    2017-05-01

    Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.

  6. Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population.

    Science.gov (United States)

    Igl, Wilmar; Kamal-Eldin, Afaf; Johansson, Asa; Liebisch, Gerhard; Gnewuch, Carsten; Schmitz, Gerd; Gyllensten, Ulf

    2013-01-01

    The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥ 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

  7. Probabilistic-Multiobjective Comparison of User-Defined Operating Rules. Case Study: Hydropower Dam in Spain

    Directory of Open Access Journals (Sweden)

    Paola Bianucci

    2015-03-01

    Full Text Available A useful tool is proposed in this paper to assist dam managers in comparing and selecting suitable operating rules. This procedure is based on well-known multiobjective and probabilistic methodologies, which were jointly applied here to assess and compare flood control strategies in hydropower reservoirs. The procedure consisted of evaluating the operating rules’ performance using a simulation fed by a representative and sufficiently large flood event series. These flood events were obtained from a synthetic rainfall series stochastically generated by using the RainSimV3 model coupled with a deterministic hydrological model. The performance of the assessed strategies was characterized using probabilistic variables. Finally, evaluation and comparison were conducted by analyzing objective functions which synthesize different aspects of the rules’ performance. These objectives were probabilistically defined in terms of risk and expected values. To assess the applicability and flexibility of the tool, it was implemented in a hydropower dam located in Galicia (Northern Spain. This procedure allowed alternative operating rule to be derived which provided a reasonable trade-off between dam safety, flood control, operability and energy production.

  8. Genome-wide association studies of mri-defined brain infarcts: Meta-analysis from the charge consortium

    NARCIS (Netherlands)

    S. Debette (Stéphanie); J.C. Bis (Joshua); M. Fornage (Myriam); H.A. Schmid (Herbert); M.A. Ikram (Arfan); S. Sigurdsson (Stefan); G. Heiss (Gerardo); M.V. Struchalin (Maksim); A.V. Smith (Albert Vernon); A. van der Lugt (Aad); C. DeCarli (Charles); T. Lumley (Thomas); D.S. Knopman (David); C. Enzinger (Christian); G. Eiriksdottir (Gudny); P.J. Koudstaal (Peter Jan); A.L. DeStefano (Anita); B.M. Psaty (Bruce); C. Dufouil (Carole); D.J. Catellier (Diane); F. Fazekas (Franz); T. Aspelund (Thor); Y.S. Aulchenko (Yurii); A. Beiser (Alexa); J.I. Rotter (Jerome); C. Tzourio (Christophe); D.K. Shibata (Dean); M. Tscherner (Maria); T.B. Harris (Tamara); F. Rivadeneira Ramirez (Fernando); L.D. Atwood (Larry); K. Rice (Kenneth); R.F. Gottesman (Rebecca); M.A. van Buchem (Mark); A.G. Uitterlinden (André); M. Kelly-Hayes (Margaret); M. Cushman (Mary Ann); Y. Zhu (Yicheng); E.A. Boerwinkle (Eric); V. Gudnason (Vilmundur); A. Hofman (Albert); J.R. Romero (Jose Rafael); M.M.B. Breteler (Monique); R. Schmidt (Reinhold); L.J. Launer (Lenore); W.T. Longstreth Jr

    2010-01-01

    textabstractBackground and Purpose-Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed

  9. Defining greed.

    Science.gov (United States)

    Seuntjens, Terri G; Zeelenberg, Marcel; Breugelmans, Seger M; van de Ven, Niels

    2015-08-01

    Although greed is both hailed as the motor of economic growth and blamed as the cause of economic crises, very little is known about its psychological underpinnings. Five studies explored lay conceptualizations of greed among U.S. and Dutch participants using a prototype analysis. Study 1 identified features related to greed. Study 2 determined the importance of these features; the most important features were classified as central (e.g., self-interested, never satisfied), whereas less important features were classified as peripheral (e.g., ambition, addiction). Subsequently, we found that, compared to peripheral features, participants recalled central features better (Study 3), faster (Study 4), and these central features were more present in real-life episodes of greed (Study 5). These findings provide a better understanding of the elements that make up the experience of greed and provide insights into how greed can be manipulated and measured in future research. © 2014 The British Psychological Society.

  10. Do Sex Differences Define Gender-Related Individual Differences within the Sexes? Evidence from Three Studies.

    Science.gov (United States)

    Lippa, Richard

    1995-01-01

    Studied three different criteria of within-sex, gender-related individual differences taken from three studies. Data showed that items displaying large sex differences tended also to correlate most strongly with independent gender-related criteria within the sexes. Discusses assessment implications for gender-related and other group-related…

  11. Defining greed

    NARCIS (Netherlands)

    Seuntjens, Terri G.; Zeelenberg, Marcel; Breugelmans, Seger M.; van de Ven, Niels

    2015-01-01

    Although greed is both hailed as the motor of economic growth and blamed as the cause of economic crises, very little is known about its psychological underpinnings. Five studies explored lay conceptualizations of greed among US and Dutch participants using a prototype analysis. Study 1 identified

  12. Defining principles for good practice: using case studies to inform health systems action on health inequalities.

    Science.gov (United States)

    Simpson, Sarah; Kelly, Michael P; Morgan, Antony

    2013-02-01

    This paper presents work using case studies as a source of data to see if we could extrapolate from the specific to the general particularly with regard to understanding what constitutes effective practice in taking action on SDHI and as a way of enabling policy makers to make better use of knowledge within the case studies and as a way of better understanding what works, in what context and why. Case studies are important to evaluators in that they are relatively straightforward to undertake and because those involved in implementing an intervention are usually keen to profile the intervention. A checklist described in this paper will enable policy advisers and evaluators to quickly review a case study and right away see if it contains enough information to assist in the development of policy options for reducing socially determined health inequalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. A framework for prospectively defining progression rules for internal pilot studies monitoring recruitment.

    Science.gov (United States)

    Hampson, Lisa V; Williamson, Paula R; Wilby, Martin J; Jaki, Thomas

    2017-01-01

    Just over half of publicly funded trials recruit their target sample size within the planned study duration. When recruitment targets are missed, the funder of a trial is faced with the decision of either committing further resources to the study or risk that a worthwhile treatment effect may be missed by an underpowered final analysis. To avoid this challenging situation, when there is insufficient prior evidence to support predicted recruitment rates, funders now require feasibility assessments to be performed in the early stages of trials. Progression criteria are usually specified and agreed with the funder ahead of time. To date, however, the progression rules used are typically ad hoc. In addition, rules routinely permit adaptations to recruitment strategies but do not stipulate criteria for evaluating their effectiveness. In this paper, we develop a framework for planning and designing internal pilot studies which permit a trial to be stopped early if recruitment is disappointing or to continue to full recruitment if enrolment during the feasibility phase is adequate. This framework enables a progression rule to be pre-specified and agreed upon prior to starting a trial. The novel two-stage designs stipulate that if neither of these situations arises, adaptations to recruitment should be made and subsequently evaluated to establish whether they have been successful. We derive optimal progression rules for internal pilot studies which minimise the expected trial overrun and maintain a high probability of completing the study when the recruitment rate is adequate. The advantages of this procedure are illustrated using a real trial example.

  14. Re-defining one's occupational self 2 years after breast cancer: a case study.

    Science.gov (United States)

    Newman, Robin M

    2013-01-01

    Margaret*, a 56 year-old Caucasian Stage III breast cancer survivor, participated in a 5 week occupational therapy pilot program, called Take Action. This program was designed for breast cancer survivors who self-reported changes in cognitive function following completion of chemotherapy. The goals of the program were to improve participants' knowledge and use of strategies to enhance occupational performance and to improve satisfaction and performance of meaningful daily activities or occupations. Through a client-centered and evidence-based approach, this case study highlights the importance of incorporating the survivors' sense of self into an occupation-based intervention. Occupational therapists play an important role in facilitating exploration of sense of self in the survivorship phase of care to support occupational performance in self care, productivity, work, leisure and social participation. This case study highlights the important work of redefining oneself in the survivorship phase of care. (*denotes name change).

  15. What defines an effective anti-tobacco TV advertisement? A pilot study among Greek adolescents.

    Science.gov (United States)

    Vardavas, Constantine I; Symvoulakis, Emmanouil K; Connolly, Gregory N; Patelarou, Evridiki; Lionis, Christos

    2010-01-01

    As the Framework Convention on Tobacco Control (FCTC) calls for public health awareness on tobacco use, mass media campaigns should be appropriately designed so as to maximize their effectiveness. In this methodological pilot study, 95 Greek adolescents (mean age 15 +/- 1.8 years), were shown seven different anti tobacco ads, and asked to rate the ad theme, message and emotional context on a 1-7 Likert scale. Health related ads were rated the highest, and as identified through the logistic regression analysis, adolescents who perceived an ad to be emotional or to have a clear message that was relevant to them, were more likely to rate the ad as more effective. The strong agreement between the above findings and the existing literature indicates the applicability of this pilot study's methodological approach.

  16. Does the Reporting Quality of Diagnostic Test Accuracy Studies, as Defined by STARD 2015, Affect Citation?

    Science.gov (United States)

    Choi, Young Jun; Chung, Mi Sun; Koo, Hyun Jung; Park, Ji Eun; Yoon, Hee Mang; Park, Seong Ho

    2016-01-01

    To determine the rate with which diagnostic test accuracy studies that are published in a general radiology journal adhere to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015, and to explore the relationship between adherence rate and citation rate while avoiding confounding by journal factors. All eligible diagnostic test accuracy studies that were published in the Korean Journal of Radiology in 2011-2015 were identified. Five reviewers assessed each article for yes/no compliance with 27 of the 30 STARD 2015 checklist items (items 28, 29, and 30 were excluded). The total STARD score (number of fulfilled STARD items) was calculated. The score of the 15 STARD items that related directly to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 was also calculated. The number of times each article was cited (as indicated by the Web of Science) after publication until March 2016 and the article exposure time (time in months between publication and March 2016) were extracted. Sixty-three articles were analyzed. The mean (range) total and QUADAS-2-related STARD scores were 20.0 (14.5-25) and 11.4 (7-15), respectively. The mean citation number was 4 (0-21). Citation number did not associate significantly with either STARD score after accounting for exposure time (total score: correlation coefficient = 0.154, p = 0.232; QUADAS-2-related score: correlation coefficient = 0.143, p = 0.266). The degree of adherence to STARD 2015 was moderate for this journal, indicating that there is room for improvement. When adjusted for exposure time, the degree of adherence did not affect the citation rate.

  17. Dose the reporting quality of diagnostic test accuracy studies, as defined by STARD 2015, affect citation?

    International Nuclear Information System (INIS)

    Choi, Young Jun; Chung, Mi Sun; Koo, Hyun Jung; Park, Ji Eun; Yoon, Hee Mang; Park, Seong Ho

    2016-01-01

    To determine the rate with which diagnostic test accuracy studies that are published in a general radiology journal adhere to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015, and to explore the relationship between adherence rate and citation rate while avoiding confounding by journal factors. All eligible diagnostic test accuracy studies that were published in the Korean Journal of Radiology in 2011–2015 were identified. Five reviewers assessed each article for yes/no compliance with 27 of the 30 STARD 2015 checklist items (items 28, 29, and 30 were excluded). The total STARD score (number of fulfilled STARD items) was calculated. The score of the 15 STARD items that related directly to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 was also calculated. The number of times each article was cited (as indicated by the Web of Science) after publication until March 2016 and the article exposure time (time in months between publication and March 2016) were extracted. Sixty-three articles were analyzed. The mean (range) total and QUADAS-2-related STARD scores were 20.0 (14.5–25) and 11.4 (7–15), respectively. The mean citation number was 4 (0–21). Citation number did not associate significantly with either STARD score after accounting for exposure time (total score: correlation coefficient = 0.154, p = 0.232; QUADAS-2-related score: correlation coefficient = 0.143, p = 0.266). The degree of adherence to STARD 2015 was moderate for this journal, indicating that there is room for improvement. When adjusted for exposure time, the degree of adherence did not affect the citation rate

  18. Dose the reporting quality of diagnostic test accuracy studies, as defined by STARD 2015, affect citation?

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Jun; Chung, Mi Sun; Koo, Hyun Jung; Park, Ji Eun; Yoon, Hee Mang; Park, Seong Ho [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2016-09-15

    To determine the rate with which diagnostic test accuracy studies that are published in a general radiology journal adhere to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015, and to explore the relationship between adherence rate and citation rate while avoiding confounding by journal factors. All eligible diagnostic test accuracy studies that were published in the Korean Journal of Radiology in 2011–2015 were identified. Five reviewers assessed each article for yes/no compliance with 27 of the 30 STARD 2015 checklist items (items 28, 29, and 30 were excluded). The total STARD score (number of fulfilled STARD items) was calculated. The score of the 15 STARD items that related directly to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 was also calculated. The number of times each article was cited (as indicated by the Web of Science) after publication until March 2016 and the article exposure time (time in months between publication and March 2016) were extracted. Sixty-three articles were analyzed. The mean (range) total and QUADAS-2-related STARD scores were 20.0 (14.5–25) and 11.4 (7–15), respectively. The mean citation number was 4 (0–21). Citation number did not associate significantly with either STARD score after accounting for exposure time (total score: correlation coefficient = 0.154, p = 0.232; QUADAS-2-related score: correlation coefficient = 0.143, p = 0.266). The degree of adherence to STARD 2015 was moderate for this journal, indicating that there is room for improvement. When adjusted for exposure time, the degree of adherence did not affect the citation rate.

  19. Defining sustainable practice in community-based health promotion: a Delphi study of practitioner perspectives.

    Science.gov (United States)

    Harris, Neil; Sandor, Maria

    2013-04-01

    Sustainability of practice must be a central imperative in the practice of community-based health promotion to achieve population health and attract a greater share of public health spending. Although there has been some consideration of sustainability at the project or program levels, often understood as intervention longevity, very limited attention has been given to understanding sustainable practice. The present study develops a definition and features of sustainable practice in community-based health promotion through a Delphi method with health promotion practitioners in Queensland, Australia. The study presents a consensus definition and features of sustainable practice. The definition highlights the importance of collaboration, health determinants and aspirations, processes and outcomes. The four features of sustainable practice identified in the study are: (1) effective relationships and partnerships; (2) evidence-based decision making and practice; (3) emphasis on building community capacity; and (4) supportive context for practice. The definition and features are, to a large extent, consistent with the limited literature around sustainability at the project and program levels of health promotion. Together, they provide insight into a form of community-based health promotion that will be both viable and productive. So what? This consensus understanding of sustainable practice articulates the foundations of working effectively with local communities in achieving improved population health within global limits.

  20. Defining and Estimating Healthy Aging in Spain: A Cross-sectional Study.

    Science.gov (United States)

    Rodriguez-Laso, Angel; McLaughlin, Sara J; Urdaneta, Elena; Yanguas, Javier

    2018-03-19

    Using an operational continuum of healthy aging developed by U.S. researchers, we sought to estimate the prevalence of healthy aging among older Spaniards, inform the development of a definition of healthy aging in Spain, and foster cross-national research on healthy aging. The ELES pilot study is a nationwide, cross-sectional survey of community-dwelling Spaniards 50 years and older. The prevalence of healthy aging was calculated for the 65 and over population using varying definitions. To evaluate their validity, we examined the association of healthy aging with the 8 foot up & go test, quality of life scores and self-perceived health using multiple linear and logistic regression. The estimated prevalence of healthy aging varied across the operational continuum, from 4.5% to 49.2%. Prevalence figures were greater for men and those aged 65 to 79 years and were higher than in the United States. Predicted mean physical performance scores were similar for 3 of the 4 definitions, suggesting that stringent definitions of healthy aging offer little advantage over a more moderate one. Similar to U.S. researchers, we recommend a definition of healthy aging that incorporates measures of functional health and limiting disease as opposed to definitions requiring the absence of all disease in studies designed to assess the effect of policy initiatives on healthy aging.

  1. Defining interdisciplinary competencies for audiological rehabilitation: findings from a modified Delphi study.

    Science.gov (United States)

    Xue, Lina; Le Bot, Gaëlle; Van Petegem, Wim; van Wieringen, Astrid

    2018-02-01

    The aim of this study is to derive a consensus on an interdisciplinary competency framework regarding a holistic approach for audiological rehabilitation (AR), which includes disciplines from medicine, engineering, social sciences and humanities. We employed a modified Delphi method. In the first round survey, experts were asked to rate an initial list of 28 generic interdisciplinary competencies and to propose specific knowledge areas for AR. In the second round, experts were asked to reconsider their answers in light of the group answers of the first round. An international panel of 27 experts from different disciplines in AR completed the first round. Twenty-two of them completed the second round. We developed a competency framework consisting of 21 generic interdisciplinary competencies grouped in five domains and nine specific competencies (knowledge areas) in three clusters. Suggestions for the implementation of the generic competencies in interdisciplinary programmes were identified. This study reveals insights into the interdisciplinary competencies that are unique for AR. The framework will be useful for educators in developing interdisciplinary programmes as well as for professionals in considering their lifelong training needs in AR.

  2. Defining a BMI Cut-Off Point for the Iranian Population: The Shiraz Heart Study.

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Babai

    Full Text Available In this study we evaluated and redefined the optimum body mass index (BMI cut-off point for the Iranian population based on metabolic syndrome (MeS risk factors. We further evaluated BMI cut-off points with and without waist circumference (WC as a cofactor of risk and compared the differences. This study is part of the largest surveillance programs conducted in Shiraz, Iran, termed the Shiraz Heart study. Our study sample included subjects between the ages of 20 to 65 years old. After excluding pregnant women, those with missing data and those with comorbid disease, a total of 12283 made up the study population. The participants underwent a series of tests and evaluations by trained professionals in accordance with WHO recommendations. Hypertension, abnormal fasting blood sugar (FBS, triglyceride (TG and high density lipoprotein cholesterol (HDL (in the context of the definition of metabolic syndrome were prevalent among 32.4%, 27.6%, 42.1 and 44.2% of our participants, respectively. Women displayed higher rates of overall obesity compared to men (based on the definition by the WHO as higher than 30 kg/m2. Regarding MeS, 38.9% of our population had the all symptoms of MeS which was more prevalent among women (41.5% vs. 36%. When excluding WC in the definition of MeS, results showed that males tend to show a higher rate of metabolic risk factors (19.2% vs. 15.6%. Results of multivariate analysis showed that parallel to an increase in BMI, the odds ratio (OR for acquiring each component of the metabolic syndrome increased (OR = 1.178; CI: 1.166-1.190. By excluding WC, the previous OR decreased (OR = 1.105; CI: 1.093-1.118. Receiver Operating Characteristic (ROC curve analysis showed that the optimum BMI cut-off point for predicting metabolic syndrome was 26.1 kg/m2 and 26.2 kg/m2 [Accuracy (Acc = 69% and 61%, respectively] for males and females, respectively. The overall BMI cut-off for both sexes was 26.2 kg/m2 (Acc = 65% with sensitivity and

  3. Switching industrial production processes from complex to defined media: method development and case study using the example of Penicillium chrysogenum.

    Science.gov (United States)

    Posch, Andreas E; Spadiut, Oliver; Herwig, Christoph

    2012-06-22

    Filamentous fungi are versatile cell factories and widely used for the production of antibiotics, organic acids, enzymes and other industrially relevant compounds at large scale. As a fact, industrial production processes employing filamentous fungi are commonly based on complex raw materials. However, considerable lot-to-lot variability of complex media ingredients not only demands for exhaustive incoming components inspection and quality control, but unavoidably affects process stability and performance. Thus, switching bioprocesses from complex to defined media is highly desirable. This study presents a strategy for strain characterization of filamentous fungi on partly complex media using redundant mass balancing techniques. Applying the suggested method, interdependencies between specific biomass and side-product formation rates, production of fructooligosaccharides, specific complex media component uptake rates and fungal strains were revealed. A 2-fold increase of the overall penicillin space time yield and a 3-fold increase in the maximum specific penicillin formation rate were reached in defined media compared to complex media. The newly developed methodology enabled fast characterization of two different industrial Penicillium chrysogenum candidate strains on complex media based on specific complex media component uptake kinetics and identification of the most promising strain for switching the process from complex to defined conditions. Characterization at different complex/defined media ratios using only a limited number of analytical methods allowed maximizing the overall industrial objectives of increasing both, method throughput and the generation of scientific process understanding.

  4. A Simulation Study of the Radiation-Induced Bystander Effect: Modeling with Stochastically Defined Signal Reemission

    Directory of Open Access Journals (Sweden)

    Kohei Sasaki

    2012-01-01

    Full Text Available The radiation-induced bystander effect (RIBE has been experimentally observed for different types of radiation, cell types, and cell culture conditions. However, the behavior of signal transmission between unirradiated and irradiated cells is not well known. In this study, we have developed a new model for RIBE based on the diffusion of soluble factors in cell cultures using a Monte Carlo technique. The model involves the signal emission probability from bystander cells following Poisson statistics. Simulations with this model show that the spatial configuration of the bystander cells agrees well with that of corresponding experiments, where the optimal emission probability is estimated through a large number of simulation runs. It was suggested that the most likely probability falls within 0.63–0.92 for mean number of the emission signals ranging from 1.0 to 2.5.

  5. STUDENT-DEFINED QUALITY BY KANO MODEL: A CASE STUDY OF ENGINEERING STUDENTS IN INDIA

    Directory of Open Access Journals (Sweden)

    Ismail Wilson Taifa

    2016-09-01

    Full Text Available Engineering Students in India like elsewhere worldwide need well designed classrooms furniture which can enable them to attend lectures without negative impact in the long run. Engineering students from India have not yet been involved in suggesting their requirements for improving the mostly out-dated furniture at their colleges. Among the available improvement techniques, Kano Model is one of the most effective improvement approaches. The main objective of the study was to identify and categorise all the main attributes regarding the classrooms furniture for the purpose of increasing student satisfaction in the long run. Kano Model has been well applied to make an exhaustive list of requirements for redesigning classroom furniture. Cronbach Alpha was computed with the help of SPSS 16.0 for validation purpose and it ranged between 0.8 and 0.9 which is a good internal consistency. Further research can be done by integrating Kano Model with Quality Function Deployment.

  6. A study to define the research and technology requirements for advanced turbo/propfan transport aircraft

    Science.gov (United States)

    Goldsmith, I. M.

    1981-01-01

    The feasibility of the propfan relative to the turbofan is summarized, using the Douglas DC-9 Super 80 (DS-8000) as the actual operational base aircraft. The 155 passenger economy class aircraft (31,775 lb 14,413 kg payload), cruise Mach at 0.80 at 31,000 ft (8,450 m) initial altitude, and an operational capability in 1985 was considered. Three propfan arrangements, wing mounted, conventional horizontal tail aft mounted, and aft fuselage pylon mounted are selected for comparison with the DC-9 Super 80 P&WA JT8D-209 turbofan powered aircraft. The configuration feasibility, aerodynamics, propulsion, structural loads, structural dynamics, sonic fatigue, acoustics, weight maintainability, performance, rough order of magnitude economics, and airline coordination are examined. The effects of alternate cruise Mach number, mission stage lengths, and propfan design characteristics are considered. Recommendations for further study, ground testing, and flight testing are included.

  7. What Defines an Effective Anti-Tobacco TV Advertisement? A Pilot Study among Greek Adolescents

    Directory of Open Access Journals (Sweden)

    Christos Lionis

    2010-01-01

    Full Text Available As the Framework Convention on Tobacco Control (FCTC calls for public health awareness on tobacco use, mass media campaigns should be appropriately designed so as to maximize their effectiveness. In this methodological pilot study, 95 Greek adolescents (mean age 15 ± 1.8 years, were shown seven different anti tobacco ads, and asked to rate the ad theme, message and emotional context on a 1−7 Likert scale. Health related ads were rated the highest, and as identified through the logistic regression analysis, adolescents who perceived an ad to be emotional or to have a clear message that was relevant to them, were more likely to rate the ad as more effective. The strong agreement between the above findings and the existing literature indicates the applicability of this pilot study’s methodological approach.

  8. Defining decision making: a qualitative study of international experts' views on surgical trainee decision making.

    Science.gov (United States)

    Rennie, Sarah C; van Rij, Andre M; Jaye, Chrystal; Hall, Katherine H

    2011-06-01

    Decision making is a key competency of surgeons; however, how best to assess decisions and decision makers is not clearly established. The aim of the present study was to identify criteria that inform judgments about surgical trainees' decision-making skills. A qualitative free text web-based survey was distributed to recognized international experts in Surgery, Medical Education, and Cognitive Research. Half the participants were asked to identify features of good decisions, characteristics of good decision makers, and essential factors for developing good decision-making skills. The other half were asked to consider these areas in relation to poor decision making. Template analysis of free text responses was performed. Twenty-nine (52%) experts responded to the survey, identifying 13 categories for judging a decision and 14 for judging a decision maker. Twelve features/characteristics overlapped (considered, informed, well timed, aware of limitations, communicated, knowledgeable, collaborative, patient-focused, flexible, able to act on the decision, evidence-based, and coherent). Fifteen categories were generated for essential factors leading to development of decision-making skills that fall into three major themes (personal qualities, training, and culture). The categories compiled from the perspectives of good/poor were predominantly the inverse of each other; however, the weighting given to some categories varied. This study provides criteria described by experts when considering surgical decisions, decision makers, and development of decision-making skills. It proposes a working definition of a good decision maker. Understanding these criteria will enable clinical teachers to better recognize and encourage good decision-making skills and identify poor decision-making skills for remediation.

  9. Defining the Key Competencies in Radiation Protection for Endovascular Procedures: A Multispecialty Delphi Consensus Study.

    Science.gov (United States)

    Doyen, Bart; Maurel, Blandine; Cole, Jonathan; Maertens, Heidi; Mastracci, Tara; Van Herzeele, Isabelle

    2018-02-01

    Radiation protection training courses currently focus on broad knowledge topics which may not always be relevant in daily practice. The goal of this study was to determine the key competencies in radiation protection that every endovascular team member should possess and apply routinely, through multispecialty clinical content expert consensus. Consensus was obtained through a two round modified Delphi methodology. The expert panel consisted of European vascular surgeons, interventional radiologists, and interventional cardiologists/angiologists experienced in endovascular procedures. An initial list of statements, covering knowledge skills, technical skills and attitudes was created, based on a literature search. Additional statements could be suggested by the experts in the first Delphi round. Each of the statements had to be rated on a 5- point Likert scale. A statement was considered to be a key competency when the internal consistency was greater than alpha = 0.80 and at least 80% of the experts agreed (rating 4/5) or strongly agreed (rating 5/5) with the statement. Questionnaires were emailed to panel members using the Surveymonkey service. Forty-one of 65 (63.1%) invited experts agreed to participate in the study. The response rates were 36 out of 41 (87.8%): overall 38 out of 41(92.6%) in the first round and 36 out of 38 (94.7%) in the second round. The 71 primary statements were supplemented with nine items suggested by the panel. The results showed excellent consensus among responders (Cronbach's alpha = 0.937 first round; 0.958 s round). Experts achieved a consensus that 30 of 33 knowledge skills (90.9%), 23 of 27 technical skills (82.1%), and 15 of 20 attitudes (75.0%) should be considered as key competencies. A multispecialty European endovascular expert panel reached consensus about the key competencies in radiation protection. These results may serve to create practical and relevant radiation protection training courses in the future, enhancing

  10. A study to define and verify a model of interactive-constructive elementary school science teaching

    Science.gov (United States)

    Henriques, Laura

    This study took place within a four year systemic reform effort collaboratively undertaken by the Science Education Center at the University of Iowa and a local school district. Key features of the inservice project included the use of children's literature as a springboard into inquiry based science investigations, activities to increase parents' involvement in children's science learning and extensive inservice opportunities for elementary teachers to increase content knowledge and content-pedagogical knowledge. The overarching goal of this elementary science teacher enhancement project was to move teachers towards an interactive-constructivist model of teaching and learning. This study had three components. The first was the definition of the prototype teacher indicated by the project's goals and supported by science education research. The second involved the generation of a model to show relationships between teacher-generated products, demographics and their subsequent teaching behaviors. The third involved the verification of the hypothesized model using data collected on 15 original participants. Demographic information, survey responses, interview and written responses to scenarios were among the data collected as source variables. These were scored using a rubric designed to measure constructivist practices in science teaching. Videotapes of science teaching and revised science curricula were collected as downstream variables and scored using an the ESTEEM observational rubric and a rubric developed for the project. Results indicate that newer teachers were more likely to implement features of the project. Those teachers who were philosophically aligned with project goals before project involvement were also more likely to implement features of the project. Other associations between reported beliefs, planning and classroom implementations were not confirmed by these data. Data show that teachers reported higher levels of implementation than their

  11. An ethnographic study of nursing home culture to define organizational realities of culture change.

    Science.gov (United States)

    Deutschman, Marian T

    2005-01-01

    The current system of delivery of nursing home care is costly both in dollars and in human terms. Culture change may provide solutions to both issues. Culture change has a different meaning for different organizations depending on where they are in the continuum of change. Detailed observation of staff members "in action" in three long-term care facilities over a period of several months was supplemented by formal and informal interviews of organization members to gain an understanding of the culture of the nursing home organization. Four three-hour observations in each of three facilities, representing privately-held and not-for-profit organizations in urban, suburban, and rural locations yielded insights into the routine, recruitment, training, teamwork, activities, leadership, role-modeling, mentoring, staff and resident satisfaction, weekend staffing and activities, bureaucratic structure, and sharing of best practices. Discussion of each of these issues may provide a starting point for all those facilities that are contemplating significant culture change. If the objective is to have facilities truly embrace a new set of values, then the change begins with the owners and administrators of nursing homes who need to focus on building new relationships with all the stakeholders. In-depth interviews of organization members and six chief executive officers in long-term care in the Western New York area culminated the study with the development of a fifty-question survey for decision makers.

  12. Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis.

    Science.gov (United States)

    Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

    2014-09-14

    To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients' age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management.

  13. Characteristics of martial art injuries in a defined Canadian population: a descriptive epidemiological study

    Directory of Open Access Journals (Sweden)

    Pickett William

    2010-12-01

    Full Text Available Abstract Background The martial arts have emerged as common activities in the Canadian population, yet few studies have investigated the occurrence of associated injuries on a population basis. Methods We performed such an investigation and suggest potential opportunities for prevention. The data source was 14 years (1993 to 2006 of records from the Kingston sites of the Canadian Hospital Injury Reporting and Prevention Program (CHIRPP. Results 920 cases were identified. Incidence rates were initially estimated using census data as denominators. We then imputed annual injury rates per 10000 using a range of published estimates of martial arts participation available from a national survey. Rates of injury in males and females were 2300 and 1033 per 10000 (0.3% participation and 575 and 258 per 10000 (1.2% participation. Injuries were most frequently reported in karate (33% and taekwondo (14%. The most common mechanisms of injury were falls, throws and jumps (33%. Fractures (20% were the most frequently reported type of injury and the lower limb was the most common site of injury (41%. Conclusions Results provide a foundation for potential interventions with a focus on falls, the use of weapons, participation in tournaments, as well as head and neck trauma.

  14. Characteristics of martial art injuries in a defined Canadian population: a descriptive epidemiological study.

    Science.gov (United States)

    McPherson, Mark; Pickett, William

    2010-12-30

    The martial arts have emerged as common activities in the Canadian population, yet few studies have investigated the occurrence of associated injuries on a population basis. We performed such an investigation and suggest potential opportunities for prevention. The data source was 14 years (1993 to 2006) of records from the Kingston sites of the Canadian Hospital Injury Reporting and Prevention Program (CHIRPP). 920 cases were identified. Incidence rates were initially estimated using census data as denominators. We then imputed annual injury rates per 10000 using a range of published estimates of martial arts participation available from a national survey. Rates of injury in males and females were 2300 and 1033 per 10000 (0.3% participation) and 575 and 258 per 10000 (1.2% participation). Injuries were most frequently reported in karate (33%) and taekwondo (14%). The most common mechanisms of injury were falls, throws and jumps (33%). Fractures (20%) were the most frequently reported type of injury and the lower limb was the most common site of injury (41%). Results provide a foundation for potential interventions with a focus on falls, the use of weapons, participation in tournaments, as well as head and neck trauma.

  15. Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, Daniel M., E-mail: daniel.trifiletti@gmail.com [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Lee, Cheng-Chia [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Kano, Hideyuki; Cohen, Jonathan [Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Janopaul-Naylor, James; Alonso-Basanta, Michelle; Lee, John Y.K. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Simonova, Gabriela; Liscak, Roman [Department of Radiation and Stereotactic Neurosurgery, Na Homolce Hospital, Prague (Czech Republic); Wolf, Amparo; Kvint, Svetlana [Department of Neurosurgery, New York University Lagone Medical Center, New York, New York (United States); Grills, Inga S.; Johnson, Matthew [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Liu, Kang-Du; Lin, Chung-Jung [Department of Neurosurgery, Neurological Institute, Taipei Veteran General Hospital, Taipei, Taiwan (China); Mathieu, David; Héroux, France [Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Québec (Canada); Silva, Danilo; Sharma, Mayur [Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio (United States); Cifarelli, Christopher P. [Departments of Neurosurgery and Radiation Oncology, West Virginia University, Morgantown, West Virginia (United States); and others

    2016-10-01

    Purpose: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). Methods and Materials: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. Results: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. Conclusions: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

  16. Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis

    Science.gov (United States)

    Lenz, Philipp; Eckelskemper, Franziska; Erichsen, Thomas; Lankisch, Tim; Dechêne, Alexander; Lubritz, Gabriele; Lenze, Frank; Beyna, Torsten; Ullerich, Hansjörg; Schmedt, Andre; Domagk, Dirk

    2014-01-01

    AIM: To develop an algorithm to improve the diagnosis and treatment of patients with biliary candidiasis. METHODS: We performed a prospective study of 127 patients who underwent endoscopic retrograde cholangiopancreatography, for various biliary disorders, at 3 tertiary referral centers in Germany from July 2011 through July 2012 (ClinicalTrials.gov: NCT01109550). Bile, buccal, and stool samples were collected. When indicated, endoscopic transpapillary bile duct biopsies were performed to clarify the etiology of bile duct strictures and to prove invasive fungal infections. RESULTS: Candida species were detected in 38 of the 127 bile samples (29.9%). By multivariate analysis patients’ age and previous endoscopic sphincterotomy were independent risk factors for biliary candidiasis (P 7 d) (P = 0.089) tend to be at risk for biliary candidiasis. One patient was negative in mycological culture of bile fluid but invasive biliary candidiasis was diagnosed histologically. Of Candida subspecies detected, 36.7% were azole-resistant, such as C glabrata. Eight patients received anti-mycotic therapy, based on our algorithm. Of these, 3 had cancer with biliary tract involvement, 2 had secondary sclerosing cholangitis, 1 had retroperitoneal fibrosis, and 5 had septicemia. In all patients contamination was ruled out by smears of the endoscope channel. CONCLUSION: Gastroenterologists should be aware of frequent candida colonization in patients with cholangitis and biliary disorders. Our suggested algorithm facilitates the further clinical management. PMID:25232260

  17. Defining antimicrobial stewardship competencies for undergraduate health professional education in the United Kingdom: A study protocol.

    Science.gov (United States)

    Courtenay, Molly; Castro-Sánchez, Enrique; Deslandes, Rhian; Hodson, Karen; Lim, Rosemary; Morris, Gary; Reeves, Scott; Weiss, Marjorie

    2018-04-16

    Multi-drug resistant infections have been identified as one of the greatest threats to human health. Healthcare professionals are involved in an array of patient care activities for which an understanding of antimicrobial stewardship is important. Although antimicrobial prescribing and stewardship competencies have been developed for healthcare professionals who adopt the role of a prescriber, competencies do not exist for other medicine-related stewardship activities. Undergraduate education provides an ideal opportunity to prepare healthcare professionals for these roles and activities. This report presents a protocol for a study designed to provide national consensus on antimicrobial stewardship competencies appropriate for undergraduate healthcare professional education. A modified Delphi process will be used in which a panel of Experts, comprising members from across the United Kingdom, with expertise in prescribing and medicines management with regard to the education and practice of healthcare professionals, and antimicrobial prescribing and stewardship, will be invited to take part in two survey rounds. The competencies developed will be applicable to all undergraduate healthcare professional education programmes. They will help to standardise curricula content and enhance the impact of antimicrobial stewardship education.

  18. Studying the Ability of 7th Grade Students to Define the Circle and Its Elements in the Context of Mathematical Language

    Science.gov (United States)

    Akarsu, Esra; Yilmaz, Süha

    2015-01-01

    In this study, it was aimed to study the mathematical language skills that the 7th grade students use in defining the circle and its elements. In the study, the mathematical language skills of students that they use in defining the circle and its elements in a scenario were compared to the mathematical language skills they use in defining them…

  19. Can play be defined?

    DEFF Research Database (Denmark)

    Eichberg, Henning

    2015-01-01

    Can play be defined? There is reason to raise critical questions about the established academic demand that at phenomenon – also in humanist studies – should first of all be defined, i.e. de-lineated and by neat lines limited to a “little box” that can be handled. The following chapter develops....... Human beings can very well understand play – or whatever phenomenon in human life – without defining it....

  20. Defining Glioblastoma Resectability Through the Wisdom of the Crowd: A Proof-of-Principle Study.

    Science.gov (United States)

    Sonabend, Adam M; Zacharia, Brad E; Cloney, Michael B; Sonabend, Aarón; Showers, Christopher; Ebiana, Victoria; Nazarian, Matthew; Swanson, Kristin R; Baldock, Anne; Brem, Henry; Bruce, Jeffrey N; Butler, William; Cahill, Daniel P; Carter, Bob; Orringer, Daniel A; Roberts, David W; Sagher, Oren; Sanai, Nader; Schwartz, Theodore H; Silbergeld, Daniel L; Sisti, Michael B; Thompson, Reid C; Waziri, Allen E; McKhann, Guy

    2017-04-01

    Extent of resection (EOR) correlates with glioblastoma outcomes. Resectability and EOR depend on anatomical, clinical, and surgeon factors. Resectability likely influences outcome in and of itself, but an accurate measurement of resectability remains elusive. An understanding of resectability and the factors that influence it may provide a means to control a confounder in clinical trials and provide reference for decision making. To provide proof of concept of the use of the collective wisdom of experienced brain tumor surgeons in assessing glioblastoma resectability. We surveyed 13 academic tumor neurosurgeons nationwide to assess the resectability of newly diagnosed glioblastoma. Participants reviewed 20 cases, including digital imaging and communications in medicine-formatted pre- and postoperative magnetic resonance images and clinical vignettes. The selected cases involved a variety of anatomical locations and a range of EOR. Participants were asked about surgical goal, eg, gross total resection, subtotal resection (STR), or biopsy, and rationale for their decision. We calculated a "resectability index" for each lesion by pooling responses from all 13 surgeons. Neurosurgeons' individual surgical goals varied significantly ( P = .015), but the resectability index calculated from the surgeons' pooled responses was strongly correlated with the percentage of contrast-enhancing residual tumor ( R = 0.817, P < .001). The collective STR goal predicted intraoperative decision of intentional STR documented on operative notes ( P < .01) and nonresectable residual ( P < .01), but not resectable residual. In this pilot study, we demonstrate the feasibility of measuring the resectability of glioblastoma through crowdsourcing. This tool could be used to quantify resectability, a potential confounder in neuro-oncology clinical trials. Copyright © 2016 by the Congress of Neurological Surgeons

  1. How do stakeholders from multiple hierarchical levels of a large provincial health system define engagement? A qualitative study.

    Science.gov (United States)

    Norris, Jill M; White, Deborah E; Nowell, Lorelli; Mrklas, Kelly; Stelfox, Henry T

    2017-08-01

    Engaging stakeholders from varied organizational levels is essential to successful healthcare quality improvement. However, engagement has been hard to achieve and to measure across diverse stakeholders. Further, current implementation science models provide little clarity about what engagement means, despite its importance. The aim of this study was to understand how stakeholders of healthcare improvement initiatives defined engagement. Participants (n = 86) in this qualitative thematic study were purposively sampled for individual interviews. Participants included leaders, core members, frontline clinicians, support personnel, and other stakeholders of Strategic Clinical Networks in Alberta Health Services, a Canadian provincial health system with over 108,000 employees. We used an iterative thematic approach to analyze participants' responses to the question, "How do you define engagement?" Regardless of their organizational role, participants defined engagement through three interrelated themes. First, engagement was active participation from willing and committed stakeholders, with levels that ranged from information sharing to full decision-making. Second, engagement centered on a shared decision-making process about meaningful change for everyone "around the table," those who are most impacted. Third, engagement was two-way interactions that began early in the change process, where exchanges were respectful and all stakeholders felt heard and understood. This study highlights the commonalities of how stakeholders in a large healthcare system defined engagement-a shared understanding and terminology-to guide and improve stakeholder engagement. Overall, engagement was an active and committed decision-making about a meaningful problem through respectful interactions and dialog where everyone's voice is considered. Our results may be used in conjunction with current implementation models to provide clarity about what engagement means and how to engage various

  2. A Case Study of Six Sigma Define-Measure-Analyze-Improve-Control (DMAIC Methodology in Garment Sector

    Directory of Open Access Journals (Sweden)

    Abdur Rahman

    2017-12-01

    Full Text Available This paper demonstrates the empirical application of Six Sigma and Define-Measure-Analyze-Improve-Control (DMAIC methodology to reduce product defects within a garments manufacturing organization in Bangladesh which follows the DMAIC methodology to investigate defects, root causes and provide a solution to eliminate these defects. The analysis from employing Six Sigma and DMAIC indicated that the broken stitch and open seam influenced the number of defective products. Design of experiments (DOE and the analysis of variance (ANOVA techniques were combined to statistically determine the correlation of the broken stitch and open seam with defects as well as to define their optimum values needed to eliminate the defects. Thus, a reduction of about 35% in the garments defect was achieved, which helped the organization studied to reduce its defects and thus improve its Sigma level from 1.7 to 3.4.

  3. Methods of staining and visualization of sphingolipid enriched and non-enriched plasma membrane regions of Arabidopsis thaliana with fluorescent dyes and lipid analogues

    Directory of Open Access Journals (Sweden)

    Blachutzik Jörg O

    2012-08-01

    Full Text Available Abstract Background Sterols and Sphingolipids form lipid clusters in the plasma membranes of cell types throughout the animal and plant kingdoms. These lipid domains provide a medium for protein signaling complexes at the plasma membrane and are also observed to be principal regions of membrane contact at the inception of infection. We visualized different specific fluorescent lipophilic stains of the both sphingolipid enriched and non-sphingolipid enriched regions in the plasma membranes of live protoplasts of Arabidopsis thaliana. Results Lipid staining protocols for several fluorescent lipid analogues in plants are presented. The most emphasis was placed on successful protocols for the single and dual staining of sphingolipid enriched regions and exclusion of sphingolipid enriched regions on the plasma membrane of Arabidopsis thaliana protoplasts. A secondary focus was placed to ensure that these staining protocols presented still maintain cell viability. Furthermore, the protocols were successfully tested with the spectrally sensitive dye Laurdan. Conclusion Almost all existing staining procedures of the plasma membrane with fluorescent lipid analogues are specified for animal cells and tissues. In order to develop lipid staining protocols for plants, procedures were established with critical steps for the plasma membrane staining of Arabidopsis leaf tissue and protoplasts. The success of the plasma membrane staining protocols was additionally verified by measurements of lipid dynamics by the fluorescence recovery after photobleaching technique and by the observation of new phenomena such as time dependent lipid polarization events in living protoplasts, for which a putative physiological relevance is suggested.

  4. MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

    Science.gov (United States)

    Khodadadian, M; Leroux, M E; Auzenne, E; Ghosh, S C; Farquhar, D; Evans, R; Spohn, W; Zou, Y; Klostergaard, J

    2009-10-01

    Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

  5. Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor

    International Nuclear Information System (INIS)

    Dewji, N.N.; Wenger, D.A.; O'Brien, J.S.

    1987-01-01

    Two cDNA clones encoding prepro-sphingolipid activator protein 1 (SAP-1) were isolated from a λ gt11 human hepatoma expression library using polyclonal antibodies. These had inserts of ≅ 2 kilobases (λ-S-1.2 and λ-S-1.3) and both were both homologous with a previously isolated clone (λ-S-1.1) for mature SAP-1. The authors report here the nucleotide sequence of the longer two EcoRI fragments of S-1.2 and S-1.3 that were not the same and the derived amino acid sequences of mature SAP-1 and its prepro form. The open reading frame encodes 19 amino acids, which are colinear with the amino-terminal sequence of mature SAP-1, and extends far beyond the predicted carboxyl terminus of mature SAP-1, indicating extensive carboxyl-terminal processing. The nucleotide sequence of cDNA encoding prepro-SAP-1 includes 1449 bases from the assigned initiation codon ATG at base-pair 472 to the stop codon TGA at base-pair 1921. The first 23 amino acids coded after the initiation ATG are characteristic of a signal peptide. The calculated molecular mass for a polypeptide encoded by 1449 bases is ≅ 53 kDa, in keeping with the reported value for pro-SAP-1. The data indicate that after removal of the signal peptide mature SAP-1 is generated by removing an additional 7 amino acids from the amino terminus and ≅ 373 amino acids from the carboxyl terminus. One potential glycosylation site was previously found in mature SAP-1. Three additional potential glycosylation sites are present in the processed carboxyl-terminal polypeptide, which they designate as P-2

  6. Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

    Directory of Open Access Journals (Sweden)

    Cremer Harold

    2011-04-01

    Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.

  7. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S; Swanevelder, Sonja

    2004-07-15

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B{sub 1} (FB{sub 1}) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB{sub 1} containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB{sub 1} dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB{sub 1} treatment in the control rats was significantly (P<0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB{sub 1} initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB{sub 1} treatment, the initiation effected by FB{sub 1} was less (P<0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB{sub 1} initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P<0.05) higher with the secondary FB{sub 1} treatment. Although, the FB{sub 1}-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  8. A laboratory validation study of comfort and limit temperatures of four sleeping bags defined according to EN 13537 (2002).

    Science.gov (United States)

    Lin, Li-Yen; Wang, Faming; Kuklane, Kalev; Gao, Chuansi; Holmér, Ingvar; Zhao, Mengmeng

    2013-03-01

    In this study, we validated comfort and limit temperatures of four sleeping bags with different levels of insulation defined according to EN 13537. Six male subjects and four female subjects underwent totally 20 two-hour exposures in four sleeping bags at four intended testing temperatures: 11.2, 3.8, 2.1 and -9.0 °C. The subjective perceptions and physiological responses of these subjects were reported and analyzed. It was found that the EN 13537 defined comfort temperature and limit temperature were underestimated for sleeping bags MA3, HAG and MAM. The predictions are so conservative that further revision may be required to meet the requirements of both manufacturers and consumers. In contrast, for the sleeping bag MA0 with a low level of insulation, the limit temperature defined by EN 13537 was slightly overestimated. In addition, two individual case studies (-28.0 and -32.0 °C) demonstrated that low toe temperatures were widely observed among the male and female subjects, although the mean skin temperatures were almost within the thermoneutrality range (32.0-34.0 °C). It seems that the IREQ model (ISO 11079) overestimated both the comfort and limit temperatures of the sleeping bags. Finally, traditional sleeping bags may be required to be re-designed to provide consumers both whole body comfort as well as local thermal comfort at feet/toes or users need to be made aware of the higher need for their insulation. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  9. Cross-study analysis of genomic data defines the ciliate multigenic epiplasmin family: strategies for functional analysis in Paramecium tetraurelia

    Directory of Open Access Journals (Sweden)

    Ravet Viviane

    2009-06-01

    Full Text Available Abstract Background The sub-membranous skeleton of the ciliate Paramecium, the epiplasm, is composed of hundreds of epiplasmic scales centered on basal bodies, and presents a complex set of proteins, epiplasmins, which belong to a multigenic family. The repeated duplications observed in the P. tetraurelia genome present an interesting model of the organization and evolution of a multigenic family within a single cell. Results To study this multigenic family, we used phylogenetic, structural, and analytical transcriptional approaches. The phylogenetic method defines 5 groups of epiplasmins in the multigenic family. A refined analysis by Hydrophobic Cluster Analysis (HCA identifies structural characteristics of 51 epiplasmins, defining five separate groups, and three classes. Depending on the sequential arrangement of their structural domains, the epiplasmins are defined as symmetric, asymmetric or atypical. The EST data aid in this classification, in the identification of putative regulating sequences such as TATA or CAAT boxes. When specific RNAi experiments were conducted using sequences from either symmetric or asymmetric classes, phenotypes were drastic. Local effects show either disrupted or ill-shaped epiplasmic scales. In either case, this results in aborted cell division. Using structural features, we show that 4 epiplasmins are also present in another ciliate, Tetrahymena thermophila. Their affiliation with the distinctive structural groups of Paramecium epiplasmins demonstrates an interspecific multigenic family. Conclusion The epiplasmin multigenic family illustrates the history of genomic duplication in Paramecium. This study provides a framework which can guide functional analysis of epiplasmins, the major components of the membrane skeleton in ciliates. We show that this set of proteins handles an important developmental information in Paramecium since maintenance of epiplasm organization is crucial for cell morphogenesis.

  10. Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome

    DEFF Research Database (Denmark)

    Llewellyn, A; McCabe, CS; Hibberd, Y

    2018-01-01

    Background: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. Objectives: To define recovery from the patient...

  11. Radiologically defining horizontal gaze using EOS imaging-a prospective study of healthy subjects and a retrospective audit.

    Science.gov (United States)

    Hey, Hwee Weng Dennis; Tan, Kimberly-Anne; Ho, Vivienne Chien-Lin; Azhar, Syifa Bte; Lim, Joel-Louis; Liu, Gabriel Ka-Po; Wong, Hee-Kit

    2018-06-01

    As sagittal alignment of the cervical spine is important for maintaining horizontal gaze, it is important to determine the former for surgical correction. However, horizontal gaze remains poorly-defined from a radiological point of view. The objective of this study was to establish radiological criteria to define horizontal gaze. This study was conducted at a tertiary health-care institution over a 1-month period. A prospective cohort of healthy patients was used to determine the best radiological criteria for defining horizontal gaze. A retrospective cohort of patients without rigid spinal deformities was used to audit the incidence of horizontal gaze. Two categories of radiological parameters for determining horizontal gaze were tested: (1) the vertical offset distances of key identifiable structures from the horizontal gaze axis and (2) imaginary lines convergent with the horizontal gaze axis. Sixty-seven healthy subjects underwent whole-body EOS radiographs taken in a directed standing posture. Horizontal gaze was radiologically defined using each parameter, as represented by their means, 95% confidence intervals (CIs), and associated 2 standard deviations (SDs). Subsequently, applying the radiological criteria, we conducted a retrospective audit of such radiographs (before the implementation of a strict radioimaging standardization). The mean age of our prospective cohort was 46.8 years, whereas that of our retrospective cohort was 37.2 years. Gender was evenly distributed across both cohorts. The four parameters with the lowest 95% CI and 2 SD were the distance offsets of the midpoint of the hard palate (A) and the base of the sella turcica (B), the horizontal convergents formed by the tangential line to the hard palate (C), and the line joining the center of the orbital orifice with the internal occipital protuberance (D). In the prospective cohort, good sensitivity (>98%) was attained when two or more parameters were used. Audit using Criterion B

  12. Psychosocial factors associated with broadly defined bulimia nervosa during early pregnancy: findings from the Norwegian Mother and Child Cohort Study.

    Science.gov (United States)

    Knoph Berg, Cecilie; Bulik, Cynthia M; Von Holle, Ann; Torgersen, Leila; Hamer, Robert; Sullivan, Patrick; Reichborn-Kjennerud, Ted

    2008-05-01

    The purpose of the present study was to investigate the relationship between psychosocial characteristics and broadly defined bulimia nervosa during early pregnancy, including factors associated with continuation, incidence and remission. A total of 41 157 women completed questionnaires at approximately gestation week 18, including items on eating disorders and psychosocial characteristics as a part of Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Incident bulimia nervosa during the first trimester was significantly associated with symptoms of anxiety and depression and low self-esteem and life satisfaction, whereas remission was significantly associated with higher self-esteem and life satisfaction. Continuation was not significantly related to any of the psychosocial variables tested. Onset of bulimia nervosa during pregnancy is associated with mood and anxiety symptoms. Remission of bulimic symptoms and new onset of bulimia nervosa are associated with opposite profiles of self-esteem, and life satisfaction measures.

  13. A STUDY OF THE IMAGE OF TULIP SYMPHONY - A DEFINING INGREDIENT IN THE DEVELOPMENT OF THE URBAN BRAND OF PITESTI

    Directory of Open Access Journals (Sweden)

    Mihaela, ASANDEI

    2014-11-01

    Full Text Available The city is a fundamental element of the identity of contemporary society, fulfilling in each urban community complex functions that depend on the needs, interests and aspirations of the people and of the political and economic system. The urban identity of Pitesti is defined by a set of features with certain significance for each inhabitant of the city. The Tulip Symphony is a symbol that has been created, developed and promoted during the past four decades by the urban community. The present study aims to study how residents of Pitesti perceive the urban product named the Tulip Symphony is and present the conclusions of a statistical survey conducted during the 37th edition of the event.

  14. Plasma membrane proteins Slm1 and Slm2 mediate activation of the AGC kinase Ypk1 by TORC2 and sphingolipids in S. cerevisiae.

    Science.gov (United States)

    Niles, Brad J; Powers, Ted

    2012-10-15

    The PH domain-containing proteins Slm1 and Slm2 were originally identified as substrates of the rapamycin-insensitive TOR complex 2 (TORC2) and as mediators of signaling by the lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) in budding yeast S. cerevisiae. More recently, these proteins have been identified as critical effectors that facilitate phosphorylation and activation of the AGC kinases Ypk1 and Ypk2 by TORC2. Here, we review the molecular basis for this regulation as well as place it within the context of recent findings that have revealed Slm1/2 and TORC2-dependent phosphorylation of Ypk1 is coupled to the biosynthesis of complex sphingolipids and to their levels within the plasma membrane (PM) as well as other forms of PM stress. Together, these studies reveal the existence of an intricate homeostatic feedback mechanism, whereby the activity of these signaling components is linked to the biosynthesis of PM lipids according to cellular need.

  15. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

    Science.gov (United States)

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-04-01

    Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Extensive sphingolipid depletion does not affect lipid raft integrity or lipid raft localization and efflux function of the ABC transporter MRP1

    NARCIS (Netherlands)

    Klappe, Karin; Dijkhuis, Anne-Jan; Hummel, Ina; van Dam, Annie; Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex; Permentier, Hjalmar; Kok, Jan W.

    2010-01-01

    We show that highly efficient depletion of sphingolipids in two different cell lines does not abrogate the ability to isolate Lubrol-based DRMs (detergent-resistant membranes) or detergent-free lipid rafts from these cells. Compared with control, DRM/detergent-free lipid raft fractions contain equal

  17. Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

    Science.gov (United States)

    N Getov, Ilko; Gocheva-Hristova, Tanya; Lebanova, Hristina V; Grigorov, Evgeni E

    2012-08-01

    To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.

  18. Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study.

    Science.gov (United States)

    Hermus, M A A; Boesveld, I C; Hitzert, M; Franx, A; de Graaf, J P; Steegers, E A P; Wiegers, T A; van der Pal-de Bruin, K M

    2017-07-03

    During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not directly applicable for use within the Dutch obstetric system. A standard definition for a birth centre in the Netherlands is lacking. This study aimed to develop a definition of birth centres for use in the Netherlands, to identify these centres and to describe their characteristics. International definitions of birth centres were analysed to find common descriptions. In July 2013 the Dutch Birth Centre Questionnaire was sent to 46 selected Dutch birth locations that might qualify as birth centre. Questions included: location, reason for establishment, women served, philosophies, facilities that support physiological birth, hotel-facilities, management, environment and transfer procedures in case of referral. Birth centres were visited to confirm the findings from the Dutch Birth Centre Questionnaire and to measure distance and time in case of referral to obstetric care. From all 46 birth locations the questionnaires were received. Based on this information a Dutch definition of a birth centre was constructed. This definition reads: "Birth centres are midwifery-managed locations that offer care to low risk women during labour and birth. They have a homelike environment and provide facilities to support physiological birth. Community midwives take primary professional responsibility for care. In case of referral the obstetric caregiver takes over the professional responsibility of care." Of the 46 selected birth locations 23 fulfilled this definition. Three types of birth centres were distinguished based on their location in relation to the nearest obstetric unit: freestanding (n = 3), alongside (n = 14) and on-site (n = 6). Transfer in case of referral was necessary for all

  19. Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs

    DEFF Research Database (Denmark)

    Halttunen, Jorma; Meisner, Søren; Aabakken, Lars

    2014-01-01

    BACKGROUND: The definition of a "difficult" cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP). AIMS: To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis. PATIENTS AND METHODS: Prospective consecutive reco...

  20. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study.

    Science.gov (United States)

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2010-01-01

    Ciguatoxins are extremely potent neurotoxins, produced by tropical marine dinoflagellates, that persistently enter into our food web. Over 100,000 people annually experience acute ciguatera poisoning from consuming toxic fish. Roughly 5% of these victims will develop chronic ciguatera (CC), a widespread, multisymptom, multisystem, chronic illness that can last tens of years. CC is marked by disproportionate disability and non-specific refractory symptoms such as fatigue, cognitive deficits and pain, and is suggestive of other illnesses. Its unknown pathophysiology makes both diagnosis and treatment difficult. We wanted to compare objective parameters of visual contrast sensitivity testing, measures of innate immune response and genetic markers in cases to controls to assess the potential for the presence of persistent inflammatory parameters that are demonstrated in other biotoxin associated illnesses at a single specialty clinic. Using 59 CC cases and 59 controls we present in retrospective review, in all cases, abnormalities in immune responses paralleling the chronic systemic inflammatory response syndrome seen in several other chronic diseases. This study defines a preliminary case definition using medical history, total symptoms, visual contrast sensitivity, HLA DR genotype analysis, reduction of regulatory neuropeptides VIP and MSH, and multiple measures of inflammatory immune response, especially C4a and TGFβ1, thereby providing a basis for identification and targeted therapy. CC provides a model for chronic human illness associated with initiation of inflammatory responses by biologically produced neurotoxins. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication.

    Directory of Open Access Journals (Sweden)

    Brittany M Ashlock

    Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.

  2. Injection of fully-defined signal mixtures: a novel high-throughput tool to study neuronal encoding and computations.

    Directory of Open Access Journals (Sweden)

    Vladimir Ilin

    Full Text Available Understanding of how neurons transform fluctuations of membrane potential, reflecting input activity, into spike responses, which communicate the ultimate results of single-neuron computation, is one of the central challenges for cellular and computational neuroscience. To study this transformation under controlled conditions, previous work has used a signal immersed in noise paradigm where neurons are injected with a current consisting of fluctuating noise that mimics on-going synaptic activity and a systematic signal whose transmission is studied. One limitation of this established paradigm is that it is designed to examine the encoding of only one signal under a specific, repeated condition. As a result, characterizing how encoding depends on neuronal properties, signal parameters, and the interaction of multiple inputs is cumbersome. Here we introduce a novel fully-defined signal mixture paradigm, which allows us to overcome these problems. In this paradigm, current for injection is synthetized as a sum of artificial postsynaptic currents (PSCs resulting from the activity of a large population of model presynaptic neurons. PSCs from any presynaptic neuron(s can be now considered as "signal", while the sum of all other inputs is considered as "noise". This allows us to study the encoding of a large number of different signals in a single experiment, thus dramatically increasing the throughput of data acquisition. Using this novel paradigm, we characterize the detection of excitatory and inhibitory PSCs from neuronal spike responses over a wide range of amplitudes and firing-rates. We show, that for moderately-sized neuronal populations the detectability of individual inputs is higher for excitatory than for inhibitory inputs during the 2-5 ms following PSC onset, but becomes comparable after 7-8 ms. This transient imbalance of sensitivity in favor of excitation may enhance propagation of balanced signals through neuronal networks. Finally, we

  3. Clinically defined non-specific symptoms in the vicinity of mobile phone base stations: A retrospective before-after study

    Energy Technology Data Exchange (ETDEWEB)

    Baliatsas, Christos, E-mail: c.baliatsas@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands); Kamp, Irene van, E-mail: irene.van.kamp@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Bolte, John, E-mail: john.bolte@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Kelfkens, Gert, E-mail: gert.kelfkens@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Dijk, Christel van, E-mail: Christel.Van.Dijk@amsterdam.nl [Department of Research, Information and Statistics (OIS), Municipality of Amsterdam, Amsterdam (Netherlands); Spreeuwenberg, Peter, E-mail: p.spreeuwenberg@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands); Hooiveld, Mariette, E-mail: m.hooiveld@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands); Lebret, Erik, E-mail: erik.lebret@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht (Netherlands); Yzermans, Joris, E-mail: J.Yzermans@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands)

    2016-09-15

    The number of mobile phone base station(s) (MPBS) has been increasing to meet the rapid technological changes and growing needs for mobile communication. The primary objective of the present study was to test possible changes in prevalence and number of NSS in relation to MPBS exposure before and after increase of installed MPBS antennas. A retrospective cohort study was conducted, comparing two time periods with high contrast in terms of number of installed MPBS. Symptom data were based on electronic health records from 1069 adult participants, registered in 9 general practices in different regions in the Netherlands. All participants were living within 500 m from the nearest bases station. Among them, 55 participants reported to be sensitive to MPBS at T1. A propagation model combined with a questionnaire was used to assess indoor exposure to RF-EMF from MPBS at T1. Estimation of exposure at T0 was based on number of antennas at T0 relative to T1. At T1, there was a > 30% increase in the total number of MPBS antennas. A higher prevalence for most NSS was observed in the MPBS-sensitive group at T1 compared to baseline. Exposure estimates were not associated with GP-registered NSS in the total sample. Some significant interactions were observed between MPBS-sensitivity and exposure estimates on risk of symptoms. Using clinically defined outcomes and a time difference of > 6 years it was demonstrated that RF-EMF exposure to MPBS was not associated with the development of NSS. Nonetheless, there was some indication for a higher risk of NSS for the MPBS-sensitive group, mainly in relation to exposure to UMTS, but this should be interpreted with caution. Results have to be verified by future longitudinal studies with a particular focus on potentially susceptible population subgroups of large sample size and integrated exposure assessment. - Highlights: • There was an important increase in the total number of MPBS at T1 compared to T0. • Prevalence of NSS was

  4. Clinically defined non-specific symptoms in the vicinity of mobile phone base stations: A retrospective before-after study

    International Nuclear Information System (INIS)

    Baliatsas, Christos; Kamp, Irene van; Bolte, John; Kelfkens, Gert; Dijk, Christel van; Spreeuwenberg, Peter; Hooiveld, Mariette; Lebret, Erik; Yzermans, Joris

    2016-01-01

    The number of mobile phone base station(s) (MPBS) has been increasing to meet the rapid technological changes and growing needs for mobile communication. The primary objective of the present study was to test possible changes in prevalence and number of NSS in relation to MPBS exposure before and after increase of installed MPBS antennas. A retrospective cohort study was conducted, comparing two time periods with high contrast in terms of number of installed MPBS. Symptom data were based on electronic health records from 1069 adult participants, registered in 9 general practices in different regions in the Netherlands. All participants were living within 500 m from the nearest bases station. Among them, 55 participants reported to be sensitive to MPBS at T1. A propagation model combined with a questionnaire was used to assess indoor exposure to RF-EMF from MPBS at T1. Estimation of exposure at T0 was based on number of antennas at T0 relative to T1. At T1, there was a > 30% increase in the total number of MPBS antennas. A higher prevalence for most NSS was observed in the MPBS-sensitive group at T1 compared to baseline. Exposure estimates were not associated with GP-registered NSS in the total sample. Some significant interactions were observed between MPBS-sensitivity and exposure estimates on risk of symptoms. Using clinically defined outcomes and a time difference of > 6 years it was demonstrated that RF-EMF exposure to MPBS was not associated with the development of NSS. Nonetheless, there was some indication for a higher risk of NSS for the MPBS-sensitive group, mainly in relation to exposure to UMTS, but this should be interpreted with caution. Results have to be verified by future longitudinal studies with a particular focus on potentially susceptible population subgroups of large sample size and integrated exposure assessment. - Highlights: • There was an important increase in the total number of MPBS at T1 compared to T0. • Prevalence of NSS was

  5. Analytical study of the effects of soft tissue artefacts on functional techniques to define axes of rotation.

    Science.gov (United States)

    De Rosario, Helios; Page, Álvaro; Besa, Antonio

    2017-09-06

    The accurate location of the main axes of rotation (AoR) is a crucial step in many applications of human movement analysis. There are different formal methods to determine the direction and position of the AoR, whose performance varies across studies, depending on the pose and the source of errors. Most methods are based on minimizing squared differences between observed and modelled marker positions or rigid motion parameters, implicitly assuming independent and uncorrelated errors, but the largest error usually results from soft tissue artefacts (STA), which do not have such statistical properties and are not effectively cancelled out by such methods. However, with adequate methods it is possible to assume that STA only account for a small fraction of the observed motion and to obtain explicit formulas through differential analysis that relate STA components to the resulting errors in AoR parameters. In this paper such formulas are derived for three different functional calibration techniques (Geometric Fitting, mean Finite Helical Axis, and SARA), to explain why each technique behaves differently from the others, and to propose strategies to compensate for those errors. These techniques were tested with published data from a sit-to-stand activity, where the true axis was defined using bi-planar fluoroscopy. All the methods were able to estimate the direction of the AoR with an error of less than 5°, whereas there were errors in the location of the axis of 30-40mm. Such location errors could be reduced to less than 17mm by the methods based on equations that use rigid motion parameters (mean Finite Helical Axis, SARA) when the translation component was calculated using the three markers nearest to the axis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Defining seascapes for marine unconsolidated shelf sediments in an eastern boundary upwelling region: The southern Benguela as a case study

    Science.gov (United States)

    Karenyi, Natasha; Sink, Kerry; Nel, Ronel

    2016-02-01

    Marine unconsolidated sediment habitats, the largest benthic ecosystem, are considered physically controlled ecosystems driven by a number of local physical processes. Depth and sediment type are recognised key drivers of these ecosystems. Seascape (i.e., marine landscape) habitat classifications are based solely on consistent geophysical features and provide an opportunity to define unconsolidated sediment habitats based on processes which may vary in distribution through space and time. This paper aimed to classify unconsolidated sediment seascapes and explore their diversity in an eastern boundary upwelling region at the macro-scale, using the South African west coast as a case study. Physical variables such as sediment grain size, depth and upwelling-related variables (i.e., maximum chlorophyll concentration, austral summer bottom oxygen concentration and sediment organic carbon content) were included in the analyses. These variables were directly measured through sampling, or collated from existing databases and the literature. These data were analysed using multivariate Cluster, Principal Components Ordination and SIMPER analyses (in PRIMER 6 + with PERMANOVA add-in package). There were four main findings; (i) eight seascapes were identified for the South African west coast based on depth, slope, sediment grain size and upwelling-related variables, (ii) three depth zones were distinguished (inner, middle and outer shelf), (iii) seascape diversity in the inner and middle shelves was greater than the outer shelf, and (iv) upwelling-related variables were responsible for the habitat diversity in both inner and middle shelves. This research demonstrates that the inclusion of productivity and its related variables, such as hypoxia and sedimentary organic carbon, in seascape classifications will enhance the ability to distinguish seascapes on continental shelves, where productivity is most variable.

  7. A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients.

    Science.gov (United States)

    Rodríguez Arrondo, Francisco; von Wichmann, Miguel Ángel; Camino, Xabier; Goenaga, Miguel Ángel; Ibarguren, Maialen; Azcune, Harkaitz; Bustinduy, María Jesús; Ferrero, Oscar; Muñoz, Josefa; Ibarra, Sofía; Aguirrebengoa, Koldo; Goicoetxea, Josune; Bereciartua, Elena; Montejo, Miguel; García, M Asunción; Martínez, Eduardo; Portu, Joseba; Metola, Luis; Silvariño, Rafael; Sarasqueta, Cristina; Arrizabalaga, Julio; Iribarren, Jose Antonio

    2018-04-23

    We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  8. Pre-defined and optional staging for the deployment of enterprise systems: a case study and a framework

    Science.gov (United States)

    Lichtenstein, Yossi; Cucuy, Shy; Fink, Lior

    2017-03-01

    The effective deployment of enterprise systems has been a major challenge for many organisations. Customising the new system, changing business processes, and integrating multiple information sources are all difficult tasks. As such, they are typically done in carefully planned stages in a process known as phased implementation. Using ideas from Option Theory, this article critiques aspects of phased implementation. One customer relationship management (CRM) project and its phased implementation are described in detail and ten other enterprise system deployments are summarised as a basis for the observation that almost all deployment stages are pre-defined operational steps rather than decision points. However, Option Theory suggests that optional stages, to be used only when risk materialises, should be integral parts of project plans. Although such optional stages are often more valuable than pre-defined stages, the evidence presented in this article shows that they are only rarely utilised. Therefore, a simple framework is presented; it first identifies risks related to the deployment of enterprise systems, then identifies optional stages that can mitigate these risks, and finally compares the costs and benefits of both pre-defined and optional stages.

  9. Case study of evaluations that go beyond clinical outcomes to assess quality improvement diabetes programmes using the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE).

    Science.gov (United States)

    Paquette-Warren, Jann; Harris, Stewart B; Naqshbandi Hayward, Mariam; Tompkins, Jordan W

    2016-10-01

    Investments in efforts to reduce the burden of diabetes on patients and health care are critical; however, more evaluation is needed to provide evidence that informs and supports future policies and programmes. The newly developed Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) incorporates the theoretical concepts needed to facilitate the capture of critical information to guide investments, policy and programmatic decision making. The aim of the study is to assess the applicability and value of DEFINE in comprehensive real-world evaluation. Using a critical and positivist approach, this intrinsic and collective case study retrospectively examines two naturalistic evaluations to demonstrate how DEFINE could be used when conducting real-world comprehensive evaluations in health care settings. The variability between the cases and the evaluation designs are described and aligned to the DEFINE goals, steps and sub-steps. The majority of the theoretical steps of DEFINE were exemplified in both cases, although limited for knowledge translation efforts. Application of DEFINE to evaluate diverse programmes that target various chronic diseases is needed to further test the inclusivity and built-in flexibility of DEFINE and its role in encouraging more comprehensive knowledge translation. This case study shows how DEFINE could be used to structure or guide comprehensive evaluations of programmes and initiatives implemented in health care settings and support scale-up of successful innovations. Future use of the framework will continue to strengthen its value in guiding programme evaluation and informing health policy to reduce the burden of diabetes and other chronic diseases. © 2016 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

  10. 19q13.12 microdeletion syndrome fibroblasts display abnormal storage of cholesterol and sphingolipids in the endo-lysosomal system.

    Science.gov (United States)

    Zhao, Kexin; van der Spoel, Aarnoud; Castiglioni, Claudia; Gale, Sarah; Fujiwara, Hideji; Ory, Daniel S; Ridgway, Neale D

    2018-06-01

    Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency syndrome characterized by intellectual deficiency, developmental delays, and neurological movement disorders. Variability in the size and interval of the deletions makes it difficult to attribute the complex clinical phenotype of this syndrome to an underlying gene(s). As an alternate approach, we examined the biochemical and metabolic features of fibroblasts from an affected individual to derive clues as to the molecular basis for the syndrome. Immunofluorescence and electron microscopy of affected fibroblasts revealed an abnormal endo-lysosomal compartment that was characterized by rapid accumulation of lysosomotropic dyes, elevated LAMP1 and LAMP2 expression and vacuoles containing membrane whorls, common features of lysosomal lipid storage disorders. The late endosomes-lysosomes (LE/LY) of affected fibroblasts accumulated low-density lipoprotein cholesterol, and displayed reduced cholesterol esterification and increased de novo cholesterol synthesis, indicative of defective cholesterol transport to the endoplasmic reticulum. Affected fibroblasts also had increased ceramide and sphingolipid mass, altered glycosphingolipid species and accumulation of a fluorescent lactosylceramide probe in LE/LY. Autophagosomes also accumulated in affected fibroblasts because of decreased fusion with autolysosomes, a defect associated with other lysosomal storage diseases. Attempts to correct the cholesterol/sphingolipid storage defect in fibroblasts with cyclodextrin, sphingolipid synthesis inhibitors or by altering ion transport were unsuccessful. Our data show that 19q13.12 deletion fibroblasts have abnormal accumulation of cholesterol and sphingolipids in the endo-lysosomal system that compromises organelle function and could be an underlying cause of the clinical features of the syndrome. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Defining the multi-dimensional aspects of household waste management: A study of reported behavior in Devon

    Energy Technology Data Exchange (ETDEWEB)

    Barr, Stewart; Gilg, Andrew; Ford, Nicholas [Department of Geography, School of Geography, Archaeology and Earth Resources, University of Exeter, Amory Building, Rennes Drive, Exeter, Devon EX4 4RJ (United Kingdom)

    2005-10-01

    This paper examines the structure of waste reduction, reuse and recycling behavior within the context of wider research on environmental action in and around the home. Using a sample of 1265 households from Devon, England, the research examined a range of environmental behaviors, focusing on energy saving, water conservation, green consumerism and waste management. Using factor analysis, the data were analysed to examine how the different behavioral variables related to each other. The research found that waste management behaviors were evident in two of the three factors identified. These related not only to recycling or reuse behaviors but also to consumption practices, such as purchasing recycled products. However, an analysis of the frequency of each of these factorially-defined behaviors revealed that recycling was still the activity most practised by individuals, with reduction behaviors least popular. This was explored further by the use of cluster analysis, which defined four distinctive behavioral types with different demographic characteristics. Accordingly, the research demonstrates that examining waste management behaviors within the context of wider environmental actions can be of use.

  12. Physical degradation of proteins in well-defined fluid flows studied within a four-roll apparatus.

    Science.gov (United States)

    Simon, S; Krause, H J; Weber, C; Peukert, W

    2011-12-01

    In most applications of biotechnology and downstream processing proteins are exposed to fluid stresses in various flow configurations which often lead to the formation of unwanted protein aggregates. In this paper we present physical degradation experiments for proteins under well-defined flow conditions in a four-roll apparatus. The flow field was characterized numerically by computational fluid dynamics (CFD) and experimentally by particle image velocimetry (PIV). The local shear strain rate as well as the local shear and elongation rate was used to characterize the hydrodynamic stress environment acting on the proteins. Lysozyme was used as a model protein and subjected to well-defined fluid stresses in high and low stress environment. By using in situ turbidity measurements during stressing the aggregate formation was monitored directly in the fluid flow. An increase in absorbance at 350 nm was attributed to a higher content of visible particles (>1 µm). In addition to lysozyme, the formation of aggregates was confirmed for two larger proteins (bovine serum albumin and alcohol dehydrogenase). Thus, the presented experimental setup is a helpful tool to monitor flow-induced protein aggregation with high reproducibility. For instance, screening experiments for formulation development of biopharmaceuticals for fill and finish operations can be performed in the lab-scale in a short time-period if the stress distributions in the application are transferred and applied in the four-roll mill. Copyright © 2011 Wiley Periodicals, Inc.

  13. Tangential vs. defined radiotherapy in early breast cancer treatment without axillary lymph node dissection. A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Nitsche, Mirko [Zentrum fuer Strahlentherapie und Radioonkologie, Bremen (Germany); Universitaet Kiel, Klinik fuer Strahlentherapie, Karl-Lennert-Krebscentrum, Kiel (Germany); Temme, Nils; Foerster, Manuela; Reible, Michael [Zentrum fuer Strahlentherapie und Radioonkologie, Bremen (Germany); Hermann, Robert Michael [Zentrum fuer Strahlentherapie und Radioonkologie, Bremen (Germany); Medizinische Hochschule Hannover, Abteilung Strahlentherapie und Spezielle Onkologie, Hannover (Germany)

    2014-08-15

    Recent studies have demonstrated low regional recurrence rates in early-stage breast cancer omitting axillary lymph node dissection (ALND) in patients who have positive nodes in sentinel lymph node dissection (SLND). This finding has triggered an active discussion about the effect of radiotherapy within this approach. The purpose of this study was to analyze the dose distribution in the axilla in standard tangential radiotherapy (SRT) for breast cancer and the effects on normal tissue exposure when anatomic level I-III axillary lymph node areas are included in the tangential radiotherapy field configuration. We prospectively analyzed the dosimetric treatment plans from 51 consecutive women with early-stage breast cancer undergoing radiotherapy. We compared and analyzed the SRT and the defined radiotherapy (DRT) methods for each patient. The clinical target volume (CTV) of SRT included the breast tissue without specific contouring of lymph node areas, whereas the CTV of DRT included the level I-III lymph node areas. We evaluated the dose given in SRT covering the axillary lymph node areas of level I-III as contoured in DRT. The mean V{sub D95} {sub %} of the entire level I-III lymph node area in SRT was 50.28 % (range, 37.31-63.24 %), V{sub D45} {sub Gy} was 70.1 % (54.8-85.4 %), and V{sub D40} {sub Gy} was 83.5 % (72.3-94.8 %). A significant difference was observed between lung dose and heart toxicity in SRT vs. DRT. The V{sub 20} {sub Gy} and V{sub 30} {sub Gy} of the right and the left lung in DRT were significantly higher in DRT than in SRT (p < 0.001). The mean heart dose in SRT was significantly lower (3.93 vs. 4.72 Gy, p = 0.005). We demonstrated a relevant dose exposure of the axilla in SRT that should substantially reduce local recurrences. Furthermore, we demonstrated a significant increase in lung and heart exposure when including the axillary lymph nodes regions in the tangential radiotherapy field set-up. (orig.) [German] Aktuelle Studien zeigen

  14. Kaolinite: Defect defined material properties – A soft X-ray and first principles study of the band gap

    Energy Technology Data Exchange (ETDEWEB)

    Pietzsch, A., E-mail: annette.pietzsch@helmholtz-berlin.de [Institute for Methods and Instrumentation in Synchrotron Radiation Research G-ISRR, Helmholtz-Zentrum für Materialien und Energie GmbH, Albert-Einstein-Str. 15, 12489 Berlin (Germany); Nisar, J. [Pakistan Atomic Energy Commission (PAEC), P.O. Box 2151, Islamabad (Pakistan); Jämstorp, E. [Swiss Light Source, Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Gråsjö, J. [Department of Pharmacy, Uppsala University, Box 580, 75123 Uppsala (Sweden); Århammar, C. [Coromant R& D, S-126 80 Stockholm (Sweden); Ahuja, R.; Rubensson, J.-E. [Department of Physics and Astronomy, Uppsala University, Box 516, 751 20 Uppsala (Sweden)

    2015-07-15

    Highlights: • The respective electronic structure of synthetic and natural kaolinite is compared. • The size of the band gap and thus many important material properties are defined by defect states in the band gap. • The oxygen-based defect states are identified and analyzed. • The band gap of kaolinite decreases significantly due to the forming of defects. - Abstract: By combining X-ray absorption spectroscopy and first principles calculations we have determined the electronic structure of synthetic and natural kaolinite as a model system for engineered and natural clay materials. We have analyzed defect states in the band gap and find that both natural and synthetic kaolinite contain defects where oxygen replaces hydrogen in one of the Al (0 0 1)-hydroxyl groups of the kaolinite clay sheets. The band gap of both synthetic and natural kaolinite is found to decrease by about 3.2 eV as this defect is formed.

  15. Kaolinite: Defect defined material properties – A soft X-ray and first principles study of the band gap

    International Nuclear Information System (INIS)

    Pietzsch, A.; Nisar, J.; Jämstorp, E.; Gråsjö, J.; Århammar, C.; Ahuja, R.; Rubensson, J.-E.

    2015-01-01

    Highlights: • The respective electronic structure of synthetic and natural kaolinite is compared. • The size of the band gap and thus many important material properties are defined by defect states in the band gap. • The oxygen-based defect states are identified and analyzed. • The band gap of kaolinite decreases significantly due to the forming of defects. - Abstract: By combining X-ray absorption spectroscopy and first principles calculations we have determined the electronic structure of synthetic and natural kaolinite as a model system for engineered and natural clay materials. We have analyzed defect states in the band gap and find that both natural and synthetic kaolinite contain defects where oxygen replaces hydrogen in one of the Al (0 0 1)-hydroxyl groups of the kaolinite clay sheets. The band gap of both synthetic and natural kaolinite is found to decrease by about 3.2 eV as this defect is formed

  16. Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma. A section-to-section comparison study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Lim, Tae-Hwan [Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Kang, Soo-Jin; Chang, Mineok; Lee, Pil Hyung; Roh, Jae-Hyung; Ahn, Jung-Min; Park, Duk-Woo; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung; Kim, Young-Hak [Asan Medical Center, University of Ulsan College of Medicine, Department of Cardiology, Seoul (Korea, Republic of); Baek, Seunghee [Asan Medical Center, University of Ulsan College of Medicine, Department of Clinical Epidemiology and Biostatistics, Seoul (Korea, Republic of); Han, Seungbong [Gachon University, Department of Applied Statistics, Gyeonggi-do (Korea, Republic of); Mintz, Gary S. [Cardiovascular Research Foundation, New York, NY (United States)

    2018-02-15

    To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA) - a precursor of plaque rupture - defined by optical coherence tomography (OCT) in a section-to-section-level comparison. From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm{sup 2}). LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. (orig.)

  17. Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions.

    Directory of Open Access Journals (Sweden)

    Mathias J Gerl

    Full Text Available Cell membranes contain hundreds to thousands of individual lipid species that are of structural importance but also specifically interact with proteins. Due to their highly controlled synthesis and role in signaling events sphingolipids are an intensely studied class of lipids. In order to investigate their metabolism and to study proteins interacting with sphingolipids, metabolic labeling based on photoactivatable sphingoid bases is the most straightforward approach. In order to monitor protein-lipid-crosslink products, sphingosine derivatives containing a reporter moiety, such as a radiolabel or a clickable group, are used. In normal cells, degradation of sphingoid bases via action of the checkpoint enzyme sphingosine-1-phosphate lyase occurs at position C2-C3 of the sphingoid base and channels the resulting hexadecenal into the glycerolipid biosynthesis pathway. In case the functionalized sphingosine looses the reporter moiety during its degradation, specificity towards sphingolipid labeling is maintained. In case degradation of a sphingosine derivative does not remove either the photoactivatable or reporter group from the resulting hexadecenal, specificity towards sphingolipid labeling can be achieved by blocking sphingosine-1-phosphate lyase activity and thus preventing sphingosine derivatives to be channeled into the sphingolipid-to-glycerolipid metabolic pathway. Here we report an approach using clustered, regularly interspaced, short palindromic repeats (CRISPR-associated nuclease Cas9 to create a sphingosine-1-phosphate lyase (SGPL1 HeLa knockout cell line to disrupt the sphingolipid-to-glycerolipid metabolic pathway. We found that the lipid and protein compositions as well as sphingolipid metabolism of SGPL1 knock-out HeLa cells only show little adaptations, which validates these cells as model systems to study transient protein-sphingolipid interactions.

  18. Delirium diagnosis defined by cluster analysis of symptoms versus diagnosis by DSM and ICD criteria: diagnostic accuracy study.

    Science.gov (United States)

    Sepulveda, Esteban; Franco, José G; Trzepacz, Paula T; Gaviria, Ana M; Meagher, David J; Palma, José; Viñuelas, Eva; Grau, Imma; Vilella, Elisabet; de Pablo, Joan

    2016-05-26

    Information on validity and reliability of delirium criteria is necessary for clinicians, researchers, and further developments of DSM or ICD. We compare four DSM and ICD delirium diagnostic criteria versions, which were developed by consensus of experts, with a phenomenology-based natural diagnosis delineated using cluster analysis of delirium features in a sample with a high prevalence of dementia. We also measured inter-rater reliability of each system when applied by two evaluators from distinct disciplines. Cross-sectional analysis of 200 consecutive patients admitted to a skilled nursing facility, independently assessed within 24-48 h after admission with the Delirium Rating Scale-Revised-98 (DRS-R98) and for DSM-III-R, DSM-IV, DSM-5, and ICD-10 criteria for delirium. Cluster analysis (CA) delineated natural delirium and nondelirium reference groups using DRS-R98 items and then diagnostic systems' performance were evaluated against the CA-defined groups using logistic regression and crosstabs for discriminant analysis (sensitivity, specificity, percentage of subjects correctly classified by each diagnostic system and their individual criteria, and performance for each system when excluding each individual criterion are reported). Kappa Index (K) was used to report inter-rater reliability for delirium diagnostic systems and their individual criteria. 117 (58.5 %) patients had preexisting dementia according to the Informant Questionnaire on Cognitive Decline in the Elderly. CA delineated 49 delirium subjects and 151 nondelirium. Against these CA groups, delirium diagnosis accuracy was highest using DSM-III-R (87.5 %) followed closely by DSM-IV (86.0 %), ICD-10 (85.5 %) and DSM-5 (84.5 %). ICD-10 had the highest specificity (96.0 %) but lowest sensitivity (53.1 %). DSM-III-R had the best sensitivity (81.6 %) and the best sensitivity-specificity balance. DSM-5 had the highest inter-rater reliability (K =0.73) while DSM-III-R criteria were the least

  19. Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis

    Directory of Open Access Journals (Sweden)

    Giaever Guri

    2009-01-01

    Full Text Available Abstract Background Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug. Results Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can be obtained by combining different chemical genomics approaches – analysis of the sensitivity of ρ0 cells lacking mitochondrial DNA, drug-induced haploinsufficiency, suppression of drug sensitivity by gene overexpression and chemical-genetic synthetic lethality screening using strains deleted of nonessential genes. Killing of yeast by this chemical requires a functional mitochondrial electron-transport chain and cytochrome c heme lyase function. However, we find that it does not require genes associated with programmed cell death in yeast. The chemical also inhibits endocytosis and intracellular vesicle trafficking and interferes with vacuolar acidification in yeast and in human cancer cells. These effects can all be ascribed to inhibition of sphingolipid biosynthesis by dihydromotuporamine C. Conclusion Despite their similar conceptual basis, namely altering drug sensitivity by modifying gene dosage, each of the screening approaches provided a distinct set of information that, when integrated, revealed a more complete picture of the mechanism of action of a drug on cells.

  20. Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

    Science.gov (United States)

    Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

    2017-01-01

    The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

  1. A hybrid mathematical modeling approach of the metabolic fate of a fluorescent sphingolipid analogue to predict cancer chemosensitivity.

    Science.gov (United States)

    Molina-Mora, J A; Kop-Montero, M; Quirós-Fernández, I; Quiros, S; Crespo-Mariño, J L; Mora-Rodríguez, R A

    2018-04-13

    Sphingolipid (SL) metabolism is a complex biological system that produces and transforms ceramides and other molecules able to modulate other cellular processes, including survival or death pathways key to cell fate decisions. This signaling pathway integrates several types of stress signals, including chemotherapy, into changes in the activity of its metabolic enzymes, altering thereby the cellular composition of bioactive SLs. Therefore, the SL pathway is a promising sensor of chemosensitivity in cancer and a target hub to overcome resistance. However, there is still a gap in our understanding of how chemotherapeutic drugs can disturb the SL pathway in order to control cellular fate. We propose to bridge this gap by a systems biology approach to integrate i) a dynamic model of SL analogue (BODIPY-FL fluorescent-sphingomyelin analogue, SM-BOD) metabolism, ii) a Gaussian mixture model (GMM) of the fluorescence features to identify how the SL pathway senses the effect of chemotherapy and iii) a fuzzy logic model (FLM) to associate SL composition with cell viability by semi-quantitative rules. Altogether, this hybrid model approach was able to predict the cell viability of double experimental perturbations with chemotherapy, indicating that the SL pathway is a promising sensor to design strategies to overcome drug resistance in cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

    Directory of Open Access Journals (Sweden)

    Anahí Capmany

    2010-11-01

    Full Text Available Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

  3. Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

    Science.gov (United States)

    Capmany, Anahí; Damiani, María Teresa

    2010-11-22

    Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

  4. Software Defined Networking challenges and future direction: A case study of implementing SDN features on OpenStack private cloud

    International Nuclear Information System (INIS)

    Shamugam, Veeramani; Murray, I; Leong, J A; Sidhu, Amandeep S

    2016-01-01

    Cloud computing provides services on demand instantly, such as access to network infrastructure consisting of computing hardware, operating systems, network storage, database and applications. Network usage and demands are growing at a very fast rate and to meet the current requirements, there is a need for automatic infrastructure scaling. Traditional networks are difficult to automate because of the distributed nature of their decision making process for switching or routing which are collocated on the same device. Managing complex environments using traditional networks is time-consuming and expensive, especially in the case of generating virtual machines, migration and network configuration. To mitigate the challenges, network operations require efficient, flexible, agile and scalable software defined networks (SDN). This paper discuss various issues in SDN and suggests how to mitigate the network management related issues. A private cloud prototype test bed was setup to implement the SDN on the OpenStack platform to test and evaluate the various network performances provided by the various configurations. (paper)

  5. Software Defined Networking challenges and future direction: A case study of implementing SDN features on OpenStack private cloud

    Science.gov (United States)

    Shamugam, Veeramani; Murray, I.; Leong, J. A.; Sidhu, Amandeep S.

    2016-03-01

    Cloud computing provides services on demand instantly, such as access to network infrastructure consisting of computing hardware, operating systems, network storage, database and applications. Network usage and demands are growing at a very fast rate and to meet the current requirements, there is a need for automatic infrastructure scaling. Traditional networks are difficult to automate because of the distributed nature of their decision making process for switching or routing which are collocated on the same device. Managing complex environments using traditional networks is time-consuming and expensive, especially in the case of generating virtual machines, migration and network configuration. To mitigate the challenges, network operations require efficient, flexible, agile and scalable software defined networks (SDN). This paper discuss various issues in SDN and suggests how to mitigate the network management related issues. A private cloud prototype test bed was setup to implement the SDN on the OpenStack platform to test and evaluate the various network performances provided by the various configurations.

  6. [How do adolescents in Germany define cyberbullying? A focus-group study of adolescents from a German major city].

    Science.gov (United States)

    Höher, Jonas; Scheithauer, Herbert; Schultze-Krumbholz, Anja

    2014-01-01

    A steadily growing number of empirical research on cyberbullying exists retaining the traditional definition of bullying. However, whether this scientific and theoretical definition represents youths' perceptions and experiences with cyberbullying is a subject of further investigation. Scenarios of cyberbullying incidents were used and later discussed in three focus groups with 20 adolescents (55 % boys, 45 % girls, 11-16 years old). Thematic and content analyses laid focus on the following questions: (1) Which terms are used by the adolescents to describe the behaviors in the incidents? (2) What are the roles of traditional bullying definition criteria (i. e. intention, repetition, and power imbalance) and two additional cyberbullying-specific criteria (i. e. anonymity and publicity)? (3) How are the behaviors perceived in comparison to each other? Results show that German adolescents perceive "cybermobbing" as the best term to describe the presented incidents. Impersonation was not perceived as cyberbullying by the adolescents, but rather viewed as a criminal act. In addition, adolescents perceived the intent to harm, the impact on the victim, and repetition relevant for defining cyberbullying. Moreover, analyses revealed an interdependence between criteria which suggests that anonymity and publicity have an effect on the severity of the behavior, however they were not essential for the definition of cyberbullying.

  7. Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

    Science.gov (United States)

    Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

    2016-01-01

    Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520

  8. Reconstituting factor concentrates: Defining Evidence of Coaching Non-Experts (DEVICE) in haemophilia--a prospective randomized feasibility study.

    Science.gov (United States)

    Bidlingmaier, C; Kurnik, K; Hölscher, G; Kappler, M

    2007-09-01

    The introduction of new needleless devices as demanded by the US Department of Labor Occupational Safety and Health Administration (OSHA) has caused problems with the reconstitution of antihaemophilic factor in emergency situations. Our aim therefore was to evaluate the feasibility of a needleless device for reconstitution of antihaemophilic factor for non-haemophilia experts and to define evidence of the need for coaching these physicians via providing two additional photographs illustrating the two key points of the factor reconstitution process. Twenty-eight physicians of a tertiary care university children's hospital were randomized into two groups, either with no further explanation of the reconstitution device or with two additional photographs, showing the two key steps of the procedure. Reconstitution of dummy-factor concentrate was video-taped and evaluated by a blinded helper. Main outcome measure was the successful reconstitution of dummy-factor concentrate and procedure failure respectively. Of the group without explanation of the reconstitution device, only two of 14 physicians were able to reconstitute the dummy-factor concentrate. Of the group receiving two photographs, nine of 14 completed the task successfully (P = 0.0068). The needleless device is not self explaining to non-haemophilia physicians involved in emergency services. Coaching via short to the point instructions as provided by simple visual educational material therefore is crucial to enable these physicians to resolve the expensive emergency drug quickly and correctly. Companies concerned with the production of any devices to dissolve drugs, especially for treatment of rare diseases as haemophilia, therefore should take measures to simplify therapy.

  9. Body mass index bias in defining obesity of diverse young adults: The Training Intervention and Genetics of Exercise Response (TIGER) Study

    Science.gov (United States)

    The BMI cut-score used to define overweight and obesity was derived primarily using data from Caucasian men and women. The present study evaluated the racial/ethnic bias of BMI to estimate the adiposity of young men and women (aged 17–35 years) using dual-energy X-ray absorptiometry (DXA) determinat...

  10. A prospective study of the influence of a thalassaemia on morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in Gambian children

    DEFF Research Database (Denmark)

    Allen, S J; Rowe, P; Allsopp, C E

    1993-01-01

    with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune...

  11. The Age of Studies and Reports: Selected Elements Concerning the Background of Encounters Defining the Power of Education

    Science.gov (United States)

    Tašner, Veronika; Gaber, Slavko

    2016-01-01

    In the present paper, we discuss the time before the "age of reports". Besides the Coleman Report in the period of Coleman, the Lady Plowden Report also appeared, while there were important studies in France (Bourdieu & Passeron, 1964; Peyre, 1959) and studies that inaugurated comprehensive education in Nordic countries. We focus on…

  12. Defining Quantum Control Flow

    OpenAIRE

    Ying, Mingsheng; Yu, Nengkun; Feng, Yuan

    2012-01-01

    A remarkable difference between quantum and classical programs is that the control flow of the former can be either classical or quantum. One of the key issues in the theory of quantum programming languages is defining and understanding quantum control flow. A functional language with quantum control flow was defined by Altenkirch and Grattage [\\textit{Proc. LICS'05}, pp. 249-258]. This paper extends their work, and we introduce a general quantum control structure by defining three new quantu...

  13. Diagnostic strategies using physical examination are minimally useful in defining carpal tunnel syndrome in population-based research studies.

    Science.gov (United States)

    Descatha, A; Dale, A-M; Franzblau, A; Coomes, J; Evanoff, B

    2010-02-01

    We evaluated the utility of physical examination manoeuvres in the prediction of carpal tunnel syndrome (CTS) in a population-based research study. We studied a cohort of 1108 newly employed workers in several industries. Each worker completed a symptom questionnaire, a structured physical examination and nerve conduction study. For each hand, our CTS case definition required both median nerve conduction abnormality and symptoms classified as "classic" or "probable" on a hand diagram. We calculated the positive predictive values and likelihood ratios for physical examination manoeuvres in subjects with and without symptoms. The prevalence of CTS in our cohort was 1.2% for the right hand and 1.0% for the left hand. The likelihood ratios of a positive test for physical provocative tests ranged from 2.0 to 3.3, and those of a negative test from 0.3 to 0.9. The post-test probability of positive testing was study found that physical examination, alone or in combination with symptoms, was not predictive of CTS in a working population. We suggest using specific symptoms as a first-level screening tool, and nerve conduction study as a confirmatory test, as a case definition strategy in research settings.

  14. Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

    Science.gov (United States)

    Giorni, Paola; Dall’Asta, Chiara; Reverberi, Massimo; Scala, Valeria; Ludovici, Matteo; Cirlini, Martina; Galaverna, Gianni; Fanelli, Corrado; Battilani, Paola

    2015-01-01

    Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open. PMID:26378580

  15. Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

    Directory of Open Access Journals (Sweden)

    Paola Giorni

    2015-09-01

    Full Text Available Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open.

  16. Assessing the Measures of and Defining Community College Institutional Effectiveness: A President's Perspective Delphi Study

    Science.gov (United States)

    Laughlin, Juliet Adair

    2016-01-01

    The purpose of this study included two main goals. The first was to provide a common definition for community college institutional effectiveness through a review of the literature and from the personal definitions of a panel of community colleges presidents leading notably effective community colleges. The second purpose was to review the…

  17. Defining and improving quality management in Dutch diabetes care groups and outpatient clinics: design of the study

    Science.gov (United States)

    2013-01-01

    Background Worldwide, the organisation of diabetes care is changing. As a result general practices and diabetes teams in hospitals are becoming part of new organisations in which multidisciplinary care programs are implemented. In the Netherlands, 97 diabetes care groups and 104 outpatient clinics are working with a diabetes care program. Both types of organisations aim to improve the quality of diabetes care. Therefore, it is essential to understand the comprehensive elements needed for optimal quality management at organisational level. This study aims to assess the current level of diabetes quality management in both care groups and outpatient clinics and its improvement after providing feedback on their quality management system and tailored support. Methods/design This study is a before-after study with a one-year follow-up comparing the levels of quality management before and after an intervention to improve diabetes quality management. To assess the status of quality management, online questionnaires were developed based on current literature. They consist of six domains: organisation of care, multidisciplinary teamwork, patient centeredness, performance management, quality improvement policy and management strategies. Based on the questionnaires, respondents will receive feedback on their score in a radar diagram and an elucidating table. They will also be granted access to an online toolbox with instruments that proved to be effective in quality of care improvement and with practical examples. If requested, personal support in implementing these tools will be available. After one year quality management will be measured again using the same questionnaire. Discussion This study will reveal a nationwide picture of quality management in diabetes care groups and outpatient clinics in the Netherlands and evaluate the effect of offering tailored support. The operationalisation of quality management on organisational level may be of interest for other countries

  18. An anatomical study of the proximal aspect of the medial femoral condyle to define the proximal-distal condylar length

    Directory of Open Access Journals (Sweden)

    Chia-Ming Chang

    2017-01-01

    Full Text Available Objective: Despite its possible role in knee arthroplasty, the proximal-distal condylar length (PDCL of the femur has never been reported in the literature. We conducted an anatomic study of the proximal aspect of the medial femoral condyle to propose a method for measuring the PDCL. Materials and Methods: Inspection of dried bone specimens was carried out to assure the most proximal condylar margin (MPCM as the eligible starting point to measure the PDCL. Simulation surgery was performed on seven pairs of cadaveric knees to verify the clinical application of measuring the PDCL after locating the MPCM. Interobserver reliability of this procedure was also analyzed. Results: Observation of the bone specimens showed that the MPCM is a concavity formed by the junction of the distal end of the supracondylar ridge and the proximal margin of the medial condyle. This anatomically distinctive structure made the MPCM an unambiguous landmark. The cadaveric simulation surgical dissection demonstrated that the MPCM is easily accessed in a surgical setting, making the measurement of the PDCL plausible. The intraclass correlation coefficient was 0.78, indicating good interobserver reliability for this technique. Conclusion: This study has suggested that the PDCL can be measured based on the MPCM in a surgical setting. PDCL measurement might be useful in joint line position management, selection of femoral component sizes, and other applications related to the proximal-distal dimension of the knee. Further investigation is required.

  19. The Age of Studies and Reports: Selected Elements Concerning the Background of Encounters Defining the Power of Education

    Directory of Open Access Journals (Sweden)

    Veronika Tašner and Slavko Gaber

    2016-06-01

    Full Text Available In the present paper, we discuss the time before the “age of reports”. Besides the Coleman Report in the period of Coleman, the Lady Plowden Report also appeared, while there were important studies in France (Bourdieu & Passeron, 1964; Peyre, 1959 and studies that inaugurated comprehensive education in Nordic countries. We focus on the period after the World War II, which was marked by rising economic nationalism, on the one hand, and by the second wave of mass education, on the other, bearing the promise of more equality and a reduction of several social inequalities, both supposed to be ensured by school. It was a period of great expectations related to the power of education and the rise of educational meritocracy. On this background, in the second part of the paper, the authors attempt to explore the phenomenon of the aforementioned reports, which significantly questioned the power of education and, at the same time, enabled the formation of evidence-based education policies. In this part of the paper, the central place is devoted to the case of socialist Yugoslavia/Slovenia and its striving for more equality and equity through education. Through the socialist ideology of more education for all, socialist Yugoslavia, with its exaggerated stress on the unified school and its overemphasised belief in simple equality, overstepped the line between relying on comprehensive education as an important mechanism for increasing the possibility of more equal and just education, on the one hand, and the myth of the almighty unified school capable of eradicating social inequalities, especially class inequalities, on the other. With this radical approach to the reduction of inequalities, socialist policy in the then Yugoslavia paradoxically reduced the opportunity for greater equality, and even more so for more equitable education.

  20. Defining the urban area for cross national comparison of health indicators: the EURO-URHIS 2 boundary study.

    Science.gov (United States)

    Higgerson, James; Birt, Christopher A; van Ameijden, Erik; Verma, Arpana

    2017-05-01

    Despite much research focusing on the impact of the city condition upon health, there still remains a lack of consensus over what constitutes an urban area (UA). This study was conducted to establish comparable boundaries for the UAs participating in EURO-URHIS 2, and to test whether the sample reflected the heterogeneity of urban living. Key UA contacts ( n = 28) completed a cross-sectional questionnaire, which included where available comparison between Urban Audit city and larger urban zone (LUZ) boundaries and public health administration areas (PHAAs). Additionally, broad health and demographic indicators were sought to test for heterogeneity of the EURO-URHIS 2 sample. Urban Audit city boundaries were found to be suitable for data collection in 100% ( n = 21) of UAs where Urban Audit data were available. The remainder ( n = 7) identified PHAA boundaries akin to the 'city' level. Heterogeneity was observed in the sample for population size and infant mortality rate. Heterogeneity could not be established for male and female life expectancy. This study was able to establish comparable boundaries for EURO-URHIS 2 data collection, with the 'city' area being selected for data collection. The homogeneity of life expectancy indicators was reflective of sub-regional similarities in life expectancy, whilst population estimates and rates of infant mortality indicated the presence of heterogeneity within the sample. Future work would trial these methods with a larger number of indicators and for a larger number of UAs. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  1. Defining a conformational consensus motif in cotransin-sensitive signal sequences: a proteomic and site-directed mutagenesis study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Klein

    Full Text Available The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity.

  2. Defining a Conformational Consensus Motif in Cotransin-Sensitive Signal Sequences: A Proteomic and Site-Directed Mutagenesis Study

    Science.gov (United States)

    Klein, Wolfgang; Westendorf, Carolin; Schmidt, Antje; Conill-Cortés, Mercè; Rutz, Claudia; Blohs, Marcus; Beyermann, Michael; Protze, Jonas; Krause, Gerd; Krause, Eberhard; Schülein, Ralf

    2015-01-01

    The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar) to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity. PMID:25806945

  3. Studies on the formation of hierarchical zeolite T aggregates with well-defined morphology in different template systems

    Science.gov (United States)

    Yin, Xiaoyan; Chu, Naibo; Lu, Xuewei; Li, Zhongfang; Guo, Hong

    2016-01-01

    In this paper, the disk-like and pumpkin-like hierarchical zeolite T aggregates consisted of primary nano-grains have been hydrothermally synthesized with and without the aid of the second template. The first template is used with tetramethylammonium hydroxide (TMAOH) and the second template is used with triethanolamine (TEA) or polyving akohol (PVA). A combination of characterization techniques, including XRD, SEM, TEM and N2 adsorption-desorption to examine the crystal crystallinity, morphology and surface properties of hierarchical zeolite T aggregates. In the single-template preparation process, the two-step varying-temperature treatment has been used to improve the meso-porosity of zeolite T aggregates. In the double-template preparation process, the amounts of PVA or TEA on the crystallinity, morphology and meso-porosity of zeolite T aggregates have been studied. It has been proved that the interstitial voids between the primary grains of aggregates are the origin of additional mesopores of samples. The micro- and meso-porosities of samples prepared with and without the second template have been contrasted in detail at last. In particular, the sample synthesized with the addition of PVA presents a hierarchical pore structure with the highest Sext value of 122 m2/g and Vmeso value of 0.255 cm3/g.

  4. Useful Bicistronic Reporter System for Studying Poly(A Site-Defining cis Elements and Regulation of Alternative Polyadenylation

    Directory of Open Access Journals (Sweden)

    Zhongyuan Deng

    2018-01-01

    Full Text Available The link between polyadenylation (pA and various biological, behavioral, and pathological events of eukaryotes underlines the need to develop in vivo polyadenylation assay methods for characterization of the cis-acting elements, trans-acting factors and environmental stimuli that affect polyadenylation efficiency and/or relative usage of two alternative polyadenylation (APA sites. The current protein-based CAT or luciferase reporter systems can measure the polyadenylation efficiency of a single pA site or candidate cis element but not the choice of two APA sites. To address this issue, we developed a set of four new bicistronic reporter vectors that harbor either two luciferase or fluorescence protein open reading frames connected with one Internal Ribosome Entry Site (IRES. Transfection of single or dual insertion constructs of these vectors into mammalian cells demonstrated that they could be utilized not only to quantify the strength of a single candidate pA site or cis element, but also to accurately measure the relative usage of two APA sites at both the mRNA (qRT-PCR and protein levels. This represents the first reporter system that can study polyadenylation efficiency of a single pA site or element and regulation of two APA sites at both the mRNA and protein levels.

  5. Defining a framework for medical teachers' competencies to teach ethnic and cultural diversity: Results of a European Delphi study.

    Science.gov (United States)

    Hordijk, Rowan; Hendrickx, Kristin; Lanting, Katja; MacFarlane, Anne; Muntinga, Maaike; Suurmond, Jeanine

    2018-02-28

    Medical students need to be trained in delivering diversity-responsive health care but unknown is what competencies teachers need. The aim of this study was to devise a framework of competencies for diversity teaching. An open-ended questionnaire about essential diversity teaching competencies was sent to a panel. This resulted in a list of 74 teaching competencies, which was sent in a second round to the panel for rating. The final framework of competencies was approved by the panel. Thirty-four experts participated. The final framework consisted of 10 competencies that were seen as essential for all medical teachers: (1) ability to critically reflect on own values and beliefs; (2) ability to communicate about individuals in a nondiscriminatory, nonstereotyping way; (3) empathy for patients regardless of ethnicity, race or nationality; (4) awareness of intersectionality; (5) awareness of own ethnic and cultural background; (6) knowledge of ethnic and social determinants of physical and mental health of migrants; (7) ability to reflect with students on the social or cultural context of the patient relevant to the medical encounter; (8) awareness that teachers are role models in the way they talk about patients from different ethnic, cultural and social backgrounds; (9) empathy for students of diverse ethnic, cultural and social background; (10) ability to engage, motivate and let all students participate. This framework of teaching competencies can be used in faculty development programs to adequately train all medical teachers.

  6. Systematic study on genetic and epimutational profile of a cohort of Amsterdam criteria-defined Lynch Syndrome in Singapore.

    Directory of Open Access Journals (Sweden)

    Yanqun Liu

    Full Text Available BACKGROUND: Germline defects of mismatch repair (MMR genes underlie Lynch Syndrome (LS. We aimed to gain comprehensive genetic and epigenetic profiles of LS families in Singapore, which will facilitate efficient molecular diagnosis of LS in Singapore and the region. METHODS: Fifty nine unrelated families were studied. Mutations in exons, splice-site junctions and promoters of five MMR genes were scanned by high resolution melting assay followed by DNA sequencing, large fragment deletions/duplications and promoter methylation in MLH1, MSH2, MSH6 and PMS2 were evaluated by multiplex ligation-dependent probe amplification. Tumor microsatellite instability (MSI was assessed with five mononucleotide markers and immunohistochemical staining (IHC was also performed. RESULTS: Pathogenic defects, all confined to MLH1 and MSH2, were identified in 17 out of 59 (28.8% families. The mutational spectrum was highly heterogeneous and 28 novel variants were identified. One recurrent mutation in MLH1 (c.793C>T was also observed. 92.9% sensitivity for indication of germline mutations conferred by IHC surpassed 64.3% sensitivity by MSI. Furthermore, 15.6% patients with MSS tumors harbored pathogenic mutations. CONCLUSIONS: Among major ethnic groups in Singapore, all pathogenic germline defects were confined to MLH1 and MSH2. Caution should be applied when the Amsterdam criteria and consensus microsatellite marker panel recommended in the revised Bethesda guidelines are applied to the local context. We recommend a screening strategy for the local LS by starting with tumor IHC and the hotspot mutation testing at MLH1 c.793C>T followed by comprehensive mutation scanning in MLH1 and MSH2 prior to proceeding to other MMR genes.

  7. Ecological thresholds as a basis for defining management triggers for National Park Service vital signs: case studies for dryland ecosystems

    Science.gov (United States)

    Bowker, Matthew A.; Miller, Mark E.; Belote, R. Travis; Garman, Steven L.

    2013-01-01

    understanding and estimating of threshold dynamics for terrestrial dryland ecosystems in national parks of the Colorado Plateau. We provide a structured approach to identify and describe degradation processes associated with threshold behavior and to estimate indicator levels that characterize the point at which a threshold crossing has occurred or is imminent (tipping points) or points where investigative or preventive management action should be triggered (assessment points). We illustrate this method for several case studies in national parks included in the Northern and Southern Colorado Plateau NPS I&M networks, where historical livestock grazing, climatic change, and invasive species are key agents of change. The approaches developed in these case studies are intended to enhance the design, effectiveness, and management-relevance of monitoring efforts in support of conservation management in dryland systems. They specifically enhance National Park Service (NPS) capacity for protecting park resources on the Colorado Plateau but have applicability to monitoring and conservation management of dryland ecosystems worldwide.

  8. Defining Overweight and Obesity

    Science.gov (United States)

    ... Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook Tweet Share Compartir ... weight for a given height is described as overweight or obese. Body Mass Index, or BMI, is ...

  9. Drinking Levels Defined

    Science.gov (United States)

    ... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... Definition of Drinking at Low Risk for Developing Alcohol Use Disorder (AUD): For women, low-risk drinking is defined ...

  10. Defining Documentary Film

    DEFF Research Database (Denmark)

    Juel, Henrik

    2006-01-01

    A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film......A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film...

  11. Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

    NARCIS (Netherlands)

    Worm, Signe W.; Bower, Mark; Reiss, Peter; Bonnet, Fabrice; Law, Matthew; Fätkenheuer, Gerd; d'Arminio Monforte, Antonella; Abrams, Donald I.; Grulich, Andrew; Fontas, Eric; Kirk, Ole; Furrer, Hansjakob; Wit, Stephane D.; Phillips, Andrew; Lundgren, Jens D.; Sabin, Caroline A.; Butcher, D.; Delforge, M.; Fanti, I.; Fontas, E.; Franquet, X.; Geffard, S.; Gras, L.; Helweg-Larsen, J.; Hillebregt, M.; Kamara, D.; Kjær, J.; Krum, E.; Lundgren, J.D.; McManus, H.; Meidahl, P.; Mocroft, A.; Nielsen, J.; Phillips, A.; Powderl, W.; Rickenbach, M.; Rode, R.; Ryom, L.; Sabin, C.A.; Salbøl Brandt, R.; Schmidt Iversen, J.; Shortman, N.; Sjøl, A.; Smith, C.; Torres, F.; Tverland, J.; Wright, S.; Zaheri, S.; de Wolf, F.; Smidt, J.; Ristola, M.; Katlama, C.; Viard, J-P.; Girard, P.-M.; Livrozet, J.M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; Degen, O.; van Lunzen, J.; Stellbrink, H.J.; Staszewski, S.; Bogner, J.; Fätkenheuer, G.; Gargalianos, P.; Kosmidis, J.; Perdios, J.; Xylomenos, G.; Filandras, A.; Karabatsaki, E.; Panos, G.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Burke, M.; Turner, D.; Yust, I.; Hassoun, G.; Pollack, S.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Gabbuti, A.; Mazzotta, F.; Lichtner, M.; Vullo, V.; Boer, K.; Geerlings, S.E.; Godfried, M.H.; Kuijpers, T.W.; Lange, J.M.A.; Nellen, F.J.B.; Pajkrt, D.; Prins, J.M.; Reiss, P.; Scherpbier, H.J.; Vrouenraets, S.M.E.; Wit, F.W.M.N.; van Vugt, M.; van der Meer, J.T.M.; van der Poll, T.; van der Valk, M.; Chirianni, A.; Gargiulo, M.; Montesarchio, E.; Antonucci, G.; Narciso, P.; Testa, A.; Vlassi, C.; Zaccarelli, M.; Castagna, A.; Gianotti, N.; Lazzarin, A.; Galli, M.; Ridolfo, A.; d'Arminio Monforte, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Bruun, J.; Maeland, A.; Ormaasen, V.; Lowe, S.; Oude Lashof, A.; Schreij, G.; Gasiorowski, J.; Knysz, B.; Bakowska, E.; Horban, A.; Flisiak, R.; Grzeszczuk, A.; Boron-Kaczmarska, A.; Parczewski, M.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Caldeira, L.; Doroana, M.; Mansinho, K.; Maltez, F.; Bravenboer, B.; Pronk, M.J.H.; Duiculescu, D.; Rakhmanova, A.; Zakharova, N.; Buzunova, S.; Jevtovic, D.; Mokráš, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Labarga, P.; Medrano, J.; Soriano, V.; Moreno, S.; Rodriguez, J.M.; Bravo, I.; Clotet, B.; Jou, A.; Paredes, R.; Puig, J.; Tural, C.; Gelinck, L.B.S.; Nouwen, J.L.; Rijnders, B.J.A.; Schurink, C.A.M.; Slobbe, L.; Verbon, A.; de Vries-Sluijs, T.E.M.S.; van der Ende, Marchina E.; van der Feltz, M.; Gatell, J.M.; Miró, J.M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M.A.; Karlsson, A.; Flamholc, L.; Ledergerber, B.; Weber, R.; Cavassini, M.; Francioli, P.; Boffi, E.; Hirschel, B.; Furrer, H.; Battegay, M.; Elzi, L.; Chentsova, N.; Kravchenko, E.; Driessen, G.J.A.; Hartwig, N.G.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A.M.; Mercey, D.; Johnson, M.A.; Mocroft, A.; Phillips, A.; Murphy, M.; Scullard, G.; Weber, J.; Fisher, M.; Leen, C.; Branger, J.; Åkerlund, B.; Morfeldt, L.; Sundström., A.; Thulin, G.; Karlsson, A.; Koppel, K.; Flamholc, L.; Ho̊kangård, C.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Moroni, M.; Perno, C.F.; Viale, P.L.; Von Schlosser, F.; Ammassari, A.; Andreoni, M.; Antinori, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M.R.; Castagna, A.; Ceccherini-Silberstein, F.; Cinque, P.; Cozzi-Lepri, A.; De Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Gori, A.; Guaraldi, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; d'Arminio Monforte, A.; Cicconi, P.; Cozzi-Lepri, A.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Costantini, A.; Giacometti, A.; Riva, A.; Angarano, G.; Carrisa, C.; Monno, L.; Lazzari, G.; Maggiolo, F.; Borderi, M.; Verucchi, G.; Viale, P.L.; Kauffmann, R.H.; Schippers, E.F.; Castelli, F.; Minardi, C.; Torti, C.; Abeli, C.; Quirino, T.; Manconi, P.E.; Piano, P.; Falasca, K.; Vecchiet, J.; Segala, D.; Sighinolfi, L.; Lo Caputo, S.; Mazzotta, F.; Alessandrini, A.; Cassola, G.; Mazzarello, G.; Piscopo, R.; Viscoli, G.; Belvisi, V.; Mastroianni, C.; Bonfanti, P.; Caramma, I.; Castelli, P.; Chiodera, A.; Alleman, M.A.; Bouwhuis, J.W.; Groeneveld, P.H.P.; Bigoloni, A.; Carenzi, L.; Castagna, A.; Cicconi, P.; Formenti, T.; Galli, A.; Galli, M.; Lazzarin, A.; Moioli, M.C.; Piolini, R.; Puoti, M.; Ridolfo, A.L.; Rizzardini, G.; Rossotti, R.; Salpietro, S.; Spagnuolo, V.; Zucchi, P.; d'Arminio Monforte, A.; Bisio, L.; Mussini, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Gargiulo, M.; Guida, M.G.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M.A.; Acinapura, R.; Andreoni, M.; Antinori, A.; Capozzi, M.; Cauda, R.; De Luca, A.; Gallo, L.; Libertone, R.; Lichtner, M.; Nicastro, E.; Tebano, G.; Tozzi, V.; Vullo, V.; Zaccarelli, M.; d'Avino, A.; Madeddu, G.; Mura, M.S.; Caramello, P.; Di Perri, G.; Orofino, G.C.; Sciandra, M.; Soetekouw, R.; ten Kate, R.W.; Manfrin, V.; Pellizzer, G.; Bernard, E.; Caissotti, C.; Cua, E.; De Salvador-Guillouet, F.; Dellamonica, P.; Dollet, K.; Durant, J.; Ferrando, S.; Fontas, E.; Mondain-Miton, V.; Naqvi, A.; Perbost, I.; Pillet, S.; Pradier, C.; Prouvost-Keller, B.; Pugliese, P.; Rahelinirina, V.; Roger, P.M.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Cellerai, C.; Dubs, R.; Egger, M.; Elzi, L.; Fehr, J.; Flepp, M.; Francioli, P.; Furrer, H.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schöni-Affolter, F.; Schüpbach, J.; Schultze, D.; Speck, R.; Taffé, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; von Wyl, V.; Arend, S.M.; Jolink, H.; Kroon, F.P.; de Boer, M.G.J.; van Dissel, J.T.; van Nieuwkoop, C.; van den Broek, P.J.; Pogany, K.; den Hollander, J.G.; Kortmann, W.; van Twillert, G.; Leyten, E.M.S.; Vriesendorp, R.; Kootstra, G.J.; ten Napel, C.H.H.; Blok, W.L.; Brinkman, K.; Frissen, P.H.J.; Schouten, W.E.M.; van den Berk, G.E.L.; Brouwer, A.E.; Juttmann, J.R.; van Kasteren, M.E.E.; Lettinga, K.D.; Veenstra, J.; Mulder, J.W.; Smit, P.M.; Weijer, S.; van Gorp, E.C.M.; Verhagen, D.W.M.; van Eeden, A.; Doedens, R.; Scholvinck, E.H.; Sprenger, H.G.; Stek, C.J.; van Assen, S.; Brouwer, A.M.; Dofferhoff, A.S.M.; Keuter, M.; Koopmans, P.P.; de Groot, R.; ter Hofstede, H.J.M.; van der Flier, M.; van der Ven, A.J.A.M.; Arends, J.E.; Ellerbroek, P.M.; Hoepelman, A.I.M.; Jaspers, C.A.J.J.; Maarschalk-Ellerbroek, L.J.; Mudrikova, T.; Oosterheert, J.J.; Peters, E.J.G.; Schneider, M.M.E.; Wassenberg, M.W.M.; van der Hilst, J.C.H.; Bierman, W.F.W.; Claessen, F.A.P.; Danner, S.A.; Perenboom, R.M.; bij de Vaate, E.A.; de Jong, E.V.; de Vocht, J.; van Agtmael, M.A.; Geelen, S.P.M.; Wolfs, T.F.W.; Gisolf, E.H.; Richter, J.P.; van der Berg, C.; Stegeman, A.; van den Berge, M.; Polée, M.B.; van Houte, D.P.F.; van Vonderen, M.G.A.; Duits, A.J.; Winkel, C.; Dabis, F.; Bonnet, F.; Chêne, G.; Dabis, F.; Dupon, M.; Fleury, H.; Lacoste, D.; Malvy, D.; Mercié, P.; Morlat, P.; Neau, D.; Pellegrin, I.; Pellegrin, J.L.; Thiébaut, R.; Titier, K.; Bruyand, M.; Chêne, G.; Dabis, F.; Lawson-Ayayi, S.; Thiébaut, R.; Wittkop, L.; Bernard, N.; Bonnal, F.; Bonnet, F.; Caunègre, L.; Cazanave, C.; Ceccaldi, J.; Chambon, D.; Chossat, I.; Courtaud, K.; Dauchy, F.A.; De Witte, S.; Duffau, P.; Dupon, M.; Dupont, A.; Dutronc, H.; Farbos, S.; Gaboriau, V.; Gemain, M.C.; Gerard, Y.; Greib, C.; Hessamfar, M.; Lacoste, D.; Lafarie-Castet, S.; Lataste, P.; Lazaro, E.; Longy-Boursier, M.; Malvy, D.; Meraud, J.P.; Mercié, P.; Monlun, E.; Morlat, P.; Neau, D.; Ochoa, A.; Pellegrin, J.L.; Pistone, T.; Ragnaud, J.M.; Receveur, M.C.; Roger-Schmeltz, J.; Tchamgoué, S.; Thibaut, P.; Vandenhende, M.A.; Viallard, J.F.; Moreau, J.F.; Pellegrin., I.; Fleury, H.; Lafon, M.E.; Masquelier, B.; Trimoulet, P.; Breilh, D.; Titier, K.; Haramburu, F.; Miremont-Salamé, G.; Blaizeau, M.J.; D'Ivernois, C.; Decoin, M.; Delaune, J.; Delveaux, S.; Hanappier, C.; Leleux, O.; Sicard, X.; Uwamaliya-Nziyumvira, B.; Geffard, S.; Leray, J.; Palmer, G.; Touchard, D.; Baker, D.; Bendall, C.; Bloch, M.; Carr, A.; Cooper, D.; Franic, T.; Law, M.; McManus, H.; Petoumenos, K.; Vale, R.; Wright, S.; Edwards, S.; Hoy, J.; Moore, R.; Nicholson, J.; Roth, N.; Watson, K.; Chuah, J.; Ngieng, M.; Nolan, D.; Skett, J.; Cadafalch, J.; Calvo, G.; Codina, C.; Del Cacho, E.; Domingo, P.; Fuster, M.; Gatell, J.; Mateu, S.; Sambeat, M.A.; Sirera, G.; Torres, F.; Vaqué, A.; Clumeck, N.; De Wit, S.; Delforge, M.; Gennotte, A.F.; Gerard, M.; Kabeya, K.; Konopnicki, D.; Libois, A.; Martin, C.; Necsoi, C.; Payen, M.C.; Semaille, P.; Van Laethem, Y.; Bartsch, G.; El-Sadr, W.M.; Krum, E.; Neaton, J.; Thompson, G.; Wentworth, D.; Luskin-Hawk, R.; Telzak, E.; El-Sadr, W.M.; Abrams, D.I.; Cohn, D.; Markowitz, N.; Arduino, R.; Mushatt, D.; Friedland, G.; Perez, G.; Tedaldi, E.; Fisher, E.; Gordin, F.; Crane, L.R.; Sampson, J.; Baxter, J.; Cozzi-Lepri, A.; Fischer, A.H.; Grint, D.; Kirk, O.; Kjaer, J.; Kowalska, J.; Lundgren, J.; Mocroft, A.; Nielsen, J.; Peters, L.; Podlekareva, D.; Reekie, J.; Tverland, J.; Elias, C.; Losso, M.; Vetter, N.; Zangerle, R.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V.M.; Suetnov, O.; Clumeck, N.; De Wit, S.; Delforge, M.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Jilich, D.; Machala, L.; Sedlacek, D.; Benfield, T.; Kronborg, G.; Larsen, M.; Nielsen, J.; Gerstoft, J.; Hansen, A.-B.E.; Katzenstein, T.; Skinhøj, P.; Pedersen, C.; Ostergaard, L.; Zilmer, K.

    2013-01-01

    Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors

  12. Arabidopsis dynamin-related protein 1E in sphingolipid-enriched plasma membrane domains is associated with the development of freezing tolerance.

    Science.gov (United States)

    Minami, Anzu; Tominaga, Yoko; Furuto, Akari; Kondo, Mariko; Kawamura, Yukio; Uemura, Matsuo

    2015-08-01

    The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin-related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol-enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye-labelled plasma membrane, providing evidence that DRP1E localizes non-uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol-enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  13. Diabetes mellitus defined by hemoglobin A1c value: Risk characterization for incidence among Japanese subjects in the JPHC Diabetes Study.

    Science.gov (United States)

    Kato, Masayuki; Takahashi, Yoshihiko; Matsushita, Yumi; Mizoue, Tetsuya; Inoue, Manami; Kadowaki, Takashi; Tsugane, Shoichiro; Noda, Mitsuhiko

    2011-10-07

    Aims/Introduction:  Although several risk factors for type 2 diabetes have been identified, most of them have been identified in studies on Western populations, and they should be evaluated in a Japanese population. In 2010, new diagnostic criteria for diabetes mellitus using hemoglobin A1c (HbA1c) were released and its use in epidemiological studies has many advantages. The aim of the present study was to evaluate risk factors for type 2 diabetes defined based on HbA1c values in a Japanese population.   A total of 9223 subjects (3076 men and 6147 women) were followed up for 5 years. Diabetes was defined based on self-report or HbA1c value. Risk factors for diabetes were evaluated as odds ratios adjusted for potential confounding factors by logistic regression.   During the 5-year follow-up period, we documented 518 incident cases of diabetes (232 men and 286 women). Of the 518 incident cases, 310 cases were diagnosed by HbA1c alone. Among the men, age, smoking (both past smoking and current smoking) and family history of diabetes significantly increased the risk of diabetes. Among the women, body mass index, family history of diabetes and hypertension significantly increased the risk of diabetes. These results did not change markedly after adjustment for the baseline HbA1c values, and the baseline HbA1c value itself was a significant risk factor for diabetes mellitus.   Known risk factors for diabetes established in Western populations also increased the risk of diabetes in a Japanese population defined on the basis of HbA1c values. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00119.x, 2011).

  14. Neurochemical metabolomics reveals disruption to sphingolipid metabolism following chronic haloperidol administration

    Science.gov (United States)

    McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Crowley, James J.; Vann, Robert E.; Beardsley, Patrick M.; van den Oord, Edwin J.

    2015-01-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects. PMID:25850894

  15. Defining Game Mechanics

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    2008-01-01

    This article defins game mechanics in relation to rules and challenges. Game mechanics are methods invoked by agents for interacting with the game world. I apply this definition to a comparative analysis of the games Rez, Every Extend Extra and Shadow of the Colossus that will show the relevance...... of a formal definition of game mechanics. Udgivelsesdato: Dec 2008...

  16. Modal Logics and Definability

    OpenAIRE

    Kuusisto, Antti

    2013-01-01

    In recent years, research into the mathematical foundations of modal logic has become increasingly popular. One of the main reasons for this is the fact that modal logic seems to adapt well to the requirements of a wide range of different fields of application. This paper is a summary of some of the author’s contributions to the understanding of modal definability theory.

  17. Software Defined Cyberinfrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Foster, Ian; Blaiszik, Ben; Chard, Kyle; Chard, Ryan

    2017-07-17

    Within and across thousands of science labs, researchers and students struggle to manage data produced in experiments, simulations, and analyses. Largely manual research data lifecycle management processes mean that much time is wasted, research results are often irreproducible, and data sharing and reuse remain rare. In response, we propose a new approach to data lifecycle management in which researchers are empowered to define the actions to be performed at individual storage systems when data are created or modified: actions such as analysis, transformation, copying, and publication. We term this approach software-defined cyberinfrastructure because users can implement powerful data management policies by deploying rules to local storage systems, much as software-defined networking allows users to configure networks by deploying rules to switches.We argue that this approach can enable a new class of responsive distributed storage infrastructure that will accelerate research innovation by allowing any researcher to associate data workflows with data sources, whether local or remote, for such purposes as data ingest, characterization, indexing, and sharing. We report on early experiments with this approach in the context of experimental science, in which a simple if-trigger-then-action (IFTA) notation is used to define rules.

  18. Defining Abnormally Low Tenders

    DEFF Research Database (Denmark)

    Ølykke, Grith Skovgaard; Nyström, Johan

    2017-01-01

    The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

  19. Software Defined Coded Networking

    DEFF Research Database (Denmark)

    Di Paola, Carla; Roetter, Daniel Enrique Lucani; Palazzo, Sergio

    2017-01-01

    the quality of each link and even across neighbouring links and using simulations to show that an additional reduction of packet transmission in the order of 40% is possible. Second, to advocate for the use of network coding (NC) jointly with software defined networking (SDN) providing an implementation...

  20. Defining depth of anesthesia.

    Science.gov (United States)

    Shafer, S L; Stanski, D R

    2008-01-01

    In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.

  1. Defining and classifying syncope

    NARCIS (Netherlands)

    Thijs, Roland D.; Wieling, Wouter; Kaufmann, Horacio; van Dijk, Gert

    2004-01-01

    There is no widely adopted definition or classification of syncope and related disorders. This lack of uniformity harms patient care, research, and medical education. In this article, syncope is defined as a form of transient loss of consciousness (TLOC) due to cerebral hypoperfusion. Differences

  2. Defining the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus: a pilot study.

    Science.gov (United States)

    Abu-Rustum, Reem S; Ziade, M Fouad; Abu-Rustum, Sameer E

    2012-09-01

    Our study aims at investigating the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus. This is a retrospective pilot study where three-dimensional and four-dimensional stored data sets were manipulated to retrieve eight anatomic planes starting from the midsagittal plane of the fetus. Standardization of volumes was performed at the level of the transverse abdominal circumference plane. Parallel shift was utilized and the spatial relationships between eight anatomic planes were established. The median and the range were calculated for each of the planes, and they were evaluated as a function of the fetal crown-rump length. P planes were found to adhere to normal distribution curves, and most of the planes were in a definable relationship to each other with statistically significant correlations. To our knowledge, this is the first study to describe the possible spatial relationships between eight two-dimensional anatomic planes in the 11+6 to 13+6 weeks fetus, utilizing a standardized approach. Defining these spatial relationships may serve as the first step for the potential future development of automation software for fetal anatomic assessment at 11+6 to 13+6 weeks. © 2012 John Wiley & Sons, Ltd.

  3. Accuracy of Blood Pressure-to-Height Ratio to Define Elevated Blood Pressure in Children and Adolescents: The CASPIAN-IV Study.

    Science.gov (United States)

    Kelishadi, Roya; Bahreynian, Maryam; Heshmat, Ramin; Motlagh, Mohammad Esmail; Djalalinia, Shirin; Naji, Fatemeh; Ardalan, Gelayol; Asayesh, Hamid; Qorbani, Mostafa

    2016-02-01

    The aim of this study was to propose a simple practical diagnostic criterion for pre-hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group. This study was conducted on a nationally representative sample of 14,880 students, aged 6-18 years. HTN and pre-HTN were defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ 95 and 90-95th percentile for age, gender, and height, respectively. By using the area under the curve (AUC) of the receiver operator characteristic curves, we estimated the diagnostic accuracy of two indexes of SBP-to-height ratio (SBPHR) and DBP-to-height (DBPHR) to define pre-HTN and HTN. Overall, SBPHR performed relatively well in classifying subjects to HTN (AUC 0.80-0.85) and pre-HTN (AUC 0.84-0.90). Likewise, DBPHR performed relatively well in classifying subjects to HTN (AUC 0.90-0.97) and pre-HTN (AUC 0.70-0.83). Two indexes of SBPHR and DBPHR are considered as valid, simple, inexpensive, and accurate tools to diagnose pre-HTN and HTN in pediatric age group.

  4. Study of a communication strategy aimed at achieving a possible better understanding of the consequence of radioactive waste management in a well defined group of public

    International Nuclear Information System (INIS)

    Vanhove, V.

    1993-01-01

    This study is performed and partially funded within the framework of the European Communities (R and D-programme on Management and Disposal of Radioactive Waste). The purpose of this study is to work out an information strategy on radioactive waste management for a selected target public (15-to-18 year old youngsters), with a view to raising public opinion and achieving a better understanding of this matter. The choice of this target public has been inspired among others by the importance of the youngsters as future opinion leaders. The results of an opinion poll, conducted in the autumn of 1991, were used to define the scope of the project and to determine the communication model and plan that will serve as a basis for the further development of the project. The first steps were taken to develop a pedagogical package, the structure, form and content of which have been determined. Preparations were also made to define the concept and the content of an information centre tuned to the pedagogical package and, like the other information, intended to inform 15-to-18 year old students. (author)

  5. Defining and Classifying Interest Groups

    DEFF Research Database (Denmark)

    Baroni, Laura; Carroll, Brendan; Chalmers, Adam

    2014-01-01

    The interest group concept is defined in many different ways in the existing literature and a range of different classification schemes are employed. This complicates comparisons between different studies and their findings. One of the important tasks faced by interest group scholars engaged...... in large-N studies is therefore to define the concept of an interest group and to determine which classification scheme to use for different group types. After reviewing the existing literature, this article sets out to compare different approaches to defining and classifying interest groups with a sample...... in the organizational attributes of specific interest group types. As expected, our comparison of coding schemes reveals a closer link between group attributes and group type in narrower classification schemes based on group organizational characteristics than those based on a behavioral definition of lobbying....

  6. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC.

    Directory of Open Access Journals (Sweden)

    Neil Murphy

    2016-04-01

    Full Text Available Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI measurements to create four metabolic health/body size phenotype categories: (1 metabolically healthy/normal weight (BMI < 25 kg/m2, (2 metabolically healthy/overweight (BMI ≥ 25 kg/m2, (3 metabolically unhealthy/normal weight (BMI < 25 kg/m2, and (4 metabolically unhealthy/overweight (BMI ≥ 25 kg/m2. Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men] were used (instead of BMI to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was

  7. Defining Plagiarism: A Literature Review

    Directory of Open Access Journals (Sweden)

    Akbar Akbar

    2018-02-01

    Full Text Available Plagiarism has repeatedly occurred in Indonesia, resulting in focusing on such academic misbehavior as a “central issue” in Indonesian higher education. One of the issues of addressing plagiarism in higher education is that there is a confusion of defining plagiarism. It seems that Indonesian academics had different perception when defining plagiarism. This article aims at exploring the issue of plagiarism by helping define plagiarism to address confusion among Indonesian academics. This article applies literature review by firs finding relevant articles after identifying databases for literature searching. After the collection of required articles for review, the articles were synthesized before presenting the findings. This study has explored the definition of plagiarism in the context of higher education. This research found that plagiarism is defined in the relation of criminal acts. The huge numbers of discursive features used position plagiaristic acts as an illegal deed. This study also found that cultural backgrounds and exposure to plagiarism were influential in defining plagiarism.

  8. Patterns of remission, continuation and incidence of broadly defined eating disorders during early pregnancy in the Norwegian Mother and Child Cohort Study (MoBa).

    Science.gov (United States)

    Bulik, Cynthia M; Von Holle, Ann; Hamer, Robert; Knoph Berg, Cecilie; Torgersen, Leila; Magnus, Per; Stoltenberg, Camilla; Siega-Riz, Anna Maria; Sullivan, Patrick; Reichborn-Kjennerud, Ted

    2007-08-01

    We explored the course of broadly defined eating disorders during pregnancy in the Norwegian Mother and Child Cohort Study (MoBa) at the Norwegian Institute of Public Health. A total of 41,157 pregnant women, enrolled at approximately 18 weeks' gestation, had valid data from the Norwegian Medical Birth Registry. We collected questionnaire-based diagnostic information on broadly defined anorexia nervosa (AN), and bulimia nervosa (BN), and eating disorders not otherwise specified (EDNOS). EDNOS subtypes included binge eating disorder (BED) and recurrent self-induced purging in the absence of binge eating (EDNOS-P). We explored rates of remission, continuation and incidence of BN, BED and EDNOS-P during pregnancy. Prepregnancy prevalence estimates were 0.1% for AN, 0.7% for BN, 3.5% for BED and 0.1% for EDNOS-P. During early pregnancy, estimates were 0.2% (BN), 4.8% (BED) and 0.1% (EDNOS-P). Proportions of individuals remitting during pregnancy were 78% (EDNOS-P), 40% (BN purging), 39% (BED), 34% (BN any type) and 29% (BN non-purging type). Additional individuals with BN achieved partial remission. Incident BN and EDNOS-P during pregnancy were rare. For BED, the incidence rate was 1.1 per 1000 person-weeks, equating to 711 new cases of BED during pregnancy. Incident BED was associated with indices of lower socio-economic status. Pregnancy appears to be a catalyst for remission of some eating disorders but also a vulnerability window for the new onset of broadly defined BED, especially in economically disadvantaged individuals. Vigilance by health-care professionals for continuation and emergence of eating disorders in pregnancy is warranted.

  9. Defining Legal Moralism

    DEFF Research Database (Denmark)

    Thaysen, Jens Damgaard

    2015-01-01

    This paper discusses how legal moralism should be defined. It is argued that legal moralism should be defined as the position that “For any X, it is always a pro tanto reason for justifiably imposing legal regulation on X that X is morally wrong (where “morally wrong” is not conceptually equivalent...... to “harmful”)”. Furthermore, a distinction between six types of legal moralism is made. The six types are grouped according to whether they are concerned with the enforcement of positive or critical morality, and whether they are concerned with criminalising, legally restricting, or refraining from legally...... protecting morally wrong behaviour. This is interesting because not all types of legal moralism are equally vulnerable to the different critiques of legal moralism that have been put forth. Indeed, I show that some interesting types of legal moralism have not been criticised at all....

  10. Defining local food

    DEFF Research Database (Denmark)

    Eriksen, Safania Normann

    2013-01-01

    Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

  11. Applying CSM-CERES-Maize to define a sowing window for irrigated maize crop - The Riacho´s Farm case study

    Directory of Open Access Journals (Sweden)

    Denise Freitas Silva

    2011-08-01

    Full Text Available Irrigation use constitutes an alternative to improve maize production in Central Minas Gerais State, Brazil. However, even under adequate water supply conditions, other environmental factors may influence maize crop growth and development and may, ultimately, affect grain yield. This study aimed to establish a sowing window for irrigated maize crop, based on simulation results obtained with the decision support model CSM-CERES-Maize. Simulations were made for crop management conditions of Riacho´s Farm, located in Matozinhos, Minas Gerais State, Brazil. It was employed the model´s seasonal tool, along with a data set containing 46 years of weather data records, to simulate maize yield for weekly sowing scenarios, starting on August 1st and ending on July 24th of each year. One defined an irrigated maize sowing window, taking into account the yield break risk that a farmer would be willing to take. The model proved to be an interesting tool to assist in decision making, regarding crop and irrigation management, for an irrigated maize production system. Assuming a 10% yield break in the expected average maximum maize yield, it was defined as sowing window, the period from January 23rd to March 6th, with February 20th as the best sowing date. Other sowing windows may be established according to the risk that the farmer would be willing to take.

  12. When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving.

    Science.gov (United States)

    Drury, Stacy S; Sánchez, Mar M; Gonzalez, Andrea

    2016-01-01

    This article is part of a Special Issue "Parental Care".Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for "optimal" caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Association between intake of less-healthy foods defined by the United Kingdom's nutrient profile model and cardiovascular disease: A population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Oliver T Mytton

    2018-01-01

    Full Text Available In the United Kingdom, the Food Standards Agency-Ofcom nutrient profiling model (FSA-Ofcom model is used to define less-healthy foods that cannot be advertised to children. However, there has been limited investigation of whether less-healthy foods defined by this model are associated with prospective health outcomes. The objective of this study was to test whether consumption of less-healthy food as defined by the FSA-Ofcom model is associated with cardiovascular disease (CVD.We used data from the European Prospective Investigation of Cancer (EPIC-Norfolk cohort study in adults (n = 25,639 aged 40-79 years who completed a 7-day diet diary between 1993 and 1997. Incident CVD (primary outcome, cardiovascular mortality, and all-cause mortality (secondary outcomes were identified using record linkage to hospital admissions data and death certificates up to 31 March 2015. Each food and beverage item reported was coded and given a continuous score, using the FSA-Ofcom model, based on the consumption of energy; saturated fat; total sugar; sodium; nonsoluble fibre; protein; and fruits, vegetables, and nuts. Items were classified as less-healthy using Ofcom regulation thresholds. We used Cox proportional hazards regression to test for an association between consumption of less-healthy food and incident CVD. Sensitivity analyses explored whether the results differed based on the definition of the exposure. Analyses were adjusted for age, sex, behavioural risk factors, clinical risk factors, and socioeconomic status. Participants were followed up for a mean of 16.4 years. During follow-up, there were 4,965 incident cases of CVD (1,524 fatal within 30 days. In the unadjusted analyses, we observed an association between consumption of less-healthy food and incident CVD (test for linear trend over quintile groups, p < 0.01. After adjustment for covariates (sociodemographic, behavioural, and indices of cardiovascular risk, we found no association between

  14. Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study.

    Science.gov (United States)

    Russell, Charlotte; Wearden, Alison J; Fairclough, Gillian; Emsley, Richard A; Kyle, Simon D

    2016-04-01

    This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS. © 2016 Associated Professional Sleep Societies, LLC.

  15. Defining the key roles and competencies of the clinician-educator of the 21st century: a national mixed-methods study.

    Science.gov (United States)

    Sherbino, Jonathan; Frank, Jason R; Snell, Linda

    2014-05-01

    To determine a consensus definition of a clinician-educator and the related domains of competence. During September 2010 to March 2011, the authors conducted a two-phase mixed-methods national study in Canada using (1) focus groups of deans of medicine and directors of medical education centers to define the attributes, domains of competence, and core competencies of clinician-educators using a grounded theory analysis, and (2) a survey of 1,130 deans, academic chairs, and residency program directors to validate the focus group results. The 22 focus group participants described being active in clinical practice, applying theory to practice, and engaging in education scholarship-but not holding a particular administrative position-as essential attributes of clinician-educators. Program directors accounted for 68% of the 350 survey respondents, academic chairs for 19%, and deans for 13% (response rate: 31%). Among respondents, 85% endorsed the need for physicians with advanced training in medical education to serve as educational consultants. Domains of clinician-educator competence endorsed by >85% of respondents as important or very important were assessment, communication, curriculum development, education theory, leadership, scholarship, and teaching. With regard to training requirements, 55% endorsed a master's degree in education as effective preparation, whereas 39% considered faculty development programs effective. On the basis of this study's findings, the authors defined a clinician-educator as a clinician active in health professional practice who applies theory to education practice, engages in education scholarship, and serves as a consultant to other health professionals on education issues.

  16. Defined contribution health benefits.

    Science.gov (United States)

    Fronstin, P

    2001-03-01

    This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

  17. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Agarwalla Vipin

    2007-02-01

    Full Text Available Abstract Background The rising prevalence of obesity and metabolic syndrome (MetS has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS and severe obesity as predictors of insulin resistance (IR in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290. Sensitivity, specificity, positive predictive values and odds ratios (OR with 95% confidence intervals (CI were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006. Sensitivities were Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for IR should be routinely performed. Further research is needed to establish threshold values of insulin measures in overweight children who may be at greater associated risk of adverse outcomes whether or not MetS is present.

  18. Defining a Structural Model for the Revitalization of the Lost Urban Spaces (City Entrances in Contemporary Urban Design Case Study: Entrance of Sanandaj

    Directory of Open Access Journals (Sweden)

    Seyed Mohammadreza Khatibi

    2015-09-01

    Full Text Available Not long ago, city gates and entryways had high spatial value and were among the landmarks for marking city boundaries. Today with cities having been expanded and developed, such aspect of the entrance concept is lost and entryways are turned to passages for transportation. In fact, the rich spatial value of such entrances has decreased as they are solely spaces for passing through out or into the city. The dissonant expansion of entryways causes irregularities in thresholds of urban structure. This is due to imprudent intrusion into city landscape entailed by ill-considered planning activities. The main problem is the lack of comprehensive visual or mental definitions in the field. In other words, the challenge includes improper sequencing, zoning, and lack of lucid scenario and interfere procedure. Through defining a scenario, this study aims to set a spatial hierarchy for urban entryways. It then uses a comparative study to examine the scenario for an existing case study. This study provides a new definition for designing and planning for the fields concerned with city entryways. This implies methods by which authorities can interfere in the process of urban design.

  19. On Defining Mass

    Science.gov (United States)

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement surrounding the Large Hadron Collider at CERN is associated with discovering the mechanism responsible for the masses of the elementary particles. This paper will first briefly examine the leading definitions, pointing out their shortcomings. Then, utilizing relativity theory, it will propose—for consideration by the community of physicists—a conceptual definition of mass predicated on the more fundamental concept of energy, more fundamental in that everything that has mass has energy, yet not everything that has energy has mass.

  20. Implementing Software Defined Radio

    CERN Document Server

    Grayver, Eugene

    2013-01-01

    Software Defined Radio makes wireless communications easier, more efficient, and more reliable. This book bridges the gap between academic research and practical implementation. When beginning a project, practicing engineers, technical managers, and graduate students can save countless hours by considering the concepts presented in these pages. The author covers the myriad options and trade-offs available when selecting an appropriate hardware architecture. As demonstrated here, the choice between hardware- and software-centric architecture can mean the difference between meeting an aggressive schedule and bogging down in endless design iterations. Because of the author’s experience overseeing dozens of failed and successful developments, he is able to present many real-life examples. Some of the key concepts covered are: Choosing the right architecture for the market – laboratory, military, or commercial Hardware platforms – FPGAs, GPPs, specialized and hybrid devices Standardization efforts to ens...

  1. Defining cyber warfare

    Directory of Open Access Journals (Sweden)

    Dragan D. Mladenović

    2012-04-01

    Full Text Available Cyber conflicts represent a new kind of warfare that is technologically developing very rapidly. Such development results in more frequent and more intensive cyber attacks undertaken by states against adversary targets, with a wide range of diverse operations, from information operations to physical destruction of targets. Nevertheless, cyber warfare is waged through the application of the same means, techniques and methods as those used in cyber criminal, terrorism and intelligence activities. Moreover, it has a very specific nature that enables states to covertly initiate attacks against their adversaries. The starting point in defining doctrines, procedures and standards in the area of cyber warfare is determining its true nature. In this paper, a contribution to this effort was made through the analysis of the existing state doctrines and international practice in the area of cyber warfare towards the determination of its nationally acceptable definition.

  2. Defining the mobilome.

    Science.gov (United States)

    Siefert, Janet L

    2009-01-01

    This chapter defines the agents that provide for the movement of genetic material which fuels the adaptive potential of life on our planet. The chapter has been structured to be broadly comprehensive, arbitrarily categorizing the mobilome into four classes: (1) transposons, (2) plasmids, (3) bacteriophage, and (4) self-splicing molecular parasites.Our increasing understanding of the mobilome is as dynamic as the mobilome itself. With continuing discovery, it is clear that nature has not confined these genomic agents of change to neat categories, but rather the classification categories overlap and intertwine. Massive sequencing efforts and their published analyses are continuing to refine our understanding of the extent of the mobilome. This chapter provides a framework to describe our current understanding of the mobilome and a foundation on which appreciation of its impact on genome evolution can be understood.

  3. Software Defined Networking

    DEFF Research Database (Denmark)

    Caba, Cosmin Marius

    Network Service Providers (NSP) often choose to overprovision their networks instead of deploying proper Quality of Services (QoS) mechanisms that allow for traffic differentiation and predictable quality. This tendency of overprovisioning is not sustainable for the simple reason that network...... resources are limited. Hence, to counteract this trend, current QoS mechanisms must become simpler to deploy and operate, in order to motivate NSPs to employ QoS techniques instead of overprovisioning. Software Defined Networking (SDN) represents a paradigm shift in the way telecommunication and data...... generic perspective (e.g. service provisioning speed, resources availability). As a result, new mechanisms for providing QoS are proposed, solutions for SDN-specific QoS challenges are designed and tested, and new network management concepts are prototyped, all aiming to improve QoS for network services...

  4. Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study.

    Science.gov (United States)

    Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie

    2017-05-01

    Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at

  5. Prevalence of Airflow Limitation Defined by Pre- and Post-Bronchodilator Spirometry in a Community-Based Health Checkup: The Hisayama Study.

    Science.gov (United States)

    Fukuyama, Satoru; Matsumoto, Koichiro; Kaneko, Yasuko; Kan-o, Keiko; Noda, Naotaka; Tajiri-Asai, Yukari; Nakano, Takako; Ishii, Yumiko; Kiyohara, Yutaka; Nakanishi, Yoichi; Inoue, Hiromasa

    2016-02-01

    Spirometry in health checkup may contribute to early diagnosis of chronic obstructive pulmonary disease (COPD) and asthma. Although post-bronchodilator airflow limitation is essential for definite diagnosis of COPD and post-bronchodilator normalization of airflow is suggestive of asthma, this test has not been prevailed in health checkup. The objective of this study was to estimate the prevalence of airflow limitation defined by pre- and post-bronchodilator spirometry in health checkup. Post-bronchodilator spirometry was conducted for participants with airflow limitation in a town-wide health checkup for residents aged 40 years and older in Hisayama, a town in the western part of Japan. The prevalence of pre- and post-bronchodilator airway limitation defined by FEV1/FVC spirometry. In males, the age of current smokers was significantly younger than those of never smokers and former smokers. In females, the ages of current- and former smokers were significantly younger than never smokers. The values of %FEV1 and %FVC in current smokers were significantly lower than those in former smokers and never smokers. Two hundred sixty nine subjects, 85% of total subjects with a pre-bronchodilator FEV1/FVC spirometry. The prevalence of pre-bronchodilator airflow limitation was 14.6% in males and 13.7% in females, and the prevalence of post-bronchodilator airway limitation was 8.7% and 8.7%, respectively. Post-bronchodilator spirometry in health checkup would reduce the number of subjects with probable COPD to two-third. Recommendation for those examinees to take further evaluations may pave the way for early intervention.

  6. The stability of baseline-defined categories of alcohol consumption during the adult life-course: a 28-year prospective cohort study.

    Science.gov (United States)

    Knott, Craig S; Bell, Steven; Britton, Annie

    2018-01-01

    Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life-course according to baseline categories of drinking. A prospective observational study. United Kingdom. A cohort of British civil servants totalling 6838 men and 3372 women aged 34-55 years at baseline, followed for a mean 19.1 (standard deviation = 9.5) years. The volume of weekly alcohol consumption was estimated from data concerning the frequency and number of drinks consumed. Baseline categories were defined: non-current drinkers, infrequent drinkers, 0.1-50.0 g/week, 50.1-100.0 g/week, 100.1-150.0 g/week, 150.1-250.0 g/week and >250.0 g/week. For women, the highest category was defined as > 100.0 g/week. Baseline frequency was derived as 'daily or almost daily' and 'not daily or almost daily'. Trajectories were estimated within baseline categories using growth curve models. Trajectories differed between men and women, but were relatively stable within light-to-moderate categories of baseline consumption. Drinking was least stable within the highest categories of baseline consumption (men: > 250.0 g/week; women: > 100.0 g/week), declining by 47.0 [95% confidence interval (CI) = 40.7, 53.2] and 16.8 g/week (95% CI = 12.6, 21.0), respectively, per 10-year increase in age. These declines were not a consequence of sudden transitions to complete abstention. Rates of decline appear greatest in older age, with trajectories converging toward moderate volumes. Among UK civil servants, consumption within baseline drinking categories is generally stable during the life-course, except among heavier baseline drinkers, for whom intakes decline with increasing age. This shift does not appear

  7. Defining the Anthropocene

    Science.gov (United States)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  8. Viewing the human microbiome through three-dimensional glasses: integrating structural and functional studies to better define the properties of myriad carbohydrate-active enzymes

    International Nuclear Information System (INIS)

    Turnbaugh, Peter J.; Henrissat, Bernard; Gordon, Jeffrey I.

    2010-01-01

    Metagenomics has unleashed a deluge of sequencing data describing the organismal, genetic, and transcriptional diversity of the human microbiome. To better understand the precise functions of the myriad proteins encoded by the microbiome, including carbohydrate-active enzymes, it will be critical to combine structural studies with functional analyses. Recent studies have provided an unprecedented view of the trillions of microbes associated with the human body. The human microbiome harbors tremendous diversity at multiple levels: the species that colonize each individual and each body habitat; the genes that are found in each organism’s genome; the expression of these genes and the interactions and activities of their protein products. The sources of this diversity are wide-ranging and reflect both environmental and host factors. A major challenge moving forward is defining the precise functions of members of various families of proteins represented in our microbiomes, including the highly diverse carbohydrate-active enzymes (CAZymes) involved in numerous biologically important chemical transformations, such as the degradation of complex dietary polysaccharides. Coupling metagenomic analyses to structural genomics initiatives and to biochemical and other functional assays of CAZymes will be essential for determining how these as well as other microbiome-encoded proteins operate to shape the properties of microbial communities and their human hosts

  9. Comparison of Risk Factor Profiles for Primary Open-Angle Glaucoma Subtypes Defined by Pattern of Visual Field Loss: A Prospective Study.

    Science.gov (United States)

    Kang, Jae H; Loomis, Stephanie J; Rosner, Bernard A; Wiggs, Janey L; Pasquale, Louis R

    2015-04-01

    We explored whether risk factor associations differed by primary open-angle glaucoma (POAG) subtypes defined by visual field (VF) loss pattern (i.e., paracentral or peripheral). We included 77,157 women in the Nurses' Health Study (NHS) and 42,773 men in the Health Professionals Follow-up Study (HPFS 1986-2010), and incident medical record confirmed cases of paracentral (n = 440) and peripheral (n = 865) POAG subtypes. We evaluated African heritage, glaucoma family history, body mass index (BMI), mean arterial blood pressure, diabetes mellitus, physical activity, smoking, caffeine intake, and alcohol intake. We used competing risk Cox regression analyses modeling age as the metameter and stratified by age, cohort, and event type. We sequentially identified factors with the least significant differences in associations with POAG subtypes ("stepwise down" approach with P for heterogeneity [P-het] 0.10) adverse associations with both POAG subtypes were observed with glaucoma family history, diabetes, African heritage, greater caffeine intake, and higher mean arterial pressure. These data indicate that POAG with early paracentral VF loss has distinct as well as common determinants compared with POAG with peripheral VF loss.

  10. The use of stable xenon-enhanced computed tomographic studies of cerebral blood flow to define changes in cerebral carbon dioxide vasoresponsivity caused by a severe head injury.

    Science.gov (United States)

    Marion, D W; Bouma, G J

    1991-12-01

    Previous studies using the xenon-133 cerebral blood flow (CBF) method have documented the impairment of CO2 vasoresponsivity after a severe head injury, but only global values can be obtained reliably with this technique. We studied CO2 vasoresponsivity using the stable xenon-enhanced computed tomographic CBF method, which provided information about well-defined cortical regions and deep brain structures not available with the xenon-133 method. In 17 patients with admission Glasgow Coma Scale scores of 8 or less, hemispheric CO2 vasoresponsivity ranged from 1.3 to 8.5% per mm Hg change in partial CO2 pressure. Lobar, cerebellar, basal ganglia, and brain stem CO2 vasoresponsivity frequently varied from the mean global value by more than 25%. In all but one patient, local CO2 vasoresponsivity in one or more of these areas differed from the mean global value by more than 50%. The greatest variability occurred in patients with acute subdural hematomas and diffuse (bihemispheric) injuries. This variability in CO2 vasoresponsivity has important implications for the effective and safe management of intracranial hypertension that frequently accompanies severe head injury.

  11. Teleology and Defining Sex.

    Science.gov (United States)

    Gamble, Nathan K; Pruski, Michal

    2018-07-01

    Disorders of sexual differentiation lead to what is often referred to as an intersex state. This state has medical, as well as some legal, recognition. Nevertheless, the question remains whether intersex persons occupy a state in between maleness and femaleness or whether they are truly men or women. To answer this question, another important conundrum needs to be first solved: what defines sex? The answer seems rather simple to most people, yet when morphology does not coincide with haplotypes, and genetics might not correlate with physiology the issue becomes more complex. This paper tackles both issues by establishing where the essence of sex is located and by superimposing that framework onto the issue of the intersex. This is achieved through giving due consideration to the biology of sexual development, as well as through the use of a teleological framework of the meaning of sex. Using a range of examples, the paper establishes that sex cannot be pinpointed to one biological variable but is rather determined by how the totality of one's biology is oriented towards biological reproduction. A brief consideration is also given to the way this situation could be comprehended from a Christian understanding of sex and suffering.

  12. Metagenomic Analysis of Dairy Bacteriophages: Extraction Method and Pilot Study on Whey Samples Derived from Using Undefined and Defined Mesophilic Starter Cultures.

    Science.gov (United States)

    Muhammed, Musemma K; Kot, Witold; Neve, Horst; Mahony, Jennifer; Castro-Mejía, Josué L; Krych, Lukasz; Hansen, Lars H; Nielsen, Dennis S; Sørensen, Søren J; Heller, Knut J; van Sinderen, Douwe; Vogensen, Finn K

    2017-10-01

    Despite being potentially highly useful for characterizing the biodiversity of phages, metagenomic studies are currently not available for dairy bacteriophages, partly due to the lack of a standard procedure for phage extraction. We optimized an extraction method that allows the removal of the bulk protein from whey and milk samples with losses of less than 50% of spiked phages. The protocol was applied to extract phages from whey in order to test the notion that members of Lactococcus lactis 936 (now Sk1virus ), P335, c2 (now C2virus ) and Leuconostoc phage groups are the most frequently encountered in the dairy environment. The relative abundance and diversity of phages in eight and four whey mixtures from dairies using undefined mesophilic mixed-strain cultures containing Lactococcus lactis subsp. lactis biovar diacetylactis and Leuconostoc species (i.e., DL starter cultures) and defined cultures, respectively, were assessed. Results obtained from transmission electron microscopy and high-throughput sequence analyses revealed the dominance of Lc. lactis 936 phages (order Caudovirales , family Siphoviridae ) in dairies using undefined DL starter cultures and Lc. lactis c2 phages (order Caudovirales , family Siphoviridae ) in dairies using defined cultures. The 936 and Leuconostoc phages demonstrated limited diversity. Possible coinduction of temperate P335 prophages and satellite phages in one of the whey mixtures was also observed. IMPORTANCE The method optimized in this study could provide an important basis for understanding the dynamics of the phage community (abundance, development, diversity, evolution, etc.) in dairies with different sizes, locations, and production strategies. It may also enable the discovery of previously unknown phages, which is crucial for the development of rapid molecular biology-based methods for phage burden surveillance systems. The dominance of only a few phage groups in the dairy environment signifies the depth of knowledge

  13. Defining an emerging disease.

    Science.gov (United States)

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future.

  14. How do people define moderation?

    Science.gov (United States)

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

    Science.gov (United States)

    Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

    2017-01-23

    Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. NCT02097667

  16. Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye.

    Science.gov (United States)

    Jia, Changkai; Zhang, Feng; Zhu, Ying; Qi, Xia; Wang, Yiqiang

    2017-10-20

    Matrix-remodeling associated 7 (MXRA7) gene was first reported in 2002 and named so for its co-expression with several genes known to relate with matrix-remodeling. However, not any studies had been intentionally performed to characterize this gene. We started defining the functions of MXRA7 by integrating bioinformatics analysis and experimental study. Data mining of MXRA7 expression in BioGPS, Gene Expression Omnibus and EurExpress platforms highlighted high level expression of Mxra7 in murine ocular tissues. Real-time PCR was employed to measure Mxra7 mRNA in tissues of adult C57BL/6 mice and demonstrated that Mxra7 was preferentially expressed at higher level in retina, corneas and lens than in other tissues. Then the inflammatory corneal neovascularization (CorNV) model and fungal corneal infections were induced in Balb/c mice, and mRNA levels of Mxra7 as well as several matrix-remodeling related genes (Mmp3, Mmp13, Ecm1, Timp1) were monitored with RT-PCR. The results demonstrated a time-dependent Mxra7 under-expression pattern (U-shape curve along timeline), while all other matrix-remodeling related genes manifested an opposite changes pattern (dome-shape curve). When limited data from BioGPS concerning human MXRA7 gene expression in human tissues were looked at, it was found that ocular tissue was also the one expressing highest level of MXRA7. To conclude, integrative assay of MXRA7 gene expression in public databank as well as domestic animal models revealed a selective high expression MXRA7 in murine and human ocular tissues, and its change patterns in two corneal disease models implied that MXRA7 might play a role in pathological processes or diseases involving injury, neovascularization and would healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Comparison of MRI-defined back muscles volume between patients with ankylosing spondylitis and control patients with chronic back pain: age and spinopelvic alignment matched study.

    Science.gov (United States)

    Bok, Doo Hee; Kim, Jihye; Kim, Tae-Hwan

    2017-02-01

    To compare MRI-defined back muscle volume between AS patients and age, and spinopelvic alignment matched control patients with chronic back pain. 51 male patients with AS were enrolled. Age and spinopelvic alignment matched controls (male) were found among non-AS patients with chronic back pain. After matching procedure, fully matched controls were found in 31 of 51 AS patients (60.8%), who represent AS patients without deformity. However, matched controls were not found in 20 of 51 AS patients (39.2%), who represent AS patients with deformity. MRI parameters of back muscle (paraspinal muscle and psoas muscle) at L4/5 disc level including cross-sectional area (CSA) and fat-free cross-sectional area (FCSA) were compared between AS patients and matched controls. Covariates, including BMI, self-reported physical activity, and the presence of chronic disease, which can influence back muscle volume, were also investigated. There were no statistical differences in age, body mass index, score of back pain (NRS), and spinopelvic alignment, and physical activity between matched AS patients and control patients except for duration of back pain. All MRI parameters for paraspinal muscle volume in matched AS patients (without deformity) were significantly less than those of control patients, and significantly larger than those of non-matched AS patients (with deformity). Body size adjusted MRI parameters (relative CSA and relative FCSA) of paraspinal muscle showed strong correlations with lumbar lordosis and sacral slope. Such relationship between paraspinal muscle and spinopelvic parameters remained significant even after multivariate adjustment. AS patients without deformity already have decreased paraspinal muscle volume compared with age and spinopelvic alignment matched non-AS patients with chronic back pain. Such decrease in paraspinal muscle volume was significantly associated with kyphotic deformity of AS patients even after multivariate adjustment. Although the result

  18. Definably compact groups definable in real closed fields.II

    OpenAIRE

    Barriga, Eliana

    2017-01-01

    We continue the analysis of definably compact groups definable in a real closed field $\\mathcal{R}$. In [3], we proved that for every definably compact definably connected semialgebraic group $G$ over $\\mathcal{R}$ there are a connected $R$-algebraic group $H$, a definable injective map $\\phi$ from a generic definable neighborhood of the identity of $G$ into the group $H\\left(R\\right)$ of $R$-points of $H$ such that $\\phi$ acts as a group homomorphism inside its domain. The above result and o...

  19. Point-prevalence survey of healthcare facility-onset healthcare-associated Clostridium difficile infection in Greek hospitals outside the intensive care unit: The C. DEFINE study.

    Science.gov (United States)

    Skoutelis, Athanasios; Pefanis, Angelos; Tsiodras, Sotirios; Sipsas, Nikolaos V; Lelekis, Moyssis; Lazanas, Marios C; Gargalianos, Panagiotis; Dalekos, George N; Roilides, Emmanuel; Samonis, George; Maltezos, Efstratios; Hatzigeorgiou, Dimitrios; Lada, Malvina; Metallidis, Symeon; Stoupis, Athena; Chrysos, Georgios; Karnesis, Lazaros; Symbardi, Styliani; Loupa, Chariclia V; Giamarellou, Helen; Kioumis, Ioannis; Sambatakou, Helen; Tsianos, Epameinondas; Kotsopoulou, Maria; Georgopali, Areti; Liakou, Klairi; Perlorentzou, Stavroula; Levidiotou, Stamatina; Giotsa-Toutouza, Marina; Tsorlini-Christoforidou, Helen; Karaiskos, Ilias; Kouppari, Georgia; Trikka-Graphakos, Eleftheria; Ntrivala, Maria-Anna; Themeli-Digalaki, Kate; Pangalis, Anastasia; Kachrimanidou, Melina; Martsoukou, Maria; Karapsias, Stergios; Panopoulou, Maria; Maraki, Sofia; Orfanou, Anagnostina; Petinaki, Efthymia; Orfanidou, Maria; Baka, Vasiliki; Stylianakis, Antonios; Spiliopoulou, Iris; Smilakou, Stavroula; Zerva, Loukia; Vogiatzakis, Evangelos; Belesiotou, Eleni; Gogos, Charalambos A

    2017-01-01

    The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013. There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea. 5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009). The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.

  20. Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Mariam Noelie Hema

    Full Text Available To study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART.The APROCO/COPILOTE cohort enrolled patients initiating a protease inhibitor-containing ART in 1997-1999. The association between occurrence of first non AIDS-defining severe events (NADE and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4, CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4 500/mm3 and CD4/CD8 ratio 500/mm3 and CD4/CD8 ratio > 1. Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion.We included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2-11.4. Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2-0.5 at baseline and 0.6 (IQR: 0.4-0.9 after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%, cardiovascular events (14% and cancers (10%. For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32-3.44.CD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.

  1. Abdominal Obesity in German Adolescents Defined by Waist-to-Height Ratio and Its Association to Elevated Blood Pressure: The KiGGS Study

    Directory of Open Access Journals (Sweden)

    Katrin Kromeyer-Hauschild

    2013-04-01

    Full Text Available Objective: The aim of this study was to compare the fixed 0.5 cut-off and the age- and sex-specific 90th percentile (P90 for waist-to-height ratio (WHtR in German adolescents with respect to the prevalence of abdominal obesity and to compare the screening ability of WHtR and BMI to identify hypertensive blood pressure (BP values. Methods: Between 2003 and 2006, the German Health Interview and Examination Survey for Children and Adolescents (KiGGS was carried out including 3,492 boys and 3,321 girls aged 11-17 years. Abdominal obesity was assessed by two WHtR cut-points (P90; 0.5. Hypertensive BP was defined as BP exceeding age-, sex- and height-specific 95th percentiles or the adult threshold for hypertension (140/90 mm Hg. Results: Agreement between the WHtR cut-offs was very good (Kappa 0.89 for boys; 0.81 for girls, and the prevalence of abdominal obesity was slightly higher using P90 (boys 12.0%; girls 11.3% compared to 0.5 (boys 10.7%; girls 8.0%. WHtR and BMI-for-age had equivalent ability to discriminate hypertensive BP (ROC-AUC Conclusion: The fixed 0.5 WHtR cut-off can be used in German adolescents to characterize abdominal obesity. However, WHtR is not suitable as a screening tool for hypertensive BP in adolescents.

  2. Multi-modality safety assessment of blood-brain barrier opening using focused ultrasound and definity microbubbles: a short-term study.

    Science.gov (United States)

    Baseri, Babak; Choi, James J; Tung, Yao-Sheng; Konofagou, Elisa E

    2010-09-01

    As a potentially viable method of brain drug delivery, the safety profile of blood-brain barrier (BBB) opening using focused ultrasound (FUS) and ultrasound contrast agents (UCA) needs to be established. In this study, we provide a short-term (30-min or 5-h survival) histological assessment of murine brains undergoing FUS-induced BBB opening. Forty-nine mice were intravenously injected with Definity microbubbles (0.05 microL/kg) and sonicated under the following parameters: frequency of 1.525 MHz, pulse length of 20 ms, pulse repetition frequency of 10 Hz, peak rarefactional acoustic pressures of 0.15-0.98 MPa and two 30-s sonication intervals with an intermittent 30-s delay. The BBB opening threshold was found to be 0.15-0.3 MPa based on fluorescence and magnetic resonance imaging of systemically injected tracers. Analysis of three histological measures in hematoxylin and eosin-stained sections revealed the safest acoustic pressure to be within the range of 0.3-0.46 MPa in all examined time periods post sonication. Across different pressure amplitudes, only the samples 30 min post opening showed significant difference (p < 0.05) in the average number of distinct damaged sites, microvacuolated sites, dark neurons and sites with extravasated erythrocytes. Enhanced fluorescence around severed microvessels was also noted and found to be associated with the largest tissue effects, whereas mildly diffuse BBB opening with uniform fluorescence in the parenchyma was associated with no or mild tissue injury. Region-specific areas of the sonicated brain (thalamus, hippocampal fissure, dentate gyrus and CA3 area of hippocampus) exhibited variation in fluorescence intensity based on the position, orientation and size of affected vessels. The results of this short-term histological analysis demonstrated the feasibility of a safe FUS-UCA-induced BBB opening under a specific set of sonication parameters and provided new insights on the mechanism of BBB opening.

  3. Defining popular iconic metaphor.

    Science.gov (United States)

    Columbus, Peter J; Boerger, Michael A

    2002-04-01

    Popular Iconic Metaphor is added to the cognitive linguistic lexicon of figurative language. Popular Iconic Metaphors employ real or fictional celebrities of popular culture as source domains in figurative discourse. Some borders of Popular Iconic Metaphor are identified, and Elvis Presley is offered as a prototype example of a popular iconic source domain, due to his ubiquity in American popular culture, which affords his figurative usage in ways consistent with decision heuristics in everyday life. Further study of Popular Iconic Metaphors may serve to illuminate how figurative expressions emerge in their localized contexts, structure conduct and experience, and affect mediation of cultural and personal meanings.

  4. Clinical, bacteriological, and histopathological characteristics of newly detected children with leprosy: A population based study in a defined rural and urban area of Maharashtra, Western India

    Directory of Open Access Journals (Sweden)

    Vanaja P Shetty

    2013-01-01

    Full Text Available Background: Leprosy has been a major public-health problem in many developing countries for centuries. According to the National Leprosy Elimination Programme report of March 2012, there were a total of about 0.13 million cases of leprosy in India, 9.7% of which were children. Numerous studies have investigated child leprosy amongst reported cases however, studies pertaining to proportion and characteristics of undetected childhood cases in the community are very few. Aim: To examine the clinical, bacteriological, and histopathological characteristics of newly detected child leprosy cases in the community. Methods: The population survey conducted from June to September 2007 and the defined rural areas, which included five primary health centers of Panvel Taluka, in Raigad district and urban areas, which included M-east ward of the municipal corporation of greater Mumbai of western Maharashtra, India. Results: House-to-house survey yielded 32 and 37 so far, undetected child cases of leprosy in the rural and urban region, and the prevalence rate was 10.5 and 1.5 per 10,000, respectively. The age of child leprosy cases detected, ranged from 3 to 14 years with a mean of 10.06 ± 3.35 years in the rural and 9.97 ± 3.12 years in the urban area. Most of the cases were paucibacillary (62%. A large proportion of children (49% had single skin lesion (SSL. Of the 19 SSL cases examined histopathologically, 15 (99% showed features of borderline tuberculoid, 1 (5% borderline lepromatous and 3 (16% had indeterminate type of leprosy. Tuberculoid leprosy was not seen in any, indicating less likelihood of self-healing. Overall, three cases had deformity (grade 1 = 1 and grade 2 = 2 and 31% of multibacillary cases were smear positive. Conclusion: The clinical, bacteriological, and histopathological characteristics of newly detected child cases in the community evidently indicate the grave nature of the problem of undetected child leprosy, recent active

  5. Defining Information Security.

    Science.gov (United States)

    Lundgren, Björn; Möller, Niklas

    2017-11-15

    This article proposes a new definition of information security, the 'Appropriate Access' definition. Apart from providing the basic criteria for a definition-correct demarcation and meaning concerning the state of security-it also aims at being a definition suitable for any information security perspective. As such, it bridges the conceptual divide between so-called 'soft issues' of information security (those including, e.g., humans, organizations, culture, ethics, policies, and law) and more technical issues. Because of this it is also suitable for various analytical purposes, such as analysing possible security breaches, or for studying conflicting attitudes on security in an organization. The need for a new definition is demonstrated by pointing to a number of problems for the standard definition type of information security-the so-called CIA definition. Besides being too broad as well as too narrow, it cannot properly handle the soft issues of information security, nor recognize the contextual and normative nature of security.

  6. High field electron paramagnetic resonance spectroscopy under ultrahigh vacuum conditions—A multipurpose machine to study paramagnetic species on well defined single crystal surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Rocker, J.; Cornu, D.; Kieseritzky, E.; Hänsel-Ziegler, W.; Freund, H.-J. [Fritz-Haber-Institut der MPG, Faradayweg 4-6, 14195 Berlin (Germany); Seiler, A. [Fritz-Haber-Institut der MPG, Faradayweg 4-6, 14195 Berlin (Germany); Laboratorium für Applikationen der Synchrotronstrahlung, KIT Campus Süd, Kaiserstr. 12, 76131 Karlsruhe (Germany); Bondarchuk, O. [Fritz-Haber-Institut der MPG, Faradayweg 4-6, 14195 Berlin (Germany); CIC energiGUNE, Parque Tecnologico, C/Albert Einstein 48, CP 01510 Minano (Alava) (Spain); Risse, T., E-mail: risse@chemie.fu-berlin.de [Fritz-Haber-Institut der MPG, Faradayweg 4-6, 14195 Berlin (Germany); Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin (Germany)

    2014-08-01

    A new ultrahigh vacuum (UHV) electron paramagnetic resonance (EPR) spectrometer operating at 94 GHz to investigate paramagnetic centers on single crystal surfaces is described. It is particularly designed to study paramagnetic centers on well-defined model catalysts using epitaxial thin oxide films grown on metal single crystals. The EPR setup is based on a commercial Bruker E600 spectrometer, which is adapted to ultrahigh vacuum conditions using a home made Fabry Perot resonator. The key idea of the resonator is to use the planar metal single crystal required to grow the single crystalline oxide films as one of the mirrors of the resonator. EPR spectroscopy is solely sensitive to paramagnetic species, which are typically minority species in such a system. Hence, additional experimental characterization tools are required to allow for a comprehensive investigation of the surface. The apparatus includes a preparation chamber hosting equipment, which is required to prepare supported model catalysts. In addition, surface characterization tools such as low energy electron diffraction (LEED)/Auger spectroscopy, temperature programmed desorption (TPD), and infrared reflection absorption spectroscopy (IRAS) are available to characterize the surfaces. A second chamber used to perform EPR spectroscopy at 94 GHz has a room temperature scanning tunneling microscope attached to it, which allows for real space structural characterization. The heart of the UHV adaptation of the EPR experiment is the sealing of the Fabry-Perot resonator against atmosphere. To this end it is possible to use a thin sapphire window glued to the backside of the coupling orifice of the Fabry Perot resonator. With the help of a variety of stabilization measures reducing vibrations as well as thermal drift it is possible to accumulate data for a time span, which is for low temperature measurements only limited by the amount of liquid helium. Test measurements show that the system can detect paramagnetic

  7. The structure of well defined SiO2 supported MoO3 clusters during sulfidation : an in situ EXAFS-study

    NARCIS (Netherlands)

    Boer, de M.; Dillen, van A.J.; Koningsberger, D.C.; Geus, J.W.; Kuroda, H.; Ohta, T.

    1993-01-01

    The sulfidation of a well defined MoO3/SiO2 catalyst has been examd. by means of TPS, EXAFS, and TEM. The oxidic clusters in a 5.6 wt% MoO3/SiO2 catalyst are transformed into almost completely sulfided particles (MoOxSy) by O-S exchange at RT. A molybdenum-sulfido particle that resembles the MoS3

  8. Accumulation of sphingolipid activator proteins (SAPs) A and D in granular osmiophilic deposits in miniature Schnauzer dogs with ceroid-lipofuscinosis.

    Science.gov (United States)

    Palmer, D N; Tyynelä, J; van Mil, H C; Westlake, V J; Jolly, R D

    1997-03-01

    The neuronal ceroid-lipofuscinoses (NCL, Batten disease) are fatal inherited neurodegenerative diseases of children characterized by retinal and brain atrophy and the accumulation of electron-dense storage bodies in cells. Mutations in different genes underlie different major forms. The infantile disease (CLN-1, McKusick 256730) is distinguished by the storage of the sphingolipid activator proteins (SAPs) A and D in distinctive granular osmiophilic deposits (GRODs). This contrasts with the other major forms, where subunit c of mitochondrial ATP synthase is stored in various multilamellar profiles. Ceroid-lipofuscinoses also occur in dogs, including a form in miniature Schnauzers with distinctive granular osmiophilic deposit-like storage bodies. Antisera to SAPs A and D reacted to these storage bodies in situ. The presence of SAP D was confirmed by Western blotting and of SAP A by protein sequencing. Neither subunit c of mitochondrial ATP synthase nor of vacuolar ATPase is stored. This suggests that there are two families of ceroid-lipofuscinoses, the subunit c-storing forms, and those in which SAPs A and D, and perhaps other proteins, accumulate. Further work is required to determine whether other forms with granular osmiophilic deposits belong to the latter class and the genetic relationships between them and the human infantile disease.

  9. Effects of orally administered fumonisin B₁ (FB₁), partially hydrolysed FB₁, hydrolysed FB₁ and N-(1-deoxy-D-fructos-1-yl) FB₁ on the sphingolipid metabolism in rats.

    Science.gov (United States)

    Hahn, Irene; Nagl, Veronika; Schwartz-Zimmermann, Heidi Elisabeth; Varga, Elisabeth; Schwarz, Christiane; Slavik, Veronika; Reisinger, Nicole; Malachová, Alexandra; Cirlini, Martina; Generotti, Silvia; Dall'Asta, Chiara; Krska, Rudolf; Moll, Wulf-Dieter; Berthiller, Franz

    2015-02-01

    Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos-1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially. We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC-MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Defining Quality in Undergraduate Education

    Directory of Open Access Journals (Sweden)

    Alison W. Bowers

    2018-01-01

    Full Text Available Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted search terms in academic databases, we identified and reviewed relevant academic literature to develop emergent themes and implications for future research. Results: The exploratory review of the literature revealed a range of thoughtful discussions and empirical studies attempting to define quality in undergraduate education. Many publications highlighted the importance of including different stakeholder perspectives and presented some of the varying perceptions of quality among different stakeholders. Conclusions: While a number of researchers have explored and written about how to define quality in undergraduate education, there is not a general consensus regarding a definition of quality in undergraduate education. Past research offers a range of insights, models, and data to inform future research. Implication for Theory and/or Practice: We provide four recommendations for future research to contribute to a high quality undergraduate educational experience. We suggest more comprehensive systematic reviews of the literature as a next step.

  11. Deficient motion-defined and texture-defined figure-ground segregation in amblyopic children.

    Science.gov (United States)

    Wang, Jane; Ho, Cindy S; Giaschi, Deborah E

    2007-01-01

    Motion-defined form deficits in the fellow eye and the amblyopic eye of children with amblyopia implicate possible direction-selective motion processing or static figure-ground segregation deficits. Deficient motion-defined form perception in the fellow eye of amblyopic children may not be fully accounted for by a general motion processing deficit. This study investigates the contribution of figure-ground segregation deficits to the motion-defined form perception deficits in amblyopia. Performances of 6 amblyopic children (5 anisometropic, 1 anisostrabismic) and 32 control children with normal vision were assessed on motion-defined form, texture-defined form, and global motion tasks. Performance on motion-defined and texture-defined form tasks was significantly worse in amblyopic children than in control children. Performance on global motion tasks was not significantly different between the 2 groups. Faulty figure-ground segregation mechanisms are likely responsible for the observed motion-defined form perception deficits in amblyopia.

  12. Solid-State NMR and DFT Studies on the Formation of Well-Defined Silica-Supported Tantallaaziridines: From Synthesis to Catalytic Application

    KAUST Repository

    Hamzaoui, Bilel

    2016-01-27

    Single-site, well-defined, silica-supported tantallaaziridine intermediates [≡Si-O-Ta(η2-NRCH2)(NMe2)2] [R=Me (2), Ph (3)] were prepared from silica-supported tetrakis(dimethylamido)tantalum [≡Si-O-Ta(NMe2)4] (1) and fully characterized by FTIR spectroscopy, elemental analysis, and 1H,13C HETCOR and DQ TQ solid-state (SS) NMR spectroscopy. The formation mechanism, by β-H abstraction, was investigated by SS NMR spectroscopy and supported by DFT calculations. The C-H activation of the dimethylamide ligand is favored for R=Ph. The results from catalytic testing in the hydroaminoalkylation of alkenes were consistent with the N-alkyl aryl amine substrates being more efficient than N-dialkyl amines. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Defining the "normal" postejaculate urinalysis.

    Science.gov (United States)

    Mehta, Akanksha; Jarow, Jonathan P; Maples, Pat; Sigman, Mark

    2012-01-01

    Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (sperm counts in PEU (sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

  14. The titration of carboxyl-terminated monolayers revisited: in situ calibrated fourier transform infrared study of well-defined monolayers on silicon.

    Science.gov (United States)

    Aureau, D; Ozanam, F; Allongue, P; Chazalviel, J-N

    2008-09-02

    The acid-base equilibrium at the surface of well-defined mixed carboxyl-terminated/methyl-terminated monolayers grafted on silicon (111) has been investigated using in situ calibrated infrared spectroscopy (attenuated total reflectance (ATR)) in the range of 900-4000 cm (-1). Spectra of surfaces in contact with electrolytes of various pH provide a direct observation of the COOH COO (-) conversion process. Quantitative analysis of the spectra shows that ionization of the carboxyl groups starts around pH 6 and extends over more than 6 pH units: approximately 85% ionization is measured at pH 11 (at higher pH, the layers become damaged). Observations are consistently accounted for by a single acid-base equilibrium and discussed in terms of change in ion solvation at the surface and electrostatic interactions between surface charges. The latter effect, which appears to be the main limitation, is qualitatively accounted for by a simple model taking into account the change in the Helmholtz potential associated with the surface charge. Furthermore, comparison of calculated curves with experimental titration curves of mixed monolayers suggests that acid and alkyl chains are segregated in the monolayer.

  15. Theoretical approaches to elections defining

    OpenAIRE

    Natalya V. Lebedeva

    2011-01-01

    Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

  16. Theoretical approaches to elections defining

    Directory of Open Access Journals (Sweden)

    Natalya V. Lebedeva

    2011-01-01

    Full Text Available Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

  17. Defining Modules, Modularity and Modularization

    DEFF Research Database (Denmark)

    Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

    The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

  18. The benefits of defining "snacks".

    Science.gov (United States)

    Hess, Julie M; Slavin, Joanne L

    2018-04-18

    Whether eating a "snack" is considered a beneficial or detrimental behavior is largely based on how "snack" is defined. The term "snack food" tends to connote energy-dense, nutrient-poor foods high in nutrients to limit (sugar, sodium, and/or saturated fat) like cakes, cookies, chips and other salty snacks, and sugar-sweetened beverages. Eating a "snack food" is often conflated with eating a "snack," however, leading to an overall perception of snacks as a dietary negative. Yet the term "snack" can also refer simply to an eating occasion outside of breakfast, lunch, or dinner. With this definition, the evidence to support health benefits or detriments to eating a "snack" remains unclear, in part because relatively few well-designed studies that specifically focus on the impact of eating frequency on health have been conducted. Despite these inconsistencies and research gaps, in much of the nutrition literature, "snacking" is still referred to as detrimental to health. As discussed in this review, however, there are multiple factors that influence the health impacts of snacking, including the definition of "snack" itself, the motivation to snack, body mass index of snack eaters, and the food selected as a snack. Without a definition of "snack" and a body of research using methodologically rigorous protocols, determining the health impact of eating a "snack" will continue to elude the nutrition research community and prevent the development of evidence-based policies about snacking that support public health. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Patient-provider communication styles in HIV treatment programs in Bamako, Mali: A mixed-methods study to define dimensions and measure patient preferences

    Directory of Open Access Journals (Sweden)

    Emily A. Hurley

    2017-12-01

    Full Text Available Effective patient-provider communication (PPC promotes patient adherence and retention in long-term care. Sub-Saharan Africa faces unprecedented demand for chronic care for HIV patients on antiretroviral therapy (ART, yet adherence and retention remain challenging. In high-income countries, research describing patient preferences for different PPC styles has guided interventions to improve PPC and patient outcomes. However, research on PPC preferences in sub-Saharan Africa is limited. We sought to define PPC dimensions relevant to ART programs in Bamako, Mali through recordings of clinical interactions, in-depth interviews and focus-group discussions with 69 patients and 17 providers. To assess preferences toward contrasting PPC styles within dimensions, we conducted a vignette-based survey with 141 patients across five ART facilities. Qualitative analysis revealed two PPC dimensions similar to those described in the literature on patient-centered communication (level of psychosocial regard, balance of power, and one unique dimension that emerged from the data (guiding patient behavior: easy/tough/sharp. Significantly more survey participants chose the vignette demonstrating high psychosocial regard (52.2% compared to a biomedical style (22.5% (p<0.001. Within balance of power, a statistically similar proportion of participants chose the vignette demonstrating shared power (40.2% compared to a provider-dominated style (35.8%. In guiding patient behavior, a similar proportion of participants preferred the vignette depicting the “easy” (38.4% and/or “tough” style (40.6%, but significantly fewer preferred the “sharp” style (14.5% (p<0.001. Highly educated participants chose biomedical and shared power styles more frequently, while less educated participants more frequently indicated “no preference”. Working to understand, develop, and tailor PPC styles to patients in chronic care may help support patient retention and ultimately

  20. A Research Study Using the Delphi Method to Define Essential Competencies for a High School Game Art and Design Course Framework at the National Level

    Science.gov (United States)

    Mack, Nayo Corenus-Geneva

    2011-01-01

    This research study reports the findings of a Delphi study conducted to determine the essential competencies and objectives for a high school Game Art and Design course framework at the national level. The Delphi panel consisted of gaming, industry and educational experts from all over the world who were members of the International Game…

  1. A Reliability and Validity Study of the Defining Issues Test: The Relationship of Age, Education, Gender and Parental Education with Moral Development

    Science.gov (United States)

    Cesur, Sevim; Topcu, Mustafa Sami

    2010-01-01

    The aim of the study is twofold: First and main aim was to develop a valid and reliable Turkish version of the DIT which is one of the most important instruments in the psychology and education research; second is to explore the relationships between moral development and age, gender, education, and parental education. The study group consists of…

  2. Modular Software-Defined Radio

    Directory of Open Access Journals (Sweden)

    Rhiemeier Arnd-Ragnar

    2005-01-01

    Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

  3. Defining and Selecting Independent Directors

    Directory of Open Access Journals (Sweden)

    Eric Pichet

    2017-10-01

    Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

  4. Two cell circuits of oriented adult hippocampal neurons on self-assembled monolayers for use in the study of neuronal communication in a defined system.

    Science.gov (United States)

    Edwards, Darin; Stancescu, Maria; Molnar, Peter; Hickman, James J

    2013-08-21

    In this study, we demonstrate the directed formation of small circuits of electrically active, synaptically connected neurons derived from the hippocampus of adult rats through the use of engineered chemically modified culture surfaces that orient the polarity of the neuronal processes. Although synaptogenesis, synaptic communication, synaptic plasticity, and brain disease pathophysiology can be studied using brain slice or dissociated embryonic neuronal culture systems, the complex elements found in neuronal synapses makes specific studies difficult in these random cultures. The study of synaptic transmission in mature adult neurons and factors affecting synaptic transmission are generally studied in organotypic cultures, in brain slices, or in vivo. However, engineered neuronal networks would allow these studies to be performed instead on simple functional neuronal circuits derived from adult brain tissue. Photolithographic patterned self-assembled monolayers (SAMs) were used to create the two-cell "bidirectional polarity" circuit patterns. This pattern consisted of a cell permissive SAM, N-1[3-(trimethoxysilyl)propyl] diethylenetriamine (DETA), and was composed of two 25 μm somal adhesion sites connected with 5 μm lines acting as surface cues for guided axonal and dendritic regeneration. Surrounding the DETA pattern was a background of a non-cell-permissive poly(ethylene glycol) (PEG) SAM. Adult hippocampal neurons were first cultured on coverslips coated with DETA monolayers and were later passaged onto the PEG-DETA bidirectional polarity patterns in serum-free medium. These neurons followed surface cues, attaching and regenerating only along the DETA substrate to form small engineered neuronal circuits. These circuits were stable for more than 21 days in vitro (DIV), during which synaptic connectivity was evaluated using basic electrophysiological methods.

  5. Cohort profile: 'Centenari a Trieste' (CaT), a study of the health status of centenarians in a small defined area of Italy.

    Science.gov (United States)

    Tettamanti, Mauro; Marcon, Gabriella

    2018-02-08

    Centenarians, a segment of the population which some 50 years ago comprised only a few individuals, now count thousands in many countries, and demographic projections forecast that this growth will continue. The study of this new population will give us new information on extreme longevity and help prepare for their health and social needs. The aim of the Centenari a Trieste study is to describe the health and health service use by centenarians, with specific focus on cognitive status. This is a population-based study of centenarians living in the province of Trieste (Italy), a small area with a high prevalence of centenarians and a close network of health and social services, which makes it possible to conduct a study. Consenting individuals were visited by a clinician, tested by neuropsychologists and also gave a sample of their blood. Administrative data were retrieved as well. Of the 163 centenarians, 70 could be contacted and participated in the study. The main reasons for non-participation were impossibility to contact the subject (70) and death (20). Centenarians were mostly women (90%), tended to live in a nursing home (60%) and were generally severely functionally impaired (Barthel Index <50: 61%). Data from the administrative database showed that about one out of five needed hospitalisation in the preceding year and more than three out of four had at least one drug prescription. In 2017, we started a new wave of the study enrolling people who had just become centenarian and reassessing subjects already seen; we hope to extend this recruitment in the next years. Subjects are now examined also by cardiologists and dental specialists. We are collecting further different biological specimens to investigate new hypotheses on the cognitive function of the centenarians. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Small angle x-ray studies reveal that Aspergillus niger glucoamylase has a defined extended conformation and can form dimers in solution

    DEFF Research Database (Denmark)

    Jørgensen, Anders Dysted; Nøhr, Jane; Kastrup, Jette Sandholm

    2008-01-01

    is poorly understood and structurally undescribed, and data regarding domain organization and intramolecular functional cooperativity are conflicting or non-comprehensive. Here, we report a combined small angle x-ray scattering and calorimetry study of Aspergillus niger glucoamylase 1, glucoamylase 2, which...

  7. Complex regional pain syndrome type I : Use of the International Association for the Study of Pain diagnostic criteria defined in 1994

    NARCIS (Netherlands)

    Reinders, M.F.; Geertzen, J.H.B.; Dijkstra, P.U.

    2002-01-01

    Objectives: The objective was to assess the reported use in recent publications of the diagnostic criteria for complex regional pain syndrome type I (CRPS 1) proposed by the International Association for the Study of Pain (IASP) in 1994. Methods: A literature search of MEDLINE (January 1996 to July

  8. ON DEFINING S-SPACES

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2013-05-01

    Full Text Available The present work is intended to be an introduction to the Superposition Theory of David Carfì. In particular I shall depict the meaning of his brand new theory, on the one hand in an informal fashion and on the other hand by giving a formal approach of the algebraic structure of the theory: the S-linear algebra. This kind of structure underpins the notion of S-spaces (or Carfì-spaces by defining both its properties and its nature. Thus I shall define the S-triple as the fundamental principle upon which the S-linear algebra is built up.

  9. Study to define and verify the personal oral hygiene requirements for extended manned space flight: Oral physiology and microbiology in Skylab manned space missions

    Science.gov (United States)

    Brown, L. R.

    1975-01-01

    Methods for metabolic fingerprinting of pathogenic oral bacteria were developed and the effects of Skylab missions on salivary electrolyte levels were studied. High resolution gas liquid chromatographic (GLC) and pyrolysis-GLC procedures were used to obtain metabolic profiles of closely related bacteria associated with dental caries and periodontal disease. It was found that the GLC procedures provide a practical and reproducible means of obtaining metabolic markers for identifying closely related strains of these organisms. Fractions of stimulated whole saliva samples from the prime and back-up crews of the three Skylab missions were used to measure salivary electrolyte concentrations. All the electrolytes previously reported as having increased in urine and feces during the missions were assessed. Sodium, potassium, calcium, magnesium, phosphorous and chloride were studied. A decrease in sodium and an increase in magnesium were observed, but the mineral imbalances attributable to the mission-related increases in urinary electrolytes were not detected.

  10. The work compatibility improvement framework: preliminary findings of a case study for defining and measuring the human-at-work system.

    Science.gov (United States)

    Genaidy, A; Karwowski, W; A-Rehim, A

    2007-11-01

    Although researchers traditionally examined the 'risk' characteristics of work settings in health studies, few work models, such as the 'demand-control' and 'motivation-hygiene theory', advocated the study of the positive and the negative aspects of work for the ultimate improvement of work performance. The objectives of the current study were: (a) to examine the positive and negative characteristics of work in the machining department in a small manufacturing plant in the Midwest USA, and, (b) to report the prevalence of musculoskeletal and stress outcomes. A focus group consisting of worker experts from the different job categories in the machining department confirmed the management's concerns. Accordingly, 56 male and female workers, employed in three shifts, were surveyed on the demand/energizer profiles of work characteristics and self-reported musculoskeletal/stress symptoms. On average, one-fourth to one-third of the workers reported 'high' demand, and over 50% of the workers documented 'low' energizers for certain work domains/sub-domains, such as 'physical task content'/'organizational' work domains and 'upper body postural loading'/'time organization' work sub-domains. The prevalence of workers who reported 'high' musculoskeletal/stress disorder cases, was in the range of 25-35% and was consistent with the results of 'high' demands and 'low' energizers. The results of this case study confirm the importance of adopting a comprehensive view for work improvement and sustainable growth opportunities. It is paramount to consider the negative and positive aspects of work characteristics to ensure optimum organizational performance. The Work Compatibility Improvement Framework, proposed in the reported research, is an important endeavor toward the ultimate improvement and sustainable growth of human and organizational performance.

  11. Comparing incident diabetes as defined by fasting plasma glucose or by HbA(1c). The AusDiab, Inter99 and DESIR studies

    DEFF Research Database (Denmark)

    Soulimane, S.; Simon, D.; Shaw, J. E.

    2011-01-01

    by the corresponding criteria. Despite Diabetes Control and Complications Trial-alignment of the three HbA(1c) assays, there was a large difference in the HbA(1c) distributions between these studies, conducted some 10 years ago. Thus, it is difficult to compare absolute values of diabetes prevalence and incidence...... based on HbA(1c) measurements from that time....

  12. Experimental study of the leakage rate through cracked reinforced concrete wall elements for defining the functional failure criteria of containment buildings

    International Nuclear Information System (INIS)

    Choun, Young Sun; Cho, Nam So

    2004-01-01

    Containment buildings in nuclear power plants should maintain their structural safety as well as their functional integrity during an operation period. To maintain the functional integrity, the wall and dome of the containment buildings have to maintain their air tightness under extreme loading conditions such as earthquakes, missile impact, and severe accidents. For evaluating the functional failure of containments, it is important to predict the leak amount through cracked concrete walls. The leakage through concrete cracks has been studied since 1972. Buss examined the flow rate of air through a pre-existing crack in a slab under air pressure. Rizkalla el al. initiated an experimental study for the leakage of prestressed concrete building segments under uniaxial and biaxial loadings to simulate the loading condition of containment buildings under an internal pressure. Recently, Salmon el al. initiated an experimental program for determining the leak rates in typical reinforced concrete shear walls subjected to beyond design basis earthquakes. This study investigates the cracking behavior of reinforced concrete containment wall elements under a uniaxial tension and addresses the outline of the leakage test for unlined containment wall elements

  13. Dietary fiber intake and risk of breast cancer defined by estrogen and progesterone receptor status: the Japan Public Health Center-based Prospective Study.

    Science.gov (United States)

    Narita, Saki; Inoue, Manami; Saito, Eiko; Abe, Sarah K; Sawada, Norie; Ishihara, Junko; Iwasaki, Motoki; Yamaji, Taiki; Shimazu, Taichi; Sasazuki, Shizuka; Shibuya, Kenji; Tsugane, Shoichiro

    2017-06-01

    Epidemiological studies have suggested a protective effect of dietary fiber intake on breast cancer risk while the results have been inconsistent. Our study aimed to investigate the association between dietary fiber intake and breast cancer risk and to explore whether this association is modified by reproductive factors and hormone receptor status of the tumor. A total of 44,444 women aged 45 to 74 years from the Japan Public Health Center-based Prospective Study were included in analyses. Dietary intake assessment was performed using a validated 138-item food frequency questionnaire (FFQ). Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence were calculated by multivariate Cox proportional hazards regression models. During 624,423 person-years of follow-up period, 681 breast cancer cases were identified. After adjusting for major confounders for breast cancer risk, inverse trends were observed but statistically non-significant. Extremely high intake of fiber was associated with decreased risk of breast cancer but this should be interpreted with caution due to limited statistical power. In stratified analyses by menopausal and hormone receptor status, null associations were observed except for ER-PR- status. Our findings suggest that extreme high fiber intake may be associated with decreased risk of breast cancer but the level of dietary fiber intake among Japanese population might not be sufficient to examine the association between dietary fiber intake and breast cancer risk.

  14. Low-pH-dependent fusion of sindbis virus with receptor-free cholesterol- and sphingolipid-containing liposomes

    NARCIS (Netherlands)

    Smit, JM; Bittman, R; Wilschut, J

    1999-01-01

    There is controversy as to whether the cell entry mechanism of Sindbis virus (SIN) involves direct fusion of the viral envelope with the plasma membrane at neutral pH Dr uptake by receptor-mediated endocytosis and subsequent low-pH-induced fusion from within acidic endosomes. Here, we studied the

  15. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

    Directory of Open Access Journals (Sweden)

    Corey Saba

    Full Text Available Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV. Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within

  16. Defining and Differentiating the Makerspace

    Science.gov (United States)

    Dousay, Tonia A.

    2017-01-01

    Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

  17. Indico CONFERENCE: Define the Programme

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial you are going to learn how to define the programme of a conference in Indico. The program of your conference is divided in different “tracks”. Tracks represent the subject matter of the conference, such as “Online Computing”, “Offline Computing”, and so on.

  18. Are conventional statistical techniques exhaustive for defining metal background concentrations in harbour sediments? A case study: The Coastal Area of Bari (Southeast Italy).

    Science.gov (United States)

    Mali, Matilda; Dell'Anna, Maria Michela; Mastrorilli, Piero; Damiani, Leonardo; Ungaro, Nicola; Belviso, Claudia; Fiore, Saverio

    2015-11-01

    Sediment contamination by metals poses significant risks to coastal ecosystems and is considered to be problematic for dredging operations. The determination of the background values of metal and metalloid distribution based on site-specific variability is fundamental in assessing pollution levels in harbour sediments. The novelty of the present work consists of addressing the scope and limitation of analysing port sediments through the use of conventional statistical techniques (such as: linear regression analysis, construction of cumulative frequency curves and the iterative 2σ technique), that are commonly employed for assessing Regional Geochemical Background (RGB) values in coastal sediments. This study ascertained that although the tout court use of such techniques in determining the RGB values in harbour sediments seems appropriate (the chemical-physical parameters of port sediments fit well with statistical equations), it should nevertheless be avoided because it may be misleading and can mask key aspects of the study area that can only be revealed by further investigations, such as mineralogical and multivariate statistical analyses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population.

    Science.gov (United States)

    Søeby, Karen; Jensen, Peter Bjødstrup; Werge, Thomas; Sørensen, Steen

    2015-09-01

    The knowledge of physiological fluctuation and variation of even commonly used biochemical quantities in extreme age groups and during development is sparse. This challenges the clinical interpretation and utility of laboratory tests in these age groups. To explore the utility of hospital laboratory data as a source of information, we analyzed enzymatic plasma creatinine as a model analyte in two large pediatric hospital samples. Plasma creatinine measurements from 9700 children aged 0-18 years were obtained from hospital laboratory databases and partitioned into high-resolution gender- and age-groups. Normal probability plots were used to deduce parameters of the normal distributions from healthy creatinine values in the mixed hospital datasets. Furthermore, temporal trajectories were generated from repeated measurements to examine developmental patterns in periods of changing creatinine levels. Creatinine shows great age dependence from birth throughout childhood. We computed and replicated 95% reference intervals in narrow gender and age bins and showed them to be comparable to those determined in healthy population studies. We identified pronounced transitions in creatinine levels at different time points after birth and around the early teens, which challenges the establishment and usefulness of reference intervals in those age groups. The study documents that hospital laboratory data may inform on the developmental aspects of creatinine, on periods with pronounced heterogeneity and valid reference intervals. Furthermore, part of the heterogeneity in creatinine distribution is likely due to differences in biological and chronological age of children and should be considered when using age-specific reference intervals.

  20. Defining safety goals. 2. Basic Consideration on Defining Safety Goals

    International Nuclear Information System (INIS)

    Hakata, T.

    2001-01-01

    The purpose of this study is to develop basic safety goals that are rational and consistent for all nuclear facilities, including nuclear power plants and fuel cycle facilities. Basic safety goals (risk limits) by an index of radiation dose are discussed, which are based on health effects of detriment and fatality and risk levels presumably accepted by society. The contents of this paper are the personal opinions of the author. The desirable structure of safety goals is assumed to be 'basic safety goals plus specific safety goals (or supplemental safety goals) for each sort of facility, which reflects their characteristics'. The requisites of the basic safety goals must include (a) rational bases (scientific and social), (b) comprehensiveness (common to all sorts of nuclear facilities covering from normal to accidental conditions), and (c) applicability. To meet the requirements, the basic safety goals might have to be a risk profile expression by an index of radiation dose. The societal rationality is consideration of absolute risk levels (10 -6 or 10 -7 /yr) and/or relative risk factors (such as 0.1% of U.S. safety goals) that the general public accepts as tolerable. The following quantitative objectives are adopted in this study for protection of average individuals in the vicinity of a nuclear facility: 1. The additive annual radiation dose during normal operation must be -4 /yr (health detriment), 2x10 -6 /yr (latent cancer and severe hereditary effects), and 10 -7 /yr (acute fatality) from the statistics in Japan. The radiation effects on human beings are determined by recommendations of UNSCEAR (Ref. 1) and ICRP. The health effects considered are non-severe stochastic health detriment, i.e., detectable opacities of lens of eye (threshold 5 0.5 to 2 Sv), depression of hematopoiesis of bone marrow (0.5 Sv), and depression of reproductive capability (temporary sterility of testes ) (0.15 Sv). The LD 50/60 of acute fatality is ∼4 Sv, and fatalities by latent

  1. Endogenous Sphingolipid Signaling Pathway Implicated in the Action of Croton membranaceus on the Prostate Gland in BPH Patients

    Directory of Open Access Journals (Sweden)

    George Awuku Asare

    2017-11-01

    Full Text Available Background: Croton membranaceus extract has apoptotic effects on BPH-1 cells. This study determined if the apoptotic effects were created through the ceramide pathway. Methods: The study was a follow-up to a previous observational study of 30 histologically confirmed patients with benign prostatic hyperplasia (BPH who were on C. membranaceus ethanolic extract at 20 mg t.i.d orally for 3 mo. Thereafter, total and free prostate-specific antigen (PSA, lipid profile plus Apo lipoprotein A and B, ceramide/Sphingophospho-kinase 1 (SphK1 and 2 (SphK2, sphingosine lyase (SPL, the cytotoxic adducts of oxidative stress 4-hydroxy-2-nonenal (4HNE and malondialdehyde (MDA, were determined. Results: Total and free PSA were significantly (p < 0.05 different after treatment. Apo lipoprotein A was significantly different (p = 0.024. The SphK1/SphK2 ratio reduced significantly (p = 0.049. Furthermore, SPL, ceramide, and MDA increased significantly after treatment (p = 0.05, p = 0.004, and p = 0.007, respectively. A weak positive correlation was found between high-density lipoprotein (HDL cholesterol and SphK1, and HDL and ceramide before treatment (p = 0.036, r = 0.3826; p = 0.018, r = 0.4286, respectively. Conclusions: C. membranaceus uses the ceramide pathway by modulating the SphK1/SphK2 ratio and increasing SPL to generate oxidative stress and consequently apoptosis.

  2. GIS-based approach for defining bioenergy facilities location: A case study in Northern Spain based on marginal delivery costs and resources competition between facilities

    Energy Technology Data Exchange (ETDEWEB)

    Panichelli, Luis; Gnansounou, Edgard [Laboratory of Energy Systems, Swiss Federal Institute of Technology, LASEN-ICARE-ENAC, Station 18, EPFL, CH-1015 Lausanne (Switzerland)

    2008-04-15

    This paper presents a GIS-based decision support system for selecting least-cost bioenergy locations when there is a significant variability in biomass farmgate price and when more than one bioenergy plant with a fixed capacity has to be placed in the region. The methodology tackles the resources competition problem between energy facilities through a location-allocation model based on least-cost biomass quantities. Whole system least delivery cost including intermediate bioenergy products is estimated. The methodology is based on a case study where forest wood residues (FWR) from final cuttings (FCs) are used to produce torrefied wood (TW) in two torrefaction plants (TUs) that supply a gasification unit (GU) in order to produce electricity. The provinces of Navarra, Bizkaia, Gipuzkoa, Alava, La Rioja, Cantabria and Burgos are assessed in order to find the best locations for settling down the TUs and the GU according to biomass availability, FWR and TW marginal delivery costs. (author)

  3. Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study.

    Science.gov (United States)

    Goéré, Diane; Souadka, Amine; Faron, Matthieu; Cloutier, Alexis S; Viana, Benjamin; Honoré, Charles; Dumont, Frédéric; Elias, Dominique

    2015-09-01

    The main prognostic factors after complete cytoreductive surgery (CCRS) of colorectal peritoneal carcinomatosis (PC) followed by intraperitoneal chemotherapy (IPC) are completeness of the resection and extent of the disease. This study aimed to determine a threshold value above which CCRS plus IPC may not offer survival benefit compared with systemic chemotherapy. Between March 2000 and May 2010, 180 patients underwent surgery for PC from colorectal cancer with intended performance of CCRS plus IPC. Among the 180 patients, CCRS plus IPC could be performed for 139 patients (curative group, 77 %), whereas it could not be performed for 41 patients (palliative group, 23 %). The two groups were comparable in terms of age, gender, primary tumor characteristics, and pre- and postoperative systemic chemotherapy. The mean peritoneal cancer index (PCI) was lower in the curative group (11 ± 7) than in the palliative group (23 ± 7) (p offer any survival benefit.

  4. Sustainability at the local scale: defining highly aggregated indices for assessing environmental performance. The province of Reggio Emilia (Italy) as a case study.

    Science.gov (United States)

    Clerici, Nicola; Bodini, Antonio; Ferrarini, Alessandro

    2004-10-01

    In order to achieve improved sustainability, local authorities need to use tools that adequately describe and synthesize environmental information. This article illustrates a methodological approach that organizes a wide suite of environmental indicators into few aggregated indices, making use of correlation, principal component analysis, and fuzzy sets. Furthermore, a weighting system, which includes stakeholders' priorities and ambitions, is applied. As a case study, the described methodology is applied to the Reggio Emilia Province in Italy, by considering environmental information from 45 municipalities. Principal component analysis is used to condense an initial set of 19 indicators into 6 fundamental dimensions that highlight patterns of environmental conditions at the provincial scale. These dimensions are further aggregated in two indices of environmental performance through fuzzy sets. The simple form of these indices makes them particularly suitable for public communication, as they condensate a wide set of heterogeneous indicators. The main outcomes of the analysis and the potential applications of the method are discussed.

  5. Large Prospective Study of Ovarian Cancer Screening in High-risk Women: CA125 Cut-point Defined by Menopausal Status

    Science.gov (United States)

    Skates, Steven J.; Mai, Phuong; Horick, Nora K.; Piedmonte, Marion; Drescher, Charles W.; Isaacs, Claudine; Armstrong, Deborah K.; Buys, Saundra S.; Rodriguez, Gustavo C.; Horowitz, Ira R.; Berchuck, Andrew; Daly, Mary B.; Domchek, Susan; Cohn, David E.; Van Le, Linda; Schorge, John O.; Newland, William; Davidson, Susan A.; Barnes, Mack; Brewster, Wendy; Azodi, Masoud; Nerenstone, Stacy; Kauff, Noah D.; Fabian, Carol J.; Sluss, Patrick M.; Nayfield, Susan G.; Kasten, Carol H.; Finkelstein, Dianne M.; Greene, Mark H.; Lu, Karen

    2011-01-01

    Background Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, while the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Methods Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the NCI-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this pre-planned analysis. Due to the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points based on the 98th percentile. Results The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. Conclusions To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (~ 50 for premenopausal women, 40 for premenopausal on OC, 35 for postmenopausal women). PMID:21893500

  6. A Prospective Pathologic Study to Define the Clinical Target Volume for Partial Breast Radiation Therapy in Women With Early Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Brandon T., E-mail: Brandon.Nguyen@act.gov.au [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Canberra Hospital, Radiation Oncology Department, Garran, ACT (Australia); Deb, Siddhartha [Department of Anatomical Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Victorian Cancer Biobank, Cancer Council of Victoria, Carlton, Victoria (Australia); Fox, Stephen [Department of Anatomical Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Hill, Prudence [Department of Anatomical Pathology, St. Vincent' s Hospital Melbourne, Fitzroy, Victoria (Australia); Collins, Marnie [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); Chua, Boon H. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia)

    2012-12-01

    Purpose: To determine an appropriate clinical target volume for partial breast radiation therapy (PBRT) based on the spatial distribution of residual invasive and in situ carcinoma after wide local excision (WLE) for early breast cancer or ductal carcinoma in situ (DCIS). Methods and Materials: We performed a prospective pathologic study of women potentially eligible for PBRT who had re-excision and/or completion mastectomy after WLE for early breast cancer or DCIS. A pathologic assessment protocol was used to determine the maximum radial extension (MRE) of residual carcinoma from the margin of the initial surgical cavity. Women were stratified by the closest initial radial margin width: negative (>1 mm), close (>0 mm and {<=}1 mm), or involved. Results: The study population was composed of 133 women with a median age of 59 years (range, 27-82 years) and the following stage groups: 0 (13.5%), I (40.6%), II (38.3%), and III (7.5%). The histologic subtypes of the primary tumor were invasive ductal carcinoma (74.4%), invasive lobular carcinoma (12.0%), and DCIS alone (13.5%). Residual carcinoma was present in the re-excision and completion mastectomy specimens in 55.4%, 14.3%, and 7.2% of women with an involved, close, and negative margin, respectively. In the 77 women with a noninvolved radial margin, the MRE of residual disease, if present, was {<=}10 mm in 97.4% (95% confidence interval 91.6-99.5) of cases. Larger MRE measurements were significantly associated with an involved margin (P<.001), tumor size >30 mm (P=.03), premenopausal status (P=.03), and negative progesterone receptor status (P=.05). Conclusions: A clinical target volume margin of 10 mm would encompass microscopic residual disease in >90% of women potentially eligible for PBRT after WLE with noninvolved resection margins.

  7. The challenge of defining and treating anemia and iron deficiency in pregnancy: A study of New Zealand midwives' management of iron status in pregnancy and the postpartum period.

    Science.gov (United States)

    Calje, Esther; Skinner, Joan

    2017-06-01

    Early recognition and management of low maternal iron status is associated with improved maternal, fetal, and neonatal outcomes. However, existing international guidelines for the testing and management of maternal iron-deficiency anemia are variable, with no national guideline for New Zealand midwives. Clinical management is complicated by normal physiological hemodilution, and complicated further by the effects of inflammation on iron metabolism, especially in populations with a high prevalence of obesity or infection. This study describes how midwives in one New Zealand area diagnose and treat anemia and iron deficiency, in the absence of established guidelines. Data on demographics, laboratory results, and documented clinical management were retrospectively collected from midwives (n=21) and women (n=189), from September to December 2013. Analysis was predominantly descriptive. A secondary analysis of iron status and body mass index (BMI) was undertaken. A total of 46% of 186 women, with hemoglobin testing at booking, did not have ferritin tested; 86% (of 385) of ferritin tests were not concurrently tested with C-reactive protein. Despite midwives prescribing iron for 48.7% of second trimester women, 47.1% still had low iron status before birth. Only 22.8% of women had hemoglobin testing postpartum. There was a significant difference between third trimester median ferritin levels in women with BMI ≥25.00 (14 μg/L) and BMI iron status was difficult to categorize, because of inconsistent testing. This study indicates the need for an evidence-based clinical guideline for New Zealand midwives and maternity care providers. © 2017 Wiley Periodicals, Inc.

  8. A Prospective Pathologic Study to Define the Clinical Target Volume for Partial Breast Radiation Therapy in Women With Early Breast Cancer

    International Nuclear Information System (INIS)

    Nguyen, Brandon T.; Deb, Siddhartha; Fox, Stephen; Hill, Prudence; Collins, Marnie; Chua, Boon H.

    2012-01-01

    Purpose: To determine an appropriate clinical target volume for partial breast radiation therapy (PBRT) based on the spatial distribution of residual invasive and in situ carcinoma after wide local excision (WLE) for early breast cancer or ductal carcinoma in situ (DCIS). Methods and Materials: We performed a prospective pathologic study of women potentially eligible for PBRT who had re-excision and/or completion mastectomy after WLE for early breast cancer or DCIS. A pathologic assessment protocol was used to determine the maximum radial extension (MRE) of residual carcinoma from the margin of the initial surgical cavity. Women were stratified by the closest initial radial margin width: negative (>1 mm), close (>0 mm and ≤1 mm), or involved. Results: The study population was composed of 133 women with a median age of 59 years (range, 27-82 years) and the following stage groups: 0 (13.5%), I (40.6%), II (38.3%), and III (7.5%). The histologic subtypes of the primary tumor were invasive ductal carcinoma (74.4%), invasive lobular carcinoma (12.0%), and DCIS alone (13.5%). Residual carcinoma was present in the re-excision and completion mastectomy specimens in 55.4%, 14.3%, and 7.2% of women with an involved, close, and negative margin, respectively. In the 77 women with a noninvolved radial margin, the MRE of residual disease, if present, was ≤10 mm in 97.4% (95% confidence interval 91.6-99.5) of cases. Larger MRE measurements were significantly associated with an involved margin (P 30 mm (P=.03), premenopausal status (P=.03), and negative progesterone receptor status (P=.05). Conclusions: A clinical target volume margin of 10 mm would encompass microscopic residual disease in >90% of women potentially eligible for PBRT after WLE with noninvolved resection margins.

  9. Defining safety culture and the nexus between safety goals and safety culture. 1. An Investigation Study on Practical Points of Safety Management

    International Nuclear Information System (INIS)

    Hasegawa, Naoko; Takano, Kenichi; Hirose, Ayako

    2001-01-01

    In a report after the Chernobyl accident, the International Atomic Energy Agency indicated the definition and the importance of safety culture and the ideal organizational state where safety culture pervades. However, the report did not mention practical approaches to enhance safety culture. In Japan, although there had been investigations that clarified the consciousness of employees and the organizational climate in the nuclear power and railway industries, organizational factors that clarified the level of organization safety and practical methods that spread safety culture in an organization had not been studied. The Central Research Institute of the Electric Power Industry conducted surveys of organizational culture for the construction, chemical, and manufacturing industries. The aim of our study was to clarify the organizational factors that influence safety in an organization expressed in employee safety consciousness, commitment to safety activities, rate of accidents, etc. If these areas were clarified, the level of organization safety might be evaluated, and practical ways could be suggested to enhance the safety culture. Consequently, a series of investigations was conducted to clarify relationships among organizational climate, employee consciousness, safety management and activities, and rate of accidents. The questionnaire surveys were conducted in 1998-1999. The subjects were (a) managers of the safety management sections in the head offices of the construction, chemical, and manufacturing industries; (b) responsible persons in factories of the chemical and manufacturing industries; and (c) general workers in factories of the chemical and manufacturing industries. The number of collected data was (a) managers in the head office: 48 from the construction industry and 58 from the chemical and manufacturing industries, (b) responsible persons in factories: 567, and (c) general workers: from 29 factories. Items in the questionnaires were selected from

  10. Phylogeny in Defining Model Plants for Lignocellulosic Ethanol Production: A Comparative Study of Brachypodium distachyon, Wheat, Maize, and Miscanthus x giganteus Leaf and Stem Biomass

    Science.gov (United States)

    Meineke, Till; Manisseri, Chithra; Voigt, Christian A.

    2014-01-01

    The production of ethanol from pretreated plant biomass during fermentation is a strategy to mitigate climate change by substituting fossil fuels. However, biomass conversion is mainly limited by the recalcitrant nature of the plant cell wall. To overcome recalcitrance, the optimization of the plant cell wall for subsequent processing is a promising approach. Based on their phylogenetic proximity to existing and emerging energy crops, model plants have been proposed to study bioenergy-related cell wall biochemistry. One example is Brachypodium distachyon, which has been considered as a general model plant for cell wall analysis in grasses. To test whether relative phylogenetic proximity would be sufficient to qualify as a model plant not only for cell wall composition but also for the complete process leading to bioethanol production, we compared the processing of leaf and stem biomass from the C3 grasses B. distachyon and Triticum aestivum (wheat) with the C4 grasses Zea mays (maize) and Miscanthus x giganteus, a perennial energy crop. Lambda scanning with a confocal laser-scanning microscope allowed a rapid qualitative analysis of biomass saccharification. A maximum of 108–117 mg ethanol·g−1 dry biomass was yielded from thermo-chemically and enzymatically pretreated stem biomass of the tested plant species. Principal component analysis revealed that a relatively strong correlation between similarities in lignocellulosic ethanol production and phylogenetic relation was only given for stem and leaf biomass of the two tested C4 grasses. Our results suggest that suitability of B. distachyon as a model plant for biomass conversion of energy crops has to be specifically tested based on applied processing parameters and biomass tissue type. PMID:25133818

  11. Defining the Relationship of Student Achievement Between STEM Subjects Through Canonical Correlation Analysis of 2011 Trends in International Mathematics and Science Study (TIMSS) Data

    Science.gov (United States)

    O'Neal, Melissa Jean

    Canonical correlation analysis was used to analyze data from Trends in International Mathematics and Science Study (TIMSS) 2011 achievement databases encompassing information from fourth/eighth grades. Student achievement in life science/biology was correlated with achievement in mathematics and other sciences across three analytical areas: mathematics and science student performance, achievement in cognitive domains, and achievement in content domains. Strong correlations between student achievement in life science/biology with achievement in mathematics and overall science occurred for both high- and low-performing education systems. Hence, partial emphases on the inter-subject connections did not always lead to a better student learning outcome in STEM education. In addition, student achievement in life science/biology was positively correlated with achievement in mathematics and science cognitive domains; these patterns held true for correlations of life science/biology with mathematics as well as other sciences. The importance of linking student learning experiences between and within STEM domains to support high performance on TIMSS assessments was indicated by correlations of moderate strength (57 TIMSS assessments was indicated by correlations of moderate strength (57 mathematics, and other sciences. At the eighth grade level, students who built increasing levels of cognitive complexity upon firm foundations were prepared for successful learning throughout their educational careers. The results from this investigation promote a holistic design of school learning opportunities to improve student achievement in life science/biology and other science, technology, engineering, and mathematics (STEM) subjects at the elementary and middle school levels. While the curriculum can vary from combined STEM subjects to separated mathematics or science courses, both professional learning communities (PLC) for teachers and problem-based learning (PBL) for learners can be

  12. Spatial landuse planning using land evaluation and dynamic system to define sustainable area of paddy field: Case study in Karawang Regency, West Java, Indonesia

    Science.gov (United States)

    Widiatmaka, Widiatmaka; Ambarwulan, Wiwin; Firmansyah, Irman; Munibah, Khursatul; Santoso, Paulus B. K.

    2015-04-01

    Indonesia is the country with the 4th largest population in the worlds; the population reached more than 237 million people. With rice as the staple food for more than 95 percent of the population, there is an important role of paddy field in Indonesian food security. Actually, paddy field in Java has produced 52,6% of the total rice production in Indonesia, showing the very high dependence of Indonesia on food production from paddy fields in Java island. Karawang Regency is one of the regions in West Java Province that contribute to the national food supply, due to its high soil fertility and its high extent of paddy field. Dynamics of land use change in this region are high because of its proximity to urban area; this dynamics has led to paddy field conversion to industry and residential landuse, which in turn change the regional rice production capacity. Decreasing paddy field landuse in this region could be serve as an example case of the general phenomena which occurred in Javanese rice production region. The objective of this study were: (i) to identify the suitable area for paddy field, (ii) to modelize the decreasing of paddy field in socio-economic context of the region, and (iii) to plan the spatial priority area of paddy field protection according to model prediction. A land evaluation for paddy was completed after a soil survey, while IKONOS imagery was analyzed to delineate paddy fields. Dynamic system model of paddy field land use is built, and then based on the model built, the land area of paddy field untill 2040 in some scenarios was developped. The research results showed that the land suitability class for paddy fields in Karawang Regency ranged from very suitable (S1) to marginally suitable (S3), with various land characteristics as limiting factors. The model predicts that if the situation of paddy field land use change continues in its business as usual path, paddy field area that would exist in the region in 2040 will stay half of the recent

  13. Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727

    Directory of Open Access Journals (Sweden)

    Law Mary

    2006-07-01

    Full Text Available Abstract Background A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning related to health outcome measures. Method/Design Physical and occupational therapists (n = 144 will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1 Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS, and 2 Online Problem-Based course (e-PBL. SHIPS will consist of face-to-face problem-based learning (PBL for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT

  14. First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study.

    Directory of Open Access Journals (Sweden)

    Fabia Zu Knyphausen

    Full Text Available BACKGROUND: Transmission of drug-resistant HIV-1 (TDR can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. METHODS: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. RESULTS: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667 in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0% and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01. Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96 and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17 remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41. CONCLUSION: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were

  15. Anti-ageing effects of a new synthetic sphingolipid (K6EAA-L12) on aged murine skin.

    Science.gov (United States)

    Jung, Minyoung; Lee, Sanghoon; Park, Hwa-young; Youm, Jong-Kyung; Jeong, Sekyoo; Bae, Jonghwan; Kwon, Mi Jung; Park, Byeong Deog; Lee, Seung Hun; Choi, Eung Ho

    2011-04-01

    Recently, we reported on the anti-ageing effects of K6PC-5. This compound induced keratinocyte differentiation and fibroblast proliferation by increasing sphingosine-1 phosphate synthesis. We performed this study to confirm the anti-ageing effects of new synthetic products (the K6EAA series) derived from K6PC-5 through an amino group induction. Cellular responses such as differentiation, proliferation and calcium mobilization were investigated using cultured human keratinocytes and fibroblasts. Also, we measured the expressions of collagen mRNA and protein using real time RT-PCR and ELISA, respectively. The K6EAA-L12 product, selected by in vitro screening, was evaluated for anti-ageing effects on intrinsically and extrinsically (photo) aged models of hairless mice. In the intrinsically aged murine skin, K6EAA-L12 showed anti-ageing effects by activating collagen synthesis, eventually causing dermal thickening. Also, in the photo-aged skin, the dermal collagen density and dermal thickness were increased. In photo-aged murine skin, K6EAA-L12 increased stratum corneum integrity by increasing corneodesmosome density and improved the barrier recovery rate. However, there were no changes in the expressions of epidermal differentiation maker proteins. In conclusion, topical K6EAA-L12, a new synthetic K6PC-5 derivative, improves intrinsically and extrinsically (photo) aged skin by increasing the collagen density and improving the skin barrier function. © 2011 John Wiley & Sons A/S.

  16. AIDS defining disease: Disseminated cryptococcosis

    Directory of Open Access Journals (Sweden)

    Roshan Anupama

    2006-01-01

    Full Text Available Disseminated cryptococcosis is one of the acquired immune deficiency syndrome defining criteria and the most common cause of life threatening meningitis. Disseminated lesions in the skin manifest as papules or nodules that mimic molluscum contagiosum (MC. We report here a human immunodeficiency virus positive patient who presented with MC like lesions. Disseminated cryptococcosis was confirmed by India ink preparation and histopathology. The condition of the patient improved with amphotercin B.

  17. How Should Energy Be Defined throughout Schooling?

    Science.gov (United States)

    Bächtold, Manuel

    2018-01-01

    The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two…

  18. Defining Virtual Reality: Dimensions Determining Telepresence.

    Science.gov (United States)

    Steuer, Jonathan

    1992-01-01

    Defines virtual reality as a particular type of experience (in terms of "presence" and "telepresence") rather than as a collection of hardware. Maintains that media technologies can be classified and studied in terms of vividness and interactivity, two attributes on which virtual reality ranks very high. (SR)

  19. Network Coded Software Defined Networking

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Roetter, Daniel Enrique Lucani

    2015-01-01

    Software Defined Networking (SDN) and Network Coding (NC) are two key concepts in networking that have garnered a large attention in recent years. On the one hand, SDN's potential to virtualize services in the Internet allows a large flexibility not only for routing data, but also to manage....... This paper advocates for the use of SDN to bring about future Internet and 5G network services by incorporating network coding (NC) functionalities. The inherent flexibility of both SDN and NC provides a fertile ground to envision more efficient, robust, and secure networking designs, that may also...

  20. Network Coded Software Defined Networking

    DEFF Research Database (Denmark)

    Hansen, Jonas; Roetter, Daniel Enrique Lucani; Krigslund, Jeppe

    2015-01-01

    Software defined networking has garnered large attention due to its potential to virtualize services in the Internet, introducing flexibility in the buffering, scheduling, processing, and routing of data in network routers. SDN breaks the deadlock that has kept Internet network protocols stagnant...... for decades, while applications and physical links have evolved. This article advocates for the use of SDN to bring about 5G network services by incorporating network coding (NC) functionalities. The latter constitutes a major leap forward compared to the state-of-the- art store and forward Internet paradigm...

  1. (Re)Defining Salesperson Motivation

    DEFF Research Database (Denmark)

    Khusainova, Rushana; de Jong, Ad; Lee, Nick

    2018-01-01

    The construct of motivation is one of the central themes in selling and sales management research. Yet, to-date no review article exists that surveys the construct (both from an extrinsic and intrinsic motivation context), critically evaluates its current status, examines various key challenges...... apparent from the extant research, and suggests new research opportunities based on a thorough review of past work. The authors explore how motivation is defined, major theories underpinning motivation, how motivation has historically been measured, and key methodologies used over time. In addition......, attention is given to principal drivers and outcomes of salesperson motivation. A summarizing appendix of key articles in salesperson motivation is provided....

  2. Defining Usability of PN Services

    DEFF Research Database (Denmark)

    Nicolajsen, Hanne Westh; Ahola, Titta; Fleury, Alexandre

    In this deliverable usability and user experience are defined in relation to MAGNET Beyond technologies, and it is described how the main MAGNET Beyond concepts can be evaluated through the involvement of users. The concepts include the new "Activity based communication approach" for interacting...... with the MAGNET Beyond system, as well as the core concepts: Personal Network, Personal Network-Federation, Service Discovery, User Profile Management, Personal Network Management, Privacy and Security and Context Awareness. The overall plans for the final usability evaluation are documented based on the present...

  3. Expressiveness and definability in circumscription

    Directory of Open Access Journals (Sweden)

    Francicleber Martins Ferreira

    2011-06-01

    Full Text Available We investigate expressiveness and definability issues with respect to minimal models, particularly in the scope of Circumscription. First, we give a proof of the failure of the Löwenheim-Skolem Theorem for Circumscription. Then we show that, if the class of P; Z-minimal models of a first-order sentence is Δ-elementary, then it is elementary. That is, whenever the circumscription of a first-order sentence is equivalent to a first-order theory, then it is equivalent to a finitely axiomatizable one. This means that classes of models of circumscribed theories are either elementary or not Δ-elementary. Finally, using the previous result, we prove that, whenever a relation Pi is defined in the class of P; Z-minimal models of a first-order sentence Φ and whenever such class of P; Z-minimal models is Δ-elementary, then there is an explicit definition ψ for Pi such that the class of P; Z-minimal models of Φ is the class of models of Φ ∧ ψ. In order words, the circumscription of P in Φ with Z varied can be replaced by Φ plus this explicit definition ψ for Pi.

  4. Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease.

    Science.gov (United States)

    Chipeaux, Caroline; de Person, Marine; Burguet, Nathalie; Billette de Villemeur, Thierry; Rose, Christian; Belmatoug, Nadia; Héron, Sylvie; Le Van Kim, Caroline; Franco, Mélanie; Moussa, Fathi

    2017-11-24

    While important advances have been recently achieved in the optimization of lipid classes' separation, information on the specific determination of medium polarity lipids such as sphingolipids (SLs) in highly complex matrices remains fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a heterogeneous group of inherited disorders affecting primarily the central nervous. Early diagnosis of these conditions is of importance notably when a corrective therapy is available. The diagnosis is generally based on the determination of specific SLs in plasma and red blood cells (RBCs). For instance, glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher disease (GD). Our main objective was to evaluate these biomarker candidates in a cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph, and S1P determination in plasma of GD patients require at least two liquid chromatographic runs. On the other hand, except for GL1 nothing is known concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS methods of SLs separation and/or determination in various media with different sample preparation approaches have been proposed since 2010. Here we focused on stationary phase selection and mobile phase composition as well as on the sample preparation step to optimize and validate an UHPLC-MS/MS method for the simultaneous quantification of the four sphingolipids in both plasma and RBCs. A comparison between seven stationary phases including two RP18, two polar embedded RP18, and three HILIC phases shows that under our conditions polar embedded RP18 phases are the most appropriate for the separation of the four SLs, in terms of efficiency, peak symmetry, and separation time. In the same way, a comparison between a single step extraction with methanol and a liquid-liquid extraction with a mixture of methanol/methyl tert

  5. Miniature EVA Software Defined Radio

    Science.gov (United States)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  6. FINANCIAL ACCOUNTING QUALITY AND ITS DEFINING CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Andra M. ACHIM

    2014-11-01

    Full Text Available The importance ofhigh-quality financial statements is highlighted by the main standard-setting institutions activating in the field of accounting and reporting. These have issued Conceptual Frameworks which state and describe the qualitative characteristics of accounting information. In this qualitative study, the research methodology consists of reviewing the literature related to the definition of accounting quality and striving for understanding how it can be explained. The main objective of the study is to identify the characteristics information should possess in order to be of high quality. These characteristics also contribute to the way of defining financial accounting quality. The main conclusions that arise from this research are represented by the facts that indeed financial accounting quality cannot be uniquely defined and that financial information is of good quality when it enhances the characteristics incorporated in the conceptual frameworks issued by both International Accounting Standards Board and Financial Accounting Standards Board.

  7. Exploring self-defining memories in schizophrenia.

    Science.gov (United States)

    Raffard, Stéphane; D'Argembeau, Arnaud; Lardi, Claudia; Bayard, Sophie; Boulenger, Jean-Philippe; Van Der Linden, Martial

    2009-01-01

    Previous studies have shown that patients with schizophrenia are impaired in recalling specific events from their personal past. However, the relationship between autobiographical memory impairments and disturbance of the sense of identity in schizophrenia has not been investigated in detail. In this study the authors investigated schizophrenic patients' ability to recall self-defining memories; that is, memories that play an important role in building and maintaining the self-concept. Results showed that patients recalled as many specific self-defining memories as healthy participants. However, patients with schizophrenia exhibited an abnormal reminiscence bump and reported different types of thematic content (i.e., they recalled less memories about past achievements and more memories regarding hospitalisation and stigmatisation of illness). Furthermore, the findings suggest that impairments in extracting meaning from personal memories could represent a core disturbance of autobiographical memory in patients with schizophrenia.

  8. How Should Energy Be Defined Throughout Schooling?

    Science.gov (United States)

    Bächtold, Manuel

    2017-02-01

    The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two main approaches in physics concerning the definition of energy, one claiming there is no satisfactory definition and taking conservation as a fundamental property, and the other based on Rankine's definition of energy as the capacity of a system to produce changes. We then present a study concerning how energy is actually defined throughout schooling in the case of France by analyzing national programs, physics textbooks, and the answers of teachers to a questionnaire. This study brings to light a consistency problem in the way energy is defined across school years: in primary school, an adapted version of Rankine's definition is introduced and conservation is ignored; in high school, conservation is introduced and Rankine's definition is ignored. Finally, we address this consistency problem by discussing possible teaching progressions. We argue in favor of the use of Rankine's definition throughout schooling: at primary school, it is a possible substitute to students' erroneous conceptions; at secondary school, it might help students become aware of the unifying role of energy and thereby overcome the compartmentalization problem.

  9. Defining Tobacco Regulatory Science Competencies.

    Science.gov (United States)

    Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

    2017-02-01

    In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Defining Issues Test-2: fidedignidade da versão brasileira e ponderações acerca de seu uso em pesquisas sobre moralidade Defining Issues Test-2: reliability of the Brazilian version and considerations concerning its use in studies on morality

    Directory of Open Access Journals (Sweden)

    Alessandra de Morais Shimizu

    2004-01-01

    Full Text Available Este estudo teve como objetivo avaliar a fidedignidade da tradução e adaptação brasileira do Definig Issues Test (DIT -2, assim como realizar algumas ponderações sobre a utilização desse instrumento e do DIT -1 em pesquisas sobre moralidade. Os testes DIT-1 e DIT-2 foram aplicados em 621 jovens brasileiros, proporcionalmente distribuídos conforme a cidade de procedência (Floriano/PI, Erechim/RS e Marília/SP, o tipo de escola (pública e particular e o ano escolar freqüentado (8º ano do ensino fundamental e 3º ano do ensino médio. Em relação à fidedignidade, notou-se que, apesar de os valores alcançados serem próximos àquele obtido na tradução e adaptação do DIT-1, revelam-se bem menores que os verificados nas versões originais americanas. Na verificação das pontuações alcançadas nos testes, foi observada a existência de tendências distintas no interior da amostra investigada, marcadas pelas variáveis controladas. Foram tecidas considerações sobre a validade e a interpretação desses testes.This study aims to evaluate the reliability of a Brazilian translation and adaptation of the Defining Issues Test (DIT -2, as well as to make considerations concerning the use of this tool and of DIT -1 in studies on morality. The DIT -1 and DIT -2 were administred to 621 Brazilian youngsters, equally distributed according to the city of origin (Floriano/PI, Erechim/RS and Marília/SP, the kind of school (public or private and the school year attended (8th grade and 11th grade. Regarding the reliability, it was noticed that although the values achieved were close to that one obtained in the translation and adaptation of DIT -1, they revealed themselves much lower than the ones verified in the American original versions. When checking the scores achieved in the tests the existence of some tendencies within the investigated sample was observed. Some considerations regarding the validity and interpretation of these tests are

  11. Defining Tiger Parenting in Chinese Americans.

    Science.gov (United States)

    Kim, Su Yeong

    2013-09-01

    "Tiger" parenting, as described by Amy Chua [2011], has instigated scholarly discourse on this phenomenon and its possible effects on families. Our eight-year longitudinal study, published in the Asian American Journal of Psychology [Kim, Wang, Orozco-Lapray, Shen, & Murtuza, 2013b], demonstrates that tiger parenting is not a common parenting profile in a sample of 444 Chinese American families. Tiger parenting also does not relate to superior academic performance in children. In fact, the best developmental outcomes were found among children of supportive parents. We examine the complexities around defining tiger parenting by reviewing classical literature on parenting styles and scholarship on Asian American parenting, along with Amy Chua's own description of her parenting method, to develop, define, and categorize variability in parenting in a sample of Chinese American families. We also provide evidence that supportive parenting is important for the optimal development of Chinese American adolescents.

  12. Defining enthesitis in spondyloarthritis by ultrasound

    DEFF Research Database (Denmark)

    Terslev, Lene; Naredo, E; Iagnocco, A

    2014-01-01

    Objective: To standardize ultrasound (US) in enthesitis. Methods: An Initial Delphi exercise was undertaken to define US detected enthesitis and its core components. These definitions were subsequently tested on static images taken from Spondyloarthritis (SpA) patients in order to evaluate...... elementary component. On static images the intra-observer reliability showed a high degree of variability for the detection of elementary lesions with kappa coefficients ranging from 0.14 - 1. The inter-observer kappa value was variable with the lowest kappa for enthesophytes (0.24) and the best for Doppler...... activity at the enthesis (0.63). Conclusion: This is the first consensus based definition of US enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work. Defining Enthesitis...

  13. HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

    DEFF Research Database (Denmark)

    Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian

    2008-01-01

    OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively......-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality...

  14. SOCIAL ROBOT: DEFINING THE CONCEPT

    Directory of Open Access Journals (Sweden)

    Nadezhda Nikolaevna Zilberman

    2016-11-01

    Practical implications. The results of the study contribute toьthe theoretical basis of the cross-disciplinary research field of social robotics and may be used by researchers. They may also be used as educational aid in teaching academic courses in social studies, robotics, ethics of technology, artificial intelligence, etc.

  15. Defining and Measuring Teacher Legitimacy

    Science.gov (United States)

    Drake, Douglass Martin

    2013-01-01

    Power and authority exist in every relationship. The relationship between teacher and student is no exception. Legitimacy is the cornerstone of authority, yet there is a dearth of research into how teacher legitimacy affects the teacher/student relationship. In the current study, I sought to identify characteristics and behaviors teachers exhibit…

  16. Building and Defining Behavioral Economics

    NARCIS (Netherlands)

    Heukelom, F.; Emmett, R.; Biddle, J.E.

    2011-01-01

    George Loewenstein, a prominent behavioral economist, recalls thatIn 1994, when Thaler, Camerer, Rabin, Prelec and I spent the year at the Center for Advanced Study in the Behavioral Sciences, we had a meeting to make a kind of final decision about what to call what we were doing. Remarkably, at

  17. Defining Platelet Function During Polytrauma

    Science.gov (United States)

    2014-04-01

    scaffold of the clot after its thrombin-induced polymerization to fibrin fibers. Formation of a stiff fibrin fiber network and its contraction by platelet...In another study (PROTEC T) Refused Participat ion (Yes=Y, No=N, W=Unqua lified , Refused further draws (agreed to keep previous data

  18. DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic.

    Science.gov (United States)

    Roberts, Jason A; De Waele, Jan J; Dimopoulos, George; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Lipman, Jeffrey

    2012-07-06

    The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals) on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study) is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs) will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

  19. DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic

    Directory of Open Access Journals (Sweden)

    Roberts Jason A

    2012-07-01

    Full Text Available Abstract Background The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. Methods DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. Discussion The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

  20. Terminology, the importance of defining.

    Science.gov (United States)

    van Mil, J W Foppe; Henman, Martin

    2016-06-01

    Multiple terms and definitions exist to describe specific aspects of pharmacy practice and service provision. This commentary explores the reasons for different interpretations of words and concepts in pharmaceutical care and pharmacy practice research. Reasons for this variation can be found in language, culture, profession and may also depend on developments over time. A list of words is provided where the authors think that currently multiple interpretations are possible. To make sure that the reader understands the essence, it seems imperative that authors include a definition of the topics that they actually study in their papers, and that they clearly cite existing definitions or refer to collections of definitions such as existing glossaries. It is important that presenters, authors and reviewers of pharmacy practice papers pay more attention to this aspect of describing studies.

  1. Production of α-galactosylceramide by a prominent member of the human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Laura C Wieland Brown

    2013-07-01

    Full Text Available While the human gut microbiota are suspected to produce diffusible small molecules that modulate host signaling pathways, few of these molecules have been identified. Species of Bacteroides and their relatives, which often comprise >50% of the gut community, are unusual among bacteria in that their membrane is rich in sphingolipids, a class of signaling molecules that play a key role in inducing apoptosis and modulating the host immune response. Although known for more than three decades, the full repertoire of Bacteroides sphingolipids has not been defined. Here, we use a combination of genetics and chemistry to identify the sphingolipids produced by Bacteroides fragilis NCTC 9343. We constructed a deletion mutant of BF2461, a putative serine palmitoyltransferase whose yeast homolog catalyzes the committed step in sphingolipid biosynthesis. We show that the Δ2461 mutant is sphingolipid deficient, enabling us to purify and solve the structures of three alkaline-stable lipids present in the wild-type strain but absent from the mutant. The first compound was the known sphingolipid ceramide phosphorylethanolamine, and the second was its corresponding dihydroceramide base. Unexpectedly, the third compound was the glycosphingolipid α-galactosylceramide (α-GalCer(Bf, which is structurally related to a sponge-derived sphingolipid (α-GalCer, KRN7000 that is the prototypical agonist of CD1d-restricted natural killer T (iNKT cells. We demonstrate that α-GalCer(Bf has similar immunological properties to KRN7000: it binds to CD1d and activates both mouse and human iNKT cells both in vitro and in vivo. Thus, our study reveals BF2461 as the first known member of the Bacteroides sphingolipid pathway, and it indicates that the committed steps of the Bacteroides and eukaryotic sphingolipid pathways are identical. Moreover, our data suggest that some Bacteroides sphingolipids might influence host immune homeostasis.

  2. Defining recovery in adult bulimia nervosa.

    Science.gov (United States)

    Yu, Jessica; Agras, W Stewart; Bryson, Susan

    2013-01-01

    To examine how different definitions of recovery lead to varying rates of recovery, maintenance of recovery, and relapse in bulimia nervosa (BN), end-of-treatment (EOT) and follow-up data were obtained from 96 adults with BN. Combining behavioral, physical, and psychological criteria led to recovery rates between 15.5% and 34.4% at EOT, though relapse was approximately 50%. Combining these criteria and requiring abstinence from binge eating and purging when defining recovery may lead to lower recovery rates than those found in previous studies; however, a strength of this definition is that individuals who meet this criteria have no remaining disordered behaviors or symptoms.

  3. Defining the Strategy of Nuclear Activity

    International Nuclear Information System (INIS)

    Racana, R.

    2006-01-01

    This article presents nuclear activity as defined within the field of the nuclear industry, which is studied from its capacity to generate electric power to its application in industry and medicine as well as a source for weapons of mass destruction. These fields of analysis introduce some problems that the nuclear activity itself must know how to confront employing action strategies aimed at becoming an activity to be kept in mind when making use of the benefits that its peaceful use contributes to human life. (Author)

  4. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  5. Software defined networking applications in distributed datacenters

    CERN Document Server

    Qi, Heng

    2016-01-01

    This SpringerBrief provides essential insights on the SDN application designing and deployment in distributed datacenters. In this book, three key problems are discussed: SDN application designing, SDN deployment and SDN management. This book demonstrates how to design the SDN-based request allocation application in distributed datacenters. It also presents solutions for SDN controller placement to deploy SDN in distributed datacenters. Finally, an SDN management system is proposed to guarantee the performance of datacenter networks which are covered and controlled by many heterogeneous controllers. Researchers and practitioners alike will find this book a valuable resource for further study on Software Defined Networking. .

  6. The problem of defining myth

    Directory of Open Access Journals (Sweden)

    Lauri Honko

    1972-01-01

    Full Text Available The first thing that one realises in trying to grasp the semantic implications of myth is that myth can cover an extremely wide field. The way in which the term myth is commonly used reveals, too, that the word is loaded with emotional overtones. These overtones creep not only into common parlance but also, somewhat surprisingly, into scientific usage. That myth does, in fact, carry emotional overtones in this way is perhaps most easily seen if we think of terms such as prayer, liturgy, ritual drama, spell: they are all used for different religious genres but would seem to be more neutral than myth. It appears to be difficult for many scholars to discuss myth simply as a form of religious communication, as one genre among other genres. If one differentiates between four levels, namely, form, content, function and context, it is much easier to encounter the varied uses which the concept has acquired in scientific literature. By this it is possible to delimit and yet be flexible at the same time. There is no need to welcome with open arms just any traditions into the fold of myth research: but nor is it necessary to exclude, for example, studies of myth where the context criterion, i.e. a context of ritual, is not fulfilled. The degree of flexibility that can be achieved is dependent on the approach that the scholar has chosen.

  7. Defining and certifying green power

    International Nuclear Information System (INIS)

    1998-02-01

    Studies have shown that as electric utilities restructure from monopolistic utilities to competitive open access retailers, there is an increasing demand by individual and institutional customers for green power. In the United States, 17 electricity suppliers have offered customers the opportunity to buy energy generated from renewable sources such as photovoltaic panels, wind turbines and biomass. Twenty other utilities are conducting market research in preparation for offering a similar program. It was suggested that in order to help the customers make their choice based on accurate information, generating facilities should be obligated to provide credible information about the environmental performance of electricity supply through standardized environmental profile labels. A list of agreed upon environmental indicators and performance levels must be established so that the 'environmental friendliness' of different generating facilities can be measured. One of the problems in tackling this issue is that there is disagreement about what constitutes green power. Opinions range from wind and solar generation being the only two forms of green power, to including even natural gas and nuclear energy (i.e. under the right conditions). The two programs that are used for the certification of green power in Canada and the United States are Canada's Environmental Choice Program and California's Green-e Renewable Electricity Branding Program. This report describes the two programs and summarizes the results of interviews conducted on the definition and certification of green power. 15 refs

  8. Defining disability: metaphysical not political.

    Science.gov (United States)

    Riddle, Christopher A

    2013-08-01

    Recent discussions surrounding the conceptualising of disability has resulted in a stalemate between British sociologists and philosophers. The stagnation of theorizing that has occurred threatens not only academic pursuits and the advancement of theoretical interpretations within the Disability Studies community, but also how we educate and advocate politically, legally, and socially. More pointedly, many activists and theorists in the UK appear to believe the British social model is the only effective means of understanding and advocating on behalf of people with disabilities. This model, largely reliant upon materialist research traditions, contends that disability is a form of social oppression and hence, is a phenomenon that should be conceptualised in social terms. Individual properties such as impairments are disregarded as they are viewed to be unimportant in the analysis of the social causes of disability. Concurrently, many bioethicists and philosophers have embraced what Tom Shakespeare has classified as an 'Interactional Approach' to disability--that "the experience of a disabled person results from the relationship between factors intrinsic to the individual, and the extrinsic factors arising from the wider context in which she finds herself". I intend to demonstrate that the benefits of the British social model are now outweighed by its burdens. I suggest, as Jerome Bickenbach has, that while it may be somewhat churlish to critique the social model in light of its political success, taken literally, it implies that people with disabilities require no additional health resources by virtue of their impairments. Despite the eloquent arguments that have preceded me by interactional theorists, none have been accepted as evidence of fallacious reasoning by British social model theorists. This article is an attempt to clarify why it is that the types of arguments British social model theorists have been offering are misguided. I suggest that the British

  9. Night work and breast cancer risk defined by human epidermal growth factor receptor-2 (HER2) and hormone receptor status: A population-based case-control study in France.

    Science.gov (United States)

    Cordina-Duverger, Emilie; Koudou, Yves; Truong, Thérèse; Arveux, Patrick; Kerbrat, Pierre; Menegaux, Florence; Guénel, Pascal

    Night work has been associated with risk of breast cancer but this association needs to be confirmed. Because breast cancer is an etiologically heterogeneous disease, we explored the association of night work with breast cancer subtypes defined by tumor status (positive of negative) for estrogen-receptor (ER), progesterone-receptor (PR) and human epidermal growth factor-receptor 2 (HER2). Using the data from a case-control study in France including 975 cases and 1317 controls, we found that the odds ratios for ER+, PR+ or HER2+ breast cancers subtypes were significantly elevated, while no association with night shift work was observed for ER, PR or HER2-negative tumors. After stratification by menopausal status, the associations of night work with receptor-positive breast tumor subtypes were clearly seen in premenopausal women (odds ratios 2.04, 1.98 and 2.80, respectively) but did not appear in postmenopausal women. This study provides evidence that working at night may increase risk of ER, PR and HER2-positive subtypes of breast cancer particularly among premenopausal women.

  10. Indico CONFERENCE: Define the Call for Abstracts

    CERN Multimedia

    CERN. Geneva; Ferreira, Pedro

    2017-01-01

    In this tutorial, you will learn how to define and open a call for abstracts. When defining a call for abstracts, you will be able to define settings related to the type of questions asked during a review of an abstract, select the users who will review the abstracts, decide when to open the call for abstracts, and more.

  11. On defining semantics of extended attribute grammars

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    1980-01-01

    Knuth has introduced attribute grammars (AGs) as a tool to define the semanitcs of context-free languages. The use of AGs in connection with programming language definitions has mostly been to define the context-sensitive syntax of the language and to define a translation in code for a hypothetic...

  12. Languages for Software-Defined Networks

    Science.gov (United States)

    2013-02-01

    switches, firewalls, and middleboxes) with closed and proprietary configuration inter- faces. Software - Defined Networks ( SDN ) are poised to change...how- ever, have seen growing interest in software - defined networks ( SDNs ), in which a logically-centralized controller manages the packet-processing...switches, firewalls, and middleboxes) with closed and proprietary configuration interfaces. Software - Defined Networks ( SDN ) are poised to change this

  13. Well-defined critical association concentration and rapid adsorption at the air/water interface of a short amphiphilic polymer, amphipol A8-35: a study by Förster resonance energy transfer and dynamic surface tension measurements.

    Science.gov (United States)

    Giusti, Fabrice; Popot, Jean-Luc; Tribet, Christophe

    2012-07-17

    Amphipols (APols) are short amphiphilic polymers designed to handle membrane proteins (MPs) in aqueous solutions as an alternative to small surfactants (detergents). APols adsorb onto the transmembrane, hydrophobic surface of MPs, forming small, water-soluble complexes, in which the protein is biochemically stabilized. At variance with MP/detergent complexes, MP/APol ones remain stable even at extreme dilutions. Pure APol solutions self-associate into well-defined micelle-like globules comprising a few APol molecules, a rather unusual behavior for amphiphilic polymers, which typically form ill-defined assemblies. The best characterized APol to date, A8-35, is a random copolymer of acrylic acid, isopropylacrylamide, and octylacrylamide. In the present work, the concentration threshold for self-association of A8-35 in salty buffer (NaCl 100 mM, Tris/HCl 20 mM, pH 8.0) has been studied by Förster resonance energy transfer (FRET) measurements and tensiometry. In a 1:1 mol/mol mixture of APols grafted with either rhodamine or 7-nitro-1,2,3-benzoxadiazole, the FRET signal as a function of A8-35 concentration is essentially zero below a threshold concentration of 0.002 g·L(-1) and increases linearly with concentration above this threshold. This indicates that assembly takes place in a narrow concentration interval around 0.002 g·L(-1). Surface tension measurements decreases regularly with concentration until a threshold of ca. 0.004 g·L(-1), beyond which it reaches a plateau at ca. 30 mN·m(-1). Within experimental uncertainties, the two techniques thus yield a comparable estimate of the critical self-assembly concentration. The kinetics of variation of the surface tension was analyzed by dynamic surface tension measurements in the time window 10 ms-100 s. The rate of surface tension decrease was similar in solutions of A8-35 and of the anionic surfactant sodium dodecylsulfate when both compounds were at a similar molar concentration of n-alkyl moieties. Overall, the

  14. Defining clogging potential for permeable concrete.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2018-08-15

    Permeable concrete is used to reduce urban flooding as it allows water to flow through normally impermeable infrastructure. It is prone to clogging by particulate matter and predicting the long-term performance of permeable concrete is challenging as there is currently no reliable means of characterising clogging potential. This paper reports on the performance of a range of laboratory-prepared and commercial permeable concretes, close packed glass spheres and aggregate particles of varying size, exposed to different clogging methods to understand this phenomena. New methods were developed to study clogging and define clogging potential. The tests involved applying flowing water containing sand and/or clay in cycles, and measuring the change in permeability. Substantial permeability reductions were observed in all samples, particularly when exposed to sand and clay simultaneously. Three methods were used to define clogging potential based on measuring the initial permeability decay, half-life cycle and number of cycles to full clogging. We show for the first time strong linear correlations between these parameters for a wide range of samples, indicating their use for service-life prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: A cross-sectional multiethnic study.

    Science.gov (United States)

    Srivanichakorn, Weerachai; Godsland, Ian F; Thomson, Hazel; Misra, Shivani; Phisalprapa, Pochamana; Charatcharoenwitthaya, Phunchai; Pramyothin, Pornpoj; Washirasaksiri, Chaiwat; Snehalatha, Chamukuttan; Ramachandran, Ambady; Alberti, K George M M; Johnston, Desmond G; Oliver, Nick S

    2017-12-01

    Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10-3.42), p 0.03) and only LDL-c with IFG (FPG 5.6 to fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study.

    Directory of Open Access Journals (Sweden)

    Ali Judd

    2018-01-01

    Full Text Available Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE, Eastern Europe (Russia and Ukraine, and Thailand.Children with perinatal HIV aged 6 months of cART death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3 years; 35% of children aged 400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

  17. Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

    Science.gov (United States)

    Monclair, Tom; Mosseri, Véronique; Cecchetto, Giovanni; De Bernardi, Bruno; Michon, Jean; Holmes, Keith

    2015-09-01

    The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning. © 2015 Wiley Periodicals, Inc.

  18. Definable Group Extensions and o-Minimal Group Cohomology via Spectral Sequences

    OpenAIRE

    BARRIGA, ELIANA

    2013-01-01

    We provide the theoretical foundation for the Lyndon-Hochschild-Serre spectral sequence as a tool to study the group cohomology and with this the group extensions in the category of definable groups. We also present various results on definable modules and actions, definable extensions and group cohomology of definable groups. These have applications to the study of non-definably compact groups definable in o-minimal theories (see [1]). Se presenta el fundamento teórico para las sucesiones...

  19. Defining nodes in complex brain networks

    Directory of Open Access Journals (Sweden)

    Matthew Lawrence Stanley

    2013-11-01

    Full Text Available Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel. The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10-20 millimeter diameter spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the correct method to be used remains an open, possibly unsolvable question that

  20. Exposing the Myths, Defining the Future

    International Nuclear Information System (INIS)

    Slavov, S.

    2013-01-01

    With this official statement, the WEC calls for policymakers and industry leaders to ''get real'' as the World Energy Council as a global energy body exposes the myths by informing the energy debate and defines a path to a more sustainable energy future. The World Energy Council urged stakeholders to take urgent and incisive actions, to develop and transform the global energy system. Failure to do so could put aspirations on the triple challenge of WEC Energy Trilemma defined by affordability, accessibility and environmental sustainability at serious risk. Through its multi-year in-depth global studies and issue-mapping the WEC has found that challenges that energy sector is facing today are much more crucial than previously envisaged. The WEC's analysis has exposed a number of myths which influence our understanding of important aspects of the global energy landscape. If not challenged, these misconceptions will lead us down a path of complacency and missed opportunities. Much has, and still is, being done to secure energy future, but the WEC' s studies reveal that current pathways fall short of delivering on global aspirations of energy access, energy security and environmental improvements. If we are to derive the full economic and social benefits from energy resources, then we must take incisive and urgent action to modify our steps to energy solutions. The usual business approaches are not effective, the business as usual is not longer a solution. The focus has moved from large universal solutions to an appreciation of regional and national contexts and sharply differentiated consumer expectations.(author)

  1. Radiotherapy for brain metastases: defining palliative response

    International Nuclear Information System (INIS)

    Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

    2001-01-01

    Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

  2. 22 CFR 92.36 - Authentication defined.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36... Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness of... recognized in another jurisdiction. Documents which may require authentication include legal instruments...

  3. A definability theorem for first order logic

    NARCIS (Netherlands)

    Butz, C.; Moerdijk, I.

    1997-01-01

    In this paper we will present a definability theorem for first order logic This theorem is very easy to state and its proof only uses elementary tools To explain the theorem let us first observe that if M is a model of a theory T in a language L then clearly any definable subset S M ie a subset S

  4. Dilution Confusion: Conventions for Defining a Dilution

    Science.gov (United States)

    Fishel, Laurence A.

    2010-01-01

    Two conventions for preparing dilutions are used in clinical laboratories. The first convention defines an "a:b" dilution as "a" volumes of solution A plus "b" volumes of solution B. The second convention defines an "a:b" dilution as "a" volumes of solution A diluted into a final volume of "b". Use of the incorrect dilution convention could affect…

  5. Defining Hardwood Veneer Log Quality Attributes

    Science.gov (United States)

    Jan Wiedenbeck; Michael Wiemann; Delton Alderman; John Baumgras; William Luppold

    2004-01-01

    This publication provides a broad spectrum of information on the hardwood veneer industry in North America. Veneer manufacturers and their customers impose guidelines in specifying wood quality attributes that are very discriminating but poorly defined (e.g., exceptional color, texture, and/or figure characteristics). To better understand and begin to define the most...

  6. DEFINED CONTRIBUTION PLANS, DEFINED BENEFIT PLANS, AND THE ACCUMULATION OF RETIREMENT WEALTH

    Science.gov (United States)

    Poterba, James; Rauh, Joshua; Venti, Steven; Wise, David

    2010-01-01

    The private pension structure in the United States, once dominated by defined benefit (DB) plans, is currently divided between defined contribution (DC) and DB plans. Wealth accumulation in DC plans depends on the participant's contribution behavior and on financial market returns, while accumulation in DB plans is sensitive to a participant's labor market experience and to plan parameters. This paper simulates the distribution of retirement wealth under representative DB and DC plans. It uses data from the Health and Retirement Study (HRS) to explore how asset returns, earnings histories, and retirement plan characteristics contribute to the variation in retirement wealth outcomes. We simulate DC plan accumulation by randomly assigning individuals a share of wages that they and their employer contribute to the plan. We consider several possible asset allocation strategies, with asset returns drawn from the historical return distribution. Our DB plan simulations draw earnings histories from the HRS, and randomly assign each individual a pension plan drawn from a sample of large private and public defined benefit plans. The simulations yield distributions of both DC and DB wealth at retirement. Average retirement wealth accruals under current DC plans exceed average accruals under private sector DB plans, although DC plans are also more likely to generate very low retirement wealth outcomes. The comparison of current DC plans with more generous public sector DB plans is less definitive, because public sector DB plans are more generous on average than their private sector counterparts. PMID:21057597

  7. Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.

    Science.gov (United States)

    Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J

    2016-01-01

    The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the

  8. Bilayer graphene quantum dot defined by topgates

    Energy Technology Data Exchange (ETDEWEB)

    Müller, André; Kaestner, Bernd; Hohls, Frank; Weimann, Thomas; Pierz, Klaus; Schumacher, Hans W., E-mail: hans.w.schumacher@ptb.de [Physikalisch-Technische Bundesanstalt, Bundesallee 100, 38116 Braunschweig (Germany)

    2014-06-21

    We investigate the application of nanoscale topgates on exfoliated bilayer graphene to define quantum dot devices. At temperatures below 500 mK, the conductance underneath the grounded gates is suppressed, which we attribute to nearest neighbour hopping and strain-induced piezoelectric fields. The gate-layout can thus be used to define resistive regions by tuning into the corresponding temperature range. We use this method to define a quantum dot structure in bilayer graphene showing Coulomb blockade oscillations consistent with the gate layout.

  9. Študija paradigm raziskovanja v magistrskih nalogah s področja družboslovja = A Study on Defining Research Paradigms in Preparing Master’s Theses from the Field of Sociology

    Directory of Open Access Journals (Sweden)

    Anita Trnavčevič

    2010-03-01

    Full Text Available The requirement for completion of post-graduate, master and doctoralstudy programs is producing an individual thesis. For many students,this is the first step into research. The research question in this article,therefore, is how students in their master thesis define the paradigms.We found that in the sample the quantitative paradigm is prevailing,while the mixed methods design is present, yet both of them are seldomdefined.

  10. A comparative study on the volume and localization of the internal gross target volume defined using the seroma and surgical clips based on 4DCT scan for external-beam partial breast irradiation after breast conserving surgery

    International Nuclear Information System (INIS)

    Ding, Yun; Li, Jianbin; Wang, Wei; Wang, Suzhen; Wang, Jinzhi; Ma, Zhifang; Shao, Qian; Xu, Min

    2014-01-01

    To explore the volume and localization of the internal gross target volume defined using the seroma and/or surgical clips based on the four-dimensional computed tomography (4DCT) during free-breathing. Fifteen breast cancer patients after breast-conserving surgery (BCS) were recruited for EB-PBI. On the ten sets CT images, the gross target volume formed by the clips, the seroma, both the clips and seroma delineated by one radiation oncologist and defined as GTVc, GTVs and GTVc + s, respectively. The ten GTVc, GTVs and GTVc + s on the ten sets CT images produced the IGTVc, IGTVs, IGTVc + s, respectively. The IGTV volume and the distance between the center of IGTVc, IGTVs, IGTVc + s were all recorded. Conformity index (CI), degree of inclusion (DI) were calculated for IGTV/IGTV, respectively. The volume of IGTVc + s were significantly larger than the IGTVc and IGTVs (p < 0.05). There was significant difference between the DIs of IGTVc vs IGTVc + s, the DIs of IGTVs vs IGTVc + s. There was significant difference among the CIs of IGTV/IGTV. The DIs and CIs of IGTV/IGTV were negatively correlated with their centroid distance (r < 0, p < 0.05). There were volume difference and spatial mismatch between the IGTVs delineated based on the surgical clips and seroma. The IGTV defined as the seroma and surgical clips provided the best overall representation of the ‘true’ moving GTV

  11. Defining food literacy: A scoping review.

    Science.gov (United States)

    Truman, Emily; Lane, Daniel; Elliott, Charlene

    2017-09-01

    The term "food literacy" describes the idea of proficiency in food related skills and knowledge. This prevalent term is broadly applied, although its core elements vary from initiative to initiative. In light of its ubiquitous use-but varying definitions-this article establishes the scope of food literacy research by identifying all articles that define 'food literacy', analysing its key conceptualizations, and reporting outcomes/measures of this concept. A scoping review was conducted to identify all articles (academic and grey literature) using the term "food literacy". Databases included Medline, Pubmed, Embase, CAB Abstracts, CINAHL, Scopus, JSTOR, and Web of Science, and Google Scholar. Of 1049 abstracts, 67 studies were included. From these, data was extracted on country of origin, study type (methodological approach), primary target population, and the primary outcomes relating to food literacy. The majority of definitions of food literacy emphasize the acquisition of critical knowledge (information and understanding) (55%) over functional knowledge (skills, abilities and choices) (8%), although some incorporate both (37%). Thematic analysis of 38 novel definitions of food literacy reveals the prevalence of six themes: skills and behaviours, food/health choices, culture, knowledge, emotions, and food systems. Study outcomes largely focus on knowledge generating measures, with very few focusing on health related outcome measures. Current definitions of food literacy incorporate components of six key themes or domains and attributes of both critical and functional knowledge. Despite this broad definition of the term, most studies aiming to improve food literacy focus on knowledge related outcomes. Few articles address health outcomes, leaving an important gap (and opportunity) for future research in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Differences in night-time and daytime ambulatory blood pressure when diurnal periods are defined by self-report, fixed-times, and actigraphy: Improving the Detection of Hypertension study.

    Science.gov (United States)

    Booth, John N; Muntner, Paul; Abdalla, Marwah; Diaz, Keith M; Viera, Anthony J; Reynolds, Kristi; Schwartz, Joseph E; Shimbo, Daichi

    2016-02-01

    To determine whether defining diurnal periods by self-report, fixed-time, or actigraphy produce different estimates of night-time and daytime ambulatory blood pressure (ABP). Over a median of 28 days, 330 participants completed two 24-h ABP and actigraphy monitoring periods with sleep diaries. Fixed night-time and daytime periods were defined as 0000-0600 h and 1000-2000 h, respectively. Using the first ABP period, within-individual differences for mean night-time and daytime ABP and kappa statistics for night-time and daytime hypertension (systolic/diastolic ABP≥120/70 mmHg and ≥135/85 mmHg, respectively) were estimated comparing self-report, fixed-time, or actigraphy for defining diurnal periods. Reproducibility of ABP was also estimated. Within-individual mean differences in night-time systolic ABP were small, suggesting little bias, when comparing the three approaches used to define diurnal periods. The distribution of differences, represented by 95% confidence intervals (CI), in night-time systolic and diastolic ABP and daytime systolic and diastolic ABP was narrowest for self-report versus actigraphy. For example, mean differences (95% CI) in night-time systolic ABP for self-report versus fixed-time was -0.53 (-6.61, +5.56) mmHg, self-report versus actigraphy was 0.91 (-3.61, +5.43) mmHg, and fixed-time versus actigraphy was 1.43 (-5.59, +8.46) mmHg. Agreement for night-time and daytime hypertension was highest for self-report versus actigraphy: kappa statistic (95% CI) = 0.91 (0.86,0.96) and 1.00 (0.98,1.00), respectively. The reproducibility of mean ABP and hypertension categories was similar using each approach. Given the high agreement with actigraphy, these data support using self-report to define diurnal periods on ABP monitoring. Further, the use of fixed-time periods may be a reasonable alternative approach.

  13. Application-Defined Decentralized Access Control

    Science.gov (United States)

    Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

    2014-01-01

    DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

  14. Software Defined Multiband EVA Radio, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of this research is to propose a reliable, lightweight, programmable, multi-band, multi-mode, miniaturized frequency-agile EVA software defined radio...

  15. Reconfigurable, Cognitive Software Defined Radio, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — IAI is actively developing Software Defined Radio platforms that can adaptively switch between different modes of operation by modifying both transmit waveforms and...

  16. Software Defined Multiband EVA Radio, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective of Phase 2 is to build a reliable, lightweight, programmable, multi-mode, miniaturized EVA Software Defined Radio (SDR) that supports data telemetry,...

  17. Reconfigurable, Cognitive Software Defined Radio, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Intelligent Automation Inc, (IAI) is currently developing a software defined radio (SDR) platform that can adaptively switch between different modes of operation for...

  18. Optimum Criteria for Developing Defined Structures

    Directory of Open Access Journals (Sweden)

    Ion IVAN

    2008-01-01

    Full Text Available Basic aspects concerning distributed applications are presented: definition, particularities and importance. For distributed applications linear, arborescent, graph structures are defined with different versions and aggregation methods. Distributed applications have associated structures which through their characteristics influence the costs of the stages in the development cycle and the exploitation costs transferred to each user. The complexity of the defined structures is analyzed. The minimum and maximum criteria are enumerated for optimizing distributed application structures.

  19. Defining Ecosystem Assets for Natural Capital Accounting.

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems' capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  20. Defining the landscape of adaptive genetic diversity.

    Science.gov (United States)

    Eckert, Andrew J; Dyer, Rodney J

    2012-06-01

    Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). © 2012 Blackwell Publishing Ltd.

  1. Defining the bacteroides ribosomal binding site.

    Science.gov (United States)

    Wegmann, Udo; Horn, Nikki; Carding, Simon R

    2013-03-01

    The human gastrointestinal tract, in particular the colon, hosts a vast number of commensal microorganisms. Representatives of the genus Bacteroides are among the most abundant bacterial species in the human colon. Bacteroidetes diverged from the common line of eubacterial descent before other eubacterial groups. As a result, they employ unique transcription initiation signals and, because of this uniqueness, they require specific genetic tools. Although some tools exist, they are not optimal for studying the roles and functions of these bacteria in the human gastrointestinal tract. Focusing on translation initiation signals in Bacteroides, we created a series of expression vectors allowing for different levels of protein expression in this genus, and we describe the use of pepI from Lactobacillus delbrueckii subsp. lactis as a novel reporter gene for Bacteroides. Furthermore, we report the identification of the 3' end of the 16S rRNA of Bacteroides ovatus and analyze in detail its ribosomal binding site, thus defining a core region necessary for efficient translation, which we have incorporated into the design of our expression vectors. Based on the sequence logo information from the 5' untranslated region of other Bacteroidales ribosomal protein genes, we conclude that our findings are relevant to all members of this order.

  2. [Defining AIDS terminology. A practical approach].

    Science.gov (United States)

    Locutura, Jaime; Almirante, Benito; Berenguer, Juan; Muñoz, Agustín; Peña, José María

    2003-01-01

    Since the appearance of AIDS, the study of this disease has generated a large amount of information and an extensive related vocabulary comprised of new terms or terms borrowed from other scientific fields. The urgent need to provide names for newly described phenomena and concepts in this field has resulted in the application of terms that are not always appropriate from the linguistic and scientific points of view. We discuss the difficulties in attempting to create adequate AIDS terminology in the Spanish language, considering both the general problems involved in building any scientific vocabulary and the specific problems inherent to this activity in a field whose defining illness has important social connotations. The pressure exerted by the predominance of the English language in reporting scientific knowledge is considered, and the inappropriate words most often found in a review of current literature are examined. Finally, attending to the two most important criteria for the creation of new scientific terms, accuracy and linguistic correction, we propose some well thought-out alternatives that conform to the essence of the Spanish language.

  3. Defining Ecosystem Assets for Natural Capital Accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks. PMID:27828969

  4. Defining ecosystem assets for natural capital accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Kenneth J.; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  5. Defined Contribution Model: Definition, Theory and an Application for Turkey

    OpenAIRE

    Metin Ercen; Deniz Gokce

    1998-01-01

    Based on a numerical application that employs social and economic parameters of the Turkish economy, this study attempts to demonstrate that the current collapse in the Turkish social security system is not unavoidable. The present social security system in Turkey is based on the defined benefit model of pension provision. On the other hand, recent proposals for reform in the social security system are based on a multipillar system, where one of the alternatives is a defined contribution pens...

  6. Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile.

    Science.gov (United States)

    Abe, Kensuke; Ohno, Yusuke; Sassa, Takayuki; Taguchi, Ryo; Çalışkan, Minal; Ober, Carole; Kihara, Akio

    2013-12-20

    Very long-chain fatty acids (VLCFAs, chain length >C20) exist in tissues throughout the body and are synthesized by repetition of the fatty acid (FA) elongation cycle composed of four successive enzymatic reactions. In mammals, the TER gene is the only gene encoding trans-2-enoyl-CoA reductase, which catalyzes the fourth reaction in the FA elongation cycle. The TER P182L mutation is the pathogenic mutation for nonsyndromic mental retardation. This mutation substitutes a leucine for a proline residue at amino acid 182 in the TER enzyme. Currently, the mechanism by which the TER P182L mutation causes nonsyndromic mental retardation is unknown. To understand the effect of this mutation on the TER enzyme and VLCFA synthesis, we have biochemically characterized the TER P182L mutant enzyme using yeast and mammalian cells transfected with the TER P182L mutant gene and analyzed the FA elongation cycle in the B-lymphoblastoid cell line with the homozygous TER P182L mutation (TER(P182L/P182L) B-lymphoblastoid cell line). We have found that TER P182L mutant enzyme exhibits reduced trans-2-enoyl-CoA reductase activity and protein stability, thereby impairing VLCFA synthesis and, in turn, altering the sphingolipid profile (i.e. decreased level of C24 sphingomyelin and C24 ceramide) in the TER(P182L/P182L) B-lymphoblastoid cell line. We have also found that in addition to the TER enzyme-catalyzed fourth reaction, the third reaction in the FA elongation cycle is affected by the TER P182L mutation. These findings provide new insight into the biochemical defects associated with this genetic mutation.

  7. Defining the critical hurdles in cancer immunotherapy

    Science.gov (United States)

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  8. Defining the critical hurdles in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Fox Bernard A

    2011-12-01

    Full Text Available Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC, convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  9. Understanding and defining bullying - adolescents' own views.

    Science.gov (United States)

    Hellström, Lisa; Persson, Louise; Hagquist, Curt

    2015-01-01

    The negative consequences of peer-victimization on children and adolescents are major public health concerns which have been subjected to extensive research. Given all efforts made to analyze and estimate the social and health consequences of peer-victimization, the adolescents' own experiences and understandings have had surprisingly little impact on the definition of bullying. Therefore, the aim of the current study is to explore adolescents' definitions of bullying. A questionnaire study (n = 128) and four focus group interviews (n = 21) were conducted among students aged 13 and 15. First, gender and age differences were analyzed with respect to what behaviors are considered bullying (questionnaire data). Second, analysis of what bullying is (focus group interviews) was conducted using qualitative content analysis. The adolescents own understanding and definition of bullying didn't just include the traditional criteria of repetition and power imbalance, but also a criterion based on the health consequences of bullying. The results showed that a single but hurtful or harmful incident also could be considered bullying irrespective of whether the traditional criteria were fulfilled or not. Further, girls and older students had a more inclusive view of bullying and reported more types of behaviors as bullying compared to boys and younger students. The results of the current study adds to the existing literature by showing that adolescents consider the victim's experience of hurt and harm as a criterion for defining bullying and not only as consequences of bullying. This may be of special relevance for the identification and classification of bullying incidents on the internet where devastating consequences have been reported from single incidents and the use of the traditional criteria of intent, repetition and power imbalance may not be as relevant as for traditional bullying. It implies that the traditional criteria included in most definitions of bullying

  10. Understanding communication between emergency and consulting physicians: a qualitative study that describes and defines the essential elements of the emergency department consultation-referral process for the junior learner.

    Science.gov (United States)

    Chan, Teresa; Orlich, Donika; Kulasegaram, Kulamakan; Sherbino, Jonathan

    2013-01-01

    To define the important elements of an emergency department (ED) consultation request and to develop a simple model of the process. From March to September 2010, 61 physicians (21 emergency medicine [EM], 20 general surgery [GS], 20 internal medicine [IM]; 31 residents, 30 attending staff) were questioned about how junior learners should be taught about ED consultation. Two investigators independently reviewed focus group and interview transcripts using grounded theory to generate an index of themes until saturation was reached. Disagreements were resolved by consensus, yielding an inventory of themes and subthemes. All transcripts were coded using this index of themes; 30% of transcripts were coded in duplicate to determine the agreement. A total of 245 themes and subthemes were identified. The agreement between reviewers was 77%. Important themes in the process were as follows: initial preparation and review of investigations by EM physician (overall endorsement 87% [range 70-100% in different groups]); identification of involved parties (patient and involved physicians) (100%); hypothesis of patient's diagnosis (75% [range 62-83%]) or question for the consulting physician (70% [range 55-95%]); urgency (100%) and stability (74% [range 62-80%]); questions from the consultant (100%); discussion/communication (98% [range 95-100%]); and feedback (98% [range 95-100%]). These components were reorganized into a simple framework (PIQUED). Each clinical specialty significantly contributed to the model (χ2  =  7.9; p value  =  0.019). Each group contributed uniquely to the final list of important elements (percent contributions: EM, 57%; GS, 41%; IM, 64%). We define important elements of an ED consultation with input from emergency and consulting physicians. We propose a model that organizes these elements into a simple framework (PIQUED) that may be valuable for junior learners.

  11. A Methodology to Define Flood Resilience

    Science.gov (United States)

    Tourbier, J.

    2012-04-01

    Flood resilience has become an internationally used term with an ever-increasing number of entries on the Internet. The SMARTeST Project is looking at approaches to flood resilience through case studies at cities in various countries, including Washington D.C. in the United States. In light of U.S. experiences a methodology is being proposed by the author that is intended to meet ecologic, spatial, structural, social, disaster relief and flood risk aspects. It concludes that: "Flood resilience combines (1) spatial, (2) structural, (3) social, and (4) risk management levels of flood preparedness." Flood resilience should incorporate all four levels, but not necessarily with equal emphasis. Stakeholders can assign priorities within different flood resilience levels and the considerations they contain, dividing 100% emphasis into four levels. This evaluation would be applied to planned and completed projects, considering existing conditions, goals and concepts. We have long known that the "road to market" for the implementation of flood resilience is linked to capacity building of stakeholders. It is a multidisciplinary enterprise, involving the integration of all the above aspects into the decision-making process. Traditional flood management has largely been influenced by what in the UK has been called "Silo Thinking", involving constituent organizations that are responsible for different elements, and are interested only in their defined part of the system. This barrier to innovation also has been called the "entrapment effect". Flood resilience is being defined as (1) SPATIAL FLOOD RESILIENCE implying the management of land by floodplain zoning, urban greening and management to reduce storm runoff through depression storage and by practicing Sustainable Urban Drainage (SUD's), Best Management Practices (BMP's, or Low Impact Development (LID). Ecologic processes and cultural elements are included. (2) STRUCTURAL FLOOD RESILIENCE referring to permanent flood defense

  12. Research Network of Tehran Defined Population: Methodology and Establishment

    Directory of Open Access Journals (Sweden)

    Ali-Asghar Kolahi

    2015-12-01

    Full Text Available Background: We need a defined population for determining prevalence and incidence of diseases, as well as conducting interventional, cohort and longitudinal studies, calculating correct and timely public health indicators, assessing actual health needs of community, performing educational programs and interventions to promote healthy lifestyle, and enhancing quality of primary health services.The objective of this project was to determine a defined population which is representative of Tehran, the Capital of Iran. This article reports the methodology and establishment of the research network of Tehran defined population.Methods: This project started by selecting two urban health centers from each of the five district health centers affiliated to Shahid Beheshti University of Medical Sciences in 2012. Inside each selected urban health center, one defined population research station was established. Two new centers have been added during 2013 and 2014. For the time being, the number of the covered population of the network has reached 40000 individuals. The most important criterion for the defined population has been to be representative of the population of Tehran. For this, we selected two urban health centers from 12 of 22 municipality districts and from each of the five different socioeconomic of Greater Tehran. Merely 80000 individuals in neighborhoods of each defined population research station were considered as control group of the project.Findings: Totally we selected 12 defined population research stations and their under-covered population developed a defined population which is representative of Tehran population.Conclusion: a population lab is ready now in metropolitan of Tehran.

  13. Hanford defined waste model limitations and improvements

    International Nuclear Information System (INIS)

    HARMSEN, R.W.

    1999-01-01

    Recommendation 93-5 Implementation Plan, Milestone 5,6.3.1.i requires issuance of this report which addresses ''updates to the tank contents model''. This report summarizes the review of the Hanford Defined Waste, Revision 4, model limitations and provides conclusions and recommendations for potential updates to the model

  14. Parallel Education and Defining the Fourth Sector.

    Science.gov (United States)

    Chessell, Diana

    1996-01-01

    Parallel to the primary, secondary, postsecondary, and adult/community education sectors is education not associated with formal programs--learning in arts and cultural sites. The emergence of cultural and educational tourism is an opportunity for adult/community education to define itself by extending lifelong learning opportunities into parallel…

  15. Bruxism defined and graded: an international consensus

    NARCIS (Netherlands)

    Lobbezoo, F.; Ahlberg, J.; Glaros, A.G.; Kato, T.; Koyano, K.; Lavigne, G.J.; de Leeuw, R.; Manfredini, D.; Svensson, P.; Winocur, E.

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined

  16. 7 CFR 28.950 - Terms defined.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Definitions § 28.950 Terms defined. As used... Agricultural Marketing Service of the U.S. Department of Agriculture. (c) Administrator. The Administrator of...

  17. 47 CFR 54.401 - Lifeline defined.

    Science.gov (United States)

    2010-10-01

    ... SERVICE Universal Service Support for Low-Income Consumers § 54.401 Lifeline defined. (a) As used in this subpart, Lifeline means a retail local service offering: (1) That is available only to qualifying low-income consumers; (2) For which qualifying low-income consumers pay reduced charges as a result of...

  18. Big data and software defined networks

    CERN Document Server

    Taheri, Javid

    2018-01-01

    Big Data Analytics and Software Defined Networking (SDN) are helping to drive the management of data usage of the extraordinary increase of computer processing power provided by Cloud Data Centres (CDCs). This new book investigates areas where Big-Data and SDN can help each other in delivering more efficient services.

  19. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  20. Towards a Southern African English Defining Vocabulary

    African Journals Online (AJOL)

    user

    of parameters, such as avoiding synonyms and antonyms, to determine which words are necessary to write definitions in a concise and simple way. It has been found that existing defining vocabularies lack certain words that would make definitions more accessible to southern African learners, and therefore there is a need ...

  1. Spaces defined by the Paley function

    Energy Technology Data Exchange (ETDEWEB)

    Astashkin, S V [Samara State University, Samara (Russian Federation); Semenov, E M [Voronezh State University, Faculty of Mathematics, Voronezh (Russian Federation)

    2013-07-31

    The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

  2. Pointwise extensions of GSOS-defined operations

    NARCIS (Netherlands)

    Hansen, H.H.; Klin, B.

    2011-01-01

    Final coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor S over a behaviour functor F). Such distributive laws correspond to abstract specification formats. One such

  3. Pointwise Extensions of GSOS-Defined Operations

    NARCIS (Netherlands)

    H.H. Hansen (Helle); B. Klin

    2011-01-01

    textabstractFinal coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor $\\FSig$ over a behaviour functor $F$). Such distributive laws correspond to abstract specification

  4. A self-defining hierarchical data system

    Science.gov (United States)

    Bailey, J.

    1992-01-01

    The Self-Defining Data System (SDS) is a system which allows the creation of self-defining hierarchical data structures in a form which allows the data to be moved between different machine architectures. Because the structures are self-defining they can be used for communication between independent modules in a distributed system. Unlike disk-based hierarchical data systems such as Starlink's HDS, SDS works entirely in memory and is very fast. Data structures are created and manipulated as internal dynamic structures in memory managed by SDS itself. A structure may then be exported into a caller supplied memory buffer in a defined external format. This structure can be written as a file or sent as a message to another machine. It remains static in structure until it is reimported into SDS. SDS is written in portable C and has been run on a number of different machine architectures. Structures are portable between machines with SDS looking after conversion of byte order, floating point format, and alignment. A Fortran callable version is also available for some machines.

  5. BcR-induced apoptosis involves differential regulation of C-16 and C-24-ceramide formation and sphingolipid-dependent activation of the proteasome

    NARCIS (Netherlands)

    Kroesen, BJ; Jacobs, Susan; Pettus, BJ; Sietsma, H; Kok, JW; Hannun, YA; de Leij, LFMH

    2003-01-01

    In this study, we describe an ordered formation of long- and very long-chain ceramide species in relation to the progression of B-cell receptor (BcR) triggering induced apoptosis. An early and caspase-independent increase in long-chain ceramide species, in which C-24-ceramide predominated, was

  6. Control of System with Defined Risk Level

    Directory of Open Access Journals (Sweden)

    Pavol Tomasov

    2002-01-01

    Full Text Available In the following paper the basic requirements for system control with defined risk level is presented. The paper should be an introduction to describe of theoretical apparatus, which was created during some years of research work in the Department of information and safety systems in this area. It a modification or creation of new parts of Information theory, System theory, and Control theory means. This parts are necessary for the analysis and synthesis tasks in the systems where dominant attribute of control is defined risk level. The basic problem is the creation of protect mechanism again the threats from inside and from controlled system environs. For each risk reduction mechanism is needed some redundancy which should be into control algorithm to put by exactly determined way.

  7. Improving network management with Software Defined Networking

    International Nuclear Information System (INIS)

    Dzhunev, Pavel

    2013-01-01

    Software-defined networking (SDN) is developed as an alternative to closed networks in centers for data processing by providing a means to separate the control layer data layer switches, and routers. SDN introduces new possibilities for network management and configuration methods. In this article, we identify problems with the current state-of-the-art network configuration and management mechanisms and introduce mechanisms to improve various aspects of network management

  8. Stateless multicast switching in software defined networks

    OpenAIRE

    Reed, Martin J.; Al-Naday, Mays; Thomos, Nikolaos; Trossen, Dirk; Petropoulos, George; Spirou, Spiros

    2016-01-01

    Multicast data delivery can significantly reduce traffic in operators' networks, but has been limited in deployment due to concerns such as the scalability of state management. This paper shows how multicast can be implemented in contemporary software defined networking (SDN) switches, with less state than existing unicast switching strategies, by utilising a Bloom Filter (BF) based switching technique. Furthermore, the proposed mechanism uses only proactive rule insertion, and thus, is not l...

  9. Defining and Distinguishing Traditional and Religious Terrorism

    OpenAIRE

    Gregg, Heather S.

    2014-01-01

    The article of record may be found at: http://dx.doi.org/10.1080/23296151.2016.1239978 thus offering few if any policy options for counterterrorism measures. This assumption about religious terrorism stems from two challenges in the literature: disproportionate attention to apocalyptic terrorism, and a lack of distinction between religious terrorism and its secular counterpart. This article, therefore, aims to do four things: define and differentiate religiously motivated terrorism from tr...

  10. Defining Trust Using Expected Utility Theory

    OpenAIRE

    Arai, Kazuhiro

    2009-01-01

    Trust has been discussed in many social sciences including economics, psychology, and sociology. However, there is no widely accepted definition of trust. Inparticular, there is no definition that can be used for economic analysis. This paper regards trust as expectation and defines it using expected utility theory together with concepts such as betrayal premium. In doing so, it rejects the widely accepted black-and-white view that (un) trustworthy people are always (un)trustworthy. This pape...

  11. On Undefined and Meaningless in Lambda Definability

    OpenAIRE

    de Vries, Fer-Jan

    2016-01-01

    We distinguish between undefined terms as used in lambda definability of partial recursive functions and meaningless terms as used in infinite lambda calculus for the infinitary terms models that generalise the Bohm model. While there are uncountable many known sets of meaningless terms, there are four known sets of undefined terms. Two of these four are sets of meaningless terms. In this paper we first present set of sufficient conditions for a set of lambda terms to se...

  12. Defining functional distances over Gene Ontology

    Directory of Open Access Journals (Sweden)

    del Pozo Angela

    2008-01-01

    Full Text Available Abstract Background A fundamental problem when trying to define the functional relationships between proteins is the difficulty in quantifying functional similarities, even when well-structured ontologies exist regarding the activity of proteins (i.e. 'gene ontology' -GO-. However, functional metrics can overcome the problems in the comparing and evaluating functional assignments and predictions. As a reference of proximity, previous approaches to compare GO terms considered linkage in terms of ontology weighted by a probability distribution that balances the non-uniform 'richness' of different parts of the Direct Acyclic Graph. Here, we have followed a different approach to quantify functional similarities between GO terms. Results We propose a new method to derive 'functional distances' between GO terms that is based on the simultaneous occurrence of terms in the same set of Interpro entries, instead of relying on the structure of the GO. The coincidence of GO terms reveals natural biological links between the GO functions and defines a distance model Df which fulfils the properties of a Metric Space. The distances obtained in this way can be represented as a hierarchical 'Functional Tree'. Conclusion The method proposed provides a new definition of distance that enables the similarity between GO terms to be quantified. Additionally, the 'Functional Tree' defines groups with biological meaning enhancing its utility for protein function comparison and prediction. Finally, this approach could be for function-based protein searches in databases, and for analysing the gene clusters produced by DNA array experiments.

  13. The study for defining the best technical and economical alternatives for the associated substation to the Tucurui hydraulic power plant - second stage; Estudo para definicao da melhor alternativa tecnico-economica para a subestacao elevadora-secionadora associada a Usina Hidroeletrica Tucurui - segunda etapa

    Energy Technology Data Exchange (ETDEWEB)

    Machado Junior, Camilo; Fukuoka, Nita; Rose, Eber Havila [ELETRONORTE, Brasilia, DF (Brazil)]. E-mail: eber@eln.gov.br; Martinez, Manuel Luis Barreira [Escola Federal de Engenharia de Itajuba, MG (Brazil). Inst. de Energia Eletrica. Dept. de Eletrotecnica; Violin, Airton

    2001-07-01

    This document presents a synthesis of the developed study for defining the switching scheme of the associated substation to the Tucurui hydraulic power plant second stage which is being constructed. In order to reduce the short circuit level in the first stage substation (in operation) to suitable values and, at the same time, to maintain the flexibility in the generator and transmission systems, it has been decided to install some series reactors between the substations in 550 Kv. The used methodology to define the suitable alternative is also discussed and the substation final configuration involving the first and second stages of the substation enlargement is presented through a illustration.

  14. Positive facial expressions during retrieval of self-defining memories.

    Science.gov (United States)

    Gandolphe, Marie Charlotte; Nandrino, Jean Louis; Delelis, Gérald; Ducro, Claire; Lavallee, Audrey; Saloppe, Xavier; Moustafa, Ahmed A; El Haj, Mohamad

    2017-11-14

    In this study, we investigated, for the first time, facial expressions during the retrieval of Self-defining memories (i.e., those vivid and emotionally intense memories of enduring concerns or unresolved conflicts). Participants self-rated the emotional valence of their Self-defining memories and autobiographical retrieval was analyzed with a facial analysis software. This software (Facereader) synthesizes the facial expression information (i.e., cheek, lips, muscles, eyebrow muscles) to describe and categorize facial expressions (i.e., neutral, happy, sad, surprised, angry, scared, and disgusted facial expressions). We found that participants showed more emotional than neutral facial expressions during the retrieval of Self-defining memories. We also found that participants showed more positive than negative facial expressions during the retrieval of Self-defining memories. Interestingly, participants attributed positive valence to the retrieved memories. These findings are the first to demonstrate the consistency between facial expressions and the emotional subjective experience of Self-defining memories. These findings provide valuable physiological information about the emotional experience of the past.

  15. On functions defined by sums of products of Bessel functions

    International Nuclear Information System (INIS)

    Martin, P A

    2008-01-01

    Various functions, defined as infinite series of products of Bessel functions of the first kind, are studied. Integral representations are obtained, and then used to deduce asymptotic approximations. Although several methods have been investigated (including power series expansions and integral transforms), methods based on Fourier series emerge as the most useful

  16. Undergraduate Performance in Solving Ill-Defined Biochemistry Problems

    Science.gov (United States)

    Sensibaugh, Cheryl A.; Madrid, Nathaniel J.; Choi, Hye-Jeong; Anderson, William L.; Osgood, Marcy P.

    2017-01-01

    With growing interest in promoting skills related to the scientific process, we studied performance in solving ill-defined problems demonstrated by graduating biochemistry majors at a public, minority-serving university. As adoption of techniques for facilitating the attainment of higher-order learning objectives broadens, so too does the need to…

  17. Defining collaborative business rules management solutions : framework and method

    NARCIS (Netherlands)

    dr. Martijn Zoet; Johan Versendaal

    2014-01-01

    From the publishers' website: The goal of this research is to define a method for configuring a collaborative business rules management solution from a value proposition perspective. In an earlier published study (Business rules management solutions: added value by means of business

  18. Defining the Shoah: An Opening Lesson for a Holocaust Unit

    Science.gov (United States)

    Lindquist, David H.

    2013-01-01

    Students often bring considerable prior information about the Holocaust to their study of the event, with much of that knowledge being inaccurate or incomplete. In addition, the Shoah's complexity necessitates that teachers establish a well-defined framework as they introduce the topic to their students. This article outlines an opening lesson for…

  19. ANALISIS PENGENDALIAN KUALITAS PRODUKSI BOGIE BARBER S2HD 9C MENGGUNAKAN METODE LEAN SIX SIGMA DENGAN PENDEKATAN DMAIC (DEFINE, MEASURE, ANALYZE, IMPROVE, CONTROL STUDI KASUS DI PT BARATA INDONESIA (PERSERO GRESIK

    Directory of Open Access Journals (Sweden)

    Suparno Suparno

    2017-01-01

    Full Text Available Penelitian ini bertujuan untuk menganalisis pengendalian kualitas dan pemborosan yang terjadi dalam produksi side frame S2HD 9C menggunakan metode lean six sigma dengan pendekatan DMAIC di PT Barata Indonesia (Persero Gresik. Side frame S2HD 9C merupakan bagian dari produk bogie barber S2HD 9C. Penelitian ini pada tahap six sigma difokuskan pada analisis defect dan capaian sigma, sedangkan pada tahap lean six sigma difokuskan pada analisis waste dan capaian sigma. Data yang digunakan dalam penelitian ini ada 2 jenis yaitu data primer dan sekunder, yang bersifat kualitatif maupun kuantitatif. Data primer diperoleh dari observasi lapangan, sedangkan data sekunder diperoleh dari telaah dokumen. Dalam penelitian ini dilakukan sesuai dengan pendekatan DMAIC ( define, measure, analyze, improve, control . Setelah dilakukan analisis pada tahap six sigma diketahui terdapat 5 jenis defect yang terjadi pada periode Januari sampai April 2016. Yaitu: defect gas terperangkap 58.18%, defect core patah 21.82%, defect sand drop 12.73%, defect brake mould 5.46% dan defect misplace core 1.82%. Dan nilai capaian tingkat sigma dari masing-masing defect adalah sebagai berikut:  defect gas terperangkap 1235.71 DPMO dengan tingkat sigma 4.52σ, defect core patah 463.392 DPMO dengan tingkat sigma 4.81σ, defect sand drop 270.312 DPMO dengan tingkat sigma 4.96σ, defect brake mould 115.848 DPMO dengan tingkat sigma 5.18σ dan defect misplace core 38.616 DPMO dengan tingkat sigma 5.45σ. Dalam tahap lean six sigma diketahui terdapat 4 jenis waste, yaitu: waste defect product, waste waiting time (delay, waste transportation dan waste excess process. Berikut ini merupakan nilai capaian dari masing-masing waste: waste defect product 6890 DPMO dengan tingkat sigma 3.96σ dan nilai capability process 1.31 dengan tingkat sigma 3.94σ, waste waiting time (delay nilai capability process 1 dengan tingkat sigma 3σ, waste transportation nilai capability process 1.31 dengan tingkat

  20. Defining Multiple Chronic Conditions for Quality Measurement.

    Science.gov (United States)

    Drye, Elizabeth E; Altaf, Faseeha K; Lipska, Kasia J; Spatz, Erica S; Montague, Julia A; Bao, Haikun; Parzynski, Craig S; Ross, Joseph S; Bernheim, Susannah M; Krumholz, Harlan M; Lin, Zhenqiu

    2018-02-01

    Patients with multiple chronic conditions (MCCs) are a critical but undefined group for quality measurement. We present a generally applicable systematic approach to defining an MCC cohort of Medicare fee-for-service beneficiaries that we developed for a national quality measure, risk-standardized rates of unplanned admissions for Accountable Care Organizations. To define the MCC cohort we: (1) identified potential chronic conditions; (2) set criteria for cohort conditions based on MCC framework and measure concept; (3) applied the criteria informed by empirical analysis, experts, and the public; (4) described "broader" and "narrower" cohorts; and (5) selected final cohort with stakeholder input. Subjects were patients with chronic conditions. Participants included 21.8 million Medicare fee-for-service beneficiaries in 2012 aged 65 years and above with ≥1 of 27 Medicare Chronic Condition Warehouse condition(s). In total, 10 chronic conditions were identified based on our criteria; 8 of these 10 were associated with notably increased admission risk when co-occurring. A broader cohort (2+ of the 8 conditions) included 4.9 million beneficiaries (23% of total cohort) with an admission rate of 70 per 100 person-years. It captured 53% of total admissions. The narrower cohort (3+ conditions) had 2.2 million beneficiaries (10%) with 100 admissions per 100 person-years and captured 32% of admissions. Most stakeholders viewed the broader cohort as best aligned with the measure concept. By systematically narrowing chronic conditions to those most relevant to the outcome and incorporating stakeholder input, we defined an MCC admission measure cohort supported by stakeholders. This approach can be used as a model for other MCC outcome measures.

  1. How do pediatric anesthesiologists define intraoperative hypotension?

    Science.gov (United States)

    Nafiu, Olubukola O; Voepel-Lewis, Terri; Morris, Michelle; Chimbira, Wilson T; Malviya, Shobha; Reynolds, Paul I; Tremper, Kevin K

    2009-11-01

    Although blood pressure (BP) monitoring is a recommended standard of care by the ASA, and pediatric anesthesiologists routinely monitor the BP of their patients and when appropriate treat deviations from 'normal', there is no robust definition of hypotension in any of the pediatric anesthesia texts or journals. Consequently, what constitutes hypotension in pediatric anesthesia is currently unknown. We designed a questionnaire-based survey of pediatric anesthesiologists to determine the BP ranges and thresholds used to define intraoperative hypotension (IOH). Members of the Society of Pediatric Anesthesia (SPA) and the Association of Paediatric Anaesthetists (APA) of Great Britain and Ireland were contacted through e-mail to participate in this survey. We asked a few demographic questions and five questions about specific definitions of hypotension for different age groups of patients undergoing inguinal herniorraphy, a common pediatric surgical procedure. The overall response rate was 56% (483/860), of which 76% were SPA members. Majority of the respondents (72%) work in academic institutions, while 8.9% work in institutions with fewer than 1000 annual pediatric surgical caseload. About 76% of respondents indicated that a 20-30% reduction in baseline systolic blood pressure (SBP) indicates significant hypotension in children under anesthesia. Most responders (86.7%) indicated that they use mean arterial pressure or SBP (72%) to define IOH. The mean SBP values for hypotension quoted by SPA members was about 5-7% lower across all pediatric age groups compared to values quoted by APA members (P = 0.001 for all age groups). There is great variability in the BP parameters used and the threshold used for defining and treating IOH among pediatric anesthesiologists. The majority of respondents considered a 20-30% reduction from baseline in SBP as indicative of significant hypotension. Lack of a consensus definition for a common clinical condition like IOH could have

  2. Defining Marriage: Classification, Interpretation, and Definitional Disputes

    Directory of Open Access Journals (Sweden)

    Fabrizio Macagno

    2016-09-01

    Full Text Available The classification of a state of affairs under a legal category can be considered as a kind of con- densed decision that can be made explicit, analyzed, and assessed us- ing argumentation schemes. In this paper, the controversial conflict of opinions concerning the nature of “marriage” in Obergefell v. Hodges is analyzed pointing out the dialecti- cal strategies used for addressing the interpretive doubts. The dispute about the same-sex couples’ right to marry hides a much deeper disa- greement not only about what mar- riage is, but more importantly about the dialectical rules for defining it.

  3. Software defined networks a comprehensive approach

    CERN Document Server

    Goransson, Paul

    2014-01-01

    Software Defined Networks discusses the historical networking environment that gave rise to SDN, as well as the latest advances in SDN technology. The book gives you the state of the art knowledge needed for successful deployment of an SDN, including: How to explain to the non-technical business decision makers in your organization the potential benefits, as well as the risks, in shifting parts of a network to the SDN modelHow to make intelligent decisions about when to integrate SDN technologies in a networkHow to decide if your organization should be developing its own SDN applications or

  4. Software Defined Radio: Basic Principles and Applications

    Directory of Open Access Journals (Sweden)

    José Raúl Machado-Fernández

    2014-12-01

    Full Text Available The author makes a review of the SDR (Software Defined Radio technology, including hardware schemes and application fields. A low performance device is presented and several tests are executed with it using free software. With the acquired experience, SDR employment opportunities are identified for low-cost solutions that can solve significant problems. In addition, a list of the most important frameworks related to the technology developed in the last years is offered, recommending the use of three of them.

  5. DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC ...

    Science.gov (United States)

    The current project aims to chemically index the genomics content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By defining the chemical space of public genomic data, it is possible to identify classes of chemicals on which to develop methodologies for the integration of chemogenomic data into predictive toxicology. The chemical space of public genomic data will be presented as well as the methodologies and tools developed to identify this chemical space.

  6. Healthcare Engineering Defined: A White Paper.

    Science.gov (United States)

    Chyu, Ming-Chien; Austin, Tony; Calisir, Fethi; Chanjaplammootil, Samuel; Davis, Mark J; Favela, Jesus; Gan, Heng; Gefen, Amit; Haddas, Ram; Hahn-Goldberg, Shoshana; Hornero, Roberto; Huang, Yu-Li; Jensen, Øystein; Jiang, Zhongwei; Katsanis, J S; Lee, Jeong-A; Lewis, Gladius; Lovell, Nigel H; Luebbers, Heinz-Theo; Morales, George G; Matis, Timothy; Matthews, Judith T; Mazur, Lukasz; Ng, Eddie Yin-Kwee; Oommen, K J; Ormand, Kevin; Rohde, Tarald; Sánchez-Morillo, Daniel; Sanz-Calcedo, Justo García; Sawan, Mohamad; Shen, Chwan-Li; Shieh, Jiann-Shing; Su, Chao-Ton; Sun, Lilly; Sun, Mingui; Sun, Yi; Tewolde, Senay N; Williams, Eric A; Yan, Chongjun; Zhang, Jiajie; Zhang, Yuan-Ting

    2015-01-01

    Engineering has been playing an important role in serving and advancing healthcare. The term "Healthcare Engineering" has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of "Healthcare Engineering" remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  7. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper

    2015-01-01

    Starch is a vital energy molecule in plants that has a wide variety of uses in industry, such as feedstock for biomaterial processing and biofuel production. Plants employ a three enzyme cyclic process utilizing kinases, amylases, and phosphatases to degrade starch in a diurnal manner. Starch...... is comprised of the branched glucan amylopectin and the more linear glucan amylose. Our lab has determined the first structures of these glucan phosphatases and we have defined their enzymatic action. Despite this progress, we lacked a means to quickly and efficiently quantify starch binding to glucan...

  8. Healthcare Engineering Defined: A White Paper

    Directory of Open Access Journals (Sweden)

    Ming-Chien Chyu

    2015-01-01

    Full Text Available Engineering has been playing an important role in serving and advancing healthcare. The term “Healthcare Engineering” has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of “Healthcare Engineering” remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  9. Software-defined reconfigurable microwave photonics processor.

    Science.gov (United States)

    Pérez, Daniel; Gasulla, Ivana; Capmany, José

    2015-06-01

    We propose, for the first time to our knowledge, a software-defined reconfigurable microwave photonics signal processor architecture that can be integrated on a chip and is capable of performing all the main functionalities by suitable programming of its control signals. The basic configuration is presented and a thorough end-to-end design model derived that accounts for the performance of the overall processor taking into consideration the impact and interdependencies of both its photonic and RF parts. We demonstrate the model versatility by applying it to several relevant application examples.

  10. Fingerprinting Software Defined Networks and Controllers

    Science.gov (United States)

    2015-03-01

    rps requests per second RTT Round-Trip Time SDN Software Defined Networking SOM Self-Organizing Map STP Spanning Tree Protocol TRW-CB Threshold Random...Protocol ( STP ) updates), in which case the frame will be “punted” from the forwarding lookup process and processed by the route processor [9]. The act of...environment 20 to accomplish the needs of B4. In addition to Google, the SDN market is expected to grow beyond $35 billion by April 2018 [31]. The rate

  11. Responsibility for proving and defining in abstract algebra class

    Science.gov (United States)

    Fukawa-Connelly, Timothy

    2016-07-01

    There is considerable variety in inquiry-oriented instruction, but what is common is that students assume roles in mathematical activity that in a traditional, lecture-based class are either assumed by the teacher (or text) or are not visible at all in traditional math classrooms. This paper is a case study of the teaching of an inquiry-based undergraduate abstract algebra course. In particular, gives a theoretical account of the defining and proving processes. The study examines the intellectual responsibility for the processes of defining and proving that the professor devolved to the students. While the professor wanted the students to engage in all aspects of defining and proving, he was only successful at devolving responsibility for certain aspects and much more successful at devolving responsibility for proving than conjecturing or defining. This study suggests that even a well-intentioned instructor may not be able to devolve responsibility to students for some aspects of mathematical practice without using a research-based curriculum or further professional development.

  12. Defining an Open Source Strategy for NASA

    Science.gov (United States)

    Mattmann, C. A.; Crichton, D. J.; Lindsay, F.; Berrick, S. W.; Marshall, J. J.; Downs, R. R.

    2011-12-01

    Over the course of the past year, we have worked to help frame a strategy for NASA and open source software. This includes defining information processes to understand open source licensing, attribution, commerciality, redistribution, communities, architectures, and interactions within the agency. Specifically we held a training session at the NASA Earth Science Data Systems Working Group meeting in Open Source software as it relates to the NASA Earth Science data systems enterprise, including EOSDIS, the Distributed Active Archive Centers (DAACs), ACCESS proposals, and the MEASURES communities, and efforts to understand how open source software can be both consumed and produced within that ecosystem. In addition, we presented at the 1st NASA Open Source Summit (OSS) and helped to define an agency-level strategy, a set of recommendations and paths forward for how to identify healthy open source communities, how to deal with issues such as contributions originating from other agencies, and how to search out talent with the right skills to develop software for NASA in the modern age. This talk will review our current recommendations for open source at NASA, and will cover the set of thirteen recommendations output from the NASA Open Source Summit and discuss some of their implications for the agency.

  13. How Do You Define an Internship?

    Science.gov (United States)

    Wilson, C. E.; Keane, C.

    2017-12-01

    According to the American Geosciences Institute's Geoscience Student Exit Survey, internship participation rates over the past four years have been low, particularly among bachelor's and doctoral graduates. In 2016, 65% of bachelor's graduates, 44% of master's graduates, and 57% of doctoral graduates did not participate in an internship while working on their degree. When asked if they submitted applications for internship opportunities, 42% of bachelor's graduates, 23% of master's graduates, and 46% of doctoral graduates claimed to not submit any applications. These statistics have raised concern at AGI because internships provide experiences that help develop critical professional skills and industry connections that can lead to jobs after graduation. However, when internships are discussed among various representatives in geoscience industries, there are disagreements in how an internship experience is defined. For example, opinions differ on whether REUs or other research experiences count as an internship. Clear definitions of internship opportunities may help academic faculty and advisors direct students towards these opportunities and help develop a collection of resources for finding future internships. This presentation will present some of the recent statistics on internship participation among geoscience graduates and present a series of questions to ascertain defining features of internships among AGU attendees and where help is needed to increase participation in internships among current geoscience students.

  14. Defining Medical Capabilities for Exploration Missions

    Science.gov (United States)

    Hailey, M.; Antonsen, E.; Blue, R.; Reyes, D.; Mulcahy, R.; Kerstman, E.; Bayuse, T.

    2018-01-01

    Exploration-class missions to the moon, Mars and beyond will require a significant change in medical capability from today's low earth orbit centric paradigm. Significant increases in autonomy will be required due to differences in duration, distance and orbital mechanics. Aerospace medicine and systems engineering teams are working together within ExMC to meet these challenges. Identifying exploration medical system needs requires accounting for planned and unplanned medical care as defined in the concept of operations. In 2017, the ExMC Clinicians group identified medical capabilities to feed into the Systems Engineering process, including: determining what and how to address planned and preventive medical care; defining an Accepted Medical Condition List (AMCL) of conditions that may occur and a subset of those that can be treated effectively within the exploration environment; and listing the medical capabilities needed to treat those conditions in the AMCL. This presentation will discuss the team's approach to addressing these issues, as well as how the outputs of the clinical process impact the systems engineering effort.

  15. Distributed controller clustering in software defined networks.

    Directory of Open Access Journals (Sweden)

    Ahmed Abdelaziz

    Full Text Available Software Defined Networking (SDN is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN SDN and Open Network Operating System (ONOS controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

  16. Distributed controller clustering in software defined networks.

    Science.gov (United States)

    Abdelaziz, Ahmed; Fong, Ang Tan; Gani, Abdullah; Garba, Usman; Khan, Suleman; Akhunzada, Adnan; Talebian, Hamid; Choo, Kim-Kwang Raymond

    2017-01-01

    Software Defined Networking (SDN) is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs) brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN) SDN and Open Network Operating System (ONOS) controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

  17. What sugar next? Dimerization of sphingolipid glycosyltransferases

    NARCIS (Netherlands)

    van Meer, G.

    2001-01-01

    One of the great riddles of glycobiology is the function of the glycosphingolipids. Their vital role is clear from the fact that the lack only of subsets of glycosphingolipids results in premature death (1). Hundreds of glycosphingolipids populate the surface of mammalian cells. These may serve a

  18. Farm elders define health as the ability to work.

    Science.gov (United States)

    Reed, Deborah B; Rayens, Mary Kay; Conley, Christina K; Westneat, Susan; Adkins, Sarah M

    2012-08-01

    Thirty percent of America's 2.2 million farms are operated by individuals older than 65 years. This study examined how older farmers define health and determined whether demographic characteristics, farm work, and physical and mental health status predict health definition. Data were collected via telephone and mailed surveys during the baseline wave of data collection in a longitudinal study of family farmers residing in two southern states (n=1,288). Nearly 42% defined health as the "ability to work" compared to a physical health-related definition. Predictors of defining health as the ability to work included being White, performing more farm tasks in the past week, taking prescription medications daily, and having minimal health-related limitations to farm work. Health behaviors are centered on the individual's perception of health. Understanding the defining attributes of health can support better approaches to health care and health promotion, particularly among rural subcultures such as farmers, whose identity is rooted in their work. Copyright 2012, SLACK Incorporated.

  19. Reconfigurable, Cognitive Software-Defined Radio

    Science.gov (United States)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  20. Nurse leader resilience: career defining moments.

    Science.gov (United States)

    Cline, Susan

    2015-01-01

    Resilience is an essential component of effective nursing leadership. It is defined as the ability to survive and thrive in the face of adversity. Resilience can be developed and internalized as a measure to improve retention and reduce burnout. Nurse leaders at all levels should develop these competencies to survive and thrive in an increasingly complex health care environment. Building positive relationships, maintaining positivity, developing emotional insight, creating work-life balance, and reflecting on successes and challenges are effective strategies for resilience building. Nurse leaders have a professional obligation to develop resilience in themselves, the teams they supervise, and the organization as a whole. Additional benefits include reduced turnover, reduced cost, and improved quality outcomes through organizational mindfulness.